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991.
992.
Intranasal and intravenous administration of octa‐arginine modified poly(lactic‐co‐glycolic acid) nanoparticles facilitates central nervous system delivery of loperamide
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993.
Brian M Cox Macdonald J Christie Lakshmi Devi Lawrence Toll John R Traynor 《British journal of pharmacology》2015,172(2):317-323
Recent developments in the study of the structure and function of opioid receptors raise significant challenges for the definition of individual receptor types and the development of a nomenclature that precisely describes isoforms that may subserve different functions in vivo. Presentations at the 2013 meeting of the International Narcotics Research Conference in Cairns, Australia, considered some of the new discoveries that are now unravelling the complexities of opioid receptor signalling. Variable processing of opioid receptor messenger RNAs may lead to the presence of several isoforms of the μ receptor. Each opioid receptor type can function either as a monomer or as part of a homo- or heterodimer or higher multimer. Additionally, recent evidence points to the existence of agonist bias in the signal transduction pathways activated through μ receptors, and to the presence of regulatory allosteric sites on the receptors. This brief review summarizes the recent discoveries that raise challenges for receptor definition and the characterization of signal transduction pathways activated by specific receptor forms.
LINKED ARTICLES
This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 相似文献994.
Mmalebuso L. Mokoena Brian H. Harvey Francois Viljoen Susanna M. Ellis Christiaan B. Brink 《Psychopharmacology》2015,232(16):2921-2938
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Jan H Beumer Venkateswaran C Pillai Robert A Parise Susan M Christner Brian F Kiesel Michelle A Rudek Raman Venkataramanan 《British journal of clinical pharmacology》2015,80(5):1097-1108
Aim
Inducers and inhibitors of CYP3A, such as ritonavir and efavirenz, may be used as part of the highly active antiretroviral therapy (HAART) to treat HIV patients. HIV patients with chronic myeloid leukemia or gastrointestinal stromal tumour may need imatinib, a CYP3A4 substrate with known exposure response–relationships. Administration of imatinib to patients on ritonavir or efavirenz may result in altered imatinib exposure leading to increased toxicity or failure of therapy, respectively. We used primary human hepatocyte cultures to evaluate the magnitude of interaction between imatinib and ritonavir/efavirenz.Methods
Hepatocytes were pre-treated with vehicle, ritonavir, ketoconazole, efavirenz or rifampicin, and the metabolism of imatinib was characterized over time. Concentrations of imatinib and metabolite were quantitated in combined lysate and medium, using LC-MS.Results
The predicted changes in imatinib CLoral (95% CI) with ketoconazole, ritonavir, rifampicin and efavirenz were 4.0-fold (0, 9.2) lower, 2.8-fold (0.04, 5.5) lower, 2.9-fold (2.2, 3.5) higher and 2.0-fold (0.42, 3.5) higher, respectively. These predictions were in good agreement with clinical single dose drug–drug interaction studies, but not with reports of imatinib interactions at steady-state. Alterations in metabolism were similar after acute or chronic imatinib exposure.Conclusions
In vitro human hepatocytes predicted increased clearance of imatinib with inducers and decreased clearance with inhibitors of CYP enzymes. The impact of HAART on imatinib may depend on whether it is being initiated or has already been dosed chronically in patients. Therapeutic drug monitoring may have a role in optimizing imatinib therapy in this patient population. 相似文献998.
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Lisa M. Kuhns Soyang Kwon Daniel T. Ryan Robert Garofalo Gregory Phillips II Brian S. Mustanski 《Journal of urban health》2015,92(1):151-167
Evidence suggests that respondent-driven sampling (RDS) is an efficient approach to sampling among varied populations of adult men who have sex with men (MSM) both in the USA and abroad, although no studies have yet evaluated its performance among younger MSM, a population with a steep rise in HIV infection in recent years. Young MSM (YMSM) may differ in terms of their connectedness to other YMSM (e.g., due to evolving sexual identity, internalization of sexual minority stigma, and lack of disclosure to others) and mobility (e.g., due to parental monitoring) which may inhibit the sampling process. The aims of this study were to evaluate the efficiency and effectiveness of RDS-based sampling among young urban MSM and to identify factors associated with recruitment success. We hypothesized that demographic, social, behavioral, and network factors, including racial/ethnic minority status, homelessness (i.e., as an indicator of socioeconomic marginalization), HIV-positive status, substance use problems, gay community connectedness, and network size would be positively related to recruitment productivity, while sexual minority stigmatization, environmental barriers (e.g., parental monitoring), and meeting sex partners on the internet (i.e., virtual venue) would be negatively related to recruitment productivity. Between December 2009 and February 2013, we used RDS to recruit a sample of 450 YMSM, ages 16–20. Findings suggest that the use of RDS for sampling among YMSM is challenging and may not be feasible based on the slow pace of recruitment and low recruitment productivity. A large number of seeds (38 % of the sample, n = 172) had to be added to the sample to maintain a reasonable pace of recruitment, which makes use of the sample for RDS-based population estimates questionable. In addition, the prevalence of short recruitment chains and segmentation in patterns of recruitment by race/ethnicity further hamper the network recruitment process. Thus, RDS was not particularly efficient in terms of the rate of recruitment or effective in generating a representative sample. Hypotheses regarding factors associated with recruitment success were supported for network size and internalized stigma (but not other factors), suggesting that participants with larger network sizes or high levels of internalized stigma may have more and less success recruiting others, respectively. 相似文献