Vias envolvidas no mecanismo de ação do efeito gastroprotetor das cascas de Tabebuia avellanedae Lorentz ex Griseb (Bignoniaceae) /

Orientadora : Maria Consuelo Andrade MarquesCo-orientador : Michel F. OtukiDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Farmacologia. Defesa: Curitiba, 2007Inclui bibliografi

A influência do polimorfismo do CYP2C9 na atrofia cerebelar em pacientes usuários de fenitoína

Resumo: Até 50% dos pacientes que utilizaram fenitoína (FNT) para tratamento de epilepsia apresentam algum grau de atrofia cerebelar, porém os mecanismos de como isto ocorre ainda não são claros. A FNT é metabolizada quase que exclusivamente pela enzima CYP2C9 (90%) e em portadores de mutação desta enzima, esta metabolização pode estar reduzida em até 50%. O objetivo do estudo é avaliar se pacientes com epilepsia que utilizaram FNT e apresentam mutação do CYP2C9, portanto com metabolização deficiente de FNT, apresentam um menor volume cerebelar (VC) que os pacientes sem esta mutação. Cem pacientes com epilepsia e usuários comprovados de FNT por pelo menos 1 ano, foram classificados conforme o perfil do CYP2C9 em selvagens (sem mutação, variante *1) e mutantes (variantes *2 e *3). De 72 pacientes sem mutação foram selecionados 19 (grupo SEL-P) que apresentavam características clínicas e demográficas mais semelhantes a 19 pacientes com mutação (Grupo MUT-P). Os dois grupos realizaram volumetria encefálica por ressonância magnética, sendo no processamento das imagens e no cálculo do volumes, utilizado o software MIPAV. As características clínicas e demográficas dos grupos SEL-P e MUT-P não apresentaram diferenças estatísticas significativas. Para comparação do VC, entre os grupos mutantes e selvagens, foram anuladas possíveis variáveis de confusão, através de teste de regressão logística. O grupo MUT-P apresentou uma redução no volume cerebelar total em relação ao grupo SEL-P (6,8% x 7,4%), porem sem significância estatística (p=0,13). Na análise isolada da substância branca cerebelar o grupo MUT-P apresentou uma redução volumétrica significativa (p=0,002) em relação ao grupo SEL-P (1,8% x 2,3%). O padrão de redução do VC, predominante na substância branca, sugere uma relação direta entre metabolização deficiente de FNT, pela presença de mutação do CYP2C9 e atrofia cerebelar, em pacientes com epilepsia e usuários de FNT

Ocorrência de mamíferos de médio e grande porte em uma área de mata Atlântica no município de São José dos Pinhais - PR

Orientador : Fernando de Camargo PassosCoorientador: André Luiz Ferreira da SilvaMonografia (Bacharelado) - Universidade Federal do Paraná. Setor de Ciências Biológicas. Curso de Graduação em Ciências Biológicas

Modulation of peritoneal macrophage activity by the saturation state of the fatty acid moiety of phosphatidylcholine

To determine the effects of saturated and unsaturated fatty acids in phosphatidylcholine (PC) on macrophage activity, peritoneal lavage cells were cultured in the presence of phosphatidylcholine rich in saturated or unsaturated fatty acids (sat PC and unsat PC, respectively), both used at concentrations of 32 and 64 µM. The treatment of peritoneal macrophages with 64 µM unsat PC increased the production of hydrogen peroxide by 48.3% compared to control (148.3 ± 16.3 vs 100.0 ± 1.8%, N = 15), and both doses of unsat PC increased adhesion capacity by nearly 50%. Moreover, 64 µM unsat PC decreased neutral red uptake by lysosomes by 32.5% compared to the untreated group (67.5 ± 6.8 vs 100.0 ± 5.5%, N = 15), while both 32 and 64 µM unsat PC decreased the production of lipopolysaccharide-elicited nitric oxide by 30.4% (13.5 ± 2.6 vs 19.4 ± 2.5 µM) and 46.4% (10.4 ± 3.1 vs 19.4 ± 2.5 µM), respectively. Unsat PC did not affect anion production in non-stimulated cells or phagocytosis of unopsonized zymosan particles. A different result pattern was obtained for macrophages treated with sat PC. Phorbol 12-miristate 13-acetate-elicited superoxide production and neutral red uptake were decreased by nearly 25% by 32 and 64 µM sat PC, respectively. Sat PC did not affect nitric oxide or hydrogen peroxide production, adhesion capacity or zymosan phagocytosis. Thus, PC modifies macrophage activity, but this effect depends on cell activation state, fatty acid saturation and esterification to PC molecule and PC concentration. Taken together, these results indicate that the fatty acid moiety of PC modulates macrophage activity and, consequently, is likely to affect immune system regulation in vivo.Fundação Araucári

Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders

Learning to associate cues or contexts with potential threats or rewards is adaptive and enhances survival. Both aversive and appetitive memories are therefore powerful drivers of behaviour, but the inappropriate expression of conditioned responding to fear- and drug-related stimuli can develop into anxiety-related and substance abuse disorders respectively. These disorders are associated with abnormally persistent emotional memories and inadequate treatment, often leading to symptom relapse. Studies show that cannabidiol, the main non-psychotomimetic phytocannabinoid found in Cannabis sativa, reduces anxiety via 5-HT1A and (indirect) cannabinoid receptor activation in paradigms assessing innate responses to threat. There is also accumulating evidence from animal studies investigating the effects of cannabidiol on fear memory processing indicating that it reduces learned fear in paradigms that are translationally relevant to phobias and post-traumatic stress disorder. Cannabidiol does so by reducing fear expression acutely and by disrupting fear memory reconsolidation and enhancing fear extinction, both of which can result in a lasting reduction of learned fear. Recent studies have also begun to elucidate the effects of cannabidiol on drug memory expression using paradigms with translational relevance to addiction. The findings suggest that cannabidiol reduces the expression of drug memories acutely and by disrupting their reconsolidation. Here, we review the literature demonstrating the anxiolytic effects of cannabidiol before focusing on studies investigating its effects on various fear and drug memory processes. Understanding how cannabidiol regulates emotion and emotional memory processing may eventually lead to its use as a treatment for anxiety-related and substance abuse disorders

Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms

Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allow identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets