Search results for: Devender Mandala
5 Facile Synthetic Process for Lamivudine and Emtricitabine
Authors: Devender Mandala, Paul Watts
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Cis-Nucleosides mainly lamivudine (3TC) and emtricitabine (FTC) are an important tool in the treatment of Human immune deficiency virus (HIV), Hepatitis B virus (HBV) and Human T-Lymotropoic virus (HTLV). Lamivudine and emtricitabine are potent nucleoside analog reverse transcriptase inhibitors (nRTI). These two drugs are synthesized by a four-stage process from the starting materials: menthyl glyoxylate hydrate and 1,4-dithane-2,5-diol to produce the 5-hydroxy oxathiolane which upon acetylation with acetic anhydride to yield 5-acetoxy oxathiolane. Then glycosylation of this acetyl product with silyl protected nucleoside to produce the intermediate. The reduction of this intermediates can provide the final targets. Although there are several different methods reported for the synthesis of lamivudine and emtricitabine as a single enantiomer, we required an efficient route, which was suitable for large-scale synthesis to support the development of these compounds. In this process, we successfully prepared the intermediates of lamivudine and emtricitabine without using any solvents and catalyst, thus promoting the green synthesis. All the synthesized compound were confirmed by TLC, GC, Mass, NMR and 13C NMR spectroscopy.Keywords: emtricitabine, green synthesis, lamivudine, nucleoside
Procedia PDF Downloads 2304 Parameter Estimation for the Oral Minimal Model and Parameter Distinctions Between Obese and Non-obese Type 2 Diabetes
Authors: Manoja Rajalakshmi Aravindakshana, Devleena Ghosha, Chittaranjan Mandala, K. V. Venkateshb, Jit Sarkarc, Partha Chakrabartic, Sujay K. Maity
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Oral Glucose Tolerance Test (OGTT) is the primary test used to diagnose type 2 diabetes mellitus (T2DM) in a clinical setting. Analysis of OGTT data using the Oral Minimal Model (OMM) along with the rate of appearance of ingested glucose (Ra) is performed to study differences in model parameters for control and T2DM groups. The differentiation of parameters of the model gives insight into the behaviour and physiology of T2DM. The model is also studied to find parameter differences among obese and non-obese T2DM subjects and the sensitive parameters were co-related to the known physiological findings. Sensitivity analysis is performed to understand changes in parameter values with model output and to support the findings, appropriate statistical tests are done. This seems to be the first preliminary application of the OMM with obesity as a distinguishing factor in understanding T2DM from estimated parameters of insulin-glucose model and relating the statistical differences in parameters to diabetes pathophysiology.Keywords: oral minimal model, OGTT, obese and non-obese T2DM, mathematical modeling, parameter estimation
Procedia PDF Downloads 933 Addressing Head Transplantation and Its Legal, Social and Neuroethical Implications
Authors: Joseph P. Mandala
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This paper examines the legal and medical ethics concerns, which proponents of human head transplantation continue to defy since the procedure was first attempted on dogs in 1908. Despite recent bioethical objections, proponents have proceeded with radical experimentation, claiming transplantation would treat incurable diseases and improve patients’ quality of life. In 2018, Italian neurosurgeon, Sergio Canavero, and Dr. Xiaoping Ren claimed to have performed a head transplant on a corpse in China. Content analysis of literature shows that the procedure failed to satisfy scientific, legal, and bioethical elements because, unlike humans, corpses cannot coordinate function. Putting a severed head onto a body that has been dead for several days is not equivalent to a transplant which would require successfully reconnecting and restoring function to a spinal cord. While reconnection without restoration of bodily function is not transplantation, the publicized procedure on animals and corpses could leapfrog to humans, sparking excitement in society likely to affect organ donors and recipients from territorial jurisdictions with varying legal and ethical regimes. As neurodiscoveries generate further excitement, the need to preemptively address the legal and medical ethics impact of head transplantation in our society cannot be overstated. A preemptive development of methods to address the impact of head transplantation will help harmonizing national and international laws on organ donations, advance directives, and laws affecting end of life. Procedia PDF Downloads 1462 Comparison of Water Curing and Carbonation Curing on Mortar Mix Incorporating Cement Kiln Dust
Authors: Devender Sharma, Shweta Goyal
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Sustainable development is a key to protect the environment for a secure future. Accelerated carbonation curing is a comparatively new technique for curing of concrete which involves sequestration of carbon dioxide gas into the precast concrete, resulting in improvement of the properties of concrete. This paper presents the results of a study to evaluate the effect of carbonation curing on cement mortars incorporating cement kiln dust (CKD) as partial replacement of cement. The mortar specimens were prepared by replacing cement with CKD in varying percentages of 0-50% by the weight of cement. The specimens were subjected to 12 hour carbonation curing, followed by sealed packing till testing age. The results were compared with the normal curing procedure, in which the specimens were water cured till the testing age. Compressive strength and microstructure of the mix were studied. It was noted that on increasing the percentage of CKD up to 10% by the weight of the cement, no considerable change was observed in the compressive strength. But as the percentage of CKD was further increased, there was a decrease in compressive strength, with strength decreasing up to 40% when 50% of the cement was replaced with CKD. The decrease in strength is due to the lesser lime content in CKD as compared to cement. High ettringite formation was observed in mixes with high percentages of CKD, thus indicating a decrease in the compressive strength. With carbonation curing, an early age strength gain was observed in mortars, even with higher percentages of CKD. The early strength of the carbonation cured mixes was found to be greater than water cured mixes irrespective of the percentage of CKD. 7 days and 28 days compressive strength of the mix was comparable for both the carbonation cured and water cured specimen. The increase in compressive strength can be attributed to the conversion of unstable Ca(OH)2 into stable CaCO3, which causes densification of the mix. CaCO3 precipitation and greater CSH gel formation was clearly observed in the SEM images of carbonation cured specimen, indicating higher compressive strength. Thus, carbonation curing can be used as an efficient method to enhance the properties of concrete.Keywords: carbonation, cement kiln dust, compressive strength, microstructure
Procedia PDF Downloads 2301 Studies of Single Nucleotide Polymorphism of Proteosomal Gene Complex and Their Association with HBV Infection Risk in India
Authors: Jasbir Singh, Devender Kumar, Davender Redhu, Surender Kumar, Vandana Bhardwaj
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Single Nucleotide polymorphism (SNP) of proteosomal gene complex is involved in the pathogenesis of hepatitis B Virus (HBV) infection. Some of such proteosomal gene complex are large multifunctional proteins (LMP) and antigen associated transporters that help in antigen presentation. Both are involved in intracellular processing and presentation of viral antigens in association with Major Histocompatability Complex (MHC) Class I molecules. A total of hundred each of hepatitis B virus infected and control samples from northern India were studied. Genomic DNA was extracted from all studied samples and PCR-RFLP method was used for genotyping at different positions of LMP genes. Genotypes at a given position were inferred from the pattern of bands and genotype frequencies and haplotype frequencies were also calculated. Homozygous SNP {A>C} was observed at codon 145 of LMP7 gene and having a protective role against HBV as there was statistically significant high distribution of this SNP among controls than cases. Heterozygous SNP {A>C} was observed at codon 145 of LMP7 gene and made individuals more susceptible to HBV infection as there was statistically significant high distribution of this SNP among cases than control. SNP {T>C} was observed at codon 60 of LMP2 gene but statistically significant differences were not observed among controls and cases. For codon 145 of LMP7 and codon 60 of LMP2 genes, four haplotypes were constructed. Haplotype I (LMP2 ‘C’ and LMP7 ‘A’) made individuals carrying it more susceptible to HBV infection as there was statistically significant high distribution of this haplotype among cases than control. Haplotype II (LMP2 ‘C’ and LMP7 ‘C’) made individuals carrying it more immune to HBV infection as there was statistically significant high distribution of this haplotype among control than cases. Thus it can be concluded that homozygous SNP {A>C} at codon 145 of LMP7 and Haplotype II (LMP2 ‘C’ and LMP7 ‘C’) has a protective role against HBV infection whereas heterozygous SNP {A>C} at codon 145 of LMP7 and Haplotype I (LMP2 ‘C’ and LMP7 ‘A’) made individuals more susceptible to HBV infection.Keywords: Hepatitis B Virus, single nucleotide polymorphism, low molecular weight proteins, transporters associated with antigen presentation
Procedia PDF Downloads 308