Antioxidative enzymes activity and malondialdehyde concentration during mitoxantrone therapy in multiple sclerosis patients.

Mitoxantrone (MX) is approved for the treatment of aggressive relapsing-remitting, secondary-progressive and progressive-relapsing form of multiple sclerosis (MS). The mechanism of its action is multiaxial, however, it is not free from side effects. The causes of the side effects are still unknown and require further investigation. The aim of this study was to investigate the influence of MX therapy on enzymatic parameters of endogenous antioxidative status: manganese and copper/zinc superoxide dismutase (MnSOD, Cu/ZnSOD), catalase (CAT), glutathione peroxidase (GSH-Px) and lipid peroxidation marker--malondialdehyde (MDA) in blood serum and cerebrospinal fluid (CSF) in patients suffering from MS. After the MX therapy serum and the CSF MDA concentrations increased significantly. We reported that MnSOD activities decrease in serum and the CSF, while, surprisingly, the serum Cu/ZnSOD activity increases after the MX therapy. We also noted a marked decrease in CSF CAT and GSH-Px activity after the MX treatment. Our results strongly suggest the influence of MX therapy on oxidation/antioxidation status of serum and the CSF. These findings open up new opportunities for a better understanding of underlying physiopathological events in MS and provide a new insight into MX's mechanisms of action, especially its potent side effects.

No differences of butyrylcholinesterase protein activity and allele frequency in Lewy body diseases.

Butyrylcholinesterase (BChE) genotypes and protein (BuChE) activity, especially in combination with Apolipoprotein E4 (ApoE4), have been investigated as risk factors for developing Alzheimer disease (AD) and may be associated with the rate of progression of cognitive decline. Despite similar pathologic (e.g. amyloid deposition) and neurochemical (e.g. cholinergic deficits) aspects between AD and Lewy body diseases (LBD), scarce data is obtainable about BChE genotypes and BuChE activity in LBD. We measured BuChE activity levels in serum and cerebrospinal fluid (CSF) of 114 LBD subjects (59 of them were demented) and 31 elderly controls. We found higher CSF BuChE activity in males compared to females, and a negative correlation of serum BuChE activity with age and cognitive function. Demented LBD patients, non-demented LBD patients and controls did not differ significantly with regard to serum and CSF BuChE activity. Furthermore, BChE K variant and ApoE4 allele frequencies were determined. The BChE K variant was significantly associated with lower serum activity; the same trend was observable in CSF. The subgroups did not differ significantly with regard to BChE K/ApoE4 occurrence. These data confirm and extend previous results on the relationship between BChE gene and BuChE activity, and argue rather against a major impact of BuChE on LBD-associated pathologies.

[Neurotoxic activity of serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients against some enzymes of glutamate metabolism]. / Neurotoksyczne dzialanie surowicy krwi i plynu mózgowo- rdzeniowego chorych na stwardnienie boczne zanikowe na aktywnosc niektórych enzymów przemiany glutaminianu.

One of the hypotheses in amyotrophic lateral sclerosis (ALS) indicates on excitatory amino acids as the cause of neuronal death. Changes in their concentration in the tissues and body fluids may be the consequence of a defect in their transport, as well as abnormal activities of glutamate metabolizing enzymes. Abnormal synthesis/degradation of these enzymes and/or influence of activators/inhibitors should be taken into account. The activity of enzymes of glutamate metabolism of rat spinal cord in vitro in the presence of serum and cerebrospinal fluid (CSF) of 20 patients with ALS and 20 healthy controls was tested. In the presence of serum of the ALS patients glutaminase was significantly stimulated, instead of being inhibited; the inhibition of GABA aminotransferase, glutamate decaboxylase and aspartate aminotransferase was less evident than in the controls, glutamate dehydrogenase lost its activity more than in control conditions, the inhibition of glutamine synthetase was comparable to that when normal serum was applied. The activity of the enzymes in the presence of CSF of ALS patients was generally similar to that of normal CSF, except of glutaminase which was stimulated and GABA aminotransferase, which was inhibited stronger than in the presence of normal CSF. This study indicates, that changes in glutamate concentration in tissues and body fluids in ALS may be caused, at least partly, by abnormalities in the activity of glutamate metabolism enzymes, which are in turn induced by neurotoxic agents present in body fluids of ALS patients.

Toxicology of Astragalus lusitanicus Lam.

Astragalus lusitanicus is a toxic legume grown in Morocco and in some other Mediterranean countries. In small ruminants, poisoning by this plant is dominated by nervous signs characterized by many cycles of excitement-depression. Macroscopic examination of poisoned animals showed congestive lesions and oedema in the brain and lungs. Microscopic lesions consisted mainly of vacuolar degeneration in neurons, hepatocytes and in spleen and kidney cells. Serum activity of AST and CK as well as blood glucose and urea were increased as a result of poisoning. However, serum activity of alpha-mannosidase was not modified as is the case in locoism. Chemical investigations showed that A. lusitanicus does not contain swainsonine or miserotoxin and its selenium concentration is very low. However, this legume contains indolizidin alkaloids and a first compound was purified and identified.

Biochemical analysis of serum and cerebrospinal fluid in clinically normal adult camels (Camelus dromedarius).

The concentrations of total protein, glucose, cholesterol, triglyceride, urea nitrogen, creatinine, sodium, potassium, chloride, calcium, inorganic phosphorus, copper, magnesium, and iron and the activities of aspartate aminotransferase (AST), alanine aminotransferase, (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LD), creatine kinase (CK) and amylase were determined in cerebrospinal fluid (CSF) and serum from 21 clinically healthy adult camels. The concentrations of sodium, potassium and chloride in CSF were similar to those of serum; whereas the values for all other constituents were significantly higher (P<0.05) in serum than in CSF.

Advances in the analysis of cerebrospinal fluid.

The laboratory examination of cerebrospinal fluid (CSF) continues to play an important role in the clinical diagnosis and treatment of various disorders of the central nervous system (CNS). The major conditions currently include, as they have in the past, infectious diseases, neoplastic processes, multiple sclerosis, other demyelinating disorders, and intracerebral hemorrhage. Recent publications suggest a variety of new laboratory tests that may be useful in the evaluation of patients with both primary and metastatic malignancies, Alzheimer's disease, Creutzfeld-Jacob disease, global ischemia, various psychiatric disorders, CSF otorrhea and rhinorrhea, and in the differential diagnosis of cortical vs lacunar stroke, among others. Examples of these recent developments and their possible clinical usefulness are discussed.

[The cerebrospinal fluid from healthy pigs and pigs with central nervous system diseases]. / Untersuchung des Liquor cerebrospinalis bei gesunden und zentralnervös erkrankten Schweinen.

CSF samples were taken from 50 healthy pigs of both sexes and cytologically and biochemically examined. With the aid of regression calculations it was investigated, whether deep freezing of CSF samples influences the laboratory results. The parameters glucose, urea, creatinine, total protein, magnesium, anorganic phosphate, AST and AP were in good agreement with the values of the original samples exhibiting only slight variations. Minor age relationship was only seen with respect to the two enzymes LDH and HBDH. A linear relationship was found between values in CSF and in serum of the parameters urea, creatinine, sodium and potassium. CSF examination should include cell count, Pandy's test and bacteriological investigation as well as the determination of the levels of the enzymes LDH and HBDH. The activity of the enzymes AST and ALT increases along with the severity of the tissue damage (meningitis). The specific gravity increases similarly to the total protein level in cases of chronic compression of the spinal cord, and Pandy's test becomes positive. However, CSF glucose levels are partly reduced in animals with central nervous symptoms. The levels of the enzymes AP and CK are often increased in central nervous disturbances, but do not admit drawing a conclusion on the degree of damage.

MR and cerebrospinal fluid enzymes as sensitive indicators of subclinical cerebral injury after open-heart valve replacement surgery.

PURPOSE: To evaluate MR imaging and lumbar cerebrospinal fluid enzymes as potential sensitive indicators of cerebral injury after open-heart valve replacement surgery. METHODS: Thirty-four patients with cardiac valvular disease were prospectively entered into this study and then underwent valve replacement or repair under cardiopulmonary bypass using a membrane oxygenator. In 26 patients, MR head images were obtained 12 to 24 hours before surgery; repeat MR images were obtained between 1 and 2 weeks after surgery. In 18 patients, lumbar puncture cerebrospinal fluid was analyzed 24 to 48 hours after surgery; the analyses included measurement of lactic dehydrogenase, creatine phosphokinase, adenylate kinase, and neuron-specific enolase. RESULTS: After surgery, MR imaging showed new ischemic lesions in 15 (58%) of 26 patients: 7 with deep white matter hyperintense lesions; 5 with brain stem, caudate, cerebellar, or thalamic/basal ganglia infarcts; 1 with intraparenchymal hemorrhage; 1 with a subdural hematoma and cortical infarct; and 1 with a corpus callosum lesion consistent with calcium or air. These new ischemic lesions seen on MR images were associated with a focal neurologic deficit in only 4 (27%) of the 15 patients. Neuron-specific enolase and lactic dehydrogenase were abnormally elevated after surgery in 5 (28%) of 18 patients. Adenylate kinase and creatine phosphokinase (brain isozymes) were elevated in one (67%) of the patients. Two (40%) of the five patients with abnormally high neuron-specific enolase or lactic dehydrogenase after surgery also showed a new focal neurologic deficit. CONCLUSIONS: MR imaging is a sensitive measure of subclinical cerebral ischemia after cardiac valve replacement under cardiopulmonary bypass. Cerebrospinal fluid neuron-specific enolase and lactic dehydrogenase are less sensitive than MR imaging for detecting subclinical cerebral ischemia, but these values were elevated after surgery more frequently than was adenylate kinase in our patients.

Five days of antibacterial therapy for bacterial meningitis in children?

We evaluated the effectiveness of 5-day antibacterial therapy for bacterial meningitis in children. The study group included 26 children from 2 months to 15 years of age, admitted with microbiologically confirmed bacterial meningitis in 1990-1993 and treated for 5 days. A historical comparison group of 49 patients treated for 8 to 15 days was used. Penicillin monotherapy (300 mg/kg body weight) was used for meningococcal and pneumococcal meningitis and ampicillin (300 mg/kg body weight) for Haemophilus influenzae b meningitis. On day 5 of therapy the activity of aspartate aminotransferase (AST), lactic dehydrogenase (LDH), creatine phosphokinase (CPK) and gamma-glutamyl-transpeptidase (gamma GT) in the CSF was determined by photocolorimetric assay and the concentration of creatine kinase BB (CK-BB) by ELISA. IL-6 was analysed using EIA technique and a cerebral ultrasound was performed at the time of the termination of the antibacterial therapy. The mean follow-up time was 1.3 years for children in the study group and 3.2 in the control group. The time of hospitalisation was shorter in children treated for 5 days (p < 0.005). Complete clinical recovery was 81% in the study group and 66% in the comparison group at the time of the termination of antibacterial therapy. No relapses occurred. The activity of AST, CPK, LDH, and gamma GT in the CSF had returned to normal by the 5th day of therapy, but almost a 7-fold higher concentration of CK-BB was registered. The concentration of IL-6 in the CSF decreased with the therapy from 1,800 pg/ml to 685 pg/ml but still remained high.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrospinal fluid variables in clinically normal foals from birth to 42 days of age.

To determine the effects of age on each analyte, CSF variables were evaluated in healthy foals from birth through 42 days of age. Cerebrospinal fluid was collected from 14 clinically normal, naturally delivered cross-bred foals and was analyzed for glucose, sodium, potassium, magnesium, and total protein concentrations, total and differential WBC counts, RBC count, and lactate dehydrogenase, aspartate transaminase, and creatine kinase activities. Samples were collected in 3 foals < 48 hours old, and at 11 to 14 days of age in 4 foals, 21 to 22 days of age in 3 foals, and 31 to 42 days of age in 4 foals. Each foal was tested only once, to avoid any effects of CSF sample collection on subsequent analysis. Regression analysis confirmed age-related effects on CSF glucose, protein, and magnesium concentrations, but did not indicate an effect of age on CSF sodium and potassium concentrations or cell counts. Results indicate that CSF glucose concentration decreases with age; foals < 2 days old had the highest CSF glucose values, 98.8 +/- 12.0 mg/dl (mean +/- 1 SD). In foals 10 to 14 days old, CSF glucose concentration was 67.3 +/- 12.0 mg/dl, was 65.3 +/- 4.5 mg/dl in foals 21 to 22 days old, was 70.0 +/- 5.4 mg/dl in foals 31 to 42 days old, and was 51.1 +/- 2.5 mg/dl in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Substance P inactivating enzymes in human cerebrospinal fluid.

The Km and Vmax values were determined for enzymes in human lumbar cerebrospinal fluid (CSF) that inactivate synthetic substance P (SP = RPKPQQFFGLM-NH2) and produce metabolic products. For the human lumbar CSF samples analyzed in this study, Km = 2.24 +/- 0.93 mM and Vmax = 0.113 +/- 0.035 nmol/ml/min (n = 10; mean +/- SEM) for the rate of decrease of SP. HPLC analysis of the incubated synthetic peptide fragments demonstrated that the primary enzymatically produced fragment is SP(3-11), with minor amounts in decreasing order of SP(1-4), SP(1-7), and SP(1-9). Electrospray ionization mass spectrometry (ESI-MS) confirmed the appropriate molecular weights for the four peptides, SP(3-11), SP(1-4), SP(1-7), and SP(1-9). These data demonstrate that the primary enzyme in human lumbar CSF that acts on synthetic SP is a post-proline cleaving enzyme (PPCE).

Composition and analysis of cerebrospinal fluid in clinically normal adult cattle.

Cerebrospinal fluid and serum were obtained from 16 clinically normal adult cows (11 dairy, 5 beef). Sodium, potassium, magnesium, total protein, and albumin concentrations, osmolality, and lactate dehydrogenase and creatine kinase activities, were quantified in CSF and serum. Total and differential cell counting, protein electrophoresis, and IgG quantification were performed on CSF. Statistical analyses of these variables, including mean, SEM, range, and 95% confidence intervals, were performed. Effects of blood contamination were evaluated, and were found to be negligible for all measured constituents. Correction factors for CSF creatine kinase and lactate dehydrogenase activities accounting for cellular contamination were developed. Total nucleated cell count was similar to counts in CSF of other species, but higher than values in healthy people. Differential leukocyte count in CSF was similar to that reported in CSF of other domestic animals: mostly lymphocytes, fewer monocytoid cells, and scant neutrophils. Cerebrospinal fluid protein concentration was higher than concentration reported for dogs, goats, and people, but was similar to values reported for horses. Beef cows had higher CSF total protein concentration than did dairy cows; also, beef cows had higher CSF gamma-globulin concentration. The concentration of sodium in CSF was slightly higher than the value in serum, and potassium concentration was lower than the value in serum. In contrast to studies of human beings, CSF osmolality was generally less than serum osmolality in the cows studied. Reference values for CSF electrolyte concentrations and osmolality are useful for diagnosis of salt poisoning and for assessment of the effects of fluid therapy. Magnesium concentration was lower in CSF, compared with serum.(ABSTRACT TRUNCATED AT 250 WORDS)

[Characteristics of the cerebrospinal fluid in the evaluation of possible mechanism of brain lesions in suppurative meningitis of meningococcal and pneumococcal etiologies]. / Kharakteristika likvora v otsenke vozmozhnogo mekhanizma porazheniia mozga pri gnoinykh meningitakh meningokokkovoi i pnevmokokkovoi étiologii.

The enzymological parameters of the CSF were studied and compared in patients with purulent meningococcal and pneumococcal meningitis in addition to the detection of the CSF levels characteristic of the dead patients. The level of enzymorachia was shown to depend on the degree of leukocyte degradation as well as on the lipid peroxidation intensity in the CSF. These data were obtained on the basis of measuring the content of cerebral and leukocytic enzymes in the acute period and on days 7-10 of the disease. It has been also noted that evident signs of meningoencephalitis are detectable even on days 7-10 according to the enzymic levels. As compared to pneumococcal infection, the lysis of leukocytes in patients with meningococcal infection turned out more noticeable, being maximal in the dead.

Pathophysiology of cerebrospinal fluid in head injury: Part 2. Biochemical markers for central nervous system trauma.

Many substances are released into the cerebrospinal fluid after head injury. The study of these substances and their relationship to the severity and outcome of head trauma has lead to the search for biochemical markers to aid in the quantification of the severity of the lesion and serve as a prognostic guide. The authors review the potential usefulness of biochemical markers, qualities of an ideal marker, and several potential enzymes that may be utilized as markers in central nervous system trauma.

[Changes in some cerebrospinal fluid enzyme activities in patients with various neurological diseases]. / Comportamento di alcune attività enzimatiche del liquor in pazienti con malattie neurologiche diverse.

The authors have examined the activities of the enzymes GOT, CPT, CK, LDH, gamma-GT, PCHE and ALP in the cerebrospinal fluid of 50 patients with various neurological diseases. The results obtained show that many activities constantly and remarkably increase in few diseases of the nervous system. Particularly, GOT, GPT, LDH and ALP demonstrated raised values in the meningitis; LDH, CK, GOT, GPT in the brain tumors; CK and LDH in the hydrocephalus. A comparison between the results of the protein and enzyme determinations in the cerebrospinal fluid of the same patients, revealed in the enzymologic reactions a more precocious and sensitive indicator of initial brain lesions.