Mamta Singh

Treatment effect of l-Norvaline on the sexual performance of male rats with streptozotocin induced diabetes.

Sexual impairment is an established risk factor in diabetes mellitus affecting about 75% of male diabetic population. In diabetes overexpression of arginase leads to decreased production of NO and diminished erectile response. Inhibition of arginase enzyme can lead to improvement in diabetes induced sexual dysfunction. In the present study diabetes mellitus was induced in adult male rats by intraperitoneal injection of single dose of streptozotocin (65mg/kg) in 0.1M Citrate buffer pH 4.5 and after 72h fasting serum glucose level was checked by glucose oxidase-peroxidase method and those animals showing FSG above 250mg/dl were selected. Diabetic animals were divided into four groups comprising six animals in each. l-Norvaline, potent arginase inhibitor was administered at a dose of 10mg/kg ip to the different groups of diabetic animals for a period of 30 days. Sildenafil at a dose of 5mg/kg orally was used as a standard drug. Mating behavior tests were performed at 0, 15th and 30th days. After 30 days, various biochemical and hormonal parameters (nitrates, LDH, urea, testosterone), testicular parameters (total protein, nitrates, LDH, total cholesterol, LDL, triglycerides, VLDL, HDL) were evaluated to find out the effect of l-Norvaline in sexual impairment. Sperm analysis was also carried out for the treated rats. l-Norvaline showed significant improvement in serum nitrates, urea, LDH, testosterone and testicular protein level as compared with diabetic group. It also improved sperm motility, count and viability in diabetic rats. Sildenafil showed no improvement in above parameters except restoration in serum nitrates level.

Stimuli-sensitive hydrogels: a novel ophthalmic drug delivery system.

Background: Stimuli-sensitive hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature and ionic change. Aim: To develop hydrogels that are sensitive to stimuli, i.e. pH, in the cul-de-sac of the eye for providing a prolonged effect and increased bioavailability with reduction in frequency of administration. Materials and Methods: Hydrogels were formulated by using timolol maleate as the model drug, polyacrylic acid as the gelling agents, hydroxyl ethyl cellulose as the viscolizer and sodium chloride as the isotonic agent. Stirring of ingredients in pH 4 phosphate buffer at high speed was carried out. The dynamic dialysis technique was used for drug release studies. In vivo study for reduction in intraocular pressure was carried out by using albino rabbits. Statistical Analysis: Drug release studies data were used for statistical analysis in first-order plots, Higuchi plots and Peppas exponential plots. Student t-test was performed for in vivo study. Results: Viscosity of the hydrogel increases from 3.84 cps to 9.54 cps due to change in pH 4 to pH 7.4. The slope value of the Peppas equation was found to be 0.3081, 0.3743 and 0.2964. Up to 80% of drug was released in an 8 h drug release study. Sterile hydrogels with no ocular irritation were obtained. Conclusions: Hydrogels show increase in viscosity due to change in pH. Hydrogels were therapeutically effacious, stable, non-irritant and showed Fickian diffusion. In vivo results clearly show a prolonged reduction in intraocular pressure, which was helpful for reduction in the frequency of administration.

Polymeric ocular hydrogels and ophthalmic inserts for controlled release of timolol maleate

Background: Ophthalmic drug delivery systems are the challenging subject for the researchers because of delicate nature of ocular membrane and preventive barriers leading to less than 1 % of Bioavailability. Reasons for reduced bioavailability are due to rapid pre corneal elimination, tear turnover, lacrimal drainage, blinking and degradation by enzymes. Less bioavailability causes short duration of action and increased frequency of administration. Materials and Methods: Timolol maleate was used as model drug. Dynamic drug release studies were used to study the polymeric hydrogels and ophthalmic inserts. Rheological studies were carried out by Brookfield Viscometer LVDV- II+. Result and Discussion: Viscosity value lies in the range of 4.08 to 31.8 cps. Drug release data was fitted to various kinetic equations such as First order plots, Higuchi plots, Peppas exponential plots. The results shows fairly linear curve and the slope value of the Peppas equation is less than 0.5 and hence follows the fickian diffusion. Conclusion: The developed hydrogels and inserts were therapeutically effacious, stable, non irritant and provide a sustained release of drug over 8 hours time period.

L-Norvaline and Alpha-tocopherol Treatment Protect Against Diabetes-Induced Oxidative Stress in Testes of Male Rats

The present study aimed to evaluate the effect of L-Norvaline and alpha-tocopherol in protection and combating the oxidative stress of testes in hyperglycemic male rats. In our study single dose of streptozotocin was used for induction of diabetes and fasting serum glucose level was checked and those animals showing FSG above 250 mg/dL were selected. The diabetic animals were randomly divided into seven groups comprising six animals in each group and one group of normal non diabetic animals received the vehicle 0.1 M citrate buffer pH 4.5. L-Norvaline was administered at higher (10 mg/kg) and lower (8 mg/kg) dose intraperitoneally to the different groups of diabetic animals along with alpha-tocopherol (900 mg/kg) orally for a period of 30 days. Sildenafil at an oral dose of 5 mg/kg was used as reference drug. After that period, testis was isolated and homogenized. The homogenized tissue was centrifuged, separating the supernatant and preserved it for assessing the oxidative stress parameters. The level of various antioxidant enzymes were assessed such as superoxide dismutase, reduced glutathione, glutathione peroxidase and glutathione reductase. Assessment of lipid peroxidation was also done in treated groups. The statistical analyses were carried out using Graph Pad Prism 5.0 software. All values were presented as Mean ± S.E.M. The level of superoxide dismutase, reduced glutathione, glutathione peroxidase and glutathione reductase were highly diminished in the diabetic rats compared with normal group. L-Norvaline alone showed no significant improvement in those enzymes parameters except in reduced glutathione (P<0.05). L-Norvaline both at higher dose and lower dose along with alpha-tocopherol showed significant improvement in the level of antioxidant enzymes as compared with diabetic group (P<0.05, P<0.01, P<0.001). Treated groups also showed a significant decrease in the level of malondialdehyde as compared to diabetic group (P<0.01, P<0.001). Standard drug, Sildenafil showed no improvement in any parameters after 30 days. The present can be concluded by establishing the fact that LNorvaline and Alpha-tocopherol could be a good combination in scavenging free radicals in testes due to streptozotocin induced hyperglycemia in male Wistar rats.

Rheumatoid Arthritis: Treatment by Film Forming Gels

Rheumatoid arthritis is an auto immune disease in which joint inflammation, synovial proliferation and destruction of articular cartilage. Gels are most commonly used dosage forms. Topical preparations are generally used for the treatment of rheumatoid and osteoarthritis disease. Gels provide certain advantages over oral route, which may lead to peptic ulcers in excessive usage of NSAIDS in tablet dosage form. Gels can be easily wiped off due to clothes on joints and films may provide dryness and irritation after prolonged usage due to adhesive in it. Thus, there is a need to develop novel drug delivery systems for the treatment of rheumatoid arthritis, which is available in gel form but when applied on skin surface transforms into film. These film forming gels are novel approach helpful in providing sustained release with increased residence time, therapeutic effect and patient comfortability.