Fermentation, Isolation, Structure, and antidiabetic activity of NFAT-133 produced by Streptomyces strain PM0324667

Type-2 diabetes is mediated by defects in either insulin secretion or insulin action. In an effort to identify extracts that may stimulate glucose uptake, similar to insulin, a high throughput-screening assay for measuring glucose uptake in skeletal muscle cells was established. During the screening studies to discover novel antidiabetic compounds from microbial resources a Streptomyces strain PM0324667 (MTCC 5543, the Strain accession number at Institute of Microbial Technology, Chandigarh, India), an isolate from arid soil was identified which expressed a secondary metabolite that induced glucose uptake in L6 skeletal muscle cells. By employing bioactivity guided fractionation techniques, a tri-substituted simple aromatic compound with anti-diabetic potential was isolated. It was characterized based on MS and 2D NMR spectral data and identified as NFAT-133 which is a known immunosuppressive agent that inhibits NFAT-dependent transcription in vitro. Our investigations revealed the antidiabetic potential of NFAT-133. The compound induced glucose uptake in differentiated L6 myotubes with an EC50 of 6.3 ± 1.8 μM without activating the peroxisome proliferator-activated receptor-γ. Further, NFAT-133 was also efficacious in vivo in diabetic animals and reduced systemic glucose levels. Thus it is a potential lead compound which can be considered for development as a therapeutic for the treatment of type-2 diabetes. We have reported herewith the isolation of the producer microbe, fermentation, purification, in vitro, and in vivo antidiabetic activity of the compound

DATA MINING USING AGGLOMERATIVE MEAN SHIFT CLUSTERING WITH EUCLIDEAN DISTANCE

Agglomerative clustering is a non parametric clustering technique. In the present paper an approach agglomerative mean shift clustering applied to a text document using a query compression technique Clustering is presented. Here a distance based technique is developed. Two types of distances one for document and one for Query are made use of. Euclidean distance is used for finding query distance between two terms.The results achieved are comparable to other distance methods showing better time and distance accuracy than the existing system. A method entitled ‘Cluster analysis ’ comprises of a grouping of allied techniques which are used to classify objects or cases of a domain into relatively like groups i.e a cluster. Each Object in a cluster tends to be similar in characteristics and different to objects in other clusters. Analysis done on Clusters is called classification analysis and is based on numerical taxonomy.[1

Preparation and Characterization of Rodent Intestinal Microsomes: Comparative Assessment of Two Methods

Small intestine plays an important role in the first-pass metabolism of orally ingested xenobiotics as a result of expression of both Phase I and Phase II metabolic enzymes, together with associated transporters. Intestinal microsomes thus can be used to study susceptibility of compounds to metabolism in vitro. The present study was undertaken to have a comparative assessment between different methods of preparation of rodent intestinal microsomes. Mouse and rat intestinal microsomes were prepared by two methods, in method A intestines were homogenized, while in method B mucosal cells were scrapped followed by homogenization. Further, microsomes were prepared by centrifugation (10000xg) followed by ultra centrifugation (100000×g) of the homogenates. The prepared microsomes were characterized for protein concentration using Bradford's method and CYP450 content using carbon monoxide bubbling method. The protein concentration and CYP450 content in microsomes prepared by method B was significantly higher than method A. In conclusion, superior quality intestinal microsomes can be obtained from rodents by using scrapped intestinal mucosal cells as compared to the intestinal homogenates

Integrated nutrient management of soyabean by using Gliricidia lopping(Marathi Version)

Not Availableसोयाबीन पीकाचे गिरीपुष्पाच्चा पाल्याव्दारे एकात्मिक अन्नद्रव्य व्यवस्थपनNot Availabl

Influence of ethanolic extract of <i>Tephrosia purpurea </i>Linn. on mast cells and erythrocytes membrane integrity

837-840The ethanolic extract of T. purpurea Linn. was studied for its in vitro effect on rat mast cell degranulation and erythrocyte membrane integrity in vitro. The extract in concentration of 25-200 μg/ml showed a dose-dependant inhibition of rat mast cell degranulation induced by compound 48/80 and egg albumin. T. purpurea extract was found to inhibit haemolysis of erythrocytes induced by hypotonic solution but accelerated haemolysis induced by heat at a concentration of 100 μg/ml. The studies reveal that the ethanolic extract of T. purpurea may inhibit degranulation of mast cells by a mechanism other than membrane stabilization

Neuroprotective Potential of Peroxisome Proliferator Activated Receptor-α Agonist in Cognitive Impairment in Parkinson’s Disease: Behavioral, Biochemical, and PBPK Profile

Parkinson’s disease (PD) is a common neurodegenerative disorder affecting 1% of the population by the age of 65 years and 4-5% of the population by the age of 85 years. PD affects functional capabilities of the patient by producing motor symptoms and nonmotor symptoms. Apart from this, it is also associated with a higher risk of cognitive impairment that may lead to memory loss, confusion, and decreased attention span. In this study, we have investigated the effect of fenofibrate, a PPAR-α agonist in cognitive impairment model in PD. Bilateral intranigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (100 µg/1 µL/side) produced significant cognitive dysfunctions. Fenofibrate treatment at 10, 30, and 100 mg/kg for twenty-five days was found to be neuroprotective and improved cognitive impairment in MPTP-induced PD model as evident from behavioral, biochemical (MDA, GSH, TNF-α, and IL-6), immunohistochemistry (TH), and DNA fragmentation (TUNEL positive cells) studies. Further, physiologically based pharmacokinetic (PBPK) modeling study was performed using GastroPlus to characterize the kinetics of fenofibric acid in the brain. A good agreement was found between pharmacokinetic parameters obtained from the actual and simulated plasma concentration-time profiles of fenofibric acid. Results of this study suggest that PPAR-α agonist (fenofibrate) is neuroprotective in PD-induced cognitive impairment

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Not AvailableThe sustainability of organic cotton (Gossypium hirsutum L.) based production system vis-a -vis non-organic system under low input, semi-arid pedo-climatic conditions was evaluated during 2001 through 2005 on farmers’ fields in Yavatmal district, Maharashtra. Mean yield of cotton, mungbean [Vigna radiata (L.) R. Wilczek], soybean (Glycine max L. Merr.) and chickpea (Cicer arietinum L.) were either similar or slightly higher under the organic system than the non-organic system. The organic system also had a higher diversity index (4.3) than the non-organic system (2.9). Organic cultivation practices did not improve fibre quality parameters. Samples from 4 soil pedons and 56 surface soils were analyzed in 2001 and again in 2005. Soils from non-organic pedons had a higher pH and ex-Na, whereas the organic carbon content was higher under organic system. During both the sampling periods, the mean organic carbon and available Zn were significantly higher in the organic system. All the soils were calcareous but the proportion of organic to total carbon was higher in organic system and between sampling periods, this increased from 54.5 to 57.5%. Thus, adoption of organic production practices improved the biophysical sustainability of the low input systems prevailing in semi-arid pedo-climatic conditions of the region.Not Availabl

Synthesis of N-(5-chloro-6-(quinolin-3-yloxy)pyridin-3-yl) benzenesulfonamide derivatives as non-TZD peroxisome proliferator-activated receptor γ (PPARγ) agonist

The thiazolidinediones (TZDs) are a class of oral antidiabetic drugs that improve insulin sensitivity in patients with type 2 diabetes. Although the mechanism by which the TZDs lower insulin resistance is unclear, they are known to target the peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor. Ligands for PPARγ regulate adipocyte production and secretion of fatty acids as well as glucose metabolism, resulting in increased insulin sensitivity in adipose tissue, liver, and skeletal muscle. However, TZDs have several adverse effects, including weight gain and liver toxicity. Herein we report identification of non-TZD PPARγ agonists which exhibit beneficial effects similar to that of TZDs in animal models, but without the associated adverse effects. © 2012 Elsevier Masson SAS. All rights reserved

Synthesis of N-(6-(4-(Piperazin-1-yl)phenoxy)pyridin-3-yl) benzenesulfonamide Derivatives for the Treatment of Metabolic Syndrome

Metabolic syndrome is a widely prevalent multifactorial disorder associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. High plasma levels of insulin and glucose due to insulin resistance are a major component of the metabolic disorder. Thiazolidinediones (TZDs) are potent PPARγ ligand and used as insulin sensitizers in the treatment of type 2 diabetes mellitus. They are potent insulin-sensitizing agents but due to adverse effects like hepatotoxicity, a safer alternative of TZDs is highly demanded. Here we report synthesis of N-(6-(4-(piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide derivatives as an alternate remedy for insulin resistance