[Therapy of intestinal parasitoses].
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A single preparation of U.S.P. pyrvinium pamoate that exhibited promutagen activity in Salmonella/mammalian microsome reverse mutation assays was subjected to in vitro mammalian cell bioassays. Cytotoxicity limiting doses of dimethyl sulfoxide-solubilized drug were without effect in the absence and/or presence of liver S9 fraction from Aroclor-1254-induced rats in an in vitro Chinese hamster ovary (CHO) cell assay for chromosome aberration and sister-chromatid exchange induction at concentrations of 0.025-0.78 microgram/ml. Forward gene mutation at the hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) locus in Chinese hamster (V-79) cells was studied with and without exogenous metabolic activation at concentrations ranging from 0.3 to 10 micrograms/ml. In concurrent promutagen controls, dimethylnitrosamine, benzo[a]pyrene, and cyclophosphamide caused significant (p less than 0.05) increases over controls in each respective assay endpoint under the metabolic activations used. These results suggest that intrinsic mutagenic activity manifested in lower microbial systems does not have a corresponding effect in mammalian cells. Coupled with the lack of solubility and poor absorption in vivo, we concluded that the drug, when used In the single oral dose mode of administration, possesses a negligible somatic and germinal genotoxicity risk.
An anthelminthic, pyrvinium pamoate (PP), 6-(dimethylamino)-2-[2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)ethenyl]-1-methyl-quinolinium pamoate salt, has been found to be extremely toxic to PANC-1 cells in glucose-free medium, but not to be toxic to the same cells cultured in ordinary medium, Dulbecco's modified Eagle's medium (DMEM). It showed the same preferential toxicity for various cancer cell lines during glucose starvation. When 0.1 microg/ml PP was added to the medium, spheroid growth of human colon cancer cell line WiDr was strongly inhibited to a diameter of 750 microm, and this finding is consistent with the concept of anti-austerity. PP was also found to exert antitumor activity against human pancreatic cancer cell line PANC-1 in nude mice and SCID mice when it was administered subcutaneously or orally. Regarding the mechanism of PP action, inhibition of Akt phosphorylation, which has been found to be essential for the austerity mechanism, was observed in vitro and in vivo. These findings indicate that PP may be useful for anticancer therapy and that anti-austerity therapy could be a novel strategy for anticancer therapy.
Thirty-eight patients presenting to their general practitioner with threadworm infestation were admitted to an open, comparative, multicentre trial of Vanquin tablets and Pripsen granules. Efficacy and tolerance were assessed. Twelve of nineteen patients treated with Vanquin had positive results from a peri-anal skin test at the start of treatment, all results were negative after twenty-one days. Fourteen of nineteen patients treated with Pripsen had positive results at the start of treatment and two of these had positive results after twenty-one days. One patient treated with Vanquin and five treated with Pripsen reported side-effects.
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A study was undertaken to compare the efficacy of three drugs in the treatment of uncomplicated strongyloidiasis in Okinawa, Japan. Two hundred and eleven patients with confirmed Strongyloides stercoralis infection were given either ivermectin, 6 mg in a single dose, albendazole, 400 mg/day for 3 days or pyrvinium pamoate, 5 mg/kg/day for 3 days. For each treatment, the same regimen was repeated once 2 weeks later. Efficacy was evaluated at 2 weeks, 6 months and 12 months after the second course of treatment. Each follow-up examination included a parasitological examination of z stool specimens, using the agar-plate culture method. Coprological cure was obtained in 65 of the 67 patients treated with ivermectin (97.0%), in 65 of the 84 patients treated with albendazole (77.4%) and only in 14 of the 60 patients who were given pyrvinium pamoate (23.3%). The cure rates were lower in males and in the patients with concurrent HTLV-1 infection. An epidemiological feature of Strongyloides infection in recent Okinawa might allow workers to evaluate the exact efficacy of the treatment for an extended period, over a year, without the possibility of reinfection from the environment.
In two new attempts to infect human subjects with pin-worms that were infested, at that time, with protozoa Dientamoeba fragilis, presence of these protoza in the intestinal canal was observed in one case for more than 84 days, and in another case for more than 31 days after contamination. The duration of latent periods fixed for Enterobius vermicularis was almost identical (51 and 50 days). New attempts implement and confirm the results of the first successful attempts to transfer the infection (Ockert, 1972b) as well as the hypothesis of the epidemiological interrelation between both parasites (Burrows and Swerdlow 1956).
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