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Zhaohui Qiu, Jie Peng, Lingli Mou, Xiao Li, Fanqi Meng, Peng Yu
Multidrug resistance (MDR) of tumors occurs when tumor cells exhibit reduced sensitivity to a large number of unrelated drugs. The molecular mechanism of MDR commonly involves overexpression of the plasma membrane drug efflux pump P-glycoprotein (P-gp). Overexpression of P-gp may be induced by the selection and/or adaptation of cells during exposure to chemotherapeutic drugs, referred to as acquired P-gp-mediated MDR. This study aimed to establish a P-gp quantification method by Ultra Performance Liquid Chromatography and Tandem Mass Spectrometry (UPLC-MS/MS) to better understand the regulation of P-gp expression and its relationship with the level of drug resistance...
March 8, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Xingyu Zhang, Di Chen, Guifeng Xu, Weichun Huang, Xing Wang
Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center...
2018: PloS One
Rajeshwar Dayal, Dipti Agarwal, Rakesh Bhatia, C Bipin, Neeraj Kumar Yadav, Santosh Kumar, Shamrendra Narayan, Ankur Goyal
OBJECTIVES: To find out the prevalence of latent tuberculosis (TB) infection and TB disease among pediatric household contacts of adult drug resistant (MDR) and drug susceptible (DS) TB patients and to identify the risk factors for occurrence of TB infection in the contacts. METHODS: Pediatric household contacts (less than 15 y age) of adult TB patients (both MDR and DS) were included in the study. They were categorized as latent TB infection (LTBI), TB disease and TB exposed based on the results of tuberculin skin testing (TST), clinical examination and chest X-ray...
March 20, 2018: Indian Journal of Pediatrics
Feng Yang, Yonggen Jiang, Lihua Yang, Juanxiu Qin, Mingquan Guo, Yuxia Lu, Hongyou Chen, Yuan Zhuang, Jinghao Zhang, Hong Zhang, Zhaoyun Dai, Min Li, Changqing Yang, Min Chen, Yanmei Zhang, Hu Zhao
Objective: To investigate prevalence of acute diarrhea in Shanghai and analyze virulence associated-genes and antibiotic resistance of major enteropathogens using combination of conventional and molecular epidemiology methods. Method: The 412 stool specimens were obtained by systematic sampling from diarrhea patients throughout entire year 2016. Bacterial and viral pathogens were identified and bacterial isolates were cultured and screened for antibiotic resistance profiles. Two most prevalent bacteria, Vibrio parahaemolyticus and Salmonella were further typed by multi-locus sequence typing (MLST) and analyzed for presence of virulence-associated genes...
2018: Frontiers in Microbiology
Alessandro Russo, Simone Giuliano, Giancarlo Ceccarelli, Francesco Alessandri, Alessandra Giordano, Grazia Brunetti, Mario Venditti
Objectives: a significant cause of mortality in intensive care unit (ICU) is represented by multidrug-resistant (MDR) gram-negative bacteria, such as MDR Acinetobacter baumannii (MDR-AB) and Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp). Aim of the present study was the comparison of clinical features, therapy and outcome of patients who developed septic shock due to either MDR-AB or KPC-Kp. Methods: were retrospectively analyzed patients admitted to the intensive care unit (ICU) of a teaching hospital, from November 2010 to December 2015, who developed septic shock due to MDR-AB or KPC-Kp infection...
March 19, 2018: Antimicrobial Agents and Chemotherapy
Francesca Forti, Dwayne R Roach, Marco Cafora, Maria E Pasini, David S Horner, Ersilia V Fiscarelli, Martina Rossitto, Lisa Cariani, Federica Briani, Laurent Debarbieux, Daniela Ghisotti
The alarming diffusion of multidrug resistant (MDR) bacterial strains requires investigations on non-antibiotic therapies. Amongst them, the use of bacteriophages (phages) as antimicrobial agents, namely phage therapy, is a promising treatment strategy with support by recent successful compassionate treatments in Europe and the U.S.A. In this work, we combined host range and genomic information to design a 6-phage cocktail killing several clinical strains of P. aeruginosa , including those collected from Italian cystic fibrosis (CF) patients, and analyzed the cocktail performance...
March 19, 2018: Antimicrobial Agents and Chemotherapy
Martin Lorenz Eisinger, Laiyin Nie, Aline Ricarda Dörrbaum, Julian David Langer, Hartmut Michel
Multidrug resistance (MDR) in bacterial pathogens has become a severe threat to public health. Membrane transporters of the multidrug and toxic compound extrusion (MATE) family contribute critically to MDR, making them promising drug targets. Despite recent advances, structures in different conformations and the mechanistic details of their antiport cycle are still elusive. Here we studied NorM_PS, a representative MATE transporter from Pseudomonas stutzeri, using biochemical assays in combination with hydrogen/deuterium exchange-mass spectrometry (HDX-MS)...
March 16, 2018: Journal of Molecular Biology
Bahare Salehi, Hossein Goudarzi, Bahram Nikmanesh, Hamidreza Houri, Mostafa Alavi-Moghaddam, Zohreh Ghalavand
RATIONALE: Acinetobacter baumannii is one of the antibiotic-resistant superbugs that threatens hospitalized patients. Emergence and spread of the multidrug-resistant (MDR) and extensively drug-resistant (XDR) clones cause erratic outbreaks following environmental contamination of hospital settings. OBJECTIVE: The present study intended to characterize the antimicrobial resistant profiles and the genotypes of clinical and environmental isolates of A. baumannii as a result of dissemination of resistant strains...
March 16, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
David W Dowdy, Grant Theron, Jeffrey A Tornheim, Robin Warren, Emily A Kendall
A novel, shorter-course regimen for treating multidrug-resistant (MDR) tuberculosis was recently recommended by the World Health Organization. However, the most appropriate use of drug susceptibility testing (DST) to support this regimen is less clear. Implementing countries must therefore often choose between using a standardized regimen despite high levels of underlying drug resistance or require more stringent DST prior to treatment initiation. The former carries a high likelihood of exposing patients to de facto monotherapy with a critical drug class (fluoroquinolones), whereas the latter could exclude large groups of patients from their most effective treatment option...
October 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Huiling DI, Sisi Liang, Qingyang Li, Lei Shi, Ayaka Shima, Hecheng Meng, He Yan, Shinji Yamasaki
Bacteria of the genus Providencia are opportunistic pathogens of clinical significance due to their association with diarrhea and urinary tract infections. The present study was conducted to examine the prevalence and antimicrobial resistance of Providencia spp. in retail meats sold in Guangzhou, China and Osaka, Japan. Out of 158 meat samples including beef, pork and chicken, 67 Providencia (42%) belonging to four species viz., P.alcalifaciens, P. rustigianii, P. stuartii and P. rettgeri were isolated, and most of them were resistant to tetracycline (91%) followed by ampicillin (69%) and streptomycin (49%)...
March 19, 2018: Journal of Veterinary Medical Science
Katarzyna Mieszala, Malgorzata Rudewicz, Agnieszka Gomulkiewicz, Katarzyna Ratajczak-Wielgomas, Jedrzej Grzegrzolka, Piotr Dziegiel, Sylwia Borska
Multidrug resistance (MDR) is a notable problem in the use of chemotherapy. Therefore, studies aimed at identifying substances capable of overcoming resistance of cancer cells are required. Examples of these compounds are polyphenols, including resveratrol, that exert a range of various biological activities. The aim of the present study was to demonstrate the effect of 3,5,4'-trihydroxy- trans -stilbene (resveratrol) on the expression of ATP binding cassette subfamily B member 1, Annexin A1 ( ANXA1 ) and thioredoxin ( TXN ) genes, and the proteins encoded by these genes, which are associated with MDR...
April 2018: Oncology Letters
Lie Yao, Jichun Gu, Yishen Mao, Xinju Zhang, Xiaoyi Wang, Chen Jin, Deliang Fu, Ji Li
The main focus of the present study was to evaluate whether ABC transporter family promoter methylation predicted multidrug resistance in gemcitabine-resistant cancer cell lines (BxPC-3/Gem and PANC-1/Gem). Using low concentrations of gemcitabine, the cell lines acquired drug resistance with different initial gemcitabine concentrations. A novel technology, methylation-sensitive high-resolution melting, was used to monitor the dynamic changes of ABC transporter family promoter methylation, including ATP binding cassette subfamily B member 1 (ABCB1), ATP binding cassette subfamily C (ABCC) and ATP binding cassette subfamily G member 2 (ABCG2) mRNA expression...
April 2018: Oncology Letters
Yan Chen, Yao Cheng, Pengxuan Zhao, Shasha Zhang, Minsi Li, Chuanchuan He, Xiaojuan Zhang, Tan Yang, Ruicong Yan, Peng Ye, Xiang Ma, Guangya Xiang
Multidrug resistance to chemotherapeutic drugs is a major obstacle to breast cancer treatment. In this study, doxorubicin (DOX) and imatinib (IM) were co-loaded into folate receptor targeted (FR-targeted) pH-sensitive liposomes (denoted as FPL-DOX/IM) to fulfill intracellular acid-sensitive release and reverse drug resistance. FPL-DOX/IM could maintain stability in blood circulation with approximate diameters of 100 nm and rapidly release encapsulated drugs in tumor acidic microenvironment. Moreover, the IM in combination therapy could overcome chemoresistance associated with DOX effectively by inhibiting ABC transporter function and improving chemotherapy sensitivity...
March 15, 2018: International Journal of Pharmaceutics
Steven A Rosenzweig
Resistance to chemotherapeutic drugs exemplifies the greatest hindrance to effective treatment of cancer patients. The molecular mechanisms responsible have been investigated for over 50 years and have revealed the lack of a single cause, but instead, multiple mechanisms including induced expression of membrane transporters that pump drugs out of cells (multidrug resistance (MDR) phenotype), changes in the glutathione system, and altered metabolism. Treatment of cancer patients/cancer cells with chemotherapeutic agents and/or molecularly targeted drugs is accompanied by acquisition of resistance to the treatment administered...
2018: Advances in Cancer Research
André Campaniço, Rui Moreira, Francisca Lopes
Tuberculosis (TB) remains a major health problem worldwide. The infectious agent, Mycobacterium tuberculosis, has a unique ability to survive within the host, alternating between active and latent disease states, and escaping the immune system defences. The extended duration of anti-TB regimens and the increasing prevalence of multidrug- (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains have created an urgent need for new antibiotics active against drug-resistant organisms and that can shorten standard therapy...
March 9, 2018: European Journal of Medicinal Chemistry
Chenglin Luo, Jingjing Cao, Rui Peng, Qiaoyun Guo, Hua Ye, Peng Wang, Kaijuan Wang, Chunhua Song
Functional polymorphisms in Linc-ROR may change its ability of regulation by regulating Linc-ROR expression. However, these functional polymorphisms in Linc-ROR and their associations with breast cancer (BC) susceptibility were scarcely reported. In this molecular epidemiological study, four SNPs (rs6420545, rs4801078, rs1942348 and rs9636089) were selected in Linc-ROR by bioinformatics method. Unconditional logistic regression model was performed to analyze the associations between four SNPs and BC susceptibility adjusted for reproductive factors...
March 16, 2018: Scientific Reports
Malgorzata Mikulska, Catherine Cordonnier
Yeshurun et al. reported the results of retrospective study with historical control in patients with multiple myeloma and lymphoma undergoing autologous transplant. The rates of bacteraemia and fever were lower during the period of ciprofloxacin prophylaxis with no effect on mortality. In the era of multidrug resistance (MDR), the efficacy of fluoroquinolone prophylaxis might be lower in settings with high level of resistance. Additionally, the benefit of fluoroquinolone prophylaxis on mortality should not be expected since the morality is mainly associated with infections due to MDR currently associated with MDR strains which could not be prevented by fluoroquinolone prophylaxis...
March 13, 2018: Clinical Microbiology and Infection
Dinesh Subedi, Ajay Kumar Vijay, Gurjeet Singh Kohli, Scott A Rice, Mark Willcox
No abstract text is available yet for this article.
March 13, 2018: Journal of Antimicrobial Chemotherapy
Deepak Reddy Gade, Amareswararao Makkapati, Rajesh Babu Yarlagadda, Godefridus J Peters, B S Sastry, V V S Rajendra Prasad
Overexpression of P-glycoprotein (P-gp) leads to the emergence of multidrug resistance (MDR) in cancer treatment. Acridones have the potential to reverse MDR and sensitize cells. In the present study, we aimed to elucidate the chemosensitization potential of acridones by employing various molecular modelling techniques. Pharmacophore modeling was performed for the dataset of chemosensitizing acridones earlier proved for cytotoxic activity against MCF7 breast cancer cell line. Gaussian-based QSAR studies also performed to predict the favored and disfavored region of the acridone molecules...
February 24, 2018: Computational Biology and Chemistry
Michael K Krapf, Jennifer Gallus, Sahel Vahdati, Michael Wiese
Multidrug resistance occurring during cancer chemotherapy is a major obstacle for effectiveness and response to therapy and is often caused by ATP-binding cassette (ABC) efflux transporters. Belonging to the family of ABC transporters, breast cancer resistance protein is getting more and more in the spotlight of research. As a strategy to overcome multidrug resistance, inhibitors of ABC transporters were synthesized, which could be applied in combination with cytostatic drugs. For this purpose, 2,4-disubstituted pyridopyrimidine derivatives were synthesized...
March 16, 2018: Journal of Medicinal Chemistry
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