Scientists find answer to parasites' drug resistance
Leishmaniasis parasites Sanjit Bagchi 26 April 2007 Source: SciDev.Net
Indian researchers have identified a mechanism of drug resistance in the parasites that cause visceral leishmaniasis, and suggest an effective way to reverse it.
The study was published in the April issue of the American Journal of Tropical Medicine and Hygiene.
Shyam Sundar, an author on the study from the Institute of Medical Sciences of Banaras Hindu University, told SciDev.Net that the resistance of the leishmaniasis parasite, Leishmania donovani, to sodium stibogluconate ― a common drug used to treat the disease ― is widespread in India.
The researchers studied leishmaniasis parasites and found that those resistant to sodium stibogluconate had an increased concentration of thiols ― sulphur-containing compounds ― in their cells.
The researchers also identified an enzyme, trypanothione reductase, and a gene, MRPA (multidrug resistance protein A) in the resistant parasites.
Sundar told SciDev.Net that these three factors increased the removal of the drug from the parasite's cell, thus resulting in drug resistance
According to the World Health Organization, India accounts for 50 per cent of global leishmaniasis burden, and rural parts of the region of Bihar account for 90 per cent of Indian cases. Bangladesh, Nepal and Sudan are also affected.
"In the most severely affected villages in Bihar, resistance is so high that stibogluconate can effectively treat only one third of the cases even when its dose is 6−8 times higher," said Sundar.
However, the researchers suggested that resistance can be reversed.
The enzyme glutathione reductase is essential in increasing the concentration of thiols in cells.
"An inhibitor of this enzyme may be used to decrease the thiol level and thus revert the drug resistance," Sundar explained.
Testing these inhibitors on the leishmaniasis parasite is the next step in future research.
Swapan Jana, secretary of the Society for Social Pharmacology ― an Indian nongovernmental organisation ― said, "Leishmaniasis predominantly affects poor people and hence despite the advent of various new drugs, stibogluconate, for its low cost, has importance in this disease."
"This study is impressive, because drug resistance is a big problem with stibogluconate, and this shows a way to revert it," he added.
Reference: American Journal Of Tropical Medicine 76, 681 (2007)
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treepatrol
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This is importatnt good find. While reading up on it I found this.
Sodium stibogluconate is a medicine used to treat leishmaniasis and is only available for administration by injection. It belongs to the class of medicines known as the pentavalent antimonials. Sodium stibogluconate is sold in the UK as Pentostam� (manufactured by GlaxoSmithKline). Widespread resistance has limited the utility of sodium stibogluconate, and in many parts of the world, amphotericin or miltefosine are used instead.
Amphotericin B (Fungilin�, Fungizone�, Abelcet�, AmBisome�, Fungisome�, Amphocil�, Amphotec�) is a polyene antimycotic drug, used intravenously in systemic fungal infections. It was originally extracted from Streptomyces nodosus, a filamentous bacterium, in 1955 at the Squibb Instittue for Medical Research from cultures of a undescribed streptomycete isolated from the soil collected in the Orinoco River region of Venezuela.
Its name originates from the chemical's amphoteric properties. Two amphotericins, Amphotericin A and Amphotericin B are known, but only B is used clinically because it is significantly more active in vivo.
Currently the drug is available as plain Amphotericin B, as cholesteryl sulfate complex, as lipid complex, and as liposomal formulation. The latter formulations have been developed to improve tolerability for the patient but may show considerable pharmacokinetic characteristics compared to plain Amphotericin B.
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Miltefosine (INN, trade names Impavido and Miltex) is an antiprotozoal drug. Originally developed as an antineoplastic, it is now registered and used by Zentaris GmbH in India, Colombia and Germany for the treatment of visceral and cutaneous leishmaniasis, and is undergoing clinical trials for this use in several other countries, such as Brazil[1] and Guatemala.[2] It is currently the only effective oral treatment for leishmaniasis.
Recent animal studies suggest miltefosine may also be effective against Trypanosoma cruzi {{{this bug acts like spirochetes itcysts up too}}}, the parasite responsible for Chagas' disease,[3] and several pathogenic fungi, including Cryptococcus neoformans, Candida, Aspergillus and Fusarium.[4]
Hexadecyltrimethylammonium bromide, a compound structurally similar to miltefosine, was recently found to exhibit potent in vitro activity against Plasmodium falciparum.[5]
This drug
Side effects The main side effects reported with miltefosine treatment are nausea and vomiting. Miltefosine has exhibited teratogenicity, and should not be administered to pregnant women.
Teratogenesis is a medical term, literally meaning monster-birth, which derives from teratology, the study of the frequency, causation, and development of congenital malformations--misleadingly called birth defects. These include gross morphological abnormalities, such as cleft lip and/or palate, dysmelia, anencephaly, or ventricular septal defect, but may also include phenomena such as increased risk of cervical cancer or discoloration of tooth enamel.
These malformations can arise from genetic abnormalities of the fetus, from adverse environmental circumstances (termed teratogens or tetragens), or a combination of these factors. Teratogenesis has gained a more specific usage for the development of abnormal cell masses during fetal growth (see pregnancy), causing physical defects in the fetus. The study of teratogenesis is called teratology.
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treepatrol
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bump up
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treepatrol
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Yes cavey the point is the drugs that are effective on these types. you jerkin my chain?
plasmodium sp
Amastigotic T. cruzi cyst
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treepatrol
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up for cavey
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treepatrol
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cavey
-------------------- Do unto others as you would have them do unto you. Remember Iam not a Doctor Just someone struggling like you with Tick Borne Diseases.
treepatrol
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-------------------- Do unto others as you would have them do unto you. Remember Iam not a Doctor Just someone struggling like you with Tick Borne Diseases.
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the point is the drugs that are effective on these types. 
you jerkin my chain? 
plasmodium sp
Amastigotic T. cruzi cyst
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