Search

By March 1989, almost 91,000 cases of AIDS had been reported, and the number of new cases has continued to rise dramatically. Complications involving the kidneys (AIDS-associated nephropathy, AAN) are more prevalent in New York City and Miami, where there are high proportions of black patients and intravenous drug abusers (IVDA), compared with San Francisco. AIDS patients at a Washington, D.C. medical center were studied to assess the possible association between race and development of AAN; the patient population had a low rate of IVDA and a high prevalence of homosexuality. In all, 330 homosexual patients were studied. Of these patients, 62 percent were black and 37 percent were white. Although there were no differences in clinical characteristics between the racial groups, there was a highly significant difference in the prevalence of chronic renal (kidney) failure; blacks were far more likely to suffer from kidney complications. A previous suggestion that homosexuality confers some kind of kidney-protective effect is not supported by this study. Previously, racial differences in the prevalence of kidney disease as a complication of high blood pressure and of kidney disease resulting from heroin abuse have been noted, along with differences in circulatory responses, plasma volume, and hormonal responses. However, it is not clear whether these differences are racial, dietary, or the result of differences in socioeconomic level. (Consumer Summary produced by Reliance Medical Information, Inc.)

En la retinopatía de la prematuridad (ROP) tipoI, el uso de bevacizumab intravítreo (IVB), el cual es un inhibidor del factor de crecimiento endotelial (VEGF), se ha popularizado a pesar de no ser una terapia aprobada por los entes regulatorios, pero que ha demostrado tener efectos positivos para detener la progresión de la enfermedad a costos menores en comparación con otras terapias anti-VEGF (ranibizumab o aflibercept). En este reporte describimos la experiencia obtenida durante el tratamiento con IVB de 102 niños colombianos con ROP tipoI, con un porcentaje de éxito del 98% (100) y complicaciones del 3,9% (4). Finalmente, se concluye que una sola dosis de IVB es una terapia efectiva para el manejo de la ROP, con un menor riesgo de complicaciones y una baja probabilidad de retratamiento.

The effects of diprafenone, a new class Ic antiarrhythmic agent, on canine hemodynamics and cardiac membrane β-receptor antagonist binding activity, were compared with those of propafenone and propranolol. Mongrel dogs (4–5/group) were anesthetized intravenously (i.v.) with pentobarbital sodium (35 mg/kg) and instrumented for measurement of aortic and coronary blood flows (AF, CBF), blood pressure (BP), and heart rate (HR). Isoproterenol (ISO) was administered as bolus injections before (0.01, 0.03, and 0.1 μg/kg, i.v.) and after (0.01–3 μg/kg, i.v.) infusions of diprafenone or propafenone (0.3, 1, and 3 mg/kg) or propranolol (0.03, 0.1, and 0.3 mg/kg, i.v.). The ability of the antiarrhythmic agents to displace [3H]dihydroalprenolol (DHA) binding from isolated cardiac ventricular membranes in vitro was also evaluated. Each antiarrhythmic agent blocked the HR and BP responses to ISO in a competitive manner and decreased the specific binding of DHA to cardiac ventricular membranes. Propranolol was 2 to 7 times more potent as a β-receptor blocking agent than diprafenone, which was 6 times more potent than propafenone. The equilibrium dissociation constants (Ki) for displacement of DHA by propranolol, diprafenone, and propafenone were 2.7, 14.3, and 252 nM, respectively, and have the same rank order of potency for in vivo inhibition of BP and HR responses to ISO. Diprafenone has significant β-adrenoceptor blocking activity which may contribute to its efficacy as an antiarrhythmic agent and allow its use in treatment of arrhythmias refractory to therapy with class I and class II agents alone.

The biosynthesis of poly(l-alanylglycine) (poly(AG)) was performed in high cell density cultures of recombinant Escherichia coli. The purity of the material was determined by amino acid analysis, elemental analysis, and ¹H NMR spectroscopy. Fed batch fermentation increased the yield of recombinant protein from levels of tens of milligrams per liter (typical of batch fermentation in rich media) to hundreds of milligrams per liter. Poly(AG) comprising 64 diads [(AG)64] was recrystallized from dichloroacetic acid solutions in the form of texture-oriented chain-folded lamellae with a lamellar stack periodicity of 3.2 nm. The crystal structure within the lamellar core is similar in general, but different in detail, to the antiparallel β-sheet structure previously reported for oriented films of poly(AG) and fibers of Bombyx mori silk fibroin (silk II). The structure consists of polar antiparallel (ap) β-sheets, with repetitive folding through γ-turns every eighth amino acid (including the fold), stacking with like surfaces together. The wide-angle X-ray diffraction signals index on an orthorhombic unit cell with a (hydrogen bond direction) = 0.948 nm, b (sheet stacking direction) = 0.922 nm, and c (chain direction) = 0.695 nm. The stacking distance (b-value) is increased by about 3% in comparison with the previously reported structure of poly(AG), owing, we believe, to steric interaction at the lamellar fold surfaces. Random shears of approximately ±a/4 and shears of ±c/2 in the ac plane are required to obtain a good fit between the calculated and measured X-ray structure factors.

The hypotensive effect of atropine sulfate was evaluated in conscious, unanesthetized hypertensive rats (spontaneously hypertensive rats and Sprague-Dawley rats made hypertensive by s.c. implantation of deoxycorticosterone acetate, tablets) and their respective normotensive controls. In all animals, atropine (5-50 mg/kg i.v.) caused an immediate and dose-dependent decrease in blood pressure. However, the hypotensive response was of greater magnitude and of longer duration in the hypertensive rats. Pretreatment of the animals with phentolamine prevented the hypotension by atropine. Plasma concentrations of atropine were determined by radioimmunoassay and were identical in both hypertensive and normotensive rats. Atropine blocked the pressor responses to norepinephrine and shifted the dose-response curve for norepinephrine to the right to a similar extent in spontaneously hypertensive and Wistar-Kyoto rats. Thus, atropine acts as a competitive antagonist of norepinephrine and this action underlies its hypotensive effect. The greater responsiveness of hypertensive rats is not due to a difference in pharmacokinetic handling of atropine nor to a greater degree of blockade of the norepinephrine pressor response in vivo, but may result from the altered sympathetic tone in the hypertensive rats. Atropine may, in addition to its action on alpha adrenergic receptors, affect other systems such as calcium handling. It is speculated that an effect on this system may contribute to the longer duration of response seen in hypertensive rats.

The administration of guanethidine to newborn rats has been shown by morphological criteria to destroy sympathetic neurons. Newborn rats were injected with guanethidine (50-100 mg/kg/day for 20 days). Upon maturation (at 10 weeks old), the degree of destruction of the sympathetic nervous system (sympathectomy) was assessed. Marked decreases (80-98%) in the norepinephrine concentration in several tissues (heart, spleen, intestine, mesentery, kidney, uterus, vas deferens) were observed in the guanethidine-treated rats when compared to saline-treated controls. No changes were observed in the epinephrine concentration in the adrenals or in the norepinephrine levels in whole brain. Analysis of brain areas showed no change in the norepinephrine levels in brain stem and cerebrum and a small (18%) decrease in the cerebellum. Stimulation of the sympathetic vasomotor outflow in the pithed rat preparation produced almost no response in guanethidine-treated animals. Periarterial nerve stimulation of the isolated perfused kidney preparation also produced essentially no response in guanethidine-treated animals. Isolated intestinal preparations from guanethidine-treated animals responded to nerve stimulation with contractions rather than relaxation as seen in preparations from control animals. Isolated vas deferens preparations responded normally to nerve stimulation despite a 95% decrease in tissue norepinephrine concentration. These data indicate that administration of guanethidine to newborn rats produces a more complete peripheral sympathectomy, especially of the vasculature, than immunosympathectomy or neonatal administration of 6-hydroxydopamine and does so with no significant effect on central noradrenergic neurons.

Nicorandil increases cyclic 3'5'-guanosine monophosphate (cGMP) in vascular smooth muscle. However, high concentrations are required to activate guanylate cyclase (GC). We examined the relationship between activation of GC, increases in cGMP and relaxation in canine mesenteric artery and vein, renal and coronary artery and thoracic aorta. Nicorandil (10-100 microM) relaxed in each of the blood vessels. Relaxation was associated with elevations of cGMP but independent of release of endothelium-derived relaxing factor, and inhibited by methylene blue and hemoglobin. The organic nitrate esters nitroglycerin, pentaerythritol tetranitrate, isosorbide dinitrate, 2-isosorbide mononitrate, and 5-isosorbide mononitrate each behaved in a similar manner. In each blood vessel pentaerythritol tetranitrate was the most potent and 5-isosorbide mononitrate the least potent relaxant and stimulant of cGMP. Each of the organic nitrate esters (1 microM to 1 mM) except nicorandil stimulated soluble GC activity in the presence of 10 mM cysteine. Nicorandil (EC50 38 mM) increased GC activity. Moreover, nicorandil (0.1 microM to 30 microM) did not inhibit cGMP phosphodiesterase. The EC50 for vascular relaxation was directly correlated with the EC50 for elevation of cGMP for each of the agonists in each blood vessel type. The EC50 for activation of GC was directly related to the reciprocal of the rate constant for nitric oxide formation for each of the organic nitrate esters. However, a direct correlation existed between the EC50 for activation of GC and the EC50 for 1) elevation of cGMP and 2) relaxation, for each of the organic nitrate esters except nicorandil. Thus, the high concentrations of nicorandil required to activate GC cannot account for the low concentrations required to elevate cGMP or relax smooth muscle. We postulate that nicorandil may interact with a membrane receptor or release a second messenger, distinct from nitric oxide or endothelium-derived relaxing factor, which then activates GC. This may represent a physiologic mechanism for regulation of GC activity in smooth muscle.