Atovaquone is a component of Malarone, a widely prescribed antimalarial combination, that targets malaria respiration. Here we show that parasites with high-level resistance to an inhibitor of dihydroorotate dehydrogenase demonstrate unexpected atovaquone tolerance. Fortunately, the tolerance is diminished with proguanil, the second partner in Malarone. It is important to understand such "genet...

Current immunotherapy of posterior uveitis is non-specific and limited by drug toxicity and unpredictable relapses on therapy. Alternative modes of therapy being investigated using the rat model of experimental autoimmune uveoretinitis (EAU) have included the induction of tolerance with oral administration of milligram quantities of retinal antigens. In this preliminary report we demonstrate th...

The goals of tolerance in patients with solid organ transplants are to eliminate the lifelong need for immunosuppressive (IS) drugs and to prevent graft loss due to rejection or drug toxicity. Tolerance with complete withdrawal of IS drugs has been achieved in recipients of HLA-matched and mismatched living donor kidney transplants in 3 medical centers using hematopoietic cell transplants to es...

The current study used 64 rats to examine the effect of context shift on tolerance to alcohol, assessed by performance on a peak-interval task. Past research has extensively studied chronic alcohol intake and the mechanisms that underlie development of tolerance to alcohol in both humans and animals (McCusker & Brown, 1990; White, Roberts, & Best, 2002). Specifically, prior research has examine...

Abstract AIMS • To determine the expression patterns of specific ATP-binding cassette (ABC) transporters in medulloblastoma assess whether ABC play a role acquired drug resistance SHH using drug-tolerant cell line models extracellular vesicles transfer drug-tolerance and mechanism by which they do this METHOD Drug-tolerant lines were generated continuous culture drug-containing medium. trans- p...

Highly optimized tolerance (HOT) is a mechanism that relates evolving structure to power laws in interconnected systems. HOT systems arise where design and evolution create complex systems sharing common features, including (1) high efficiency, performance, and robustness to designed-for uncertainties, (2) hypersensitivity to design flaws and unanticipated perturbations, (3) nongeneric, special...

Drug addiction is likely to affect all of our lives, with any luck not through our own actions but probably because of one or more of our family and friends. Now firmly entrenched as a brain disease (Leshner, 1999; Wise, 2000), drug addiction is among the most costly such diseases in modern society. Drug addiction is most often defined as a chronically relapsing disorder in which the addict exp...

Drug allergy is one type of adverse reaction to drugs and encompasses a spectrum of hypersensitivity reactions with heterogeneous mechanisms and clinical presentations. A thorough history is essential to the management of drug allergy. Laboratory testing has a very limited role in the management of drug allergy. Graded dose challenges and procedures to induce drug tolerance might be required in...