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.

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.

Electrocardiographic characterization in Trypanosoma cruzi reinfected mice.

Chagas' disease, caused by Trypanosoma cruzi, affects approximately 20 million people. There are 3 stages in the disease: acute, intermediate and chronic, the diversity and severity of the symptoms range from a mild electrocardiographic alteration to sudden death. We have previously demonstrated that when reinfections were carried out in the acute phase they produce greater cardiac damage. The aim of the present work was to investigate whether T. cruzi reinfected mice present electrocardiographic abnormalities that could be characteristic and only achieved after reinfections. Of the mice reinfected during the acute phase 100% showed abnormalities from days 90 post-infection, with a predominance of auricle ventricle blocks (67-71%). All the mice reinfected during the chronic infection showed electrocardiographic alteration after 30 days post-first reinfection. Of the mice infected, without reinfection, 60% exhibited electrocardiographic dysfunction at 90 days post-infection. Our results demonstrated that when the host was reinfected in the acute phase, more serious electrocardiographic alterations were developed than when the reinfections were carried out in the chronic stage. Sudden death described in some chagasic patients, might be related to some of the findings described here.

Profisetinidin type tannins responsible for antioxidant activity in Copaifera reticulata.

The in vitro antioxidant and free radical scavenging properties in bark extracts of South American tree Copaifera reticulata Ducke. (Caesalpinaceae) were studied using different bioassays. Lipid peroxidation was assessed by means of the production of thiobarbituric acid reactive substances (TBARS) in rat liver homogenate. All the extracts tested were effective in this method. The highest activity was observed in the aqueous extract, showing an IC50 of 30 micrograms/ml. DNA sugar damage induced by Fe (II) salts was also used to determine the capacity of the samples to suppress hydroxyl radical-mediated degradation of DNA. Although all the extracts tested were effective in reducing oxidation of DNA, the highest activity was observed in the methanol extract, showing an IC50 of 2 micrograms/ml. Bioassay-guided fractionation of a total methanol extract monitored by luminol-enhanced chemiluminescence, together with structural elucidation using 13C NMR and FABMS, led to the identification of profisetinidin type tannins in a semi-pure fraction. The fraction containing the active compounds also reduced the production of TBARS in rat liver homogenates (IC50 = 530 micrograms/ml) and DNA damage (IC50 = 1 microgram/ml), suggesting that profisetinidins could be responsible for the free radical scavenging and antioxidant activities observed in the extracts.

Synthesis of (+/-)-11alpha-hydroxy-3-oxo-6alphaH,7alphaH, 10betaMe-eudesman-1,2-4,5-dien-6,12-olide.

The synthesis of (+/-)-11alpha-hydroxy-3-oxo-6alphaH,7alphaH, 10betaMe-eudesman-1,2-4,5-dien-6,12-olide (1), previously isolated from Melanoselinum decipiens, is described, and its structure has been corrected.

Factores que influyen en el resultado de la reseccion pancreaticoduodena. / Factors influencing the result pancreaticoduodenal resection

Se analizan los resultados obtenidos en 63 pacientes con enoplasias periampulares. El sitio, el tamamnho y la evolucion del cancer periampular, justifican una seleccion cuidadosa de cada uno de los pacientes susceptibles de tratamiento quirurgico La seleccion de los enfermos y la simplificacion del procedimiento, mediante la ligadura del munon pancreatico, son determinantes para disminuir hasta cero la mortalidad operatoria, como ocurrio en los ultimos 10 pacientes referidos en esta serie. La supervivencia a cinco anos tambien se mejora, y la morbilidad operatoria no incapacita a los enfermos si se les prescribe una dieta adecuada, con pocas grasa