Ascaris reaction

A system for study of respiratory reactions was developed in the previously described primate with Ascaris by aerosol challenge that was reproducible CFig. 5) simple to do, and easy to adapt to studying the effects of pharmacologic agents on the respiratory parameters involved in the Ascaris reaction (20). 

Karsten, W.E., Gavva, S.R., Park, S.H. and Cook, P.E. (1995). Metal ion activator effects on intrinsic isotope effects for hydride transfer from decarboxylation in the reaction catalyzed by the NAD-malic enzyme from Ascaris suum. Biochemistry 34, 3253-3260... 

Anti-allergenic activity. Hot water extract of the of the dried rhizome, administered by gastric intubation to mice at a dose of 100 mg/kg, was inactive vs type IV reaction with contact dermatitis induced by picryl chloride and type I reaction induced by antidinitrophenylated ascaris-IgE serum in 48 hours homologous PCA in rats. Dosing... 

In some organisms, such as the parasitic Ascaris suum, PEPCK functions principally as a means of synthesis of oxaloacetate by reaction of PEP with C02... 

Some enzymes contain bound NAD+ which oxidizes a substrate alcohol to facilitate a reaction step and is then regenerated. For example, the malolactic enzyme found in some lactic acid bacteria and also in Ascaris decarboxylates L-malate to lactate (Eq. 15-12). This reaction is similar to those of isocitrate dehydrogenase,110-112 6-phosphogluconate dehydrogenase,113 and the malic enzyme (Eq. 13-45)114 which utilize free NAD+ to first dehydrogenate the substrate to a bound oxoacid whose (3 carbonyl group facilitates decarboxylation. Likewise, the bound NAD+ of the malolactic... 

Type 3 fermentation, characterised by a series of reactions between mitochondrial end-products that yield branched-chain fatty acids (e.g. 2-methylvalerate, 2-methylbutyrate), occurs in Ascaris, a number of other intestinal nematodes and in some trematodes (490). However, cestodes, with the exception of Bothriocephalus scorpii, which excretes methyl-butyrate (107), have not been shown to produce branched-chain fatty acids as end-products of respiratory metabolism. Some or all of the enzymes of the TCA cycle may be present in cestodes in addition to the type 1 and type 2 fermentation pathways. The extent to which the cycle may contribute to carbohydrate metabolism in cestodes is considered below. 

Next to fumarate reduction, some organisms use specific reactions in lipid biosynthesis as an electron sink to maintain redox balance in anaerobically functioning mitochondria. In anaerobic mitochondria two variants are known the production of branched-chain fatty acids and the production of wax esters. The parasitic nematode Ascaris suum reduces fumarate in its anaerobic mitochondria, but instead of only producing acetate and succinate or propionate, like most other parasitic helminths, this organism also use the intermediates acetyl-CoA and propionyl-CoA to form branched-chain fatty acids (Komuniecki et al. 1989). This pathway is similar to reversal of P-oxidation and a complex mixture of the end products acetate, propionate, succinate and branched-chain fatty acids is excreted. In this pathway, the... 

The formation of succinate from fumarate by fumarate reductase (FR) and anaerobic phosphorylation of ADP to ATP are amongst the important reactions taking place in the mitochondria to provide energy to the helminths. The FR system of helminths differs from succinate dehydrogenase (SDH) of mammalian tissues in several ways. For example (a) FR requires NAD while SDH utilizes flavin nucleotide (FAD) as the coenzyme (b) FR acts only in one direction but SDH is a reversible enzyme (c) FR acts as the terminal electron acceptor under anaerobic conditions while SDH has no such property. Levamisole was shown to inhibit the FR in Ascaris [43]. 

A few other oxidation reactions have been reported in helminths. The cytosolic fractions of Moniezia expansa and Ascaris suum catalyze the sulfoxidation of several xenobiotics, including the benzimidazole derivatives albendazole and fenbendazole, to the corresponding sulfoxides (10). The reaction requires NADPH and molecular oxygen, but unlike mammalian sulfoxidase, it is not associated with the microsomal fraction. Although parasite sulfoxidases have not been purified, their properties suggest they are soluble forms of flavin-linked monooxygenase. 

Figure 3. Individual oedema indices for Ascaris coeloma fluid (ACF 1 100) and histamine reactions at various times after oral administration of oxatomide in the...

Comments on the Dog Experiments. A procedure similar to the presently described dog Ascaris allergy test has been used to study the anti-allergic activity of BM 06. 001 (46). Apparently oxatomide is a much more potent inhibitor of both the allergic and the histamine-induced skin reactions, when compared to BM 06. 001. Furthermore oxatomide virtually abolished the skin oedemas at doses below those inducing behavioural changes in the animals. 

Oxatomide has been selected from a new chemical series of benzimidazolones and benzimidazoles on the basis of its activity on hypersensitivity and histamine-induced reactions in three species, the guinea-pig, the rat and the dog. In a well-known model, the guinea-pig anaphylaxis, oxatomide was at least as effective on the anaphylactic shock as on the histamine oedema induced in the same animals. In the rat, the new compound was an orally active inhibitor of PCA-reactions. Compound 48/80-induced lethal shock was prevented at doses of the same order as those required to inhibit histamine skin reactions. In the dog inhibition of allergic reactions, induced by Ascaris allergens in the skin of hypersensitive dogs, inhibition of histamine skin reactions and reduction of circulating histamine released by Cremophor EL were obtained by virtually the same oral doses. 

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