Characterization of glutamate-gated chloride channels in the pharynx of wild-type and mutant Caenorhabditis elegans delineates the role of the subunit GluCl-alpha2 in the function of the native receptor. (33/284)

Glutamate-gated chloride (GluCl) channels are the site of action of the anthelmintic ivermectin. Previously, the Xenopus laevis oocyte expression system has been used to characterize GluCl channels cloned from Caenorhabditis elegans. However, information on the native, pharmacologically relevant receptors is lacking. Here, we have used a quantitative pharmacological approach and intracellular recording techniques of C. elegans pharynx to characterize them. The glutamate response was a rapidly desensitizing, reversible, chloride-dependent depolarization (EC(50) = 166 microM), only weakly antagonized by picrotoxin. The order of potency of agonists was ibotenate > L-glutamate > kainate = quisqualate. Ivermectin potently and irreversibly depolarized the muscle (EC(50) = 2.7 nM). No further depolarization was seen with coapplication of maximal glutamate during the maximal ivermectin response, indicating that ivermectin depolarizes the muscle by the same ionic mechanism as glutamate (i.e., chloride). The potency of ivermectin on the pharynx was greater than at any of the GluCl subunits expressed in X. laevis oocytes. This effect of ivermectin was abolished in the mutant avr-15, which lacks a functional GluCl-alpha2 subunit. However, a chloride-dependent, nondesensitizing response to glutamate persisted. Therefore, the GluCl-alpha2 subunit confers ivermectin sensitivity and a high-affinity desensitizing glutamate response on the native pharyngeal GluCl receptor.  (+info)

Ivermectin treatment of a traveler who returned from Peru with cutaneous gnathostomiasis. (34/284)

We describe a 21-year-old patient who experienced a relapse of cutaneous gnathostomiasis after receiving initial treatment with albendazole and who had a successful outcome after receiving a short course of ivermectin for the relapse. This is the first reported case of gnathostomiasis acquired by a human in Peru.  (+info)

Diagnosis of Strongyloides stercoralis infection. (35/284)

Strongyloides stercoralis infects 30 million people in 70 countries. Infection usually results in asymptomatic chronic disease of the gut, which can remain undetected for decades. However, in patients receiving long-term corticosteroid therapy, hyperinfection can occur, resulting in high mortality rates (up to 87%). Strongyloidiasis is difficult to diagnose because the parasite load is low and the larval output is irregular. Results of a single stool examination by use of conventional techniques fail to detect larvae in up to 70% of cases. Several immunodiagnostic assays have been found ineffective in detecting disseminated infections and show extensive cross-reactivity with hookworms, filariae, and schistosomes. Although it is important to detect latent S. stercoralis infections before administering chemotherapy or before the onset of immunosuppression in patients at risk, a specific and sensitive diagnostic test is lacking. This review describes the clinical manifestations of strongyloidiasis, as well as various diagnostic tests and treatment strategies.  (+info)

Community-based ivermectin therapy for onchocerciasis: comparison of three methods of dose assessment. (36/284)

A new method of assessment based on mid-upper arm circumference (MUAC) is described for dosage adjustment for community-based ivermectin distribution. We studied 878 subjects eligible for ivermectin dosing in Awhum, Nigeria. In a previous preliminary study of 40 persons, MUAC (in cm) correlated with weight (kg) in the first 20 male (r = 0.97, r2 = 0.95, P < 0.0001) and the first 20 female subjects (r = 0.94, r2 = 0.88, P < 0.0001). We therefore studied the use of height, physical appearance, and MUAC for calculating the dose of ivermectin. The MUAC-based schedule underdosed only 4.1% of the population. The methods based on height underdosed 3.3% and 21.1%, and assignment based on physical appearance underdosed 10.2% of the population studied. This MUAC-based method (13-15 cm, 0.5 tablet; 16-20 cm, 1.0 tablet; 21-27 cm, 1.5 tablets; > or = 28 cm, 2.0 tablets) is more convenient and corresponds closely to dosing by weight. An adaptation of this method with reference to other prevalent tropical diseases and their respective drugs is therefore advocated.  (+info)

In vitro study on thiabendazole action on viability of Ascaris lumbricoides (Lineu, 1758) eggs. (37/284)

The in vitro activity of thiabendazole on Ascaris lumbricoides eggs, which were recovered from uteri of worm excreted after chemotherapeutic treatment, was studied. Four concentrations of the drug were used: 1 - 2.5 - 5 - and 10 ppm during 24, 48 and 72 hours of exposure. Subsequently, the eggs were centrifuged, washed three times and H(2)SO(4)0.1N was added. The eggs were maintained in an incubator for 20 days at 28 degrees C. Finally, the percentage of embryonated eggs was determined under a lightmicroscope at a 100X magnification. After 48 and 72 hours of thiabendazole exposure, at a concentration of 10ppm, the drug showed complete inhibition of egg embryonation.  (+info)

Macrofilaricides and onchocerciasis control, mathematical modelling of the prospects for elimination. (38/284)

BACKGROUND: In most endemic parts of the world, onchocerciasis (river blindness) control relies, or will soon rely, exclusively on mass treatment with the microfilaricide ivermectin. Worldwide eradication of the parasite by means of this drug is unlikely. Macrofilaricidal drugs are currently being developed for human use. METHODS: We used ONCHOSIM, a microsimulation mathematical model of the dynamics of onchocerciasis transmission, to explore the potentials of a hypothetical macrofilaricidal drug for the elimination of onchocerciasis under different epidemiological conditions, as characterized by previous intervention strategies, vectorial capacity and levels of coverage. RESULTS: With a high vector biting rate and poor coverage, a very effective macrofilaricide would appear to have a substantially higher potential for achieving elimination of the parasite than does ivermectin. CONCLUSIONS: Macrofilaricides have a substantially higher potential for achieving onchocerciasis elimination than ivermectin, but high coverage levels are still key. When these drugs become available, onchocerciasis elimination strategies should be reconsidered. In view of the impact of control efforts preceding the introduction of macrofilaricides on the success of elimination, it is important to sustain current control efforts.  (+info)

Regulation of distinct muscle behaviors controls the C. elegans male's copulatory spicules during mating. (39/284)

We demonstrate through cell ablation, molecular genetic, and pharmacological approaches that during C. elegans male mating behavior, the male inserts his copulatory spicules into the hermaphrodite by regulating periodic and prolonged spicule muscle contractions. Distinct cholinergic neurons use different ACh receptors and calcium channels in the spicule muscles to mediate these contractile behaviors. The PCB and PCC sensory neurons facilitate periodic contraction through muscle-encoded UNC-68 ryanodine receptor calcium channels. The SPC motor neurons trigger prolonged contraction through EGL-19 L-type voltage-gated calcium channels. The male gonad then lengthens the duration of EGL-19-mediated prolonged muscle contraction. This regulation of muscle contraction provides a paradigm to explain how animals initiate, monitor, and maintain a behavioral motor program.  (+info)

New biotransformation products of nemadectins. (40/284)

Selected nemadectins (formerly LL-F28249 series) have been fed to a panel of microorganisms with the aim of generating new derivatives. In addition to products resulting from the oxidation of the terminal methyl group (C-29), a unique phosphorylated nemadectin was isolated. The phosphate group was determined to be at C-23 by HMBC between phosphorus and H-23. Milbemycin or nemadectin derivatives with natural substituents involving the 23-hydroxyl group were hitherto unknown.  (+info)