Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The paper records the numbers of 1-2 mm shotty papules developing in the author's skin after 2-day courses of diethylcarbamazine (DEC) repeated every 16 days before, during and after a 7.1 G suramin course for cutaneous onchocerciasis. Assuming, from biopsy evidence, that each papule represented a dead Onchocerca volvulus microfilaria (mf), the number of mfs reaching the skin every 16 days did not begin to fall until 96 days after the first full dose of suramin; and only reached zero by day 224. The histopathology of nodules excised from Cameroonian patients before, and at intervals of 56-335 days after, the start of a 7.1 G suramin course, revealed changes in the worms that correlated over time with the disappearance of mfs from the skin. Suramin sterilized and killed the male worms between days 77 and 105 and, in the females, it adversely affected the staining and subsequent development of small morulae from about day 56. It was estimated that new embryogenesis ceased about 56-77 days after the first full dose; development of the last viable embryos to mfs was complete by about 136 days; and the last mfs, perhaps having reduced vitality, emerged from the females by 160 days and reached the skin within 16-32 days.
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PMID:Suramin and the time it takes to kill Onchocerca volvulus. 179 31

A rational strategy for chemotherapy demands that dosage schedules be based on an adequate knowledge of clinical and biochemical pharmacology. Many anthelmintic drugs (e.g. suramin, diethylcarbamazine, hycanthone) were introduced before modern techniques for drug evaluation (controlled clinical trials) and before the development of specific and sensitive analytical methods for the assay of drugs and metabolites in biological fluids. Thus, many of the regimens used today for the treatment of parasitic diseases are largely empirically derived. By means of specific analytical methodology (high performance liquid chromatography, gas chromatography and mass-spectrometry) introduced in the 1960s, it is now possible to measure drugs and their metabolites with specificity and sensitivity. Much of this review deals with compounds which are active against the major systemic helminths, i.e., filariae (diethylcarbamazine, ivermectin and suramin) and schistosomes (niridazole, metrifonate, oxamniquine and praziquantel), but recent advances in the treatment of hydatid disease involving the benzimidazole carbamates albendazole and mebendazole are also discussed. Among the imidazole derivatives, mebendazole, a broad-spectrum anthelmintic, is poorly absorbed from the gastrointestinal tract after a therapeutic dose, but that fraction which is absorbed and escapes hepatic first-pass extraction is pharmacologically active against systemic helminths. Albendazole is more completely absorbed, but is almost undetectable in plasma due to its rapid conversion to an active sulphoxide metabolite. This compound may well become the drug of choice for the chemotherapy of echinococcosis. Levamisole, the 1-isomer of tetramisole, is rapidly and completely absorbed, but has not been widely used in systemic helminthiases because of severe side effects associated with prolonged dosage. Diethylcarbamazine is microfilaricidal against Onchocerca volvulus, but its use has been associated with major adverse effects resulting from its action on the microfilariae. These effects are related to the concentration of the drug in the plasma which, in turn, is influenced by urinary pH. The elimination half-life of diethylcarbamazine is prolonged and renal clearance reduced in alkaline urine. Under these conditions the microfilaricidal effect is enhanced, but the adverse reactions to treatment are more severe. Suramin is the only available antifilarial agent with macrofilaricidal activity. It has a long elimination half-life (36 to 54 days), and is highly (99.7%) bound to plasma protein which limits its removal from the blood.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of anthelmintic drugs. 306 52

Glucose-6-phosphate dehydrogenase (E.C. 1.1.1.49) was partially purified from the extracts of adult Onchocerca volvulus by affinity chromatography on 2'5'ADP-Sepharose-4B. Kinetic studies revealed a typical bell-shaped pH profile with an optimum lying between pH 7.3 and 7.8. The apparent Km for glucose-6-phosphate was 5.66 x 10(-5) M, whereas that for NADP was 2.17 x 10(-6) M. Suramin, a filaricidal drug, inhibited the enzyme competitively with respect to NADP as a substrate: the apparent Ki values were 2.23 x 10(-6) M and 4.21 x 10(-7) M, respectively, for the crude and purified enzyme preparations. Glucose-6-phosphate dehydrogenase therefore, could be one of the targets of suramin in vivo.
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PMID:Studies on glucose-6-phosphate dehydrogenase from the human parasite, Onchocerca volvulus. 338 9

Suramin and Mel W are the only two drugs at present known to be effective against the adult worms of Onchocerca volvulus, but in view of the unpredictable occurrence of fatal arsenical encephalopathy in a small proportion of patients receiving Mel W, suramin remains the preferred macrofilaricide in the treatment of onchocerciasis. It is therefore important to determine the suramin dosage schedules that will produce parasitological cures with minimal concomitant risks of toxic reactions. The criteria by which cures should be judged must also be appreciated.Courses of different duration and employing doses of 1.0 g, 0.5 g and 0.25 g suramin have been investigated for their action on adult worms and microfilariae, for the toxic reactions which they produce on the kidney, and for the level of suramin reached in the serum during treatment. A course of 5 or 6 weekly doses of 1.0 g has been shown to be the optimum for adults.It is sometimes stated without good foundation that different brands of suramin differ in their purity and chemical composition, thus producing inconsistent effects on the parasites and grave risks of toxic manifestations. The three main brands in current use in Africa (Antrypol, Moranyl and Naganol) have therefore been compared in a group of patients, using the same optimum dosage schedule for each preparation and recording the action of the various brands on the parasites, as well as their comparative toxicities and the serum suramin levels achieved. No significant differences between the brands were recorded.
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PMID:The effects of drugs on Onchocerca volvulus. 3. Trials of suramin at different dosages and a comparison of the brands Antrypol, Moranyl and Naganol. 488 Oct 68

The best hope for the control of transmission of Onchocerca volvulus over much of Africa lies in combining larvicidal measures directed against the Simulium vectors with chemotherapeutic measures designed to reduce the reservoir of transmissible microfilariae in man.There are few drugs effective against O. volvulus. Diethylcarbamazine kills the microfilariae but has virtually no effect on the adult worms. Suramin kills adult worms and many, but not all, of the microfilariae. Mel W kills adult worms but has little or no action on microfilariae. All these drugs suffer at present from disadvantages of toxicity, which tend to limit their use on a mass scale in the field. Nevertheless, before they, or indeed any new drugs with similar actions on the parasites, can be used intelligently for the control of onchocerciasis transmission, it is necessary to have accurate quantitative information on the effect that each of them has on the microfilarial population available for intake by Simulium, as well as on their actions on the developmental potential of those microfilariae ingested by the flies.The present paper describes the effects of treatment with various courses of diethylcarbamazine, suramin or Mel W on the numbers of microfilariae ingested by groups of S. damnosum and on the numbers of infective larvae developing therefrom.
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PMID:The intake and transmissibility of Onchocerca volvulus microfilariae by Simulium damnosum fed on patients treated with Diethylcarbamazine, suramin or Mel W. 488 Oct 69

NADP-linked malic enzyme (malate dehydrogenase (oxaloacetate-decarboxylating) NADP+, EC 1.1.1.40) has been partially purified from adult Onchocerca volvulus and Dirofilaria immitis. Suramin was found to inhibit the activity of malic enzyme from both filarial worms. The inhibition constants for suramin were calculated to be 0.011 microM and 0.015 microM for the enzymes from O. volvulus and D. immitis, respectively. In the case of NADP-linked malic enzyme from Trypanosoma brucei and chicken liver the inhibition by suramin was less pronounced. The inhibition constants were found to be 0.8 microM and 2.5 microM for the protozoan and vertebrate enzymes, respectively. The type of inhibition was competitive with respect to malate. The Michaelis constants for malate and pyruvate were determined to be 0.9 and 4.5 mM for O. volvulus and 0.85 and 5.0 mM for D. immitis, respectively. The low Km values for malate compared to those for pyruvate and the about 15-fold greater turnover in the direction of decarboxylation compared to carboxylation indicated that malic enzyme from both filarial sources might be involved in an alternative pathway leading from phosphoenolpyruvate via oxaleacetate, malate and pyruvate to lactate. It is suggested, that the inhibition of malic enzyme activity from O. volvulus by suramin might interfere with the generation of NADPH for biosynthetic reactions.
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PMID:Inhibition of NADP-linked malic enzyme from Onchocerca volvulus and Dirofilaria immitis by suramin. 732 87