OBJECTIVE: To examine the acute and chronic effects of aspirin on peripheral blood and bone marrow counts and hepatic ferritin expression in mice. MATERIAL AND METHODS: Adult male albino mice were orally administered aspirin at a dose of 600 mg/kg thrice daily for 7 days or 150 mg/kg once daily for 6/7 days up to 25 weeks. At the end of the experiment the red and white blood cell counts, hemoglobin, and packed cell volume were estimated. Bone marrow films were studied to estimate the rate of erythropoiesis and leucopoiesis. Expression of liver ferritin was tested by immunohistochemistry. RESULTS: Acute or chronic doses of aspirin reduced the RBC count, hemoglobin and other red cell indices as compared to controls. The WBC counts were higher in the treated animals as compared to the untreated animals. Both the treatment regimens appeared to suppress the rate of erythropoiesis in the marrow, while the rate of leucopoiesis appeared to increase in the marrow of the treated animals. Aspirin treatment did not significantly affect the expression of ferritin in the liver. CONCLUSION: Aspirin in either acute or chronic doses induces anemia associated with leucocytosis in mice; the anemia does not seem to be induced due to alterations in iron metabolism. The drug appears to use multiple targets which affect red cell production and maturation processes.

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Diabetes mellitus is a group of syndromes characterized by hyperglycemia, altered metabolism of lipids, carbohydrates and protein and an increased risk of complication of vascular diseases. Type 2 diabetes mellitus is characterized by derangement of insulin secretion and an inability of the peripheral tissues to respond to insulin. In spite of the availability of many animal models for Type 2 diabetes mellitus including genetic and chemically induced, none of them simulate human Type 2 diabetes mellitus. An attempt has been made in the present review, to evaluate the neonatal streptozotocin-induced rat (n-STZ rats) model of Type 2 diabetes mellitus, for its potential advantages as a suitable model over the others. The n-STZ model (with alteration of dose and day of STZ injection) exhibits various stages of Type 2 diabetes mellitus such as impaired glucose tolerance, and mild, moderate and severe glycemia. The cells in n-STZ rats bear a resemblance to insulin secretory characteristics found in patients with Type 2 diabetes mellitus. Thus the n-STZ model can be considered as one of the suitable animal models of Type 2 diabetes mellitus.

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OBJECTIVE: To find out the hypoglycemic activity of Ficus hispida Linn. (bark) in normal and diabetic albino rats and to evaluate its probable mechanism of hypoglycemic activity if any. MATERIAL AND METHODS: Albino rats were divided into groups (n=6) receiving different treatments consisting of vehicle, water-soluble portion of the ethanol extract of Ficus hispida bark (FH) (1.25 g/kg) and standard antidiabetic drugs, glibenclamide (0.5 mg/kg) and 0.24 units of insulin (0.62 ml of 0.40 units/ml). Blood glucose was estimated by the glucose oxidase method in both normal and alloxan-induced diabetic rats before and 2 h after the administration of drugs. To find out the probable mechanism of action of FH as a hypoglycemic agent, i) the glycogen content of the liver, skeletal muscle and cardiac muscle, and ii) glucose uptake by isolated rat hemi-diaphragm were estimated. RESULTS: FH showed significant reduction of blood glucose level both in the normal (P<0.01) and diabetic (P<0.001) rats. However, the reduction in the blood glucose level was less than that of the standard drug, glibenclamide. FH also increased the uptake of glucose by rat hemi-diaphragm significantly (P<0.001). There was a significant increase in the glycogen content of the liver (P<0.05), skeletal muscle (P<0.01) and cardiac muscle (P<0.001). The amount of glycogen present in the cardiac muscle was more than the glycogen present in the skeletal muscle and liver. CONCLUSION: FH has significant hypoglycemic activity. Increased glycogenesis and enhanced peripheral uptake of glucose are the probable mechanisms involved in its hypoglycemic activity.

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OBJECTIVE: To standardize a high-performance liquid chromatography (HPLC) method for the determination of rifampicin (RMP) and its major metabolite desacetyl rifampicin (DRMP) in plasma and urine. MATERIAL AND METHODS: A simple, specific and sensitive HPLC method was developed for the determination of RMP and DRMP in plasma and urine. Separation in both was achieved by reverse-phase chromatography on a C18 column with a mobile phase composition of 0.05 M phosphate buffer: acetonitrile (55:45 v/v) at 254 nm. RESULTS: The retention times of DRMP, RMP and Rifapentine (RPN), the internal standard were 2.9, 4.8 and 10.5 min respectively. The assay was linear from 0.25 to 15.0 g ml-1 for plasma and 2.5 to 80.0 g ml-1 for urine. Both intra-day and inter-day accuracy and precision data showed good reproducibility. CONCLUSION: The HPLC method described is sensitive, selective and linear for the wide range of concentrations for RMP and DRMP in plasma and urine. Thus, the method developed is well suited for the pharmacokinetic studies.

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OBJECTIVE: To study the cardio-respiratory effects of DRDE-07, a new prophylactic agent for sulphur mustard. MATERIAL AND METHODS: The effect of DRDE-07 was studied in anesthetized male rats (Wistar), by administering it either by intraperitoneal or oral routes. Different doses (0.25, 0.5, 1.0 and 2.0 LD50) were used and various cardio-respiratory parameters viz., mean arterial blood pressure, heart rate, respiratory rate and tidal volume were monitored on an oscillograph. RESULTS: Intraperitoneal administration of 0.5 and 1.0 LD50 and oral administration of 0.25 LD50 of DRDE-07 did not produce any effect on the cardio-respiratory variables. Oral administration of 0.5 and 1.0 LD50 showed a significant decrease in mean arterial blood pressure after 60 min. None of the animals died in the two-hour monitoring period. Two (2.0) LD50 administration of DRDE-07 either by intraperitoneal or oral routes induced a sudden decrease in the mean arterial blood pressure and the animals died within one hour. CONCLUSION: DRDE-07 did not show any significant effect on the cardio-respiratory variables at a dose of 0.25 LD50 by oral route and 1.0 LD50 by intraperitoneal route. The death after intraperitoneal or oral administration (2.0 LD50) of DRDE-07 is due to the sudden fall in the mean arterial blood pressure.

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Bioequivalence (BE) means the absence of a greater-than-allowable difference between the systemic bioavailability of a test product and that of a reference product. Studies to test the BE of drug products, and the statistical basis for their design, analysis and interpretation, have evolved over the last two decades. A crossover design is preferred over a parallel-group design as it segregates the inter-subject variation (which is not product-dependent) from the intra-subject variation (which is product-dependent). The value of testing two one-sided null hypotheses of non-equivalence at a significance level of 0.05, and the importance of estimating a 90% confidence interval of the ratio (test/reference) of mean AUC and Cmax values, and of the difference between mean Tmax values, are now recognized and form the current standards for BE. The number of subjects required for a BE study with the desired power (at least 0.80) and significance level (0.05), depends on the expected deviation of the test product from the reference product and the error variance associated with the bioavailability parameters (AUC, Cmax, Tmax etc.) of the drug substance. At present, according to the Indian regulatory authority, the number of subjects required to conduct a BE study is 12 which is inadequate for most drug substances by the current international standards and criteria. This review expounds the foregoing principles of BE testing.

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OBJECTIVE: To investigate the antineoplastic potential of a novel antiestrogen (AE) centchroman (CENT) using cell morphology, viability and cathepsin-D (Cath-D) gene expression as indices in MCF-7 human breast cancer cell line. MATERIAL AND METHODS: MCF-7 cells were incubated with CENT (1 µM, 10 µM) in the absence and presence of 17- estradiol (E2, 10 nM) for 4 days. Investigations were carried out on alterations in cell morphology, number, Cath-D gene expression using Phase Contrast Microscopy, Trypan-blue dye exclusion and spectrophotometric assay. A standard antiestrogen and antibreast cancer agent tamoxifen (TAM -1 µM, 10 µM) was used as a positive control. RESULTS: E2 (10 nM) alone significantly up-regulated the cells morphologically, numerically and biochemically thus establishing their hormonal responsiveness. TAM and CENT at 1 µM each enhanced and reduced the viable cell number respectively whereas both elevated the Cath-D activity. However, 35mm photographic evidence did not indicate any cytotoxic effect with either drug as compared to control. Addition of E2 to the two ligands separately affected the three parameters similar to that in E2 alone. With 10 µM TAM and CENT individually, the cells were visually devastated and so were the viable cell numbers and Cath-D gene expression. Supplementation of E2 under similar conditions failed to undo the damage to the cells morphologically and quantitatively. However, disparate results were observed with regards to the enzyme activity where TAM+E2 caused inhibition and CENT+E2 resulted in an induction. CONCLUSION: It can be concluded that both the AEs TAM and CENT displayed similarities in their antineoplastic action on MCF-7 cells as observed by morphological and viability studies except that the latter proved cytotoxic even at 1µM concentration. TAM and CENT showed a similar effect on Cath-D gene expression except at the higher dose (10 µM). These results suggest that the antiestrogen CENT has better antineoplastic potential as opposed to TAM.

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