The SLC22A1 influx transporter is expressed on the basolateral membrane of hepatocytes and is involved in the excretion of numerous cations. Inhibition of SLC22A1 by several antiretrovirals, such as the protease inhibitor darunavir, has not previously been determined. In order to better understand and predict drug-SLC22A1 interactions, a range of antiretrovirals were screened for SLC22A1-associ...

As an experimental model for resistance to ciVdiamminedichloroplatinum(II) (</\-l)!)!'). murine leukemia LI210 cells have been exposed to a stepwise increase in c/s-DDP concentration to produce a variety of resistant cell lines. Intraspecies hybrids of the sensitive and resistant cells were made to determine whether cis-DDP resistance is a dominant or recessive trait. Hybrid cells displayed a p...

: Niemann-Pick disease type A (NPA) is a lysosomal storage disease caused by mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM). Deficiency in ASM function results in lysosomal accumulation of sphingomyelin and neurodegeneration. Currently, there is no effective treatment for NPA. To accelerate drug discovery for treatment of NPA, we generated induced pluripotent stem cells fr...

P-Glycoprotein (P-gp) is an ATP-dependent drug efflux transporter involved in multidrug resistance and drug disposition in many organ systems. A majority of P-gp substrates are lipophilic amine drugs which also exhibit rapid extensive accumulation in lung tissue. P-gp is expressed in lung tissue, and the very nature of this drug efflux mechanism suggests a moderating role in pulmonary drug disp...

OBJECTIVE HIV mutation accumulation has great implications for pharmacoeconomics and clinical care, yet scarcity of data has hindered its representation in decision analytic models. Our objective is to determine the accuracy with which mutation accumulation and other unmeasured parameters could be estimated during model calibration. METHODS We used a second-order Monte Carlo simulation of HIV...

Cyclosporin A abrogates pleiotropic drug resistance in certain experimental tumors. Its impact on drug-sensitive tumors has not been investigated. Our studies show that in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 cyclosporin A enhances daunorubicin inhibition of DNA synthesis in vitro and prolongs survival of host mice in vivo. Of particular interest is that cyclosporin A conve...

Drug discovery is a long process in which only a few successful new therapeutic discoveries are made and identification of drug target candidate proteins requires considerable time and efforts. However, the accumulation of information on drugs has made it possible to devise new computational methods for classifying drug target candidates. In this paper, we devise a Drug Target Protein (DT-P) cl...

Acrolein (AC) and chloroacetaldehyde (CHA) are metabolites of the non-multidrug resistance cytotoxic drugs cyclophosphamide and ifosfamide. It has previously been reported that both metabolites can induce extensive depletion of glutathione (GSH) in vitro and in vivo and that this depletion occurs at drug concentrations in the micromolar range. A link between the function of the multidrug resist...

conclusions after paravertebral implantation of rifapentine polylactic acid sustained-release microspheres, the concentration of rifapentine in local vertebral bone tissues was maintained above the tb minimum inhibitory concentration for up to 60 days with no apparent accumulation of the drug in other tissues. methods this study is a basic animal experimental study that began on july 17, 2014 i...