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- ItemAcesso aberto (Open Access)Efeito do ácido ursodesoxicólico e o papel da mucosa no desenvolvimento de dismotilidade esofagiana: estudo experimental com cobaias(Universidade Federal de São Paulo (UNIFESP), 2010-05-26) Rocha, Marcelo Eustáquio Siqueira [UNIFESP]; Fernandes, Fernando Augusto Mardiros Herbella [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Background and Aims: Esophageal motor abnormalities are frequently found in patients with gastroesophageal reflux disease. The role of bile in reflux-induced dysmotility is still elusive. Furthermore, it is questionable weather mucosal or muscular stimulation leads to motor modification. The aims of this study were: (a) analyze the effect of bile infusion in the amplitude of esophageal contractions and (b) analyze the effect of mucosal vs muscular stimulation. Methods: 18 guinea-pig esophagi were isolated and its contractility assessed with force transducers. Three groups were studied. In group A (n= 6) the entire esophagus was used and incubated in 100 ìML ursodeocycholic acid for 2 hours. In group B (n=6) the mucosal layer was removed and the muscular layer incubated in 100 ìML ursodeocycholic acid for 1 hours. In group C (n=6) (control group) the entire esophagus was used and incubated in saline solution. In all groups, five sequential contractions spaced by 1 minute were measured before and after incubation. Contractions were recorded after KCl 40 mM stimulation. Results: Contractions before incubation did differed among groups (p= 0,006) and averaged 1,319(A),0,306(B) and 1,795(C). After incubation amplitude of contraction was 0,709 , 0,278 and 1,353 for groups A, B and C respectively. Before incubation there were no diferrences between groups A and C (p=0,633) there was difference between groups A and B (p=0,039) and B and C (p=0,048). After incubation when we compare average within groups (before and after) there was difference only in group A (p=0,030). Conclusion: Our results show that bile exposure may induce ineffective esophageal motility and the mucosa seems to take an important role in esophageal motility. Disclosure Statement: No author has commercial associations that might create a conflict of interest. No competing financial interests exist.
- ItemAcesso aberto (Open Access)Revisão sistemática da literatura de estudos clínicos e experimentais sobre os efeitos antitumorais dos canabinóides(Universidade Federal de São Paulo (UNIFESP), 2010-04-28) Rocha, Francisco Carlos Machado [UNIFESP]; Silveira, Dartiu Xavier da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objective: To evaluate, through a systematic review of the literature, the antitumoral effects of cannabinoids on any type of cancer, involving both human beings and animal samples, as well as cultured tumor cells. Method: Research included the following electronic databases: PUBMED, EMBASE, LILACS and "The Cochrane Collaboration Controlled Trials Register. All published studies involving the antitumoral effects (cellular and molecular mechanisms) of cannabinoids were considered for this review. Thus, not only clinical trials (randomized or not) but experimental studies (both in vivo and in vitro) were taken into account. The bibliography search strategy included all publications of each of these databases until December 31, 2009. The scrutiny of all the references from the relevant articles for this review (which included review articles) was also performed, in order to select items that could not have been captured by the chosen electronic search strategy. Results: From 3,920 initially identified articles, 117 fulfilled the inclusion criteria for this review. All the studies included in this systematic review were experimental (in vivo and/or in vitro), except for a pilot clinical trial phase I/II involving humans. In all experimental studies included, cannabinoids exerted antitumoral activity in vitro and/or antitumoral evidence in vivo in several models of tumor cells and tumors, respectively. The antitumor activity included: antiproliferative effects (cell cycle arrest), decreased viability and cell death by toxicity, apoptosis, necrosis, autophagy, as well as antiangiogenic and antimigratory effects. Antitumoral evidence included: reduction in tumor size, antiangiogenic, and antimetastatic effects. Additionally, most of the studies described that the canabinnoids exercised selective antitumoral action in several distinct tumor models. Furthermore, normal cells used as controls were not affected. The safety factor in the cannabinoids’ administration has also been demonstrated in vivo in rats with tumors which were marked with tumor cells. The sole study in humans demonstrated safety in intratumoral administration of delta-9- THC in patients with recurrent glioblastoma multiforme. Conclusions: The various cannabinoids tested in multiple tumor models showed antitumoral effects both in vitro and in vivo. These findings indicate that cannabinoids are promising compounds for the treatment of cancer. However, methodologically well conducted research on humans through clinical trials has yet to be performed in order to evaluate their effectiveness. This is the case of delta-9-THC and cannabidiol, which have been tested and approved for use in humans in other clinical conditions. In the case of other cannabinoids, however, further pharmacokinetic as well as pharmacodynamic and toxicological studies are required before their being tested in humans.