Enzymes intestinal parasites

Paromomycin sulfate is an aminoglycoside antibiotic that until recently was used in parasitology only for oral therapy of intestinal parasitic infections (see previous text). It has recently been developed for the treatment of visceral leishmaniasis. A phase 3 trial in India showed excellent efficacy for this disease, with a daily intramuscular dosage of 11 mg/kg for 21 days yielding a 95% cure rate, and noninferiority compared with amphotericin. The drug was registered for the treatment of visceral leishmaniasis in India in 2006. In initial studies, paromomycin was well tolerated, with common mild injection pain, uncommon ototoxicity and reversible liver enzyme elevations, and no nephrotoxicity. Paromomycin is much less expensive than liposomal amphotericin or miltefosine, the other promising new therapies for visceral leishmaniasis. 

Rasero, F. S., Monteoliva, M. Mayor, F. (1968). Enzymes related to 4-aminobutyrate metabolism in intestinal parasites. Comparative Biochemistry and Physiology, 25 693-701. 

Fig. 11.4. Model for cholinergic signalling in the intestinal mucosa, providing a possible rationale for AChE secretion by parasitic nematodes. ACh released from enteric cholinergic motor neurons stimulates chloride secretion, mucus secretion and Paneth cell exocytosis through muscarinic receptors. Secretory responses may be modulated by mast cell mediators, either directly or via the induction of neural reflex programmes. The role of muscarinic receptor-positive cells in the lamina propria of rats infected with N. brasiliensis is undetermined, as are potential mechanisms of trans-epithelial transport of the enzymes. Adapted from Cooke (1984).

Thiabendazole. This benzimidazole derivative (12) is an effective oral drug used in the treatment of intestinal roundworms and selected tissue parasites. Infections with S. stercorahs are commonly treated with thiabendazole for two days. Disseminated strongyloidiasis is treated for at least five days. Satisfactory results have been reported when used for T. spirahs infections however, its effectiveness on encapsulated muscle larvae has not been clinically demonstrated. Extensively used in veterinary medicine, thiabendazole was the first broad-spectrum benzimidazole anthelmintic. It is widely used in the United States. The mechanism of action is not clearly understood, but it has been shown that thiabendazole inhibits the enzyme fiima.ra.te reductase, which is found specifically in the mitochondria of helminths (31). 

The intestine is also an important site for secretion of digestive enzymes. In A. suum several disaccharidases are abundant on the microvilli, including sucrase, palatinase, maltase and trehalase, with maltase activity predominating. Endopeptidases that break down hemoglobin and other host proteins are also present. Lipases have been detected in intestinal cells of several species, and their activity depends extensively on the diet of the parasite. In Strongylus edentatus, which feeds on host mucosal tissue, lipase activity in the intestine is 12-fold greater than that for A. suum, a saprophagous feeder (141). 

Enzyme changes occur in several gastrointestinal conditions, such as intestinal infarction or obstruction, parasitic infections, obstruction of the biliary system, and contraction of the sphincter of Oddi by drugs such as morphine, withdrawal of food, and age-related changes. 

By similar localization, difluoromethylornithine (9.88) cures coccidiosis in poultry. The protozoon Eimeria) which causes this economically disastrous disease, multiplies in and damages the endothelium of the chicken gut. The drug, which works by inhibiting the parasite s ornithine decarboxylase, spares the host s enzyme by being unable to penetrate beyond the intestinal wall (see Section 9.7.2). 

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