[Effect of atorvastatin on Fas (CD95/Apo-1) expression in normal or ischemic brain]. / Efecto de la atorvastatina en la expresión de Fas (CD95/Apo-1) en tejido cerebral normal e isquémico.

BACKGROUND: The physiopathology of the brain ischemia includes many events such as important apoptotic mechanisms were Fas protein is expressed. Statins have neuroprotector effects that are independent of their blood lipid reducing actions. OBJECTIVE: Study of the atorvastatin effect on Fas expression in brain ischemia. MATERIAL AND METHODS: Fifteen male Sprague Dawley rats were distributed in three groups (n=5), the control group without cerebral ischemia, in the other two experimental groups (1 and 2) a global cerebral ischemia were induced by respiratory arrest (D-tubocurarin). Experimental group 2 was treated with atorvastatin (10 mg/Kg/d, p.o.) during two weeks before the induction of the ischemia. Immunohistochemical study of brain frontal specimens was done by the Avidin-Biotin-Peroxidase method. RESULTS: Fas was expressed in 38% of cells in non ischemic brain, this expression increased to 63% of cells in ischemic brain samples (P = 0.0003) Fas expression in ischemia was significantly inhibited by atorvastatin in 23% (P = 0.0007). CONCLUSIONS: Atorvastatin decreased Fas expression in ischemic brain. This fact must be taken into account to explain the atorvastatin neuroprotection and suggests the potential use such as primary prevention for ischemic attacks.

Primary cardiomyopathy in identical twins.

Seventeen year old identical twin brothers with no family history of cardiopathy began experiencing palpitations almost simultaneously. In both, examination revealed marked cardiomegaly and hypokinesia of the ventricular walls, and clinical and radiologic signs of progressive cardiac failure developed a few days later. Both boys died suddenly, 49 days and 5 months, respectively, after the initial examination. Electrocardiographic and vectorcardiographic studies revealed a severe intraventricular conduction disturbance that coincided with histologic changes in the myocardial tissue, including profuse interstitial fibrosis, hypertrophy and degeneration of the myocardial fibers, aberrant arrangement of the muscular fibers and considerable alteration of the structure of cardiac tissue. In the absence of hereditary and chromosomal factors, and excluding possible viral intervention during fetal life, it is believed that a teratogenic factor can produce the structural alterations of the tissue and derangement of the fibers observed in these hearts. The irregular contractions of the heart at the level of the net-like meshwork, disarrangement of myocardial fibers, and adaptative mechanisms of the heart inherent in the destruction of the contractile tissue contributed to the functional cardiac disorders that resulted in congestive heart failure and sudden death in these twins.

Overexpression of neural cell adhesion molecule in Chagas' myocarditis.

The expression of the neural cell adhesion molecule (NCAM) was studied in normal human myocardium and in Chagas' disease myocarditis. We found that NCAM is expressed in the conduction system as well as the myocardium in the fetal heart, but its expression is restricted to the conduction system and absent in the adult myocardium. Chagas' disease is an American endemic disease caused by the Trypanosoma cruzi parasite, which produces myocarditis and a blockade of the conduction system, resulting in cardiac dysfunction. We studied the expression of NCAM in paraffin-embedded human heart tissues from 34 autopsies of patients with Chagas' myocarditis and from murine and canine experimental acute Chagas' myocarditis, using a polyclonal anti-NCAM antibody and immunohistochemistry. Our results show a dramatic upregulation of NCAM expression in the intercalated discs of cardiomyocytes in acute and chronic Chagas' myocarditis. Surprisingly, the NCAM signal was detected in intracellular nests of amastigote forms of the parasite, within infected cardiomyocytes of human and experimental Chagas' myocarditis. In contrast, cardiac cell-cell adhesion proteins, N-cadherin and beta-catenin, were found in intercalated discs distorted by the infection but absent from the amastigote nests. Proteins reactive to several antibodies against NCAM were detected by Western immunoblotting in cultured T cruzi parasites and in trypomastigote forms of T cruzi extracted from the blood of infected mice. The upregulation of NCAM in Chagas' myocarditis and the expression of NCAM or a NCAM-like protein by T cruzi suggest that NCAM may act as a receptor for tissue targeting and cellular invasion by T cruzi in Chagas' disease.

[Extrarenal effects of furosemide on normal and ischemic cerebral tissue in the rat]. / Efectos extrarrenales de la furosemida en el tejido cerebral normal e isquémico de la rata.

INTRODUCTION: Recent studies suggest that furosemide (FUR), a chloride cotransporting antagonist, acts directly on neurons of central nervous system modifying the ionic flow. OBJECTIVE: The aim of the present study was to determine the extrarenal antiedema effect of FUR. MATERIAL AND METHODS: Male Sprague-Dawley rats were anesthetized with tiobarbital (60 mg/kg-1 ip), bilaterally nephrectomized and perfunded iv with solution of Ringer (RIN) (n= 5) or FUR (40 mg/kg-1) (n= 6), in equivalent volumes. The diuretic effect of FUR was excluded by bilateral nephrectomy. Two tungsten microelectrodes implanted on the cerebral cortex, registered the tissue impedance by the voltage fall of a square wave electric pulse (100 mA, 10 ms) tested every 120 seconds, before and after infusion of FUR or RIN and during global cerebral ischemia by D-tubocurarine induced respiratory arrest. RESULTS: Preischemic FUR infusion induced a significant increase of voltage (t= 15.68; p< 0.0001). During global cerebral ischemia, the voltage fall was significantly lower in FUR than for RIN infusion (Wilcoxon Z= 3.9; p< 0.00001). CONCLUSION: These results suggest that FUR reduced significantly the cerebral impedance i.e. antiedema effect, by an extrarenal action, under both basal and ischemia conditions.

Efecto de la atorvastatina en la expresión de Fas (CD95/Apo-1) en tejido cerebral normal e isquémico / Effect of atorvastatin on Fas (CD95/Apo-1) expression in normal or ischemic brain

Introducción: La fisiopatología de la isquemia cerebral involucramúltiples eventos, entre ellos, importantes mecanismos apoptóticos dondela proteína Fas es expresada. Las estatinas poseen efectos neuroprotectoresindependientes de sus acciones hipolipemiantes.Objetivo: Estudiar el efecto de la atorvastatina sobre la expresión deFas en tejido cerebral isquémico.Material y métodos: Quince ratas Sprague Dawley, machos, fuerondistribuidas en tres grupos (n = 5): un grupo control sin isquemia cerebral ydos experimentales (1 y 2) sometidos a isquemia cerebral global inducidapor paro respiratorio con D-tubocurarina. El grupo experimental 2 recibióatorvastatina durante las dos semanas previas a la inducción de isquemia(10 mg/kg/día, v.o.). Se realizó inmunohistoquímica por el sistema Avidina-Biotina-Peroxidasa a muestras de la corteza cerebral frontal.Resultados: Fas se expresó en el 38% de las células del tejido noisquémico. Esta expresión aumentó en el tejido cerebral isquémico a63% (P = 0,0003). La atorvastatina inhibió significativamente la expresiónde Fas en tejido cerebral isquémico en un 23% (P = 0,0007).Conclusiones: La atorvastatina disminuyó la expresión de Fas enisquemia cerebral, contribuyendo posiblemente a una inhibición de laapoptosis. Este mecanismo de acción pudiera explicar parte de su efectoneuroprotector. Estos hallazgos sugieren que la atorvastatina pudieraresultar beneficiosa en la prevención primaria de los ataques isquémicos

Background: The physiopathology of the brain ischemia includes many events such as important apoptotic mechanisms were Fas protein is expressed. Statins have neuroprotector effects that are independent of their blood lipid reducing actions. Objective: Study of the atorvastatin effect on Fas expression in brain ischemia. Material and methods: Fifteen male Sprague Dawley rats were distributed in three groups (n=5), the control group without cerebral ischemia, in the other two experimental groups (1 and 2) a global cerebral ischemia were induced by respiratory arrest (D-tubocurarin). Experimental group 2 was treated with atorvastatin (10 mg/Kg/d, p.o.) during two weeks before the induction of the ischemia. Inmunohistochemical study of brain frontal specimens was done by the Avidin- Biotin-Peroxidase method. Results: Fas was expressed in 38% of cells in non ischemic brain, this expression increased to 63% of cells in inchemic brain samples (P = 0.0003) Fas expression in ischemia was significantly inhibited by atorvastatin in 23% (P = 0.0007) Conclusions: Atorvastatin decreased Fas expression in ischemic brain. This fact must be taken into account to explain the atorvastatin neuroprotection and suggests the potential use such as primary prevention for ischemic attacks

Efectos extrarrenales de la furosemidaen el tejido cerebral normal e isquémico de la rata / Extrarenal effects of furosemide on normal and ischemic cerebral tissue in the rat

Introducción. Recientes estudios sugieren que la furosemida (FUR), conocido antagonista del cotransportador de cloruro, actúa directamente en las neuronas del sistema nervioso central modificando el flujo iónico. Objetivo. El objetivo del presente estudio fue determinar esta acción de FUR sobre el edema isquémico cerebral. Material y métodos. Once ratas Sprague-Dawley machos fueron anestesiadas con tiobarbital (60 mg/kg-1 ip), nefrectomizadas bilateralmente y perfundidas con solución de Ringer iv (RIN) (n= 5) o FUR (40 mg/kg-1) (n= 6), en volúmenes equivalentes. El volumen extracelular en la corteza cerebral fue estimado mediante el uso de dos microelectrodos de tungsteno, registrándose la caída de voltaje de un pulso eléctrico de onda cuadrada (100 mA, 10 ms) aplicado cada 120 segundos, antes y durante la infusión de FUR o RIN y durante la isquemia cerebral global inducida por paro respiratorio debido a D-tubocurarina. Resultados. La infusión de FUR en el período preisquémico indujo una disminución significativa de la impedancia tisular cerebral (t= 15,68; p< 0,0001). Durante la isquemia cerebral global, la caída del voltaje fue significativamente más baja para FUR que para RIN (Wilcoxon Z= 3,9; p< 0,00001).Conclusión. Estos resultados sugieren que la furosemida redujo significativamente la impedancia cerebral y, por lo tanto, disminuyó el volumen extracelular cerebral por una acción extrarrenal, tanto en condiciones basales como durante la isquemia (AU)