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The World Health Organization defines orphan diseases, as all pathological conditions, affecting 0.65-1 out of every 1000 inhabitants. They are usually not studied for their pathophysiology or for newer therapeutic options, as these are not economically viable. The Orphan Drug Act was passed on January 28, 1983 by USA to stimulate the research, development and approval of those products that treat orphan diseases. Till date, 11 drugs (4.87%) for tropical infectious diseases have been designated with orphan drug status and as many drugs for other infectious diseases. Several drugs with orphan status are used in the treatment of diseases that no longer meet orphan status criteria, such as AIDS and end-stage renal disease. Understanding of the human genome, nuclear cloning, rational drug designing and application of high throughput screening in drug discovery programs, might lead to new drug discoveries for orphan diseases. Hence, there is hope in future for patients neglected by for-profit drug discovery efforts.

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Objectives: To investigate the chemopreventive potential and antilipidperoxidative effects of ethanolic root extract of Tephrosia purpurea (Linn.) Pers. (TpEt) on 7,12-dimethylbenz(a)anthracene (DMBA)- induced hamster buccal pouch carcinoma. Materials and Methods: Oral squamous cell carcinoma was developed in the buccal pouch of Syrian golden hamsters, by painting with 0.5% DMBA in liquid paraffin, thrice a week, for 14 weeks. The tumor incidence, volume and burden were determined. Oral administration of TpEt at a dose of 300 mg/kg, b.w., to DMBA (on alternate days for 14 weeks)- painted animals significantly prevented the incidence, volume and burden of the tumor. Results: TpEt showed potent antilipidperoxidative effect, as well as enhanced the antioxidant status in DMBA- painted animals. Conclusion: TpEt has potent chemopreventive efficacy and significant antilipidperoxidative effect, in DMBA-induced oral carcinogenesis. Further studies are needed to isolate and characterize the bioactive principle.

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Objective: To study the analgesic activity of venlafaxine and its interactions with tramadol, celecoxib and amlodipine. Materials and Methods: Antinociceptive action of venlafaxine (5, 7.5, 10 and 22.5 mg/kg) was studied in mice (tail flick and writhing tests). Sub-analgesic doses of venlafaxine, tramadol, celecoxib and amlodipine were obtained using these methods. A sub-analgesic dose of venlafaxine was combined with sub-analgesic doses of tramadol, celecoxib and amlodipine to study their interactions. Results: The antinociceptive action of venlafaxine was found only at higher doses (10 and 22.5 mg/kg). When a sub-analgesic dose of venlafaxine was combined with sub-analgesic doses of tramadol, amlodipine or celecoxib, the combination resulted in a significant antinociceptive effect. Conclusion: Evidence of analgesic activity, as indicated by increase in tail flick latency and decrease in number of writhing movements following venlafaxine treatment, suggests that it could possibly have central as well as peripheral action. The findings indicate that the potential use of venlafaxine in antidepressant dose could produce marked pain relief. Thus patients of depression, who are on venlafaxine, may be able to tolerate mild to moderate pain without any additional analgesic.

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Objective: The current study examined the effects of the methylene chloride/methanol extract of root bark of Ceiba pentandra (L) in normal and streptozotocin-induced diabetic rats. Materials and Methods: Diabetes was induced by intravenous streptozotocin (55 mg/kg) in adult male albino Wistar rats. Single and multiple dose studies were carried out. Blood glucose levels were determined after oral administration of graded doses of C. pentandra (40, 75, 150 and 300 mg/kg) in fasting normal and diabetic groups for the single dose study; and before and at the end of day 3 of the treatment period for the multiple dose study. Results: In both the groups, the extract (40 and 75 mg/kg) significantly reduced the blood glucose 5 hours after administration, in a consistent and time-dependent manner. C. pentandra at the lower dose (40 mg/kg) produced 40% and 48.9% lowering of blood-glucose in normal and diabetic rats, respectively compared to the initial values. In the multiple dose studies, the diabetic rats were treated orally by gavage, twice a day for three days. On day 3, C. pentandra (40 and 75 mg/kg) significantly decreased blood and urine glucose, compared to initial values. With 40 and 75 mg/kg of drug, the 14 h fasting blood glucose concentration was reduced by 59.8% and 42.8% with corresponding reductions of urine glucose levels by 95.7% and 63.6%, respectively. Conclusion: These results indicate that C. pentandra possesses a hypoglycaemic effect. The plant extract is capable of ameliorating hyperglycaemia in streptozotocin-induced diabetic rats and is a potential source for isolation of new orally active agent(s) for diabetes mellitus.

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Objective: To investigate the effect of Hemidesmus indicus extract on activities of human peripheral blood lymphocytes in vitro . Materials and Methods: The total extract of the raw herb was obtained by methanol: isopropyl alcohol: acetone extraction and used at different concentrations. Human peripheral blood lymphocytes (PBLs) were isolated, stimulated to proliferate using phytohaemagglutinin (PHA) or lipopolysaccharide (LPS), with and without different concentration of herbal extracts. Adenosine deaminase (ADA) activity and immunoglobulin (IgG) secretion from cultured PBLs were studied with the herbal extracts and appropriate controls. Results: Hemidesmus indicus extract stimulated the cell proliferation at 1 mg/ml concentration significantly, after 72 h in culture. Viability of extract-treated PBLs was also maintained after culture. The extract increased the IgG production from cultured PBLs, when used at 1 mg/ml concentration. It also increased the ADA activity of PBLs after 72 h in culture. Conclusion: An immunomodulatory activity of H.indicus, related to IgG secretion and ADA activity, is revealed during the study. The herbal extract has shown to promote the release of IgG by lymphocytes and also the ADA activity after 72 h of culture.

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Objective: To investigate the bactericidal activity of manganese (IV) complex of 2-methylamino-pyridine against Streptococcus pyogenes ( S. pyogenes ) and Staphylococcus aureus ( S. aureus ). Materials and Methods: The inhibitory effect of the complex was studied on the molecular level and by turbidity measurement. Treatment of bacteria was carried out using 5, 10, 25, 50 and 100 µmol of the complex per ml of culture media. Results: The results showed that the growth of S. pyogenes rapidly decreased with increasing concentrations of the complex. In contrast, the complex caused no significant decrease in the growth rate of S. aureus . The molecular level studies showed that four protein bands, with apparent molecular weights of 19, 23, 30 and 54 Kda, respectively, increased in the protein pattern of the S. pyogenes extract after the complex treatment using silver stained polyacrylamide gels, under reducing condition . However, there was no detectable change in the protein pattern of the S. aureus extract after the complex treatment . No DNA damage was detected while using agarose gel electrophoresis and ethidium bromide staining in both types of bacteria. Conclusion: Manganese (IV) complex of 2-methylamino-pyridine showed an apparent antibacterial inhibitory effect against S. pyogenes, but S. aureus was apparently resistant.

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