Homology modeling and docking studies of human Bcl-2L10 protein.

Cancer, an unrestrained proliferation of cells, is one of the lead cause of death. Nearly 12.5 million people are diagnosed with cancer worldwide, 7.5 million people die of which 2.5 million cases are from India. Major cause for cancer is restriction of programmed cell death (apoptosis). Multiple signaling pathways regulate apoptosis. Bcl-2 (B - Cell Lymphomas-2) family proteins play a vital role as central regulators of apoptosis. Bcl-2L10, a novel anti-apoptotic protein, blocks apoptosis by mitochondrial dependent mechanism. The present study evaluates the 3D structure of Bcl-2L10 protein using homology modeling and aims to understand plausible functional and binding interactions between Bcl-2L10 with BH3 domain of BAX using protein - protein docking. The docking studies show binding of BH3 domain at Lys 110, Trp-111, Pro-115, Glu-119 and Asp-127 in the groove of BH 1, 2 and 3 domains of Bcl-2L10. Heterodimerization of anti-apoptotic Bcl-2 and BH3 domain of pro-apoptotic Bcl-2 proteins instigates apoptosis. Profound understanding of Bcl-2 pathway may prove useful in identification of future therapeutic targets for cancer.

Induction of meiotic chromosomal aberrations by sulphaguanidine.

Cytological investigations on the effects of sulphaguanidine on meiotic cells have been carried out. Concentrations of 4.165, 6.25 and 8.33 mg of the drug were orally administered to Swiss albino male mice as single and cumulative doses. In the latter the drug was fed consecutively for 5 days at 24 h intervals. Meiotic chromosomal preparations were made after 24 h and at weekly intervals up to the fifth week following drug administration. Structural aberrations like gaps, breaks, fragments and multivalent associations (translocations) were scored for assessing clastogenic activity. Mitoclasic effects were analysed by scoring the polyploids. A high rate of both autosomal and sex chromosomal univalents were recorded in the series treated. A non-clastogenic and a very weak mitoclasic property of the drug is suggestive and is comparable to observations on the effects of sulphadiazine previously reported.

Cytogenetical action of Paracetamol on meiotic cells of male mice.

Cytogenetical effects of the analgesic and antipyretic agent Paracetamol have been studied on meiotic cells of C3 H/He strain male mice for a period of five weeks after administering it at 0.625, 1.25 and 2.5 mg doses. Two series of experiments were carried out. In the single dose series the animals received the drug only once, while in the cumulative series, simulating continuous therapy, the drug was given consecutively to the same animals for three days at 24 h intervals. Adequate controls were employed. Quantitative studies have been made and statistical tests applied to the data. Univalents of auto- and sex-chromosomal types were higher during the first week in both series. There was a preponderance of autosomal univalents in all doses over the sex chromosomal ones up to the fourth week. Polyploid cells and translocations occurred with a low incidence. The implications of these observations are discussed.

Evaluation of triflupromazine as a sedative in camels (Camelus dromedarius).

Effects of administration of triflupromazine were evaluated in 11 adult domesticated camels (Camelus dromedarius) weighing 403 +/- 29.5 kg (Mean +/- SE). Six camels were used to evaluate sedative properties of the drug and its effects on haematological and blood biochemical parameters. In the remaining 5 camels, effects on haemodynamics, acid base status and blood gases were studied. In all the animals triflupromazine was administered intramuscularly in the gluteal region at the rate of 2 mg/kg. Camels voluntarily sat down 48.9 +/- 5.4 min after administration of the drug but stood up again if disturbed. Drowsiness, drooping of lower lip and salivation were evident. The animals stood on their own and started walking with ataxia after 159 +/- 7 min and recovered completely from the effect of drug within 259 +/- 23 min. The drug caused a significant tachycardia and a moderate hypotension. The decrease in central venous pressure was also significant. Rectal temperature, respiratory rate, acid base status, blood gases, haemoglobin concentration, packed cell volume, total erythrocyte count, total leucocyte count, differential leukocyte count, blood urea nitrogen, plasma alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, blood glucose and plasma concentrations of sodium, potassium, chloride and inorganic phosphate were not significantly affected by triflupromazine.