urea-stibamine and Leishmaniasis--Visceral

In the 19(th) century, a devastating epidemic of visceral leishmaniasis (kala-azar) swept through northeast India. After identification of the pathogenic agent, Leishmania donovani, in 1903, the question of its transmission remained to be resolved. In 1904, thanks to work by L. Rogers on cultures of this parasite it became probable that a haematophagous arthropod was responsible for transmission. J.A. Sinton suggested, in 1925, the distribution of the sand fly Phlebotomus argentipes was similar to that of the disease and, thereafter, two independent teams led by H.E. Shortt in Assam and R. Knowles and L. Napier in Calcutta concentrated on this potential vector. Parallel work was in progress in China, directed by E. Hindle and W. S. Patton for the Royal Society Kala-azar Commission, on another species of sand fly. In 1942 the Assam workers transmitted L. donovani to five human volunteers by the bites of colonised P. argentipes and the race was over.

Topics: Animals; Antiprotozoal Agents; History, 20th Century; Humans; India; Insect Bites and Stings; Insect Vectors; Leishmania donovani; Leishmaniasis, Visceral; Nontherapeutic Human Experimentation; Organometallic Compounds; Phlebotomus; Tropical Medicine; Urea

The uptake of glycoside-bearing liposomes by macrophages has been studied in vitro. Since the uptake was found to be specific for the end sugar attached to the glycoside, the possibility is raised that glycoside-bearing liposomes might be used in vivo as systems to deliver drugs to macrophages. Using the antileishmanial drug urea stibamine, these delivery systems have been tested in vivo against model leishmaniasis. The results indicate that the drug encapsulated in sugar-coated liposomes is much more potent in comparison with normal liposome-encapsulated drug or to the free drug. Mannose-grafted liposomes are more efficient in transportation of drugs compared with those bearing glucose. Toxicity studies involving blood parameters, histological staining of tissues and specific enzyme activities related to liver function, show no apparent toxicity with the drugs. Hence, drug encapsulated sugar-coated liposomes may have possible applications to humans.

Topics: Animals; Antiprotozoal Agents; Cricetinae; Disease Models, Animal; Drug Carriers; Drug Compounding; Glucose; Glycosides; Leishmaniasis, Visceral; Liposomes; Liver; Macrophages; Male; Mannose; Mesocricetus; Mice; Organometallic Compounds; Urea

The antileishmanial antimonial drug urea stibamine was encapsulated in mannosylated and nonmannosylated liposomes and was tested against experimental leishmanial infection in hamsters. The study demonstrated that liposome encapsulation of urea stibamine enhanced its effectiveness, an effect which was greater when mannosylated liposomes were used.

Topics: Animals; Antiprotozoal Agents; Cricetinae; Drug Carriers; Leishmaniasis, Visceral; Liposomes; Mannose; Mesocricetus; Mononuclear Phagocyte System; Organometallic Compounds; Urea

Ureastibamine, a pentavalent antimonial, reduced the parasitic load in the 60-day model of infection of L. donovani in hamsters. It also inhibited the in vivo multiplication of I donovani amastigotes in hamster peritoneal macrophages. No inhibition in either promastigote multiplication or amastigotes transformation was noted with filtrate obtained after incubation of the drugs for 72 h in the macrophage culture. Incubation of macrophages with ureastibamine revealed an impairment in the uptake of deoxyglucose. The effect of ureastibamine was compared with that of another pentavalent antimonial, sodium stibogluconate. It is suggested that impairment of macrophage membrane may contribute towards the adverse effect of these drugs against the intracellular parasite.

Topics: Animals; Antiprotozoal Agents; Cricetinae; Disease Models, Animal; Leishmania donovani; Leishmaniasis, Visceral; Male; Mesocricetus; Organometallic Compounds; Urea

Topics: Antimony; Antiprotozoal Agents; History, 20th Century; Humans; Leishmaniasis, Visceral; Organometallic Compounds; Urea

An improved method for preparation of urea stibamine was developed. The crude p-acetylaminophenyl stibonic acid (II) prepared was purified by dissolving it in Na2CO3 solution, whererin acid (II) dissolved leaving behind the impurities. Acid (II) was directly combined with urea without hydrolyzing the acetyl group to give urea stibamine. Biological activity of the drug in vitro as well as in vivo was also studied. The drug had no inhibitory effect on growth, respiration, incorporation of radiolabeled precursors into promastigotes of L. donovani, and on transformation of amastigotes to promastigotes. In infected hamster, the effect of the drug was highly significant in vivo., as it removed the parasitic burden completely.

Topics: Animals; Antimony; Antiprotozoal Agents; Cricetinae; DNA Replication; Glycolysis; Indicators and Reagents; Leishmania donovani; Leishmaniasis, Visceral; Mesocricetus; Organometallic Compounds; Protein Biosynthesis; RNA; Urea

Topics: Humans; Leishmaniasis; Leishmaniasis, Visceral; Organometallic Compounds; Urea

Topics: Humans; Leishmania; Leishmaniasis; Leishmaniasis, Visceral; Organometallic Compounds; Urea