- Email: [email protected]
Interfacial tensiometry and dilational surface visco-elasticity of biological liquids in medicine
Interfacial tensiometry and dilational surface visco-elasticity of biological liquids in medicine V.B. Fainerman, D.V. Trukhin, Igor I. Zinkovych, R. Miller PII: DOI: Reference:
S0001-8686(17)30007-6 doi:10.1016/j.cis.2017.08.002 CIS 1820
To appear in:
Advances in Colloid and Interface Science
Received date: Revised date: Accepted date:
10 January 2017 31 July 2017 7 August 2017
Please cite this article as: Fainerman VB, Trukhin DV, Zinkovych Igor I., Miller R, Interfacial tensiometry and dilational surface visco-elasticity of biological liquids in medicine, Advances in Colloid and Interface Science (2017), doi:10.1016/j.cis.2017.08.002
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Interfacial tensiometry and dilational surface visco-elasticity of biological liquids in medicine
IP
T
V.B. Fainerman1, D.V. Trukhin2, Igor I. Zinkovych3 and R. Miller4 1
NU
SC R
SINTERFACE Technologies, Berlin, Germany; Donetsk National Medical University, Ukraine 2 Odessa National Medical University, Odessa, Ukraine 3 Donetsk National Medical University, Ukraine 4 Max-Planck-Institut für Kolloid- und Grenzflächenforschung, Potsdam, Germany
MA
Contents
AC
CE P
TE
D
1. Introduction 2. Experimental methods 3. Surface characteristics of biological liquids for healthy persons 4. Influence of diseases on surface characteristics of biologic liquids 4.1. Oncology 4.2. Oral liquid, effect of carious lesion of teeth 4.3. Neurosyphilis 4.4. Congenital pneumonia of premature newborns 4.5. Chronic recurrent pancreatitis 4.6. Acute renal failure 4.7. Women with infertility 4.8. Arthritis, chronic bronchitis and chronic obstructive pulmonary disease 4.9. Other diseases 4.10. Influence of fluorocarbon gases on lung phospholipid monolayers 5. Conclusions 6. Acknowledgement 7. References
1
ACCEPTED MANUSCRIPT
2
ABSTRACT Dynamic surface tensions and dilational visco-elasticity are easy accessible parameters of liquids. For human body liquids, such as urine, blood serum, amniotic fluid, gastric juice,
T
saliva and others, these parameters are very characteristic for the health status of people. In
IP
case of a disease the composition of certain liquids specifically changes and the measured
SC R
characteristics of dynamic surface tension of the dilational surface elasticity and viscosity reflect these changes in a clear way. Thus, this kind of physico-chemical measurements represent sensitive tools for evaluating the severity of a disease and can serve as control tool
NU
for the efficiency of applied therapies. The overview summarises the results of a successful work over about 25 years on this subject and gives specific insight into a number of diseases for which the diagnostics as well as the therapy control have been significantly improved by
MA
the application of physico-chemical experimental techniques.
D
Keywords: dynamic surface tension, drop profile analysis tensiometry, dilational visco-
AC
CE P
TE
elasticity, human biological liquids, blood serum, urine, amniotic fluid, gastric juice, saliva
ACCEPTED MANUSCRIPT
3
1. Introduction Interfaces play an important role in our daily life. The advanced knowledge achieved in surface science during the last decades led to various applications in many industries. For
T
instance, interfaces are of crucial importance in pharmacy, biotechnology and medicine. The
IP
biological liquids in a human body contain various surface active molecules which adsorb at
SC R
liquid interfaces and lead to changes in surface tension and in the interfacial dilational viscoelasticity. The earliest works on surface tension of biological liquids were performed as early as the beginning of the 20th century [1, 2]. Original studies and overviews on the surface
NU
tension of biologic liquids were published in [3-22]. In the papers before 1940 mainly blood serum was studied [3-6], while in more recent papers [7-20] various biological liquids had been the target of investigations. The results of our studies were summarized in a monograph
MA
[21] and a review article [22]. Measurements of surface and interfacial tension are extensively involved into the research and development of medicaments, and can be used routinely to
D
solve pharmaceutical problems and improve product quality [23]. Many biological and natural processes involve the understanding of wetting and
TE
interfacial tension as many biochemical reactions happen at interfaces. Human biological liquids such as urine, blood serum, amniotic fluid, gastric juice, saliva, expired air condensate,
CE P
fluids of the urinary and reproductive tracts, endocrine glands, cerebrospinal and alveolar lining fluid, contain smaller or larger amounts of surfactants, proteins and lipids. These low and high-molecular weight compounds are surface active and common materials in various
AC
tissues of the body which control surface tension of human interfaces. The physico-chemical processes taking place at these interfaces are of fundamental importance for various tissues and the vital function of human organs. As an example in medical science, the studies of lung surfactant systems are a field where surface tensiometry is intensively investigated. In medical research, measurements of surface tension are performed for patients with various pathological states of lung surfactants such as the adult respiratory distress syndrome, bronchial asthma, and pneumonia. In this particular field, a significant clinical progress was made in respect to the treatment of pathologies related to disorders in the lung surfactant system [24-26]. The role of fluorocarbon gases (FC) in medicine, for example, in therapies for the acute respiratory distress syndrome and other pulmonary disease were reviewed in [2734]. FC in the gas phase decreases the surface tension significantly, and the adsorption processes at the liquid/vapor interface are remarkably accelerated.
ACCEPTED MANUSCRIPT
4
Diseases change the composition of human biologic liquids and this causes changes the properties of the corresponding interfacial layers. Studies of surface tensiometry and dilational rheometry allow to conclude about the actual composition of interfacial layers and
T
can therefore assist the physician as a diagnostic tool for identifying the development of a
IP
disease or evaluating the efficiency of therapeutic treatments. Studies of dynamic surface
SC R
tension of biologic liquids taken from clinical patients and from healthy persons (for example stuff members) of Donetsk Medical University were initiated in 1993, and performed since then in the Physicochemical Laboratory of the Donetsk Institute of technical ecology. The results were found to be interesting and promising. Therefore, in 1999 the Physicochemical
NU
Laboratory was shifted to the Donetsk National Medical University, aiming at systematic studies of surface tension and dilation surface visco-elasticity of biologic liquids. It should be
MA
noted that, in line with the experimental studies of biological liquids, the staff of the laboratory closely cooperates with the companies LAUDA and SINTERFACE Technologies in order to develop and improve the instruments and measurement protocols [35-41].
D
Since the foundation of the laboratory more than 20000 analyses of various human
TE
biologic liquids were made; the results thus obtained were reported and discussed in more than 180 publications in physicochemical and medical periodicals. The samples of biological
CE P
liquids were taken from patients with various diseases, who were treated in a number of departments of the University clinics and other hospitals in Donetsk. These studies were performed with the participation of post-graduates and staff members of various departments
AC
such as of rheumatology, gastroenterology, physical therapy, obstetrics and gynaecology, anaesthesiology, oncology, stomatology, neonatology, dermatology, endocrinology, neurology, venereal diseases, departmental surgery, infectious diseases, hospital surgery, eye microsurgery. The laboratory also processed many samples of biologic liquids provided by medical universities in cities like Poltava, Kharkov and Lugansk. The results of dynamic surface tension studies of human biological liquids were summarised in a monograph [22]. In a recent book chapter published in 2009 problems concerning the dilational surface rheology of some biological liquids, mainly blood serum, urine, breath condensate and cerebrospinal liquid, with special reference to rheumatic, neurological, pulmonary and some other internal diseases [21]. The main results of our overview given here were reported in original papers and reviews [42-57]. Tensiometry and dilational surface rheology are used mainly in scientific studies, and for some pathologies (for example, rheumatology) also in the medical practice. To obtain a deeper insight into the results
ACCEPTED MANUSCRIPT
5
obtained with biologic liquids, theoretical models for mixed solutions of proteins and surfactants were developed which are capable for the description of surface tension, adsorption and dilational visco-elasticity under harmonic oscillations of the surface area [58-
T
64]. The validity of the models was verified using relevant model experiments [49].
IP
The present review discusses problems concerning the surface tension and dilational
SC R
rheology of biological liquids for various diseases. It was shown that surface tension and visco-elasticity parameters have a large potential for differential diagnosis and monitoring of the efficiency of therapies. These parameters for different diseases are capable of reflecting the general composition of surfactants, including pathological proteins and other compounds
NU
formed and accumulated during the development of a disease.
MA
2. Experimental methods
For the measurements of dynamic surface tension γ in the relevant short lifetime range, the maximum bubble pressure method (MBPM) is most appropriate for medical applications
D
involving biological liquids [65-71]. The main advantages of MBPM are the small sample
TE
volume (1 ml), and the wide range of surface lifetime (0.001 s to 30-50 s) [22, 35]. The dynamic surface tension data were measured using the tensiometers MPT1 or MPT2
CE P
(LAUDA, Germany), or more recently, the BPA-1P and BPA-1S (SINTERFACE Technologies, Germany) [35-37]. All these tensiometers allow direct measurements of the bubble surface lifetime within the time (t) range of 0.01 s (or less) up to 50 s. The results are
AC
called tensiograms (dependencies of vs t), from which the characteristic values are determined: at t = 0.01 s (1), t = 1 s (2), and the 3 value, obtained by the extrapolation of the dependence vs t−1/2 towards t→∞. Also the slope values of tensiometric curve plotted in the coordinates γ(t1/2) and γ(t-1/2) were calculated as 0 −(dγ/dt1/2)t →0 and 1 (dγ/dt−1/2)t →∞, respectively. A large number of tensiograms were presented in [22, 42-49]. Figure 1 shows (as an examples) three versions of the dependency of surface tension for blood serum taken from healthy a volunteer: 1a - vs t dependence; 1b - dependence on t1/2; and 1c - dependence on t−1/2. In Figs. 1b and 1с, dependencies on the effective adsorption time te=(3/7)tl are shown. The effective adsorption time te is shorter than the bubble life time tl and related to the expansion of the bubble surface during the experiment [35,36]. As we can see in Fig. 1b, the dynamic surface tension is linear when plotted over the effective time in the range 0.004 to 0.2 s, while in Fig. 1с it is linear in the effective time interval between 3 and 25 s. The presented plots over the effective time are linear in the given intervals for all studied
ACCEPTED MANUSCRIPT
6
biological liquids. The tangents shown in Fig. 1 are used to determine the slopes 0, 1, and
MA
NU
SC R
IP
T
the limiting surface tension value γ3.
AC
CE P
TE
D
.
7
TE
D
MA
NU
SC R
IP
T
ACCEPTED MANUSCRIPT
Fig. 1. Dependence of dynamic surface tension on the bubble lifetime (MPT2) for a healthy
CE P
person (a), the same data are plotted as dependencies on t1/2 (b) and t−1/2 (c).
The dependencies of surface tension on time mentioned above have certain physical
AC
meanings. For short times (t 0) a simple relation for multicomponent solution can be written as [22]:
d 2RT n c Di i dt1 2 i1 t0
(1)
Here R is the gas law constant, T is the absolute temperature, is the surface tension of the solution, D the diffusion coefficient, c the bulk concentrations, and the subscript ‘i’ refers to the components. The derivative on the left-hand side of this equation is the slope of the dependence of γ on t1/2. One more important relation is valid for long surface lifetimes. This equation, generalised for multicomponent system, reads [22]:
d RT n i2 dt1/ 2 2 Di i1 ci t
(2)
ACCEPTED MANUSCRIPT
8
where i is the adsorption value for ith surface active component. Here the derivative on the left-hand side of this equation is taken with respect to t-1/2, and is calculated in the limit t (that is, t-1/2 0). As for most surface active components the ratio i/ci is constant (the so
T
called Henry constant Ki i/ci), the sum in the right hand side of Eq. (2) is an approximate
IP
expression for the total adsorption of all mixture components with reference to their adsorption
SC R
activity Ki. The γ3 value calculated from the MВPМ data is the obtained by drop/bubble profile analysis tensiometry (PAT) at a surface age of 100 ± 20 s.
Surface tension experiments were also performed using the drop/bubble profile
NU
analysis tensiometry (PAT1 and PAT2 from SINTERFACE Technologies, Germany). In this study the configuration of pendant drops was used. The procedure of how the surface tension is calculated from the profile of a drop/bubble has been discussed in detail for example in [38-
MA
41]. A drop of the studied liquid was rapidly formed (during 1-2 s) at the tip of a Teflon capillary, and the dynamic surface tension was measured every 5-10 s in a time interval up to
D
1200-1800 s. The drop surface is automatically kept constant by the instrument’s software during the whole measurement. The equilibrium surface tension of human biologic liquids γ4
TE
was estimated by extrapolation of the tensiograms plotted as vs t−1/2 to t → ∞, and the slope
CE P
of the tensiograms was used as 2 (dγ/dt-1/2)t . Figure 2 illustrates example experiments obtained by using the РAТ2 tensiometer with stress deformations at 1200 s. The surface dilational visco-elasticity was studied also by the pendant drop method. After a time of 1200-1800 s, the drop was subjected to stress deformations, i.e. a rapid increase
AC
of the surface area by about 5-8 %, and the corresponding visco-elasticity modulus E of the surface layer was calculated as:
E
A A
(3)
where A is the initial surface area of the drop, γ is the initial surface tension jump caused by the stepwise increase of the drop surface area A. The variation in surface tension induced by the stress deformation γt obeys the exponential equation [22]:
t exp t / where t is the time expired since the deformation, is the corresponding relaxation time.
(4)
9
TE
D
MA
NU
SC R
IP
T
ACCEPTED MANUSCRIPT
CE P
Fig. 2. Dependence of dynamic surface tension on drop lifetime of cerebrospinal fluid (CSF) for patient with discirculatory encephalopathy () and patient from the reference group ().
AC
To study the dilational elasticity for harmonic oscillations, after stress experiments and having re-established the adsorption equilibrium the solution drop was subjected to surface oscillations at frequencies f between 0.005 Hz and 0.2 Hz, with oscillation amplitudes of 78% [21, 49]. For compression/expansion perturbations the surface dilational modulus E is defined by an expression similar to Eq. (3) but in the differential form:
E
d d ln A
(5)
The determined modulus E can be presented as a complex number E = Er + iEi, where the real part Er is the storage modulus or dilational elasticity, and the imaginary part Ei is the loss modulus corresponding to the dilational viscosity d = Ei/f is the angular frequency of the generated area variations). The results of experiments with harmonic oscillations were analysed using the Fourier transformation [21,49]:
ACCEPTED MANUSCRIPT E(i) A
F[ ] F[A]
10
(6)
The complex value E = Er + iEi is transformed into the expressions for the visco-
IP
,
arctanEi Er .
(7)
SC R
E Er2 Ei2
T
elasticity modulus |E| and phase angle :
For some diseases, the values of modulus and phase angle at fixed oscillation frequencies obtained for the respective fluids taken from healthy persons were compared with
NU
those obtained from sick persons. It was experimentally shown that for many biological liquids both components of the complex visco-elasticity modulus in the frequency range
Er a1 b1 lg , Ei a2 b2 lg
MA
studied depend linearly on the logarithm of the oscillation frequency f = /2 [11, 43]: (8)
D
The coefficients ai in these linear equations correspond to = 1 rad/s and hence
TE
become approximately equal to the real and imaginary parts of the visco-elasticity at the maximum studied frequency of 0.2 Hz. This data presentation is convenient to be used for a
CE P
statistical processing of experimental studies of blood serum rheology and other biological liquids, because all characteristics of the studied samples can be described by these four coefficients. Figure 3 demonstrates (as examples) the experimental dependencies of the real
AC
and imaginary components on the oscillation frequency, along with the straight lines calculated using Eqs. (8). Note that almost all experiments were performed with fresh biological fluids, selected from volunteers and patients in sterile clean test tubes. In some special cases, the liquids have been stored no more than 48 hours at 5ºС. For longer time in the fridge, the tensiometric characteristics differ from those of fresh liquids. The experimental results were analysed statistically using common programs with the definition of the mean value M, mean standard deviation , the dispersion mean or the standard error of the mean value m (m /n1/2, where n is the number of volunteers or ill persons), correlation coefficients (r) and the calculated reliability of the statistical (Student’s t-distribution) probability of a wrong conclusion p. The range of measured values within the limits M ± 3m for the normal statistical distribution involves almost all obtained results (with a probability of 99.7 %).
11
TE
D
MA
NU
SC R
IP
T
ACCEPTED MANUSCRIPT
CE P
Fig. 3. Dependence of real () and imaginary () visco-elasticity components for umbilical blood on the oscillation frequency; curves are calculated using Eq. (8).
AC
3. Surface characteristics of biologic liquids for healthy persons All biological liquids of the human organism contain surface active compounds, such as proteins, lipids, and molecules of other nature. These surfactants are characterized by a high adsorption activity at low bulk concentrations which significantly affects equilibrium interfacial properties and the kinetics of physicochemical processes taking place at interfaces. Table 1 summarises averaged values of dynamic surface tension parameters for serum and urine samples obtained from healthy persons that were between 15 to 65 years old. The γ1, γ2, γ3, λ0 and λ1 parameters were obtained by maximum bubble pressure tensiometry for 80 volunteers of both genders. Other parameters were obtained by the drop profile analysis method for 40 volunteers of different age. The data listed in Table 1 correspond to stress deformations of liquid drops.
ACCEPTED MANUSCRIPT
12
Table 1. Values of dynamic surface tension parameters for blood serum and urine obtained from healthy volunteers (M ± m). Parameter
Biological liquid Urine
T
Serum γ [mN/m]
70.0 ± 0.41
γ [mN/m]
67.7 ± 0.35
γ [mN/m]
60.0 ± 0.44
γ [mN/m]
45.7 ± 1.02
0 [mNm-1s-1/2]
4.5 0.74
[mN/m-1s1/2]
12.6 ± 0.54
13.5 ± 0.47
[mN/m-1s1/2]
194.6 ± 16.9
209.6 ± 25.4
E [mN/m]
32.2 ± 1.56
15.7 ± 1.36
τ, s
120.5 ± 5.8
258.4 ± 16.7
IP
71.5 ± 0.33
61.8 ± 0.36 44.5 ± 1.61 4.9 0.65
D
MA
NU
SC R
69.3 ± 0.21
TE
The results of tensiometric studies of serum and urine taken from healthy persons show that there are certain specific features in dynamic surface tensiograms, which are determined
CE P
by the age and gender of the volunteers. Table 2 summarises averaged tensiography parameters of these biological liquids with respect to the person’s gender. These results, obtained by the maximum bubble pressure method show some differences between the
AC
genders. In particular, the surface tension value γ3 obtained for females are higher than those for males. The slopes λ1 of the tensiograms are also different: for serum it is higher for males, while for urine it is higher for females. Relatively high γ3 values for female serum can in part be attributed to a lower content of some proteins, lipids and hydrocarbon components.
ACCEPTED MANUSCRIPT
13
Table 2. Surface tension parameters of blood serum and urine for healthy persons with respect to gender (M ± m). Parameter
Male
Female
Serum
γ1, mN/m
69.2 ± 0.50
70.8 ± 0.59
γ2, mN/m
67.1 ± 0.39
γ3, mN/m
59.3 ± 0.18
61.3 ± 0.65
0, mNm-1s-1/2
4.9 0.90
1, mNm-1s1/2
15.3 ± 0.61
8.2 ± 0.60
γ1, mN/m
71.6 ± 0.24
71.5 ± 0.21
IP
γ3, mN/m
MA
0, mNm-1s-1/2
69.2 ± 0.27
69.3 ± 0.32
56.6 ± 1.81
61.1 ± 0.36
5.5 0.70
5.2 0.65
11.7 ± 0.43
15.2 ± 0.54
D
1, mNm-1s1/2
SC R
γ2, mN/m
68.3 ± 0.54 3.6 0.70
NU
Urine
T
Biological liquid
TE
The person’s age also affects the dynamic surface tension of biologic liquids. These results have been described in detail elsewhere [21, 22]. The tensiographic parameters γ3 and
CE P
λ1 of serum and urine were analysed in detail with respect to the person’s age. It was explained in [21, 22] that with increasing age the surface tension of serum increases (by 5 mN/m with the increase of age from 20 to 60 years), while the surface tension of urine decreases by 4
AC
mN/m in the same age range. The value of 1 for urine tensiograms increases over the first 40 years of life and then remains virtually constant, the 1 value of serum gradually decreases with age. The fact that certain relations exist between various tensiometric parameters is quite expectable. We have found correlations between particular interfacial tensiometric parameters that are gender related. For example, in serum and urine samples from males the relation between γ2 and γ3 is stronger than in samples from females. Strong correlations exist between 1 values of urine and γ1 or γ2 values of serum for males, while for females, such correlations were generally not detected. However, the correlation between the dynamic surface tension parameters for serum in the short and medium surface lifetime range (γ1 or γ2), and the γ3 for urine becomes stronger. For both genders, the 1 values of serum are strongly correlated with the γ1 value of urine. The tensiometry and visco-elasticity parameters of other biologic liquids for healthy volunteers are listed in Table 3. The number of volunteers in the group for each liquid was 40 to 140 persons. The dispersion of values shown in Table 3 for different liquids is roughly the
ACCEPTED MANUSCRIPT
14
same: 0.5-1.5% for all surface tension parameters i, 5-10% for all slopes i, about 5% for E and . It is seen that the surface activity values of the liquids are essentially different from each other due to differences in the chemical composition of their surface-active components.
T
Among all liquids listed in Table 3, the expired air condensate exhibits the lowest surface
IP
activity (maximum 4 value), while the highest surface activity is characteristic for the
SC R
duodenal fluid. The duodenal glands produce a liquid which contains about 2% proteins, nucleic acids and lipids, and more than 3% of mucin. The mucins possess a specific amino acid composition, with high contents of serine, threonine and proline, and also carbohydrates;
NU
all these substances exhibit surface activity.
The dynamic surface tension of serum and amniotic liquid obtained from 52 pregnant
MA
women was studied at various gestation stages. For 10 women, two and more analyses were performed. With increase of the gestation period, a gradual decrease in both dynamic and equilibrium surface tension of serum occurs, while a sharp increase of 1 is observed. It should
D
be noted that up to the 20th week of gestation, the surface tension values in the short and
TE
medium time range are quite similar to those characteristic for the reference group of nonpregnant women of corresponding age. The correlation coefficients for interfacial
CE P
tensiometric parameters of serum and amniotic liquid depend on the gestation period. This may indicate near parturition, thus being of certain practical interest. Table 3. Average values of surface tension parameters for various biologic liquids obtained
AC
from healthy volunteers (the total of 360 persons). The standard deviation of all tensiometric parameters was less than ±1% and for rheometric parameters less than ±4%. γ1,
γ2,
γ3,
γ4,
2 ,
mN/m
mN/m
mN/m
mN/m
mNm1s1/2 mN/m
s
Cerebrospinal fluid
71.7
66.6
60.4
47.3
286
29.7
287
Oral liquid
71.9
68.7
58.9
44.9
166
30.6
186
Breath condensate
72.2
69.7
61.4
53.2
309.4
25.8
461
Hepatic bile
72.0
65.2
54.1
42.6
89.1
11.7
94.0
Duodenal contents
69.3
60.8
51.9
38.6
126.7
28.4
219.8
Liquids
E,
τ,
As another example, in [50] data of oral liquid were performed with 142 volunteers in the age between 7 and 63 years. The gender of 66 patients was male and 76 was female. Non
ACCEPTED MANUSCRIPT
15
of the volunteers suffered from any acute inflammation in the oral cavity or chronic somatic diseases. The average values of measured tensiometric and rheological parameters are summarized in Table 3. Some of the obtained tensiometric parameters show a statistically
T
reliable relation to the age of the patients’. This is true for the equilibrium surface tension γ4
IP
(M±ε=48.0±2.3 mN/m) which is highest for the age of 5–9 years, while for the age group of
SC R
10–15 years this value is already decreased (46.3±2.6 mN/m). In groups of higher age this trend continues, i.e. for the group of 40–55 years the respective value is 42.3±3.5 mN/m. Finally, for patients of 55 years and older this value increases again to 45.7±2.9 mN/m. Differences are observed in the tensiometric parameters of saliva, which are most pronounced
NU
in the age of 7–15 years. As can be seen, the standard deviation ε is used for the analysis, and therefore the average values of γ4, calculated as M ± ε, overlap for different age groups. If we
MA
calculate the standard error of the mean value m, and determine the mean value as M ± m, then the overlap disappears, since m is 3-5 times smaller than ε. Another study of salivary gland secretion was performed with 14 healthy volunteers,
D
having an age between 19 and 25 years. For the collection of the secretion of the parotid gland,
TE
a special device was developed, while the secretion of sub-mandibular and sub-lingual glands was taken from the sub-lingual region using a micropipette. Overall, the tensiometric data of
CE P
the secretions of the greater salivary glands agree with those of the oral liquid as a whole. Some of the results are summarised in Table 4.
AC
Table 4. Tensiometric characteristics of secretions of parotid (P), sub-mandibular (SM) and sub-lingual (SL) glands (M±m); according to [50] Parameters
Oral liquid
Secretion of salivary glands P
SM and SL
γ4 , mN/m
44.2±0.6
45.3±1.8
43.4±1.3
λ2 , mN·m –1s 1/2
178±7
191±11
223±12
Е, mN/m
33.3±1.5
23.3±1.5
42.8±3.8
τ,s
215±7
202±6
302±23
As one can see the mixed secretion of sub-mandibular and sub-lingual glands show a larger visco-elasticity E (about 30% higher) than the oral liquid and it is about twice as high as the corresponding value for the secretion of the parotid salivary gland. The mixed secretion of sub-mandibular and sub-lingual glands has also a maximum in the surface tension relaxation time (τ), and there is also a difference in the tensiograms’ slope. The average slope
ACCEPTED MANUSCRIPT
16
for the oral liquid (a mixture of the secretions released by all salivary glands) is almost equal to the value of the parotid gland secretion, and about 30% lower than the value measured for saliva excreted by the sub-mandibular and sub-lingual glands. The observed differences for
T
these secretions in the tensiometric data should most probably be ascribed to the peculiarities
IP
of the biochemical composition.
SC R
4. Influence of diseases on surface characteristics of biologic liquids This section summarises the results of tensiometric and surface rheologic studies of various biologic liquids taken from the patients suffering from different diseases; the studies
NU
were performed in the Physicochemical Laboratory of the Donetsk National Medical University. Some results were reported earlier in [21,22,42-57,72-74] and (for some diseases)
MA
discussed in details in the review [18]. Also data published by other authors [7-17, 75-89] concerning the tensiometry of biologic liquids are considered in the analysis presented here. However, it should be noted that these studies do not present any systematic tensiometric and
TE
D
surface rheological studies to match those made in our laboratory. 4.1. Oncology
CE P
For patients suffering from cancer at various localisations, increased concentrations of γ-globulin, 2-microglobulin, 2-glycoprotein, ferritin, immune complexes, T-globulin, Creactive protein, ferritin, haptoglobin and α-antitrypsin in blood were detected. The
AC
concentration of albumin, pre-albumin and α2NS-glycoprotein correlate inversely with the extent of tumor invasion. Usually a decreased glucose level in blood is observed for extended tumour processes. The hypoglycaemic stress acts as a factor which initiates an increased secretion of the somatotrophic hormone. These factors change the surface tension parameters and help to evaluate cancerous phenotype, cell metastasis and therapeutic efficacy. Fatty acids increase in blood due to an increased cell death. The presence of malignant tumour is accompanied by the increase in the amount of serum mucoids and sialic acids. Therefore, the existence of malignant tumour of any localisation leads to certain distortions of the homeostasis. These changes take place in the organism and affect the biochemical composition of blood, generally leading to the decrease of surface tension at medium and high surface lifetime. The application of radiotherapy results in a normalisation of the state of the antioxidant system and of the phospholipid levels: these characteristics become closer to those common for patients at early stages of tumour processes. In a number of cases the
ACCEPTED MANUSCRIPT
17
radiotherapeutic treatment is accompanied with the development of certain inflammatory complications in the intestine and urinary tracts (rectites, colites, cystites, urethrites with various degrees of severity). As the clinical symptoms of the inflammation process are the
IP
T
final consequences of quite prolonged alteration (damaging) processes taking place in the tissue, one can expect to detect the inflammation products in the serum long before the
SC R
inflammation becomes clinically evident. The dynamic interfacial tensiometry, being quite sensitive to such changes, enables one to predict the development of complications caused by radiotherapy even at early stages of the treatment. Comprehensive prophylactic
NU
actions aimed at the prevention of complications, if taken promptly, would be of much help in the treatment of female reproductive organs’ neoplasm.
MA
The dynamic surface tension of blood serum for 46 patients suffering from malignant neoplasm of corpus uteri (7) and cervix uteri (39) was studied. The serum taken
D
from patients was studied with regard to the course of the disease: before the medical
TE
treatment started, i.e. on admission of the patient, during the treatment (radiotherapy) and after the treatment. Therefore, the studies included three stages: Stage I, prior to
CE P
medical treatment; Stage II, during the treatment; and Stage III, after the treatment. The surface tension of serum was studied using the two experimental methods described above. Among 46 patients studied, for 14 cases (30.5%) certain complications (colitis, rectitis and
AC
cystitis in various forms) developed. The variations in the mean values of tensiometric parameters during the radiotherapy process for the two patient groups are listed in Table 5 [52,53,72,73].
ACCEPTED MANUSCRIPT
18
Table 5. Mean values of the serum dynamic interface parameters for malignant neoplasm of cervix and corpus uteri in the process of combined radiotherapy, differentiated with respect to the presence or absence of inflammations caused by irradiation (M±ε). Stage I
Stage II
persons
With
SC R
Without
Stage III
T
Healthy
IP
Parameters
Without
With
inflam.
inflam.
inflam.
γ1 (mN/m)
70.82.8
71.32.0
70.62.8
70.42.7
70.72.4
70.43.0
γ2 (mN/m)
68.33.0
65.53.5
65.04.0
63.44.3
66.33.2
64.44.0
γ3 (mN/m)
61.33.4
52.8 4.2 54.84.4
52.04.6
58.14.0
56.04.8
1[(mN/m)s1/2]
8.23.0
17.65.5
NU
inflam.
14.15.2
10.74.3
12.24.2
MA
12.94.0
D
It is seen that a significant decrease of the γ2 and especially of γ3 (by almost 10 mN/m
TE
lower) values in the group of patients with malignant neoplasm. as compared to the values for normal females. In the group of patients with complications the increase of γ2 and γ3 was not
CE P
very pronounced. Moreover, at the intermediate stage of the treatment the γ3 value even becomes somewhat lower as compared to the value observed before the treatment. The λ1 variation during the treatment is also determined by complications, which, if developed, result in less a pronounced decrease of λ1 with respect to the initial level. If the radiotherapy is not
AC
accompanied by inflammatory reactions, then a significant decrease of this parameter is observed, which approaches the reference values for healthy females at the end of the radiotherapy. At the end of a radiotherapy treatment the differences between tensiometric parameters of serum obtained from patients and healthy females become essentially (by 6070%) less significant. As mentioned above, the use of the standard error of the mean value m in contrast to the variance ε excludes overlapping of the compared parameters. The most pronounced differences between the studied patients’ groups were found with respect to the dynamics of the tensiographic parameters measured for each particular patient. This means that the differences between the corresponding parameters (3) measured during the therapy and before the therapy were used rather than the absolute values of the parameters. More specifically, these differences were obtained by subtracting the parameter value before the treatment from that measured after Stage II or Stage III for each particular patient, respectively. The results thus obtained were averaged over the two groups studied, i.e.
ACCEPTED MANUSCRIPT
19
with and without any complications. In Figs. 4 the distribution curves after Stage II are plotted against the number of cases studied: it is seen that the distribution areas of γ3 values are
CE P
TE
D
MA
NU
SC R
IP
T
overlapped in ca. 15 % of cases.
AC
Fig.4. Probability distribution curve for γ3 values after stage II with the presence (dashed curve) and absence (solid curve) of inflammatory complications. Similar values were obtained also for γ2 (10 % cases) and ∆λ1 while for this overlap is observed in approximately 20% of all cases. Therefore, from the analysis of the sign of the variation of ∆γ2 and ∆γ3 only, one can predict, for 85% of all cases, possible complications during the radiotherapy. It should be noted that these variations of the tensiometric parameters are detectable prior to the moment when any clinical evidence becomes evident; this enables one to start the complication-preventing therapy at an early stage of the radiotherapeutic treatment. As the tensiometric techniques are relatively simple, these methods can be proposed for the clinical practice.
ACCEPTED MANUSCRIPT
20
4.2. Oral liquid, effect of carious lesion of teeth The study was performed with 23 children of age 4–6 with milk occlusion, divided into two groups. The caries free group was composed of 6 girls and 5 boys; the other 12
T
examined children (6 girls and 6 boys) constituted the caries-active group. The comparison
IP
between the tensiometric parameters of oral liquid samples taken from caries-free and caries-
SC R
active children has revealed significant differences between the corresponding values of γ1, γ3 and λ1. The surface tension γ3 of oral liquid for caries-active children was found to be 3 mN/m lower than that for caries-free children, while λ1 value was by 29% higher. This indicates that
NU
the amount of surfactants (or their surface activity) in the oral liquid of caries-active children is higher than that of caries-free children. The tensiometric characteristics of the oral liquid of caries-free children are found within the limits indicated in Table 1 for healthy volunteers.
MA
The comparison of biochemical parameters of oral liquid (the contents of total protein, calcium, phosphorus and triglycerides) did not exhibit any statistically reliable differences
D
between the groups of caries-active and caries-free children. To summarise at this point, essential differences between the tensiometric parameters
TE
of oral liquid taken from caries-free children were found as compared with those of cariesactive children. This indicates the promising prospects of dynamic interfacial tensiometry of
CE P
saliva as applied in dentistry for the development of new diagnostic criteria and approaches for the estimation of caries-resistant tooth enamel. These studies also help understand the
AC
physico-chemical nature of caries. 4.3. Neurosyphilis
Neurosyphilis (NS) is the lesion of the nervous system caused by a syphilitic infection. It results in specific changes of the liquor cerebrospinalis (cerebrospinal fluid, CSF). Due to the syphilitic process in the nervous systems its diagnostics can be complicated. Traditionally, the initial diagnostics of NS is mainly based serological studies of blood and CSF, and the probability of a correct diagnosis is only between 30 and 70 %. Hence, new and more informative methods are required for its diagnostics. The results we want to present here were obtained in [51] in a study with 75 patients suffering from various forms of NS and syphilis. The first group of 22 patients had clinical (manifested) forms of NS with a main diagnosis of an early cerebral meningovascular syphilis (14 patients). The second group of 23 patients suffered from latent (asymptomatic) NS showing no neurologic symptoms but had a positive syphilitic tests and changes in the clinical analysis of CSF. In a third group the 15 patients had syphilis accompanied by a neurologic
ACCEPTED MANUSCRIPT
21
disease like discirculatory or toxic encephalopathy. In a reference group the 15 patients had syphilis without any additional neurologic diseases. The results of dilational rheology studies are summarized in Table 6.
T
It is seen that the value of the dilational stress modulus E for the patients from all three
IP
screened groups is lower as compared with the value (29.7 ± 1.5 mN/m) for the reference
SC R
group. Thus, the observed decrease of the value of E indicates a pathology of the nervous system.
Table 6. Surface rheological parameters of the CSF (M ± m) for different groups of patients;
NU
according to [51] First, n = 22
Second, n = 23
Third, n = 15
Reference, n = 15
E, mN/m
24.7±1.2
25.4±1.1
21.1±1.1
29.7±1.5
τ, s
261.1±16.1
253.0±12.9
238.2±16.6
286.8±15.3
a1, mN/m
34.6±1.7
35.9±1.6
31.2±1.5
41.3±1.7
b1, mN/m
8.6±0.5
8.2±0.6
7.4±0.8
9.8±0.9
a2, mN/m
6.7±0.35
6.5±0.4
6.3±0.4
8.2±0.7
b2, mN/m
-0.13±0.14
0.05±0.13
0.09±0.20
0.2±0.25
CE P
TE
D
MA
Parameter
The lowest E values (21.1 ± 1.1 mN/m) were observed for patients in group three. Compared with the reference group of patients, the parameters for the three groups a1, a2 and
AC
b1 were essentially different (p < 0.1). For the groups one and three, for the parameter a1 (the elasticity at a frequency of 1 rad/s) the largest differences (p < 0.05) were observed. Note, there is a strong correlation (r = 0.9) between a1 and E for all groups, which however is expected, because these parameters refer to different methods of the dilational surface rheology studies. The correlations discussed here reveal the applicability of dilational rheology parameters for the diagnostics of neurosyphilis, and the differential diagnostics of accompanied diseases. Value of a1 larger than 40 mN/m undoubtedly indicate the absence of pathologies of the nervous system for the patients with syphilis. For value lower than 32 mN/m, we can conclude that the syphilis is accompanied by a neurologic disease, mainly by a discirculatory or toxic encephalopathy.
ACCEPTED MANUSCRIPT
22
4.4. Congenital pneumonia of premature newborns Common diagnostic methods of congenital pneumonia are based on X-ray examinations. X-ray technique allows detecting the main symptom for most new-borns with
T
congenital pneumonia only rather late. Thus, new methods for an early recognition of
IP
congenital pneumonia is an urgent need in neonatology. The umbilical blood and expired air
SC R
condensate of 60 premature new-borns in the gestational age 22-36 weeks suffering from a respiratory distress at birth were studied. The 60 patients were divided into three equal sized groups. The first group consisted of patients with congenital pneumonia (CGP); the second of
NU
patients with a respiratory distress syndrome (RDS), and the third consisted of patients with both pathologies. Ten healthy breast-fed premature new-borns (gestational age of 35-36 weeks) have been taken as reference group. The surface rheological parameters of the
MA
umbilical blood for all studied groups did not show differences to the reference group. This can probably be explained by the fact that the scattering of data is rather large (cf. Table 6). However, strong differences are observed for the phase angle φ obtained from Eq. (5) at the
D
highest frequency. The respective φ values at the frequency of 1 rad/s = 0.16 Hz for the four
TE
groups are: reference group (19.6±1.4)°; CGP, (22.1±0.7)°; RDS, (17.3±1.0)°; and CGP + RDS, (20.6±0.7)°. One can see that the values for the two groups CGP and RDS are essentially
CE P
different from those for the reference group (with a reliability level of p < 0.1), i.e. for the CGP group the phase angle is reliably higher than for the reference group, while for the RDS group it is reliably lower.
AC
However, the rheological parameters of the expired air condensate for the premature new-borns (CGP, RDS, CGP + RDS) with respiratory impairments are the same (within measurement errors) as those for the reference group, and no remarkable dependence of the phase angle value was observed. At low oscillation frequencies the imaginary part of the visco-ealsticity is higher while the real part is lower as compared with the values at higher frequencies. Hence, the phase angle becomes much higher with decreasing oscillation frequency. The phase angle φ for the CGP and RDS groups at a frequency of 0.016 Hz was close to the values for the reference group (12.0±1.0)°, while for the group of CGP + RDS it was (13.8±0.6)°. Therefore, studies of the surface dilational rheology of expired air condensate can support the diagnostics of respiratory impairments of premature new-borns. Note, some studies showed very low dynamic surface tensions of the umbilical blood of premature new-borns suffering from severe respiratory impairments and hence requiring artificial pulmonary ventilation. The mentioned results are shown in Fig. 5.
23
TE
D
MA
NU
SC R
IP
T
ACCEPTED MANUSCRIPT
CE P
Fig. 5. Dependence of the dynamic surface tension of the umbilical blood taken during the first day of life; curve 1 () - premature new-born from the reference group; curves 2 () and 3 () - premature new-borns with congenital pneumonia.
AC
For all new-borns the gestational age was small and the weight at birth was less than 2 kg. Moreover, a congenital pneumonia was observed and also the pregnancies of all mothers were abnormal.
4.5. Chronic recurrent pancreatitis The chronic recurrent pancreatitis (CRP) leads to changes in the contents of surface active substances (proteins, lipids, electrolytes, hormones) in the biologic liquids; this in turn results in changes of the tensiometric parameters of blood, urine and pancreatic secretion [74]. To study these effects, 72 CRP patients (34 males and 38 females, age 20 to 63) in an acute stage were screened, along with 30 healthy volunteers (13 males and 17 females, age 20 to 60). In Table 7 the data obtained by interfacial tensiometry and surface rheology of blood, urine and duodenal liquid from CRP patients are compared with those obtained from healthy
ACCEPTED MANUSCRIPT
24
persons. The dispersion of values shown was: 1.0-1.5% for the surface tension; 7-10% for all parameters; about 4% for Е and τ. All blood tensiometric and rheology values (except 2) for CRP patients exhibit reliable difference from corresponding values for healthy persons; in
T
particular, for sick persons the γ1, λ1, λ2 and τ values are higher, and γ3, γ4 and Е values are
IP
lower. For urine and duodenal liquid the disease leads to a significant decrease of γ2, γ3 and
SC R
γ4. Thus, the results of the correlation analysis indicate the possibility to apply interfacial tensiometry and rheology for the estimation of the CRP progress and the efficiency of applied therapy: the trends of the parameters to the values characteristic for sick persons evidences the exacerbation of the disease, while the changes towards the normal values of the parameters
NU
indicate the efficiency of curation and future remission.
MA
Table 7. Tensiometric and surface rheological parameters of blood, urine and duodenal liquids for CRP patients and healthy volunteers Fluid n
γ1,
γ2,
mN/m
mN/m
γ4,
λ1,
λ2,
mN/m
mN/m
(mN/m)·s
(mN/m)·s
1/2
Е, 1/2
τ, s
mN/m
D
parameters
γ3,
TE
Blood 72
74.38
68.40
57.18
41.22
18.23
246.28
28.65
112.8
Sick
30
70.00
67.70
60.00
45.50
12.60
189.20
32.80
103.7
Urine Healthy
72
69.80
63.15
57.24
50.86
15.87
129.52
29.62
112.6
30
71.50
69.40
61.80
51.60
13.40
111.00
30.30
110.2
AC
Sick
CE P
Healthy
Duodenal liquid Healthy
72
61.16
53.26
46.36
31.72
10.62
98.63
38.12
262.1
Sick
30
69.32
60.82
51.87
38.62
15.40
126.70
28.40
219.8
4.6. Acute renal failure Tensiometric and surface rheological parameters of blood serum for acute renal failure (ARF) patients were shown to differ significantly from the values for healthy persons. These parameters for ARF patients depend on the clinical progression of the disease. For patients with a severe disease form in the pre-dialysis period these differences as compared to the reference group are illustrated in Table 8. The essential decrease of γ1, γ2, γ3, λ2 and E, and the increase of are evident; this indicates that the development of a severe ARF form results either in the increase of the concentration or the enhancement of the adsorption properties of
ACCEPTED MANUSCRIPT
25
surfactants in the blood serum. Table 8. Tensiometric and rheologic parameters of blood serum for ARF patients immediately
T
before a dialysis treatment (M±m) compared with a reference group. ARF persons
(n=20)
(n=68)
γ1, mN/m
72.94±0.34
71.66±0.23
γ2, mN/m
68.35±0.33
γ3, mN/m
58.72±0.49
γ4, mN/m
45.57±0.66
λ1, mN/m-1s1/2
17.12±0.96
λ2, mN/m-1s1/2
193.68±15.45
Е, mN/m
29.54±1.23
18.26±0.90
τ, s
110.18±8.29
138.92±10.21
SC R
IP
Reference group
67.41±0.23
NU
54.81±0.48 46.07±0.42 21.31±1.05 122.46±6.80
D
MA
Parameter
TE
To specify the influence of clinical factors and the homeostasis parameters on the physicochemical properties of blood serum, the correlation analysis was employed. It was
CE P
shown that a correlation exists between the tensiometric and rheological values of blood serum with the creatinine level, leukocytal intoxication index, erythrocyte sedimentation rate, platelets concentration, fibrinogen level, and the estimated severity of the patient’s condition.
AC
These multiple correlations demonstrate that the tensiometric and rheometric parameters are useful for a comprehensive estimation of the clinical progress of ARF. The improvement of the clinical state during medical treatment is also accompanied by significant changes (increase) of certain tensiometric and rheometric parameters as compared with initial (pre-treatment) values for patients with ARF, in particular λ2 from 121.6±10.28 to 168.8±12.4 mN/m−1s1/2, Е from 19.0±1.17 to 25.6±2.6 mN/m. This was found also for patients with a multiple organ failure during the positive dynamics of the disease progress: λ2 from 121.9±9.2 to 167.2±19.8 mN/m−1s1/2 and Е from 17.3±1.7 to 25.1±1.5 mN/m. Also, in these groups of patients the 3 value increases and becomes indistinguishable from its value for the reference group. 4.7. Women with infertility The tension and rheology parameters of blood and oral liquid of women with infertility and thyroiditis were studied for 40 women with infertility for which the assisted reproductive
ACCEPTED MANUSCRIPT
26
medical treatment was unnecessary. Two groups of patients were studied: (1) 20 women with the Hashimoto’s thyroiditis, and (2) 20 women without any thyroid pathology. No changes have been found in tension and rheology parameters of blood for women with infertility and
T
autoimmune thyroiditis compared to women with infertility and normal function of the
IP
thyroid. However, the parameters of oral liquid for the two groups of women were different
SC R
(see Table 9).
Table 9. Tensiometric and surface rheological parameters of oral liquid (comparison between groups 1 and 2, M±m). Group 1
Е, mN/m
43.0±2.8
39.6±3.8
τ. s
174.2±8.3
175.9±6.1
γ4. mN/m
47.4±0.52
43.9±0.55
λ2. mN/m–1·s1/2
108.6±8.5
132.8±4.4
Group 2
D
MA
NU
Parameter
TE
It is seen that the parameter γ4 becomes increased and λ2 is decreased for women with infertility and autoimmune thyroiditis, as compared to women with thyroiditis and a normal
CE P
thyroid function. The increase of γ4 and strong negative correlation with the level of lymphocytes in blood could be used as an additional marker for the estimation of the state of cellular immunity for women with infertility and autoimmune thyroiditis. Therefore, the
AC
analysis of oral liquid taken from women with infertility could be used for the early detection of autoimmune processes in thyroid. 4.8. Arthritis, chronic bronchitis and chronic obstructive pulmonary disease For rheumatoid arthritis, the rheological characteristics of breath condensate (stress experiment) were found to depend on the patients’ gender and age, and the extent of the pathologic process activity. With the increase of the disease duration, a decrease of both the pH and visco-elastic modulus E of the breath condensate was observed. The corresponding properties depend on the presence and extent of the respiratory pathology: in absence of pheumopathy, E = 29.8±1.7 mN/m and = 486±60 s; otherwise E = 21.3±1.8 mN/m and = 667±145 s. The catadrome of the rheumatoid pheumopathy is accompanied by a decrease of the visco-elastic modulus of the breath condensate. A value for E < 15 mN/m appears to be indicative of severe rheumatoid pheumopathy. For patients with nephropathy the observed values of E and of urine are lower as compared with other patients suffering from rheumatoid
ACCEPTED MANUSCRIPT
27
arthritis. In absence of a nephropathy we found E = 26.9±0.8 mN/m and = 290±12.2 s; while with nephropathy we obtained E = 24.3±0.8 mN/m and = 238±9.8 s. The modulus E of urine correlates inversely with the duration of a disease, and directly with the degree of the activity
T
of the pathologic process. A correlation exists between the extent of kidney injury and the
IP
physico-chemical parameters of urine. In particular, the E and values correlate inversely
SC R
with the severity of the nephropathy, which is of high practical significance. For the juvenile rheumatoid arthritis, a remarkable increase of the plasma viscosity (PV) as compared with that of healthy children was observed. Also, the dilational surface
NU
stress experiments indicate a significant decrease of the E and values of blood serum, as one can see in Table 10. It is important to note that the equilibrium surface tension of blood serum is almost the same for sick and healthy children (45.7±0.9 and 45.9±1.0 mN/m, respectively).
MA
This fact reveals essentially higher sensitivity of the surface rheological methods used here to study the interfacial characteristics of human biologic liquids.
D
Table 10. Rheological characteristics of blood serum for patients with juvenile rheumatoid
TE
arthritis and healthy children for compare (M±m). Parameters
Sick
Healthy
PV, mPa·s
2.1±0.08
1.6±0.03
E, mN/m
26.5±0.6
33.1±1.5
, s
104.1±3.4
127.4±4.1
CE P AC
Examined groups
The univariate dispersion and regression analysis demonstrates a direct correlation between the activity of juvenile rheumatoid arthritis and the parameters of plasma viscosity and relaxation time . The concentration of serum fibrinogen is positively correlated with the PV and negatively correlated with the E values. For patients with reactive arthritis, an inverse correlation was found between the dynamic surface tension of blood serum and the erythrocytes’ aggregation index. It was reliably shown that the E and decrease with the increase in plasma viscosity. The modulus E depends on the degree to which the tendovaginitis or autonomic imbalances are expressed. A direct correlation was found between E and the degree of angioneurosis. The extent of ophtalmopathy correlates inversely with E and , and also with the blood serum equilibrium surface tension. The development of a pathology of the aortic valve leads to changes in the
ACCEPTED MANUSCRIPT
28
blood serum equilibrium surface tension 4. From the obtained results, it was concluded that for the reactive arthritis any values 4 > 50 mN/m indicate an unfavourable affect of the aortic valve. For patients with reactive arthritis a nephropathy results in increasing dynamic surface
T
tensions and E modules of urine, accompanied by decreased values for 4 and . The
IP
rheological properties of urine do not depend on the patients’ age and total activity of the
SC R
disease, while at the same time these parameters are determined by the duration of the disease. The development of a nephric pathology results in decreased values of 1, 3 and 4 and simultaneously increases E, as shown in Table 11.
NU
Table 11. Properties of urine for patients with reactive arthritis and kidney damage without nephropathy (M±m).
Examined groups
MA
Parameters
Nephropathy present
γ1, mN/m
72.6±0.30
70.7±0.38
γ3, mN/m
62.0±0.58
59.0±0.53
49.8±0.40
46.3±0.46
16.3±0.43
20.0±0.53
160±5.5
148±3.9
, s
CE P
E, mN/m
TE
γ4, mN/m
D
Nephropathy absent
The values of γ1 and γ4 correlate inversely with the total proteinuria, leukocytouria and
AC
fibronectynuria levels. Also, correlations exist for the albumin concentration in the urea and 3 and E, of the leukocyte concentration with 3, and fibronectin concentration with . For patients with chronic bronchitis and a chronic obstructive pulmonary disease the rheological properties of breath condensate are determined by the character of the respiratory moisture excretion. For these two diseases, the rate and extent of respiratory moisture excretion affect the parameters E and . The patients’ gender and age significantly affect the rheological properties of breath condensate. The development of a chronic obstructive pulmonary disease is accompanied by a significant increase of E. The character of bronchial obstruction affects the values of E and , while a bronchial restriction influences only the E value of the respiratory fluid. For patients with a chronic obstructive pulmonary disease the values of 1, E and of blood serum are significantly higher than the values typical for healthy persons. For patients with chronic bronchitis, of the breath condensate becomes lower, for a chronic obstructive pulmonary disease this value becomes higher, and if both pathologies are
ACCEPTED MANUSCRIPT
29
present, an increase in E is observed. From the analysis of the data it can be concluded that for the breath condensate values of E > 40 mN/m for chronic bronchitis, and E > 50 mN/m for a chronic obstructive pulmonary disease accompanied by coronary heart disease, are
IP
T
indicative of a negative prognosis for the development of the disease. 4.9. Other diseases
SC R
In this part we will shortly review the results of the following diseases: gout, lupus erythematosus. scleroderma systematic, purpura rheumatic, chronic rheumatic heart disease,
periodontitis and microcholelithiasis.
NU
chronic pyelonephritis, diabetic nephropathy, peptic gastroduodenal ulcer, chronic For gout, there is a significant decrease of E and of the blood serum: the relaxation
MA
time decreases for 85% of the patients, while the elasticity modulus decreases for 79% of the patients. The dynamic surface tension of blood serum depends on the development of a metabolic syndrome. The increase of 1 and 3 of the blood serum for patients with chronic
D
gouty arthritis was detected in 87% and 53% of cases, respectively. Decreased values of λ 1
TE
for blood serum were found for 73% of screened patients with an intermittent form of the articular syndrome, while for the chronic form this value becomes 97%. The degree of severity
CE P
of the articular syndrome is closely related to the surface tension 1 of the blood serum: its decrease indicates a most probable unfavourable prognosis of the development of gouty arthritis. For patients with gout, the dynamic surface tension of urine and the relaxation time
AC
is lower for sick than for healthy persons. With the development of renal insufficiency we observed a significant decrease of the dynamic surface tensions of the blood serum and urine, which was especially significant in the short time range. To summarise, gout leads to a decrease of the parameters E and for the blood serum. Also changes in the physico-chemical characteristics of breath condensate (decrease of 4 and ) were observed, caused by the patients’ age and the duration of the disease. For patients with a gouty nephropathy an increase of the dynamic surface tension and a decrease of the relaxation time for urine were observed. Systemic lupus erythematosus leads to a decrease of pH of the breath condensate and to a significant (by more than a factor of two) decrease of from 462.6±25.5 mN/m to 214.8±10.6 mN/m. While traditional methods are able to detect pulmonary changes in 39% of the cases, decrease values of 4 and for the breath condensate were found for 80% and 97% of patients, respectively. The systemic lupus erythematosus is characterized by increased values of the surface tension and λ1. When the peripheral nervous system is affected, also the
ACCEPTED MANUSCRIPT
30
dynamic surface tension γ3 of blood serum is lowered. It was shown that the values of 3 > 60 mN/m are indicative of damages to the central nervous system, and values 3 < 55 mN/m reflect the presence of peripheral nervous disorders. The development of
T
neurolupus is accompanied by increasing values of E and of the blood serum. The anti-
IP
phospholipid syndrome leads to significantly increased values of E and for blood serum and
SC R
1 for the cerebrospinal liquid. For the lupous nephritis, an increase of E by a factor of two, and a significant increase of the surface tension of urine in the range of short and intermediate surface ages were observed, while the γ3 decreased (cf. see Table 12). The nephrotic syndrome
NU
is related to the 1, while the renal function has its influence on the majority of physicochemical parameters, including the dynamic surface tension, E and .
MA
Table 12. Physico-chemical parameters of urine for patients with lupous nephritis and healthy persons (M±m).
Examined groups Healthy
γ1, mN/m
71.9±0.18
69.5±0.33
γ2, mN/m
67.9±0.28
66.3±0.56
γ3, mN/m
49.1±0.59
51.6±0.66
Е, mN/m
31.3±1.70
16.0±0.58
CE P
D
Sick
TE
Parameters
AC
The rheological parameters of urine exhibit unambiguous reactions to the deteriorating renal function: relaxation times < 170 s indicate a negative prognosis of the lupous nephritis development. Our statistical analysis has revealed that values E > 40 mN/m and < 170 s correspond to a mesangium capillary glomerulonephritis, while E < 25 mN/m and > 240 s are characteristic for a mesangium proliferative glomerulonephritis. The dermatic lupus erythematosus leads to a significant decrease of the E and parameters for blood serum as compared to those of healthy persons. The severity of each type of skin pathology affects the values of 3, 4 and E. The results indicate that values of 4 < 40 mN/m and E < 25 mN/m are indicative of a negative prognosis with respect to the course of telangiectasises for patients with dermatic lupus erythematosus. Relaxation times < 90 s indicate an unfavourable prognosis for the extent of pathologic processes. Scleroderma systematica leads to increased values of 1 and 3 for blood serum, and of 1 for urine. The values of λ1 for blood serum increase and for urine decrease, respectively.
ACCEPTED MANUSCRIPT
31
These changes in the dynamic interfacial tensiometric parameters are specific to the scleroderma systematica, in contrast to other systemic diseases of the connective tissue. Values of λ1 > 10 mN·m1s1/2 for blood serum indicate an ongoing activity of the pathologic
T
processes during a pathogenetic therapy. For patients suffering from scleroderma systematica
IP
the pH value of the breath condensate is decreased, and the values of and of this fluid
SC R
become significantly lower. The patients with purpura rheumatica exhibit statistically significantly increased values of γ2, γ3, and decreased values (by almost 30%) of E and as compared to healthy persons (cf. Table 13). It was shown that values 3 > 50 mN/m are
NU
indicative for a negative prognosis of the development of the disease. Table 13. Rheometric and tensiometric parameters of blood serum for patients with purpura
MA
rheumatica and healthy persons (M±m)
Parameters Examined groups Healthy
E, mN/m
24.5±0.3 33.7±1.1
, s
101±2.1
γ2, mN/m
69.0±0.2 68.3±0.1
γ3, mN/m
59.9±0.3 58.2±0.25
CE P
TE
D
Sick
128±3.5
For chronic rheumatic heart, a significant decrease (by almost 50%) of the relaxation
AC
time τ of breath condensate is observed: from 463 s to 282 s. For breath condensate, the value of depends on the rheumatism activity and the degree of blood circulation inefficiency. It was shown that dynamic interfacial tensiometry and rheometry data of breath condensate provide information on s lesser circulation: values E > 45 mN/m for patients with chronic rheumatic heart disease are indicative of a pulmonary hypertension. For the chronic pyelonephritis decreased equilibrium surface tensions of blood serum were observed, both for male and female patients. For female patients, in addition, a decrease in the 1 values of blood serum and urine is observed. The deterioration of the renal function is accompanied by a significant increase of λ1 of urine. This fact could be used as one of the negative prognostic criteria of the development of this disease. Peculiar features for cases of chronic pyelonephritis with respect to the presence or absence of diabetes mellitus are differences in the values of γ3 and λ1 of blood serum, and the surface tensions of urine. While for the patients with diabetes mellitus the surface tension increases in the short and
ACCEPTED MANUSCRIPT
32
intermediate surface lifetime range, for patients without diabetes mellitus a decrease of this parameter is observed. This detail is of a firm diagnostic value, and can be ascribed to the presence of glucosuria. In the moment, it can be stated that tensiometric parameters for cases
T
of diabetic nephropathy are quite informative.
IP
The renal lesion caused by diabetes mellitus is accompanied by high values of λ1. For
SC R
patients with a diabetic nephropathy the surface tension of urine becomes lower, but in cases with chronic pyelonephritis the equilibrium values of the surface tension γ4 aa well as the dynamic surface tension 1 increase. For diabetes mellitus, the decrease or increase of the 1 value for urine could be a reliable differential diagnostic indicator of diabetic nephropathy vs
NU
chronic pyelonephritis. The presence of a nephrotic syndrome affects significantly the 2 value for urine. Pyelonephritis in a chronic stage also affects the parameters of dynamic interfacial
MA
tensiograms of some liquids. In the analysis of the interfacial tensiometric parameters, deviations in the urine parameters are more frequent. In particular, the deviations of 1 from
D
its normal value were detected in 52% of all cases (in 72% of male patients), and of 3 in 76%
TE
of all cases (in 91% of male patients). The development of a nephritic syndrome is accompanied by a surface tension decrease for blood serum and urine in the range of
CE P
intermediate surface ages. For patients with diabetic nephropathy the 2 values of blood serum and urine reflect the severity of the disease: a decrease of this parameter below 67 mN/m and 68 mN/m for blood serum and urine, respectively, indicate a negative prognosis of the course of the diabetic nephropathy.
AC
For patients with peptic gastroduodenal ulcer the rheological parameters of gastric juice are: E = 17.8±1.5 mN/m, = 240±13 s. Also a dependence of the dynamic and equilibrium surface tensions on patients’ gender and age was found. The blood serum parameters for these patients are E = 42.8±1.4 mN/m, = 166±9 s. For peptic gastroduodenal ulcer the parameter values for E and are higher than those for healthy persons. In cases of gastroesophagal reflux a decrease of of the gastric juice is observed, while for a duodenogastral reflux the dynamic surface tension becomes lower. If a duodenitis is present, an increase of both parameters occurs. For patients with duodenogastral reflux a decrease of the E value of the gastric juice was observed, while duodenitis leads to a decrease of 4. If the disease is accompanied by cholecystitis and biliary dyskinesia, the values E and become lower. For chronic periodontitis a significant decrease of the surface tension values, and of E and of the oral fluid as compared with those for healthy persons weres observed. The
ACCEPTED MANUSCRIPT
33
decrease of the values of 1, 2 and of the oral fluid was found in 78%, 79% and 59% of patients, respectively. The severity of chronic periodontitis affects the rheological properties of the oral fluid. It was shown that values γ3 > 60 mN/m and > 160 s, and also γ4 < 40 mN/m
T
indicate a grave course of the disease, which is of large practical importance.
IP
The microcholelithiasis is the initial stage of cholelithiasis. The study of the interfacial
SC R
dilational rheology of bile has shown that the visco-elasticity modulus E and the relaxation time for patients with this pathology are 12.52.8 mN/m and 274.333.5 s, respectively, while for healthy persons and for patients with microcholelithiasis after medical treatment,
NU
the E values were zero within the experimental error (±0.2 mN/m). The fact that E is close to zero can be attributed to an extremely rapid exchange between the solution bulk and surface layer, which is usual for adsorption layers of low molecular weight surfactants, if their
MA
concentration in the bulk is sufficiently high. On the contrary, the E and values for microcholelithiasis patients before medical treatment indicate much lower surfactants
D
concentration in the bile. Therefore, the visco-elasticity modulus could be used in the
TE
microcholelithiasis diagnostics and for monitoring the medical treatment. 4.10. Influence of fluorocarbon gases on lung phospholipid monolayers
CE P
Fluorocarbon gases are used for pulmonary disease therapies [27-35,90]. Langmuir monolayers of dipalmitoylphosphatidylcholine (DPPC – the main component of the native lung surfactant) have been studied in [27, 28]. It was found that upon compression in the
AC
region of the LE/LC (liquid-expanded/liquid-condensed) phase transition domains are not formed when the atmosphere above the monolayer was saturated with fluorocarbon gases. The adsorption dynamics of some phospholipids from aqueous solutions or dispersions was investigated by bubble profile analysis tensiometry in the presence of perfluorohexane (PFH) in the gas phase [33]. The presence of PFH strongly increased the adsorption rate as well as decreased the equilibrium interfacial tension of the phospholipid monolayers. For both effects, the strong interaction of PFH with the phospholipids in the monolayers is responsible, PFH acting as a co-surfactant. In [91] the theoretical model derived in [92] for mixed adsorption layers was used to describe the co-adsorption of a soluble surfactant from an aqueous solution and a second compound from the vapor phase. It was found that the adsorption equilibrium constant for DPPC is increased in presence of PFH in the gas atmosphere.
ACCEPTED MANUSCRIPT
34
For insoluble monolayers a complicated model was used in [93, 94] which takes into account: 1) LE/LC phase transition; 2) bimodal distribution (large clusters and monomers); 3) different molar area in the aggregate and of free monomers; 4) a non-ideal entropy of mixing.
T
This leads to a more realistic characterization of the amphiphilic compounds in the monolayer.
IP
When fluorocarbon molecules are adsorbed at the surface covered by DPPC and interact with
SC R
them via attraction forces, the mutual interaction energy between DPPC molecules in the surface layer is reduced, leading to a very effective fluidization of the monolayer. 5. Conclusions
NU
Surfaces are critically important for nearly all aspects of biological phenomena. Various diseases influence the composition and interfacial tension not only of human body
MA
fluids [95]. To further confirm these changes, the dynamic surface tension and dilational visco-elasticity can be used as an indicator of some pathologies. Such studies are of significant practical interest, due to the capability of providing a differential diagnosis and tools for
D
monitoring of the efficiency of a therapy. A better understanding of pathological disease is
TE
possible if various techniques are used. The surface tensiometry and rheometry are sensitive methods which can reveal changes in the surfactant content of biological liquids. Such
CE P
methods are easy to use and require small amounts of sample liquids only. We described here extensive studies of dynamic surface tensions and rheological parameters of various human liquids, such as blood serum, urine, breathing air condensates, cerebrospinal liquor. The
AC
results for healthy persons are compared with data obtained for people suffering from various diseases in oncology, nephrology, rheumatology, pulmonology and others. Some examples are also given for the evolution of measured data of biological liquids under a medical treatment. It becomes evident that such measurements are very useful for the medical practice. We envisage that studies on the surface properties of human biological liquids will provide additional useful information in medicine. 6. Acknowledgement The authors express their gratitude to the post-graduates and personnel of the Donetsk National Medical University for the collection of samples of biological liquids and the statistical analysis of the results of measured data. We especially acknowledge the efforts of the staff of the Physicochemical Laboratory of the University, in particular, S.V. Lylyk for her thorough rhelological and tensiometric measurements, and V.D. Mys, A.A. Rytikov and
ACCEPTED MANUSCRIPT
35
S.A. Zholob for various adaptations and modifications of the instruments and the development of different measurement programs.
T
7. References
IP
1. Morgan JLR, Woodward HE. The weight of a falling drop and the laws of Tate. J Am Chem Soc 1913; 35:1249–62
SC R
2. Harkins WD, Brown FE. A simple apparatus for the accurate and easy determination of surface tension with a metal thermoregulator for the quick adjustment of temperature. J Am Chem Soc 1916; 38:246–52.
NU
3. Harkins HN, Harkins WD. The surface tension of blood serum. and the determination of the surface tension of biological liquids. J Clin Invest 1929; 7:263–81. 4. DuNouy PL. Surface equilibria of biological and organic colloids. New York: The Chemical Catalog Co.; 1926.
MA
5. DuNouy PL. Surface tension of serum. XIII. On certain physicochemical changes in serum as a result of immunization. J Exp Med 1925; 41:779–93.
D
6. Zozaya J. A physicochemical study of blood serum II: analysis of 500 cases. J Phys Chem 1938; 42:191–207.
TE
7. Hrncir E, Rosina J. Surface tension of blood. Physiol Res 1997; 46:319–21
CE P
8. Anandi Krishnan, Arwen Wilson, Jacqueline Sturgeon, Christopher A. Siedlecki, Erwin A. Vogler. Liquid–vapor interfacial tension of blood plasma, serum and purified protein constituents thereof. Biomaterials 2005; 26: 3445–3453 9. Glantz P, The surface tension of saliva. Odontol Revy 1970; 21: 119–127.
AC
10. Kirkness JP, Christenson HK, Garlick SR, Parikh R, Kairaitis K, Wheatley JR & Amis TC, Decreased surface tension of upper airway mucosal lining liquid increases upper airway patency in anaesthetised rabbits. J Physiol 2003; 547: 603–611. 11. Brydon HL, Hayward R, Harkness W, Bayston R. Physical properties of cerebrospinal fluid of relevance to shunt function. 2: The effect of protein upon CSF surface tension and contact angle. British J Neurosurgery 1995; 9: 645-651. 12. Efentakis M, Dressman JB. Gastric juice as a dissolution medium: surface tension and pH. Euro J Drug Metabol and Pharmacokin 1998; 23: 97-102. 13. Joura EA, Kainz C, Joura EM, Bohm R, Gruber W, Gitsch G. Comparison of surface tension with determination of the L/S ratio in amniotic fluid for prediction of fetal lung maturity. Zeitschrift für Geburtshilfe und Neonatologie 1995; 199: 78-80. 14. Adamczyk E, Arnebrant T, Glantz PO. Time-dependent interfacial tension of whole saliva and saliva-bacteria mixes. Acta Odontol Scand 1997; 55: 384-389. 15. Boda D, Eck E, Boda K. Measurement of surface tension in biological liquids by a pulsating capillary technique. J Perinat Med 1997; 25: 146-152.
ACCEPTED MANUSCRIPT
36
16. Manalo E, Merritt TA, Kheiter A, Amirkhanian J, Cochrane C. Comparative effects of some serum components and proteolytic products of fibrinogen on surface tensionlowering abilities of beractant and a synthetic peptide containing surfactant KL4. Pediatr Res 1996; 39: 947-952.
IP
T
17. J. Rosina, E. Kvasnak, D. Šuta, H. Kolarova, J. Malek, L. Krajci. Temperature Dependence of Blood Surface Tension. Physiol. Res. 2007; 56: 93-98.
SC R
18. A. Fathi-Azarbayjani, A. Jouyban. Surface tension in human pathophysiology and its application as a medical diagnostic tool. Bio Impacts. 2015; 5:29-44 19. C.O. Mills, E. Ellas, G.H.B. Martin, M.T.C. Woo, A.F. Winder. Surface Tension Properties of Human Urine: Relationship with Bile Salt Concentration. J. Clin. Chem. Clin. Biochem., 1988; 26: 187-194.
MA
NU
20. Krishnan A., Wilson A., Sturgeon J., Siedlecki CA., Vogler EA.. Liquid-vapor interfacial tension of blood plasma. serum and purified protein constituents thereof. Biomaterials. 2005; 26: 3445-53.
D
21. V.N. Kazakov, V.M. Knyazevich, O.V. Sinyachenko, V.B. Fainerman and R. Miller. Interfacial Rheology of Biological Liquids: Application in Medical Diagnostics and Treatment Monitoring. in “Interfacial Rheology”. Vol. 1. Progress in Colloid and Interface Science. R. Miller and L. Liggieri (Eds.). Brill Publ., Leiden. 2009, p. 519-566.
TE
22. V.N. Kazakov, O.V. Sinyachenko, V.B. Fainerman, U. Pison and R. Miller - Dynamic Surface Tension of Biological Liquids in Medicine. in “Studies in Interface Science”. Vol. 8. D. Möbius and R. Miller (Editors). Elsevier. Amsterdam. 2000.
CE P
23. Anahita Fathi-Azarbayjani, Abolghasem Jouyban, Sui Yung Chan. Impact of Surface Tension in Pharmaceutical Sciences. J Pharm Pharmaceut Sci. 2009; 12: 218-228
AC
24. Pulmonary Surfactant: From Molecular Biology to Clinical Practice. Eds. B. Robertson. L.M.G. Van Golde and J.J. Batenburg. Elsevier. Amsterdam. 1992. 25. R. Wüstneck, V.B Fainerman, N. Wüstneck and U. Pison. Interfacial behavior of spread SP-B and SP-C layers and the influence of oligomerization and secondary structure. J. Phys. Chem. B. 2004; 108: 1766-1770. 26. R. Wüstneck, J. Perez-Gil, N. Wüstneck, A. Cruz, V.B. Fainerman and U. Pison. Interfacial Properties of Pulmonary Surfactant Layers. Adv. Colloid Interface Sci. 2005; 117: 33-58. 27. F. Gerber, V. P. Krafft, T. F. Vandamme, M. Goldmann, P. Fontaine. Fluidization of a dipalmitoyl phosphatidylcholine monolayer by fluorocarbon gases: Potential use in lung surfactant therapy. Biophys. J. 2006; 90: 3184–3192. 28. F. Gerber, V. P. Krafft, T. F. Vandamme, M. Goldmann, P. Fontaine. Preventing crystallization of phospholipids in monolayers: a new approach to lung surfactant therapy. Angew. Chem. Int. Ed. 2005; 44: 2749-2752. 29. J. G. Riess. Fluorous materials for biomedical uses. In: Handbook of Fluorous Chemistry (Eds: J. A. Gladysz, I. Horvath, D. P. Curran). Wiley-VCH. Weinheim. Germany 2004, p. 521–573.
ACCEPTED MANUSCRIPT
37
30. M. Sukumar, M. Bommaraju, J. E. Fisher, F. C. Morin, M. C. Papo, B. P. Fuhrman, L. J. Hernan, C. L. Leach. High-frequency partial liquid ventilation in respiratory distress syndrome: Hemodynamics and gas exchange. J. Appl. Physiol. 1998; 84: 327– 334.
IP
T
31. M. P. Krafft, J. G. Riess. Perfluorocarbons. life sciences and biomedical uses. J. Polymer. Sci. A: Polymer. Chem. 2007; 45: 1185−1198.
SC R
32. J. G. Riess. Injectable oxygen-carriers (blood substitutes) – Raison d’être. chemistry. and some physiology. Chem. Rev. 2001; 101: 2797-2920. 33. P. N. Nguyen, T. T. Trinh Dang, G. Waton, T. Vandamme, M. P. Krafft. A nonpolar. nonamphiphilic molecule can accelerate adsorption of phospholipids and lower their surface tension at the air/water interface. ChemPhysChem 2011; 12: 2646–2652.
MA
NU
34. P. N. Nguyen, M. Veschgini, M. Tanaka, G. Waton, T. Vandamme, M. P. Krafft. Counteracting the inhibitory effect of proteins towards lung surfactant substitutes: a fluorocarbon gas helps displace albumin at the air/water interface. Chem. Commun. 2014; 50: 11576-11579.
TE
D
35. V.B. Fainerman and R. Miller. Maximum bubble pressure tensiometry: theory, analysis of experimental constrains and applications. in “Bubble and Drop Interfaces”. Vol. 2. Progress in Colloid and Interface Science. R. Miller and L. Liggieri (Eds.). Brill Publ.. Leiden. 2011, p. 75-118.
CE P
36. V.B. Fainerman, A.V. Makievski and R. Miller. Accurate analysis of the bubble formation process in maximum bubble pressure tensiometry. Rev. Sci. Instruments. 2004; 75:213-221. 37. V.B. Fainerman, V.D. Mys, A.V. Makievski and R. Miller. Correction for the aerodynamic resistance and viscosity in maximum bubble pressure tensiometry. Langmuir. 2004; 20:1721 – 1723
AC
38. S.A. Zholob, A.V. Makievski, R. Miller and V.B. Fainerman. Optimisation of calculation methods for determination of surface tensions by drop profile analysis tensiometry. Adv. Colloid Interface Sci. 2007; 134-135: 322-329 39. S.A. Zholob, V.I. Kovalchuk, A.V. Makievski, J. Krägel, V.B. Fainerman and R. Miller. Determination of the dilational elasticity and viscosity from the surface tension response to harmonic area perturbations. in “Interfacial Rheology”. Vol. 1. Progress in Colloid and Interface Science. R. Miller and L. Liggieri (Eds.). Brill Publ., Leiden. 2009, p. 77102. 40. S.A. Zholob, A.V. Makievski, R. Miller and V.B. Fainerman. Application of axisymmetric profile analysis for measuring surface tension at harmonic surface oscillations. Methods and Devices of Quality Control. 2012; 29: 25-36. 41. S.A. Zholob, A.V. Makievski, R. Miller and V.B. Fainerman. Advances in calculation methods for the determination of surface tensions in drop profile analysis tensiometry. in “Bubble and Drop Interfaces”. Vol. 2. Progress in Colloid and Interface Science. R. Miller and L. Liggieri (Eds.). Brill Publ., Leiden. 2011; P. 39-60.
ACCEPTED MANUSCRIPT
38
42. V.N. Kasakov, V.B. Fainerman, O.V. Sinyachenko, R. Miller, P. Joos, S.V. Lylyk, A.E. Aiko, D.V. Truchin and M.V. Ermolaeva. Dynamic surface tension of blood and urine in cases of renal pathology. Arch. Klin. Eksper. Mediciny. 1995; 29: 3-9.
IP
T
43. O.V. Sinyachenko, V.N. Kazakov, E.F. Barinov, V.B. Fainerman, R. Miller, M.V. Ermolaeva, A.E. Ayko, I.A. Sidorenko, D.V. Trukhin. Dynamic surface tension of blood and urine at chronic glumerulonephritis. Likarska Sprava 1997; 1:48-51
SC R
44. V.N. Kazakov, R. Miller, N.G. Semikov, O.V. Sinyachenko, D.V. Trukhin, V.B. Fainerman and Y.I. Yakovets. Dynamic interfacial tensiometry as a new method for studying human biologic liquids: I. Procedures used. Vestnik novych medicinskich technologij. 1997; 4:100-103
NU
45. V.N. Kazakov, O.V. Sinyachenko, V.B. Fainerman and R. Miller. Dynamic surface tension of biological liquids in medicine. Izd. Donetsk. Med. Univ. Donetsk. 1997 (in Russian)
MA
46. O.V. Sinyachenko, V.N. Kazakov, V.B. Fainerman, R. Miller, P. Joos and M.V. Yermolayeva. Dynamic surface tension of synovial liquid in rheumatoid arthritis. Terapevticheskij Archiv. 1998; 1:46-49
TE
D
47. V.N. Kazakov, O.V. Sinyachenko, M.V. Pustovaya, V.B. Fainerman, R. Miller and D.V. Trukhin. Interfacial tensiometry of biological liquids: questions of theory. methods. and perspectives of clinical use. Archive Clinical Experimental Medicine. 1998; 7:5-10.
CE P
48. R. Miller, V.B. Fainerman, A.V. Makievski, J. Krägel, D.O. Grigoriev, V.N. Kazakov and O.V. Sinyachenko. Dynamics of protein and mixed protein/surfactant adsorption layers at the water/fluid interface. Adv. Colloid Interface Sci. 2000; 86: 39-82. 49. V.N. Kazakov, V.B. Fainerman, P.G. Kondratenko, A.F. Elin, O.V. Sinyachenko and R. Miller. Dilational rheology of serum albumin and blood serum solutions as studied by oscillating drop tensiometry. Colloids Surfaces B. 2008; 62:77–82.
AC
50. V.N. Kazakov, A.A. Udod, I.I. Zynkovich, V.B. Fainerman and R. Miller. Dynamic surface tension of saliva: application in medical diagnostics. Colloids Surfaces B. 2009; 74: 457–461. 51. V.N. Kazakov, E.L. Barkalova, L.A. Levchenko, T.M. Klimenko, V.B. Fainerman and R. Miller. Dilation rheology as medical diagnostics of human biological liquids. Colloids Surfaces A. 2011; 391:190-194. 52. V.N. Kazakov, A.F. Vozianov, O.V. Sinyachenko, D.V. Trukhin, V.I. Kovalchuk and. U. Pison. Studies on the application of dynamic surface tensiometry of blood and cerebrospinal liquid for the diagnostics and treatment control of rheumatic, neurological and oncological diseases. Adv. Colloid Interface Sci. 2000; 86: 1-38 53. Kazakov V.N., Sinyachenko O.V., Trukhin D.V., Pison U. Dynamic interfacial tensiometry of biologic liquids – does it have an impact on medicine. Colloids Surf. A: Physicochem. Eng. Aspects. 1998; 143: 441-459. 54. Е.A. Statinova, R.Ya. Omelchenko. Dynamic interfacial tensiometry of cerebro_spinal liquid in the diagnosis of neurological diseases. Ukrainian Neurological Journal. 2010; 2: 59-63.
ACCEPTED MANUSCRIPT
39
55. V. I. Cherniy, V. A. Stepanyuk. Potentialities of Program Analysis of Probable Outcome in Patients with Acute Poisoning by Mushrooms. Obsch. Reanim. 2006; 11: 2-6. 56. E.L.Barkalova. Surface Tension of the Cerebrospinal Fluid of Patients with Neurosyphilis. Buk. Med. Herald. 2011; 15: 143-145.
IP
T
57. I.G. Gerasimov, V.B. Fainerman, I.A. Zaitsev and M.A. Kotel'nitskii. Simulation of the Dynamic Surface Tension of Aqueous Solutions of Some Proteins and Biological liquids. Russian J. Phys. Chem. 2003; 77: 666-670.
SC R
58. V.B. Fainerman, S.A. Zholob, M.E. Leser, M. Michel and R. Miller. Adsorption from mixed ionic surfactant/protein solutions - analysis of ion binding. J. Phys. Chem. 2004; 108: 16780-16785.
NU
59. O.Yu. Milyaeva, B.A. Noskov, S.-Y. Lin, G. Loglio and R. Miller. Influence of polyelectrolyte on dynamic surface properties of BSA solutions. Colloids Surfaces A. 2014; 442: 63-68.
TE
D
MA
60. R. Miller, E.V. Aksenenko, V.S. Alahverdjieva, V.B. Fainerman, Cs. Kotsmar, J. Krägel, M.E. Leser, J. Maldonado-Valderrama, B.A. Noskov, V. Pradines, C. Stefaniu, A. Stocco and R. Wüstneck. Thermodynamic and kinetics of mixed protein/surfactant adsorption layers at liquid interfaces. in “Proteins in solution and at interfaces: Methods and Applications in Biotechnology and Materials Science”. J.M. Ruso and Á. Piñeiro (Eds.). John Wiley & So. 2013. p. 389-426.
CE P
61. Cs. Kotsmar, V. Pradines, V.S. Alahverdjieva, E.V. Aksenenko, V.B. Fainerman, V.I. Kovalchuk, J. Krägel, M.E. Leser and R. Miller. Thermodynamics, adsorption kinetics and rheology of mixed protein-surfactant interfacial layers. Adv. Colloid Interface Sci. 2009; 150: 41–54. 62. R. Miller, V.S. Alahverdjieva and V.B. Fainerman, Thermodynamics and rheology of mixed protein/surfactant adsorption layers, Soft Matter, 2008; 4: 1141-1146.
AC
63. E.V. Aksenenko, V.I. Kovalchuk, V.B. Fainerman and R. Miller, Surface Dilational Rheology of Mixed Surfactant Layers at Liquid Interfaces, J. Phys. Chem. C. 2007; 111: 14713-14719. 64. V.B. Fainerman and R. Miller. Adsorption isotherms at liquid interfaces, Encyclopedia of Surface and Colloid Science. P. Somasundaran and A. Hubbard (Eds.). 2nd. Edition. 2009; 1:1-15. 65. P.R. Garrett and R.D. Ward. A reexamination of the measurement of dynamic surface tensions using the maximum bubble pressure method. J. Colloid Interface Sci. 1989; 132: 475-490. 66. R.L. Bendure. Dynamic surface tension determination with the maximum bubble pressure method. J. Colloid Interface Sci. 1971; 35: 238-248. 67. J. Kloubek. Measurement of the dynamic surface tensionby the maximum bubble pressure method. II. Calculation of the effective age of the solution-air interface. J. Colloid Interface Sci. 1972; 41: 1-6.
ACCEPTED MANUSCRIPT
40
68. J. Kloubek. Measurement of the dynamic surface tension by the maximum bubble pressure method. III. Factors influencing the measurements at high frequency of the bubble formation and an extension of the evaluation to zero age of the surface. J. Colloid Interface Sci. 1972; 41: 7-16.
IP
T
69. J. Kloubek. Measurements of the dynamic surface tension by the maximum bubble pressure method. IV. Surface tension of aqueous solutions of sodium dodecylsulfate. J. Colloid Interface. Sci. 1972; 41: 17-22.
SC R
70. K.J. Mysels. Improvements in the maximum-bubble pressure method of measuring surface tension. Langmuir. 1986; 2: 428-432. 71. K.J. Mysels. The maximum bubble pressure method of measuring surface tension. revisited. Colloids Surfaces. 1990; 43: 241-262.
MA
NU
72. Kazakov VN, Trukhin DV, Sinyachenko OV, Bondar GV, Yakovetz YI, Semikoz NG, Fainerman VB, Miller R. Dynamic middle-phase tensiometry of blood and urine in female patients with malignant tumors of the reproductive organs. Voprosi Oncologii 1998; 44: 334-336.
D
73. Trukhin DV, Sinyachenko OV, Kazakov VN, Lylyk SV, Belokon AM, Pison U. Dynamic surface tension and surface rheology of biological Liquids, Colloid Surf B 2001; 21: 231–238.
TE
74. Chronic Pancreatitis. Novel Concepts in Biology and Therapy / Edited by M. W. Buchler. H. Friess. W. Unl. P. Malfertheiner. Berlin; Wien: Wissenchafts-Verlag A Blackwell Publishing Company. 2002. 614 р.
CE P
75. de Queiroz AA, Barrak ÉR, de Castro SC. Thermodynamic analysis of the surface of biomaterials. J Mol Struct (Theochem) 1997; 394: 271-279.
AC
76. Harnett EM, Alderman J, Wood T. The surface energy of various biomaterials coated with adhesion molecules used in cell culture. Colloids Surf B 2007; 55: 90-97. 77. Zhou F, Escher J, Cui S. Bifurcation for a free boundary problem with surface tension modeling the growth of multi-layer tumors. J Math Anal Appl 2008; 337: 443- 457, 78. Anand P, Huilgol N, Banerjee R. Interfacial properties as predictors of radioresistance in cervical cancer. J Colloid Int Sci 2007; 314: 63-70. 79. Preetha A, Banerjee R, Huilgol N. Dynamic surface tensiometry of tissues using Langmuir films, Colloids Surf B 2005; 40: 35-43. 80. Robertson B, Johansson J, Curstedt T. Synthetic surfactants to treat neonatal lung disease. Mol Med Today 2000;6: 119-124. 81. Ikegami M, Hacobs H, Jobe A. Surfactant function in respiratory distress sysndrome. J Pediat 1983;102:443- 447. 82. Richardson PS, Phipps RJ. The anatomy, physiology, pharmacology and pathology of tracheobronchial mucus secretion and the use of expectorant drugs in human disease. Pharmac Ther B 1978; 3: 441-479.
ACCEPTED MANUSCRIPT
41
83. Gilljam H, Andersson O, Ellin A, Robertson B, Strandvik B. Composition and surface properties of the bronchial lipids in adult patients with cystic fibrosis. Clinica Chimica Acta 1988; 116:29-38.
IP
T
84. Jokic R, Klimaszewski A, Crossley M. Positional treatment vs continuous positive airway pressure in patients with positional obstructive sleep apnea syndrome. Chest 1999; 115:771-781.
SC R
85. Bradshaw DA. What are the nonsurgical treatment options for obstructive sleep apnea syndrome? Am Otolaryngol 2001;22:124-131. 86. Reid G. Importance of Surface Properties in Bacterial Adhesion to Biomaterials, with Particular Reference to the Urinary Tract. International Biodeterioration & Biodegradation 1992;30: 105-122.
MA
NU
87. Kirkness JP, Christenson HK, Wheatley JR, Amis TC. Application of the pull-off method for measurement of the surface tension of upper airway mucosal lining liquid. Physiol Meas 2005; 26:677-688. 88. Brydon HL, Hayward R, Harkness W, Bayston R. Physical properties of cerebrospinal fluid of relevance to shunt function. 2. The effect of protein upon CSF surface tension and contact angle Brit. J Neurosurg 1995;9:645- 651.
TE
D
89. Krishnan A, Wilson A, Sturgeon J, Siedlecki CA, Vogler EA. Liquid-vapor interfacial tension of blood plasma, serum and purified protein constituents thereof. Biomater 2005; 26: 3445-3453.
CE P
90. E. Unger, T. Porter, J. Lindner and P. Grayburn, Cardiovascular drug delivery with ultrasound and microbubbles. Adv. Drug Delivery Rev., 2014; 72: 110-126.
AC
91. M.P. Krafft, V.B. Fainerman, and R. Miller, Modeling of the effect of fluorocarbon gases on the properties of phospholipid monolayers and the adsorption dynamics of their aqueous solutions or dispersions, Colloid Polym Sci 2015; 293:3091–3097. 92. N. Mucic, N. Moradi, A. Javadi, E.V. Aksenenko, V.B. Fainerman and R. Miller, Mixed adsorption layers at the aqueous CnTAB solution / hexane vapor interface, Colloids Surfaces A, 2014; 442: 50-55. 93. V.B. Fainerman and D. Vollhardt, Equation of state for the phase coexistence region of insoluble monolayers under consideration of the entropy nonideality, J. Phys. Chem. B, 2008; 112: 1477-1481. 94. V. B. Fainerman and D. Vollhardt, Equation of state for monolayers with additional phase transition between condensed phases of different compressibility, J. Phys. Chem. B, 2009; 113: 6311–6313. 95. S. Zaitsev, Dynamic surface tension measurements as general approach to the analysis of animal blood plasma and serum, Adv. Colloid Interface Sci., 2016, 235: 201–213.
AC
TE
CE P
Graphical abstract
D
MA
NU
SC R
IP
T
ACCEPTED MANUSCRIPT
42
ACCEPTED MANUSCRIPT
43
Highlights Dynamic surface tension are sensitive to changes in the composition of human body fluids.
The dilational visco-elasticity can also serve as indicator of pathologies.
Measurements of both parameters are simple and require small amounts of liquid.
The parameter can serve for diagnostics of diseases.
The same parameters are also useful for the control of therapies.
AC
CE P
TE
D
MA
NU
SC R
IP
T
S0001-8686(17)30007-6 doi:10.1016/j.cis.2017.08.002 CIS 1820
To appear in:
Advances in Colloid and Interface Science
Received date: Revised date: Accepted date:
10 January 2017 31 July 2017 7 August 2017
Please cite this article as: Fainerman VB, Trukhin DV, Zinkovych Igor I., Miller R, Interfacial tensiometry and dilational surface visco-elasticity of biological liquids in medicine, Advances in Colloid and Interface Science (2017), doi:10.1016/j.cis.2017.08.002
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Interfacial tensiometry and dilational surface visco-elasticity of biological liquids in medicine
IP
T
V.B. Fainerman1, D.V. Trukhin2, Igor I. Zinkovych3 and R. Miller4 1
NU
SC R
SINTERFACE Technologies, Berlin, Germany; Donetsk National Medical University, Ukraine 2 Odessa National Medical University, Odessa, Ukraine 3 Donetsk National Medical University, Ukraine 4 Max-Planck-Institut für Kolloid- und Grenzflächenforschung, Potsdam, Germany
MA
Contents
AC
CE P
TE
D
1. Introduction 2. Experimental methods 3. Surface characteristics of biological liquids for healthy persons 4. Influence of diseases on surface characteristics of biologic liquids 4.1. Oncology 4.2. Oral liquid, effect of carious lesion of teeth 4.3. Neurosyphilis 4.4. Congenital pneumonia of premature newborns 4.5. Chronic recurrent pancreatitis 4.6. Acute renal failure 4.7. Women with infertility 4.8. Arthritis, chronic bronchitis and chronic obstructive pulmonary disease 4.9. Other diseases 4.10. Influence of fluorocarbon gases on lung phospholipid monolayers 5. Conclusions 6. Acknowledgement 7. References
1
ACCEPTED MANUSCRIPT
2
ABSTRACT Dynamic surface tensions and dilational visco-elasticity are easy accessible parameters of liquids. For human body liquids, such as urine, blood serum, amniotic fluid, gastric juice,
T
saliva and others, these parameters are very characteristic for the health status of people. In
IP
case of a disease the composition of certain liquids specifically changes and the measured
SC R
characteristics of dynamic surface tension of the dilational surface elasticity and viscosity reflect these changes in a clear way. Thus, this kind of physico-chemical measurements represent sensitive tools for evaluating the severity of a disease and can serve as control tool
NU
for the efficiency of applied therapies. The overview summarises the results of a successful work over about 25 years on this subject and gives specific insight into a number of diseases for which the diagnostics as well as the therapy control have been significantly improved by
MA
the application of physico-chemical experimental techniques.
D
Keywords: dynamic surface tension, drop profile analysis tensiometry, dilational visco-
AC
CE P
TE
elasticity, human biological liquids, blood serum, urine, amniotic fluid, gastric juice, saliva
ACCEPTED MANUSCRIPT
3
1. Introduction Interfaces play an important role in our daily life. The advanced knowledge achieved in surface science during the last decades led to various applications in many industries. For
T
instance, interfaces are of crucial importance in pharmacy, biotechnology and medicine. The
IP
biological liquids in a human body contain various surface active molecules which adsorb at
SC R
liquid interfaces and lead to changes in surface tension and in the interfacial dilational viscoelasticity. The earliest works on surface tension of biological liquids were performed as early as the beginning of the 20th century [1, 2]. Original studies and overviews on the surface
NU
tension of biologic liquids were published in [3-22]. In the papers before 1940 mainly blood serum was studied [3-6], while in more recent papers [7-20] various biological liquids had been the target of investigations. The results of our studies were summarized in a monograph
MA
[21] and a review article [22]. Measurements of surface and interfacial tension are extensively involved into the research and development of medicaments, and can be used routinely to
D
solve pharmaceutical problems and improve product quality [23]. Many biological and natural processes involve the understanding of wetting and
TE
interfacial tension as many biochemical reactions happen at interfaces. Human biological liquids such as urine, blood serum, amniotic fluid, gastric juice, saliva, expired air condensate,
CE P
fluids of the urinary and reproductive tracts, endocrine glands, cerebrospinal and alveolar lining fluid, contain smaller or larger amounts of surfactants, proteins and lipids. These low and high-molecular weight compounds are surface active and common materials in various
AC
tissues of the body which control surface tension of human interfaces. The physico-chemical processes taking place at these interfaces are of fundamental importance for various tissues and the vital function of human organs. As an example in medical science, the studies of lung surfactant systems are a field where surface tensiometry is intensively investigated. In medical research, measurements of surface tension are performed for patients with various pathological states of lung surfactants such as the adult respiratory distress syndrome, bronchial asthma, and pneumonia. In this particular field, a significant clinical progress was made in respect to the treatment of pathologies related to disorders in the lung surfactant system [24-26]. The role of fluorocarbon gases (FC) in medicine, for example, in therapies for the acute respiratory distress syndrome and other pulmonary disease were reviewed in [2734]. FC in the gas phase decreases the surface tension significantly, and the adsorption processes at the liquid/vapor interface are remarkably accelerated.
ACCEPTED MANUSCRIPT
4
Diseases change the composition of human biologic liquids and this causes changes the properties of the corresponding interfacial layers. Studies of surface tensiometry and dilational rheometry allow to conclude about the actual composition of interfacial layers and
T
can therefore assist the physician as a diagnostic tool for identifying the development of a
IP
disease or evaluating the efficiency of therapeutic treatments. Studies of dynamic surface
SC R
tension of biologic liquids taken from clinical patients and from healthy persons (for example stuff members) of Donetsk Medical University were initiated in 1993, and performed since then in the Physicochemical Laboratory of the Donetsk Institute of technical ecology. The results were found to be interesting and promising. Therefore, in 1999 the Physicochemical
NU
Laboratory was shifted to the Donetsk National Medical University, aiming at systematic studies of surface tension and dilation surface visco-elasticity of biologic liquids. It should be
MA
noted that, in line with the experimental studies of biological liquids, the staff of the laboratory closely cooperates with the companies LAUDA and SINTERFACE Technologies in order to develop and improve the instruments and measurement protocols [35-41].
D
Since the foundation of the laboratory more than 20000 analyses of various human
TE
biologic liquids were made; the results thus obtained were reported and discussed in more than 180 publications in physicochemical and medical periodicals. The samples of biological
CE P
liquids were taken from patients with various diseases, who were treated in a number of departments of the University clinics and other hospitals in Donetsk. These studies were performed with the participation of post-graduates and staff members of various departments
AC
such as of rheumatology, gastroenterology, physical therapy, obstetrics and gynaecology, anaesthesiology, oncology, stomatology, neonatology, dermatology, endocrinology, neurology, venereal diseases, departmental surgery, infectious diseases, hospital surgery, eye microsurgery. The laboratory also processed many samples of biologic liquids provided by medical universities in cities like Poltava, Kharkov and Lugansk. The results of dynamic surface tension studies of human biological liquids were summarised in a monograph [22]. In a recent book chapter published in 2009 problems concerning the dilational surface rheology of some biological liquids, mainly blood serum, urine, breath condensate and cerebrospinal liquid, with special reference to rheumatic, neurological, pulmonary and some other internal diseases [21]. The main results of our overview given here were reported in original papers and reviews [42-57]. Tensiometry and dilational surface rheology are used mainly in scientific studies, and for some pathologies (for example, rheumatology) also in the medical practice. To obtain a deeper insight into the results
ACCEPTED MANUSCRIPT
5
obtained with biologic liquids, theoretical models for mixed solutions of proteins and surfactants were developed which are capable for the description of surface tension, adsorption and dilational visco-elasticity under harmonic oscillations of the surface area [58-
T
64]. The validity of the models was verified using relevant model experiments [49].
IP
The present review discusses problems concerning the surface tension and dilational
SC R
rheology of biological liquids for various diseases. It was shown that surface tension and visco-elasticity parameters have a large potential for differential diagnosis and monitoring of the efficiency of therapies. These parameters for different diseases are capable of reflecting the general composition of surfactants, including pathological proteins and other compounds
NU
formed and accumulated during the development of a disease.
MA
2. Experimental methods
For the measurements of dynamic surface tension γ in the relevant short lifetime range, the maximum bubble pressure method (MBPM) is most appropriate for medical applications
D
involving biological liquids [65-71]. The main advantages of MBPM are the small sample
TE
volume (1 ml), and the wide range of surface lifetime (0.001 s to 30-50 s) [22, 35]. The dynamic surface tension data were measured using the tensiometers MPT1 or MPT2
CE P
(LAUDA, Germany), or more recently, the BPA-1P and BPA-1S (SINTERFACE Technologies, Germany) [35-37]. All these tensiometers allow direct measurements of the bubble surface lifetime within the time (t) range of 0.01 s (or less) up to 50 s. The results are
AC
called tensiograms (dependencies of vs t), from which the characteristic values are determined: at t = 0.01 s (1), t = 1 s (2), and the 3 value, obtained by the extrapolation of the dependence vs t−1/2 towards t→∞. Also the slope values of tensiometric curve plotted in the coordinates γ(t1/2) and γ(t-1/2) were calculated as 0 −(dγ/dt1/2)t →0 and 1 (dγ/dt−1/2)t →∞, respectively. A large number of tensiograms were presented in [22, 42-49]. Figure 1 shows (as an examples) three versions of the dependency of surface tension for blood serum taken from healthy a volunteer: 1a - vs t dependence; 1b - dependence on t1/2; and 1c - dependence on t−1/2. In Figs. 1b and 1с, dependencies on the effective adsorption time te=(3/7)tl are shown. The effective adsorption time te is shorter than the bubble life time tl and related to the expansion of the bubble surface during the experiment [35,36]. As we can see in Fig. 1b, the dynamic surface tension is linear when plotted over the effective time in the range 0.004 to 0.2 s, while in Fig. 1с it is linear in the effective time interval between 3 and 25 s. The presented plots over the effective time are linear in the given intervals for all studied
ACCEPTED MANUSCRIPT
6
biological liquids. The tangents shown in Fig. 1 are used to determine the slopes 0, 1, and
MA
NU
SC R
IP
T
the limiting surface tension value γ3.
AC
CE P
TE
D
.
7
TE
D
MA
NU
SC R
IP
T
ACCEPTED MANUSCRIPT
Fig. 1. Dependence of dynamic surface tension on the bubble lifetime (MPT2) for a healthy
CE P
person (a), the same data are plotted as dependencies on t1/2 (b) and t−1/2 (c).
The dependencies of surface tension on time mentioned above have certain physical
AC
meanings. For short times (t 0) a simple relation for multicomponent solution can be written as [22]:
d 2RT n c Di i dt1 2 i1 t0
(1)
Here R is the gas law constant, T is the absolute temperature, is the surface tension of the solution, D the diffusion coefficient, c the bulk concentrations, and the subscript ‘i’ refers to the components. The derivative on the left-hand side of this equation is the slope of the dependence of γ on t1/2. One more important relation is valid for long surface lifetimes. This equation, generalised for multicomponent system, reads [22]:
d RT n i2 dt1/ 2 2 Di i1 ci t
(2)
ACCEPTED MANUSCRIPT
8
where i is the adsorption value for ith surface active component. Here the derivative on the left-hand side of this equation is taken with respect to t-1/2, and is calculated in the limit t (that is, t-1/2 0). As for most surface active components the ratio i/ci is constant (the so
T
called Henry constant Ki i/ci), the sum in the right hand side of Eq. (2) is an approximate
IP
expression for the total adsorption of all mixture components with reference to their adsorption
SC R
activity Ki. The γ3 value calculated from the MВPМ data is the obtained by drop/bubble profile analysis tensiometry (PAT) at a surface age of 100 ± 20 s.
Surface tension experiments were also performed using the drop/bubble profile
NU
analysis tensiometry (PAT1 and PAT2 from SINTERFACE Technologies, Germany). In this study the configuration of pendant drops was used. The procedure of how the surface tension is calculated from the profile of a drop/bubble has been discussed in detail for example in [38-
MA
41]. A drop of the studied liquid was rapidly formed (during 1-2 s) at the tip of a Teflon capillary, and the dynamic surface tension was measured every 5-10 s in a time interval up to
D
1200-1800 s. The drop surface is automatically kept constant by the instrument’s software during the whole measurement. The equilibrium surface tension of human biologic liquids γ4
TE
was estimated by extrapolation of the tensiograms plotted as vs t−1/2 to t → ∞, and the slope
CE P
of the tensiograms was used as 2 (dγ/dt-1/2)t . Figure 2 illustrates example experiments obtained by using the РAТ2 tensiometer with stress deformations at 1200 s. The surface dilational visco-elasticity was studied also by the pendant drop method. After a time of 1200-1800 s, the drop was subjected to stress deformations, i.e. a rapid increase
AC
of the surface area by about 5-8 %, and the corresponding visco-elasticity modulus E of the surface layer was calculated as:
E
A A
(3)
where A is the initial surface area of the drop, γ is the initial surface tension jump caused by the stepwise increase of the drop surface area A. The variation in surface tension induced by the stress deformation γt obeys the exponential equation [22]:
t exp t / where t is the time expired since the deformation, is the corresponding relaxation time.
(4)
9
TE
D
MA
NU
SC R
IP
T
ACCEPTED MANUSCRIPT
CE P
Fig. 2. Dependence of dynamic surface tension on drop lifetime of cerebrospinal fluid (CSF) for patient with discirculatory encephalopathy () and patient from the reference group ().
AC
To study the dilational elasticity for harmonic oscillations, after stress experiments and having re-established the adsorption equilibrium the solution drop was subjected to surface oscillations at frequencies f between 0.005 Hz and 0.2 Hz, with oscillation amplitudes of 78% [21, 49]. For compression/expansion perturbations the surface dilational modulus E is defined by an expression similar to Eq. (3) but in the differential form:
E
d d ln A
(5)
The determined modulus E can be presented as a complex number E = Er + iEi, where the real part Er is the storage modulus or dilational elasticity, and the imaginary part Ei is the loss modulus corresponding to the dilational viscosity d = Ei/f is the angular frequency of the generated area variations). The results of experiments with harmonic oscillations were analysed using the Fourier transformation [21,49]:
ACCEPTED MANUSCRIPT E(i) A
F[ ] F[A]
10
(6)
The complex value E = Er + iEi is transformed into the expressions for the visco-
IP
,
arctanEi Er .
(7)
SC R
E Er2 Ei2
T
elasticity modulus |E| and phase angle :
For some diseases, the values of modulus and phase angle at fixed oscillation frequencies obtained for the respective fluids taken from healthy persons were compared with
NU
those obtained from sick persons. It was experimentally shown that for many biological liquids both components of the complex visco-elasticity modulus in the frequency range
Er a1 b1 lg , Ei a2 b2 lg
MA
studied depend linearly on the logarithm of the oscillation frequency f = /2 [11, 43]: (8)
D
The coefficients ai in these linear equations correspond to = 1 rad/s and hence
TE
become approximately equal to the real and imaginary parts of the visco-elasticity at the maximum studied frequency of 0.2 Hz. This data presentation is convenient to be used for a
CE P
statistical processing of experimental studies of blood serum rheology and other biological liquids, because all characteristics of the studied samples can be described by these four coefficients. Figure 3 demonstrates (as examples) the experimental dependencies of the real
AC
and imaginary components on the oscillation frequency, along with the straight lines calculated using Eqs. (8). Note that almost all experiments were performed with fresh biological fluids, selected from volunteers and patients in sterile clean test tubes. In some special cases, the liquids have been stored no more than 48 hours at 5ºС. For longer time in the fridge, the tensiometric characteristics differ from those of fresh liquids. The experimental results were analysed statistically using common programs with the definition of the mean value M, mean standard deviation , the dispersion mean or the standard error of the mean value m (m /n1/2, where n is the number of volunteers or ill persons), correlation coefficients (r) and the calculated reliability of the statistical (Student’s t-distribution) probability of a wrong conclusion p. The range of measured values within the limits M ± 3m for the normal statistical distribution involves almost all obtained results (with a probability of 99.7 %).
11
TE
D
MA
NU
SC R
IP
T
ACCEPTED MANUSCRIPT
CE P
Fig. 3. Dependence of real () and imaginary () visco-elasticity components for umbilical blood on the oscillation frequency; curves are calculated using Eq. (8).
AC
3. Surface characteristics of biologic liquids for healthy persons All biological liquids of the human organism contain surface active compounds, such as proteins, lipids, and molecules of other nature. These surfactants are characterized by a high adsorption activity at low bulk concentrations which significantly affects equilibrium interfacial properties and the kinetics of physicochemical processes taking place at interfaces. Table 1 summarises averaged values of dynamic surface tension parameters for serum and urine samples obtained from healthy persons that were between 15 to 65 years old. The γ1, γ2, γ3, λ0 and λ1 parameters were obtained by maximum bubble pressure tensiometry for 80 volunteers of both genders. Other parameters were obtained by the drop profile analysis method for 40 volunteers of different age. The data listed in Table 1 correspond to stress deformations of liquid drops.
ACCEPTED MANUSCRIPT
12
Table 1. Values of dynamic surface tension parameters for blood serum and urine obtained from healthy volunteers (M ± m). Parameter
Biological liquid Urine
T
Serum γ [mN/m]
70.0 ± 0.41
γ [mN/m]
67.7 ± 0.35
γ [mN/m]
60.0 ± 0.44
γ [mN/m]
45.7 ± 1.02
0 [mNm-1s-1/2]
4.5 0.74
[mN/m-1s1/2]
12.6 ± 0.54
13.5 ± 0.47
[mN/m-1s1/2]
194.6 ± 16.9
209.6 ± 25.4
E [mN/m]
32.2 ± 1.56
15.7 ± 1.36
τ, s
120.5 ± 5.8
258.4 ± 16.7
IP
71.5 ± 0.33
61.8 ± 0.36 44.5 ± 1.61 4.9 0.65
D
MA
NU
SC R
69.3 ± 0.21
TE
The results of tensiometric studies of serum and urine taken from healthy persons show that there are certain specific features in dynamic surface tensiograms, which are determined
CE P
by the age and gender of the volunteers. Table 2 summarises averaged tensiography parameters of these biological liquids with respect to the person’s gender. These results, obtained by the maximum bubble pressure method show some differences between the
AC
genders. In particular, the surface tension value γ3 obtained for females are higher than those for males. The slopes λ1 of the tensiograms are also different: for serum it is higher for males, while for urine it is higher for females. Relatively high γ3 values for female serum can in part be attributed to a lower content of some proteins, lipids and hydrocarbon components.
ACCEPTED MANUSCRIPT
13
Table 2. Surface tension parameters of blood serum and urine for healthy persons with respect to gender (M ± m). Parameter
Male
Female
Serum
γ1, mN/m
69.2 ± 0.50
70.8 ± 0.59
γ2, mN/m
67.1 ± 0.39
γ3, mN/m
59.3 ± 0.18
61.3 ± 0.65
0, mNm-1s-1/2
4.9 0.90
1, mNm-1s1/2
15.3 ± 0.61
8.2 ± 0.60
γ1, mN/m
71.6 ± 0.24
71.5 ± 0.21
IP
γ3, mN/m
MA
0, mNm-1s-1/2
69.2 ± 0.27
69.3 ± 0.32
56.6 ± 1.81
61.1 ± 0.36
5.5 0.70
5.2 0.65
11.7 ± 0.43
15.2 ± 0.54
D
1, mNm-1s1/2
SC R
γ2, mN/m
68.3 ± 0.54 3.6 0.70
NU
Urine
T
Biological liquid
TE
The person’s age also affects the dynamic surface tension of biologic liquids. These results have been described in detail elsewhere [21, 22]. The tensiographic parameters γ3 and
CE P
λ1 of serum and urine were analysed in detail with respect to the person’s age. It was explained in [21, 22] that with increasing age the surface tension of serum increases (by 5 mN/m with the increase of age from 20 to 60 years), while the surface tension of urine decreases by 4
AC
mN/m in the same age range. The value of 1 for urine tensiograms increases over the first 40 years of life and then remains virtually constant, the 1 value of serum gradually decreases with age. The fact that certain relations exist between various tensiometric parameters is quite expectable. We have found correlations between particular interfacial tensiometric parameters that are gender related. For example, in serum and urine samples from males the relation between γ2 and γ3 is stronger than in samples from females. Strong correlations exist between 1 values of urine and γ1 or γ2 values of serum for males, while for females, such correlations were generally not detected. However, the correlation between the dynamic surface tension parameters for serum in the short and medium surface lifetime range (γ1 or γ2), and the γ3 for urine becomes stronger. For both genders, the 1 values of serum are strongly correlated with the γ1 value of urine. The tensiometry and visco-elasticity parameters of other biologic liquids for healthy volunteers are listed in Table 3. The number of volunteers in the group for each liquid was 40 to 140 persons. The dispersion of values shown in Table 3 for different liquids is roughly the
ACCEPTED MANUSCRIPT
14
same: 0.5-1.5% for all surface tension parameters i, 5-10% for all slopes i, about 5% for E and . It is seen that the surface activity values of the liquids are essentially different from each other due to differences in the chemical composition of their surface-active components.
T
Among all liquids listed in Table 3, the expired air condensate exhibits the lowest surface
IP
activity (maximum 4 value), while the highest surface activity is characteristic for the
SC R
duodenal fluid. The duodenal glands produce a liquid which contains about 2% proteins, nucleic acids and lipids, and more than 3% of mucin. The mucins possess a specific amino acid composition, with high contents of serine, threonine and proline, and also carbohydrates;
NU
all these substances exhibit surface activity.
The dynamic surface tension of serum and amniotic liquid obtained from 52 pregnant
MA
women was studied at various gestation stages. For 10 women, two and more analyses were performed. With increase of the gestation period, a gradual decrease in both dynamic and equilibrium surface tension of serum occurs, while a sharp increase of 1 is observed. It should
D
be noted that up to the 20th week of gestation, the surface tension values in the short and
TE
medium time range are quite similar to those characteristic for the reference group of nonpregnant women of corresponding age. The correlation coefficients for interfacial
CE P
tensiometric parameters of serum and amniotic liquid depend on the gestation period. This may indicate near parturition, thus being of certain practical interest. Table 3. Average values of surface tension parameters for various biologic liquids obtained
AC
from healthy volunteers (the total of 360 persons). The standard deviation of all tensiometric parameters was less than ±1% and for rheometric parameters less than ±4%. γ1,
γ2,
γ3,
γ4,
2 ,
mN/m
mN/m
mN/m
mN/m
mNm1s1/2 mN/m
s
Cerebrospinal fluid
71.7
66.6
60.4
47.3
286
29.7
287
Oral liquid
71.9
68.7
58.9
44.9
166
30.6
186
Breath condensate
72.2
69.7
61.4
53.2
309.4
25.8
461
Hepatic bile
72.0
65.2
54.1
42.6
89.1
11.7
94.0
Duodenal contents
69.3
60.8
51.9
38.6
126.7
28.4
219.8
Liquids
E,
τ,
As another example, in [50] data of oral liquid were performed with 142 volunteers in the age between 7 and 63 years. The gender of 66 patients was male and 76 was female. Non
ACCEPTED MANUSCRIPT
15
of the volunteers suffered from any acute inflammation in the oral cavity or chronic somatic diseases. The average values of measured tensiometric and rheological parameters are summarized in Table 3. Some of the obtained tensiometric parameters show a statistically
T
reliable relation to the age of the patients’. This is true for the equilibrium surface tension γ4
IP
(M±ε=48.0±2.3 mN/m) which is highest for the age of 5–9 years, while for the age group of
SC R
10–15 years this value is already decreased (46.3±2.6 mN/m). In groups of higher age this trend continues, i.e. for the group of 40–55 years the respective value is 42.3±3.5 mN/m. Finally, for patients of 55 years and older this value increases again to 45.7±2.9 mN/m. Differences are observed in the tensiometric parameters of saliva, which are most pronounced
NU
in the age of 7–15 years. As can be seen, the standard deviation ε is used for the analysis, and therefore the average values of γ4, calculated as M ± ε, overlap for different age groups. If we
MA
calculate the standard error of the mean value m, and determine the mean value as M ± m, then the overlap disappears, since m is 3-5 times smaller than ε. Another study of salivary gland secretion was performed with 14 healthy volunteers,
D
having an age between 19 and 25 years. For the collection of the secretion of the parotid gland,
TE
a special device was developed, while the secretion of sub-mandibular and sub-lingual glands was taken from the sub-lingual region using a micropipette. Overall, the tensiometric data of
CE P
the secretions of the greater salivary glands agree with those of the oral liquid as a whole. Some of the results are summarised in Table 4.
AC
Table 4. Tensiometric characteristics of secretions of parotid (P), sub-mandibular (SM) and sub-lingual (SL) glands (M±m); according to [50] Parameters
Oral liquid
Secretion of salivary glands P
SM and SL
γ4 , mN/m
44.2±0.6
45.3±1.8
43.4±1.3
λ2 , mN·m –1s 1/2
178±7
191±11
223±12
Е, mN/m
33.3±1.5
23.3±1.5
42.8±3.8
τ,s
215±7
202±6
302±23
As one can see the mixed secretion of sub-mandibular and sub-lingual glands show a larger visco-elasticity E (about 30% higher) than the oral liquid and it is about twice as high as the corresponding value for the secretion of the parotid salivary gland. The mixed secretion of sub-mandibular and sub-lingual glands has also a maximum in the surface tension relaxation time (τ), and there is also a difference in the tensiograms’ slope. The average slope
ACCEPTED MANUSCRIPT
16
for the oral liquid (a mixture of the secretions released by all salivary glands) is almost equal to the value of the parotid gland secretion, and about 30% lower than the value measured for saliva excreted by the sub-mandibular and sub-lingual glands. The observed differences for
T
these secretions in the tensiometric data should most probably be ascribed to the peculiarities
IP
of the biochemical composition.
SC R
4. Influence of diseases on surface characteristics of biologic liquids This section summarises the results of tensiometric and surface rheologic studies of various biologic liquids taken from the patients suffering from different diseases; the studies
NU
were performed in the Physicochemical Laboratory of the Donetsk National Medical University. Some results were reported earlier in [21,22,42-57,72-74] and (for some diseases)
MA
discussed in details in the review [18]. Also data published by other authors [7-17, 75-89] concerning the tensiometry of biologic liquids are considered in the analysis presented here. However, it should be noted that these studies do not present any systematic tensiometric and
TE
D
surface rheological studies to match those made in our laboratory. 4.1. Oncology
CE P
For patients suffering from cancer at various localisations, increased concentrations of γ-globulin, 2-microglobulin, 2-glycoprotein, ferritin, immune complexes, T-globulin, Creactive protein, ferritin, haptoglobin and α-antitrypsin in blood were detected. The
AC
concentration of albumin, pre-albumin and α2NS-glycoprotein correlate inversely with the extent of tumor invasion. Usually a decreased glucose level in blood is observed for extended tumour processes. The hypoglycaemic stress acts as a factor which initiates an increased secretion of the somatotrophic hormone. These factors change the surface tension parameters and help to evaluate cancerous phenotype, cell metastasis and therapeutic efficacy. Fatty acids increase in blood due to an increased cell death. The presence of malignant tumour is accompanied by the increase in the amount of serum mucoids and sialic acids. Therefore, the existence of malignant tumour of any localisation leads to certain distortions of the homeostasis. These changes take place in the organism and affect the biochemical composition of blood, generally leading to the decrease of surface tension at medium and high surface lifetime. The application of radiotherapy results in a normalisation of the state of the antioxidant system and of the phospholipid levels: these characteristics become closer to those common for patients at early stages of tumour processes. In a number of cases the
ACCEPTED MANUSCRIPT
17
radiotherapeutic treatment is accompanied with the development of certain inflammatory complications in the intestine and urinary tracts (rectites, colites, cystites, urethrites with various degrees of severity). As the clinical symptoms of the inflammation process are the
IP
T
final consequences of quite prolonged alteration (damaging) processes taking place in the tissue, one can expect to detect the inflammation products in the serum long before the
SC R
inflammation becomes clinically evident. The dynamic interfacial tensiometry, being quite sensitive to such changes, enables one to predict the development of complications caused by radiotherapy even at early stages of the treatment. Comprehensive prophylactic
NU
actions aimed at the prevention of complications, if taken promptly, would be of much help in the treatment of female reproductive organs’ neoplasm.
MA
The dynamic surface tension of blood serum for 46 patients suffering from malignant neoplasm of corpus uteri (7) and cervix uteri (39) was studied. The serum taken
D
from patients was studied with regard to the course of the disease: before the medical
TE
treatment started, i.e. on admission of the patient, during the treatment (radiotherapy) and after the treatment. Therefore, the studies included three stages: Stage I, prior to
CE P
medical treatment; Stage II, during the treatment; and Stage III, after the treatment. The surface tension of serum was studied using the two experimental methods described above. Among 46 patients studied, for 14 cases (30.5%) certain complications (colitis, rectitis and
AC
cystitis in various forms) developed. The variations in the mean values of tensiometric parameters during the radiotherapy process for the two patient groups are listed in Table 5 [52,53,72,73].
ACCEPTED MANUSCRIPT
18
Table 5. Mean values of the serum dynamic interface parameters for malignant neoplasm of cervix and corpus uteri in the process of combined radiotherapy, differentiated with respect to the presence or absence of inflammations caused by irradiation (M±ε). Stage I
Stage II
persons
With
SC R
Without
Stage III
T
Healthy
IP
Parameters
Without
With
inflam.
inflam.
inflam.
γ1 (mN/m)
70.82.8
71.32.0
70.62.8
70.42.7
70.72.4
70.43.0
γ2 (mN/m)
68.33.0
65.53.5
65.04.0
63.44.3
66.33.2
64.44.0
γ3 (mN/m)
61.33.4
52.8 4.2 54.84.4
52.04.6
58.14.0
56.04.8
1[(mN/m)s1/2]
8.23.0
17.65.5
NU
inflam.
14.15.2
10.74.3
12.24.2
MA
12.94.0
D
It is seen that a significant decrease of the γ2 and especially of γ3 (by almost 10 mN/m
TE
lower) values in the group of patients with malignant neoplasm. as compared to the values for normal females. In the group of patients with complications the increase of γ2 and γ3 was not
CE P
very pronounced. Moreover, at the intermediate stage of the treatment the γ3 value even becomes somewhat lower as compared to the value observed before the treatment. The λ1 variation during the treatment is also determined by complications, which, if developed, result in less a pronounced decrease of λ1 with respect to the initial level. If the radiotherapy is not
AC
accompanied by inflammatory reactions, then a significant decrease of this parameter is observed, which approaches the reference values for healthy females at the end of the radiotherapy. At the end of a radiotherapy treatment the differences between tensiometric parameters of serum obtained from patients and healthy females become essentially (by 6070%) less significant. As mentioned above, the use of the standard error of the mean value m in contrast to the variance ε excludes overlapping of the compared parameters. The most pronounced differences between the studied patients’ groups were found with respect to the dynamics of the tensiographic parameters measured for each particular patient. This means that the differences between the corresponding parameters (3) measured during the therapy and before the therapy were used rather than the absolute values of the parameters. More specifically, these differences were obtained by subtracting the parameter value before the treatment from that measured after Stage II or Stage III for each particular patient, respectively. The results thus obtained were averaged over the two groups studied, i.e.
ACCEPTED MANUSCRIPT
19
with and without any complications. In Figs. 4 the distribution curves after Stage II are plotted against the number of cases studied: it is seen that the distribution areas of γ3 values are
CE P
TE
D
MA
NU
SC R
IP
T
overlapped in ca. 15 % of cases.
AC
Fig.4. Probability distribution curve for γ3 values after stage II with the presence (dashed curve) and absence (solid curve) of inflammatory complications. Similar values were obtained also for γ2 (10 % cases) and ∆λ1 while for this overlap is observed in approximately 20% of all cases. Therefore, from the analysis of the sign of the variation of ∆γ2 and ∆γ3 only, one can predict, for 85% of all cases, possible complications during the radiotherapy. It should be noted that these variations of the tensiometric parameters are detectable prior to the moment when any clinical evidence becomes evident; this enables one to start the complication-preventing therapy at an early stage of the radiotherapeutic treatment. As the tensiometric techniques are relatively simple, these methods can be proposed for the clinical practice.
ACCEPTED MANUSCRIPT
20
4.2. Oral liquid, effect of carious lesion of teeth The study was performed with 23 children of age 4–6 with milk occlusion, divided into two groups. The caries free group was composed of 6 girls and 5 boys; the other 12
T
examined children (6 girls and 6 boys) constituted the caries-active group. The comparison
IP
between the tensiometric parameters of oral liquid samples taken from caries-free and caries-
SC R
active children has revealed significant differences between the corresponding values of γ1, γ3 and λ1. The surface tension γ3 of oral liquid for caries-active children was found to be 3 mN/m lower than that for caries-free children, while λ1 value was by 29% higher. This indicates that
NU
the amount of surfactants (or their surface activity) in the oral liquid of caries-active children is higher than that of caries-free children. The tensiometric characteristics of the oral liquid of caries-free children are found within the limits indicated in Table 1 for healthy volunteers.
MA
The comparison of biochemical parameters of oral liquid (the contents of total protein, calcium, phosphorus and triglycerides) did not exhibit any statistically reliable differences
D
between the groups of caries-active and caries-free children. To summarise at this point, essential differences between the tensiometric parameters
TE
of oral liquid taken from caries-free children were found as compared with those of cariesactive children. This indicates the promising prospects of dynamic interfacial tensiometry of
CE P
saliva as applied in dentistry for the development of new diagnostic criteria and approaches for the estimation of caries-resistant tooth enamel. These studies also help understand the
AC
physico-chemical nature of caries. 4.3. Neurosyphilis
Neurosyphilis (NS) is the lesion of the nervous system caused by a syphilitic infection. It results in specific changes of the liquor cerebrospinalis (cerebrospinal fluid, CSF). Due to the syphilitic process in the nervous systems its diagnostics can be complicated. Traditionally, the initial diagnostics of NS is mainly based serological studies of blood and CSF, and the probability of a correct diagnosis is only between 30 and 70 %. Hence, new and more informative methods are required for its diagnostics. The results we want to present here were obtained in [51] in a study with 75 patients suffering from various forms of NS and syphilis. The first group of 22 patients had clinical (manifested) forms of NS with a main diagnosis of an early cerebral meningovascular syphilis (14 patients). The second group of 23 patients suffered from latent (asymptomatic) NS showing no neurologic symptoms but had a positive syphilitic tests and changes in the clinical analysis of CSF. In a third group the 15 patients had syphilis accompanied by a neurologic
ACCEPTED MANUSCRIPT
21
disease like discirculatory or toxic encephalopathy. In a reference group the 15 patients had syphilis without any additional neurologic diseases. The results of dilational rheology studies are summarized in Table 6.
T
It is seen that the value of the dilational stress modulus E for the patients from all three
IP
screened groups is lower as compared with the value (29.7 ± 1.5 mN/m) for the reference
SC R
group. Thus, the observed decrease of the value of E indicates a pathology of the nervous system.
Table 6. Surface rheological parameters of the CSF (M ± m) for different groups of patients;
NU
according to [51] First, n = 22
Second, n = 23
Third, n = 15
Reference, n = 15
E, mN/m
24.7±1.2
25.4±1.1
21.1±1.1
29.7±1.5
τ, s
261.1±16.1
253.0±12.9
238.2±16.6
286.8±15.3
a1, mN/m
34.6±1.7
35.9±1.6
31.2±1.5
41.3±1.7
b1, mN/m
8.6±0.5
8.2±0.6
7.4±0.8
9.8±0.9
a2, mN/m
6.7±0.35
6.5±0.4
6.3±0.4
8.2±0.7
b2, mN/m
-0.13±0.14
0.05±0.13
0.09±0.20
0.2±0.25
CE P
TE
D
MA
Parameter
The lowest E values (21.1 ± 1.1 mN/m) were observed for patients in group three. Compared with the reference group of patients, the parameters for the three groups a1, a2 and
AC
b1 were essentially different (p < 0.1). For the groups one and three, for the parameter a1 (the elasticity at a frequency of 1 rad/s) the largest differences (p < 0.05) were observed. Note, there is a strong correlation (r = 0.9) between a1 and E for all groups, which however is expected, because these parameters refer to different methods of the dilational surface rheology studies. The correlations discussed here reveal the applicability of dilational rheology parameters for the diagnostics of neurosyphilis, and the differential diagnostics of accompanied diseases. Value of a1 larger than 40 mN/m undoubtedly indicate the absence of pathologies of the nervous system for the patients with syphilis. For value lower than 32 mN/m, we can conclude that the syphilis is accompanied by a neurologic disease, mainly by a discirculatory or toxic encephalopathy.
ACCEPTED MANUSCRIPT
22
4.4. Congenital pneumonia of premature newborns Common diagnostic methods of congenital pneumonia are based on X-ray examinations. X-ray technique allows detecting the main symptom for most new-borns with
T
congenital pneumonia only rather late. Thus, new methods for an early recognition of
IP
congenital pneumonia is an urgent need in neonatology. The umbilical blood and expired air
SC R
condensate of 60 premature new-borns in the gestational age 22-36 weeks suffering from a respiratory distress at birth were studied. The 60 patients were divided into three equal sized groups. The first group consisted of patients with congenital pneumonia (CGP); the second of
NU
patients with a respiratory distress syndrome (RDS), and the third consisted of patients with both pathologies. Ten healthy breast-fed premature new-borns (gestational age of 35-36 weeks) have been taken as reference group. The surface rheological parameters of the
MA
umbilical blood for all studied groups did not show differences to the reference group. This can probably be explained by the fact that the scattering of data is rather large (cf. Table 6). However, strong differences are observed for the phase angle φ obtained from Eq. (5) at the
D
highest frequency. The respective φ values at the frequency of 1 rad/s = 0.16 Hz for the four
TE
groups are: reference group (19.6±1.4)°; CGP, (22.1±0.7)°; RDS, (17.3±1.0)°; and CGP + RDS, (20.6±0.7)°. One can see that the values for the two groups CGP and RDS are essentially
CE P
different from those for the reference group (with a reliability level of p < 0.1), i.e. for the CGP group the phase angle is reliably higher than for the reference group, while for the RDS group it is reliably lower.
AC
However, the rheological parameters of the expired air condensate for the premature new-borns (CGP, RDS, CGP + RDS) with respiratory impairments are the same (within measurement errors) as those for the reference group, and no remarkable dependence of the phase angle value was observed. At low oscillation frequencies the imaginary part of the visco-ealsticity is higher while the real part is lower as compared with the values at higher frequencies. Hence, the phase angle becomes much higher with decreasing oscillation frequency. The phase angle φ for the CGP and RDS groups at a frequency of 0.016 Hz was close to the values for the reference group (12.0±1.0)°, while for the group of CGP + RDS it was (13.8±0.6)°. Therefore, studies of the surface dilational rheology of expired air condensate can support the diagnostics of respiratory impairments of premature new-borns. Note, some studies showed very low dynamic surface tensions of the umbilical blood of premature new-borns suffering from severe respiratory impairments and hence requiring artificial pulmonary ventilation. The mentioned results are shown in Fig. 5.
23
TE
D
MA
NU
SC R
IP
T
ACCEPTED MANUSCRIPT
CE P
Fig. 5. Dependence of the dynamic surface tension of the umbilical blood taken during the first day of life; curve 1 () - premature new-born from the reference group; curves 2 () and 3 () - premature new-borns with congenital pneumonia.
AC
For all new-borns the gestational age was small and the weight at birth was less than 2 kg. Moreover, a congenital pneumonia was observed and also the pregnancies of all mothers were abnormal.
4.5. Chronic recurrent pancreatitis The chronic recurrent pancreatitis (CRP) leads to changes in the contents of surface active substances (proteins, lipids, electrolytes, hormones) in the biologic liquids; this in turn results in changes of the tensiometric parameters of blood, urine and pancreatic secretion [74]. To study these effects, 72 CRP patients (34 males and 38 females, age 20 to 63) in an acute stage were screened, along with 30 healthy volunteers (13 males and 17 females, age 20 to 60). In Table 7 the data obtained by interfacial tensiometry and surface rheology of blood, urine and duodenal liquid from CRP patients are compared with those obtained from healthy
ACCEPTED MANUSCRIPT
24
persons. The dispersion of values shown was: 1.0-1.5% for the surface tension; 7-10% for all parameters; about 4% for Е and τ. All blood tensiometric and rheology values (except 2) for CRP patients exhibit reliable difference from corresponding values for healthy persons; in
T
particular, for sick persons the γ1, λ1, λ2 and τ values are higher, and γ3, γ4 and Е values are
IP
lower. For urine and duodenal liquid the disease leads to a significant decrease of γ2, γ3 and
SC R
γ4. Thus, the results of the correlation analysis indicate the possibility to apply interfacial tensiometry and rheology for the estimation of the CRP progress and the efficiency of applied therapy: the trends of the parameters to the values characteristic for sick persons evidences the exacerbation of the disease, while the changes towards the normal values of the parameters
NU
indicate the efficiency of curation and future remission.
MA
Table 7. Tensiometric and surface rheological parameters of blood, urine and duodenal liquids for CRP patients and healthy volunteers Fluid n
γ1,
γ2,
mN/m
mN/m
γ4,
λ1,
λ2,
mN/m
mN/m
(mN/m)·s
(mN/m)·s
1/2
Е, 1/2
τ, s
mN/m
D
parameters
γ3,
TE
Blood 72
74.38
68.40
57.18
41.22
18.23
246.28
28.65
112.8
Sick
30
70.00
67.70
60.00
45.50
12.60
189.20
32.80
103.7
Urine Healthy
72
69.80
63.15
57.24
50.86
15.87
129.52
29.62
112.6
30
71.50
69.40
61.80
51.60
13.40
111.00
30.30
110.2
AC
Sick
CE P
Healthy
Duodenal liquid Healthy
72
61.16
53.26
46.36
31.72
10.62
98.63
38.12
262.1
Sick
30
69.32
60.82
51.87
38.62
15.40
126.70
28.40
219.8
4.6. Acute renal failure Tensiometric and surface rheological parameters of blood serum for acute renal failure (ARF) patients were shown to differ significantly from the values for healthy persons. These parameters for ARF patients depend on the clinical progression of the disease. For patients with a severe disease form in the pre-dialysis period these differences as compared to the reference group are illustrated in Table 8. The essential decrease of γ1, γ2, γ3, λ2 and E, and the increase of are evident; this indicates that the development of a severe ARF form results either in the increase of the concentration or the enhancement of the adsorption properties of
ACCEPTED MANUSCRIPT
25
surfactants in the blood serum. Table 8. Tensiometric and rheologic parameters of blood serum for ARF patients immediately
T
before a dialysis treatment (M±m) compared with a reference group. ARF persons
(n=20)
(n=68)
γ1, mN/m
72.94±0.34
71.66±0.23
γ2, mN/m
68.35±0.33
γ3, mN/m
58.72±0.49
γ4, mN/m
45.57±0.66
λ1, mN/m-1s1/2
17.12±0.96
λ2, mN/m-1s1/2
193.68±15.45
Е, mN/m
29.54±1.23
18.26±0.90
τ, s
110.18±8.29
138.92±10.21
SC R
IP
Reference group
67.41±0.23
NU
54.81±0.48 46.07±0.42 21.31±1.05 122.46±6.80
D
MA
Parameter
TE
To specify the influence of clinical factors and the homeostasis parameters on the physicochemical properties of blood serum, the correlation analysis was employed. It was
CE P
shown that a correlation exists between the tensiometric and rheological values of blood serum with the creatinine level, leukocytal intoxication index, erythrocyte sedimentation rate, platelets concentration, fibrinogen level, and the estimated severity of the patient’s condition.
AC
These multiple correlations demonstrate that the tensiometric and rheometric parameters are useful for a comprehensive estimation of the clinical progress of ARF. The improvement of the clinical state during medical treatment is also accompanied by significant changes (increase) of certain tensiometric and rheometric parameters as compared with initial (pre-treatment) values for patients with ARF, in particular λ2 from 121.6±10.28 to 168.8±12.4 mN/m−1s1/2, Е from 19.0±1.17 to 25.6±2.6 mN/m. This was found also for patients with a multiple organ failure during the positive dynamics of the disease progress: λ2 from 121.9±9.2 to 167.2±19.8 mN/m−1s1/2 and Е from 17.3±1.7 to 25.1±1.5 mN/m. Also, in these groups of patients the 3 value increases and becomes indistinguishable from its value for the reference group. 4.7. Women with infertility The tension and rheology parameters of blood and oral liquid of women with infertility and thyroiditis were studied for 40 women with infertility for which the assisted reproductive
ACCEPTED MANUSCRIPT
26
medical treatment was unnecessary. Two groups of patients were studied: (1) 20 women with the Hashimoto’s thyroiditis, and (2) 20 women without any thyroid pathology. No changes have been found in tension and rheology parameters of blood for women with infertility and
T
autoimmune thyroiditis compared to women with infertility and normal function of the
IP
thyroid. However, the parameters of oral liquid for the two groups of women were different
SC R
(see Table 9).
Table 9. Tensiometric and surface rheological parameters of oral liquid (comparison between groups 1 and 2, M±m). Group 1
Е, mN/m
43.0±2.8
39.6±3.8
τ. s
174.2±8.3
175.9±6.1
γ4. mN/m
47.4±0.52
43.9±0.55
λ2. mN/m–1·s1/2
108.6±8.5
132.8±4.4
Group 2
D
MA
NU
Parameter
TE
It is seen that the parameter γ4 becomes increased and λ2 is decreased for women with infertility and autoimmune thyroiditis, as compared to women with thyroiditis and a normal
CE P
thyroid function. The increase of γ4 and strong negative correlation with the level of lymphocytes in blood could be used as an additional marker for the estimation of the state of cellular immunity for women with infertility and autoimmune thyroiditis. Therefore, the
AC
analysis of oral liquid taken from women with infertility could be used for the early detection of autoimmune processes in thyroid. 4.8. Arthritis, chronic bronchitis and chronic obstructive pulmonary disease For rheumatoid arthritis, the rheological characteristics of breath condensate (stress experiment) were found to depend on the patients’ gender and age, and the extent of the pathologic process activity. With the increase of the disease duration, a decrease of both the pH and visco-elastic modulus E of the breath condensate was observed. The corresponding properties depend on the presence and extent of the respiratory pathology: in absence of pheumopathy, E = 29.8±1.7 mN/m and = 486±60 s; otherwise E = 21.3±1.8 mN/m and = 667±145 s. The catadrome of the rheumatoid pheumopathy is accompanied by a decrease of the visco-elastic modulus of the breath condensate. A value for E < 15 mN/m appears to be indicative of severe rheumatoid pheumopathy. For patients with nephropathy the observed values of E and of urine are lower as compared with other patients suffering from rheumatoid
ACCEPTED MANUSCRIPT
27
arthritis. In absence of a nephropathy we found E = 26.9±0.8 mN/m and = 290±12.2 s; while with nephropathy we obtained E = 24.3±0.8 mN/m and = 238±9.8 s. The modulus E of urine correlates inversely with the duration of a disease, and directly with the degree of the activity
T
of the pathologic process. A correlation exists between the extent of kidney injury and the
IP
physico-chemical parameters of urine. In particular, the E and values correlate inversely
SC R
with the severity of the nephropathy, which is of high practical significance. For the juvenile rheumatoid arthritis, a remarkable increase of the plasma viscosity (PV) as compared with that of healthy children was observed. Also, the dilational surface
NU
stress experiments indicate a significant decrease of the E and values of blood serum, as one can see in Table 10. It is important to note that the equilibrium surface tension of blood serum is almost the same for sick and healthy children (45.7±0.9 and 45.9±1.0 mN/m, respectively).
MA
This fact reveals essentially higher sensitivity of the surface rheological methods used here to study the interfacial characteristics of human biologic liquids.
D
Table 10. Rheological characteristics of blood serum for patients with juvenile rheumatoid
TE
arthritis and healthy children for compare (M±m). Parameters
Sick
Healthy
PV, mPa·s
2.1±0.08
1.6±0.03
E, mN/m
26.5±0.6
33.1±1.5
, s
104.1±3.4
127.4±4.1
CE P AC
Examined groups
The univariate dispersion and regression analysis demonstrates a direct correlation between the activity of juvenile rheumatoid arthritis and the parameters of plasma viscosity and relaxation time . The concentration of serum fibrinogen is positively correlated with the PV and negatively correlated with the E values. For patients with reactive arthritis, an inverse correlation was found between the dynamic surface tension of blood serum and the erythrocytes’ aggregation index. It was reliably shown that the E and decrease with the increase in plasma viscosity. The modulus E depends on the degree to which the tendovaginitis or autonomic imbalances are expressed. A direct correlation was found between E and the degree of angioneurosis. The extent of ophtalmopathy correlates inversely with E and , and also with the blood serum equilibrium surface tension. The development of a pathology of the aortic valve leads to changes in the
ACCEPTED MANUSCRIPT
28
blood serum equilibrium surface tension 4. From the obtained results, it was concluded that for the reactive arthritis any values 4 > 50 mN/m indicate an unfavourable affect of the aortic valve. For patients with reactive arthritis a nephropathy results in increasing dynamic surface
T
tensions and E modules of urine, accompanied by decreased values for 4 and . The
IP
rheological properties of urine do not depend on the patients’ age and total activity of the
SC R
disease, while at the same time these parameters are determined by the duration of the disease. The development of a nephric pathology results in decreased values of 1, 3 and 4 and simultaneously increases E, as shown in Table 11.
NU
Table 11. Properties of urine for patients with reactive arthritis and kidney damage without nephropathy (M±m).
Examined groups
MA
Parameters
Nephropathy present
γ1, mN/m
72.6±0.30
70.7±0.38
γ3, mN/m
62.0±0.58
59.0±0.53
49.8±0.40
46.3±0.46
16.3±0.43
20.0±0.53
160±5.5
148±3.9
, s
CE P
E, mN/m
TE
γ4, mN/m
D
Nephropathy absent
The values of γ1 and γ4 correlate inversely with the total proteinuria, leukocytouria and
AC
fibronectynuria levels. Also, correlations exist for the albumin concentration in the urea and 3 and E, of the leukocyte concentration with 3, and fibronectin concentration with . For patients with chronic bronchitis and a chronic obstructive pulmonary disease the rheological properties of breath condensate are determined by the character of the respiratory moisture excretion. For these two diseases, the rate and extent of respiratory moisture excretion affect the parameters E and . The patients’ gender and age significantly affect the rheological properties of breath condensate. The development of a chronic obstructive pulmonary disease is accompanied by a significant increase of E. The character of bronchial obstruction affects the values of E and , while a bronchial restriction influences only the E value of the respiratory fluid. For patients with a chronic obstructive pulmonary disease the values of 1, E and of blood serum are significantly higher than the values typical for healthy persons. For patients with chronic bronchitis, of the breath condensate becomes lower, for a chronic obstructive pulmonary disease this value becomes higher, and if both pathologies are
ACCEPTED MANUSCRIPT
29
present, an increase in E is observed. From the analysis of the data it can be concluded that for the breath condensate values of E > 40 mN/m for chronic bronchitis, and E > 50 mN/m for a chronic obstructive pulmonary disease accompanied by coronary heart disease, are
IP
T
indicative of a negative prognosis for the development of the disease. 4.9. Other diseases
SC R
In this part we will shortly review the results of the following diseases: gout, lupus erythematosus. scleroderma systematic, purpura rheumatic, chronic rheumatic heart disease,
periodontitis and microcholelithiasis.
NU
chronic pyelonephritis, diabetic nephropathy, peptic gastroduodenal ulcer, chronic For gout, there is a significant decrease of E and of the blood serum: the relaxation
MA
time decreases for 85% of the patients, while the elasticity modulus decreases for 79% of the patients. The dynamic surface tension of blood serum depends on the development of a metabolic syndrome. The increase of 1 and 3 of the blood serum for patients with chronic
D
gouty arthritis was detected in 87% and 53% of cases, respectively. Decreased values of λ 1
TE
for blood serum were found for 73% of screened patients with an intermittent form of the articular syndrome, while for the chronic form this value becomes 97%. The degree of severity
CE P
of the articular syndrome is closely related to the surface tension 1 of the blood serum: its decrease indicates a most probable unfavourable prognosis of the development of gouty arthritis. For patients with gout, the dynamic surface tension of urine and the relaxation time
AC
is lower for sick than for healthy persons. With the development of renal insufficiency we observed a significant decrease of the dynamic surface tensions of the blood serum and urine, which was especially significant in the short time range. To summarise, gout leads to a decrease of the parameters E and for the blood serum. Also changes in the physico-chemical characteristics of breath condensate (decrease of 4 and ) were observed, caused by the patients’ age and the duration of the disease. For patients with a gouty nephropathy an increase of the dynamic surface tension and a decrease of the relaxation time for urine were observed. Systemic lupus erythematosus leads to a decrease of pH of the breath condensate and to a significant (by more than a factor of two) decrease of from 462.6±25.5 mN/m to 214.8±10.6 mN/m. While traditional methods are able to detect pulmonary changes in 39% of the cases, decrease values of 4 and for the breath condensate were found for 80% and 97% of patients, respectively. The systemic lupus erythematosus is characterized by increased values of the surface tension and λ1. When the peripheral nervous system is affected, also the
ACCEPTED MANUSCRIPT
30
dynamic surface tension γ3 of blood serum is lowered. It was shown that the values of 3 > 60 mN/m are indicative of damages to the central nervous system, and values 3 < 55 mN/m reflect the presence of peripheral nervous disorders. The development of
T
neurolupus is accompanied by increasing values of E and of the blood serum. The anti-
IP
phospholipid syndrome leads to significantly increased values of E and for blood serum and
SC R
1 for the cerebrospinal liquid. For the lupous nephritis, an increase of E by a factor of two, and a significant increase of the surface tension of urine in the range of short and intermediate surface ages were observed, while the γ3 decreased (cf. see Table 12). The nephrotic syndrome
NU
is related to the 1, while the renal function has its influence on the majority of physicochemical parameters, including the dynamic surface tension, E and .
MA
Table 12. Physico-chemical parameters of urine for patients with lupous nephritis and healthy persons (M±m).
Examined groups Healthy
γ1, mN/m
71.9±0.18
69.5±0.33
γ2, mN/m
67.9±0.28
66.3±0.56
γ3, mN/m
49.1±0.59
51.6±0.66
Е, mN/m
31.3±1.70
16.0±0.58
CE P
D
Sick
TE
Parameters
AC
The rheological parameters of urine exhibit unambiguous reactions to the deteriorating renal function: relaxation times < 170 s indicate a negative prognosis of the lupous nephritis development. Our statistical analysis has revealed that values E > 40 mN/m and < 170 s correspond to a mesangium capillary glomerulonephritis, while E < 25 mN/m and > 240 s are characteristic for a mesangium proliferative glomerulonephritis. The dermatic lupus erythematosus leads to a significant decrease of the E and parameters for blood serum as compared to those of healthy persons. The severity of each type of skin pathology affects the values of 3, 4 and E. The results indicate that values of 4 < 40 mN/m and E < 25 mN/m are indicative of a negative prognosis with respect to the course of telangiectasises for patients with dermatic lupus erythematosus. Relaxation times < 90 s indicate an unfavourable prognosis for the extent of pathologic processes. Scleroderma systematica leads to increased values of 1 and 3 for blood serum, and of 1 for urine. The values of λ1 for blood serum increase and for urine decrease, respectively.
ACCEPTED MANUSCRIPT
31
These changes in the dynamic interfacial tensiometric parameters are specific to the scleroderma systematica, in contrast to other systemic diseases of the connective tissue. Values of λ1 > 10 mN·m1s1/2 for blood serum indicate an ongoing activity of the pathologic
T
processes during a pathogenetic therapy. For patients suffering from scleroderma systematica
IP
the pH value of the breath condensate is decreased, and the values of and of this fluid
SC R
become significantly lower. The patients with purpura rheumatica exhibit statistically significantly increased values of γ2, γ3, and decreased values (by almost 30%) of E and as compared to healthy persons (cf. Table 13). It was shown that values 3 > 50 mN/m are
NU
indicative for a negative prognosis of the development of the disease. Table 13. Rheometric and tensiometric parameters of blood serum for patients with purpura
MA
rheumatica and healthy persons (M±m)
Parameters Examined groups Healthy
E, mN/m
24.5±0.3 33.7±1.1
, s
101±2.1
γ2, mN/m
69.0±0.2 68.3±0.1
γ3, mN/m
59.9±0.3 58.2±0.25
CE P
TE
D
Sick
128±3.5
For chronic rheumatic heart, a significant decrease (by almost 50%) of the relaxation
AC
time τ of breath condensate is observed: from 463 s to 282 s. For breath condensate, the value of depends on the rheumatism activity and the degree of blood circulation inefficiency. It was shown that dynamic interfacial tensiometry and rheometry data of breath condensate provide information on s lesser circulation: values E > 45 mN/m for patients with chronic rheumatic heart disease are indicative of a pulmonary hypertension. For the chronic pyelonephritis decreased equilibrium surface tensions of blood serum were observed, both for male and female patients. For female patients, in addition, a decrease in the 1 values of blood serum and urine is observed. The deterioration of the renal function is accompanied by a significant increase of λ1 of urine. This fact could be used as one of the negative prognostic criteria of the development of this disease. Peculiar features for cases of chronic pyelonephritis with respect to the presence or absence of diabetes mellitus are differences in the values of γ3 and λ1 of blood serum, and the surface tensions of urine. While for the patients with diabetes mellitus the surface tension increases in the short and
ACCEPTED MANUSCRIPT
32
intermediate surface lifetime range, for patients without diabetes mellitus a decrease of this parameter is observed. This detail is of a firm diagnostic value, and can be ascribed to the presence of glucosuria. In the moment, it can be stated that tensiometric parameters for cases
T
of diabetic nephropathy are quite informative.
IP
The renal lesion caused by diabetes mellitus is accompanied by high values of λ1. For
SC R
patients with a diabetic nephropathy the surface tension of urine becomes lower, but in cases with chronic pyelonephritis the equilibrium values of the surface tension γ4 aa well as the dynamic surface tension 1 increase. For diabetes mellitus, the decrease or increase of the 1 value for urine could be a reliable differential diagnostic indicator of diabetic nephropathy vs
NU
chronic pyelonephritis. The presence of a nephrotic syndrome affects significantly the 2 value for urine. Pyelonephritis in a chronic stage also affects the parameters of dynamic interfacial
MA
tensiograms of some liquids. In the analysis of the interfacial tensiometric parameters, deviations in the urine parameters are more frequent. In particular, the deviations of 1 from
D
its normal value were detected in 52% of all cases (in 72% of male patients), and of 3 in 76%
TE
of all cases (in 91% of male patients). The development of a nephritic syndrome is accompanied by a surface tension decrease for blood serum and urine in the range of
CE P
intermediate surface ages. For patients with diabetic nephropathy the 2 values of blood serum and urine reflect the severity of the disease: a decrease of this parameter below 67 mN/m and 68 mN/m for blood serum and urine, respectively, indicate a negative prognosis of the course of the diabetic nephropathy.
AC
For patients with peptic gastroduodenal ulcer the rheological parameters of gastric juice are: E = 17.8±1.5 mN/m, = 240±13 s. Also a dependence of the dynamic and equilibrium surface tensions on patients’ gender and age was found. The blood serum parameters for these patients are E = 42.8±1.4 mN/m, = 166±9 s. For peptic gastroduodenal ulcer the parameter values for E and are higher than those for healthy persons. In cases of gastroesophagal reflux a decrease of of the gastric juice is observed, while for a duodenogastral reflux the dynamic surface tension becomes lower. If a duodenitis is present, an increase of both parameters occurs. For patients with duodenogastral reflux a decrease of the E value of the gastric juice was observed, while duodenitis leads to a decrease of 4. If the disease is accompanied by cholecystitis and biliary dyskinesia, the values E and become lower. For chronic periodontitis a significant decrease of the surface tension values, and of E and of the oral fluid as compared with those for healthy persons weres observed. The
ACCEPTED MANUSCRIPT
33
decrease of the values of 1, 2 and of the oral fluid was found in 78%, 79% and 59% of patients, respectively. The severity of chronic periodontitis affects the rheological properties of the oral fluid. It was shown that values γ3 > 60 mN/m and > 160 s, and also γ4 < 40 mN/m
T
indicate a grave course of the disease, which is of large practical importance.
IP
The microcholelithiasis is the initial stage of cholelithiasis. The study of the interfacial
SC R
dilational rheology of bile has shown that the visco-elasticity modulus E and the relaxation time for patients with this pathology are 12.52.8 mN/m and 274.333.5 s, respectively, while for healthy persons and for patients with microcholelithiasis after medical treatment,
NU
the E values were zero within the experimental error (±0.2 mN/m). The fact that E is close to zero can be attributed to an extremely rapid exchange between the solution bulk and surface layer, which is usual for adsorption layers of low molecular weight surfactants, if their
MA
concentration in the bulk is sufficiently high. On the contrary, the E and values for microcholelithiasis patients before medical treatment indicate much lower surfactants
D
concentration in the bile. Therefore, the visco-elasticity modulus could be used in the
TE
microcholelithiasis diagnostics and for monitoring the medical treatment. 4.10. Influence of fluorocarbon gases on lung phospholipid monolayers
CE P
Fluorocarbon gases are used for pulmonary disease therapies [27-35,90]. Langmuir monolayers of dipalmitoylphosphatidylcholine (DPPC – the main component of the native lung surfactant) have been studied in [27, 28]. It was found that upon compression in the
AC
region of the LE/LC (liquid-expanded/liquid-condensed) phase transition domains are not formed when the atmosphere above the monolayer was saturated with fluorocarbon gases. The adsorption dynamics of some phospholipids from aqueous solutions or dispersions was investigated by bubble profile analysis tensiometry in the presence of perfluorohexane (PFH) in the gas phase [33]. The presence of PFH strongly increased the adsorption rate as well as decreased the equilibrium interfacial tension of the phospholipid monolayers. For both effects, the strong interaction of PFH with the phospholipids in the monolayers is responsible, PFH acting as a co-surfactant. In [91] the theoretical model derived in [92] for mixed adsorption layers was used to describe the co-adsorption of a soluble surfactant from an aqueous solution and a second compound from the vapor phase. It was found that the adsorption equilibrium constant for DPPC is increased in presence of PFH in the gas atmosphere.
ACCEPTED MANUSCRIPT
34
For insoluble monolayers a complicated model was used in [93, 94] which takes into account: 1) LE/LC phase transition; 2) bimodal distribution (large clusters and monomers); 3) different molar area in the aggregate and of free monomers; 4) a non-ideal entropy of mixing.
T
This leads to a more realistic characterization of the amphiphilic compounds in the monolayer.
IP
When fluorocarbon molecules are adsorbed at the surface covered by DPPC and interact with
SC R
them via attraction forces, the mutual interaction energy between DPPC molecules in the surface layer is reduced, leading to a very effective fluidization of the monolayer. 5. Conclusions
NU
Surfaces are critically important for nearly all aspects of biological phenomena. Various diseases influence the composition and interfacial tension not only of human body
MA
fluids [95]. To further confirm these changes, the dynamic surface tension and dilational visco-elasticity can be used as an indicator of some pathologies. Such studies are of significant practical interest, due to the capability of providing a differential diagnosis and tools for
D
monitoring of the efficiency of a therapy. A better understanding of pathological disease is
TE
possible if various techniques are used. The surface tensiometry and rheometry are sensitive methods which can reveal changes in the surfactant content of biological liquids. Such
CE P
methods are easy to use and require small amounts of sample liquids only. We described here extensive studies of dynamic surface tensions and rheological parameters of various human liquids, such as blood serum, urine, breathing air condensates, cerebrospinal liquor. The
AC
results for healthy persons are compared with data obtained for people suffering from various diseases in oncology, nephrology, rheumatology, pulmonology and others. Some examples are also given for the evolution of measured data of biological liquids under a medical treatment. It becomes evident that such measurements are very useful for the medical practice. We envisage that studies on the surface properties of human biological liquids will provide additional useful information in medicine. 6. Acknowledgement The authors express their gratitude to the post-graduates and personnel of the Donetsk National Medical University for the collection of samples of biological liquids and the statistical analysis of the results of measured data. We especially acknowledge the efforts of the staff of the Physicochemical Laboratory of the University, in particular, S.V. Lylyk for her thorough rhelological and tensiometric measurements, and V.D. Mys, A.A. Rytikov and
ACCEPTED MANUSCRIPT
35
S.A. Zholob for various adaptations and modifications of the instruments and the development of different measurement programs.
T
7. References
IP
1. Morgan JLR, Woodward HE. The weight of a falling drop and the laws of Tate. J Am Chem Soc 1913; 35:1249–62
SC R
2. Harkins WD, Brown FE. A simple apparatus for the accurate and easy determination of surface tension with a metal thermoregulator for the quick adjustment of temperature. J Am Chem Soc 1916; 38:246–52.
NU
3. Harkins HN, Harkins WD. The surface tension of blood serum. and the determination of the surface tension of biological liquids. J Clin Invest 1929; 7:263–81. 4. DuNouy PL. Surface equilibria of biological and organic colloids. New York: The Chemical Catalog Co.; 1926.
MA
5. DuNouy PL. Surface tension of serum. XIII. On certain physicochemical changes in serum as a result of immunization. J Exp Med 1925; 41:779–93.
D
6. Zozaya J. A physicochemical study of blood serum II: analysis of 500 cases. J Phys Chem 1938; 42:191–207.
TE
7. Hrncir E, Rosina J. Surface tension of blood. Physiol Res 1997; 46:319–21
CE P
8. Anandi Krishnan, Arwen Wilson, Jacqueline Sturgeon, Christopher A. Siedlecki, Erwin A. Vogler. Liquid–vapor interfacial tension of blood plasma, serum and purified protein constituents thereof. Biomaterials 2005; 26: 3445–3453 9. Glantz P, The surface tension of saliva. Odontol Revy 1970; 21: 119–127.
AC
10. Kirkness JP, Christenson HK, Garlick SR, Parikh R, Kairaitis K, Wheatley JR & Amis TC, Decreased surface tension of upper airway mucosal lining liquid increases upper airway patency in anaesthetised rabbits. J Physiol 2003; 547: 603–611. 11. Brydon HL, Hayward R, Harkness W, Bayston R. Physical properties of cerebrospinal fluid of relevance to shunt function. 2: The effect of protein upon CSF surface tension and contact angle. British J Neurosurgery 1995; 9: 645-651. 12. Efentakis M, Dressman JB. Gastric juice as a dissolution medium: surface tension and pH. Euro J Drug Metabol and Pharmacokin 1998; 23: 97-102. 13. Joura EA, Kainz C, Joura EM, Bohm R, Gruber W, Gitsch G. Comparison of surface tension with determination of the L/S ratio in amniotic fluid for prediction of fetal lung maturity. Zeitschrift für Geburtshilfe und Neonatologie 1995; 199: 78-80. 14. Adamczyk E, Arnebrant T, Glantz PO. Time-dependent interfacial tension of whole saliva and saliva-bacteria mixes. Acta Odontol Scand 1997; 55: 384-389. 15. Boda D, Eck E, Boda K. Measurement of surface tension in biological liquids by a pulsating capillary technique. J Perinat Med 1997; 25: 146-152.
ACCEPTED MANUSCRIPT
36
16. Manalo E, Merritt TA, Kheiter A, Amirkhanian J, Cochrane C. Comparative effects of some serum components and proteolytic products of fibrinogen on surface tensionlowering abilities of beractant and a synthetic peptide containing surfactant KL4. Pediatr Res 1996; 39: 947-952.
IP
T
17. J. Rosina, E. Kvasnak, D. Šuta, H. Kolarova, J. Malek, L. Krajci. Temperature Dependence of Blood Surface Tension. Physiol. Res. 2007; 56: 93-98.
SC R
18. A. Fathi-Azarbayjani, A. Jouyban. Surface tension in human pathophysiology and its application as a medical diagnostic tool. Bio Impacts. 2015; 5:29-44 19. C.O. Mills, E. Ellas, G.H.B. Martin, M.T.C. Woo, A.F. Winder. Surface Tension Properties of Human Urine: Relationship with Bile Salt Concentration. J. Clin. Chem. Clin. Biochem., 1988; 26: 187-194.
MA
NU
20. Krishnan A., Wilson A., Sturgeon J., Siedlecki CA., Vogler EA.. Liquid-vapor interfacial tension of blood plasma. serum and purified protein constituents thereof. Biomaterials. 2005; 26: 3445-53.
D
21. V.N. Kazakov, V.M. Knyazevich, O.V. Sinyachenko, V.B. Fainerman and R. Miller. Interfacial Rheology of Biological Liquids: Application in Medical Diagnostics and Treatment Monitoring. in “Interfacial Rheology”. Vol. 1. Progress in Colloid and Interface Science. R. Miller and L. Liggieri (Eds.). Brill Publ., Leiden. 2009, p. 519-566.
TE
22. V.N. Kazakov, O.V. Sinyachenko, V.B. Fainerman, U. Pison and R. Miller - Dynamic Surface Tension of Biological Liquids in Medicine. in “Studies in Interface Science”. Vol. 8. D. Möbius and R. Miller (Editors). Elsevier. Amsterdam. 2000.
CE P
23. Anahita Fathi-Azarbayjani, Abolghasem Jouyban, Sui Yung Chan. Impact of Surface Tension in Pharmaceutical Sciences. J Pharm Pharmaceut Sci. 2009; 12: 218-228
AC
24. Pulmonary Surfactant: From Molecular Biology to Clinical Practice. Eds. B. Robertson. L.M.G. Van Golde and J.J. Batenburg. Elsevier. Amsterdam. 1992. 25. R. Wüstneck, V.B Fainerman, N. Wüstneck and U. Pison. Interfacial behavior of spread SP-B and SP-C layers and the influence of oligomerization and secondary structure. J. Phys. Chem. B. 2004; 108: 1766-1770. 26. R. Wüstneck, J. Perez-Gil, N. Wüstneck, A. Cruz, V.B. Fainerman and U. Pison. Interfacial Properties of Pulmonary Surfactant Layers. Adv. Colloid Interface Sci. 2005; 117: 33-58. 27. F. Gerber, V. P. Krafft, T. F. Vandamme, M. Goldmann, P. Fontaine. Fluidization of a dipalmitoyl phosphatidylcholine monolayer by fluorocarbon gases: Potential use in lung surfactant therapy. Biophys. J. 2006; 90: 3184–3192. 28. F. Gerber, V. P. Krafft, T. F. Vandamme, M. Goldmann, P. Fontaine. Preventing crystallization of phospholipids in monolayers: a new approach to lung surfactant therapy. Angew. Chem. Int. Ed. 2005; 44: 2749-2752. 29. J. G. Riess. Fluorous materials for biomedical uses. In: Handbook of Fluorous Chemistry (Eds: J. A. Gladysz, I. Horvath, D. P. Curran). Wiley-VCH. Weinheim. Germany 2004, p. 521–573.
ACCEPTED MANUSCRIPT
37
30. M. Sukumar, M. Bommaraju, J. E. Fisher, F. C. Morin, M. C. Papo, B. P. Fuhrman, L. J. Hernan, C. L. Leach. High-frequency partial liquid ventilation in respiratory distress syndrome: Hemodynamics and gas exchange. J. Appl. Physiol. 1998; 84: 327– 334.
IP
T
31. M. P. Krafft, J. G. Riess. Perfluorocarbons. life sciences and biomedical uses. J. Polymer. Sci. A: Polymer. Chem. 2007; 45: 1185−1198.
SC R
32. J. G. Riess. Injectable oxygen-carriers (blood substitutes) – Raison d’être. chemistry. and some physiology. Chem. Rev. 2001; 101: 2797-2920. 33. P. N. Nguyen, T. T. Trinh Dang, G. Waton, T. Vandamme, M. P. Krafft. A nonpolar. nonamphiphilic molecule can accelerate adsorption of phospholipids and lower their surface tension at the air/water interface. ChemPhysChem 2011; 12: 2646–2652.
MA
NU
34. P. N. Nguyen, M. Veschgini, M. Tanaka, G. Waton, T. Vandamme, M. P. Krafft. Counteracting the inhibitory effect of proteins towards lung surfactant substitutes: a fluorocarbon gas helps displace albumin at the air/water interface. Chem. Commun. 2014; 50: 11576-11579.
TE
D
35. V.B. Fainerman and R. Miller. Maximum bubble pressure tensiometry: theory, analysis of experimental constrains and applications. in “Bubble and Drop Interfaces”. Vol. 2. Progress in Colloid and Interface Science. R. Miller and L. Liggieri (Eds.). Brill Publ.. Leiden. 2011, p. 75-118.
CE P
36. V.B. Fainerman, A.V. Makievski and R. Miller. Accurate analysis of the bubble formation process in maximum bubble pressure tensiometry. Rev. Sci. Instruments. 2004; 75:213-221. 37. V.B. Fainerman, V.D. Mys, A.V. Makievski and R. Miller. Correction for the aerodynamic resistance and viscosity in maximum bubble pressure tensiometry. Langmuir. 2004; 20:1721 – 1723
AC
38. S.A. Zholob, A.V. Makievski, R. Miller and V.B. Fainerman. Optimisation of calculation methods for determination of surface tensions by drop profile analysis tensiometry. Adv. Colloid Interface Sci. 2007; 134-135: 322-329 39. S.A. Zholob, V.I. Kovalchuk, A.V. Makievski, J. Krägel, V.B. Fainerman and R. Miller. Determination of the dilational elasticity and viscosity from the surface tension response to harmonic area perturbations. in “Interfacial Rheology”. Vol. 1. Progress in Colloid and Interface Science. R. Miller and L. Liggieri (Eds.). Brill Publ., Leiden. 2009, p. 77102. 40. S.A. Zholob, A.V. Makievski, R. Miller and V.B. Fainerman. Application of axisymmetric profile analysis for measuring surface tension at harmonic surface oscillations. Methods and Devices of Quality Control. 2012; 29: 25-36. 41. S.A. Zholob, A.V. Makievski, R. Miller and V.B. Fainerman. Advances in calculation methods for the determination of surface tensions in drop profile analysis tensiometry. in “Bubble and Drop Interfaces”. Vol. 2. Progress in Colloid and Interface Science. R. Miller and L. Liggieri (Eds.). Brill Publ., Leiden. 2011; P. 39-60.
ACCEPTED MANUSCRIPT
38
42. V.N. Kasakov, V.B. Fainerman, O.V. Sinyachenko, R. Miller, P. Joos, S.V. Lylyk, A.E. Aiko, D.V. Truchin and M.V. Ermolaeva. Dynamic surface tension of blood and urine in cases of renal pathology. Arch. Klin. Eksper. Mediciny. 1995; 29: 3-9.
IP
T
43. O.V. Sinyachenko, V.N. Kazakov, E.F. Barinov, V.B. Fainerman, R. Miller, M.V. Ermolaeva, A.E. Ayko, I.A. Sidorenko, D.V. Trukhin. Dynamic surface tension of blood and urine at chronic glumerulonephritis. Likarska Sprava 1997; 1:48-51
SC R
44. V.N. Kazakov, R. Miller, N.G. Semikov, O.V. Sinyachenko, D.V. Trukhin, V.B. Fainerman and Y.I. Yakovets. Dynamic interfacial tensiometry as a new method for studying human biologic liquids: I. Procedures used. Vestnik novych medicinskich technologij. 1997; 4:100-103
NU
45. V.N. Kazakov, O.V. Sinyachenko, V.B. Fainerman and R. Miller. Dynamic surface tension of biological liquids in medicine. Izd. Donetsk. Med. Univ. Donetsk. 1997 (in Russian)
MA
46. O.V. Sinyachenko, V.N. Kazakov, V.B. Fainerman, R. Miller, P. Joos and M.V. Yermolayeva. Dynamic surface tension of synovial liquid in rheumatoid arthritis. Terapevticheskij Archiv. 1998; 1:46-49
TE
D
47. V.N. Kazakov, O.V. Sinyachenko, M.V. Pustovaya, V.B. Fainerman, R. Miller and D.V. Trukhin. Interfacial tensiometry of biological liquids: questions of theory. methods. and perspectives of clinical use. Archive Clinical Experimental Medicine. 1998; 7:5-10.
CE P
48. R. Miller, V.B. Fainerman, A.V. Makievski, J. Krägel, D.O. Grigoriev, V.N. Kazakov and O.V. Sinyachenko. Dynamics of protein and mixed protein/surfactant adsorption layers at the water/fluid interface. Adv. Colloid Interface Sci. 2000; 86: 39-82. 49. V.N. Kazakov, V.B. Fainerman, P.G. Kondratenko, A.F. Elin, O.V. Sinyachenko and R. Miller. Dilational rheology of serum albumin and blood serum solutions as studied by oscillating drop tensiometry. Colloids Surfaces B. 2008; 62:77–82.
AC
50. V.N. Kazakov, A.A. Udod, I.I. Zynkovich, V.B. Fainerman and R. Miller. Dynamic surface tension of saliva: application in medical diagnostics. Colloids Surfaces B. 2009; 74: 457–461. 51. V.N. Kazakov, E.L. Barkalova, L.A. Levchenko, T.M. Klimenko, V.B. Fainerman and R. Miller. Dilation rheology as medical diagnostics of human biological liquids. Colloids Surfaces A. 2011; 391:190-194. 52. V.N. Kazakov, A.F. Vozianov, O.V. Sinyachenko, D.V. Trukhin, V.I. Kovalchuk and. U. Pison. Studies on the application of dynamic surface tensiometry of blood and cerebrospinal liquid for the diagnostics and treatment control of rheumatic, neurological and oncological diseases. Adv. Colloid Interface Sci. 2000; 86: 1-38 53. Kazakov V.N., Sinyachenko O.V., Trukhin D.V., Pison U. Dynamic interfacial tensiometry of biologic liquids – does it have an impact on medicine. Colloids Surf. A: Physicochem. Eng. Aspects. 1998; 143: 441-459. 54. Е.A. Statinova, R.Ya. Omelchenko. Dynamic interfacial tensiometry of cerebro_spinal liquid in the diagnosis of neurological diseases. Ukrainian Neurological Journal. 2010; 2: 59-63.
ACCEPTED MANUSCRIPT
39
55. V. I. Cherniy, V. A. Stepanyuk. Potentialities of Program Analysis of Probable Outcome in Patients with Acute Poisoning by Mushrooms. Obsch. Reanim. 2006; 11: 2-6. 56. E.L.Barkalova. Surface Tension of the Cerebrospinal Fluid of Patients with Neurosyphilis. Buk. Med. Herald. 2011; 15: 143-145.
IP
T
57. I.G. Gerasimov, V.B. Fainerman, I.A. Zaitsev and M.A. Kotel'nitskii. Simulation of the Dynamic Surface Tension of Aqueous Solutions of Some Proteins and Biological liquids. Russian J. Phys. Chem. 2003; 77: 666-670.
SC R
58. V.B. Fainerman, S.A. Zholob, M.E. Leser, M. Michel and R. Miller. Adsorption from mixed ionic surfactant/protein solutions - analysis of ion binding. J. Phys. Chem. 2004; 108: 16780-16785.
NU
59. O.Yu. Milyaeva, B.A. Noskov, S.-Y. Lin, G. Loglio and R. Miller. Influence of polyelectrolyte on dynamic surface properties of BSA solutions. Colloids Surfaces A. 2014; 442: 63-68.
TE
D
MA
60. R. Miller, E.V. Aksenenko, V.S. Alahverdjieva, V.B. Fainerman, Cs. Kotsmar, J. Krägel, M.E. Leser, J. Maldonado-Valderrama, B.A. Noskov, V. Pradines, C. Stefaniu, A. Stocco and R. Wüstneck. Thermodynamic and kinetics of mixed protein/surfactant adsorption layers at liquid interfaces. in “Proteins in solution and at interfaces: Methods and Applications in Biotechnology and Materials Science”. J.M. Ruso and Á. Piñeiro (Eds.). John Wiley & So. 2013. p. 389-426.
CE P
61. Cs. Kotsmar, V. Pradines, V.S. Alahverdjieva, E.V. Aksenenko, V.B. Fainerman, V.I. Kovalchuk, J. Krägel, M.E. Leser and R. Miller. Thermodynamics, adsorption kinetics and rheology of mixed protein-surfactant interfacial layers. Adv. Colloid Interface Sci. 2009; 150: 41–54. 62. R. Miller, V.S. Alahverdjieva and V.B. Fainerman, Thermodynamics and rheology of mixed protein/surfactant adsorption layers, Soft Matter, 2008; 4: 1141-1146.
AC
63. E.V. Aksenenko, V.I. Kovalchuk, V.B. Fainerman and R. Miller, Surface Dilational Rheology of Mixed Surfactant Layers at Liquid Interfaces, J. Phys. Chem. C. 2007; 111: 14713-14719. 64. V.B. Fainerman and R. Miller. Adsorption isotherms at liquid interfaces, Encyclopedia of Surface and Colloid Science. P. Somasundaran and A. Hubbard (Eds.). 2nd. Edition. 2009; 1:1-15. 65. P.R. Garrett and R.D. Ward. A reexamination of the measurement of dynamic surface tensions using the maximum bubble pressure method. J. Colloid Interface Sci. 1989; 132: 475-490. 66. R.L. Bendure. Dynamic surface tension determination with the maximum bubble pressure method. J. Colloid Interface Sci. 1971; 35: 238-248. 67. J. Kloubek. Measurement of the dynamic surface tensionby the maximum bubble pressure method. II. Calculation of the effective age of the solution-air interface. J. Colloid Interface Sci. 1972; 41: 1-6.
ACCEPTED MANUSCRIPT
40
68. J. Kloubek. Measurement of the dynamic surface tension by the maximum bubble pressure method. III. Factors influencing the measurements at high frequency of the bubble formation and an extension of the evaluation to zero age of the surface. J. Colloid Interface Sci. 1972; 41: 7-16.
IP
T
69. J. Kloubek. Measurements of the dynamic surface tension by the maximum bubble pressure method. IV. Surface tension of aqueous solutions of sodium dodecylsulfate. J. Colloid Interface. Sci. 1972; 41: 17-22.
SC R
70. K.J. Mysels. Improvements in the maximum-bubble pressure method of measuring surface tension. Langmuir. 1986; 2: 428-432. 71. K.J. Mysels. The maximum bubble pressure method of measuring surface tension. revisited. Colloids Surfaces. 1990; 43: 241-262.
MA
NU
72. Kazakov VN, Trukhin DV, Sinyachenko OV, Bondar GV, Yakovetz YI, Semikoz NG, Fainerman VB, Miller R. Dynamic middle-phase tensiometry of blood and urine in female patients with malignant tumors of the reproductive organs. Voprosi Oncologii 1998; 44: 334-336.
D
73. Trukhin DV, Sinyachenko OV, Kazakov VN, Lylyk SV, Belokon AM, Pison U. Dynamic surface tension and surface rheology of biological Liquids, Colloid Surf B 2001; 21: 231–238.
TE
74. Chronic Pancreatitis. Novel Concepts in Biology and Therapy / Edited by M. W. Buchler. H. Friess. W. Unl. P. Malfertheiner. Berlin; Wien: Wissenchafts-Verlag A Blackwell Publishing Company. 2002. 614 р.
CE P
75. de Queiroz AA, Barrak ÉR, de Castro SC. Thermodynamic analysis of the surface of biomaterials. J Mol Struct (Theochem) 1997; 394: 271-279.
AC
76. Harnett EM, Alderman J, Wood T. The surface energy of various biomaterials coated with adhesion molecules used in cell culture. Colloids Surf B 2007; 55: 90-97. 77. Zhou F, Escher J, Cui S. Bifurcation for a free boundary problem with surface tension modeling the growth of multi-layer tumors. J Math Anal Appl 2008; 337: 443- 457, 78. Anand P, Huilgol N, Banerjee R. Interfacial properties as predictors of radioresistance in cervical cancer. J Colloid Int Sci 2007; 314: 63-70. 79. Preetha A, Banerjee R, Huilgol N. Dynamic surface tensiometry of tissues using Langmuir films, Colloids Surf B 2005; 40: 35-43. 80. Robertson B, Johansson J, Curstedt T. Synthetic surfactants to treat neonatal lung disease. Mol Med Today 2000;6: 119-124. 81. Ikegami M, Hacobs H, Jobe A. Surfactant function in respiratory distress sysndrome. J Pediat 1983;102:443- 447. 82. Richardson PS, Phipps RJ. The anatomy, physiology, pharmacology and pathology of tracheobronchial mucus secretion and the use of expectorant drugs in human disease. Pharmac Ther B 1978; 3: 441-479.
ACCEPTED MANUSCRIPT
41
83. Gilljam H, Andersson O, Ellin A, Robertson B, Strandvik B. Composition and surface properties of the bronchial lipids in adult patients with cystic fibrosis. Clinica Chimica Acta 1988; 116:29-38.
IP
T
84. Jokic R, Klimaszewski A, Crossley M. Positional treatment vs continuous positive airway pressure in patients with positional obstructive sleep apnea syndrome. Chest 1999; 115:771-781.
SC R
85. Bradshaw DA. What are the nonsurgical treatment options for obstructive sleep apnea syndrome? Am Otolaryngol 2001;22:124-131. 86. Reid G. Importance of Surface Properties in Bacterial Adhesion to Biomaterials, with Particular Reference to the Urinary Tract. International Biodeterioration & Biodegradation 1992;30: 105-122.
MA
NU
87. Kirkness JP, Christenson HK, Wheatley JR, Amis TC. Application of the pull-off method for measurement of the surface tension of upper airway mucosal lining liquid. Physiol Meas 2005; 26:677-688. 88. Brydon HL, Hayward R, Harkness W, Bayston R. Physical properties of cerebrospinal fluid of relevance to shunt function. 2. The effect of protein upon CSF surface tension and contact angle Brit. J Neurosurg 1995;9:645- 651.
TE
D
89. Krishnan A, Wilson A, Sturgeon J, Siedlecki CA, Vogler EA. Liquid-vapor interfacial tension of blood plasma, serum and purified protein constituents thereof. Biomater 2005; 26: 3445-3453.
CE P
90. E. Unger, T. Porter, J. Lindner and P. Grayburn, Cardiovascular drug delivery with ultrasound and microbubbles. Adv. Drug Delivery Rev., 2014; 72: 110-126.
AC
91. M.P. Krafft, V.B. Fainerman, and R. Miller, Modeling of the effect of fluorocarbon gases on the properties of phospholipid monolayers and the adsorption dynamics of their aqueous solutions or dispersions, Colloid Polym Sci 2015; 293:3091–3097. 92. N. Mucic, N. Moradi, A. Javadi, E.V. Aksenenko, V.B. Fainerman and R. Miller, Mixed adsorption layers at the aqueous CnTAB solution / hexane vapor interface, Colloids Surfaces A, 2014; 442: 50-55. 93. V.B. Fainerman and D. Vollhardt, Equation of state for the phase coexistence region of insoluble monolayers under consideration of the entropy nonideality, J. Phys. Chem. B, 2008; 112: 1477-1481. 94. V. B. Fainerman and D. Vollhardt, Equation of state for monolayers with additional phase transition between condensed phases of different compressibility, J. Phys. Chem. B, 2009; 113: 6311–6313. 95. S. Zaitsev, Dynamic surface tension measurements as general approach to the analysis of animal blood plasma and serum, Adv. Colloid Interface Sci., 2016, 235: 201–213.
AC
TE
CE P
Graphical abstract
D
MA
NU
SC R
IP
T
ACCEPTED MANUSCRIPT
42
ACCEPTED MANUSCRIPT
43
Highlights Dynamic surface tension are sensitive to changes in the composition of human body fluids.
The dilational visco-elasticity can also serve as indicator of pathologies.
Measurements of both parameters are simple and require small amounts of liquid.
The parameter can serve for diagnostics of diseases.
The same parameters are also useful for the control of therapies.
AC
CE P
TE
D
MA
NU
SC R
IP
T