Defining novel functions for cerebrospinal fluid in ALS pathophysiology

Despite the considerable progress made towards understanding ALS pathophysiology, several key features of ALS remain unexplained, from its aetiology to its epidemiological aspects. The glymphatic system, which has recently been recognised as a major clearance pathway for the brain, has received considerable attention in several neurological conditions, particularly Alzheimer's disease. Its significance in ALS has, however, been little addressed. This perspective article therefore aims to assess the possibility of CSF contribution in ALS by considering various lines of evidence, including the abnormal composition of ALS-CSF, its toxicity and the evidence for impaired CSF dynamics in ALS patients. We also describe a potential role for CSF circulation in determining disease spread as well as the importance of CSF dynamics in ALS neurotherapeutics. We propose that a CSF model could potentially offer additional avenues to explore currently unexplained features of ALS, ultimately leading to new treatment options for people with ALS.</p

Readdressing the role of therapeutic drug monitoring for antiepileptic drugs – A tertiary care hospital experience

Background: Therapeutic drug monitoring is a beneficial tool to supervise patients when they do not respond to a therapeutic dose. Inter individual variability in the concentration of an antiepileptic drug that produces optimal therapeutic response is highly significant. Therefore, this retrospective study was taken up to study the inter relation between antiepileptic drug dosages, serum concentration sand clinical condition in the Indian patients. Materials and Methods: This is a retrospective study, in which the data of the samples of adult patients of either gender, analyzed for Phenytoin, Valproate, Carbamazepine and Phenobarbitone were included. The samples were stratified based on dosage prescribed. The endpoints were to estimate the percentage of samples of each stratum having sub therapeutic, therapeutic and supra therapeutic concentrations. Results: Of the 134 samples included, 114 (85%) were analyzed for phenytoin, 9 for valproate, 7 for carbamazepine and 4 for phenobarbitone. Of the 114 samples analyzed for phenytoin, 61(53.5%) samples were having sub therapeutic concentrations, 22 samples (19.3%) had therapeutic concentrations and 31 samples (27.2%) had toxic concentrations. Among the 61 samples having sub therapeutic concentrations, 54.1% were prescribed dose of 300-350mg/day, 16.4% were on 350-400 mg/day and 1.6% were taking above 400mg/day. Of the total cases referred, 41.8 % had H/O of seizures and 30.6% presented with toxic symptoms. Conclusion: This study demonstrated unpredictable inter individual variability in clinical response based on reference ranges. However, the relevance of individual reference concentrations for predicting outcomes can only be confirmed through adequately controlled randomized studies

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Not AvailableThe pink stem borer Sesamia inferens Walker is an important pest of winter maize, causing dead hearts and significant yield losses. In an attempt to decipher biochemical basis of resistance against S. inferens, total soluble phenolics, bound phenolics, total tannin content, total flavonoid content, cell wall bound hydroxycinnamic acids-p-coumaric acid (p-CA) and ferulic acid were measured in leaf at 10, 20 days after germination(DAG); stem at 20,40 DAG; pith and rind tissues at 60 DAG (stem differentiated). Higher quantities of phenolic compounds except total soluble phenolics and total flavonoid contents were found in either resistant (DMRE63) or moderately resistant lines (WNZPBTL3,WNZExotic Pool) compared to susceptible genotypes (BML6, CM202). Significant negative correlation (r=-0.8441*) between leaf injury rating and p-CA content in stem tissues at 40 DAG indicated its role in expression of resistance to S. inferens. The proportion of spread of various biochemical constituents of different genotypes ranged from 50.59 to 19.19% as determined according to Eigen analysis. From the results, it can be concluded that higher concentrations of p-CA, ferulic acid and total tannin content are the possible biochemical defense mechanisms in maize against S.inferens.Not Availabl

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Not Availablesignificant implications for sustainable pest management. The present study demonstrated that PSB feeding, mechanical wounding, a combination of mechanical wounding and PSB regurgitation and exogenous application of methyl jasmonate have induced phenolic compound mediated defense responses both at short term (within 2 days of treatment) and long term (in 15 days of treatment) in leaf and stalk tissues of maize. The quantification of two major defense related phenolic compounds namely p-Coumaric acid (p-CA) and ferulic acid (FA) was carried out through ultra-fast liquid chromatography (UFLC) at 2 and 15 days after imposing the above treatments. The p-CA content induced in leaf tissues of maize genotypes were intrinsically higher when challenged by PSB attack at V3 and V6 stages in short- and long-term responses. Higher p-CA content was observed in stalk tissues upon wounding and regurgitation in short- and long-term responses at V3 and V6 stages. Significant accumulation of FA content was also observed in leaf tissues in response to PSB feeding at V3 stage in long-term response while at V6 stage it was observed both in short- and long-term responses. In stalk tissues, methyl jasmonate induced higher FA content in short-term response at V3 stage. However, at V6 stage PSB feeding induced FA accumulation in the short-term while, wounding and regurgitation treatment-induced defense responses in the long-term. In general, the resistant (DMRE 63, CM 500) and moderately resistant genotypes (WNZ ExoticPool) accumulated significantly higher contents of p-CA and FA content than susceptible ones (CM 202, BML 6) in most of the cases. The study indicates that phenolic mediated defense responses in maize are induced by PSB attack followed by wounding and regurgitation compared to the other induced treatments. Furthermore, the study confirmed that induced defense responses vary with plant genotype, stage of crop growth, plant tissue and short and long-term responses. The results of the study suggested that the Phenolic acids i.e. p-CA and FA may contribute to maize resistance mechanisms in the maize-PSB interaction system.Not Availabl

Effect of genome and environment on metabolic and inflammatory profiles.

Twin and family studies have established the contribution of genetic factors to variation in metabolic, hematologic and immunological parameters. The majority of these studies analyzed single or combined traits into pre-defined syndromes. In the present study, we explore an alternative multivariate approach in which a broad range of metabolic, hematologic, and immunological traits are analyzed simultaneously to determine the resemblance of monozygotic (MZ) twin pairs, twin-spouse pairs and unrelated, non-cohabiting individuals. A total of 517 participants from the Netherlands Twin Register, including 210 MZ twin pairs and 64 twin-spouse pairs, took part in the study. Data were collected on body composition, blood pressure, heart rate, and multiple biomarkers assessed in fasting blood samples, including lipid levels, glucose, insulin, liver enzymes, hematological measurements and cytokine levels. For all 51 measured traits, pair-wise Pearson correlations, correcting for family relatedness, were calculated across all the individuals in the cohort. Hierarchical clustering techniques were applied to group the measured traits into sub-clusters based on similarity. Sub-clusters were observed among metabolic traits and among inflammatory markers. We defined a phenotypic profile as the collection of all the traits measured for a given individual. Average within-pair similarity of phenotypic profiles was determined for the groups of MZ twin pairs, spouse pairs and pairs of unrelated individuals. The average similarity across the full phenotypic profile was higher for MZ twin pairs than for spouse pairs, and lowest for pairs of unrelated individuals. Cohabiting MZ twins were more similar in their phenotypic profile compared to MZ twins who no longer lived together. The correspondence in the phenotypic profile is therefore determined to a large degree by familial, mostly genetic, factors, while household factors contribute to a lesser degree to profile similarity