Interaction of apoptosis and pluripotency related transcripts for developmental potential of ovine embryos produced in vitro at different oxygen concentrations.

The present study in sheep model was to find out the interaction of apoptotic transcripts, that is, Bcl2, Bax, Casp3, PCNA and p53 and pluripotency related transcripts, that is, Sox2, Nanog and Oct4 in ovine embryos produced in vitro at different O2 concentrations (20% and 5% O2) to compare their developmental potential. Oxygen concentrations did not influence the maturation and cleavage rate but the percentage of morula and blastocysts was significantly more at 5% as compared to 20% O2. A significant upregulated expression of Bcl2 and PCNA genes and significantly downregulated expression of Casp3 and p53 were observed in the blastocysts at 5% than those at 20% O2. The expression of Bax was not influenced by the O2 concentration. Among the pluripotency related transcripts, the expression of Oct4 was significantly upregulated and the expression of Sox2 and Nanog was significantly downregulated in embryos at 5% than at 20% O2. The study concluded that the embryos produced in vitro at low O2 (5%) concentration regulate the expression of developmental genes related to apoptosis and pluripotency to improve the developmental potential of embryos as compared to high O2 (20%) concentration.

Design, synthesis, optimization and antiviral activity of a class of hybrid dengue virus E protein inhibitors.

The ß-OG pocket is a cavity in the flavivirus envelope (E) protein that was identified by Proc. Natl. Acad. Sci. U.S.A.2003, 100, 6986 as a promising site for the design of antiviral agents that interfere with virus entry into the host cell. The availability of the X-ray crystal structure of the dengue virus (DENV) E protein provided an opportunity for in silico drug design efforts to identify candidate inhibitors. The present study was set up to explore whether it is possible to generate a novel class of molecules that are hybrids between two hit compounds that have been reported previously by ACS. Chem. Biol.2008, 3, 765 following an in silico screening effort against the DENV E protein. First, a library of twenty hybrid molecules were designed and synthesized to explore the feasibility of this strategy. Antiviral evaluation in a virus-cell-based assay for DENV proved this approach to be successful, after which another twenty-four molecules were produced to further explore and optimize the potency of this novel class of hybrid inhibitors. In the end, a molecule was obtained with an EC50 against dengue virus serotype 2 in the low micromolar range (23, 1.32±0.41µM).

Closed wedge osteotomy for middle phalanx physeal injuries associated with angulation deformities in children.

BACKGROUND: Middle phalanx physeal fractures in children are rare, and proper treatment gives good results. Despite treatment, these fractures may lead to physeal arrest and growth disturbances leading to severe angulation deformities. Closed wedge osteotomy with internal fixation efficiently corrects the angulation deformities in children. METHODS: We did a retrospective study analyzing 11 children with middle phalanx physeal injuries and severe angulation. Closed wedge osteotomy and internal fixation with plate and screw were done. We interpreted the pre- and postoperative correction of angles, middle phalanx length discrepancy, technical aspects, range of movement, grip strength, pain, and functional outcomes. RESULTS: The mean age of the patients was 10.5 years. The mean follow-up was 28 months (range 24-30 months). Ten of the 11 patients achieved good radiological union, range of motion, and good outcome. None of the patients had growth plate deformity in the follow-up. All patients had a significant correction of angulation/deformity, length, and improvement of grip strength in the postoperative period (p < 0.05). None had physeal disturbances/abnormalities in the follow-up. CONCLUSIONS: Though middle phalanx physeal fractures are rare and innocuous, adequate treatment is essential to prevent angulation and growth disturbances. Close wedge corrective osteotomy and internal fixation with plates and screws provide stable and rigid fixation. Greater attention is needed to follow-up them until skeletal maturity. LEVEL OF EVIDENCE: IV.