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https://www.readbyqxmd.com/read/28231276/alterations-in-cellular-pharmacokinetics-and-pharmacodynamics-of-elvitegravir-in-response-to-ethanol-exposure-in-hiv-1-infected-monocytic-u1-cells
#1
Narasimha M Midde, Namita Sinha, Pradeep B Lukka, Bernd Meibohm, Santosh Kumar
Ethanol consumption is negatively associated with antiretroviral therapy (ART) adherence and general health in HIV positive individuals. Previously, we demonstrated ethanol-mediated alterations to metabolism of elvitegravir (EVG) in human liver microsomes. In the current study, we investigated ethanol influence on the pharmacokinetic and pharmacodynamic interactions of EVG in HIV infected monocytic (U1) cells. U1 cells were treated with 5 μM EVG, 2 μM Cobicistat (COBI), a booster drug, and 20 mM ethanol for up to 24 hours...
2017: PloS One
https://www.readbyqxmd.com/read/28230738/clinical-implications-of-20-hydroxyeicosatetraenoic-acid-in-the-kidney-liver-lung-and-brain-an-emerging-therapeutic-target
#2
REVIEW
Osama H Elshenawy, Sherif M Shoieb, Anwar Mohamed, Ayman O S El-Kadi
Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport...
February 20, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28229921/protective-effect-of-a-polysaccharide-from-anoectochilus-roxburghii-against-carbon-tetrachloride-induced-acute-liver-injury-in-mice
#3
Biyu Zeng, Minghua Su, Qingxi Chen, Qiang Chang, Wei Wang, Huihua Li
ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus roxburghii (Wall.) Lindl. is traditionally used for the treatment of various types of chronic and acute hepatitis in China. Considering that Anoectochilus roxburghii polysaccharide (ARPT) is the main constituent of Anoectochilus roxburghii, the present study was designed to investigate the hepatoprotective effect of ARPT and its possible mechanism in carbon tetrachloride (CCl4)-induced mice. MATERIAL AND METHODS: The hepatoprotective activity of ARPT (150, 300 and 500 mg/kg) were investigated on CCl4-induced acute liver damage in mice...
February 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28229443/-desvenlafaxine-and-neuropathic-pain-additional-clinical-benefits-of-a-second-generation-serotonin-noradrenaline-reuptake-inhibitor
#4
REVIEW
A Alcantara-Montero
INTRODUCTION: Desvenlafaxine is the third antidepressant within the group of serotonin-norepinephrine reuptake inhibitors. The latest clinical practice guidelines consulted agree that tricyclic antidepressants, dual (venlafaxine/duloxetine) and gabapentin/pregabalin antiepileptics, are the first-line drugs in the treatment of neuropathic pain, being tramadol, lidocaine 5% patches and capsaicin 8% patches of second-line drugs, while strong opioids constitute a third line treatment. The interaction between the binomial pain and depression is very frequent, being the psychological complication more frequent in patients with chronic pain...
March 1, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28229379/a-novel-frameshift-mutation-in-the-sterol-27-hydroxylase-gene-in-an-egyptian-family-with-cerebrotendinous-xanthomatosis-without-cataract
#5
Mohamed S Abdel-Hamid, Mahmoud Y Issa, Ghada A Otaify, Maha S Zaki
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder caused by deficiency of the mitochondrial cytochrome P450 sterol 27-hydroxylase enzyme encoded by CYP27A1 gene. CTX is characterized by tendon xanthomas, juvenile cataracts and multiple progressive neurological symptoms. Here we report on the clinical and molecular findings of a 35-years old Egyptian patient with CTX without cataract. Parents were first cousins with family history of two deceased sibs with mild impaired cognitive functions and epilepsy without appearance of tendon xanthomas...
February 22, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28229376/the-pharmacogenetics-of-tacrolimus-in-corticosteroid-sparse-pediatric-and-adult-kidney-transplant-recipients
#6
Mads Juul Madsen, Troels K Bergmann, Kim Brøsen, Helle Charlotte Thiesson
INTRODUCTION: Tacrolimus is a calcineurin inhibitor used as an immunosuppressant drug in solid organ transplantation, and is mainly metabolized by cytochrome P450 (CYP) 3A4 and CYP3A5. Studies have shown an association between the CYP3A5 genotype and tacrolimus dose-adjusted trough concentrations. Variants in the genes PPARA, POR and CYP3A4 have recently been shown to influence tacrolimus metabolism. Furthermore, pharmacokinetic interaction between corticosteroid treatment and tacrolimus has been shown...
February 22, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28229374/effect-of-short-term-fasting-on-systemic-cytochrome-p450-mediated-drug-metabolism-in-healthy-subjects-a-randomized-controlled-crossover-study-using-a-cocktail-approach
#7
Laureen A Lammers, Roos Achterbergh, Ron H N van Schaik, Johannes A Romijn, Ron A A Mathôt
BACKGROUND AND OBJECTIVE: Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. METHODS: In a randomized, controlled, crossover trial, 12 healthy subjects received a single administration of a cytochrome P450 (CYP) probe cocktail, consisting of caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and warfarin (CYP2C9), on four occasions: an oral (1) and intravenous (2) administration after an overnight fast (control) and an oral (3) and intravenous (4) administration after 36 h of fasting...
February 22, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28228093/comparative-profiling-of-hepatopancreas-transcriptomes-in-satiated-and-starving-pomacea-canaliculata
#8
Lei Yang, Tian-Yin Cheng, Fei-Yan Zhao
BACKGROUND: Although Pomacea canaliculata is native to South and Central America, it has become one of the most abundant invasive species worldwide and causes extensive damage to agriculture and horticulture. Conventional physical and chemical techniques have been used to eliminate P. canaliculata, but the effects are not ideal. Therefore, it is important to devise a new method based on a greater understanding of the biology of P. canaliculata. However, the molecular mechanisms underlying digestion and absorption in P...
February 22, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28224916/transcriptional-markers-enable-identification-of-rye-grass-lolium-sp-plants-with-non-target-site-based-resistance-to-herbicides-inhibiting-acetolactate-synthase
#9
Arnaud Duhoux, Sébastien Carrère, Alexis Duhoux, Christophe Délye
Molecular detection of herbicide non-target-site-based resistance (NTSR) classically requires extensively validated NTSR genes. We assessed the feasibility of predicting NTSR phenotypes using expression data of NTSR transcriptional markers, i.e., transcripts which expression levels are statistically correlated to NTSR. Markers were sought by comparative RNA-Seq analysis of untreated NTSR or sensitive plants from four rye-grass populations followed by expression quantification in 299 individual plants with characterised sensitivity to two acetolactate-synthase-inhibiting herbicides...
April 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28223967/secretome-prediction-of-two-m-tuberculosis-clinical-isolates-reveals-their-high-antigenic-density-and-potential-drug-targets
#10
Fernanda Cornejo-Granados, Zyanya L Zatarain-Barrón, Vito A Cantu-Robles, Alfredo Mendoza-Vargas, Camilo Molina-Romero, Filiberto Sánchez, Luis Del Pozo-Yauner, Rogelio Hernández-Pando, Adrián Ochoa-Leyva
The Excreted/Secreted (ES) proteins play important roles during Mycobacterium tuberculosis invasion, virulence, and survival inside the host and they are a major source of immunogenic proteins. However, the molecular complexity of the bacillus cell wall has made difficult the experimental isolation of the total bacterial ES proteins. Here, we reported the genomes of two Beijing genotype M. tuberculosis clinical isolates obtained from patients from Vietnam (isolate 46) and South Africa (isolate 48). We developed a bioinformatics pipeline to predict their secretomes and observed that ~12% of the genome-encoded proteins are ES, being PE, PE-PGRS, and PPE the most abundant protein domains...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28223151/testosterone-rapidly-increases-ca-2-activated-k-currents-causing-hyperpolarization-in-human-coronary-artery-endothelial-cells
#11
Katesirin Ruamyod, Wattana B Watanapa, Chairat Shayakul
Testosterone has endothelium-dependent vasodilatory effects on the coronary artery, with some reports suggesting endothelial ion channel involvement. This study employed the whole-cell patch clamp technique to investigate the effect of testosterone on ion channels in human coronary artery endothelial cells (HCAECs) and the mechanisms involved. We found that 0.03-3μM testosterone significantly induced a rapid, concentration-dependent increase in total HCAEC current (EC50, 71.96±1.66nM; maximum increase, 59...
February 18, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28221037/computational-investigation-of-ligand-binding-to-the-peripheral-site-in-cyp3a4-conformational-dynamics-and-inhibitor-discovery
#12
Hanwen Du, Junhao Li, Yingchun Cai, Hongxiao Zhang, Guixia Liu, Yun Tang, Weihua Li
Human cytochrome P450 3A4 (CYP3A4) is a major drug-metabolizing enzyme responsible for the metabolism of ~50% of clinically used drugs and is often involved in drug-drug interactions. It exhibits atypical binding and kinetic behavior towards many ligands. Binding of ligands to CYP3A4 is a complex process. Recent studies from both crystallography and biochemistry suggested the existence of a peripheral ligand-binding site at the enzyme surface. However, the stability of ligand bound at this peripheral site and the possibility of discovering new CYP3A4 ligands based on this site remain unclear...
February 21, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28220904/recent-advances-in-occupational-and-environmental-health-hazards-of-workers-exposed-to-gasoline-compounds
#13
REVIEW
Christopher E Ekpenyong, Asuquo E Asuquo
The impact of health and environmental hazards, associated with the constituents of gasoline, on occupationally exposed workers has been recorded over the past few decades. However, the scientific literature on their pathogenic potential remains incomplete, which could affect the current understanding of the associated health risks. This review provides current information based on recently improved research techniques to evaluate gasoline toxicity profiles for humans. Our current knowledge provides insight into the intricate mechanism of gasoline-induced adverse effects, including the formation of reactive metabolites via bio-activation and subsequent generation of reactive oxygen species (ROS) and oxidative stress, which are involved in multiple mechanisms that are central to the aetiology of gasoline-induced toxicity...
February 21, 2017: International Journal of Occupational Medicine and Environmental Health
https://www.readbyqxmd.com/read/28219743/significant-association-of-cyp19a-promoter-methylation-with-environmental-factors-and-gonadal-differentiation-in-olive-flounder-paralichthys-olivaceus
#14
Zhaofei Fan, Yuxia Zou, Shuang Jiao, Xungang Tan, Zhihao Wu, DongDong Liang, Peijun Zhang, Feng You
The sex ratio of olive flounder Paralichthys olivaceus is sensitive to temperature or exogenous hormone exposures in the period of gonadal differentiation. Among sex-related genes, cyp19a, encoding cytochrome P450 aromatase,exhibits significant sex-dimorphic expression pattern and plays an important role in fish gonadal differentiation and development. The present study investigated the expression levels and promoter methylation dynamics of cyp19a and its regulators (nr5a2 and nr0b1), and sex-steroid hormone levels during flounder gonadal differentiation under the treatments of high temperature and estradiol-17β (E2)...
February 17, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28219710/unique-effect-of-4-hydroxyestradiol-and-its-methylation-metabolites-on-lipid-and-cholesterol-profiles-in-ovariectomized-female-rats
#15
Pan Wang, Bao-Ting Zhu
Animal studies have shown that endogenous estrogens such as 17β-estradiol (E2) can modulate lipid profiles in vivo, and this effect is generally thought to be mediated by the estrogen receptors (ERs). The present study sought to test a hypothesis that some of the endogenous estrogen metabolites that have very weak estrogenic activity may exert some of their modulating effects on lipid metabolism in an ER-independent manner. Using ovariectomized female rats as an in vivo model, we found that 4-hydroxyestradiol (4-OH-E2) has a markedly stronger effect in reducing the adipocyte size and serum cholesterol level in rats compared to E2, despite the weaker estrogenic activity of 4-OH-E2...
February 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28219593/betel-nut-chewing-is-associated-with-reduced-tacrolimus-concentration-in-taiwanese-liver-transplant-recipients
#16
W-Y Chen, C-Y Lee, P-Y Lin, C-E Hsieh, C-J Ko, K-H Lin, C-C Lin, Y-Z Ming, Y-L Chen
PURPOSE: Studies have shown that arecoline, the major alkaloid component of betel nuts, alters the activity of enzymes in the cytochrome P450 (CYP-450) family. Tacrolimus, an immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. We aimed to investigate whether dose-adjusted blood trough levels of tacrolimus differed over time between betel nut-chewing and non-betel nut-chewing liver transplant recipients...
March 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28218515/chlorinated-glycopeptide-antibiotic-peptide-precursors-improve-cytochrome-p450-catalyzed-cyclization-cascade-efficiency
#17
Madeleine Peschke, Clara Brieke, Rob J A Goode, Ralf B Schittenhelm, Max J Cryle
The activity of glycopeptide antibiotics (GPAs) depends upon important structural modifications to their precursor heptapeptide backbone: specifically, the cytochrome P450-catalyzed oxidative cross-linking of aromatic side chains as well as the halogenation of specific residues within the peptide. The timing of halogenation and its effect on the cyclization of the peptide are currently unclear. Our results show that chlorination of peptide precursors improves their processing by P450 enzymes in vitro, which provides support for GPA halogenation occurring prior to peptide cyclization during nonribosomal peptide synthesis...
February 24, 2017: Biochemistry
https://www.readbyqxmd.com/read/28218310/crispr-knockout-rat-cytochrome-p450-3a1-2-model-for-advancing-drug-metabolism-and-pharmacokinetics-research
#18
Jian Lu, Yanjiao Shao, Xuan Qin, Daozhi Liu, Ang Chen, Dali Li, Mingyao Liu, Xin Wang
Cytochrome P450 (CYP) 3A accounts for nearly 30% of the total CYP enzymes in the human liver and participates in the metabolism of over 50% of clinical drugs. Moreover, CYP3A plays an important role in chemical metabolism, toxicity, and carcinogenicity. New animal models are needed to investigate CYP3A functions, especially for drug metabolism. In this report, Cyp3a1/2 double knockout (KO) rats were generated by CRISPR-Cas9 technology, and then were characterized for viability and physiological status. The Cyp3a1/2 double KO rats were viable and fertile, and had no obvious physiological abnormities...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28215799/comprehensive-understanding-of-pm2-5-on-gene-and-microrna-expression-patterns-in-zebrafish-danio-rerio-model
#19
Junchao Duan, Yang Yu, Yang Li, Li Jing, Man Yang, Ji Wang, Yanbo Li, Xianqing Zhou, Mark R Miller, Zhiwei Sun
PM2.5 is a major public health concern and some severe diseases have been attributed to exposure to PM2.5. However, a comprehensive understanding of gene and microRNA expression patterns induced by PM2.5 is missing. The objective of this study was to evaluate the toxicity of PM2.5 via genome-wide transcriptional analysis in the model teleost fish, zebrafish (Danio rerio). Gene ontology analysis revealed that the most impact gene functional categories induced by PM2.5 included oxidation-reduction process, transport, response to xenobiotic stimulus, response to chemical stimulus and metabolic process...
February 16, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28215634/isolation-and-expansion-of-human-pluripotent-stem-cell-derived-hepatic-progenitor-cells-by-growth-factor-defined-serum-free-culture-conditions
#20
Takayuki Fukuda, Kazuo Takayama, Mitsuhi Hirata, Yu-Jung Liu, Kana Yanagihara, Mika Suga, Hiroyuki Mizuguchi, Miho K Furue
Limited growth potential, narrow ranges of sources, and difference in variability and functions from batch to batch of primary hepatocytes cause a problem for predicting drug-induced hepatotoxicity during drug development. Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells in vitro are expected as a tool for predicting drug-induced hepatotoxicity. Several studies have already reported efficient methods for differentiating hPSCs into hepatocyte-like cells, however its differentiation process is time-consuming, labor-intensive, cost-intensive, and unstable...
February 17, 2017: Experimental Cell Research
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