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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ivermectin, a recently developed macrocyclic lactone with broad antiparasitic activity, has been shown by a series of clinical trials to be safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction as is seen with diethylcarbamazine treatment. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/Kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement, although ivermectin has no known long-lasting effects on the adult worms. With treatment there is no significant exacerbation of either anterior or posterior segment eye disease even in those with severe ocular disease. Treatment leads to a marked and prolonged improvement in ocular status. Because of its safety and efficacy, ivermectin can be used on a mass scale and promises to revolutionize the treatment of onchocerciasis.
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PMID:Ivermectin treatment of ocular onchocerciasis. 219 51

The annulated cuticles of third- and fourth-stage larvae of Onchocerca volvulus have the typical structure of other nematodes but the cuticle of fourth-stage larvae was thinner. The surface of the third-stage larva was wrinkled and fuzzy, while that of the fourth-stage was smooth. Intermediate stages in the formation of the new cuticle and epicuticle beneath the old basal layer and of the separation of the cuticles are shown. Monoclonal antibodies specific to the surface of third-stage larvae did not react with the surface of the fourth-stage larvae. Binding of the monoclonal antibodies to the third-stage larvae was abrogated by treatment of the worms with trypsin and proteinase K, but was unaffected by treatment with periodate or the detergents sodium deoxycholate and SDS. The lectins RCA120 and WGA, but not any of the other lectins tested, bound only to the surface of fourth-stage larvae, and not to that of third-stage larvae. The surfaces of third- and fourth-stage larvae were shown to be different and contained stage-specific surface epitopes.
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PMID:Onchocerca volvulus: biochemical and morphological characteristics of the surface of third- and fourth-stage larvae. 222 9

Specific, serological diagnosis is one of the main goals in onchocerciasis research. To date this objective has been hampered by (a) scarcity of parasite material, and (b) antigenic cross-reaction between Onchocerca volvulus and other nematode species. In order to obtain specific antigens, and in amounts suitable for study, molecular biological techniques have been adopted. A lambda gt11 cDNA expression library prepared from O. volvulus adult female worms was screened using infected human sera from onchocerciasis patients and rabbit hyperimmune sera raised against Onchocerca and genus-specific Onchocerca antigen extracts. Five clones were selected and their inserts expressed as beta-galactosidase fusion proteins. The fusion proteins were examined using individual sera from patients with O. volvulus or Wuchereria bancrofti infections. Three of the fusion proteins were recognised by more than 80% of O. volvulus sera and exhibited weak reactivity with a few W. bancrofti sera. One of these three clones was recognised to a significantly greater degree by sera from sowda than from generalised onchocerciasis patients.
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PMID:Cloning of specific diagnostic antigens of Onchocerca volvulus. 225 40

This paper assesses the effects on adult Onchocerca volvulus of monthly doses of ivermectin (150 micrograms/kg) given over 4, 8, and 12 months to patients in Guatemala. Nodules were removed 4 months after the last dose; the adult O. volvulus were extracted by collagenase digestion, studied by histological techniques, and compared with worms from untreated patients. Twelve monthly doses killed a proportion of the adult worms (12% of males and 22% of females), leaving the remainder relatively unaffected and the females slowly resuming embryogenesis. After 8 and 12 doses, a number of female worms had resumed embryogenesis in 1 genital tract only, and in 1 female a total degeneration of 1 ovary was seen. Ivermectin also led to a marked drop in the number of male worms in nodules. No serious adverse reactions occurred and the treatment was well accepted.
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PMID:Effects of multiple monthly doses of ivermectin on adult Onchocerca volvulus. 226 70

Eosinophil infiltration and degranulation around the tissue-invasive stages of several species of helminths have been observed. Release of eosinophil granule contents upon the worms is supported by localization of two of the major granule proteins, major basic protein (MBP) and eosinophil peroxidase (EPO), on and around species of trematodes, nematodes, and cestodes. In the case of filarial worms, MBP is deposited on degenerating microfilariae (mf) of Onchocerca volvulus. Here, we performed in vitro assays of the toxicity of four purified eosinophil granule proteins, namely, MBP, EPO, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), for the mf of Brugia pahangi and Brugia malayi. MBP, ECP, and EDN killed these worms in a dose-related manner although relatively high concentrations of EDN were necessary. EPO, in the presence of a H2O2-generating system and a halide, was the most potent toxin on a molar basis; here, the most potent halide was I- followed by Br- and Cl-. Surprisingly, EPO in the absence of H2O2 killed mf at concentrations comparable to those required for MBP and ECP. The toxicity of EPO + H2O2 + halide was inhibited by heparin, catalase, or 1% BSA, whereas the toxicity of EPO alone was inhibited only by heparin. Heparin also inhibited killing by both MBP and ECP. Despite the homology of ECP with certain RNases, placental RNasin, an RNase inhibitor, was unable to inhibit ECP-mediated toxicity. These results indicate that all of the eosinophil granule proteins are toxic to mf and they support the hypothesis that eosinophil degranulation causes death of mf in vivo.
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PMID:In vitro killing of microfilariae of Brugia pahangi and Brugia malayi by eosinophil granule proteins. 232 97

Using female Acanthocheilonema viteae we have investigated the bioreduction of the tetrazolium reagent XTT (2,3-bis(2-methoxy-4-nitro-sulphonyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide). Unlike the formazan formed by other tetrazolium salts, that derived from XTT readily diffuses out of A. viteae in vitro. Formazan formation can therefore be quantified by direct absorbance reading of the incubation medium, eliminating the need for a DMSO solubilization step. Optimum assay conditions involved a 4 h incubation, in the presence of the electron coupling agent phenazine methosulphate (PMS). Repeat 4 h incubations with XTT-PMS were well tolerated by worms for 5 consecutive days. This confirmed the low toxicity of XTT formazan and its usefulness in the semi-continuous assessment of filarial viability. In comparison to our previously reported MTT (3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide)-reduction assay XTT-PMS reduction showed comparable drug sensitivity and accuracy, however XTT-PMS appears to be at least 10-15 times less efficiently reduced by A. viteae females. A possible application of the XTT assay using female Onchocerca volvulus is discussed.
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PMID:Potential of a soluble tetrazolium/formazan assay for the evaluation of filarial viability. 233 82

The effects of co-culture with monkey kidney cells (LLCMK2), cell-conditioned medium and decreased atmospheric oxygen on the in vitro molting and viability of infective stage larvae (L3) of Onchocerca lienalis and O. volvulus were examined. O. lienalis L3 were cultured in an RPMI 1640-based medium in the presence of an LLCMK2 cell monolayer or in medium which had been conditioned for three days by cells. In paired experiments cell conditioned medium alone in 95% air/5% CO2 produced molting levels of 54 +/- 14% which increased to 67 +/- 20% in treatments cultured under decreased oxygen; this value equalled the level of molting of worms cocultured with LLCMK2 cells. Worm survival in the three environments was similar. In seven additional experiments using O. lienalis (n = 186), overall levels of 74 +/- 12 percent molting and 75 +/- 7% viability on days 21-33 were obtained. Worms increased in length from 503 +/- 50 mu as L3 to 638 +/- 74 mu as L4 on day 21 (p = 0.0001, n = 42-44). Ultrastructural comparison of an in vitro derived L4, (39 days in culture) vs a vector-derived L3 revealed fewer annulations and decreased osmiophilia on the epicuticle of the L4 while the hypodermis showed increased morphogenetic definition. O. volvulus molted at an average rate of 74% (n = 40) with a mean viability on day 28 of 95%. L3 increased in length from a mean of 635 +/- 50 mu to 775 +/- 45 mu as L4 on day 28 (p = 0.0001). Larvae of both species were cultured under these conditions for periods of time exceeding 100 days.
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PMID:The use of cell-conditioned medium for the in vitro culture of Onchocerca spp. larvae (Nematoda: Filarioidea). 233 42

This study compiles observations on the reproductive capacity of O. volvulus. Adult parasites enzymatically isolated from excised onchocercomata of untreated and chemotherapeutically treated patients, and from inhabitants living in areas with long vector control, were investigated to assess their fecundity. Changes of microfilaria development in utero and microfilaria release were assessed or estimated after treatment of patients with micro-filaricidal drugs that interfered with the development of intra-uterine stages. Intra-uterine production of microfilariae: After treatment of patients with ivermectin a daily development of 2500 to 4000 uterine microfilariae per female worm was observed. Actual output of microfilariae: Microfilariae left actively the female worms. The daily microfilaria release in vivo was 700 to 900 microfilariae, assessed after treatment of patients with mebendazole. In vitro most worms isolated from untreated patients shed between 500 to 1500 microfilariae per day.-The microfilarial load of 56 adult patients calculated from microfilarial skin counts was 12 million on the average. Taken for granted a mean life span of a microfilaria of 1.0 to 1.5 years, 22 to 47 female worms per patient would suffice to maintain this microfilarial load on a constant level. Excision of all palpable nodules showed a geometric mean of 15.9 female worms in these patients. It is suggested that factors intrinsic in the host and the adult worms partially operate together to regulate and maintain a stable microfilarial density.
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PMID:Observations on the reproductive biology of Onchocerca volvulus. 237 10

The viability of adult Onchocerca volvulus and the effect of 12 known anthelmintic compounds on the parasites have been evaluated in an in vitro culture system. Three different parameters, a colorimetric assay, using NADH-dependent reduction of a tetrazolium salt to dark blue formazan by living adult worms, motility indices of male worms and lactate excretion of female worms were used to determine worm viability. The experiments showed that over a short term period of six days the viability of the worms did not decline significantly. The use of males isolated by dissection of whole nodules for the evaluation of drug effects in vitro is preferable to collagenase isolated worms. Mel W, milbemycin a and d, ivermectin, levamisole, CGP 6140 and, to a lesser extent, suramin immobilized male worms or significantly reduced the motility indices at a concentration of 10 microM. The tetrazolium reduction by male worms was not affected by levamisole, whereas the other active compounds demonstrated significant inhibitory effects. Diethylcarbamazine, mebendazole, flubendazole, metrifonate and CGP 20376 had no significant effect on male viability. Comparable activity was seen with the intact female worms isolated by collagenase digestion. Mel W, the milbemycins and ivermectin significantly inhibited tetrazolium reduction, whereas suramin and the other compounds had only slight or no inhibitory effects on female O. volvulus. Although one still has to aim at an improvement of the culture conditions, the in vitro test system using adult O. volvulus provides a basis for further research on potential antifilarial compounds.
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PMID:In vitro assessment of the activity of anthelmintic compounds on adults of Onchocerca volvulus. 237 12

Suitable drugs for the elimination of adult Onchocerca volvulus are still needed since ivermectin, the new microfilaricide, appears to be ineffective against this parasite stage. Herein we report on the identification of filaricides in three medicinal plants. The compounds carapolide A, mexicanolide-methylangolensate mixture from Carapa procera and oliverine from Polyalthia suaveolens or Pachypodanthium staudtii when tested at 10-100 micrograms.ml-1 were found to exhibit considerable microfilaricidal activity after 24 hours of incubation. Oliverine was found to be filaricidal when tested against adult female worms at 100 micrograms.ml-1. Preliminary toxicity studies in mice showed carapolide A and the mexicanolide-methylangolensate mixture to be relatively non-toxic, whereas, oliverine had a minimal lethal dose of 8 mg.Kg-1 of body weight. Based on the above results further pharmacologic studies are recommended to determine, the potential application of the active compounds on the treatment of onchocerciasis.
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PMID:Novel Onchocerca volvulus filaricides from Carapa procera, Polyalthia suaveolens and Pachypodanthium staudtii. 237 19


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