Atovaquone Proguanil Malarone

ATQ and proguanil operate synergistically. ATQ is a 2-hydroxynaphtoquinolone that disrupts electron transport in the parasite mitochondria at the cytochrome bc1 complex and collapses membrane potential, without affecting the host mitochondria.[25,26] Proguanil significantly enhances the ability of ATQ to collapse mitochon-drial membrane potential, and the combination drug should slow the emergence of AVQ-resistant parasites. However, mutations in the cytochrome b1 gene have appeared and are associated with ATQ/Pro resistance in vitro and in vivo. A P. falciparum isolate from a Thai patient with recrudescence after ATQ therapy showed a mutation at codon 268 with a tyrosine-for-serine substitution and an increased IC50 of almost 10,000-fold. A small number of ATQ/Pro treatment failures have now been reported primarily in nonimmune patients. Most have involved a N268S mutation, although one patient isolate contained a tyrosine-for-asparagine substitution at the same position.[8,9,27,28] ATQ resistance parasites generated in vitro may possess additional mutations in cytochrome b, including mutations at positions 133, 272, and 280, although these mutations impart lower levels of resistance in vitro and have not been observed in patient isolates to date.[29]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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