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https://www.readbyqxmd.com/read/28077325/role-of-14-3-3-sigma-in-over-expression-of-p-gp-by-rifampin-and-paclitaxel-stimulation-through-interaction-with-pxr
#1
So Won Kim, Md Hasanuzzaman, Munju Cho, Nam Hyun Kim, Hye-Young Choi, Jung Woo Han, Hyun June Park, Ji Won Oh, Jae-Gook Shin
In this study, we presented the role of 14-3-3σ to activate CK2-Hsp90β-PXR-MDR1 pathway on rifampin and paclitaxel treated LS174T cells and in vivo LS174T cell-xenografted nude mouse model. Following several in vitro and in vivo experiments, rifampin and paclitaxel were found to be stimulated the CK2-Hsp90β-PXR-MDR1 pathway. Of the proteins in this pathway, Pregnane X receptor (PXR) is a representative transcription factor of multidrug resistance protein 1 (MDR1). We constructed FLAG-PXR-LS174T stable cell lines and discovered 22 proteins that interacted with PXR on rifampin treatment...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28052338/quantitative-prediction-of-the-effect-of-cyp3a-inhibitors-and-inducers-on-venetoclax-pharmacokinetics-using-a-physiologically-based-pharmacokinetic-model
#2
Kevin J Freise, Mohamad Shebley, Ahmed Hamed Salem
The objectives of the analysis were to develop and verify a venetoclax physiologically based pharmacokinetic (PBPK) model to predict the effects of cytochrome P450 3A (CYP3A) inhibitors and inducers on the PK of venetoclax and inform dosing recommendations. A minimal PBPK model was developed based on prior in vitro and in vivo clinical data using a "middle-out" approach. The PBPK model was independently verified against clinical studies of the strong CYP3A inhibitor ketoconazole, the strong CYP3A inducer, multiple-dose rifampin, and the steady-state venetoclax PK in chronic lymphocytic leukemia (CLL) subjects by comparing predicted to observed ratios of the venetoclax maximum concentration (Cmax R) and area under the curve from time 0 to infinity (AUC∞ R) from these studies...
January 4, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28043605/xpert-mtb-rif-for-rapid-detection-of-rifampicin-resistant-mycobacterium-tuberculosis-from-pulmonary-tuberculosis-patients-in-southwest-ethiopia
#3
Mulualem Tadesse, Dossegnaw Aragaw, Belayneh Dimah, Feyisa Efa, Gemeda Abebe
OBJECTIVE/BACKGROUND: Accurate and rapid detection of drug-resistant strains of tuberculosis (TB) is critical for early initiation of treatment and for limiting the transmission of drug-resistant TB. Here, we investigated the accuracy of Xpert MTB/RIF for detection of rifampicin (RIF) resistance, and whether this detection predicts the presence of multidrug resistant (MDR) TB in Southwest Ethiopia. METHODS: Smear- or culture-positive sputa obtained from TB patients with increased suspicion of drug resistance were included in this study...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043565/drug-susceptibility-testing-of-mycobacterium-avium-subsp-avium-isolates-from-naturally-infected-domestic-pigeons-to-avian-tuberculosis
#4
Kaveh Parvandar, Mansour Mayahi, Nader Mosavari, Reza Aref Pajoohi
OBJECTIVE: Avian tuberculosis is one of the most important infections affecting most species of birds. Several mycobacterial species have been identified causing avian tuberculosis, and the organisms confirmed most frequently are Mycobacterium avium and Mycobacterium genavense. Any species of birds can be infected with M. avium. Generally, domesticated fowl or captive wild birds are affected more frequently than those living in the wild. M. avium can not only infect all species of birds, but can also infect some domesticated mammals to cause disease, usually with localized lesion...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043515/evaluation-of-rifampicin-resistance-and-81-bp-rifampicin-resistant-determinant-region-of-rpob-gene-mutations-of-mycobacterium-tuberculosis-detected-with-xpertmtb-rif-in-cross-river-state-nigeria
#5
Ernest A Ochang, Ubong A Udoh, Ubleni E Emanghe, Gerald O Tiku, Jonah B Offor, Micheal Odo, Emmanuel Nkombe, Oju E Owuna, Sunday M Obeten, Martin M Meremikwu
OBJECTIVE/BACKGROUND: World Health Organization tuberculosis (TB) indices from 2014 to 2016 showed that Nigeria had the 6th highest prevalence, 4th highest incidence, and the highest mortality rate globally. In efforts to improve TB care, the XpertMTB/Rif (GeneXpert) technology, Cepheid, Sunnyvale, California, USA, which has revolutionized TB detection with concomitant rifampicin-resistance molecular detection, was introduced in Cross River State, South-South Nigeria, in 2014. The GeneXpert uses molecular beacons to detect five overlapping 81-bp regions in the rpoB gene known as the Rifampicin Resistant Determinant Region (RRDR)...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28042217/performance-of-xpert-mtb-rif-on-ascitic-fluid-samples-for-detection-of-abdominal-tuberculosis
#6
Syed Beenish Rufai, Sarman Singh, Amit Singh, Parveen Kumar, Jitendra Singh, Anand Vishal
BACKGROUND: Diagnosis of abdominal tuberculosis (TB) from ascitic fluid samples using routinely available diagnostic methods is challenging due to its paucibacillary nature. Although performance of Xpert MTB/RIF assay has been evaluated extensively on pulmonary samples, its performance on extrapulmonary samples is still under evaluation. OBJECTIVES: The objective of this study was to find out the performance of Xpert MTB/RIF on ascitic fluid samples obtained from suspected cases of abdominal TB...
January 2017: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/28040477/design-of-novel-antimicrobial-peptide-dimer-analogues-with-enhanced-antimicrobial-activity-in-vitro-and-in-vivo-by-intermolecular-triazole-bridge-strategy
#7
Beijun Liu, Haifeng Huang, Zhibin Yang, Beiyin Liu, Sanhu Gou, Chao Zhong, Xiufeng Han, Yun Zhang, Jingman Ni, Rui Wang
Currently, antimicrobial peptides have attracted considerable attention because of their broad-sprectum activity and low prognostic to induce antibiotic resistance. In our study, for the first time, a series of side-chain hybrid dimer peptides J-AA (Anoplin-Anoplin), J-RR (RW-RW), and J-AR (Anoplin-RW) based on the wasp peptide Anoplin and the arginine- and tryptophan-rich hexapeptide RW were designed and synthesized by click chemistry, with the intent to improve the antimicrobial efficacy of peptides against bacterial pathogens...
December 28, 2016: Peptides
https://www.readbyqxmd.com/read/27993285/analysis-of-discrepant-results-between-the-genotype-%C3%A2-mtbdrplus-assay-and-an-antimicrobial-drug-susceptibility-test-for-isoniazid-resistant-tuberculosis
#8
Kyung-Wook Jo, Yoomi Yeo, Heungsup Sung, Mi-Na Kim, Tae Sun Shim
BACKGROUND: We investigated discrepant results determined using the Genotype(®)MTBDRplus assay and a conventional antimicrobial drug susceptibility test (ADST) for isoniazid (INH) resistance using sequencing analysis and analyzed the clinical course of patients with discrepant results. METHODS: Among 1373 MTBDRplus assays performed at our tertiary referral center in South Korea between August 2009 and December 2015, the results for 46 (3.4%) differed from those for ADST...
January 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/27987927/synthesis-and-characterization-of-acetylated-amylose-and-development-of-inclusion-complexes-with-rifampicin
#9
Andresa C Ribeiro, Ângelo Rocha, Rosane M D Soares, Luís P Fonseca, Nádya P da Silveira
Amylose (AM) tends to form single helical inclusion complexes with suitable agents. These complexes are considered promising biomaterial carrier since the guest molecules can be released later, leading to many applications, especially in the pharmaceutical industry. Rifampicin (RIF) has long been recognized as an active drug against Mycobacterium tuberculosis, however, the administration of RIF in high dosages can originate unwanted side-effects. Due to the fact that the use of native amylose (AM) in the formation of complexes is limited by their low water solubility, it was acetylated with a medium degree of substitution (DS), allowing solubilizing (0...
February 10, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/27956422/role-of-pyrazinamide-in-the-emergence-of-extensively-drug-resistant-tuberculosis-a-multi-strain-mathematical-model
#10
Mariam O Fofana, Sourya Shrestha, Gwenan M Knight, Ted Cohen, Richard G White, Frank Cobelens, David W Dowdy
Several infectious diseases of global importance - e.g. HIV, tuberculosis (TB) - require prolonged treatment with combination antimicrobial regimens, typically involving high-potency "core" agents coupled with additional "companion" drugs that protect against de novo emergence of mutations conferring resistance to the core agents. Often, the most effective (or least toxic) companion agents are re-used in sequential (first-line, second-line, etc…) regimens. We used a multi-strain model of M. tuberculosis transmission in Southeast Asia to investigate how this practice might facilitate the emergence of extensive drug resistance, i...
December 12, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919693/performance-evaluation-of-xpert-mtb-rif-in-a-moderate-tuberculosis-incidence-compared-with-taqman-mtb-and-trcrapid-m-tb
#11
Kazunari Tsuyuguchi, Hideaki Nagai, Kenji Ogawa, Tomoshige Matsumoto, Kozo Morimoto, Akiko Takaki, Satoshi Mitarai
Xpert MTB/RIF is an automated nucleic acid amplification test (NAT) that can detect the presence of Mycobacterium tuberculosis complex (MTC) in clinical specimens as well as rifampicin (RIF) resistance resulting from rpoB mutation. Despite its high sensitivity and specificity for diagnosing tuberculosis (TB) with or without RIF resistance, the clinical performance of the test is variable. In this study, we evaluated the performance of Xpert MTB/RIF in a setting of moderate TB burden and high medical resources...
February 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/27916487/evaluation-of-hepatoprotective-potential-of-erythrina-indica-leaves-against-antitubercular-drugs-induced-hepatotoxicity-in-experimental-rats
#12
Mohd Mujahid, Talib Hussain, Hefazat Hussain Siddiqui, Arshad Hussain
BACKGROUND: Erythrina indica Lam. traditionally used in the treatment of laxative, diuretic, worm infestation, liver ailment and joints pain. OBJECTIVE: To evaluate the antihepatotoxic potential of Erythrina indica against isoniazid (INH) and rifampicin (RIF) induced hepatotoxicity in rats. METHODS AND MATERIAL: Liver toxicity was induced by antitubercular drugs (INH+ RIF) at dose level of 50 mg/kg each, p.o for 28 days. 50% methanolic extract of Erythrina indica (100 and 200 mg/kg) were administered orally once daily for 28 days...
December 1, 2016: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/27915038/intrauterine-administration-of-hcg-activated-autologous-human-peripheral-blood-mononuclear-cells-pbmc-promotes-live-birth-rates-in-frozen-thawed-embryo-transfer-cycles-of-patients-with-repeated-implantation-failure
#13
Saijiao Li, Jing Wang, Yan Cheng, Danni Zhou, Tailang Yin, Wangming Xu, Nan Yu, Jing Yang
Recurrent implantation failure refers to unsuccessful implantation after repeated transfers of morphologically good quality embryos into a normal uterus. Recently, accumulating evidence has suggested that local immune cells at the implantation site have actively contributed to embryo implantation. Our aim was to study the effects of intrauterine administration of hCG-activated autologous human PBMC on clinical pregnancy, implantation rates and live birth rate of patients who received frozen/thawed embryo transfer...
November 27, 2016: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/27914363/new-insights-into-the-sar-and-drug-combination-synergy-of-2-quinolin-4-yloxy-acetamides-against-mycobacterium-tuberculosis
#14
Bruno Couto Giacobbo, Kenia Pissinate, Valnês Rodrigues-Junior, Anne Drumond Villela, Estêvão Silveira Grams, Bruno Lopes Abbadi, Fernanda Teixeira Subtil, Nathalia Sperotto, Rogério Valim Trindade, Davi Fernando Back, Maria Martha Campos, Luiz Augusto Basso, Pablo Machado, Diógenes Santiago Santos
2-(Quinolin-4-yloxy)acetamides have been described as potent and selective in vitro inhibitors of Mycobacterium tuberculosis (Mtb) growth. Herein, a new series of optimized compounds were found to demonstrate highly potent antitubercular activity, with minimum inhibitory concentration (MIC) values against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains in the submicromolar range. Furthermore, the most active compounds had no apparent toxicity to mammalian cells, and they showed intracellular activities similar to those of isoniazid and rifampin in a macrophage model of Mtb infection...
November 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27891336/mycobacterium-tuberculosis-beijing-genotype-in-western-iran-distribution-and-drug-resistance
#15
Parviz Mohajeri, Sakineh Moradi, Sara Atashi, Abbas Farahani
INTRODUCTION: Mycobacterium tuberculosis Beijing genotype is gaining importance all over the world because this genotype is highly prevalent in several areas and is also frequently associated with drug resistance. AIM: To identify and determine the frequency of Beijing genotype and mix infection with Beijing and non-Beijing in west of Iran and analyse the association between Beijing genotype and drug resistance. MATERIALS AND METHODS: This cross-sectional study was conducted on 146 Tuberculosis (TB) samples collected at the TB reference laboratory in Kermanshah west of Iran from January 2014 to February 2015, Mycobacterium tuberculosis isolates from sputum samples, detected by microcopy, biochemical tests and solid culture were included and then the confirmed samples with Cepheid Xpert MTB/RIF assay were subjected to drug susceptibility tests for rifampicin, isoniazid, ethambutol using proportional method...
October 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27815731/hepatic-uptake-mechanism-of-ophiopogonin-d-mediated-by-organic-anion-transporting-polypeptides
#16
Wen Zhang, Xiaomin Xiong, Lin Chen, Mingyi Liu, Yuqing Xiong, Hong Zhang, Shibo Huang, Chunhua Xia
BACKGROUND AND OBJECTIVES: Ophiopogonin D (OPD) is one of the main active ingredients of SMI (Shenmai injection) which is widely used in clinical practice in China. Our previous study indicated  that OPD might be transported from blood into liver mediated by organic anion transporting polypeptides (OATPs/oatps). This study aims to explore the hepatic uptake mechanism of OPD in rat and human. METHODS: Rosuvastatin (a competitive inhibitor of oatp1b2, oatp1a1, and oatp1a4), glycyrrhizic acid (a specific inhibitor of oatp1b2), digoxin (a specific inhibitor of oatp1a4), bromosulfophthalein (BSP), and ibuprofen (a specific inhibitor of oatp1a1) were used to study the uptake of OPD in rat hepatocytes...
November 4, 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27775462/reduced-ability-to-detect-surface-related-biofilm-bacteria-after-antibiotic-exposure-under-in-vitro-conditions
#17
Christen Ravn, Ulrika Furustrand Tafin, Bertrand Bétrisey, Søren Overgaard, Andrej Trampuz
Background and purpose - Antibiotic treatment of patients before specimen collection reduces the ability to detect organisms by culture. We investigated the suppressive effect of antibiotics on the growth of non-adherent, planktonic, and surface-related biofilm bacteria in vitro by using sonication and microcalorimetry methods. Patients and methods - Biofilms of Staphylococcus aureus, S. epidermidis, Escherichia coli, and Propionibacterium acnes were formed on porous glass beads and exposed for 24 h to antibiotic concentrations from 1 to 1,024 times the minimal inhibitory concentration (MIC) of vancomycin, daptomycin, rifampin, flucloxacillin, or ciprofloxacin...
December 2016: Acta Orthopaedica
https://www.readbyqxmd.com/read/27742636/drug-concentration-thresholds-predictive-of-therapy-failure-and-death-in-children-with-tuberculosis-bread-crumb-trails-in-random-forests
#18
Soumya Swaminathan, Jotam G Pasipanodya, Geetha Ramachandran, A K Hemanth Kumar, Shashikant Srivastava, Devyani Deshpande, Eric Nuermberger, Tawanda Gumbo
BACKGROUND:  The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown. METHODS:  Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27737841/diagnostic-test-accuracy-in-childhood-pulmonary-tuberculosis-a-bayesian-latent-class-analysis
#19
Samuel G Schumacher, Maarten van Smeden, Nandini Dendukuri, Lawrence Joseph, Mark P Nicol, Madhukar Pai, Heather J Zar
Evaluation of tests for the diagnosis of childhood pulmonary tuberculosis (CPTB) is complicated by the absence of an accurate reference test. We present a Bayesian latent class analysis in which we evaluated the accuracy of 5 diagnostic tests for CPTB. We used data from a study of 749 hospitalized South African children suspected to have CPTB from 2009 to 2014. The following tests were used: mycobacterial culture, smear microscopy, Xpert MTB/RIF (Cepheid Inc.), tuberculin skin test (TST), and chest radiography...
November 1, 2016: American Journal of Epidemiology
https://www.readbyqxmd.com/read/27733634/xpert-mtb-rif-assay-shows-faster-clearance-of-mycobacterium-tuberculosis-dna-with-higher-levels-of-rifapentine-exposure
#20
A Jayakumar, R M Savic, C K Everett, D Benator, D Alland, C M Heilig, M Weiner, S O Friedrich, N A Martinson, A Kerrigan, C Zamudio, S V Goldberg, W C Whitworth, J L Davis, P Nahid
The Xpert MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle threshold (CT) values, which may provide a dynamic measure of sputum bacillary burden when used longitudinally. We evaluated the relationship between Xpert CT trajectory and drug exposure during tuberculosis (TB) treatment to assess the potential utility of Xpert CT for treatment monitoring. We obtained serial sputum samples from patients with smear-positive pulmonary TB who were consecutively enrolled at 10 international clinical trial sites participating in study 29X, a CDC-sponsored Tuberculosis Trials Consortium study evaluating the tolerability, safety, and antimicrobial activity of rifapentine at daily doses of up to 20 mg/kg of body weight...
December 2016: Journal of Clinical Microbiology
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