The Mukaiyama type aldol reaction for the synthesis of trans-2,6-disubstituted tetrahydropyrans: synthesis of diospongin A and B.

An efficient synthesis protocol for the preparation of trans-2,6-disubstituted tetrahydropyrans by the reaction of 1-phenyl-1-triemthylsiloxyethylene with six membered cyclic hemiacetals in the presence of iodine is developed. This reaction proceeds smoothly under mild conditions employing a catalytic amount of molecular iodine. The feature of this novel conversion includes milder reaction conditions, broader substrate scope, functional group tolerance and good diastereoselectivity. The efficiency and practicality of the current method were successfully displayed in the total synthesis of diospongin A and B in good yields.

In-vitro fertilisation in women aged 40 years and above.

INTRODUCTION: To compare the results of in-vitro fertilisation (IVF) in women aged less than 40 years with those aged 40 years and above with baseline follicle-stimulating hormone (FSH) levels less than 15iu and using their own oocytes. METHODS: A total of 2179 fresh IVF cycles were started in KK Women's and Children's Hospital IVF Centre from 1997 to 2002, of which 247 cycles were done in women 40 to 45 years with FSH levels less than 15iu. The remaining 1932 cycles were performed in another group of women aged less than 40 years old. All couples were treated using our hospital's IVF protocol, and the same clinical and embryological team was involved in all treatments. The medical records of patient outcomes were retrospectively reviewed. The main outcomes measured were clinical pregnancy, miscarriage and delivery rates. RESULTS: The total number of fresh cycles performed in women over 40 years was 247 cycles. Of these, 186 (75.3 percent) cycles reached oocyte collection, and 179 (72.5 percent) cycles reached embryo transfer. The total number of pregnancies was 22 (12.3 percent). The number of cancelled cycles was 61 (24.7 percent). Women less than 40 years of age demonstrated higher rates in cycles reaching oocyte collection (89.2 percent), embryo transfer (84.6 percent), pregnancy rates (32.9 percent) and live-birth rates (24.0 percent). They also reported a lower miscarriage (36.1 percent) and cancellation rate (10.9 percent) as compared to the group of older women. CONCLUSION: As older women seek IVF treatment, it is necessary for them to understand that chances of pregnancy decrease with increasing age. Our results show that as women exceed 40 years old, pregnancy and live-birth rates fall with concurrent rising miscarriage and cycle cancellation rates.

Hypersensitivity Reaction Associated with Abacavir Therapy in an Indian HIV Patient - A Case Report.

The most important and unique adverse effect of abacavir (ABC) is fatal hypersensitivity reaction (HSR). The objective of this report is to describe a case of ABC induced HSR that occurred in an Indian HIV patient during treatment. Although this adverse effect is not uncommon, it is perhaps underreported or has never been reported so far in an Indian case scenario. A 44-year-old known case of HIV-1 was admitted in view of his worsening condition and very low CD4 cell counts 3 cells/µL. He was on anti-retroviral therapy since three years but not regular. On the basis of treatment failure, non-compliance and progressive low CD4 counts, the anti HIV regime was switched over to abacavir 600 mg+ atazanavir/ ritonavir 300mg/100mg Two weeks after ABC therapy he presented with maculopapular rash, headache and signs of hepatic damage (serum AST, ALP and ALT increased to 3-4 fold) suggestive of hypersensitivity reaction. As we know discontinuation of the drug is the ultimate litmus test to confirm diagnosis of drug induced adverse reaction. We did confirm ABC induced HSR by de-challenge wherein, rash disappeared within 2-3 days and LFT came back to normal within 5 days. However, no rechallenge was done. HSR was more in favour of ABC because atazanavir failed to produce any similar reaction after re-challenge.

Screening of mutations affecting protein stability and dynamics of FGFR1-A simulation analysis.

Single amino acid substitutions in Fibroblast Growth Factor Receptor 1 (FGFR1) destabilize protein and have been implicated in several genetic disorders like various forms of cancer, Kallamann syndrome, Pfeiffer syndrome, Jackson Weiss syndrome, etc. In order to gain functional insight into mutation caused by amino acid substitution to protein function and expression, special emphasis was laid on molecular dynamics simulation techniques in combination with in silico tools such as SIFT, PolyPhen 2.0, I-Mutant 3.0 and SNAP. It has been estimated that 68% nsSNPs were predicted to be deleterious by I-Mutant, slightly higher than SIFT (37%), PolyPhen 2.0 (61%) and SNAP (58%). From the observed results, P722S mutation was found to be most deleterious by comparing results of all in silico tools. By molecular dynamics approach, we have shown that P722S mutation leads to increase in flexibility, and deviated more from the native structure which was supported by the decrease in the number of hydrogen bonds. In addition, biophysical analysis revealed a clear insight of stability loss due to P722S mutation in FGFR1 protein. Majority of mutations predicted by these in silico tools were in good concordance with the experimental results.