Pharmacological activity of novel 2-hydroxyacetophenone isatin derivatives on cardiac and vascular smooth muscles in rats.

Isatin (1H-indole-2,3 dione) is an endogenous compound with biological activities. Many of its derivatives have pharmacological effects, including inhibition of cyclic guanosine monophosphate levels in cardiac tissue; sedative-hypnotic profiles; anticonvulsant, analgesic, antithermic, and anti-inflammatory activities; and anxiolytic, antimicrobial, and proapoptotic effects. Carbamates derived from isatin have a vasorelaxant profile. This study investigated the activity of 2 novel 2-hydroxyacetophenone derivatives of isatin (named MB101 and MB130) on the contractility of rat aorta and papillary muscles. Both compounds induced a concentration-dependent relaxation (5-100 µM) in the endothelium-intact aorta that was abolished by N-nitro-L-arginine methyl ester. Atropine, a muscarinic receptor antagonist, significantly prevented vasodilatation of 100 µM MB101. In contrast, atropine caused no significant alteration in MB130-induced vasorelaxation. Naloxone, a nonselective opioid receptor antagonist, completely prevented the relaxing effect of MB101 and MB130 at all concentrations. In papillary muscles, only MB130 induced a significant depression, and this contractile response was not altered by propranolol and atropine. Both the compounds reduced systolic and diastolic pressures in a dose-dependent manner in anesthetized rats. The 2-hydroxyacetophenones produced direct effects on vascular tonus through either muscarinic or opioid pathways. MB130 produced cardiac depression by opioid receptors and bradykinin because pretreatment HOE140 or with naloxone, an antagonist of type-2, bradykinin were able to partially block the decrease in twitch amplitude in papillary muscles induced by MB130. These findings provide information for designing new strategies for the treatment of cardiovascular disorders.

Sedative-hypnotic profile of novel isatin ketals.

Isatin (1H-indol-2,3-dione) is an endogenous compound found in many tissues and fluids. Isatin and its derivatives exert pharmacological effects on the central nervous system, including anxiogenic, sedative and anticonvulsant activities. Two new groups of isatin derivatives were synthesized (nine dioxolane ketals and nine dioxane ketals) and studied for their sedative, hypnotic and anesthetic effects using pentobarbital-induced sleeping time, locomotor activity evaluation and intravenous infusion. The dioxolane ketals were more potent than dioxane ketals for inducing sedative-hypnotic states, causing up to a three-fold increase in pentobarbital hypnosis. The dioxolane ketals produced sedation, demonstrated by decreased spontaneous locomotor activity in an open field. Hypnosis and anesthesia were observed during intravenous infusion of 5'-chlorospiro-[1,3-dioxolane-2,3'-indolin]-2'-one (T3) in conscious Wistar rats. Complete recovery from hypnosis and anesthesia required 39.1+/-7.3 and 6.8+/-2.4 min, respectively. Changes in hemodynamic parameters after infusion of 5.0 mg/kg/min were minimal. These findings suggest that these new isatin derivatives represent potential candidates for the development of new drugs that act on the central nervous system and may lead to a new centrally acting anesthetic with no toxic effects on the cardiovascular or respiratory systems.

Areas de seccão transversa do braco: implicacões técnicas e aplicacões para avaliacão da composicão corporal e da forca dinâmica máxima / Arm cross-section areas: technical implications and applications for body composition and maximal dynamic strength evaluation

As áreas do tecido muscular (A MB) e do anel de gordura do braco (A GB), podem ser estimadas por medidas antropométricas. OBJETIVO: Investigar a validade e o erro intertestador da antropometria para inferência A MB e do A GB. Secundariamente, estudou-se a previsão da forca dos membros superiores e tronco através da A MB. MÉTODOS: Foram voluntários para este estudo 40 adultos masculinos jovens (25 n 6 anos; 72,6 n 9,4kg), divididos aleatoriamente nos grupos de validade interna (VI, n = 30) e validade externa (VE, n = 10). Determinou-se para VI, através de conceitos geométricos, a área total do braco (A TB), A MB, A GB e área percentual de gordura do braco. O somatório de oito dobras cutâneas (S DC8) foi empregado como índice da adiposidade corporal. A forca dos membros superiores e do tronco foi medida através da carga máxima alcancada no exercício supino reto livre (1-RM). As medidas antropométricas foram realizadas por dois avaliadores independentes. Os dados foram tratados por meio da análise de regressão, coeficiente de correlacão intraclasse (ICC) e teste t de Student pareado (a < 0,05). RESULTADOS: A variância do S DC8 pode ser explicada em 93 por cento (EPE = 14,6mm) a partir da A GB e do peso corporal. A A MB explicou em 66,1 por cento (EPE = 9kg) a 1-RM. Não se observou diferenca significativa, para o grupo VE, entre os valores medidos (84,2 n 16,2kg) e preditos (78,4 n 14,2kg) de 1-RM. Observou-se pouca variacão entre os avaliadores para A MB (ICC = 0,99), A GB (ICC = 0,96) e A TB (ICC = 0,99). CONCLUSAO: A antropometria pode ser empregada para inferência da A MB e do A GB, com boa concordância entre avaliadores, para estimativa da adiposidade corporal e da forca dos membros superiores e tronco.