Capillary zone electrophoretic determination of organic acids in cerebrospinal fluid from patients with central nervous system diseases.

Organic acids in cerebrospinal fluid (CSF) from patients with various central nervous system (CNS) diseases were determined by capillary zone electrophoresis (CZE). Under one of the two sets of conditions employed, several anionic components of CSF were separated into corresponding peaks on the electropherograms and determined. The other conditions employed were also useful in measurement of the lactate contents in CSF. The CSF levels of lactate and pyruvate and the ratios of lactate to pyruvate were elevated in patients with cerebral infarction and bacterial meningitis, whereas CSF ascorbate was reduced mainly in inflammatory disorders of the CNS. The results showed that CZE can become a powerful tool in the biochemical diagnosis of CNS diseases.

Sodium dodecyl sulfate-capillary gel electrophoretic analysis of molecular mass microheterogeneity of beta-trace protein in cerebrospinal fluid from patients with central nervous system diseases.

Molecular mass (M(r)) microheterogeneity of beta-trace protein (beta TP) in cerebrospinal fluid (CSF) from patients with various neurological disorders was analyzed by sodium dodecyl sulfate capillary gel electrophoresis. Under the conditions employed, beta TP with a M(r) distribution of 23,000-30,000 was roughly separated into two subfractions containing the major peaks with M(r) of 26,000 and 28,500, respectively. The peak area ratios of the two subfractions of the electropherograms varied among the samples examined, and elevation in the total beta TP level in the CSF from patients with organic diseases in the central nervous system (CNS) was often accompanied by changes in the ratios of the subfractions. The quantitative changes in the subfraction level in CSF beta TP are considered to reflect the pathological alterations in the CNS.

Capillary electrophoretic analyses of beta-trace protein and other low molecular weight proteins in cerebrospinal fluid from patients with central nervous system diseases.

Ordinary capillary-zone electrophoresis (CZE), as well as CZE in a sodium dodecylsulfate-containing polymer solution (SDS-CZE) and capillary isoelectrofocusing (CIEF), was applied to the analysis of low molecular weight proteins in cerebrospinal fluid (CSF) from patients with various neuropsychiatric disorders. Under the CZE conditions employed, a peaks of beta-trace protein (beta TP), which is the most abundant low MW protein in CSF, was clearly detected on the electropherograms of all the samples examined, and the CSF beta TP level could be tentatively determined using allylamine added at a constant concentration as the internal standard. The results revealed that beta TP in CSF was non-specifically increased in organic disease in the central nervous system (CNS), especially in ones giving severe physical damage to the brain tissues. On the other hand, SDS-CZE allowed us to determine simultaneously the CSF minor low MW proteins other than beta TP, such as beta 2-microglobulin, gamma-trace protein, myelin basic protein, etc., while the CIEF electropherograms suggested that beta TP were separated into several fractions with the different PI values. These capillary electrophoresis systems seem to be powerful as aids in the biochemical examinations of beta TP and other low molecular weight proteins in CSF from patients with CNS diseases.

Reduction in blood free carnitine levels in association with changes in sodium valproate (VPA) disposition in epileptic patients treated with VPA and other anti-epileptic drugs.

Reduction in the blood free carnitine (FC) level as a side effect of sodium valproate (VPA) given epileptic patients was pharmacokinetically studied in connection with changes in the VPA disposition. The serum FC level in patients taking at least one of phenobarbital (PB), phenytoin (PHT) and/or carbamazepine (CBZ) in addition to VPA was significantly lower than that in the controls given only these other anti-epileptic drugs (AEDs). Patients medicated only with VPA also tended to have a lower serum FC level than the controls, although the difference was not significant. Among all the patients taking VPA with or without other AED(s), a significantly positive correlation was observed between the serum FC level and the value of dose and level ratio (L/D) of VPA, indicating that both the serum FC concentration and the L/D value of VPA were remarkably reduced in those patients receiving both medications. These results suggested that reduction in the blood FC level as a side effect of VPA reflected FC deficiency associated with the accelerated degradation of VPA in liver; such a condition appears to result from medication with VPA and other AED(s) which induce(s) enzyme(s) for the VPA metabolism.

Analysis of low-molecular-mass proteins in cerebrospinal fluid by sodium dodecyl sulfate capillary gel electrophoresis.

Proteins of low molecular (M(r)) in human cerebrospinal fluid (CSF) were analyzed by capillary electrophoresis in a sodium dodecyl sulfate-containing polymer solution. Under the conditions employed, peaks of beta 2-microglobulin (beta MG) (M(r): 11,700), gamma-trace protein (12,300), myelin basic protein (18,000), beta-trace protein (beta TP) (23,000 to 30,000) and alpha 1-acid glycoprotein (42,000) were detected on the electropherograms. The concentrations of beta MG and beta TP were determined based on the peak area relative to that of an internal standard, Orange G, which was added at a constant amount as the front marker. It was demonstrated that their levels in CSF change under various pathological conditions in the central nervous system.