Inorganic Substances

Brand, Theodor von

doi:10.1016/b978-0-12-724160-9.50005-7

Cited by 3 publications

(2 citation statements)

References 302 publications

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“…namely, aerobic glycolysis. It is estimated that the organism consumes its dry weight in glucose every 90 min (17). Glucose is metabolized only as far as pyruvate (20); the NAD reduced during glycolysis is regenerated in microbodies by the reduction of dihydroxyacetone phosphate (19,20).…”

Section: Assessment Of Trypanocidal Activity In Vivomentioning

confidence: 99%

An approach to the development of new drugs for African trypanosomiasis.

Meshnick¹,

Blobstein²,

Grady³

et al. 1978

The Journal of Experimental Medicine

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African sleeping sickness is caused by Trypanosoma brucei gambiense and T. b. rhodesiense. This disease resulted in the deaths of several million people during the first half of the twentieth century (1) and continues to pose a threat of new epidemics (2). Of even more significance is the fact that animal trypanosomiasis or nagana (T. congolense, T. b. brucei, and T. vivax) makes four million square miles of the African continent unsuitable for the production of cattle and other livestock (3). The first trypanocidal agents were developed by Ehrlich and his collaborators in the early part of this century. Over the next 50 yr, drugs such as tryparsarnide, suramin, pentamidine, berenil, ethidium, Antrycide, and melarsoprol became available for use in the treatment of both sleeping sickness and nagana (4). For the past 20 yr, however, there have been no new chemotherapeutic agents introduced. Moreover, the therapeutic usefulness of the older drugs is diminishing due to the increased incidence of resistant strains (5).We have been attempting to develop new chemotherapeutic agents by elucidating biochemical differences between trypanosomes and their hosts and then designing drugs to take advantage of these differences. The present communication describes such an approach to drug development. The biochemical difference we have exploited is the inability of T. b. brucei to synthesize heine (6). As a result of this deficiency and the avid binding of heine to serum proteins in mammalian hosts, the bloodstream form of this organism has no detectable heine (S. R. Meshnick and S. Sassa, unpublished results) or hemoproteins such as cytochromes (7) or catalase (8). In a previous communication (9) we reported that the lack ofcatalase in T. b. brucei leads to an accumulation of intracellular hydrogen peroxide (H202) in these organisms, which should increase their susceptibility to killing by agents that promote the homolytic cleavage of H202 yielding hydrexy (HO.) or hydroperoxy (HOO.) radicals. Presumably, these radicals would react with unsaturated lipids and other cell constituents, thereby leading to cell destruction. Heme proved to be trypanocidal in vitro, whereas several other porphyrins showed in vivo activity (9). We ascribed this to their acting as initiators of homolytic cleavage. To enhance the efficacy of this therapeutic approach, we have attempted to determine the site of H202 production, the fate of the H202 generated, a means of increasing H202 production, and lastly, ways of rendering trypanosomes more susceptible to radical damage. J. ExP. MED.

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Section: Assessment Of Trypanocidal Activity In Vivomentioning

confidence: 99%

An approach to the development of new drugs for African trypanosomiasis.

Meshnick¹,

Blobstein²,

Grady³

et al. 1978

The Journal of Experimental Medicine

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“…There is extensive evidence of the beneficial effects of small quantities of cobalt on growth and development in many plants, animals and microorganisms. However, information on the concentration of this element in helminths is scanty (Von Brand, 1966,1973. In the recent past there have been a few attempts to identify and quantify certain inorganic elements in individual helminths (Nadakal & Nair, 1982;Lai & Kumar, 1985;Goldsmid, 1986;Pandey & Chowdhry, 1989) or individual elements in different groups of helminths (Chowdhury & Singh, 1989).…”

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confidence: 99%

Distribution of cobalt in parasitic helminths

Chowdhury

Singh

1995

J. Helminthol.

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The distribution of cobalt in parasitic helminths belonging to the trematodes, cestodes or nematodes was determined by the use of an atomic absorption spectrophotometer. The results of these analyses have demonstrated that growing trematodes (smaller forms) with active oogenesis and spermatogenesis contained more cobalt than older forms (large or very old adults) with empty uteri and large lobulated testes. In cestodes, the neck region of cysticerci and immature proglottids of adults showed more cobalt than the cyst portion of cysticerci and hydatid or mature and gravid proglottids of worms. Similarly, the youngest endogenous daughter cysts of Echinococcus granulosus showed more cobalt in their walls than those of larger forms. The element was found more concentrated in nematode eggs than in adult females, irrespective of species of host.

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Element composition and biochemical components of Dirofilaria immitis

Bowen

2001

Veterinary Parasitology

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Inorganic Substances

Cited by 3 publications

References 302 publications

An approach to the development of new drugs for African trypanosomiasis.

An approach to the development of new drugs for African trypanosomiasis.

Distribution of cobalt in parasitic helminths

Element composition and biochemical components of Dirofilaria immitis

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