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Author(s): A. K. Pautova [sup.1] , N. A. Burnakova [sup.2] , N. V. Beloborodova [sup.1] , A. I. Revelsky [sup.2] Author Affiliations: (1) grid.513061.0, Federal Research and Clinical Center of [...], Aromatic, short-chain fatty and dicarboxylic acids are low-molecular-weight microbial and mitochondrial metabolites; therefore, their simultaneous screening in biological samples, including cerebrospinal fluid, is a promising solution to an important problem - the timely differential diagnosis of various diseases and pathologies, in particular, those associated with the disruption of the central nervous system. There is a need in developing a sensitive method for the simultaneous determination of these compounds, because they are most often present in biological samples in trace amounts. Blood serum and cerebrospinal fluid are complex matrices including various compounds. Aromatic, short-chain fatty and dicarboxylic acids were isolated and preconcentrated in the present study by traditional liquid-liquid extraction modified at the derivatization stage: the organic extractant was not evaporated and derivatization was carried out directly in the volume of diethyl ether. The different volatilities and polarities of the compounds was taken into account; therefore, derivatization was carried out with moderate heating (60°C) using various silylating reagents. Depending on the type of silyl derivatives, we set the analysis mode of gas chromatography-mass spectrometry method in order to achieve an acceptable analysis time, increase sensitivity to target compounds, and carry out a complete gas chromatographic separation of all analytes. To assess the applicability of the developed conditions, analytical characteristics were determined in model solutions and in the blood serum of healthy donors. For all the developed analysis conditions, linearity was observed in a clinically significant range; the lower limits of quantitation were in the range from 0.06 to 0.9 mol L.sup.-1, which made it possible to analyze samples of the cerebrospinal fluid of neurosurgical patients (n = 6).

Author(s): Alexandra M. Miller [sup.1] , Ronak H. Shah [sup.2] [sup.3] [sup.12] , Elena I. Pentsova [sup.1] , Maryam Pourmaleki [sup.4] , Samuel Briggs [sup.1] , Natalie Distefano [sup.5] , [...], Diffuse gliomas are the most common malignant brain tumours in adults and include glioblastomas and World Health Organization (WHO) grade II and grade III tumours (sometimes referred to as lower-grade gliomas). Genetic tumour profiling is used to classify disease and guide therapy.sup.1,2, but involves brain surgery for tissue collection; repeated tumour biopsies may be necessary for accurate genotyping over the course of the disease.sup.3-10. While the detection of circulating tumour DNA (ctDNA) in the blood of patients with primary brain tumours remains challenging.sup.11,12, sequencing of ctDNA from the cerebrospinal fluid (CSF) may provide an alternative way to genotype gliomas with lower morbidity and cost.sup.13,14. We therefore evaluated the representation of the glioma genome in CSF from 85 patients with gliomas who underwent a lumbar puncture because they showed neurological signs or symptoms. Here we show that tumour-derived DNA was detected in CSF from 42 out of 85 patients (49.4%) and was associated with disease burden and adverse outcome. The genomic landscape of glioma in the CSF included a broad spectrum of genetic alterations and closely resembled the genomes of tumour biopsies. Alterations that occur early during tumorigenesis, such as co-deletion of chromosome arms 1p and 19q (1p/19q codeletion) and mutations in the metabolic genes isocitrate dehydrogenase 1 (IDH1) or IDH2.sup.1,2, were shared in all matched ctDNA-positive CSF-tumour pairs, whereas growth factor receptor signalling pathways showed considerable evolution. The ability to monitor the evolution of the glioma genome through a minimally invasive technique could advance the clinical development and use of genotype-directed therapies for glioma, one of the most aggressive human cancers. Identification and sequencing of circulating tumour DNA in the cerebrospinal fluid of patients with glioma.

OBJECTIVE: To determine the sensitivity, specificity, and negative and positive predictive values of cerebrospinal fluid (CSF) xanthochromia for detection of ruptured cerebral aneurysms in patients with thunderclap headache (sudden and [...]

An amperometric method suitable for the continuous online measurement of cerebral hydrogen peroxide from a microdialysate has been successfully performed for the first time by using an enzyme-modified ring--disk plastic carbon film electrode (PCFE) in a thin-layer radial flow cell. PCFE consists of a ring electrode modified with horseradish peroxidase to detect [H.sub.2][O.sub.2] at 0.0 V (vs Ag/ AgCl) and a disk electrode coated with ascorbate oxidase (AOx) to preoxidize ascorbic acid (AA) and thus suppress interference via direct oxidation. Analytes in solution (brain dialysates or standards) are mixed on-line with a phosphate-buffered solution containing dissolved oxygen and chelating agent, EDTA. The buffered solution is used to provide the [O.sub.2] necessary for the AOx catalytic reaction, stabilize the changes in dialysate pH that are associated with the in vivo formation of [H.sub.2][O.sub.2], and remove heavy metal ion impurities and thus suppress reactions between AA and [H.sub.2][O.sub.2]. This procedure enables trace levels of [H.sub.2][O.sub.2] to be readily monitored, virtually interference-free from physiological levels of AA, uric acid, electroactive neurotransmitters and their principle metabolites, in a continuous-flow system.

After subarachnoid haemorrhage (SAH), cerebral angiography is usually performed to establish a site of bleeding, which may then be treated surgically to prevent a potentially catastrophic rebleed. The investigation of [...]

The authors note that the combination of ritonavir and saquinavir are effective in keeping viral blood count low, but that the blood-brain barrier may keep the drugs from the cerebrospinal fluid (CSF), thereby allowing a safe haven for the HIV virus. Despite many variable factors which further study might clarify, the HIV RNA levels seem equally low in CSF as in blood.

The authors compared samples of cerebrospinal fluid (CSF) and plasma in which levels of HIV virus had been measured with samples from patients treated with lamivudine. They found a mutation which resists lamivudine in both CSF and plasma, which indicates that CSF and plasma HIV levels are related.

The authors examined the proportional relationships between certain types of measurements used in HIV management, such as cerebrospinal fluid (CSF) viral load and others. They found, unexpectedly, that in patients with a CD4 count below 200, there was a direct correlation to the CSF viral load.

To purify and characterize low-abundance proteins in complex biological mixtures, we used a novel strategy that combined preparative two-dimensional liquid-phase electrophoresis (2D-LPE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDITOF MS). Preparative 2D-LPE is based on the same isoelectric focusing and gel electrophoresis principles as the widely used analytical 2D gel electrophoresis, except that analytes remain in solution throughout separation. This novel approach shows many improvements compared to analytical 2D gel electrophoresis for the separation of proteins in biological fluids. For example, larger volumes/amounts of samples can be loaded, yielding sufficient amounts of low-abundance proteins for further characterization. Since proteins remain in liquid phase during the entire procedure, extra steps such as electro-elution, extraction, or transfer to membranes from the gels prior to mass spectrometric analysis are obviated. We report the usefulness of 2D-LPE combined with MALDITOF MS for the purification and characterization of cystatin C and [Beta]-2 microglobulin in human cerebrospinal fluid. This method should be applicable to a wide range of biological fluids, such as cerebrospinal fluid, serum, tissue extracts, cell media, whole cells, and bacterial lysates.

To allow rat brain lactate measurement in vivo, a specific sensor based on a carbon fiber ([Phi] = 30[[micro]meter]) microelectrode coated with lactate oxidase was prepared. Combined with the differential normal pulse voltammetry measurement method, such a sensor, with a sensitivity of 9.15 [+ or -] 0.91 mA [multiplied by][M.sup.-1][multiplied by][cm.sup.-2], provided a lactate linear response in concentrations ranging from 0.1 to 2.0 mM. The measurements performed appeared to be essentially insensitive to usual interference caused by the electroactive compounds present in the brain (ascorbic acid and peptides). In vivo detection performed in the cortex of the anesthetized rat led to the determination of a lactate concentration of 0.41 [+ or -] 0.02 mM. Moreover, to validate the results obtained in vivo, an ex vivo determination of the lactate level was also performed in samples of brain tissue, plasma, and cerebrospinal fluid, using both voltammetry and a clinical analyzer with colorimetric-based detection. A good correlation was observed between the sets of data established by both methods.

A study was conducted on the effect of oral feeding of essence of chicken on the level of 5-hydroxyindole acetic acid in the cerebrospinal fluid of the rat. The results suggest that the consumption of essence of chicken causes a rise in brain 5-hydroxytryptamine (HT) activity which may lead to the activation of 5-HT-dependent physiological processes such as mood elevation, analgesia, sleep improvement, facilitation of motor output and regulation of circadian rhythm.

The study of the origin and pathogenetic relevance of the oligoclonal antibodies present in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients has been hampered by a lack of specific ligands. We recently reported a general strategy, based on phage-displayed random peptide libraries, to identify ligands for disease-specific antibodies even in the absence of any information on the nature of the pathologic antigen. With this procedure, we identified several peptides specifically recognized by antibodies present in the CSF of MS patients. Using these peptides as reagents, we demonstrated that they mimic different natural epitopes and react with antibodies enriched in the CSF of MS patients. Antibodies recognizing the selected peptides are commonly found with equal frequency in the sera of MS patients and of normal individuals. In contrast, the repertoire of CSF antibodies appears to be individual-specific and is probably the result of a nonspecific immunodysregulation rather than a stereotyped response to a single antigen/agent.

A new assay can detect the presence of a specific brain protein in cerebrospinal fluid that could be a marker for spongiform encephalopathies. This group of diseases is characterized by a degeneration of brain tissue and includes Creutzfeldt-Jakob disease in humans and mad cow disease. Two proteins discovered in cerebrospinal fluid have been found to be identical to the 14-3-3 brain protein. The immunoassay can detect the protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease with a 95% accuracy. It also ruled out the disease in 96% of the patients with other types of dementia.

The postprandial cerebrospinal fluid (CSF) glucose concentration remains unchanged in the obese patient with binge eating disorder and bipolar depression studied after consumption of a glucose-rich, mixed liquid meal. The fasting serum glucose level is normal and fasting CSF glucose concentration is lower in the bulimic patient than in normal women. The low level of postprandial passage of glucose in the central nervous system may lead to the binge eating.

Capillary electrophoresis with laser-induced fluorescence detection is used to analyze 10 [[micro]liter] samples of human cerebrospinal fluid. Primary amine-containing compounds in untreated cerebrospinal fluid are labeled with 3-(4-carboxybenzoyl)-2-quinolinecarboxaldehyde prior to analysis, producing fluorescent isoindoles. Electropherograms containing approximately 50 peaks are obtained in less than 35 min from cerebrospinal fluid samples. Ten peaks in the electropherograms have been identified and quantitated: arginine, glutamine, threonine, valine, [Gamma]-amino-n-butyric acid, serine, alanine, glycine, glutamic acid, and aspartic acid. Detection limits for these 10 amino acids range from 0.29 nM for [Gamma]-amino-n-butyric acid to 100 nM for threonine, and separation efficiencies as high as 190 000 theoretical plates are obtained for these analytes. Electropherograms of cerebrospinal fluid samples from patients with Alzheimer's disease and from children with different neurological disorders are compared to those of healthy controls. Differences in individual amino acid levels are observed between the patient groups, and these differences appear to be disease and age related. These results indicate that analysis of cerebrospinal fluid by capillary electrophoresis will be useful as a selective, rapid, and sensitive tool for both diagnosis of central nervous system disorders and for study of the mechanisms of these disorders.

Analysis of the time course of edema resolution by the brain vasculature and from brain to cerebrospinal fluid (CSF) reveals that the majority of radioiodinated cat serum albumin (RICSA) clearance occurs through CSF pathways. The critical stage of resolution exhibits minimum vascular clearance. Processes required for clearance of RICSA from the extracellular space remain active during the acute stage of edema resolution.

A rise in the cerebrospinal fluid (CSF) formation rate in new born rats corresponds to the rise in blood flow to choroid plexus in postnatal rats. Choroidal blood flow changes induce corresponding changes in the choroidal vascular system to incorporate a rise in secretory activities of the developing choroidal epithelium. The primary CSF source is the choroid plexus found in the four cerebral ventricles.

Children with central nervous system leukemia who have immature blood cells (blasts) in their cerebrospinal fluid but few white blood cells may require intensive chemotherapy and radiation therapy. This contradicts the present policy, which recommends intensive therapy only for those with more than five white blood cells per microliter of cerebrospinal fluid. Of 351 children with acute lymphoblastic leukemia affecting the central nervous system, 291 had no evidence of blasts in their cerebrospinal fluid, 42 had blasts but fewer than five white blood cells per microliter and 18 had blasts and more than five white blood cells per microliter. All the children received chemotherapy for one year and those at high risk of relapse received chemotherapy and radiation treatment one year after remission. Five-year survival rates were similar in the two groups that had blasts in their cerebrospinal fluid, regardless of the level of white blood cells. Nine of these children experienced a relapse, all within the first year of therapy. Five had fewer than five white blood cells per microliter of cerebrospinal fluid.