Effect of mebendazole and praziquantel on glucosephosphate isomerase and glyceraldehydephosphate dehydrogenase in Echinococcus granulosus cyst wall harbored in mice.
AIM: To study effects of antihydatid drugs on glucosephosphate isomerase (GPI) and glyceraldehydephosphate dehydrogenase (GAPDH) in Echinococcus granulosus cyst wall. METHODS: Mice infected with the parasite for 8-10 months were treated i.g. with mebendazole (Meb) or praziquantel (Pra). The activities of GPI and GAPDH in the cysts were measured by the formation of NADH or NADPH. RESULTS: GPI activity in the cyst wall was 197 +/- 103 U, while that of GAPDH was 25 +/- 13 U. When infected mice were treated i.g. with Meb 25-50 mg.kg-1.d-1 for 7-14 d, no apparent effect on the GAPDH activity in the cyst was found. In mice treated i.g. with praziquantel (Pra) 500 mg.kg-1.d-1 for 14 d, the GAPDH activity in the cyst wall was inhibited by 26.5%. As to GPI activity only the group treated i.g. with Meb 25 mg.kg-1.d-1 for 14 d showed 33.2% inhibition of the enzyme in the collapsed cyst wall. CONCLUSION: GPI and GAPDH are not the major targets attacked by the antihydatid drug. (+info)
Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979.
Beauveria sp. FO-6979, a soil isolate, was found to produce inhibitors of lipid droplet formation in mouse peritoneal macrophages. A new compound beauveriolide III was isolated along with a known compound beauveriolide I from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography, silica gel column chromatography and preparative HPLC. Beauveriolides I and III caused a reduction in the number and size of cytosolic lipid droplets in macrophages at 10 microM without any cytotoxic effect on macrophages. (+info)
Resistance to levamisole resolved at the single-channel level.
Levamisole is commonly used to treat nematode parasite infections but therapy is limited by resistance. The purpose of this study was to determine the mechanism of resistance to this selective nicotinic drug. Levamisole receptor channel currents in muscle patches from levamisole-sensitive and levamisole-resistant isolates of the parasitic nematode Oesophagostomum dentatum were compared. The number of channels present in patches of sensitive and resistant isolates was similar at 10 microM levamisole, but at 30 microM and 100 microM the resistant isolate contained fewer active patches, suggesting desensitization. Mean Po and open times were reduced in resistant isolates. The distribution of conductances of channels in the sensitive isolate revealed a heterogeneous receptor population and the presence of G25, G35, G40, and G45 subtypes. A G35 subtype was missing in the resistant isolate. Resistance to levamisole was produced by changes in the averaged properties of the levamisole receptor population, with some receptors from sensitive and resistant isolates having indistinguishable characteristics. (+info)
Maintaining compliance to ivermectin in communities in two West African countries.
We have investigated various aspects related to managing wide-scale ivermectin distribution schemes within randomized controlled trials in communities where onchocerciasis is endemic. Multiple logistic regression analysis of determinants of compliance to five doses of ivermectin in 589 people in Sierra Leone showed independent significant associations with leopard skin depigmentation, the severity of side effects of treatment, fulfilling the exclusion criteria for treatment, and long-term residence in the community. These results are useful for tailoring health promotion messages in Sierra Leone, but the associations may differ in other West African societies. In Nigeria 1847 people were interviewed about various subjective responses, including itching. None of these showed clear improvement after three years of ivermectin treatment. Positive comments about treatment were generally non-specific and similar in the placebo and ivermectin groups. Negative comments were usually related to adverse reactions, especially itching and rash, and were more common after ivermectin. The lack of any benefit attributable to ivermectin that is discernible to its recipients may make it difficult to maintain the high compliance rates needed for long periods if mass dosing programmes are to have a lasting impact on onchocerciasis. In addition, no consistent effects of ivermectin were found by measuring visual acuity, height, weight or haematocrit in comparison with placebo. This may indicate that evidence of clinical impact is very slow to develop and is hard to measure using simple objective methods after only three doses of treatment. At present it seems that parasitological, entomological and detailed ophthalmological or dermatological methods are required to demonstrate the impact of ivermectin treatment in the medium-term. (+info)
Case studies in international medicine.
Family physicians in the United States are increasingly called on to manage the complex clinical problems of newly arrived immigrants and refugees. Case studies and discussions are provided in this article to update physicians on the diagnosis and management of potentially unfamiliar ailments, including strongyloidiasis, hookworm infection, cysticercosis, clonorchiasis and tropical pancreatitis. Albendazole and ivermectin, two important drugs in the treatment of some worm infections, are now available in the United States. (+info)
A controlled evaluation of two school-based anthelminthic chemotherapy regimens on intensity of intestinal helminth infections.
BACKGROUND: School-based deworming programmes have been promoted as a cost-effective strategy for control of nematode infection in developing countries. While numerous efficacy studies have been conducted, there is little information on actual programme effectiveness in areas of intense transmission. METHODS: A randomized trial of a school-based deworming programme was conducted in 12 primary schools on Pemba Island, Zanzibar. Four schools each were randomized to control, twice a year deworming with single dose mebendazole or three times a year deworming. Baseline and 12-month follow-up data on helminth infection using the Kato-Katz technique, demographic information and nutritional status were collected on 3028 children from March 1994 to May 1995. RESULTS: Intensity of infection measured as eggs per gram of faeces (epg) declined significantly for Ascaris lumbricoides, Trichuris trichiura and hookworm infections in both treatment groups. A. lumbricoides infection intensity declined 63.1% and 96.7% in the twice and three times per year treatment groups compared to the controls. T. trichiura infection intensity declined 40.4% and 75.9% respectively and hookworm intensity declined 35.3% and 57.2% respectively compared to control schools. CONCLUSIONS: These results suggest that school-based programmes can be a cost-effective approach for controlling the intensity of intestinal helminth infection even in environments where transmission is high. (+info)
Liver tumor promoting effects of fenbendazole in rats.
In order to examine whether fenbendazole has tumor-promoting activity, a total of 70 male Fischer 344 rats were initiated with a single intraperitoneal injection of 100 mg/kg of diethylnitrosamine (DEN) or were given the saline vehicle alone; beginning 1 wk later, rats were given a diet containing 3,600; 1,800; 600; 200; 70; or 0 ppm of fenbendazole for 8 wk. Subgroups of 5 rats each from the DEN+ 1,800; DEN+0; 1,800; and 0 ppm groups were euthanatized after 1 wk of fenbendazole treatment, and the remaining animals were euthanatized at 8 wk. After 1 wk, relative liver weights (ratios to body weights) were significantly increased in the DEN+ 1,800 and 1,800 ppm groups, and based on light microscopy, periportal hepatocellular hypertrophy was evident in these groups. After 8 wk, relative liver weights were significantly increased in the groups given > or =600 ppm with or without DEN initiation. Periportal hepatocellular hypertrophy, characterized by a marked increase in smooth endoplasmic reticulum, was observed in the groups given > or =600 ppm with or without DEN initiation. Induction of cytochrome P-450 (CYP) 1A2, 2B1, or 4A1 was noted in the fenbendazole-treated groups with or without DEN initiation; that associated with CYP 1A2 was most marked. Positive immunostaining for anti-CYP 1A1/2 or CYP 2B1/2 was observed diffusely in the livers of animals in the DEN+1,800 and DEN+3,600 ppm groups. The numbers and areas of connexin 32 (Cx32)-positive spots per square centimeter in centrilobular hepatocytes were significantly decreased in an almost dose-dependent manner with fenbendazole treatment after DEN initiation. In situ hybridization for Cx32 mRNA revealed a remarkable decrease in its expression in the centrilobular hepatocytes in the DEN+70 ppm group. The numbers of glutathione S-transferase placental-form positive single cells (plus mini foci) were significantly increased in the DEN+ 1,800 and DEN+3,600 ppm groups. Since those agents that induce CYP 2B1/2 isozymes and reduce Cx32 in centrilobular hepatocytes have been suggested to be liver tumor promoters, the present results indicate that fenbendazole may be a liver tumor promoter. (+info)
Structures of flagranones A, B and C, cyclohexenoxide antibiotics from the nematode-trapping fungus Duddingtonia flagrans.
Spectroscopic data define the structures of the flagranones A (2), B (3) and C (4) from the nematode-trapping fungus Duddingtonia flagrans. These antibiotics are structurally related to the farnesylated cyclohexenoxides of the oligosporon group recently isolated from the nematode-trapping fungus Arthrobotrys oligospora, and show similar antimicrobial activity. (+info)