The effect of a free radical generator pyrogallol on gastric emptying was studied in rats. Pyrogallol at doses of 25, 50, 100 and 150 mg/kg (i.p.) produced dose-dependent inhibition of gastric emptying. Pretreatment with vitamin C (100 and 500 mg/kg, p.o.), and vitamin E (100 and 500 mg/kg, p.o.) significantly reversed the inhibition in gastric emptying caused by pyrogallol 100 mg/kg. However, the combination of vitamin C and vitamin E (100 mg/kg) produced synergistic effect. Glutathione (100 mg/kg i.v.) 5-min pretreatment also reversed the inhibition of gastric emptying caused by pyrogallol 100 mg/kg. Ondansetron (3 mg/kg, p.o.) significantly reversed the pyrogallol effect. The effect of pyrogallol on malondialdehyde (MDA) levels and 5-HT levels in the stomach tissue was also studied. Pyrogallol at a dose of 100 mg/kg, i.p., significantly increased MDA levels and 5-HT levels in the stomach. Pretreatment with a combination of vitamin C and vitamin E (100 mg/kg, p.o.) and glutathione (100 mg/kg, i.v.) significantly ameliorated the rise in stomach tissue MDA caused by pyrogallol but had no significant effect on the rise in 5-HT levels caused by pyrogallol. The effect of different doses of 5-HT on gastric emptying was also studied. 5-HT had a differential effect on gastric emptying. The low and high doses (0.1, 0.3 and 30 mg/kg, i.p.) significantly inhibited the gastric emptying while doses ranging from 1 to 10 mg/kg, i.p., had no significant effect on the gastric emptying. The pretreatment with antioxidants, combination of vitamin C and vitamin E (100 mg/kg each, p.o.) and glutathione (100 mg/kg, i.v.) had no effect on the 5-HT (0.3 mg/kg, i.p.)-induced delay in gastric emptying. The result indicate the role of free radicals gastric emptying, and antioxidants may be of potential therapeutic value in disease conditions where free radicals are known to be released and the gastrointestinal effects are observed as symptoms or side effects of drug therapy.
The new age clinical research professional is now geared toward an “integrated monitoring” approach. A number of critical activities at the site level and at the sponsor’s organization need convergence to harness rich dividends in early study start and quick close of the study. The field monitor needs full integration to ensure standard of care, train the site in protocol, select the right site, ensure regulatory support, ensure excellent project management skills, coach, support the logistics team, manage the vendor, ensure good documentation practices, develop patient recruitment and retention, lean the applicable process, as well as ensure effective site management amongst the myriad activities assigned toward developing the drug in the clinic.
In the beginning of his scientific career, he was interested in the development of neuropeptidergic systems in the brain (oxytocin, vasopressin, prolactin) and their regulation by glucocorticoids.Then in the UK, he focused on the role of neuroactive steroids during brain development and their input to the sexual differentiation of brain functions. Back in Germany, he focused his research for several years on novel signal perception and intracellular signal transduction mechanisms of estrogens in the CNS, so-called nongenomic steroid signaling. After moving to Aachen, the scientific orientation of his team turned to the molecular and biochemical understanding of acute neurological and chronic neurodegenerative diseases of the brain.In particular, animal models for multiples sclerosis, amyotrophic lateral sclerosis, and acute ischemic stroke and spinal cord injury were established in his group and served to analyze the underlying neuroinflammatory processes and neuroprotective strategies. Novel and only recently started research projects are concerned with the influence of steroid hormones such as estrogens for the therapeutic treatment of psychiatric disorders such as eating disorders and aggression.
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