Armando O. Ramos

EVIDENCE FOR KININ FORMATION RESULTING FROM NEURAL ACTIVITY EVOKED BY NOXIOUS STIMULATION

Shortly after human skin is injured, the area for several centimeters surrounding the site of injury gradually becomes reddened. This flare is a component of the inflammatory response, represents neurogenic vasodilation, and probably is mediated through the release of one or more vasodilator substances.* The existence of a non-cholinergic vasodilator substance released following electrical stimulation of a nerve, the chorda tympani, has been postulated since the observations of Heidenhain in 18743 that atropine blocks salivary secretion resulting from such stimulation but fails to block the vasodilatation that is also induced. In 1934, Feldberg and Guimarais4 demonstrated that saliva contains a hypotensive substance that is neither acetylcholine nor histamine. Ungar and Parrot5 identified the active agent in saliva as kallikrein, a kinin-forming enzyme. They suggested that kallikrein could act in some circumstances as a neurohumoral mediator. Recently, Hilton and Lewis6 directly demonstrated the appearance of a kinin-forming enzyme in salivary gland perfusate following chorda typani stimulation. Foerster’s report’ that painful sensations were induced by stimulation of the peripheral portion of transected dorsal roots in man, and the observations of Bilisoly et aL8 that the pain threshold is lowered in regions of flare induced by noxious stimulation of skin, raise the possibility that the vasodilator mediator substance associated with the flare response of the skin to noxious stimulation also has the property of lowering the threshold for activating the neurons subserving pain sensation. Experimental evidence for such a threshold lowering substance was furnished recently by Habgood.B Studying isolated pieces of frog skin with several cutaneous nerves preserved in such a way that the areas subserved by two of them overlapped, he showed that stimulation of one nerve led to responses in the adjoining nerve. Thus, much evidence indicates that a humoral agent or series of agents is released as a result of neural activity evoked by noxious stimulation. The following studies were concerned with the possibility that vasodilator polypeptides (kinins) are implicated in this reaction.

Experimental pyelonephritis and bacteriuria, pyuria, and renal injury

agents. However, this relationship has not yet been demonstrated. Drugs which have been successfully used are diiodohydroxyquin, iodochlorohydroxyquin, and chloroquine. Each of these compounds is a halogenated quinoline with an antiparasitic action. The relatively poor absorption of diiodohydroxyquin suggests a local action on the intestinal mucosa. The generalized nature of the diseas% manifested by growth failure and epidermal lesions, suggests the absence of some essential metabolic compound. This absence could result from a primary transport defect or from malabsorption secondary to the toxic effect of some metabolite on a transport system. These possibilities led us to think of a defect in essential fatty acid transport; the blood level of fatty acids, however, apparently exclude such an explanation. Hopefully, a more detailed knowledge of the metabolism of halogenated quinoline compounds in humans may lead to an explanation of this disease.

Atividade dilatadora da l-hexil-3,7-dimetilxantina sôbre os vasos piais

The authors studied the action of the l-hexyl-3,7-dimethylxanthine on the blood pressure and on the caliber of the pial vessels of the dog. In 15 dogs anesthetized by sodium penthobarbital (30 mg/kg) the arterial blood pressure was recorded with a mercury manometer. The pial vessels were observed through a window made in the temporal bone with the aid of binocular stereoscopic microscope. For photography one of the oculars of the microscope was replaced by an appropriate camera. The procedure was that proposed by Forbes4 modified by Melaragno5. Groups of 4 animals received respectively 15, 30 and 60 mg/kg of the drug by the oral route and were observed until 240 minutes. The other three animals were used as control and observed by the same interval of time, receiving only the anesthetic. The oral administration of the l-hexyl-3,7-dimethylxanthine induced marked relaxation of the pial vessels without concomitant fall of the arterial blood pressure, in spite of the doses of 15 mg/kg.

Produção de hipotermia localizada no sistema nervoso central por meio de perfusão dos ventrículos cerebrais do cão

A perfusao com Tyrode a 39°C nao ocasionou modificacoes apreciaveis das temperaturas cerebral e retal. Da mesma forma, nao se observaram alteracoes pronunciadas da respiracao e da pressao arterial. As seguintes alteracoes foram verificadas com a perfusao a 0°C: a) A temperatura cerebral baixou gradativamente ate o nivel minimo de 21°C. b) A temperatura retal nao foi influenciada pela perfusao fria. As eventuais diminuicoes observadas, podem ser atribuidas a anestesia, pois ocorreram em caes utilizados para controle e, por outro lado, o aquecimento do animal preveniu a referida queda de temperatura, c) Depressao e/ou parada respiratoria foram fenomenos observados de maneira constante em todas as perfusoes. A depressao respiratoria ocorreu mesmo com temperatura cerebral ao redor de 30°C. Reiniciadas as perfusoes a 39°C, houve pronta recuperacao respiratoria, d) Bradicardia, suscetivel de ser inibida pela atropina, foi verificada em 3 animais, acompanhando-se de hipotensao arterial. Entretanto, as respostas tensionais foram variaveis: hipotensao ou hipertensao, e) Elevacao da temperatura cerebral (com tendencia a valores normais), durante a perfusao fria, foi observada em alguns animais. Conquanto nao se possa, ainda, explicar convenientemente o fato, talvez decorra de vasodilatacao secundaria, f) Em 2 animais ocorreu parada cardiaca, passivel de tratamento pela adrenalina.