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https://www.readbyqxmd.com/read/29055041/the-possible-clinical-impact-of-risperidone-on-p-glycoprotein-mediated-transport-of-tacrolimus-a-case-report-and-in-vitro-study
#1
Nao Watanabe, Hiroki Higashi, Saki Nakamura, Keiko Nomura, Yuichi Adachi, Masato Taguchi
The authors encountered the case of an 8-fold increase in the concentration/dose (C/D) ratio of tacrolimus (TAC) following the coadministration of voriconazole (VRCZ) in a hematopoietic stem cell transplantation (HSCT) recipient. The interaction observed was much greater than expected and the patient had also been treated with oral risperidone (RSP). We hypothesized that cytochrome P450 (CYP)3A inhibition of the small intestine by VRCZ and P-glycoprotein (P-gp) inhibition of the small intestine by RSP exerted a synergistic effect on the bioavailability of TAC...
October 20, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29054049/individual-variability-in-clinical-effect-and-tolerability-of-opioid-analgesics-importance-of-drug-interactions-and-pharmacogenetics
#2
REVIEW
Vigdis Solhaug, Espen Molden
BACKGROUND: As pain is often a comorbid condition, many patients use opioid analgesics in combination with several other drugs. This implies a generally increased risk of drug interactions, which along with inherent pharmacogenetic variability and other factors may cause differences in therapeutic response of opioids. AIM: To provide an overview of interactions and pharmacogenetic variability of relevance for individual differences in effect and tolerability of opioid analgesics, which physicians and other healthcare professionals should be aware of in clinical practice...
October 17, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29052919/oamdp-a-novel-podophyllotoxin-derivative-induces-apoptosis-cell-cycle-arrest-and-autophagy-in-hepatoma-hepg2-cells
#3
Jie Ren, Yu Liu, Lixia Li, Yuexin Zhao, Zhongyu Li, Chao Wu, Lin Chen, Kun Hu
4β-(1,3,4-oxadiazole-2-amino-5-methyl)-4-deoxypodophyllotoxin (OAMDP), a novel podophyllotoxin derivative, has demonstrated potent anti-tumor activity with significant cytotoxic effect. Here we report the anti-proliferative effect of OAMDP, for which OAMDP could suppress the proliferation of HepG2 cells (human hepatoma cell line) in a dose- and time-dependent manner. After treating with OAMDP, cell apoptosis was confirmed by Annexin V-FITC/PI double staining assay. Furthermore, flow cytometry analysis revealed the loss of mitochondrial membrane potential and the increase of intracellular reactive oxygen species in HepG2 cells...
October 20, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29050365/mitochondrial-genome-variation-and-prostate-cancer-a-review-of-the-mutational-landscape-and-application-to-clinical-management
#4
REVIEW
Anton M F Kalsbeek, Eva K F Chan, Niall M Corcoran, Christopher M Hovens, Vanessa M Hayes
Prostate cancer is a genetic disease. While next generation sequencing has allowed for the emergence of molecular taxonomy, classification is restricted to the nuclear genome. Mutations within the maternally inherited mitochondrial genome are known to impact cancer pathogenesis, as a result of disturbances in energy metabolism and apoptosis. With a higher mutation rate, limited repair and increased copy number compared to the nuclear genome, the clinical relevance of mitochondrial DNA (mtDNA) variation requires deeper exploration...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050321/interaction-among-cyp2c8-gpiiia-and-p2y12-variants-increase-susceptibility-to-ischemic-stroke-in-chinese-population
#5
Xingyang Yi, Jing Lin, Yanfen Wang, Ju Zhou, Qiang Zhou
PURPOSE: Genetic variants in cytochrome P450 (CYP), platelet membrane receptor (P2Y12, P2Y1), and glycoprotein IIIa (GPIIIa) genes are associated with the efficacy of clopidogrel and adverse clinical events on ischemic stroke (IS) patients. However, few studies have assessed whether gene-gene interactions among these genes influence the risk of IS. The aim of the present study was to investigate the association of fifteen variants with IS and to determine whether these gene-gene interactions increase the risk of IS...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048755/nifedipine-prevents-apoptosis-of-alcohol-exposed-first-trimester-trophoblast-cells
#6
Alan D Bolnick, Jay M Bolnick, Hamid-Reza Kohan-Ghadr, Brian A Kilburn, Michael Hertz, Jing Dai, Sascha Drewlo, D Randall Armant
BACKGROUND: Maternal alcohol abuse leading to fetal alcohol spectrum disorder (FASD) includes fetal growth restriction (FGR). Ethanol induces apoptosis of human placental trophoblast cells, possibly disrupting placentation and contributing to FGR in FASD. Ethanol facilitates apoptosis in several embryonic tissues, including human trophoblasts, by raising intracellular Ca(2+) . We previously found that acute ethanol exposure increases trophoblast apoptosis due to signaling from both intracellular and extracellular Ca(2+) ...
October 19, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29044108/echinochloa-crus-galli-genome-analysis-provides-insight-into-its-adaptation-and-invasiveness-as-a-weed
#7
Longbiao Guo, Jie Qiu, Chuyu Ye, Gulei Jin, Lingfeng Mao, Haiqiang Zhang, Xuefang Yang, Qiong Peng, Yingying Wang, Lei Jia, Zhangxiang Lin, Gengmi Li, Fei Fu, Chen Liu, Li Chen, Enhui Shen, Weidi Wang, Qinjie Chu, Dongya Wu, Sanling Wu, Chenyang Xia, Yongfei Zhang, Xiaomao Zhou, Lifeng Wang, Lamei Wu, Weijie Song, Yunfei Wang, Qingyao Shu, Daisuke Aoki, Emi Yumoto, Takao Yokota, Koji Miyamoto, Kazunori Okada, Do-Soon Kim, Daguang Cai, Chulong Zhang, Yonggen Lou, Qian Qian, Hirofumi Yamaguchi, Hisakazu Yamane, Chui-Hua Kong, Michael P Timko, Lianyang Bai, Longjiang Fan
Barnyardgrass (Echinochloa crus-galli) is a pernicious weed in agricultural fields worldwide. The molecular mechanisms underlying its success in the absence of human intervention are presently unknown. Here we report a draft genome sequence of the hexaploid species E. crus-galli, i.e., a 1.27 Gb assembly representing 90.7% of the predicted genome size. An extremely large repertoire of genes encoding cytochrome P450 monooxygenases and glutathione S-transferases associated with detoxification are found. Two gene clusters involved in the biosynthesis of an allelochemical 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and a phytoalexin momilactone A are found in the E...
October 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/29042943/suxiao-jiuxin-pill-protects-cardiomyocytes-against-mitochondrial-injury-and-alters-gene-expression-during-ischemic-injury
#8
Xiaofen Ruan, Tiejun Chen, Xiaolong Wang, Yiping Li
Suxiao Jiuxin Pill (SX), a traditional Chinese medicine compound consisting primarily of tetramethylpyrazine and borneol, has been reported to protect against ischemic heart disease. However, the effects of SX on mitochondrial injury and gene expression in various signaling pathways are unclear. The aim of the present study was to investigate the effects of SX on mitochondrial injury and to screen the expression of genes potentially altered by SX using a cell culture model of ischemic injury. Simulated ischemia was established by culturing HL-1 cardiomyocytes in Dulbecco's modified Eagle medium without glucose or serum in a hypoxic chamber containing 95% N2 and 5% CO2 for 24 h...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042257/in-vivo-pharmacokinetic-interaction-by-ethanolic-extract-of-gymnema-sylvestre-with-cyp2c9-tolbutamide-cyp3a4-amlodipine-and-cyp1a2-phenacetin-in-rats
#9
Madhuri Vaghela, Niteshkumar Sahu, Prashant Kharkar, Nancy Pandita
Gymnema sylvestre (GS) is a medicinal herb used for diabetes mellitus (DM). Herbs are gaining popularity as medicines in DM for its safety purpose. The aim of the present study was to evaluate in vivo pharmacokinetic (PK) interaction between allopathic drugs tolbutamide (TOLBU), amlodipine (AMLO), and phenacetin (PHENA) at low (L) and high (H) doses with ethanolic extract (EL) from GS. EL was extracted and subjected to TLC, total triterpenoid content (19.76 ± 0.02 W/W) and sterol content (0.1837 ± 0...
October 14, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29040572/biallelic-mutations-in-the-ferredoxin-reductase-gene-cause-novel-mitochondriopathy-with-optic-atrophy
#10
Yanyan Peng, Deepali N Shinde, Alex C Valencia, Jun-Song Mo, Jill Rosenfeld, Megan Truitt Cho, Adam Chamberlin, Zhuo Li, Jie Liu, Baoheng Gui, Rachel Brockhage, Alice Basinger, Brenda Alvarez-Leon, Peter Heydemann, Pilar L Magoulas, Andrea M Lewis, Fernando Scaglia, Solange Gril, Shuk Ching Chong, Matthew Bower, Kristin G Monaghan, Rebecca Willaert, Maria-Renee Plona, Rich Dineen, Francisca Milan, George Hoganson, Zoe Powis, Katherine L Helbig, Jennifer Keller-Ramey, Belinda Harris, Laura C Anderson, Torrian Green, Stacey J Sukoff Rizzo, Julie Kaylor, Jiani Chen, Min-Xin Guan, Elizabeth Sellars, Steven P Sparagana, James B Gibson, Laura G Reinholdt, Sha Tang, Taosheng Huang
Iron-sulfur (Fe-S) clusters are ubiquitous cofactors essential to various cellular processes, including mitochondrial respiration, DNA repair, and iron homeostasis. A steadily increasing number of disorders are being associated with disrupted biogenesis of Fe-S clusters. Here, we conducted whole-exome sequencing of patients with optic atrophy and other neurological signs of mitochondriopathy and identified 17 individuals from 13 unrelated families with recessive mutations in FDXR, encoding the mitochondrial membrane-associated flavoprotein ferrodoxin reductase required for electron transport from NADPH to cytochrome P450...
October 5, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29040533/hippocampal-phosphorylated-tau-induced-cognitive-decline-dendritic-spine-loss-and-mitochondrial-abnormalities-in-a-mouse-model-of-alzheimer-s-disease
#11
Ramesh Kandimalla, Maria Manczak, Xiangling Yin, Rui Wang, P Hemachandra Reddy
The purpose of our study was to understand the toxic effects of hippocampal phosphorylated tau in tau mice. Using rotarod and Morris Water Maze tests, immunoblotting & immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, measured protein levels of mitochondrial dynamics, MAP2, total & phosphorylated tau, and quantified dendritic spines and mitochondrial number and length in 12-month-old tau mice with P301L mutation. Mitochondrial function was assessed by measuring the levels of H2O2, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP...
October 12, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29038839/hepatotoxic-combination-effects-of-three-azole-fungicides-in-a-broad-dose-range
#12
T Heise, F Schmidt, C Knebel, S Rieke, W Haider, I Geburek, L Niemann, P Marx-Stoelting
Single active substances of pesticides are thoroughly examined for their toxicity before approval. In this context, the liver is frequently found to be the main target organ. Since consumers are generally exposed to multiple residues of different active substances via the diet, it is important to analyse combinations of active substances for potential mixture effects. For the (tri-)azoles, a group of agricultural fungicides and antifungal drugs, combination effects on the liver are likely because of a similar mode of action...
October 16, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29037134/effect-of-cyanide-on-mitochondrial-membrane-depolarization-induced-by-uncouplers
#13
L S Khailova, T I Rokitskaya, E A Kotova, Y N Antonenko
In this work, it was found that the ability of common uncouplers - carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and 2,4-dinitrophenol (DNP) - to reduce membrane potential of isolated rat liver mitochondria was diminished in the presence of millimolar concentrations of the known cytochrome c oxidase inhibitor - cyanide. In the experiments, mitochondria were energized by addition of ATP in the presence of rotenone, inhibiting oxidation of endogenous substrates via respiratory complex I. Cyanide also reduced the uncoupling effect of FCCP and DNP on mitochondria energized by succinate in the presence of ferricyanide...
October 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29031807/cytochrome-c-peroxidase-regulates-intracellular-reactive-oxygen-species-and-methylglyoxal-via-enzyme-activities-of-erythroascorbate-peroxidase-and-glutathione-related-enzymes-in-candida-albicans
#14
YoungHo Shin, Sungkyoung Lee, MyungHee Ku, Min-Kyu Kwak, Sa-Ouk Kang
D-erythroascorbate peroxidase (EAPX1) deficiency causes glutathione deprivation, leading to the accumulation of methylglyoxal and reactive oxygen species (ROS), and especially, induction of cytochrome c peroxidase (Ccp1) in Candida albicans. Nevertheless, reciprocal effects between changes in Ccp1 activity and the antioxidative D-erythroascorbic acid- and glutathione-dependent redox status, which reflects methylglyoxal biosynthesis altering pathophysiology are unclear in eukaryotes. To elucidate the effect of CCP1 expression on EAPX1 and glutathione reductase (Glr1) activity-mediated D-erythroascorbic acid biosynthesis and redox homeostasis, the CCP1 gene was disrupted and overexpressed...
October 12, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29029135/small-increase-in-dolutegravir-trough-but-equivalent-total-dolutegravir-exposure-with-simeprevir-in-hiv-hcv-seronegative-volunteers
#15
Christine E MacBrayne, Jose Castillo-Mancilla, James R Burton, Samantha MaWhinney, Charlotte B Wagner, Kestutis Micke, Jordan Fey, Ryan T Huntley, Bayli Larson, Lane R Bushman, Jennifer J Kiser
Background: Dolutegravir, an HIV integrase strand-transfer inhibitor, and simeprevir, an HCV NS3/4A PI, have the potential to interact as dolutegravir is a P-glycoprotein, uridine glucuronosyl transferase 1A1 and cytochrome P450 3A substrate and simeprevir has been shown to mildly inhibit these. Objectives: To compare dolutegravir and simeprevir pharmacokinetics (PK) when given separately versus in combination. Methods: Healthy volunteers received: (i) 150 mg of simeprevir once daily for 7 days; (ii) 50 mg of dolutegravir once daily for 7 days; and (iii) 150 mg of simeprevir once daily plus 50 mg of dolutegravir once daily for 7 days, with randomization to treatment sequence...
October 4, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29027437/-rhaponticum-uniflorum-inhibits-h2o2-induced-apoptosis-of-liver-cells-via-jnk-and-nf-%C3%AE%C2%BAb-pathways
#16
Xin He, Chun-Yan Liu, Ji-Feng Yin, Ai-Hua Jin, Xue-Zhe Yin, Ji-Shu Quan
To study the inhibitory effect of Rhaponticum uniflorum on apoptosis induced by H2O2 in HepG2 cells. Human HepG2 cells injury models were established by H2O2, then cell survival rate was assayed by MTT method; levels of LDH, ALT, and AST were detected by chemical colorimetric method;SOD activity was detected by xanthine oxidase method; GSH content was detected by dithio-bis-nitrobenzoic acid(DTNB); MDA level was detected by thiobarbituric acid (TBA) method;and the relative activities of Caspase-3, 8 and 9 were measured by Colorimetry...
March 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29027090/morphological-and-molecular-data-for-a-new-species-of-pomphorhynchus-monticelli-1905-acanthocephala-pomphorhynchidae-in-the-mexican-redhorse-moxostoma-austrinum-bean-cypriniformes-catostomidae-in-central-mexico
#17
Martín García-Varela, Berenit Mendoza-Garfias, Anindo Choudhury, Gerardo Pérez-Ponce de León
Pomphorhynchus purhepechus n. sp. is described from the intestine of the Mexican redhorse Moxostoma austrinum Bean (Catostomidae) in central Mexico. The new species can be distinguished from the other seven described species of Pomphorhynchus Monticelli, 1905 in the Americas by a subspherical proboscis and 14 longitudinal rows with 16-18 hooks each; the third and the fourth row of hooks are alternately longest. Sequences of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene and the large subunit (LSU) rDNA (including the domains D2-D3) were used to corroborate the morphological distinction between the new species and Pomphorhynchus bulbocolli Linkins in Van Cleave, 1919, a species widely distributed in several freshwater fish species across Canada, USA, and Mexico...
October 12, 2017: Systematic Parasitology
https://www.readbyqxmd.com/read/29026425/effect-of-cytochrome-p450-2c19-17-allelic-variant-on-cardiovascular-and-cerebrovascular-outcomes-in-clopidogrel-treated-patients-a-systematic-review-and-meta-analysis
#18
REVIEW
Bo Huang, De-Jun Cui, Ying Ren, Bin Han, Da-Ping Yang, Xun Zhao
BACKGROUND: We aimed to evaluate the associations of gain-of-function allele of CYP2C19*17 and risk of clinical events in clopidogrel-treated patients with cardiovascular and cerebrovascular diseases (CCVDs). MATERIALS AND METHODS: Literature search was conducted in PubMed, EMBASE, and Cochrane Library. Odds ratio (OR) combined with 95% confidence interval (CI) was the pooled statistics. Subgroup analysis was performed by disease type, bleeding events, and race...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/29026393/in-vitro-investigation-of-clofazimine-analogues-for-antiplasmodial-cytotoxic-and-pro-oxidative-activities
#19
E M Makgatho, E F Mbajiorgu
BACKGROUND: Tetramethyl-piperidine-substituted, B4119 and B4158 have been shown to exhibit antiplasmodial activity. OBJECTIVES: The in vitro antiplasmodial, cytotoxic and oxidative activities of clofazimine and its analogues, all TMP (tetramethylpiperidyl)-substituted phenazines except B669, were evaluated in this study. METHODS: The antiplasmodial activity of the compounds against RB-1 and pfUP10 laboratory strains of Plasmodium falciparum was investigated by flow cytometry...
March 2017: African Health Sciences
https://www.readbyqxmd.com/read/29023376/altered-protein-expression-of-cardiac-cyp2j-and-hepatic-cyp2c-cyp4a-and-cyp4f-in-a-mouse-model-of-type-ii-diabetes-a-link-in-the-onset-and-development-of-cardiovascular-disease
#20
Benoit Drolet, Sylvie Pilote, Carolanne Gélinas, Alida-Douce Kamaliza, Audrey Blais-Boilard, Jessica Virgili, Dany Patoine, Chantale Simard
Arachidonic acid can be metabolized by cytochrome P450 (CYP450) enzymes in a tissue- and cell-specific manner to generate vasoactive products such as epoxyeicosatrienoic acids (EETs-cardioprotective) and hydroxyeicosatetraenoic acids (HETEs-cardiotoxic). Type II diabetes is a well-recognized risk factor for developing cardiovascular disease. A mouse model of Type II diabetes (C57BLKS/J-db/db) was used. After sacrifice, livers and hearts were collected, washed, and snap frozen. Total proteins were extracted...
October 12, 2017: Pharmaceutics
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