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https://www.readbyqxmd.com/read/28550384/investigation-of-glycochenodeoxycholate-sulfate-and-chenodeoxycholate-glucuronide-as-surrogate-endogenous-probes-for-drug-interaction-studies-of-oatp1b1-and-oatp1b3-in-healthy-japanese-volunteers
#1
Issey Takehara, Hanano Terashima, Takeshi Nakayama, Takashi Yoshikado, Miwa Yoshida, Kenichi Furihata, Nobuaki Watanabe, Kazuya Maeda, Osamu Ando, Yuichi Sugiyama, Hiroyuki Kusuhara
PURPOSE: To assess the use of glycochenodeoxycholate-3-sulfate (GCDCA-S) and chenodeoxycholate 3- or 24-glucuronide (CDCA-3G or -24G) as surrogate endogenous substrates in the investigation of drug interactions involving OATP1B1 and OATP1B3. METHODS: Uptake of GCDCA-S and CDCA-24G was examined in HEK293 cells transfected with cDNA for OATP1B1, OATP1B3, and NTCP and in cryopreserved human hepatocytes. Plasma concentrations of bile acids and their metabolites (GCDCA-S, CDCA-3G, and CDCA-24G) were determined by LC-MS/MS in eight healthy volunteers with or without administration of rifampicin (600 mg, po)...
May 26, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28546421/statins-attenuate-activation-of-the-nlrp3-inflammasome-by-oxidized-ldl-or-tnf-%C3%AE-in-vascular-endothelial-cells-through-a-pxr-dependent-mechanism
#2
Shaolan Wang, Xinya Xie, Ting Lei, Kang Zhang, Baochang Lai, Zihui Zhang, Youfei Guan, Guangmei Mao, Lei Xiao, Nanping Wang
Excessive activation of the NLRP3 inflammasome is implicated in cardiovascular diseases. Statins exert an anti-inflammatory effect independent of their cholesterol lowering effect. This study investigated the potential role of statins in the activation of the NLRP3 inflammasome in endothelial cells (ECs). Western blotting and qRT-PCR showed that oxidized-LDL (oxLDL) or tumor necrosis factor alpha (TNFα) activated the NLRP3 inflammasome in ECs. Simvastatin or mevastatin significantly suppressed the effects of oxLDL or TNFα...
May 25, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28546420/alterations-of-histone-modifications-contribute-to-pregnane-x-receptor-mediated-induction-of-cyp3a4-by-rifampicin
#3
Liang Yan, Yiting Wang, Jingyang Liu, Yali Nie, Xiaobo Zhong, Quancheng Kan, Lirong Zhang
Cytochrome P450 3A4 (CYP3A4) is one of the major drug-metabolizing enzymes in human and is responsible for the metabolism of 60% of the clinically used drugs. Many drugs are able to induce the expression of CYP3A4, which usually causes drug-drug interactions and adverse drug reactions. This study aims to explore the role of histone modifications in rifampicin-induced expression of CYP3A4 in LS174T cells. We found that the induction of CYP3A4 mRNA by rifampicin in LS174T cells was associated with increased levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3 acetylation and a decreased level of histone H3 lysine 27 trimethylation (H3K27me3) in the CYP3A4 promoter...
May 25, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28546104/development-of-a-paediatric-physiologically-based-pharmacokinetic-model-to-assess-the-impact-of-drug-drug-interactions-in-tuberculosis-co-infected-malaria-subjects-a-case-study-with-artemether-lumefantrine-and-the-cyp3a4-inducer-rifampicin
#4
Olusola Olafuyi, Michael Coleman, Raj K S Badhan
The fixed dosed combination of artemether and lumefantrine (AL) is widely used for the treatment of malaria in adults and children in sub-Sahara Africa, with lumefantrine day 7 concentrations being widely used as a marker for clinical efficacy. Both are substrates for CYP3A4 and susceptible to drug-drug interactions (DDIs); indeed, knowledge of the impact of these factors is currently sparse in paediatric population groups. Confounding malaria treatment is the co-infection of patients with tuberculosis. The concomitant treatment of AL with tuberculosis chemotherapy, which includes the CYP3A4 inducer rifampicin, increases the risk of parasite recrudescence and malaria treatment failure...
May 22, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28543876/application-of-molecular-microbiological-and-immunological-tests-for-the-diagnosis-of-bone-and-joint-tuberculosis
#5
Yinghua Tang, Lianli Yin, Shifu Tang, Hongyu Zhang, Jihui Lan
BACKGROUND: To evaluate the application of interferon gamma release assay (IGRA), rifampicin resistant real-time fluorescence quantitative PCR technique Xpert Mycobacterium tuberculosis/rifampicin (Xpert MTB/RIF), and the levels of TNF-α and TGF-β in the diagnosis of bone and joint tuberculosis. METHODS: Eighty-six patients with bone and joint tuberculosis, diagnosed by pathology or microbiology, were examined by Xpert MTB/RIF and IGRA (T-SPOT. TB) for Mycobacterium tuberculosis infection, and the TNF-α and TGF-β levels of the patients were measured...
May 22, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28543702/microencapsulation-of-rifampicin-a-technique-to-preserve-the-mechanical-properties-of-bone-cement
#6
P Sanz-Ruiz, E Carbó-Laso, J C Del Real-Romero, F Arán-Ais, Y Ballesteros-Iglesias, E Paz-Jiménez, M Sánchez-Navarro, M A Pérez-Limiñana, J Vaquero-Martín
Two-stage exchange with antibiotic-loaded bone cement spacers remains the gold standard for chronic periprosthetic joint infection(PJI). Rifampicin is highly efficient on stationary-phase staphylococci in biofilm; however, its addition to PMMA to manufacture spacers prevents polymerization and reduces mechanical properties. Isolation of rifampicin during polymerization by microencapsulation could allow manufacturing rifampicin-loaded bone cement maintaining elution and mechanical properties. Microcapsules of rifampicin with alginate, polyhydroxybutyratehydroxyvalerate (PHBV), ethylcellulose and stearic acid (SA) were synthesized...
May 23, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28542441/dot-or-sat-for-rifampicin-resistant-tuberculosis-a-non-randomized-comparison-in-a-high-hiv-prevalence-setting
#7
Erika Mohr, Johnny Daniels, Busisiwe Beko, Petros Isaakidis, Vivian Cox, Sarah Jane Steele, Odelia Muller, Leigh Snyman, Virginia De Azevedo, Amir Shroufi, Laura Trivino Duran, Jennifer Hughes
BACKGROUND: Daily directly-observed therapy (DOT) is recommended for rifampicin-resistant tuberculosis (RR-TB) patients throughout treatment. We assessed the impact of self-administered treatment (SAT) in a South African township with high rates of RR-TB and HIV. METHODS: Community-supported SAT for patients who completed the intensive phase was piloted in five primary care clinics in Khayelitsha. We compared final treatment outcomes among RR-TB patients initiating treatment before (standard-of-care (SOC)-cohort, January 2010-July 2013) and after the implementation of the pilot (SAT-cohort, January 2012-December 2014)...
2017: PloS One
https://www.readbyqxmd.com/read/28540152/epidemiological-clinical-and-microbiological-characteristics-of-patients-with-post-traumatic-osteomyelitis-of-limb-fractures-in-southwest-china-a-hospital-based-study
#8
Jiachen Peng, Youliang Ren, Wenbin He, Zhengdao Li, Jin Yang, Yi Liu, Zhonghui Zheng, Stephen L Kates, Edward M Schwarz, Chao Xie, Youjia Xu
Objective To determine the epidemiological, clinical and microbiological characteristics, of patients with post-traumatic osteomyelitis of extremity fractures, and provide evidence-based guidelines for early diagnosis and treatment, including empiric antibiotic therapy. Methods Human subject research was performed using institutional review board approved protocols. A retrospective chart review was conducted on 5,368 patients diagnosed with extremity traumatic fractures from January 1, 2012 to December 31, 2015, to identify osteomyelitis patients...
2017: J Bone Jt Infect
https://www.readbyqxmd.com/read/28539243/synthesis-sar-and-molecular-docking-studies-of-benzo-d-thiazole-hydrazones-as-potential-antibacterial-and-antifungal-agents
#9
Gao-Feng Zha, Jing Leng, N Darshini, T Shubhavathi, H K Vivek, Abdullah M Asiri, Hadi M Marwani, K P Rakesh, N Mallesha, Hua-Li Qin
A series of new benzo[d]thiazole-hydrazones analogues were synthesized and screened for their in vitro antibacterial and antifungal activities. The results revealed that compounds 13, 14, 15, 19, 20, 28 and 30 exhibited superior antibacterial potency compared to the reference drug chloramphenicol and rifampicin. Compounds 5, 9, 10, 11, 12, 28 and 30 were found to be good antifungal activity compared to the standard drug ketoconazole. A preliminary study of the structure-activity relationship (SAR) revealed that the antimicrobial activity depended on the effect of different substituents on the phenyl ring...
May 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28535976/oatp-and-efflux-transporter-mediated-hepatic-uptake-and-biliary-excretion-of-cilostazol-and-its-metabolites-in-rats-and-humans
#10
Chong Wang, Xiaokui Huo, Changyuan Wang, Qiang Meng, Zhihao Liu, Pengyuan Sun, Jian Cang, Huijun Sun, Kexin Liu
Cilostazol undergoes extensive liver metabolism. However, the transporter-mediated hepatic disposition of cilostazol remains unknown. The present study was performed to investigate the hepatic uptake and biliary excretion of cilostazol and its metabolites (OPC-13015 and OPC-13213) using rat liver and human transporter-transfected cells in vitro. Cilostazol uptake by rat liver slices and isolated rat hepatocytes exhibited time-, concentration-, and temperature-dependency and was decreased by Oatp inhibitors, which suggested that Oatp was involved in the hepatic uptake of cilostazol...
May 20, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28535897/treatment-of-latent-tuberculosis-in-patients-with-juvenile-rheumatic-diseases-a-systematic-review
#11
José Cleosmaque Leite Júnior, Regina Terse Trindade Ramos, Teresa Cristina Martins Vicente Robazzi
INTRODUCTION: Children and adolescents with rheumatic diseases receiving TNF blockers are at risk for the activation of latent Mycobacterium tuberculosis infection (LTBI). Although LTBI treatment is indicated in this group, there are different therapeutic regimens in the literature, without a definite consensus. OBJECTIVES: To review in the literature therapeutic schemes used and indicated for the treatment of LTBI in these patients. METHODS: Systematic review of the literature, using health databases, selecting studies that addressed the treatment of LTBI in patients with juvenile rheumatic diseases using TNF blockers, from 1990 to 2015...
May 2017: Revista Brasileira de Reumatologia
https://www.readbyqxmd.com/read/28535345/natural-predominance-of-abscisic-acid-in-pongammia-pinnata-karanj-honey-contributed-to-its-strong-antimutagenicity
#12
Sudhanshu Saxena, Jyoti Tripathi, Suchandra Chatterjee, Satyendra Gautam
Various samples of raw (unprocessed) floral honey collected from different geographical locations of India were assayed for its antimutagenicity against ethyl methanesulfonate in E. coli MG1655 cells through rifampicin resistance assay. A monofloral honey ('Pongammia pinnata', local name 'Karanj') displayed maximum antimutagenicity (78.0 ± 1.7; P≤0.05). Solid phase extraction (using amberlite XAD-2 resin) followed by HPLC resulted into different peaks displaying varying antimutagenicity. Peak at retention time (Rt) 27...
May 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28533691/microbiome-disruption-and-recovery-in-the-fish-gambusia-affinis-following-exposure-to-broad-spectrum-antibiotic
#13
Jeanette M Carlson, Annie B Leonard, Embriette R Hyde, Joseph F Petrosino, Todd P Primm
Antibiotics are a relatively common disturbance to the normal microbiota of humans and agricultural animals, sometimes resulting in severe side effects such as antibiotic-associated enterocolitis. Gambusia affinis was used as a vertebrate model for effects of a broad-spectrum antibiotic, rifampicin, on the skin and gut mucosal microbiomes. The fish were exposed to the antibiotic in the water column for 1 week, and then monitored during recovery. As observed via culture, viable counts from the skin microbiome dropped strongly yet returned to pretreatment levels by 1...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/28533232/potentiation-of-antibiotic-activity-by-a-novel-cationic-peptide-potency-and-spectrum-of-activity-of-spr741
#14
David Corbett, Andrew Wise, Tara Langley, Kirsty Skinner, Emily Trimby, Stephen Birchall, Alain Dorali, Stephanie Sandiford, Jennifer Williams, Peter Warn, Martti Vaara, Troy Lister
Novel approaches to the treatment of multi-drug resistant Gram-negative bacterial infections are urgently required. One approach is to potentiate the efficacy of existing antibiotics whose spectrum of activity is limited by the permeability barrier presented by the Gram-negative outer membrane. Cationic peptides derived from polymyxin B have been used to permeabilize the outer membrane, granting antibiotics that would otherwise be excluded access to their targets. We assessed the in vitro efficacy of combinations of SPR741 with conventional antibiotics against Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii Of 35 antibiotics tested, the MICs of eight were reduced 32- to 8,000-fold against E...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28532245/applicability-of-ribosome-engineering-to-vitamin-b12-production-by-propionibacterium-shermanii
#15
Yukinori Tanaka, Ken Kasahara, Masumi Izawa, Kozo Ochi
Ribosome engineering has been widely utilized for strain improvement, especially for the activation of bacterial secondary metabolism. This study assessed ribosome engineering technology to modulate primary metabolism, taking vitamin B12 production as a representative example. The introduction into Propionibacterium shermanii of mutations conferring resistance to rifampicin, gentamicin, and erythromycin, respectively, increased per cell production (μg/L/OD600) of vitamin B12 5.2-fold, although net production (μg/L) was unchanged, as the cell mass of the mutants was reduced...
May 22, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28531287/bacterial-rna-polymerase-caps-rna-with-various-cofactors-and-cell-wall-precursors
#16
Christina Julius, Yulia Yuzenkova
Bacterial RNA polymerase is able to initiate transcription with adenosine-containing cofactor NAD+, which was proposed to result in a portion of cellular RNAs being 'capped' at the 5΄ end with NAD+, reminiscent of eukaryotic cap. Here we show that, apart from NAD+, another adenosine-containing cofactor FAD and highly abundant uridine-containing cell wall precursors, UDP-Glucose and UDP-N-acetylglucosamine are efficiently used to initiate transcription in vitro. We show that the affinity to NAD+ and UDP-containing factors during initiation is much lower than their cellular concentrations, and that initiation with them stimulates promoter escape...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28528545/discovery-and-biosynthesis-of-gladiolin-a-burkholderia-gladioli-antibiotic-with-promising-activity-against-mycobacterium-tuberculosis
#17
Lijiang Song, Matthew Jenner, Joleen Masschelein, Cerith Jones, Matthew J Bull, Simon R Harris, Ruben C Hartkoorn, Anthony Vocat, Isolda Romero-Canelón, Paul Coupland, Gordon Webster, Matthew Dunn, Rebecca Weiser, Christopher Paisey, Stewart T Cole, Julian Parkhill, Eshwar Mahenthiralingam, Gregory L Challis
An antimicrobial activity screen of Burkholderia gladioli BCC0238, a clinical isolate from a cystic fibrosis patient, led to the discovery of gladiolin, a novel macrolide antibiotic with potent activity against Mycobacterium tuberculosis H37Rv. Gladiolin is structurally-related to etnangien, a highly unstable antibiotic from Sorangium cellulosum that is also active against Mycobacteria. Like etnangien, gladiolin was found to inhibit RNA polymerase, a validated drug target in M. tuberculosis. However, gladiolin lacks the highly labile hexaene moiety of etnangien and was thus found to possess significantly increased chemical stability...
May 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28527252/-characterization-of-clinical-isolates-of-mycobacterium-tuberculosis-from-hiv-positive-individuals-in-colombia-2012
#18
Claudia Castro, Alba Ricardo, Angie Zabaleta, Claudia Llerena, Gloria Puerto
INTRODUCTION: One third of the increase in tuberculosis cases is attributed to the spread of HIV. In 2012, 1,397 HIV-associated tuberculosis cases were reported in Colombia, i.e., 11.8% of the total cases. Molecular epidemiology tools help to understand the transmission of tuberculosis. OBJECTIVE: To characterize clinical isolates of Mycobacterium tuberculosis derived from HIV-infected individuals, received at the Laboratorio Nacional de Referencia in the Instituto Nacional de Salud...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28527245/-description-of-mycobacterium-tuberculosis-mutations-conferring-resistance-to-rifampicin-and-isoniazid-detected-by-genotype%C3%A2-mtbdrplus-v-2-in-colombia
#19
Claudia Llerena, Raquel Medina
INTRODUCTION: The GenoType®MTBDRplusV.2 assay is a molecular technique endorsed by the World Health Organization and the Pan American Health Organization that allows for the identification of the Mycobacterium tuberculosis complex and the detection of mutations in the rpoβ gene for rifampicin resistance, and katG and inhA genes for isoniazid resistance. Due to the genetic variability in the circulating strains around the world, the national tuberculosis control programs should assess the performance of these new diagnostic technologies and their use under program conditions as rapid tests...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28526334/regulatory-cis-and-trans-elements-of-mitochondrial-d-loop-driven-reporter-genes-in-budding-tunicates
#20
Kaz Kawamura, Yuhya Saitoh, Loriano Ballarin, Takeshi Sunanaga
To unveil the underlying mechanism of mitochondrial gene regulation associated with ageing and budding in the tunicate Polyandrocarpa misakiensis, mitochondrial non-coding-region (NCR)-containing reporter genes were constructed. PmNCR2.3K/GFP was expressed spatiotemporally in a pattern quite similar to mitochondrial 16SrRNA. The reporter gene expression was sensitive to high dose of rifampicin similar to mitochondrial genes, suggesting that the transcription indeed occurs in mitochondria. However, the gene expression also occurred in vivo in the cell nucleus and in vitro in the nuclear extracts...
May 16, 2017: Mitochondrion
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