Drug-resistant cell lines are essential tools for investigating the mechanisms of resistance to molecular-targeted anti-cancer drugs. However, little is known about how to establish clinically relevant drug-resistant cell lines. Our study examined the impact of a drug-free period on the establishment of a cell line with clinically relevant resistance to molecular-targeted drugs. We used PC9 cel...

Acute nicotinic acid (NiAc) administration results in rapid reduction of plasma FFA concentrations. However, sustained NiAc exposure is associated with tolerance development resulting in return of FFA to pretreatment levels. The aim of this study was to determine whether a 12 h rectangular exposure profile (intermittent dose group) could avoid tolerance development and thereby reverse insulin r...

This study assessed the association between longitudinal patterns of illicit drug use and clinical progression of human immunodeficiency virus (HIV) disease. Confidential computer-based interviews, which addressed illicit drug use and other factors, were completed by HIV-infected participants in Baltimore, Maryland, at 6-month intervals from 1998 onward. To assess this association, the authors ...

CONTEXT In HIV-infected patients having virologic suppression (plasma HIV RNA <50 copies/mL) with antiretroviral therapy, intermittent episodes of low-level viremia have been correlated with slower decay rates of latently infected cells and increased levels of viral evolution, but the clinical significance of these episodes is unknown. OBJECTIVE To determine if HIV-infected patients with inte...

Sensitization to the effects of drugs of abuse and associated stimuli contributes to drug craving, compulsive drug use, and relapse in addiction. Repeated opiate exposure produces behavioral sensitization that is hypothesized to result from neural plasticity in specific limbic, striatal and cortical systems. ΔFosB and FosB are members of the Fos family of transcription factors that are implicat...

Beta-lactams are regularly administered in intermittent short-term infusions. The percentage of the dosing interval during which free drug concentrations exceed the MIC (fT(>MIC)) is the measure of drug exposure that best correlates with clinical outcome for beta-lactams. Therefore, administration by continuous infusion has gained increasing interest recently. We studied 20 critically ill patie...

Obstructive sleep apnea is associated with high cardiovascular morbidity and mortality. Intermittent hypoxia of obstructive sleep apnea is implicated in the development and progression of insulin resistance and atherosclerosis, which have been attributed to systemic inflammation. Intermittent hypoxia leads to pro-inflammatory gene up-regulation in cell culture, but the effects of intermittent h...

Yoshikawa, Hiroyasu, Zuheng Ma, Anneli Björklund, and Valdemar Grill. Short-term intermittent exposure to diazoxide improves functional performance of -cells in a high-glucose environment. Am J Physiol Endocrinol Metab 287: E1202–E1208, 2004. First published August 3, 2004; doi:10.1152/ajpendo.00255.2004.—Prolonged periods of “ -cell rest” exert beneficial effects on insulin secretion from panc...

A pharmacokinetic-pharmacodynamic (PKPD) model that characterizes the full time course of in vitro time-kill curve experiments of antibacterial drugs was here evaluated in its capacity to predict the previously determined PK/PD indices. Six drugs (benzylpenicillin, cefuroxime, erythromycin, gentamicin, moxifloxacin, and vancomycin), representing a broad selection of mechanisms of action and PK ...

ethods: Plasma ACTH levels were measured after restraint stress in 19 male monkeys pretreated with saline or hydrocortisone. Monkeys ere then randomized to an undisturbed control condition or intermittent social separations followed by new pair formations. After 17 onths of exposure to the intermittent social manipulations, restraint stress tests were repeated to determine test/retest correlati...