SYNTHESIS AND ANTI-EPILEPTIC ACTIVITY OF SOME NOVEL 3-(4-(4-(SUBSTITUTED BENZYLIDENEAMINO)-5-MERCAPTO-4-1,2,4-TRIAZOLE-3-YL)PHENYLIMINO)-1-((DIMETHYL AMINO) METHYL)-5-FLUOROINDOLIN-2-ONE DERIVATIVES

Objective: Synthesis and anti-epileptic evaluation of some novel Schiff and Mannich bases of isatin derivatives. Methods: A series of novel 3-(4-(4-(substituted benzylideneamino)-5-mercapto-4-1,2,4-triazole-3-yl)phenylimino)-1-((dimethyl amino) methyl)-5-fluoroindolin-2-one Schiff and Mannich base derivatives were synthesized by using various aromatic aldehydes with isatin derivatives. The chemical structures of all synthesized compounds were confirmed by IR, 1H-NMR, Mass spectra and elemental analysis. All the synthesized compounds were screened for its anti-epileptic activity by MES and scPTZ methods using Phenytoin and Ethosuximide as standards. Results: The results of anti-epileptic activity showed that some of the synthesized compounds were exhibited significant results. Conclusion: This investigation identified the potent anti-epileptic agents and these molecules will be subjected to further studies in our laboratory

SYNTHESIS, ANALGESIC, ANTI-INFLAMMATORY AND IN VITRO ANTIMICROBIAL STUDIES OF SOME NOVEL SCHIFF AND MANNICH BASE OF 5-SUBSTITUTED ISATIN DERIVATIVES

Objective: Synthesis and analgesic, anti-inflammatory and antimicrobial evaluation of some novel Schiff and Mannich bases of isatin derivatives. Methods: A series of novel 3-(4-(2-(substituted benzylideneamino)thiazol-4-yl)phenylimino)-1-((dimethylamino)methyl)-5-fluoroindolin-2-one Schiff and Mannich base derivatives were synthesized by using various aromatic aldehydes with isatin derivatives. The chemical structures of all synthesized compounds were confirmed by IR, 1H-NMR, Mass spectra and elemental analysis. All the synthesized compounds were screened for its analgesic, anti-inflammatory and antimicrobial activity. Results: The results of analgesic, anti-inflammatory and antimicrobial activity showed that some of the synthesized compounds were exhibited promising results. Conclusion: This investigation identified the potent analgesic, anti-inflammatory and anti-microbial agents and these molecules will be subjected to further studies in our laboratory

Group III PLA2 from the scorpion, Mesobuthus tamulus: cloning and recombinant expression in E. coli

Phospholipases A2 (PLA2) are enzymes that specifically hydrolyze the sn-2 fatty acid acyl bond of phospholipids, producing a free fatty acid and a lyso-phospholipid. We report the cloning and expression of a secretory phospholipase A2 (sPLA2) from Mesobuthus tamulus, Indian red scorpion. The nucleotide sequence codes for a 167 residue enzyme. The open reading frame codes for a 31 amino acid signal peptide followed by a mature portion of the protein. The primary structure shows the calcium binding motif, catalytic residues, 8 highly-conserved cysteines and C-terminal extension which classify it as a group III PLA2. The entire transcript was expressed in Escherichia coli and was purified by metal affinity chromatography under denaturing conditions. The protein was refolded by serial dilutions in the refolding buffer to its active form. Hemolytic assays indicate that the protein adopts a functional conformation. The functional requisites such as optimum pH of 8 and calcium dependency are shown. This report provides a simple but robust methodology for recombinant expression of toxic proteins

Young onset diabetes in Asian Indians is associated with lower measured and genetically determined beta-cell function:an INSPIRED study

Aims/hypothesis: South Asians in general, and Asian Indians in particular, have higher risk of type 2 diabetes compared with white Europeans, and a younger age of onset. The reasons for the younger age of onset in relation to obesity, beta cell function and insulin sensitivity are under-explored. Methods: Two cohorts of Asian Indians, the ICMR-INDIAB cohort (Indian Council of Medical Research-India Diabetes Study) and the DMDSC cohort (Dr Mohan’s Diabetes Specialties Centre), and one of white Europeans, the ESDC (East Scotland Diabetes Cohort), were used. Using a cross-sectional design, we examined the comparative prevalence of healthy, overweight and obese participants with young-onset diabetes, classified according to their BMI. We explored the role of clinically measured beta cell function in diabetes onset in Asian Indians. Finally, the comparative distribution of a partitioned polygenic score (pPS) for risk of diabetes due to poor beta cell function was examined. Replication of the genetic findings was sought using data from the UK Biobank. Results: The prevalence of young-onset diabetes with normal BMI was 9.3% amongst white Europeans and 24–39% amongst Asian Indians. In Asian Indians with young-onset diabetes, after adjustment for family history of type 2 diabetes, sex, insulin sensitivity and HDL-cholesterol, stimulated C-peptide was 492 pmol/ml (IQR 353–616, p<0.0001) lower in lean compared with obese individuals. Asian Indians in our study, and South Asians from the UK Biobank, had a higher number of risk alleles than white Europeans. After weighting the pPS for beta cell function, Asian Indians have lower genetically determined beta cell function than white Europeans (p<0.0001). The pPS was associated with age of diagnosis in Asian Indians but not in white Europeans. The pPS explained 2% of the variation in clinically measured beta cell function, and 1.2%, 0.97%, and 0.36% of variance in age of diabetes amongst Asian Indians with normal BMI, or classified as overweight and obese BMI, respectively. Conclusions/interpretation: The prevalence of lean BMI in young-onset diabetes is over two times higher in Asian Indians compared with white Europeans. This phenotype of lean, young-onset diabetes appears driven in part by lower beta cell function. We demonstrate that Asian Indians with diabetes also have lower genetically determined beta cell function

Residues involved in the mechanism of the bifunctional methylenetetrahydrofolate dehydrogenasecyclohydrolase

The human bifunctional dehydrogenase/cyclohydrolase domain catalyzes the interconversion of 5,10-methyleneH4folate and 10-formylH 4folate. Although previous structure and mutagenesis studies indicated the importance of lysine56 in cyclohydrolase catalysis, the role of several surrounding residues had not been explored. In addition to further defining the role of lysine56, the work presented in this thesis explores the functions of glutamine100 and aspartate125 through the use of site-directed mutagenesis and chemical modification. The results indicate that the function of glutamine100 is to polarize lysine56 for cyclohydrolase catalysis, and that of aspartate125 is for the binding of the H4folate substrates. In highlighting the importance of these residues, a new catalytic mechanisms is proposed for both activities, as well as a novel explanation for the differences in channeling between the forward and reverse directions

Experimental design and performance analysis of alumina coatings deposited by a detonation spray process

The increasing demands for high-quality coatings has made it inevitable that the surface coating industry would put more effort into precisely controlling the coating process. Statistical design of experiments is an effective method for finding the optimum spray parameters to enhance thermal spray coating properties. In the present investigation, an attempt is made to produce high-quality alumina (Al2O3) coatings by optimizing the detonation spray process parameters following a (L16-24) factorial design approach. The process parameters that were varied include the fuel ratio, carrier gas flow rate, frequency of detonations and spray distance. The coating characteristics were quantified with respect to roughness, hardness and porosity. The performance of the coatings was quantitively evaluated using erosion, abrasion and sliding wear testing. Through statistical analysis of the experimental results, performed by the ANOVA method, the significance of each process parameter together with an optimal variable combination was obtained for the desired coating attributes. Confirmation experiments were conducted to verify the optimal spray parameter combination, which clearly showed the possibility of producing high-quality Al2O3 coatings

Persistent mullerian duct syndrome: A single-center experience

Context: Persistent Mullerian duct syndrome (PMDS) is a rare disorder. It is a type of male pseudohermaphroditism, usually presenting as “Hernia Uteri Inguinalis”. Aims: This study aims to present our experience of PMDS, over a 7-year period. Settings and Design: Our center is a tertiary care facility, situated in Tamil Nadu, a southern state of India. Subjects and Methods: This is a retrospective study. The study period was from 2007 to 2015. Seven cases presented during that period. The difficulties in diagnosis, treatment options discussed, along with a review of literature are presented. Results: Seven cases of PMDS presented over 8 years. Only four were diagnosed preoperatively. Mullerian remnants were excised in five cases. Conclusions: PMDS is rare. Orchiopexy should be the goal of treatment

Influence of spraying variables on structure and properties of plasma sprayed alumina coatings

An experimental statistical design study on the plasma spraying of alumina powder has been carried out. Coating experiments were conducted, using a Taguchi full factorial L<SUB>16</SUB> design parametric approach, to study the effect of four key plasma processing variables on the coating quality, namely, primary gas flow rate, arc current, powder feed rate, and spray distance. Optical microscopy, scanning electron microscopy, XRD, image analysis, and hardness testing were used for characterisation. The resulting as sprayed coating characteristics were quantified with respect to roughness, microhardness, porosity, and microstructure. Through statistical calculation (analysis of variance), the parameters that have significant influence on the structure and properties of the coatings were identified and their relative importance and contribution ratios to overall variance were studied. The Taguchi evaluation employed in the present investigation showed that an improvement in the coating properties could be achieved using an optimum combination of variables