This study was undertaken to determine the effects of progesterone on the peripheral circulation. In prepubertal female pigs anesthetized with sodium pentobarbitone, changes in the superior mesenteric, left renal and left external iliac flow caused by intravenous infusion of progesterone were assessed using electromagnetic flow meters. Changes in heart rate and arterial blood pressure were prevented by atrial pacing and by connecting the arterial system to a pressurized reservoir containing Ringer solution. In 20 pigs, infusion of 1 mg/kg of progesterone increased mesenteric, renal and iliac flow. In a further 4 pigs, the vasodilatory effects of the hormone were enhanced by graded increases in the dose between 1, 2 and 3 mg/kg. The mechanisms of these responses were studied in the 20 pigs by repeating the experiment after hemodynamic variables had returned to the control values before infusion. In 5 pigs, blockade of adrenergic receptors with propranolol and phentolamine did not affect the responses elicited by progesterone. The increases in mesenteric, renal and iliac flow to progesterone were prevented, respectively, by the injection of N(omega)-nitro-L-arginine methyl ester into the mesenteric (5 pigs), the renal (5 pigs) or the iliac artery (5 pigs). The present study shows that intravenous infusion of progesterone dilated mesenteric, renal and iliac circulations. The mechanism of this response involved the release of nitric oxide.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Effects of insulin on coronary blood flow in anesthetized pigs.

Insulin can influence the vasculature by a sympathetically mediated vasoconstriction and a vasodilatation; the latter effect predominates in the renal circulation of anesthetized pigs. We determined the effect of intravenous infusion of insulin on coronary blood flow in pentobarbitone-anesthetized pigs at constant heart rate, arterial pressure and blood levels of glucose and potassium. In 6 pigs, infusion of 0.004 IU kg(-1) min(-1) of insulin decreased coronary flow despite increasing left ventricular dP dT(max)(-1); when the latter was abolished by propranolol, the coronary flow response was augmented. The mechanisms of this response were examined in 22 pigs given propranolol. Phentolamine changed coronary flow response to an increase (6 pigs) and this was abolished by intracoronary injection of N(omega)-nitro-L-arginine methyl ester (L-NAME; 5 pigs). L-NAME augmented coronary flow response (6 pigs) and this was abolished by phentolamine (5 pigs). In 18 pigs given propranolol, three incremental doses of insulin caused graded coronary flow decreases whether L-NAME was given (6 pigs) or not (6 pigs) beforehand, and caused graded coronary flow increases after phentolamine (6 pigs). Thus insulin caused a coronary vasoconstriction mediated by sympathetic alpha-adrenergic effects and a vasodilatation related to the release of nitric oxide. The net effect was a coronary vasoconstriction.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Prognostic value of mutations in TP53 and RAS genes in breast cancer.

The identification of molecular indicators of higher risk for specific subgroups of cancer patients may allow to develop more aggressive therapeutic strategies aimed at cases with the highest likelihood of response. This would avoid unnecessary toxicity to patients and alleviate the burden of cancer care for healthcare systems. Activated oncogenes and mutated tumor suppressor genes are causal determinants of the appearance and progression of tumors in man. They therefore represent potential indicators of prognosis and/or response to therapy. However, even in cases of well-studied oncogenes and tumor suppressor genes such as TP53 and RAS, their attributed prognostic and predictive value is often based on studies of insufficient statistical power that often lead to conflicting conclusions. Findings in favor or against the use of TP53 and RAS as prognostic and predictive indicators in breast cancer are reviewed and discussed here.

Animals↗

PubMedDate not supplied

[Effect of Bunaftine on the ventricular tachycardia due to aconitine in the dog].

Suppression of aconitine-induced ventricular tachycardia in the dog with various doses of Bunaftine was attempted. Stable re-establishment of the sinus rhythm was achieved in only 3/15 cases, whereas in 3 tachicardia was unchanged, and in 9 fibrillation appeared, due, it is thought, to the effect of the drug on myocardial conductivity, since fibrillation was the most frequent outcome when high doses were used.

Aconitine↗