M. L. Chance

Bio: M. L. Chance is an academic researcher. The author has contributed to research in topics: Leishmaniasis & Visceral leishmaniasis. The author has an hindex of 1, co-authored 1 publications receiving 6 citations.

Pentavalent antimonials: old drugs for new diseases

Abstract: Clinicians like myself feel a sense of pressure because things change so slowly for the patient in spite of the volume of current research. This is currently the case in the chemotherapy of leishmaniasis where the drug formulations used in the first line treatment have not changed for four decades. Neither is a practical altemative on the horizon. There is no money to be made in treating the poor people of rural areas suffering from this disease. The small efforts that have been extended in this direction have not met with success. Therefore we must try to use antimonials more efficiently for the benefit o f the patient and this is the chief purpose of this review.

Drug delivery system: targeting of pentamidines to specific sites using sugar grafted liposomes

Abstract: Different sugar-grafted liposomes were prepared and tested against experimental leishmaniasis in vivo using the classical drug pentamidine isethionate and its methoxy derivative. Both the drugs, when encapsulated in sugar-grafted liposomes were found to be more potent in comparison to normal liposome-encapsulated drug or to the free drug. Moreover, the mannose-grafted liposomes were adjudged to be the best in lowering of spleen parasite load in comparison with those bearing glucose or galactose. When encapsulated in mannose-grafted liposomes the therapeutic efficacy of pentamidine isethionate was found to be better than that of its methoxy derivative, although the latter seemed to be less toxic than the pentamidine isethionate itself.

Receptor-mediated targeting of drugs

Abstract: Richard J. Youle and David M. Neville, Jr. National Institute of Mental Health Laboratory of Neurochemistry Section on Biophysical Chemistry 9000 Rockville Pike Bethesda, Maryland 20205 A monocional anti-ThYl I-ricin A chain conjugate (OX-7-A chain) inactivated protein synthesis in ThYl 1 positive cells with first order kinetics for 15 h. After this period, the surviving cells began growing again. The maximal rate of protein synthesis inactivation was one log inactivation each 10 h and was reached when the cell surface antigen was saturated with conjugate. Therefore, the maximal inactivation of one addition of conjugate over the 15 h lifetime would leave 3% survivors. If the ricin B chain was added to cells treated with OX-7-A chain, the maximal rate of protein synthesis inactivation was increased three-fold, but the length of time the conjugate was effective (15 h) was not changed. Extrapolation shows that the maximum cell killing with OX-7-A chain plus B chain would leave only 0.003% survivors. We tested the effect of a second addition of conjugate after the first had reached its maximal inhibition of protein synthesis. OX-7-A was incubated at subsaturating concentrations with cells for 30 h and the survivors were then treated with a second addition of OX-7-A at the same concentration as the first. The survivors were inhibited by the second incubation only 5-20% as much as the initial cell population was inhibited by the first addition. Identical results were found for second additions of OX-7-A plus Band for OX-7-ricin plus lactose. Therefore, repeated additions of conjugate do not give repeated inhibition of cell growth. This result is consistent with a model that the target cell population was heterogenous in sensitivity to antibody-toxin conjugates and

The six diseases of WHO. Leishmaniasis.

Abstract: Leishmaniasis is not a single disease; rather, it is a collection of diseases caused by several different species of Leishmania, each of which has its own potential to cause a characteristic set of symptoms in man. No reliable estimates of the incidence and prevalence of leishmaniasis exist. It has been estimated that there are 400 000 new cases of leishmaniasis every year,' but the importance to public health is perhaps better gauged from the estimates of the number of cases in the recent epidemic of visceral leishmaniasis in Bihar, when it was conservatively estimated that there were 18 000 cases in 1977 and 40 000 in 1978 (R W Ashford, personal communication). Within the vertebrate host the protozoan parasite is restricted almost exclusively to cells of the mononuclear phagocyte (reticuloendothelial) system, in which they are present as amastigotes. Two main clinical manifestations of leishmaniasis exist-cutaneous and visceral-the distribution of which is 0 shown in fig 1. In the cutaneous disease the parasites are restricted to macrophages of the skin, whereas in the visceral manifestation, though amastigotes may be found in many tissues, the major centres of infection are within the phagocytic cells of the liver, spleen, and bone marrow. No convincing explanation of these different tissue tropisms has been presented. Arguments based on differences in temperature sensitivity or metabolic control are difficult to reconcile with the observation that the same parasite may cause visceral leishmaniasis in one individual . but a cutaneous manifestation in another.3 FIG 1-Geographical distribi In both the cutaneous and visceral infections the organism is transmitted to man by an insect vector, phlebotomine sandflies. Within the alimentary canal of the sandfly the amastigotes that are ingested together with the blood meal transform to a spindleshaped flagellated form-the promastigote. These are the infective form and are the stage of the life cycle that may be easily grown in vitro on blood-agar slopes. When an infective sandfly takes its next blood meal promastigotes are delivered from the anterior portion of the alimentary canal into the skin and thus a new infection begins. For many years progress on several aspects of leishmaniasis was handicapped by the difficulties of differentiating morphologically among the various species of Leishmania. Recent ultrastructural studies4 have shown differences in the size of amastigotes, but the main advance in identifying parasites has been the introduction of the techniques of biochemical taxonomy.56 The subdivision of the genus is complicated and to some extent controversial. An oversimplified classification includes L donovani, the causative organism of visceral leishmaniasis throughout the world. In India and some parts of East Africa transmission of this parasite is from man to man, while in other areas dogs and wild canids act as an animal reservoir. In the