SYNTHESIS, SPECTRAL, AND PHARMACOLOGICAL EVALUATION OF 3 AND 5 SUBSTITUTED 2,4-THIAZOLIDINEDIONE DERIVATIVES

Background: 2,4-Thiazolidinedione derivatives was launched as antidiabetics in 90's. Later the derivatives of 2,4-thiazolidinedione were banned due to hepatotoxicity. To the date, much research has been directed toward the synthesis and novel uses of 2,4-thiazolidinedione compounds.Aim: The aim of the present study is to synthesize a set of 3,5-disudstituted-2,4-thiazolidinediones as antimicrobial. These compounds were evaluated for their antimicrobial activity.Method: First, the 2,4-thiazolidinedione was substituted at the position of 3 using sodium hydroxide and ethanol and then substituted at the position of 5 in the presence of piperdine by the Knoevenagel condensation method. The structures of the compounds were established on the basis of infrared and nuclear magnetic resonance spectral studies.Result: 3,5-disubstituted-5-benzylidine-2,4-thiazolidinediones derivative was synthesized using benzyl halides and aromatic aldehydes. The results obtained showed that TZ-1 exhibited good activity against Bacillus subtilis while no activity against Escherichia coli.Conclusion: Attachment of more heterocyclic rings containing Nitrogen on the 3rd position of 2,4-thiazolidinedione can enhance the antimicrobial activity. Addition of more lipophilic agents may increase the bioavailability and efficacy of the drug. Long alkyl chains on the benzylidene ring can also increase the lipophilic character, and further attachment of these kind of agents on benzylidene chain may produce safe and effective compounds in future

PREPARATION AND EVALUATION OF MODIFIED TAMARIND SEED GUM AS A NOVEL SUPERDISINTEGRANT

The aim of present study was to preparation and evaluation of modified Tamarind seed as natural superdisintegrant. The extracted gum from the Tamarind seed was modified chemically by carboxymethylation of extracted gum was done to improve the hydrophilic nature of the gum. Futher, carboxymethylated gum was complexed by using calcium chloride to enhances  the wetting capacity of the gum. The modification in functional group of extracted gum, carboxymethyled gum, Calcium complexed gum was studied by FT-IR spectrophotometer. The DSC studies shows that the changes in melting point of the carboxymethyled gum and the calcium complexed gum as compared to the extracted gum without undergoing chemical modification. The modified gum was then subjected to different studies like color, pH of gum solution, swelling indexetc. The dummy tablet prepared with calcium complexed modified Tamarind seed gum to check its disintegration effect of the tablet. The various pre-compression parameters of the tablet blend was determined like bulk density, tapped density, Carr's index, angle of repose and Hausner's ratio. The disintegration time of these dummy tablet carry the calcium complexed tamarind seed gum was compared to formulate tablet with marketed superdisintegrant i.e. sodium starch glycolate . The disintegration time of calcium complexed Tamarind seed gum was observed to be 1 min. approx. 32.5 sec. -35.2 sec. showing good disintegrating property. It can be concluded that Fast disintegrating tablet using modified Tamarind seed gum as natural superdisintegrant improves the disintegration time of the tablet. Keywords: FDT tablet, Tamarind seed gum, Sodium starch glycolate, Swelling time.&nbsp

A review on polymers in natural or modified form used in sustained release tablet

Tablet is a solid dosage form which is used to deliver the drug to the body to make pharmacological action. The oral dosage form should disperse into small particles to deliver active ingredients in the body, the disperse time of the dosage form depends on the ingredients which are used in the tablet. To make the tablet disintegrate slow usually sustained release agents are used. The sustained release tablets helps in maintaining the drug concentration in the body for the higher time. In this review article various polymers of natural origin and their modified forms are studied, which can be used in the sustained release tablet. In this review article the polymers studied were, Psyllium husk, HPMC K100M, Cellulose polymers, Cellulose ether polymers, Xanthan gum, Guar gum, Eudragit RLPO, Eudragit RSPO, Eudragit RL 100, Eudragit RS 100, Kollidone SR and Carnauba wax. Now a day the sustained release tablets are used more than the conventional tablets because of the patient incompliance. The main part of the sustained release tablets are the polymers. In the study it was found that the modified forms of natural polymers works better than in their natural form. In the study it was found that the hydrophilic polymers also work better like Xanthan gum and Guar gum, they are effecting and non-toxic in nature. The cellulose derivatives were studied and it was found that Substituted cellulose-methylcellulose, hydroxypropylcellulose and hydroxypropylmethylcellulose works better in the combination form. Keywords: Sustained release, Xanthan gum, Guar gum, Eudragit, Kollidone, HPM

Formulation and evaluation of sustained release matrix tablet of metoprolol succinate by using xanthan gum and carbopol

Metoprolol succinate is a β1 selective antagonist used as an Anti-hypertensive, Anti arrhythmic, Anti Angina. The aim of present investigation was to develop matrix tablets of Metoprolol succinate using different polymers.Metoprolol succinate matrix tablet was prepared by use of xanthan gum and carbopol-934 as a polymer initially by direct compression methods. Physicochemical compatibility of the drug with polymer was confirmed by IR spectroscopy and DSC. Metoprolol succinate matrix tablets were prepared by direct compression and wet granulation method using different polymers. All the formulations were evaluated for weight variation, thickness, hardness, friability and dissolution. The result of matrix tablets formulation (A-4) showed drug release 94.12% in 720 min. Therefore it was concluded that formulation (A-4) containing carbopol-934 and xanthan gum in the ratio of 80:20 showing promising result for sustained release of Metoprolol succinate, further for improvement of release profile in situ interpolymeric complexes of both carbopol and xanthan gum were tried. All the formulations were evaluated for weight variation, thickness, hardness, friability and dissolution. The results of IPC formulation B-11 showed drug release 96.29% in 720 min. It was concluded that tablets were prepared by using in-situ inter polymer complex formed with 70:30 ratio of Carbopol and Xanthan gum solution as binder. Formulation B-11 showed promising result because of its resistance in pH 1.2 HCL buffer for more than 2 hrs showed the maximum sustained release as compared to simple matrix tablet because of more acid resistance of the complex. Thus, sustained release matrix tablets of Metoprolol succinate using biocompatible polymers were successfully formulated, evaluated and found to be suitable candidates in extending the release of the drug from the matrix tablets. Keywords: Metoprolol succinate, Sustained release Matrix tablets, Direct compression, Wet granulation method.&nbsp

Isolation of Two Strong Poly (U) Binding Proteins from Moderate Halophile Halomonas eurihalina and Their Identification as Cold Shock Proteins

Cold shock proteins (Csp) are known to be expressed in response to sudden decrease in temperature. They are thought to be involved in a number of cellular processes viz., RNA chaperone activity, translation, transcription, nucleoid condensation. During our studies on ribosomal protein S1 in moderate halophile Halomonas eurihalina, we observed the presence of two strong poly (U) binding proteins in abundance in cell extracts from cells grown under normal growth conditions. The proteins can be isolated in a single step using Poly (U) cellulose chromatography. The proteins were identified as major cold shock proteins belonging to Csp A family by MALDI-TOF and bioinformatic analysis. Csp 12 kDa was found in both exponential and stationary phases whereas Csp 8 kDa is found only in exponential phase

Binary IS Typing for Staphylococcus aureus

Background: We present an easily applicable test for rapid binary typing of Staphylococcus aureus: binary interspace (IS) typing. This test is a further development of a previously described molecular typing technique that is based on length polymorphisms of the 16S-23S rDNA interspace region of S. aureus. Methodology/Principal Findings: A novel approach of IS-typing was performed in which binary profiles are created. 424 human and animal derived MRSA and MSSA isolates were tested and a subset of these isolates was compared with multi locus sequence typing (MLST) and Amplified Fragment Length Polymorphism (AFLP). Binary IS typing had a high discriminatory potential and a good correlation with MLST and AFLP. Conclusions/Significance: Binary IS typing is easy to perform and binary profiles can be generated in a standardized fashion. These two features, combined with the high correlation with MLST clonal complexes, make the techniqu

Escherichia coli genome-wide promoter analysis: Identification of additional AtoC binding target elements

<p>Abstract</p> <p>Background</p> <p>Studies on bacterial signal transduction systems have revealed complex networks of functional interactions, where the response regulators play a pivotal role. The AtoSC system of <it>E. coli </it>activates the expression of <it>atoDAEB </it>operon genes, and the subsequent catabolism of short-chain fatty acids, upon acetoacetate induction. Transcriptome and phenotypic analyses suggested that <it>atoSC </it>is also involved in several other cellular activities, although we have recently reported a palindromic repeat within the <it>atoDAEB </it>promoter as the single, <it>cis</it>-regulatory binding site of the AtoC response regulator. In this work, we used a computational approach to explore the presence of yet unidentified AtoC binding sites within other parts of the <it>E. coli </it>genome.</p> <p>Results</p> <p>Through the implementation of a computational <it>de novo </it>motif detection workflow, a set of candidate motifs was generated, representing putative AtoC binding targets within the <it>E. coli </it>genome. In order to assess the biological relevance of the motifs and to select for experimental validation of those sequences related robustly with distinct cellular functions, we implemented a novel approach that applies Gene Ontology Term Analysis to the motif hits and selected those that were qualified through this procedure. The computational results were validated using Chromatin Immunoprecipitation assays to assess the <it>in vivo </it>binding of AtoC to the predicted sites. This process verified twenty-two additional AtoC binding sites, located not only within intergenic regions, but also within gene-encoding sequences.</p> <p>Conclusions</p> <p>This study, by tracing a number of putative AtoC binding sites, has indicated an AtoC-related cross-regulatory function. This highlights the significance of computational genome-wide approaches in elucidating complex patterns of bacterial cell regulation.</p

Gabapentin for the hemodynamic response to intubation: systematic review and meta-analysis

Purpose Endotracheal intubation is the gold standard for securing the airway before surgery. Nevertheless, this procedure can produce an activation of the sympathetic nervous system and result in a hemodynamic response which, in high-risk patients, may lead to cardiovascular instability and myocardial ischemia. The aim of this review was to evaluate whether gabapentin can attenuate this response and whether such an attenuation could translate into reduced myocardial ischemia and mortality. Source We searched MEDLINE®, EMBASE™, CINAHL, AMED, and unpublished clinical trial databases for randomized-controlled trials that compared gabapentin with control, fentanyl, clonidine, or beta blockers for attenuating the hemodynamic response to intubation. Primary outcomes were mortality, myocardial infarction, and myocardial ischemia. Secondary outcomes were hemodynamic changes following intubation. Principal findings We included 29 randomized trials with only two studies at low risk of bias. No data were provided for the primary outcomes and no studies included high-risk patients. The use of gabapentin resulted in attenuation in the rise in mean arterial blood pressure [mean difference (MD), −12 mmHg; 95% confidence interval (CI), −17 to −8] and heart rate (MD, −8 beats·min−1; 95% CI, −11 to −5) one minute after intubation. Gabapentin also reduced the risk of hypertension or tachycardia requiring treatment (risk ratio, 0.15; 95% CI, 0.05 to 0.48). Data were limited on adverse hemodynamic events such as bradycardia and hypotension. Conclusion It remains unknown whether gabapentin improves clinically relevant outcomes such as death and myocardial infarction since studies failed to report on these. Nevertheless, gabapentin attenuated increases in heart rate and blood pressure following intubation when compared with the control group. Even so, the studies included in this review were at potential risk of bias. Moreover, they did not include high-risk patients or report adverse hemodynamic outcomes. Future studies are required to address these limitations

Brugia malayi Excreted/Secreted Proteins at the Host/Parasite Interface: Stage- and Gender-Specific Proteomic Profiling

Relatively little is known about the filarial proteins that interact with the human host. Although the filarial genome has recently been completed, protein profiles have been limited to only a few recombinants or purified proteins of interest. Here, we describe a large-scale proteomic analysis using microcapillary reverse-phase liquid chromatography-tandem-mass spectrometry to identify the excretory-secretory (ES) products of the L3, L3 to L4 molting ES, adult male, adult female, and microfilarial stages of the filarial parasite Brugia malayi. The analysis of the ES products from adult male, adult female, microfilariae (Mf), L3, and molting L3 larvae identified 852 proteins. Annotation suggests that the functional and component distribution was very similar across each of the stages studied; however, the Mf contributed a higher proportion to the total number of identified proteins than the other stages. Of the 852 proteins identified in the ES, only 229 had previous confirmatory expressed sequence tags (ESTs) in the available databases. Moreover, this analysis was able to confirm the presence of 274 “hypothetical” proteins inferred from gene prediction algorithms applied to the B. malayi (Bm) genome. Not surprisingly, the majority (160/274) of these “hypothetical” proteins were predicted to be secreted by Signal IP and/or SecretomeP 2.0 analysis. Of major interest is the abundance of previously characterized immunomodulatory proteins such as ES-62 (leucyl aminopeptidase), MIF-1, SERPIN, glutathione peroxidase, and galectin in the ES of microfilariae (and Mf-containing adult females) compared to the adult males. In addition, searching the ES protein spectra against the Wolbachia database resulted in the identification of 90 Wolbachia-specific proteins, most of which were metabolic enzymes that have not been shown to be immunogenic. This proteomic analysis extends our knowledge of the ES and provides insight into the host–parasite interaction