Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C.
The anticryptosporidial activity of four macrolides alone and in combination with other antimicrobial agents was investigated against ten clinical isolates of Cryptosporidium parvum recovered from stools of AIDS patients. The susceptibility tests were performed by inoculation of the protozoa on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C.
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Antimarial drug resistance develops when spontaneously occurring parasite mutants with reduced susceptibility are selected, and are then transmitted. Drugs for which a single point mutation confers a marked reduction in susceptibility are particularly vulnerable. Low clearance and a shallow concentration-effect relationship increase the chance of selection.
Antimalarial screening was performed for microbial metabolites that simulate artemisinin in their mode of action, a potent antimalarial component of an herbal remedy with a characteristic peroxide structure. Nanaomycin A was identified in this screen as an antimalarial compound, together with radicicol and several other compounds already reported (J. Antibiotics 51: 153 approximately 160, 1998). Nanaomycin A inhibited in vitro growth of the human malaria parasite Plasmodium falciparum with an IC80 value of 33.1 nM. It was as potent as radicicol and about 1/10 as potent as artemisinin.
The interactions of artemisinin with atovaquone, quinine, and mefloquine were investigated in three Plasmodium falciparum strains (strains F-32, FCR-3, and K-1) by an in vitro culture assay. The parasites were cultured for 48 h in the presence of different concentrations and proportions of two drugs at a time in a checkerboard design. The response parameters were determined, and the sums of the fractional inhibitory concentrations (sigmaFICs) of the drug combinations were calculated for different degrees of inhibition (50% effective concentration [EC50], EC90, and EC99).
Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
In an open-label trial carried out on the northwest border of Thailand, 1596 patients with uncomplicated multidrug-resistant falciparum malaria were randomly assigned to receive atovaquone-proguanil, atovaquone-proguanil-artesunate, or artesunate-mefloquine and were followed up for 42 days. All 3 regimens were highly effective and well tolerated. Fever duration and parasite clearance times were significantly shorter among patients who received artesunate (P<.001).
A modified fixed-ratio isobologram method for studying the in vitro interactions between antiplasmodial drugs is described. This method was used to examine the interactions between atovaquone, proguanil, and dihydroartemisinin. The interaction between atovaquone and proguanil was synergistic against atovaquone-sensitive strains K1 and T996; however, there was a loss of synergy against atovaquone-resistant strain NGATV01 isolated after Malarone (the combination of atovaquone and proguanil) treatment failure.
BACKGROUND: There is no safe, practical, and effective treatment for pregnant women infected with multidrug-resistant Plasmodium falciparum. METHODS: We recruited pregnant Karen women in the second or third trimesters of pregnancy who had uncomplicated falciparum malaria for a randomized, open-label trial with a restricted sequential trial design of 7 days of supervised quinine (SQ7) versus 3 days of artesunate-atovaquone-proguanil (AAP). RESULTS: Eight-one pregnant women entered the study between December 2001 and July 2003; 42 were treated with SQ7 and 39 were treated with AAP.
The American Journal of Tropical Medicine and Hygiene
Combinations are set to become the mainstay in treatment and prophylaxis of malaria due to Plasmodium falciparum. Various antimalarials have been implicated in cardiotoxicity via prolongation of the QTc interval. Atovaquone-proguanil is an effective and increasingly popular antimalarial choice when used alone or with artesunate in areas of drug resistance. We report the results of an investigation carried out on the Thai-Burmese border in 42 patients randomized to receive either atovaquone-proguanil or atovaquone-proguanil-artesunate for three days.
BACKGROUND: The use of anti-malarial drug combinations with artemisinin or with one of its derivatives is now widely recommended to overcome drug resistance in falciparum as well as vivax malaria. The fixed oral dose artemisinin-naphthoquine combination (ANQ, ARCO) is a newer artemisinin-based combination (ACT) therapy undergoing clinical assessment. A study was undertaken to assess the safety, efficacy and tolerability of ANQ combination in areas of multi-drug resistance to generate preliminary baseline data in adult population of Papua New Guinea.