The Caenorhabditis elegans unc-63 gene encodes a levamisole-sensitive nicotinic acetylcholine receptor alpha subunit.
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The anthelmintic drug levamisole causes hypercontraction of body wall muscles and lethality in nematode worms. In the nematode Caenorhabditis elegans, a genetic screen for levamisole resistance has identified 12 genes, three of which (unc-38, unc-29, and lev-1) encode nicotinic acetylcholine receptor (nAChR) subunits. Here we describe the molecular and functional characterization of another levamisole-resistant gene, unc-63, encoding a nAChR alpha subunit with a predicted amino acid sequence most similar to that of UNC-38. Like UNC-38 and UNC-29, UNC-63 is expressed in body wall muscles. In addition, UNC-63 is expressed in vulval muscles and neurons. We also show that LEV-1 is expressed in body wall muscle, thus overlapping the cellular localization of UNC-63, UNC-38, and UNC-29 and suggesting possible association in vivo. This is supported by electrophysiological studies on body wall muscle, which demonstrate that a levamisole-sensitive nAChR present at the C. elegans neuromuscular junction requires both UNC-63 and LEV-1 subunits. Thus, at least four subunits, two alpha types (UNC-38 and UNC-63) and two non-alpha types (UNC-29 and LEV-1), can contribute to levamisole-sensitive muscle nAChRs in nematodes. (+info)
A transmembrane protein required for acetylcholine receptor clustering in Caenorhabditis elegans.
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Clustering neurotransmitter receptors at the synapse is crucial for efficient neurotransmission. Here we identify a Caenorhabditis elegans locus, lev-10, required for postsynaptic aggregation of ionotropic acetylcholine receptors (AChRs). lev-10 mutants were identified on the basis of weak resistance to the anthelminthic drug levamisole, a nematode-specific cholinergic agonist that activates AChRs present at neuromuscular junctions (NMJs) resulting in muscle hypercontraction and death at high concentrations. In lev-10 mutants, the density of levamisole-sensitive AChRs at NMJs is markedly reduced, yet the number of functional AChRs present at the muscle cell surface remains unchanged. LEV-10 is a transmembrane protein localized to cholinergic NMJs and required in body-wall muscles for AChR clustering. We also show that the LEV-10 extracellular region, containing five predicted CUB domains and one LDLa domain, is sufficient to rescue AChR aggregation in lev-10 mutants. This suggests a mechanism for AChR clustering that relies on extracellular protein-protein interactions. Such a mechanism is likely to be evolutionarily conserved because CUB/LDL transmembrane proteins similar to LEV-10, but lacking any assigned function, are expressed in the mammalian nervous system and might be used to cluster ionotropic receptors in vertebrates. (+info)
Pulmonary strongyloidiasis in a patient receiving prednisolone therapy.
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Strongyloidiasis is widely distributed in tropical and subtropical areas. Disseminated strongyloidiasis may develop in patients with immunodeficiencies. In the absence of early diagnosis and treatment, the prognosis of disseminated strongyloidiasis is extremely poor. We report a case of pulmonary strongyloidiasis that was successfully treated. The patient was an 83-year-old woman who had been receiving long-term oral prednisolone therapy for uveitis. The patient visited our emergency department complaining of breathing difficulties and diarrhea. A chest X-ray revealed a diffuse enhancement of interstitial shadows. A bronchoalveolar lavage (BAL) was performed, and both Gram staining and Grocott's staining revealed the presence of multiple filariform larvae of Strongyloides stercoralis in the bronchoalveolar lavage fluid (BALF). A stool examination performed at the same time also yielded S. stercoralis. The patient was diagnosed as having pulmonary strongyloidiasis and was treated with thiabendazole and ivermectin, in addition to antimicrobial agents; her respiratory symptoms and diarrhea improved, and S. stercoralis was not detected in subsequent follow-up examinations thereafter. In endemic areas of S. stercoralis, pulmonary strongyloidiasis should be considered as part of a differential diagnosis if chest imaging findings like alveolar and interstitial shadow patterns or lobar pneumonia are seen in patients with immunodeficiencies. (+info)
Synthesis and antinematodal activity of 3-n-alkylphenols.
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Several 3-alkylphenols including 3-undecylphenol, which was isolated from a Sumatran rainforest plant, were synthesized to investigate their antinematodal activity against the phytopathogenic nematodes, Bursapherencus xylophilus. A three-step synthesis involving the treatment of 2-cyclohexen-1-one with the Grignard reagent, oxidation of the resulting 1-alkyl-2-cyclohexen-1-ol and subsequent aromatization of 3-alkyl-2-cyclohexen-1-one successfully afforded such phenols. Among the 3-alkylphenols, 3-nonylphenol showed the highest activity, while 3-decylphenol and 3-undecylphenol also showed high activity. (+info)
The cost-effectiveness of ivermectin vs. albendazole in the presumptive treatment of strongyloidiasis in immigrants to the United States.
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The presumptive treatment of parasitosis among immigrants with albendazole has been shown to save both money and lives, primarily via a reduction in the burden of Strongyloides stercoralis. Ivermectin is more effective than albendazole, but is also more expensive. This coupled with confusion surrounding the cost-effectiveness of guiding therapy based on eosinophil counts has led to disparate practices. We used the newly arrived year 2000 immigrant population as a hypothetical cohort in a decision analysis model to examine the cost-effectiveness of various interventions to reduce parasitosis among immigrants. When the prevalence of S. stercoralis is greater than 2%, the incremental cost-effectiveness ratios of all presumptive treatment strategies were similar. Ivermectin is associated with an incremental cost-effectiveness ratio of 1700 dollars per QALY gained for treatment with 12 mg ivermectin relative to 5 days of albendazole when the prevalence is 10%. Any presumptive treatment strategy is cost-effective when compared with most common medical interventions. (+info)
Efficacy of albendazole against the whipworm trichuris trichiura--a randomised, controlled trial.
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OBJECTIVES AND DESIGN: To test the efficacy of albendazole against the whipworm Trichuris trichiura for school-based deworming in the south-western Cape, South Africa. Children infected with Trichuris were randomised to 3 doses of albendazole (400, 800 or 1200 mg), each repeated 4 times. The boy/girl ratio was 1. A group not infected with worms was treated with placebo, creating a negative control. SUBJECTS AND SETTING: Pupils at a primary school serving a wine-producing area approximately 90 km east of Cape Town. OUTCOME MEASURES: Trichuris cure rates and reduction in the number of eggs/g in faeces, as well as the infection dynamics of Trichuris and Ascaris during treatment with placebo. RESULTS: Albendazole treatment was associated with Trichuris cure rates of 23% (400 mg), 56% (800 mg) and 67% (1200 mg) after the final treatment. The corresponding reductions in the number of eggs/g of faeces were 96.8%, 99.3% and 99.7%. Environmental pollution by human faeces was confirmed because worm egg-negative children in the placebo group became egg-positive while the study was in progress. CONCLUSION: The 400 mg stat dose had a low Trichuris cure rate. To repeat the dose on 2 or 3 days would increase cost, reduce compliance and complicate management. Albendazole cannot be used in deworming programmes in South Africa because it is a Schedule 4 prescription medicine. De-scheduling is needed urgently, particularly because of high efficacy against hookworm in KwaZulu-Natal and neighbouring countries. (+info)
Nematicidal activity and chemical component of Poria cocos.
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Poria cocos, a famous traditional Chinese medicine, was found to have nematicidal activity in experiments searching for nematicidal fungi. The experiment showed it could kill 94.9% of the saprophytic nematode, Panagrellus redivivue, 92.6% of the root-knot nematode, Meloidogyne arenaria, and 93.5% of the pine nematode, Bursaphelenchus xylophilus, on PDA plate within 12 hours. According to the nematicidal activity, three new compounds, 2, 4, 6-triacetylenic octane diacid, 2, 4, 5, 6-tetrahydroxyhexanoic acid and 3, 4-dihydroxy-2-keto-n-butyl 2,4,5,6-tetrahydroxyhexanate, were isolated from submerged cultures of Poria cocos. Of these, 2, 4, 6-triacetylenic octane diacid could kill 83.9% Meloidogyne arenaria and 73.4% Panagrellus redivivus at 500 ppm within 12 hours. Here, it is reported for the first time that Poria cocos has nematicidal activity. (+info)
An unusual case of ectopic tungiasis with pseudoepitheliomatous hyperplasia.
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Tungiasis is caused by the penetration of the female sand flea Tunga penetrans into the epidermis, and subsequent hypertrophy of the parasite. In most cases lesions are confined to the feet. During a cross-sectional study, an unusual case of ectopic tungiasis in the inguinal area was detected. Histological examination of tissue samples showed a remarkable pseudoepitheliomatous aspect of the epidermis. Clinical features and differential diagnoses are discussed. (+info)