Cytochrome P-450 and drug metabolism in Trypanosoma cruzi: effects of phenobarbital.

The epimastigotes of Trypanosoma cruzi hydroxylate drugs at substantial rates. The activity, which is of the mixed-function oxidase type, is increased by phenobarbital and is inhibited by CO, SKF 525-A, and metyrapone. The hydroxylation is paralleled by increases in free and membrane-bound ribosomes.

Fasciola hepatica cysteine proteinases: immunodominant antigens in human fascioliasis.

Fasciola hepatica adult worm cysteine proteinases were active-site, affinity radio-labeled with benzyloxicarbonyl-L-tyrosine-L-alanine diazomethylketone (Z-Tyr125I-Ala-CHN2). Sera from patients with fascioliasis and from rabbits experimentally infected with F. hepatica immunoprecipitated the radiolabeled parasite cysteine proteinases in immunoelectrophoresis assays. Two purified antigens were identified as part of the complex mosaic of antigens immunoprecipitated by the sera of infected patients. These antigens (Fas1 and Fas2) have been shown to be an important part of the Fharc2 precipitin band used for serologic diagnosis in humans and cattle. They showed cysteine proteinase activity with different proteolytic specificities and partial identity in double immunodiffusion assays. The results obtained in this work show that the Fas1 and Fas2 antigens are sensitive and specific antigens for diagnosis of this serious helminthic disease in humans and other susceptible hosts.

Ivermectin for human strongyloidiasis and other intestinal helminths.

Since ivermectin, a mixture of 2 closely related macrocyclic lactones, has proven highly effective against animal intestinal nematodes, trials were undertaken to determine its efficacy against human intestinal nematodes. We tested 110 patients with strongyloidiasis and 90 with enterobiasis; many had other intercurrent intestinal nematode infections. Stool examinations were done before and after patients were given a single dose of oral ivermectin capsules (50, 100, 150, or 200 micrograms/kg body wt); 55 recipients of 100 or 200 micrograms/kg doses received a second identical dose the next day. Kato and saline smears, ethyl acetate concentration, modified Baermann's technique, and Harada-Mori cultures were repeated; cure was defined as complete absence of eggs and/or larvae from stools tested 30 days after dosing. Ivermectin was well tolerated. Overall cure rates at all doses 30 days after therapy averaged 88% for strongyloidiasis, 100% for ascariasis, 85% for trichuriasis, and 85% for enterobiasis. Ancylostoma duodenale and Necator americanus were little affected.

Preclinical and clinical studies with latex from Ficus glabrata HBK, a traditional intestinal anthelminthic in the Amazonian area.

Ficus glabrata latex has been a well-known anthelminthic remedy in the neotropical regions since ancient times. The latex has been commercially exploited for decades because of its content of the proteolytic enzyme-complex ficin. A safe dosage regimen with direct use of the latex has been elucidated to control intestinal helminthiasis in the Indian and non-Indian rural population. Helminthiasis was common in three Amazonian villages, field bases for the clinical study, with an overall prevalence of 92%. Specific prevalences were: Ascaris 68%, Strongyloides 42%, Trichuris 41%, Ancylostoma/Necator 26% and Taenia 1%. Variation in the biological activity of the latex was estimated by using a milk coagulating test. Pharmacological studies with live Ascaris demonstrated a lethal effect at concentrations down to 0.05% latex in physiological saline solution. A clinical trial on 181 persons has resulted in a recommended dosage of 1.0 cm3 of prepared latex/kg per day for 3 days to be repeated every 3 months.

[AMEBIOSIS] / Amebiosis.

This is a short review of the infection and disease caused by Entamoeba histolytica. The morphology of the evolutive stages and the life cycle of the parasite is described, including biochemical and immunological data.The intestinal and extraintestinal forms of this disease are briefly characterized as well as the diagnosis by images and laboratory. Differentiation between E. histolytica and E. dispar (known as nonpathogenic E. histolytica) with similar morphology is crucial for individual or mass treatment.This treatment is dealing with the better known drugs and their recommended dosis. The infection by E. histolytica/E. dispar is widely distributed in Peru with variable rates of prevalence (1 to 28%), according with the applied methodology, and the studied population. Recently, the presence of both amoebas has been confirmed by biochemical characterization, and their real prevalence must be determined. The profilaxis and control of this parasitism is based in avoiding fecalism. Sanitary education, environmental sanitation, and mass treatment of risk groups would be the most important measures against ameblasis.

Translation of Taenia crassiceps mRNA in cell-free heterologous systems.

1. mRNA isolated from larval Taenia crassiceps directs efficiently the synthesis of proteins in cell-free heterologous systems. 2. Part of the newly synthesized proteins in a reticulocyte system are precipitable by a rabbit antiserum against T. crassiceps proteins. 3. Analysis of the antiserum-protein dissociated complex by sodium dodecyl sulfate polyacrylamide gel electrophoresis indicates that most of the proteins synthesized are of low molecular weight (13,000-22,000) although a protein of mol. wt. 260,000 is also produced. 4. Whether the newly synthesized proteins which are precipitable by specific antisera correspond to parasite antigens or to proteins with closely antigenic similarities remains to be established.

Effect of food on the bioavailability of triclabendazole in patients with fascioliasis.

AIMS: Preliminary results indicate higher absorption of triclabendazole (TCBZ) administered postprandially. Therefore, the influence of food on the pharmacokinetics of TCBZ and its active sulphoxide (TCBZ-SO) and sulphone (TCBZ-SO2) metabolites was investigated. METHODS: Two single doses (10 mg kg(-1)) of TCBZ were administered to 20 patients with fascioliasis. Ten patients were first given the drug after a high energy breakfast and then, 48 h later, after an overnight fast. The other 10 patients first received the drug in fasting state and then, 48 h later, after breakfast. A low energy breakfast was served 2 h after drug administration for fasting state. RESULTS: Compared with the fasting state, an increased AUC and Cmax after food intake (significant, P < 0.0001) was shown from the values of TCBZ, TCBZ-SO and TCBZ-SO2. The mean AUC for TCBZ (fasting: 1.55, fed: 5.72 micromol l(-1) h), TCBZ-SO (fasting: 177, fed: 386 micromol l(-1) h) and TCBZ-SO2 (fasting: 13.9, fed: 30.5 micromol l(-1) h) indicated a large availability increase with food and the strong systemic predominance of the active sulphoxide metabolite over the unchanged drug. (All patients were cured at the end of the trial except one who required a second course of two postprandial doses of triclabendazole (10 mg kg(-1) each). Tolerability to the treatment among the patients was good. CONCLUSIONS: The administration of triclabendazole with food is recommended for improved systemic availability in patients with fascioliasis or paragonimiasis.

[Unwanted children: incidence and characteristics among puerperal women in a hospital of Santiago]. / Hijo no deseado: incidecia y carcterísticas en puérperas de un hospital de Santiago.

A scoring instrument to detect unwanted newborns was applied to 556 living-in women at a Santiago urban hospital in december 1987. Based upon previous research a scoring instrument including 10 items was designed and applied within 24 hours following delivery. According to the total score each newborn was classified as wanted (W), unwanted (U) or doubtful situation: 37.6% of children were born to unwed mothers. In a total of 556 children 4.5% (n = 25) were classified as U, 91.4% as W (n = 508) and 4.1% as doubtful (n = 23). Comparing U and W children the former had mothers with poorer education, higher frequency of bad relationships with their partners as well as higher proportion of three or more previous deliveries and late beginning of prenatal care (significant). On the other hand no significant differences were detected in age distribution of the mothers or their socio-economic level. The applicability of this scoring system and the magnitude and importance of the problem are analyzed and discussed. The need for further research on the natural history of the sequence unwanted pregnancy-unwanted child is stressed.

A simplified cuture method for blastocystis hominis

Aquí es descrito un método simplificado de cultivo de Blastocystis hominis. Se inocularon doscientas muestras fecales frescas en tubos que contenían un medio de Pavlova modificado. Los tubos herméticos fueron incubados a 36oC sin ningún sistema adicional de anaerobiosis convencional. Los cultivos fueron examinados después de 24, 48 y 72 horas. En conjunto, 140 (70 por ciento) de los cultivos fueron positivos para B. hominis, mientras que el monto del examen microscópico en fresco fue positivo sólo en 42 (21 por ciento) muestras. Se observaron las diferentes formas del parásito descritas con el método estándar. Este método es propuesto como una alternativa al convencional.