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Phosphodiesterase inhibitory properties of losartan. Design and synthesis of new lead compounds.


Cases with cardiac hydatid cyst disease are uncommon, being approximately 0.2-2% of all cases. Most cardiac hydatid cysts are located in the interventricular septum or left ventricular wall. Pericardial location is very rare. We report a 42-year old Turkish man with pericardial hydatid cyst disease who was otherwise asymptomatic, having no cardiac symptomatology. The most appropriate therapeutical option for a hydatid cyst is surgical removal of the cyst mass. However, our patient refused surgical treatment and thus medical treatment with albendazole was initiated. Following the first month of the drug therapy, pericardial effusion disappeared. The cystic nature of the mass disappeared and was solidified at the 6th month of treatment. The patient has been followed-up by us asymptomatically.

Protoscolices of Echinococcus granulosus were incubated in vitro with praziquantel (PZ), albendazole (ABZ), or a combination of both (PZ + ABZ). PZ and ABZ displayed slower protoscolicidal activity when applied separately than when used in combination. Despite the low PZ + ABZ concentrations used, protoscolex viability dropped rapidly (within 15 days). At this time, cysts did not develop following their inoculation into mice. The ultrastructural changes induced in the protoscolices by PZ + ABZ were (a) the loss of sucker concavity, (b tegumental contraction of the soma region, (c) the formation of digitiform tegumental extensions, (d) destruction of the tegument, and (e) the degeneration of parenchyma cells as reflected by the presence of numerous lamellar bodies. The PZ + ABZ treatment was effective only against small cysts, which had collapsed at 10 days postinoculation (p.i.). This treatment caused the following alterations: (a) loss of cyst turgidity at 6 days p.i.; (b) separation of the laminated and germinal layers; (c) loss of microtriches; (d) the appearance of numerous lipid droplets in the inner region of the germinal layer, (e) vacuolation of the cyton cytoplasm; and (f) the formation of abundant autophagosomes, which finally led to loss of the integrity of the germinal layer.

Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis and causes severe disease in the human liver, and occasionally in other organs, that is fatal when treatment is unsuccessful. The present chemotherapy against AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, is parasitostatic rather than parasiticidal, and usually involves the lifelong uptake of large doses of drugs. Thus, new treatment options are urgently needed. In this study we investigated the in vitro and in vivo efficacy of mefloquine against E. multilocularis metacestodes. Treatment using mefloquine (20 μM) against in vitro cultures of metacestodes resulted in rapid and complete detachment of large parts of the germinal layer from the inner surface of the laminated layer within a few hours. The in vitro activity of mefloquine was dependent on the dosage. In vitro culture of metacestodes in the presence of 24 μM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 μM was not. Oral application of mefloquine (25 mg/kg of body weight administered twice a week for a period of 8 weeks) in E. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, whereas treatment with albendazole (200 mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to the reduction seen with oral albendazole application. Combined application of both drugs did not increase the treatment efficacy. In conclusion, mefloquine represents an interesting drug candidate for the treatment of AE, and these results should be followed up in appropriate in vivo studies.

During 13 months of follow-up, the incidence rate of malaria was 0.27 episodes/person-year in the repeated treatment group and 0.26 episodes/person-year in the annual treatment group (incidence difference, 0.01; 95% confidence interval, -.03 to .06). The prevalence and density of malaria parasitemia did not differ by treatment group at any of the cross-sectional surveys.

This study analyzed the prevalence of intestinal parasitoses diagnosed shortly after arrival in the United States among African refugees before and after implementation of an overseas program of empirical treatment with albendazole. Variables included results of microscopy of a single stool specimen, age, sex, ethnicity, departure origin, and receipt of albendazole. Of 1,254 refugees, 56% had intestinal parasites. Fourteen percent had helminths, and 2% had multiple helminths. In addition, 52% had protozoans with 25% having multiple protozoans. The most common pathogens were Giardia lamblia (14%) and Trichuris trichiura (9%). Overall, refugees who arrived in Massachusetts after implementation of the treatment program were less likely to have any parasites (odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.47-0.78) and helminths (OR = 0.15, 95% CI = 0.09-0.24) than refugees who arrived previously. These more recently arrived refugees were also less likely to have hookworm (OR = 0.03, 95% CI = 0.00-0.29), Trichuris (OR = 0.05, 95% CI = 0.02-0.13), Ascaris (OR = 0.07, 95% CI = 0.01-0.58), and Entamoeba histolytica (OR = 0.47, 95% CI = 0.26-0.86). Empirically treating refugees prior to departure for the United States appears to have resulted in decreases in intestinal helminths and possibly some protozoans among African refugees tested shortly after arrival in this country.