Pharmacophore-based virtual screening from phytocannabinoids as antagonist r-CB1.

Search for new pharmacological alternatives for obesity is based on the design and development of compounds that can aid in weight loss so that they can be used safely and effectively over a long period while maintaining their function. The endocannabinoid system is related to obesity by increasing orexigenic signals and reducing satiety signals. Cannabis sativa is a medicinal plant of polypharmaceutical potential that has been widely studied for various medicinal purposes. The in silico evaluation of their natural cannabinoids (also called phytocannabinoids) for anti-obesity purpose stems from the existence of synthetic cannabinoid compounds that have already presented this result, but which did not guarantee patient safety. In order to find new molecules from C. sativa phytocannabinoids, with the potential to interact peripherally with the pharmacological target cannabinoid receptor 1, a pharmacophore-based virtual screening was performed, including the evaluation of physicochemical, pharmacokinetic, toxicological predictions and molecular docking. The results obtained from the ZINC12 database pointed to Zinc 69 (ZINC33053402) and Zinc 70 (ZINC19084698) molecules as promising anti-obesity agents. Molecular dynamics (MD) studies disclose that both complexes were stable by analyzing the RMSD (root mean square deviation) values, and the binding free energy values demonstrate that the selected structures can interact and inhibit their catalytic activity.

Toxicological evaluation of acute and sub-chronic ingestion of hydroalcoholic extract of Solanum cernuum Vell. in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum cernuum Vellozo is a Brazilian shrub or small tree, restricted to Southwest states of the country. It has been widely used for the treatment of many ailments. The pharmacological activity of the extract on gastric ulcer has been the major therapeutic target proposed by the population investigated. MATERIALS AND METHODS: In the acute toxicity test was used increasing doses of the extract (2, 4, 8, 12, 16, 20 and 25 g of extract per kilogram of body weight). The animal behavior was observed from 5h after a single administration of the extract and subsequently monitored daily until the fourteenth day, beyond the calculation of the estimated LD50 of the extract. In the test sub-chronic toxicity was used two doses of the extract (0.1 and 1.4 g/kg) and the parameters analyzed over 31 days were: body weight, food intake, behavior, respiratory rate, movement and mortality of animals. After anesthesia, blood samples were collected for hematological and biochemical analysis. The animals were euthanized followed by macroscopic analysis of the stomach and intestine. Liver, lungs and kidneys were removed, weighed and analyzed histopathologically. RESULTS: In the acute toxicity test was observed a dose-dependent mortality and the value of estimated LD50 was 14.50 g/kg. In the hematological and biochemical analyses there were significant increase in the activities of AST and ALT indicating liver toxicity, but the extract was not able to alter food intake, body weight and organ weights after 31 days of treatment and it did not produce significant histopathological changes. CONCLUSION: Therefore we can consider the hydroalcoholic extract of Solanum cernuum Vell as practically non-toxic in acute administration and safe in the sub-chronic administration, as hepatotoxicity was observed only with the highest dose used, not with the dose routinely used by the native population.

[Radiotherapy using a combination of photons and protons for locally aggressive intracranial tumors. Preliminary results of protocol CPO 94-C1]. / Radiothérapie des tumeurs intracrâniennes localement agressives par une combinaison de photons et de protons. Résultats préliminaires du protocole CPO 94-C1.

PURPOSE: From October 1993 through July 1998, 48 assessable adult patients with non-resectable aggressive intracranial tumors were treated by a combination of high dose photon + proton therapy at the Centre de Protonthérapie d'Orsay. PATIENTS AND METHODS: Grade 1 and 4 gliomas were excluded. Patients benefited from a 3D dose calculation based on high-definition CT and MRI, a stereotactic positioning using implanted fiducial markers and a thermoplastic mask. Mean tumor dose ranged between 63 and 67 Gy delivered in five weekly sessions of 1.8 Gy in most patients, according to the histological types (doses in Co Gy Equivalent, with a mean proton-RBE of 1.1). RESULTS: With a median 18-month follow-up (range: four-58 months), local control in tumors located in the envelopes and in the skull base was 97% (33/34), and in parenchymal tumors, 43% (6/14) only. Two patients (5%) presented with a clinically severe radiation-induced necrosis (temporal lobe and chiasm). CONCLUSION: In our experience, high-dose radiation combining photons and protons is a safe and highly efficient procedure in selected malignancies of the skull base and envelopes.