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Sialic acid levels in serum and cerebrospinal fluid (CSF) in infectious and noninfectious conditions
BIOCHEMICAL
Sialic
MEDICINE
18, 99-101 (1977)
Acid Levels in Serum and Cerebrospinal Fluid in Infectious and Noninfectious Conditions S. V. BHIDE,"
A. J. PAREKH,~ AND M. P.
(CSF)
DESAI?
*Cancer Research Insrirure, Bombay 400012, and tJerbai Wadia Children’s Hospital. Bombay 400012. India
Received May 20. 1976
Sialic acid is widely distributed in the body mucopolysaccharides, mucoproteins, and brain lipids such as gangliosides. Sialic acid is known to be present in milk, semen, serum, and cerebrospinal fluid (CSF) (l-4). Sialic acid levels and its distribution in albumin and globulin proteins of human serum in normal and pathological conditions have been studied extensively (5, 6). However, this is not the case with CSF, though it has been studied in various degenerative conditions of the central nervous system (CNS). We have made an attempt to study total sialic acid levels in CSF and serum of children suffering from common infective and noninfective conditions of one CNS. Present study reports salient observations on sialic acid in CSF and serum of those patients. MATERIAL
AND METHODS
Sixty-five cases, from both sexes between the ages of 5 months and 10 years, admitted to a genera1 children’s hospital for complaints of convulsions were included in the present study. Blood and cerebrospinal fluid for routine and biochemical investigations were collected before giving any medication. Along with routine examination of blood, serum calcium, phosphorous, and alkaline phosphatase were estimated wherever indicated. Blood sugar was estimated in every case. Serum sialic acid was measured as N-acetyl neuraminic acid by Warren’s method (7) and expressed as micrograms per milligram of protein. Routine examination of CSF, along with sialic acid estimation, was done in all cases. The protein content of CSF was measured by Lowry et al.‘s method (8). Serum sialic acid was also estimated in 10 normal children to establish the normal standard, but it was not possible to estimate CSF sialic acid in normal individuals. 99 Copyright @ 1977 by Academic Press. Inc. 411 rights of reproduction in any fom~ reserved.
ISSN CKMX-2944
100
BHIDE. PAREKH.
AND DESAI
OBSERVATIONS AND DISCUSSION Table I gives the sialic acid content of serum and CSF in children suffering from TB and pyrogenic meningitis, febrile convulsion, tetany, epilepsy, encephalitis, and poliomyelitis. It may be observed that CSF values ranged from 13.5 in epilepsy to 21.7 in tetany. Since the normal values of CSF are not available it is difficult to state whether these are higher or lower than normal. Further, there was variation within each disease group and it was not possible to establish any correlation between the sialic acid values and the cell count, or the amount of sugar or protein in the CSF. In the cases of TB and meningitis an attempt was also made to determine whether the sialic acid values showed any correlation with recovery from the disease. However, the sialic acid values in the CSF from the first puncture and the second puncture when the disease had relatively regressed ranged from 14.2 to 25.5 irrespective of the state of disease. Serum sialic acid values, however, were higher in all the diseases when compared to normal serum levels (7.8 t 0.6 mg of protein). Considering the above data one fact is quite clear, i.e., there is variation in sialic acid levels of CSF within each group, as well as in different pathological conditions of the CNS. As in the present study, Warren (7) has also reported that there is no correlation between CSF protein and CSF sialic acids. On the other hand, O’Toole et al. (9) have observed a very good correlation between high concentrations of protein content and the elevated total N-acetyl neuraminic acid content of CSF in meningitis caused by neuraminidase-producing pneumococci. These workers further suggested that the increased sialic acid levels of CSF might be due to the release of n-acetyl neuraminic acid from gangliosides by the action of neuraminidase. Another noteworthy observation from the present studies is that serum TABLE
I
SIALIC ACID CONTENT IN CSF AND SERUM OF PATIENTS SUFFERING FROM INFECTIVE AND NONINFECTIVE CONDITIONS OF CNS”
CNS condition TB and meningitis Pyrogenic Fibrile convulsion Tetany Epilepsy Encephalitis Poliomyelitis
CSF 17.5 20.0 17.0 21.7 13.5 14.5 14.6
2 k t + + i +
1.5 (19)b 1.2 (6) 0.9 (21) 2.4 (4) 1.4 (4) 3.3 (4) 0.66 (4)
Serum 22.9 18.8 18.3 14.3 16.9 15.0 19.2
t 0.9 (17) ‘-c 1.0 (6) -c I.0 (20) t 0.9 (5) 5 1.6 (4) -c 1.4 (4) -c I.1 (4)
a Sialic acid content is expressed in terms of micrograms of n-acetyl neuraminic acid per milligram of protein. h Figures in parentheses are one number of samples used in each group.
SIALIC ACID LEVELS
IN SERUM AND CSF
101
sialic acid levels are significantly increased in all the cases studied. Increase in serum sialic acid with infection is reported in the literature (lo- 12). It is thus conceivable that in the present studies serum sialic acid was increased in conditions such as TB and meningitis, poliomyelitis, encephalitis, etc. In the case of febrile convulsion also, the increased sialic acids are possible since the convulsions are precipitated by the presence of infection elsewhere in the body. Summarizing other observations, it may be stated that the sialic acid content of CSF shows variations in diseases of the central nervous system, and this study did not show any correlation between the type or state of disease and sialic acid content. SUMMARY
Sialic acid levels in serum and CSF of children suffering from infectious and noninfectious types of CNS diseases were studied. It was observed that there was variation in sialic acid values of CSF in each group and there was no correlation between the metabolic parameters, number of cells in CSF, or progress of the disease. It was also observed that the serum sialic acid levels in various diseases are distinctly higher than those observed in normal serum. REFERENCES 1. Odin, L., Acto Chim. Stand. 9, 862 (1955). 2. Saifer, A., Aronson, S. M.. Zumaris, M. C., and Yolk, B. W.. Proc. Sot. Exp. Biol. Med. 9, 394 (1956). 3. Hoover, T. R. F., Braun, G. A., and Gyorgy, P.. Arch. &o&em. Biophys. 47, 216 (1953). 4. Svenerholm, L., Actn Chim. Stand. 12, 547 (1958). 5. Goftschalk, A., in ‘Chemistry and Biology of Sialic Acids and Related Substances.’ p. 88. Cambridge University Press, Cambridge, lY60. 6. Volk, B. W., Aronso, S. M., and Saifer, A., J. Lab. C/in. Med. 50, 26 (1957). 7. Warren, L., J. Biol. Chem. 234, 1971 (1959). 8. Lowry, 0. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J., J. Biol. Chem. 193, 265 (1951). 9. O’Toole, R. D., Goode, L., and Howe, C., .I. Clin. JO, 979 (1971). 10. Jacoby, R. K., and Warren, L., Neurology, 11, 232 (1961). 11. Soboczynsk, A., and Wahgora, A., Chem. Abstr. 68, 2043lY (1%8). 12. Agishev, V. G., Chem. Abstr. 73, 128886t (1970).
Sialic
MEDICINE
18, 99-101 (1977)
Acid Levels in Serum and Cerebrospinal Fluid in Infectious and Noninfectious Conditions S. V. BHIDE,"
A. J. PAREKH,~ AND M. P.
(CSF)
DESAI?
*Cancer Research Insrirure, Bombay 400012, and tJerbai Wadia Children’s Hospital. Bombay 400012. India
Received May 20. 1976
Sialic acid is widely distributed in the body mucopolysaccharides, mucoproteins, and brain lipids such as gangliosides. Sialic acid is known to be present in milk, semen, serum, and cerebrospinal fluid (CSF) (l-4). Sialic acid levels and its distribution in albumin and globulin proteins of human serum in normal and pathological conditions have been studied extensively (5, 6). However, this is not the case with CSF, though it has been studied in various degenerative conditions of the central nervous system (CNS). We have made an attempt to study total sialic acid levels in CSF and serum of children suffering from common infective and noninfective conditions of one CNS. Present study reports salient observations on sialic acid in CSF and serum of those patients. MATERIAL
AND METHODS
Sixty-five cases, from both sexes between the ages of 5 months and 10 years, admitted to a genera1 children’s hospital for complaints of convulsions were included in the present study. Blood and cerebrospinal fluid for routine and biochemical investigations were collected before giving any medication. Along with routine examination of blood, serum calcium, phosphorous, and alkaline phosphatase were estimated wherever indicated. Blood sugar was estimated in every case. Serum sialic acid was measured as N-acetyl neuraminic acid by Warren’s method (7) and expressed as micrograms per milligram of protein. Routine examination of CSF, along with sialic acid estimation, was done in all cases. The protein content of CSF was measured by Lowry et al.‘s method (8). Serum sialic acid was also estimated in 10 normal children to establish the normal standard, but it was not possible to estimate CSF sialic acid in normal individuals. 99 Copyright @ 1977 by Academic Press. Inc. 411 rights of reproduction in any fom~ reserved.
ISSN CKMX-2944
100
BHIDE. PAREKH.
AND DESAI
OBSERVATIONS AND DISCUSSION Table I gives the sialic acid content of serum and CSF in children suffering from TB and pyrogenic meningitis, febrile convulsion, tetany, epilepsy, encephalitis, and poliomyelitis. It may be observed that CSF values ranged from 13.5 in epilepsy to 21.7 in tetany. Since the normal values of CSF are not available it is difficult to state whether these are higher or lower than normal. Further, there was variation within each disease group and it was not possible to establish any correlation between the sialic acid values and the cell count, or the amount of sugar or protein in the CSF. In the cases of TB and meningitis an attempt was also made to determine whether the sialic acid values showed any correlation with recovery from the disease. However, the sialic acid values in the CSF from the first puncture and the second puncture when the disease had relatively regressed ranged from 14.2 to 25.5 irrespective of the state of disease. Serum sialic acid values, however, were higher in all the diseases when compared to normal serum levels (7.8 t 0.6 mg of protein). Considering the above data one fact is quite clear, i.e., there is variation in sialic acid levels of CSF within each group, as well as in different pathological conditions of the CNS. As in the present study, Warren (7) has also reported that there is no correlation between CSF protein and CSF sialic acids. On the other hand, O’Toole et al. (9) have observed a very good correlation between high concentrations of protein content and the elevated total N-acetyl neuraminic acid content of CSF in meningitis caused by neuraminidase-producing pneumococci. These workers further suggested that the increased sialic acid levels of CSF might be due to the release of n-acetyl neuraminic acid from gangliosides by the action of neuraminidase. Another noteworthy observation from the present studies is that serum TABLE
I
SIALIC ACID CONTENT IN CSF AND SERUM OF PATIENTS SUFFERING FROM INFECTIVE AND NONINFECTIVE CONDITIONS OF CNS”
CNS condition TB and meningitis Pyrogenic Fibrile convulsion Tetany Epilepsy Encephalitis Poliomyelitis
CSF 17.5 20.0 17.0 21.7 13.5 14.5 14.6
2 k t + + i +
1.5 (19)b 1.2 (6) 0.9 (21) 2.4 (4) 1.4 (4) 3.3 (4) 0.66 (4)
Serum 22.9 18.8 18.3 14.3 16.9 15.0 19.2
t 0.9 (17) ‘-c 1.0 (6) -c I.0 (20) t 0.9 (5) 5 1.6 (4) -c 1.4 (4) -c I.1 (4)
a Sialic acid content is expressed in terms of micrograms of n-acetyl neuraminic acid per milligram of protein. h Figures in parentheses are one number of samples used in each group.
SIALIC ACID LEVELS
IN SERUM AND CSF
101
sialic acid levels are significantly increased in all the cases studied. Increase in serum sialic acid with infection is reported in the literature (lo- 12). It is thus conceivable that in the present studies serum sialic acid was increased in conditions such as TB and meningitis, poliomyelitis, encephalitis, etc. In the case of febrile convulsion also, the increased sialic acids are possible since the convulsions are precipitated by the presence of infection elsewhere in the body. Summarizing other observations, it may be stated that the sialic acid content of CSF shows variations in diseases of the central nervous system, and this study did not show any correlation between the type or state of disease and sialic acid content. SUMMARY
Sialic acid levels in serum and CSF of children suffering from infectious and noninfectious types of CNS diseases were studied. It was observed that there was variation in sialic acid values of CSF in each group and there was no correlation between the metabolic parameters, number of cells in CSF, or progress of the disease. It was also observed that the serum sialic acid levels in various diseases are distinctly higher than those observed in normal serum. REFERENCES 1. Odin, L., Acto Chim. Stand. 9, 862 (1955). 2. Saifer, A., Aronson, S. M.. Zumaris, M. C., and Yolk, B. W.. Proc. Sot. Exp. Biol. Med. 9, 394 (1956). 3. Hoover, T. R. F., Braun, G. A., and Gyorgy, P.. Arch. &o&em. Biophys. 47, 216 (1953). 4. Svenerholm, L., Actn Chim. Stand. 12, 547 (1958). 5. Goftschalk, A., in ‘Chemistry and Biology of Sialic Acids and Related Substances.’ p. 88. Cambridge University Press, Cambridge, lY60. 6. Volk, B. W., Aronso, S. M., and Saifer, A., J. Lab. C/in. Med. 50, 26 (1957). 7. Warren, L., J. Biol. Chem. 234, 1971 (1959). 8. Lowry, 0. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J., J. Biol. Chem. 193, 265 (1951). 9. O’Toole, R. D., Goode, L., and Howe, C., .I. Clin. JO, 979 (1971). 10. Jacoby, R. K., and Warren, L., Neurology, 11, 232 (1961). 11. Soboczynsk, A., and Wahgora, A., Chem. Abstr. 68, 2043lY (1%8). 12. Agishev, V. G., Chem. Abstr. 73, 128886t (1970).