- Email: [email protected]
Ultrasonic sonoporation can enhance the prostate permeability
Medical Hypotheses 74 (2010) 449–451
Contents lists available at ScienceDirect
Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
Ultrasonic sonoporation can enhance the prostate permeability Yongliang Liu a,1, Zheng Liu b,2, Tao Li c,*, Gang Ye a,* a
Department of Urology, Xinqiao Hospital of Third Military Medical University, Chongqing 400037, China Department of Ultrasound, Xinqiao Hospital of Third Military Medical University, Chongqing, China c Department of Ultrasound, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China b
a r t i c l e
i n f o
Article history: Received 21 September 2009 Accepted 27 September 2009
s u m m a r y As possible existence of the blood–prostate barrier and decreased prostate permeability due to inflammation, it is difficult to form an effective drug concentration in prostate tissues, which influences medication efficacy. This is one of principal reasons why it is difficult to treat prostate diseases including prostatitis etc. How to increase the permeability of drugs into prostate is inevitable to become an issue concerned by clinical research. Ultrasonic sonoporation may increase permeability of cells and tissues, so we propose a hypothesis that sonoporation induced by ultrasonic cavitation may increase the permeability of prostate tissues. This may be a non-invasive physical treatment method, and it has better safety and validity, and higher clinical value. Ó 2009 Elsevier Ltd. All rights reserved.
Background
Hypothesis
Including prostatitis, prostate diseases are common ailment of male adults [1], and it seriously influence the quality of life [2,3]. Until now, pathogenesis and pathophysiologic alteration of these diseases are not very clear. Previous studies about chronic prostatitis suggested the possible presence of blood–prostate barrier [4]. When chronic inflammation occurred, scars around the prostate acinar and tissues around the abscess would become fibrosis, and fiber desmohemoblast obviously thickened, which had more significant barrier actions to drugs [5]. It was very difficult for hydrosoluble, acidic and low-dissociation constant antibiotics to enter into prostate tissues. Therefore, it was more difficult to form an effective drug concentration in the gland for oral administration or intravenous injection, which limited effectiveness of drug treatment to a large extent. As a result, many doctors felt very troublesome in clinical treatment. However, studies on ultrasonic cavitation increasing the permeability of the tissues brought the hope of effective treatment for prostate diseases. The ultrasonic cavitation could increase permeability of the blood–brain barrier [6]. Whether could it increase the permeability of prostate tissues and maximality increase drug concentration in prostate tissues to achieve a more powerful therapeutic effect? At present, there was no relevant research reports and it is necessary to study further.
Our hypothesis is to tend to resolve the problems of intravenous administration having a lower drug concentration in prostate tissues, explore a new non-invasive physical treatment method to improve the permeability of prostate tissues for increasing medication effects on prostate diseases. Intravenously inject the ultrasound contrast agent microbubbles [7] (exogenous cavitation nuclei) into the blood circulation of animals, accurately display and position the prostate by abdomen or perineal diagnostic ultrasound, and observe perfusion states of microbubbles in the prostate. In the perfusion peak, make use of diagnostic ultrasound or intermittent emitted pulsed focused ultrasound of set energy parameters to radiate the prostate in the fixed orientation and point, and stimulate the cavitation of microbubbles in local micro-circulation. And then make use of sonoporation induced by ultrasonic cavitation to open tight junctions between vascular endothelial cells, followed by reperfusing microbubbles into the desmohemoblast. Under the intermittent ultrasound, open cell junctions of the desmohemoblast and glandular epithelium, thus open the whole blood–prostate barrier and enhance the permeability of prostate tissues. On this basis, establish the animal models with prostatitis, and observe that ultrasonic cavitation increased the permeability of prostate tissues in inflammatory state. At a constant drug concentration in blood, increasing drug concentrations in prostate desmohemoblast and glandular cavity could promote drugs as antibiotics etc., to locally thicken in order to bring into full play a more powerful therapeutic effect. Meanwhile, observe the type and dose of microbubbles and effects of ultrasonic cavitation generated by different energy parameters of ultrasound
* Corresponding authors. Tel.: +86 023 68757582 (T. Li), +86 023 68774624 (G. Ye). E-mail addresses: [email protected] (Y. Liu), [email protected] (T. Li), [email protected] (G. Ye). 1 Tel.: +86 023 68774624. 2 He contributed equally to this work. 0306-9877/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2009.09.052
450
Y. Liu et al. / Medical Hypotheses 74 (2010) 449–451
on the prostate and its ambient tissues, and explore the appropriate conditions for reversibly opening the blood–prostate barrier, and observe opening and recovery time of the barrier and whether white blood cells can or not enter the glandular cavity through the barrier.
Evaluation of the hypothesis As one of the biological effects of ultrasound, ultrasonic cavitation refers to an action that by ultrasonic irradiation, microbubbles in a liquid generate a series of dynamic processes as shock, expansion, shrinkage and implosion so on, with multifarious acts of energy release as transient high temperature, high pressure, shock wave, discharge and internal jet so on [8]. When ultrasonic cavitation took place at the interface of tissue acoustics, concomitant physical mechanical energy, as internal jet and shock wave, can damage tissue interface and enhance the permeability of cell membrane, namely ‘‘sonoporation” [9,10]. However, endogenous cavitation nuclei insufficient and cavitation threshold is higher in vivo. As a highly effective exogenous cavitation nuclei, the ultrasound contrast agent microbubbles, can significantly increase the quantity and concentration of cavitation nuclei in vivo via intravenous injection, which consequently decreases the cavitation threshold and increases the ultrasound cavitation erosion. Several researches showed that when the mechanical index of the diagnosis ultrasound was above 1.3, the physical effects of ultrasound cavitation mediated by microbubbles can produce significant biological effect, leading to increased cell membrane permeability and open tight junction of vascular endothelial cells [11]. In recent years, increased number of researches have utilized ultrasonic sonoporation to improve permeability of cell membrane or vascular endothelial cells in models such as cultural cell in vitro, myocardial tissues in vivo, kidney and blood–brain barrier [12–15]. However, little has been investigated on the ultrasonic sonoporation to open the blood–prostate barrier for enhancing permeability. This concept of blood–prostate barrier has not yet been thoroughly understood until today, which lacks a clear definition in histology and contradicts with many literature discussions. The blood–prostate barrier has been suggested to be made up of microvessel endothelial cells, basement membrane, fiber desmohemoblast, glandular epithelium and other tissues. Its basic function involves blocking of certain matters trafficking into the prostate glandular cavity during blood circulation, and preventing detrimental factors from retrograde spreading into stroma to invade male urogenital system via glandular epithelium [16]. As the integrity of its barrier and reduced permeability of tissues due to chronic inflammation [17], the drug concentrations in the desmohemoblast and glandular cavity were less than the drug concentration in blood, which cannot locally form an effective drug concentration to play its proper effect. In addition, due to the abundant blood supply of prostate tissues, microbubbles perfusion in microcirculation of prostate tissues were sufficient after intravenous injection, and its tissue imaging and blood-flow imaging were significantly improved [18,19]. These provided preconditions for ultrasonic sonoporation enhancing prostate permeability. However, the blood supply of tissues around the prostate (such as bladder wall, pubic symphysis) was insufficient, perfused microbubbles of them was significantly less than that of prostate tissues, and structures of these tissues were tough, less susceptible to lowintensity ultrasonic cavitation damage. Based on the biological phenomena that ultrasound contrast agent microbubbles activated in the sound field could generate the effect of ultrasonic cavitation that it changes the permeability of tissues, and the abundant blood supply of prostate tissues, we
propose that ultrasonic sonoporation can enhance the permeability of prostate tissues, not only by enhancing the permeability of vascular endothelial cells and basal membrane, but also by enhancing the permeability of prostate fiber desmohemoblast, lipid membrane of acinar epithelium and cell membrane of glandular epithelium. Possible implementation of this hypothesis are taken as follows: (1) Abdominal or perineal sonography can clearly show enhanced perfusion effect of ultrasound contrast agent microbubbles of the prostate and provide necessary conditions and feasibility for making real-time monitoring and fixed-point emission of the ultrasound. (2) After microbubbles are activated by high mechanical index (MI > 1.3) diagnostic ultrasound or the lowintensity ultrasound of set energy parameters, changes of the permeability of prostate tissues can be traced and quantified by the microvascular tracer Evans Blue. After entering the blood circulation, Evans Blue will form large molecular complexes with plasma albumin. When blood vessel endothelium is integrate, it will not penetrate outside blood vessel. If the blood–prostate barrier is open, Evans Blue-albumin complex can enter the desmohemoblast and glandular cavity. Lanthanum particles trace transmission electron microscopy can also be used to observe changes of prostate permeability. Lanthanum particles with 2 nm diameter, usually can not cross the plasma membrane into cells. When the membrane molecule gaps increase, leading to increase membrane permeability, lanthanum particles can enter the cytoplasm and organelles, or can enter and pass the damaged cell junction. Therefore, according to the possible attachment sites of lanthanum particles used as a ‘‘probe” (vascular wall, basement membrane, fiber desmohemoblast, lipid membrane of acinar epithelium etc.), assess whether or not the blood–prostate barrier were open, and whether or not prostate permeability was increased. (3) Verify the mechanism of prostate permeability enhanced by sonoporation, including opening of tight junctions of vascular endothelial cell, widening of the adjacent cells spacing, ‘‘sonoporation” formation of cell membranes, vesicles transport enhanced, loose states of fiber desmohemoblast, structural changes of lipid membrane of acinar epithelium and expression changes of vascular endothelial cell gap junction protein so on. (4) Investigate the amount–effect relationship between ultrasonic energy parameters (such as the peak negative pressure, pulse width, duty ratio, emission frequency, irradiation time), microbubbles type, microbubbles dose and opening of the blood–prostate barrier. (5) Evaluate the safety of this method. Observe if these changes of prostate tissues is repairable and how long the possible opening and recovery time of the blood–prostate barrier is and whether the tissues around the prostate have vice injuries. Effective and safe method should be momently and reversibly open the blood–prostate barrier to promote drugs to penetrate into the desmohemoblast and glandular cavity, using compatible ultrasonic energy parameters and microbubble dose, meanwhile maintaining the state of original immune isolation to maximum extent. In Summary, our hypothesis is to explore the feasibility, efficiency, regularity and safety of a new physical method that microbubble-mediated ultrasonic cavitation can open the blood– prostate barrier and enhance the permeability of prostate tissues (i.e., ultrasonic sonoporation), and further investigate the corresponding mechanisms. To provide theoretical guidance and experimental evidences for improving better therapeutic efficacy by means of promoting the drug in the blood to permeate into prostate tissues. Further demonstration of the hypothesis should have a greater prospect for clinical application.
Conflict of interest statement None declared.
Y. Liu et al. / Medical Hypotheses 74 (2010) 449–451
Acknowledgement The present study was supported by Chongqing Science and Technology Project (Item No. CSTC2008AC0002).
References [1] Krieger JN, Riley DE, Cheah PY, et al. Epidemiology of prostatitis: new evidence for a world-wide problem. World J Urol 2003;2:70–4. [2] Tripp DA, Nickel JC, Landist JR, et al. Predictor of quality of life and pain in chronic prostatitis/chronic pelvic pain syndrome: findings from the National Institutes of Health Chronic Prostatitis Cohort Study. Brit J Urol Int 2004;94:1279–82. [3] Wenninger K, Heiman JR, Rothman I, et al. Sickness impact of chronic nonbacterial prostatitis and its correlates. J Urol 1996;155:965–8. [4] Fulmer BR, Turner TT. A blood–prostate barrier restricts cell and molecular movement across the rat ventral prostate epithelium. J Urol 2000;163: 1591–4. [5] Yamamoto M, Hibi H, Satoshi K, Miyake K. Chronic bacterial prostatitis treated with intraprostatic injection of antibiotics. Scand J Urol Nephrol 1996;30:199–202. [6] Stephen M, Angelika A. Ultrasound, microbubbles and the blood–brain barrier. Biophys Mol Biol 2007;93:354–62. [7] Liu Z, Yang L, Tan KB, et al. The preparation of anionic lipid-coated microbubbles. Ultrasound Med Biol 2006;32(Suppl. 1):177. [8] Feng N. Ultrasonic cavitation and ultrasound in medicine. Chin J Ultrasonogr 2004;13:63–5.
451
[9] Wu J. Theoretical study on shear stress generated by microstreaming surrounding contrast agents attached to living cells. Ultrasound Med Biol 2002;28:125–9. [10] Prentice P, Cuschieri A, Dholakia K, et al. Membrane disruption by optically controlled microbubble cavitation. Nat Phys 2005;1:107–10. [11] Miller DL, Quddus J. Lysis and sonoporation of epidermoid and phagocytic monolayer cells diagnostic ultrasound activation of contrast agent gas bodies. Ultrasound Med Biol 2001;27:1107–13. [12] Li P, Armstrong WF, Miller ML. Impact of myocardial contrast echocardiography on vascular permeability: comparison of three different contrast agents. Ultrasound Med Biol 2004;30:83–91. [13] Wible Jr JH, Garen P, Wojdyla JK, Hughes MS, Klibanov AL, Barandenburger GH. Microbubbles induced renal hemorrhage when exposed to diagnostic ultrasound in anesthetized rats. Ultrasound Med Biol 2002;28:1535–46. [14] Hynynen K, McDannold N, Martin H, Jolesz FA, Vykhodtseva N. The threshold for brain damage in rabbits induced by bursts of ultrasound in the presence of an ultrasound contrast agent (OPTISON). Ultrasound Med Biol 2003;29:473–81. [15] Sheikov N, McDannold N, Vykhodtseva N, Jolesz F, Hynynen K. Cellular mechanisms of the blood–brain barrier opening induced by ultrasound in presence of microbubbles. Ultrasound Med Biol 2004;30:979–89. [16] El-Alfy M, Pelletier G, Hermo LS, Labrie F. Unique features of the basal cells of human prostate epithelium. Microsc Res Tech 2000;51:436–46. [17] Campbell MF. Campbell’s urology. Philadelphia, Pa: Elsevier Science. Health Sci Div 2002: 617–8. [18] Hagen EK, Forsberg F, Liu JB, Gomella LG, Aksnes AK, Merton DA, et al. Contrast-enhanced power doppler imaging of normal and decreased blood flow in canine prostates. Ultrasound Med Biol 2001;27:909–13. [19] Mitterberger M, Pelzer A, Colleselli D, Bartsch G, Strasser H, Pallwein L, et al. Contrast-enhanced ultrasound for diagnosis of prostate cancer and kidney lesions. Eur J Radiol 2007;64:231–8.
Contents lists available at ScienceDirect
Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
Ultrasonic sonoporation can enhance the prostate permeability Yongliang Liu a,1, Zheng Liu b,2, Tao Li c,*, Gang Ye a,* a
Department of Urology, Xinqiao Hospital of Third Military Medical University, Chongqing 400037, China Department of Ultrasound, Xinqiao Hospital of Third Military Medical University, Chongqing, China c Department of Ultrasound, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China b
a r t i c l e
i n f o
Article history: Received 21 September 2009 Accepted 27 September 2009
s u m m a r y As possible existence of the blood–prostate barrier and decreased prostate permeability due to inflammation, it is difficult to form an effective drug concentration in prostate tissues, which influences medication efficacy. This is one of principal reasons why it is difficult to treat prostate diseases including prostatitis etc. How to increase the permeability of drugs into prostate is inevitable to become an issue concerned by clinical research. Ultrasonic sonoporation may increase permeability of cells and tissues, so we propose a hypothesis that sonoporation induced by ultrasonic cavitation may increase the permeability of prostate tissues. This may be a non-invasive physical treatment method, and it has better safety and validity, and higher clinical value. Ó 2009 Elsevier Ltd. All rights reserved.
Background
Hypothesis
Including prostatitis, prostate diseases are common ailment of male adults [1], and it seriously influence the quality of life [2,3]. Until now, pathogenesis and pathophysiologic alteration of these diseases are not very clear. Previous studies about chronic prostatitis suggested the possible presence of blood–prostate barrier [4]. When chronic inflammation occurred, scars around the prostate acinar and tissues around the abscess would become fibrosis, and fiber desmohemoblast obviously thickened, which had more significant barrier actions to drugs [5]. It was very difficult for hydrosoluble, acidic and low-dissociation constant antibiotics to enter into prostate tissues. Therefore, it was more difficult to form an effective drug concentration in the gland for oral administration or intravenous injection, which limited effectiveness of drug treatment to a large extent. As a result, many doctors felt very troublesome in clinical treatment. However, studies on ultrasonic cavitation increasing the permeability of the tissues brought the hope of effective treatment for prostate diseases. The ultrasonic cavitation could increase permeability of the blood–brain barrier [6]. Whether could it increase the permeability of prostate tissues and maximality increase drug concentration in prostate tissues to achieve a more powerful therapeutic effect? At present, there was no relevant research reports and it is necessary to study further.
Our hypothesis is to tend to resolve the problems of intravenous administration having a lower drug concentration in prostate tissues, explore a new non-invasive physical treatment method to improve the permeability of prostate tissues for increasing medication effects on prostate diseases. Intravenously inject the ultrasound contrast agent microbubbles [7] (exogenous cavitation nuclei) into the blood circulation of animals, accurately display and position the prostate by abdomen or perineal diagnostic ultrasound, and observe perfusion states of microbubbles in the prostate. In the perfusion peak, make use of diagnostic ultrasound or intermittent emitted pulsed focused ultrasound of set energy parameters to radiate the prostate in the fixed orientation and point, and stimulate the cavitation of microbubbles in local micro-circulation. And then make use of sonoporation induced by ultrasonic cavitation to open tight junctions between vascular endothelial cells, followed by reperfusing microbubbles into the desmohemoblast. Under the intermittent ultrasound, open cell junctions of the desmohemoblast and glandular epithelium, thus open the whole blood–prostate barrier and enhance the permeability of prostate tissues. On this basis, establish the animal models with prostatitis, and observe that ultrasonic cavitation increased the permeability of prostate tissues in inflammatory state. At a constant drug concentration in blood, increasing drug concentrations in prostate desmohemoblast and glandular cavity could promote drugs as antibiotics etc., to locally thicken in order to bring into full play a more powerful therapeutic effect. Meanwhile, observe the type and dose of microbubbles and effects of ultrasonic cavitation generated by different energy parameters of ultrasound
* Corresponding authors. Tel.: +86 023 68757582 (T. Li), +86 023 68774624 (G. Ye). E-mail addresses: [email protected] (Y. Liu), [email protected] (T. Li), [email protected] (G. Ye). 1 Tel.: +86 023 68774624. 2 He contributed equally to this work. 0306-9877/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2009.09.052
450
Y. Liu et al. / Medical Hypotheses 74 (2010) 449–451
on the prostate and its ambient tissues, and explore the appropriate conditions for reversibly opening the blood–prostate barrier, and observe opening and recovery time of the barrier and whether white blood cells can or not enter the glandular cavity through the barrier.
Evaluation of the hypothesis As one of the biological effects of ultrasound, ultrasonic cavitation refers to an action that by ultrasonic irradiation, microbubbles in a liquid generate a series of dynamic processes as shock, expansion, shrinkage and implosion so on, with multifarious acts of energy release as transient high temperature, high pressure, shock wave, discharge and internal jet so on [8]. When ultrasonic cavitation took place at the interface of tissue acoustics, concomitant physical mechanical energy, as internal jet and shock wave, can damage tissue interface and enhance the permeability of cell membrane, namely ‘‘sonoporation” [9,10]. However, endogenous cavitation nuclei insufficient and cavitation threshold is higher in vivo. As a highly effective exogenous cavitation nuclei, the ultrasound contrast agent microbubbles, can significantly increase the quantity and concentration of cavitation nuclei in vivo via intravenous injection, which consequently decreases the cavitation threshold and increases the ultrasound cavitation erosion. Several researches showed that when the mechanical index of the diagnosis ultrasound was above 1.3, the physical effects of ultrasound cavitation mediated by microbubbles can produce significant biological effect, leading to increased cell membrane permeability and open tight junction of vascular endothelial cells [11]. In recent years, increased number of researches have utilized ultrasonic sonoporation to improve permeability of cell membrane or vascular endothelial cells in models such as cultural cell in vitro, myocardial tissues in vivo, kidney and blood–brain barrier [12–15]. However, little has been investigated on the ultrasonic sonoporation to open the blood–prostate barrier for enhancing permeability. This concept of blood–prostate barrier has not yet been thoroughly understood until today, which lacks a clear definition in histology and contradicts with many literature discussions. The blood–prostate barrier has been suggested to be made up of microvessel endothelial cells, basement membrane, fiber desmohemoblast, glandular epithelium and other tissues. Its basic function involves blocking of certain matters trafficking into the prostate glandular cavity during blood circulation, and preventing detrimental factors from retrograde spreading into stroma to invade male urogenital system via glandular epithelium [16]. As the integrity of its barrier and reduced permeability of tissues due to chronic inflammation [17], the drug concentrations in the desmohemoblast and glandular cavity were less than the drug concentration in blood, which cannot locally form an effective drug concentration to play its proper effect. In addition, due to the abundant blood supply of prostate tissues, microbubbles perfusion in microcirculation of prostate tissues were sufficient after intravenous injection, and its tissue imaging and blood-flow imaging were significantly improved [18,19]. These provided preconditions for ultrasonic sonoporation enhancing prostate permeability. However, the blood supply of tissues around the prostate (such as bladder wall, pubic symphysis) was insufficient, perfused microbubbles of them was significantly less than that of prostate tissues, and structures of these tissues were tough, less susceptible to lowintensity ultrasonic cavitation damage. Based on the biological phenomena that ultrasound contrast agent microbubbles activated in the sound field could generate the effect of ultrasonic cavitation that it changes the permeability of tissues, and the abundant blood supply of prostate tissues, we
propose that ultrasonic sonoporation can enhance the permeability of prostate tissues, not only by enhancing the permeability of vascular endothelial cells and basal membrane, but also by enhancing the permeability of prostate fiber desmohemoblast, lipid membrane of acinar epithelium and cell membrane of glandular epithelium. Possible implementation of this hypothesis are taken as follows: (1) Abdominal or perineal sonography can clearly show enhanced perfusion effect of ultrasound contrast agent microbubbles of the prostate and provide necessary conditions and feasibility for making real-time monitoring and fixed-point emission of the ultrasound. (2) After microbubbles are activated by high mechanical index (MI > 1.3) diagnostic ultrasound or the lowintensity ultrasound of set energy parameters, changes of the permeability of prostate tissues can be traced and quantified by the microvascular tracer Evans Blue. After entering the blood circulation, Evans Blue will form large molecular complexes with plasma albumin. When blood vessel endothelium is integrate, it will not penetrate outside blood vessel. If the blood–prostate barrier is open, Evans Blue-albumin complex can enter the desmohemoblast and glandular cavity. Lanthanum particles trace transmission electron microscopy can also be used to observe changes of prostate permeability. Lanthanum particles with 2 nm diameter, usually can not cross the plasma membrane into cells. When the membrane molecule gaps increase, leading to increase membrane permeability, lanthanum particles can enter the cytoplasm and organelles, or can enter and pass the damaged cell junction. Therefore, according to the possible attachment sites of lanthanum particles used as a ‘‘probe” (vascular wall, basement membrane, fiber desmohemoblast, lipid membrane of acinar epithelium etc.), assess whether or not the blood–prostate barrier were open, and whether or not prostate permeability was increased. (3) Verify the mechanism of prostate permeability enhanced by sonoporation, including opening of tight junctions of vascular endothelial cell, widening of the adjacent cells spacing, ‘‘sonoporation” formation of cell membranes, vesicles transport enhanced, loose states of fiber desmohemoblast, structural changes of lipid membrane of acinar epithelium and expression changes of vascular endothelial cell gap junction protein so on. (4) Investigate the amount–effect relationship between ultrasonic energy parameters (such as the peak negative pressure, pulse width, duty ratio, emission frequency, irradiation time), microbubbles type, microbubbles dose and opening of the blood–prostate barrier. (5) Evaluate the safety of this method. Observe if these changes of prostate tissues is repairable and how long the possible opening and recovery time of the blood–prostate barrier is and whether the tissues around the prostate have vice injuries. Effective and safe method should be momently and reversibly open the blood–prostate barrier to promote drugs to penetrate into the desmohemoblast and glandular cavity, using compatible ultrasonic energy parameters and microbubble dose, meanwhile maintaining the state of original immune isolation to maximum extent. In Summary, our hypothesis is to explore the feasibility, efficiency, regularity and safety of a new physical method that microbubble-mediated ultrasonic cavitation can open the blood– prostate barrier and enhance the permeability of prostate tissues (i.e., ultrasonic sonoporation), and further investigate the corresponding mechanisms. To provide theoretical guidance and experimental evidences for improving better therapeutic efficacy by means of promoting the drug in the blood to permeate into prostate tissues. Further demonstration of the hypothesis should have a greater prospect for clinical application.
Conflict of interest statement None declared.
Y. Liu et al. / Medical Hypotheses 74 (2010) 449–451
Acknowledgement The present study was supported by Chongqing Science and Technology Project (Item No. CSTC2008AC0002).
References [1] Krieger JN, Riley DE, Cheah PY, et al. Epidemiology of prostatitis: new evidence for a world-wide problem. World J Urol 2003;2:70–4. [2] Tripp DA, Nickel JC, Landist JR, et al. Predictor of quality of life and pain in chronic prostatitis/chronic pelvic pain syndrome: findings from the National Institutes of Health Chronic Prostatitis Cohort Study. Brit J Urol Int 2004;94:1279–82. [3] Wenninger K, Heiman JR, Rothman I, et al. Sickness impact of chronic nonbacterial prostatitis and its correlates. J Urol 1996;155:965–8. [4] Fulmer BR, Turner TT. A blood–prostate barrier restricts cell and molecular movement across the rat ventral prostate epithelium. J Urol 2000;163: 1591–4. [5] Yamamoto M, Hibi H, Satoshi K, Miyake K. Chronic bacterial prostatitis treated with intraprostatic injection of antibiotics. Scand J Urol Nephrol 1996;30:199–202. [6] Stephen M, Angelika A. Ultrasound, microbubbles and the blood–brain barrier. Biophys Mol Biol 2007;93:354–62. [7] Liu Z, Yang L, Tan KB, et al. The preparation of anionic lipid-coated microbubbles. Ultrasound Med Biol 2006;32(Suppl. 1):177. [8] Feng N. Ultrasonic cavitation and ultrasound in medicine. Chin J Ultrasonogr 2004;13:63–5.
451
[9] Wu J. Theoretical study on shear stress generated by microstreaming surrounding contrast agents attached to living cells. Ultrasound Med Biol 2002;28:125–9. [10] Prentice P, Cuschieri A, Dholakia K, et al. Membrane disruption by optically controlled microbubble cavitation. Nat Phys 2005;1:107–10. [11] Miller DL, Quddus J. Lysis and sonoporation of epidermoid and phagocytic monolayer cells diagnostic ultrasound activation of contrast agent gas bodies. Ultrasound Med Biol 2001;27:1107–13. [12] Li P, Armstrong WF, Miller ML. Impact of myocardial contrast echocardiography on vascular permeability: comparison of three different contrast agents. Ultrasound Med Biol 2004;30:83–91. [13] Wible Jr JH, Garen P, Wojdyla JK, Hughes MS, Klibanov AL, Barandenburger GH. Microbubbles induced renal hemorrhage when exposed to diagnostic ultrasound in anesthetized rats. Ultrasound Med Biol 2002;28:1535–46. [14] Hynynen K, McDannold N, Martin H, Jolesz FA, Vykhodtseva N. The threshold for brain damage in rabbits induced by bursts of ultrasound in the presence of an ultrasound contrast agent (OPTISON). Ultrasound Med Biol 2003;29:473–81. [15] Sheikov N, McDannold N, Vykhodtseva N, Jolesz F, Hynynen K. Cellular mechanisms of the blood–brain barrier opening induced by ultrasound in presence of microbubbles. Ultrasound Med Biol 2004;30:979–89. [16] El-Alfy M, Pelletier G, Hermo LS, Labrie F. Unique features of the basal cells of human prostate epithelium. Microsc Res Tech 2000;51:436–46. [17] Campbell MF. Campbell’s urology. Philadelphia, Pa: Elsevier Science. Health Sci Div 2002: 617–8. [18] Hagen EK, Forsberg F, Liu JB, Gomella LG, Aksnes AK, Merton DA, et al. Contrast-enhanced power doppler imaging of normal and decreased blood flow in canine prostates. Ultrasound Med Biol 2001;27:909–13. [19] Mitterberger M, Pelzer A, Colleselli D, Bartsch G, Strasser H, Pallwein L, et al. Contrast-enhanced ultrasound for diagnosis of prostate cancer and kidney lesions. Eur J Radiol 2007;64:231–8.