Altered Cerebrospinal Fluid Concentrations of Hydrophobic and Hydrophilic Compounds in Early Stages of Multiple Sclerosis-Metabolic Profile Analyses.

The lack of a single predictive or diagnostic test in multiple sclerosis (MS) remains a major obstacle in the patient's care. The aim of this study was to investigate metabolic profiles, especially lipids in cerebrospinal fluid (CSF) using 1H-NMR spectroscopy and metabolomics analysis to discriminate MS patient group from the control ones. In this study, 19 MS patients and 19 controls, without neurological problems, patients were enrolled. To obtain the CSF metabolic profiles, NMR spectroscopy was used. Hydrophilic and hydrophobic compounds were analyzed using univariate and multivariate supervised analysis orthogonal partial least square discriminant analysis (OPLS-DA). Targeted OPLS-DA analysis of 32 hydrophilic and 17 hydrophobic compounds obtained 9 hydrophilic metabolites and 8 lipid functional groups which had the highest contribution to patient's group separation. Lower concentrations of CSF hydrophilic and hydrophobic compounds were observed in MS patients as compared to control group. Acetone, choline, urea, 1,3-dimethylurate, creatinine, isoleucine, myo-inositol, leucine, and 3-OH butyrate; saturated and monounsaturated acyl groups of ω-9, ω-7, ω-6, ω-3, and fatty acid, triglycerides, 1,3-DG, 1-MG, and unassigned component signal at 3.33 ppm were the most important signal compounds in group separation. Analysis of metabolic profile of raw CSF and their lipid extract shows decreased levels of many compounds and led to the conclusion that MS patients could have a disturbance in many metabolic pathways perhaps leading to the decreased level of acetyl-CoA and/or inflammation. CSF metabolic profile analyses could be used as a fingerprint for early MS diagnosis.

Electrolytes and Biochemical Changes in Cerebrospinal Fluid in Drowning: Experimental Rabbit Model.

The diagnosis of drowning is still a difficult task in forensic science. Biochemical changes in different body fluids have been examined for the identification of drowning. However, none of them alone gives accurate results in the diagnosis of drowning and differentiation of saltwater and freshwater drowning. This study aimed to examine cerebrospinal fluid changes in drowned rabbits. Six groups of rabbits were used including immersed dead rabbits in freshwater or saltwater (as control groups), alive fully conscious rabbits drowned in freshwater and saltwater, and anesthetized rabbits drowned in freshwater and saltwater. Cerebrospinal fluid electrolytes except for potassium levels were significantly higher in rabbits drowned consciously in saltwater than their level in the control group. In rabbit drowned in freshwater, the examined electrolytes decreased significantly. In addition, urea, creatinine, uric acid, glucose, and tumor necrosis factor were different in cases of freshwater and saltwater drowning from those of control rabbits. Electrolytes and biochemical changes of unconscious rabbits drowned in water showed no significant difference from those of control rabbits. Cerebrospinal fluid examination in drowning gives promising results in the diagnosis of drowning. In addition, the differentiation between freshwater and saltwater drowning was possible.

Cerebrospinal fluid: postmortem biochemical study.

UNLABELLED: Postmortem phenomena can change and alter biochemical components in body fluids such as blood and as cerebrospinal fluid (CSF). AIMS OF THE STUDY WERE: (a) to analyse urea, glucose, potassium, chloride, protein, creatinine, calcium, alkaline phosphatase and cortisol in CSF fluid and (b) to compare results between two age groups, between groups with or without mental or degenerative neurological illness and between a group reported as dying from natural causes and a group that had a violent death. MATERIALS AND METHODS: The study was carried out in Hospitalet de Llobregat (Barcelona) of 55 corpses. Samples were obtained following section of the corpus callosus, through the lateral ventricles and frozen to -80 degrees C until processed. RESULTS: Significant differences were found in urea levels between the two age groups, in protein between natural and violent death groups and in alkaline phosphatase between the two age groups and between the natural and violent death group. Cortisol levels revealed significant difference between the two age groups and is those supplying natural and violent death. CONCLUSIONS: The study indicates to the need for further studies designed to include groups with defined diagnose of mental or degenerative disorders as well as different age groups.

Effects of acute and chronic hypertension on the labyrinthine barriers in rat.

Hearing loss, vertigo, and tinnitus have been related to arterial hypertension. The aim of the present work was to study the permeability of the blood-perilymph and of the labyrinthine barrier, between endolymph and perilymph, to small molecules during chronic and acute hypertension. Experiments were performed in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Acute hypertension was induced by phenylephrine. Perilymph was sampled from the first turn of the scala vestibuli and the Na, K, urea, and radioactive concentrations ((14)C-urea and (3)H-mannitol) were measured. In another experimental set, the endocochlear potential was recorded from the basal turn of scala media, before and after phenylephrine injection. The composition of the perilymph and the kinetic constants for (14)C-urea and (3)H-mannitol were similar in WKY and SHR, and not modified after acute hypertension. In endolymph, the endocochlear potential in SHR (+80+/-2.7 mV, n=24) was lower (P<0.001) than in WKY (+98+/-1.5 mV, n=29). The endocochlear potential was decreased by 40 mV during acute hypertensive peak in seven out of 19 WKY but not in SHR rats (n=13). In conclusion, chronic or acute hypertension did not severely alter the permeability to small molecules of the blood-perilymph barrier. The relationship between the low endocochlear potential and hypertension in SHR remains to be evaluated. After acute hypertensive peak, the presence of vascular protective mechanisms in the cochlea could account for the stable endocochlear potential recorded in SHR and 60% of normotensive rats.

[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.

Immunoreactive parathyroid hormones in the circulation and cerebrospinal fluid from patients with renal failure: possible restriction of parathyroid hormone by the blood-brain barrier.

Parathyroid hormone is reported to be a possible causal factor of abnormalities of electroencephalograms of patients with renal failure. In this study, the parathyroid hormone levels were compared in the circulation and cerebrospinal fluid of seven normal subjects and 22 patients with renal failure including those who showed abnormal electroencephalograms. The circulating levels of both C-terminal and N-terminal parathyroid hormone in the subjects studied showed a positive correlation (C-terminal, r = 0.58, P less than 0.01; N-terminal, r = 0.61, P less than 0.01) with the grade of abnormality of the electroencephalogram. However, the levels of C-terminal and N-terminal parathyroid hormone in the cerebrospinal fluid of both normal subjects and patients with renal failure were below the detectable limit (C-terminal, less than 0.1 ng/ml; N-terminal, less than 2.3 pg/ml). These data suggest that in patients with renal failure, the effect of parathyroid hormone on the central nervous system is mediated in some other way than via the cerebrospinal fluid.

A profile of ammonia-urea values in blood and cerebrospinal fluid in children with protein energy malnutrition.

The study comprised 25 children suffering from PEM. Ten of them were non-oedematous and the rest were oedematous. A group of 10 children of similar age served as the controls. A state of hyperammonaemia with slightly reduced blood urea was found in both forms of PEM but was more marked in kwashiorkor. There was also a highly significant increase in CSF ammonia in all cases of PEM studied. Some of the mental changes which have been observed in kwashiorkor may be, at least in part, due to ammonia intoxication.

[Cerebrospinal fluid composition in newborn piglets]. / Analyse de la composition du liquide céphalo-rachidien chez le porcelet nouveau-né.

Cerebrospinal fluid composition has been studied in low and normal birthweight piglets. Values for urea, Ca, K, Cl and P did not differ between the two groups. However, glucose concentration was lower in low birthweight subjects and Mg and Na values were higher. Total leukocytes were also higher in low birthweight piglets. These differences may suggest that blood-brain-barrier is not at the same stage of maturation in low birthweight as in normal birthweight subjects.

Postmortem biochemical changes in canine cerebrospinal fluid.

Time and temperature effects on postmortem cerebrospinal fluid samples from 60 adult mongrel dogs were studied. After death the dogs were held at 4, 20, or 37 degrees C for intervals of 3, 6, 12, 24, or 48 h. Antemortem and postmortem cerebrospinal fluid was evaluated for sodium, chloride, potassium, urea nitrogen, glucose, creatinine, calcium, phosphorus, and carbon dioxide. Sodium and urea nitrogen values remained stable. Chloride may be of forensic science value. Low levels of postmortem calcium might indicate antemortem hypocalcemia; high levels of postmortem glucose may indicate antemortem hyperglycemia. Calcium and creatinine levels increased slightly but continually after death; carbon dioxide values dropped.

Effect of urea on osmolality of perilymph.

Blood osmolality was altered in chinchillas by intravenous administration of urea. Serum osmolality peaked rapidly at 30 minutes after administration and decreased slightly to a plateau for 180 minutes. Perilymph and CSF osmolality lagged substantially behind the increase in serum osmolality and equaled serum osmolality only after one hour. Perilymph osmolality followed changes in the serum up to 60 minutes with a definite time lag. This phenomenon suggests the existence of a selective blood-labyrinth barrier that is permeable to urea and water. However, the time lag due to the barrier may permit the reduction of hydrostatic pressure in the labyrinth. The results of the present study seem to render partial explanation of improved hearing in patients with Meniere's disease who were treated with urea.

The effect of haemodialysis on cerebrospinal fluid and plasma amino acids.

The concentration of free amino acids in CSF and plasma has been measured in 19 patients with renal disease undergoing haemodialysis therapy. The values obtained have been compared with those measured in non-haemodialysed patients. At the end of a 10-h dialysis period, the total CSF amino acid concentration had fallen by only 23.3% compared with a 57.7% fall in plasma. Examination of the results for individual amino acid concentrations showed 3 different patterns of inter-relationship between plasma and CSF.

Uptake of [14C]urea by the in vivo choroid plexus--cerebrospinal fluid--brain system: identification of sites of molecular sieving.

1. The time course of the uptake of [(14)C]urea by the lateral ventricular choroid plexus of the adult rat in vivo was analysed to delineate further the permeability characteristics of the epithelial membrane of this secretory tissue.2. Eight hours after I.P. injection, [(14)C]urea attained a steady-state distribution in 78% of the tissue water of lateral ventricular choroid plexus; similarly, approximately 8 hr was required for radiourea to reach a steady-state concentration in both the cerebral cortex and cerebrospinal fluid (c.s.f.).3. Results obtained for compartment analysis were used to calculate the concentration of [(14)C]urea in the epithelium of the lateral ventricular plexus during the approach to and at steady-state distribution. Even after 1 hr of distribution, the [(14)C]urea concentration in choroid cell water was less than 15% of that in plasma water.4. Although the concentration of radiourea in choroid cell water continually increased after 3 hr, it remained in equilibrium with the concentration of [(14)C]urea in c.s.f. water. At the steady state (i.e., 8 hr), the distribution of [(14)C]urea between the water of plasma and that of the choroidal epithelium was considerably away from equilibrium (i.e., by 25-30%).5. An analysis of the concentration gradients for [(14)C]urea across both the apical (c.s.f.-facing) and basolateral (plasma-facing) membranes of the epithelium of the lateral ventricular plexus suggests that the movement of urea is hindered to a greater extent by the basolateral membrane than by the apical membrane.6. Only a single half-time component (1.3 hr) can be resolved from analysis of the curve describing the time course of uptake of radiourea by the choroid epithelial cell compartment.7. The concentration gradient data suggest that urea penetrates from blood to c.s.f. via the choroid plexus by a transcellular pathway; however, it is not possible to rule out a paracellular pathway for urea movement.8. At the steady state, radiourea distributes into 88% of the water of cerebral cortex. This observation, together with the finding of a steady-state concentration gradient for [(14)C]urea from cortical tissue to c.s.f., constitutes evidence that urea movement is hindered at the blood-brain barrier as well as at the blood-c.s.f. barrier.

Composition of fluid from the notochordal canal of the coelacanth, Latimeria chalumnae.

Fluid from the notochordal canal of the coelacanth, Latimeria chalumnae, was analyzed for major inorganic and organic constituents and compared with blood serum from the same fish. Significantly or suggestively lower levels of sodium, magnesium, calcium, bicarbonate, sulfate, total carbohydrates, glucose, lactate, cholesterol, bound phosphate and total proteins were found in notochordal fluid than in serum, whereas potassium, chloride, urea, trimethylamine oxide, and total free amino acids were higher and inorganic phosphorus essentially identical. Osmolarity of notochordal fluid (1058 mOsm) exceeds that of serum (942 mOsm). A whitish precipitate in the fluid consisted of a matrix of fibers 100 A in diameter and of indefinite length. It resembled a sialoglycoprotein in composition and was stabilized by disulfide bonds. The fluid contained cellular debris.