Involvement of the beta-adrenergic system in the cardiac chronic form of experimental Trypanosoma cruzi infection.

Changes in the cardiac beta-adrenergic system in early stages of Trypanosoma cruzi infection have been described. Here, we studied an early (135 days post-infection-p.i.) and a late stage (365 days p.i.) of the cardiac chronic form of the experimental infection (Tulahuen or SGO-Z12 strains), determining plasma epinephrine and norepinephrine levels, beta-receptor density, affinity and function, cardiac cAMP concentration and phosphodiesterase activity, cardiac contractility, and the presence of beta-receptor autoantibodies. Tulahuen-infected mice presented lower epinephrine and norepinephrine levels; lower beta-receptor affinity and density; a diminished norepinephrine response and higher cAMP levels in the early stage, and a basal contractility similar to non-infected controls in the early and augmented in the late stage. The Tulahuen strain induced autoantibodies with weak beta-receptor interaction. SGO-Z12-infected mice presented lower norepinephrine levels and epinephrine levels that diminished with the evolution of the infection; lower beta-receptor affinity and an increased density; unchanged epinephrine and norepinephrine response in the early and a diminished response in the late stage; higher cAMP levels and unchanged basal contractility. The SGO-Z12 isolate induced beta-receptor autoantibodies with strong interaction with the beta-receptors. None of the antibodies, however, acted a as beta-receptor agonist. The present results demonstrate that this system is seriously compromised in the cardiac chronic stage of T. cruzi infection.

Thioridazine treatment prevents cardiopathy in Trypanosoma cruzi infected mice.

Trypanosoma cruzi trypanothione reductase is an enzyme that has been identified as a potential target for chemotherapy. Thioridazine inhibits it and prevented cardiopathy in mice infected with T. cruzi Tulahuen strain. As not all T. cruzi strains respond to treatment in the same way, an isolate from a chronic patient (SGO Z12) was used; parasitaemias were studied along with, survival, serology, electrocardiography, histology and cardiac beta receptor function. Parasitaemia in thioridazine (80 mg/(kg day) for 3 days) treated mice was less and lasted for a shorter period (P < 0.01), there were reduced electrocardiographic and histological alterations and significantly improved survival (80% of non-treated died). Treated mice had lower receptor affinity and higher density as a compensatory mechanism, modifying the course of T. cruzi infection (SGO Z12 isolate) and preventing the consequent cardiopathy.

Effects of clomipramine on Trypanosoma cruzi infection in mice.

Trypanosoma cruzi, widely distributed in Latin American countries, provokes Chagas disease, characterized by cardiomyopathy and mega-viscera. The drugs used currently for treatment of acute Chagas disease are highly toxic; the side-effects are undesirable and patients may abandon treatment. We have previously demonstrated that clomipramine (CLO) exerts trypanocidal effects upon epimastigotes and trypomastigotes in vitro with anticalmodulin activity. The present study analyses the effectiveness of CLO treatment in mice infected with a low number of T. cruzi, an animal model that reproduces acute, indeterminate and chronic phases of this trypanosomiasis. In this work, our results demonstrated that CLO 5 mg/kg daily for 30 days, or 2 doses of CLO 40 mg/kg given intraperitoneally at 1 h and 7 days after infection, was not toxic for the host, but was effective against the parasite in that parasitaemias became negative and only mild heart structural and electrocardiographic alterations were detected in the chronic phase in the group treated with CLO 5 mg/kg. In mice treated with CLO 40 mg/kg, none of these alterations was detected. Cardiac beta receptor density and affinity returned to normal in the chronic stage in both experimental groups. T. cruzi enzymes such as calmodulin and trypanothione reductase represent potential drug targets. It has been reported that both can be inhibited by CLO, a tricyclic drug used in clinical therapeutics. We have shown that CLO strongly decreased the mortality rate and electrocardiographic alterations; in addition cardiac beta receptor density and heart histology returned to, or close to, normality 135 days post infection. These results clearly demonstrated that CLO treatment modified significantly the natural evolution of T. cruzi infection.

Cardiac beta-receptors in experimental Chagas' disease.

Experimental Chagas' disease (45 to 90 days post-infection) showed serious cardiac alterations in the contractility and in the pharmacological response to beta adrenergic receptors in normal and T. cruzi infected mice (post-acute phase). Chagasic infection did not change the beta receptors density (78.591 +/- 3.125 fmol/mg protein and 73.647 +/- 2.194 fmol/mg protein for controls) but their affinity was significantly diminished (Kd = 7.299 +/- 0.426 significantly diminished (Kd = 7.299 +/- 0.426 nM and Kd = 3.759 +/- 0.212 nM for the control) p < 0.001. This results demonstrate that the alterations in pharmacological response previously reported in chagasic myocardium are related to a significantly less beta cardiac receptor affinity. During this experimental period serious cardiac cell alterations take place and functional consequences will be detected in the chronic phase.

Consumption of psychoactive substances in educational institutions: an inquiry into the state of affairs in the schools of Córdoba.

This study describes and analyses the consumption of psychoactive substances in educational institutions, the school environment conditions and its relation to the school standing of the students. In the first stage, a quantitative evaluation was performed, based on the records of the Second National Survey of Secondary School Students carried out in Córdoba in 2005; the second stage used a qualitative approach. A multistage probabilistic sample of 4593 students was used for the quantitative assessment. The analysis comprised summary measurements, multivariate and factorial correspondence analysis, in all cases with a significance level of p < 0.05. For the qualitative stage, an ethnographic approach was applied. The state schools were chosen using an intentional, cumulative and sequential sampling method. Ten in-depth interviews were carried out to gather qualitative data that was analyzed using the comparative constant method. Results evince that consumption is lower among morning-shift students and that grade repetition and behavior problems are associated to consumption of illegal drugs. Furthermore, it was detected that students in night-shift schools with low academic and disciplinary demand standards have a higher probability of consumption. It is clear that as academic standards decrease, consumption increases.

Mortalidad por trastornos mentales y por causas externas: análisis de una Década en Argentina / Mortality due to mental disorders and external causes: analysis of a decade in Argentina

Objetivo: analizar las tasas de mortalidad de Trastornos Mentales y del Comportamiento (TMyC) y de las Causas Externas (CE) en las Estadísticas Vitales de Argentina, periodo 2000-2009.Metodología: se utilizó las bases de datos de defunciones, Argentina, años 2000 a 2009, de la Dirección de Estadísticas e Información en Salud Ministerial. Se construyeron tasas generales y específicas. Las estimaciones poblacionales, se obtuvieron a partir del aplicativo AGEINT. Según la distribución de la variable, se utilizó análisis de la varianza o test no paramétricos. Resultados: se observa un comportamiento disímil de la tasa de mortalidad por TMyC según sexo, pero con un comportamiento similar por cada año. Los TMyC y las CE, comprometen a la población adulta del país, con tasas mayores en el grupo de varones.Conclusión: tener en cuenta el impacto de los TMyC y CE, permite diseñar políticas públicas en salud adecuadas a las realidades de cada contexto

Objective: To analyze mortality rates due to mental and behavioral disorders (MBD) and external causes (EC) using Vital Statistics of Argentina, 2000-2009.Methods: Mortality data 2000-2009 were obtained from the Bureau of Statistics and Information, Ministry of Health, Argentina. General and specific rates were set up. Population estimates were obtained from the AGEINT application. According to the distribution of the variable, analysis of variance or nonparametric tests were used.Results: Dissimilar MBD mortality rates according to sex were observed, but with a similar pattern each year. The MBD and EC affect the adult population of the country, with higher rates in the male group.Conclusion: Taking into account the impact of MBD and EC, allows the design of public policies suitable to the realities of each health context

Trypanosoma cruzi: chemotherapeutic effects of clomipramine in mice infected with an isolate obtained from an endemic area.

The susceptibility of Trypanosoma cruzi strains to nifurtimox and benznidazole has been investigated and resistant strains have been described. Some tricyclic drugs are lethal for trypomastigote and epimastigote forms of T. cruzi (Tulahuen strain) and prevent the disease in mice. We investigated whether clomipramine, a tricyclic antidepressant drug with anti-trypanothione reductase and anti-calmodulin effects, could be effective in treating Albino Swiss mice infected with trypomastigotes of a new T. cruzi isolate from a chronic patient from an endemic area of Argentina in two different treatment schedules. Both treatment schedules were effective in reducing electrocardiographic changes and preventing myocardial structural damage. The cardiac beta-receptors low affinity was compensated for by an increment in their density. This probably maintained cardiac function since 70% of the mice survived for more than 2 years even though anti-cruzipain titers remained high. These results demonstrate that clomipramine, clinically used as a neuroleptic, could be a promising trypanocidal agent for the treatment of Chagas' disease.

Cardiac beta receptors' density or affinity modified by different Trypanosoma cruzi amount.

Chagas' disease presents complex physiopathogenic mechanism, many of them poorly understood, that in our country generally produce cardiac lesions. The acute phase related with the presence of the parasite is usually asymptomatic. This report studies if the amount of T. cruzi that induced acute infection could modify the myocardiopathy evolution. Previous works have shown that Albino Swiss mice inoculated with 45 tripomastigotes (AcL) presented alterations in the cardiac pharmacological response to adrenergic agonist and antagonist studied at 30 days post-infection (p.i). Mice inoculated with 7 x 10(4) parasites/animal showed similar behaviour at 7 days p.i. We studied the involvement of the affinity and density of cardiac beta receptors in both acute groups by binding with 3H/DHA. The AcH group presented less cardiac beta receptors number (p < 0.001), but their affinity was conserved. The AcL model presented significantly less affinity (p < 0.01) but density was not different from non infected animals. beta receptors' affinity of both infected groups were similar, but AcH density was significantly diminished when compared with AcL. These studies demonstrates that the amount of T. cruzi received by the host determines and acelerates the evolution of the chagasic myocardiopathy.

Thioridazine treatment modifies the evolution of Trypanosoma cruzi infection in mice.

Thioridazine, a tricyclic drug, is known to have a direct effect on Trypanosoma cruzi, disrupting the parasites' mitochondria and kinetoplasts. In the present study, the drug was used orally, at 80 mg/kg.day for 3 days, to treat mice inoculated with low numbers of T. cruzi. The drug caused no apparent toxicity in the host. It cleared trypomastigotes from the bloodstream, prevented the histological and functional alterations of the heart normally observed in the chronic phase of the experimental disease, and greatly reduced the mortality rate compared with that in untreated, infected controls. When checked 135 days post-infection, the density of cardiac beta receptors and the cardiac histology of the treated mice were indistinguishable from those of uninfected, untreated controls. The drug is already used to treat humans, as a neuroleptic drug. It appears to be able to prevent acute infection with T. cruzi evolving into chronic disease, at least in mice, and may be a useful base from which to design new agents for the treatment of Chagas disease.

Consumption of psychoactive substances in educational institutions: an inquiry into the state of affairs in the schools of Córdoba / Consumption of psychoactive substances in educational institutions: an inquiry into the state of affairs in the schools of Córdoba.

This study describes and analyses the consumption of psychoactive substances in educational institutions, the school environment conditions and its relation to the school standing of the students. In the first stage, a quantitative evaluation was performed, based on the records of the Second National Survey of Secondary School Students carried out in Córdoba in 2005; the second stage used a qualitative approach. A multistage probabilistic sample of 4593 students was used for the quantitative assessment. The analysis comprised summary measurements, multivariate and factorial correspondence analysis, in all cases with a significance level of p < 0.05. For the qualitative stage, an ethnographic approach was applied. The state schools were chosen using an intentional, cumulative and sequential sampling method. Ten in-depth interviews were carried out to gather qualitative data that was analyzed using the comparative constant method. Results evince that consumption is lower among morning-shift students and that grade repetition and behavior problems are associated to consumption of illegal drugs. Furthermore, it was detected that students in night-shift schools with low academic and disciplinary demand standards have a higher probability of consumption. It is clear that as academic standards decrease, consumption increases.