Biomedical subjects
R Castilla
Publications and source records attributed to R Castilla.
N-acetyl-D-glucosamine induces germination in Candida albicans through a mechanism sensitive to inhibitors of cAMP-dependent protein kinase.
The present study examines the involvement of cAMP-dependent protein kinase (PKA) in the dimorphic transition of Candida albicans by assessing the in vivo effect of two permeable PKA inhibitors on N-acetyl-D-glucosamine (GlcNAc)- and serum-induced differentiation. The permeable myristoylated derivative of the heat-stable PKA inhibitor (MyrPKI), which inhibited C. albicans PKA in vitro, caused a concentration-dependent inhibition of germ-tube formation in cultures induced to germinate by GlcNAc; germination halted irrespective of the time of addition of the inhibitor. MyrPKI also blocked dibutyryl-cAMP (dbcAMP)- and glucagon-stimulated germination but did not affect serum-induced germination. H-89, another highly specific PKA inhibitor, displayed the same effect on germination. Neither MyrPKI nor H-89 had any effect on budding of yeast cells. In conclusion, our results indicate that cAMP-mediated activation of PKA plays a pivotal role in the biochemical mechanism underlying morphogenesis.
Reassessment of the effect of glucagon and nucleotides on Candida albicans germ tube formation.
The role of cyclic AMP in the process of germ tube formation in Candida albicans was investigated. The exogenous supply of the nucleotide or of agents that raise its intracellular levels stimulated germination induced by N-acetyl-D-glucosamine; glucagon showed this same stimulatory effect on yeast cell transition to the hyphal form. Compounds, included glucagon, that stimulated hyphal formation, also notably enhanced the development of hyphae. The stimulatory effect of glucagon on germination was blocked by the specific antagonist des His1 [Glu9] glucagon amide, probably indicating an interaction of the hormone with a glucagon-like receptor on the membrane of the cells. Indirect immunofluorescence experiments showed that glucagon binds to the yeast cell surface. When N-acetyl-D-glucosamine was replaced by serum as inducing agent of germination, the stimulatory effect of glucagon was substantially augmented, the resulting of germination being more than 2.5-fold greater than that attained in the presence of N-acetyl-D-glucosamine; moreover, the glucagon concentration needed for half maximal stimulatory activity with serum as inducing agent was at least 50-fold lower than with N-acetyl-D-glucosamine. Monoclonal and polyclonal anti-glucagon antibodies blocked the effect of the hormone. An interesting result observed during these experiments was the fact that a definite period of incubation of C. albicans yeast cells with N-acetyl-D-glucosamine as inducer commits them to hyphal development. When serum was used as inducer, only yeast cells evaginated during the initial incubation period evolved to the hyphal form upon further incubation in the absence of serum.
Giant T waves simulating apical hypertrophic myocardiopathy that disappear with sodium nitroprusside administration. Case report of pheochromocytoma.
Giant inverted T waves (amplitude greater than 1 mV) in precordial leads have been described in various disease processes. However, the pathophysiology of these anomalies has not been studied in depth. This paper analyzes repolarization abnormalities occurring in a case of pheochromocytoma in which giant T waves were unaffected by alpha-adrenergic blockade but were affected by administration of sodium nitroprusside. It is postulated that the probable cause of this aberration is myocardial ischemia of noncoronary origin resulting from an imbalance of supply and demand of oxygen that is relieved by the hemodynamic action of nitroprusside when left ventricular wall stress is reduced.
[Postoperative course of prosthetic valve replacement].
In order to know the post-operative outcome of patients with valvular replacement due to prosthetic dysfunction, we reviewed the clinical charts of 94 patients operated at the Instituto Nacional de Cardiología "Ignacio Chávez" between January 1986 and December 1988. Eighty four cases were replaced by the first time the remaining 10 by a second time. Diagnosis of prosthetic dysfunction was made by clinical, radiological, echocardiographic and haemodynamic parameters. The most frequent causes of dysfunction were the rupture of prosthetic leaflets, stenosis with calcific deposition and paravalvular leaks. The global mortality rate was 19.15%, higher than the native valve replacement group. The most important predictors of surgical mortality were: 1) poor ventricular function (functional classes III and IV), 2) aortic clamping period, 3) the need of a second prosthetic replacement and 4) the time of prosthetic dysfunction. Thus, we conclude that it is of great importance the early recognition of prosthetic valve dysfunction. The need of special surgical procedures in these cases should be evaluated in order to reduce morbidity and mortality.
[Public health campaign against superficial mycoses in the Province of Granada. 1st results].
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