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https://www.readbyqxmd.com/read/28429672/the-molecular-mechanisms-of-thalidomide-teratogenicity-and-implications-for-modern-medicine
#1
J Knobloch, D Jungck, A Koch
Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and anti-angiogenic activities are considered in many other refractory diseases...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28420614/applications-of-genome-editing-tools-in-precision-medicine-research
#2
Li Shuang, Yang Yuanyuan, Qiu Yan, Chen Yanhao, Xu Luwei, Ding Qiurong
The emergence of genome editing tools, such as the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, has enabled researchers to achieve somatic and germline genomic manipulations in cell lines and model organisms. Within a couple of years, genome editing is now being rapidly developed for multiple applications and widely used in biomedical researches, including creation of disease models with desired genetic mutations, screening in a high-throughput manner for drug resistance genes, and making appropriate editions to genes in vivo for disease treatment...
March 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28398275/natural-killer-t-cell-lymphomas-in-pediatric-and-adolescent-patients
#3
REVIEW
Amanda M Termuhlen
Natural killer/T-cell (NK/T-cell) lymphomas are rare in children and adolescents and consist predominantly of nasal-type extranodal NK/T-cell lymphomas. More than half of pediatric/adolescent patients with NK/T-cell lymphomas present with localized nasal/sinus involvement, but the disease may involve many organs. NK/T-cell lymphoma cells are cytotoxic and associated with necrosis and angioinvasion; they express CD56, CD2, cytoplasmic CD3 epsilon, and to a variable degree CD30. The cells contain Epstein-Barr virus (EBV)-encoded RNA...
March 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28392829/a-robust-protocol-for-efficient-generation-and-genomic-characterization-of-insertional-mutants-of-chlamydomonas-reinhardtii
#4
Steve V Pollock, Bratati Mukherjee, Joanna Bajsa-Hirschel, Marylou C Machingura, Ananya Mukherjee, Arthur R Grossman, James V Moroney
BACKGROUND: Random insertional mutagenesis of Chlamydomonas reinhardtii using drug resistance cassettes has contributed to the generation of tens of thousands of transformants in dozens of labs around the world. In many instances these insertional mutants have helped elucidate the genetic basis of various physiological processes in this model organism. Unfortunately, the insertion sites of many interesting mutants are never defined due to experimental difficulties in establishing the location of the inserted cassette in the Chlamydomonas genome...
2017: Plant Methods
https://www.readbyqxmd.com/read/28392413/isolation-and-identification-of-multiple-drug-resistant-nontuberculous-mycobacteria-from-organs-of-cattle-produced-typical-granuloma-lesions
#5
Guangyu Cheng, Donglei Xu, Jinling Wang, Chunfa Liu, Yang Zhou, Yongyong Cui, Hancan Liu, Kanglin Wan, Xiangmei Zhou
Nontuberculosis mycobacteria are widespread in the environment and some are zoonotic. 320 tissue samples with visible lesions were obtained from dairy cows and examined by histopathology. Eleven samples showed typical granulomatous lesions and a total of 8 strains were cultured. Three genes (16S rRNA, hsp65 and rpoB) were sequenced for species identification. All mycobacterial isolates were tested for rifampicin, isoniazid, ethambutol, streptomycin, capreomycin, kanamycin, para-aminosalicylic acid susceptibility...
April 6, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28387179/chemotherapy-of-tuberculosis
#6
Thomas E Dobbs, Risa M Webb
The management of tuberculosis (TB) can be a challenging process that has implications both for the affected patient and public health. Effective anti-TB chemotherapy both cures and renders the patient noncontagious. Biological factors specific to M. tuberculosis necessitate the use of multiple drugs for prolonged durations to adequately eradicate infection. Recommended regimens address the complexities of eliminating organisms from diverse reservoirs while preventing the emergence of drug resistance. First-line anti-TB therapy for drug susceptible disease effectively cures almost all patients within 6-9 months...
April 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28361737/therapy-of-multidrug-resistant-and-extensively-drug-resistant-tuberculosis
#7
Barbara J Seaworth, David E Griffith
The global epidemic of multidrug-resistant tuberculosis (MDR-TB) caused by Mycobacterium tuberculosis strains resistant to at least isoniazid and rifampin was recently reported as larger than previously estimated, with at least 580,000 new cases reported in 2015. Extensively drug-resistant tuberculosis (XDR-TB), MDR-TB with additional resistance to a second-line fluoroquinolone and injectable, continues to account for nearly 10% of MDR cases globally. Cases in India, China, and the Russian Federation account for >45% of the cases of MDR-TB...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28357319/phylogenetic-profiles-of-all-membrane-transport-proteins
#8
January Weiner, Taco W A Kooij
In order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. Proteins that are essential to survival and specific to malaria parasites are key candidates. To survive within host cells, the parasites need to acquire nutrients and dispose of waste products across multiple membranes. Additionally, like all eukaryotes, they must redistribute ions and organic molecules between their various internal membrane bound compartments. Membrane transport proteins mediate all of these processes and are considered important mediators of drug resistance as well as drug targets in their own right...
August 30, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28352198/antimicrobial-susceptibility-profile-treatment-outcome-and-serotype-distribution-of-clinical-isolates-of-salmonella-enterica-subspecies-enterica-a-2-year-study-from-kerala-south-india
#9
Deepa Harichandran, Kavitha Radhakrishnan Dinesh
BACKGROUND/PURPOSE: Typhoid and paratyphoid fever continue to be important causes of illness and death in parts of Asia, being associated with poor sanitation and consumption of unsafe food and water. Antimicrobial resistance has emerged to traditional first-line drugs, namely, the fluoroquinolones, as well as to third-generation cephalosporins, posing challenges to treatment. Azithromycin has proven to be an effective alternative for treatment of uncomplicated typhoid fever. The purpose of this study was to determine the antimicrobial susceptibility, clinical outcome and serotype distribution pattern of clinical isolates belonging to Salmonella enterica subspecies enterica...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/28347174/autophagy-as-a-target-for-development-of-anti-diabetes-drugs-derived-from-natural-compounds
#10
REVIEW
Xiao-Wei Zhang, Ji-Chao Zhou, Zhuo-Wei Hu
Patients with diabetes have a high level of blood glucose because their body cannot produce enough insulin or properly respond to this hormone. In both situations, it has become evident that persistent high concentrations of glucose, insulin, insulin-like growth factor, and insulin resistance lead to dysfunction and destruction of autophagic activity in the cells of islet and other organs involved in complications of diabetes, including the liver, cardiovascular, and nervous systems. Accumulating evidences have revealed that autophagy is a novel therapeutic target with a wide range of beneficial effects on diabetes and that plenty of drugs and natural products are involved in autophagy modulation, either inducing or inhibiting autophagy, through multiple signaling pathways...
April 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28346803/carbapenemase-producing-aeromonas-veronii-disseminated-in-the-environment-of-an-equine-specialty-hospital
#11
Rachael J Adams, Dimitria A Mathys, Dixie F Mollenkopf, Andrea Whittle, Joshua B Daniels, Thomas E Wittum
The emergence of bacterial resistance to carbapenem antibiotics is an urgent public health threat. Carbapenem drugs are a last resort treatment option for life-threatening infections. The frequent use of broad-spectrum antibiotics to treat hospitalized patients provides significant selection pressure favoring the emergence and dissemination of resistant organisms, including carbapenem-resistant Enterobacteriaceae (CRE). CREs have been reported in animal populations, but only rarely in horses. Our objective was to determine the prevalence of CRE in the environment of a referral equine specialty hospital...
March 27, 2017: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/28329693/lanthanide-integrated-supramolecular-polymeric-nanoassembly-with-multiple-regulation-characteristics-for-multidrug-resistant-cancer-therapy
#12
Weihong Jin, Qiwen Wang, Min Wu, Yang Li, Guping Tang, Yuan Ping, Paul K Chu
Cancer treatment can in principle be enhanced by the synergistic effects of chemo- and nucleic acid-based combination therapies but the lack of efficient drug nanocarriers and occurrence of multidrug resistance (MDR) are major obstacles adversely affecting the effectiveness. Herein, a lanthanide-integrated supramolecular polymeric nanoassembly that delivers anticancer drugs and siRNA for more effective cancer therapy is described. This nanotherapeutic system is prepared by loading adamantane-modified doxorubicin (Dox) into polyethylenimine-crosslinked-γ-cyclodextrin (PC) through the supramolecular assembly to form the interior Dox-loaded PC (PCD) followed by electrostatically driven self-assembly of siRNA and PCD to produce the PCD/siRNA nanocomplexes...
March 16, 2017: Biomaterials
https://www.readbyqxmd.com/read/28296768/difficult-clinical-management-of-antituberculosis-dress-syndrome-complicated-by-mrsa-infection-a-case-report
#13
Li Wang, Lin-Feng Li
RATIONALE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity reaction characterized by skin rash, fever, blood abnormalities, and multiple organ involvement. The diagnosis of DRESS syndrome is often delayed because of its variable presentation. Prompt withdrawal of the culprit drug is the definitive treatment. DRESS syndrome induced by antituberculosis drugs has rarely been reported. PATIENT CONCERNS: A 50-year-old man admitted to our hospital with recurrent episodes of progressive rash, fever, eosinophilia, lymphadenopathy, hepatic, and pulmonary involvement were experienced after repeat trials of the same antituberculosis drugs...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28296193/investigating-transporter-mediated-drug-drug-interactions-using-a-physiologically-based-pharmacokinetic-model-of-rosuvastatin
#14
Q Wang, M Zheng, T Leil
Rosuvastatin is a frequently used probe in transporter-mediated drug-drug interaction (DDI) studies. This report describes the development of a physiologically based pharmacokinetic (PBPK) model of rosuvastatin for prediction of pharmacokinetic (PK) DDIs. The rosuvastatin model predicted the observed single (i.v. and oral) and multiple dose PK profiles, as well as the impact of coadministration with transporter inhibitors. The predicted effects of rifampin and cyclosporine (6.58-fold and 5.07-fold increase in rosuvastatin area under the curve (AUC), respectively) were mediated primarily via inhibition of hepatic organic anion-transporting polypeptide (OATP)1B1 (Inhibition constant (Ki ) ∼1...
April 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28289911/transcriptomics-as-a-tool-to-discover-new-antibacterial-targets
#15
REVIEW
Ángel Domínguez, Elisa Muñoz, M Carmen López, Miguel Cordero, José Pedro Martínez, Miguel Viñas
The emergence of antibiotic-resistant pathogens, multiple drug-resistance, and extremely drug-resistant strains demonstrates the need for improved strategies to discover new drug-based compounds. The development of transcriptomics, proteomics, and metabolomics has provided new tools for global studies of living organisms. However, the compendium of expression profiles produced by these methods has introduced new scientific challenges into antimicrobial research. In this review, we discuss the practical value of transcriptomic techniques as well as their difficulties and pitfalls...
March 13, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28258008/high-content-screening-of-clinically-tested-anticancer-drugs-identifies-novel-inhibitors-of-human-mrp1-abcc1
#16
Brian G Peterson, Kee W Tan, Bremansu Osa-Andrews, Surtaj H Iram
Multidrug resistance protein 1 (MRP1/ABCC1), an integral transmembrane efflux transporter, belongs to the ATP-binding cassette (ABC) protein superfamily. MRP1 governs the absorption and disposition of a wide variety of endogenous and xenobiotic substrates including various drugs across organs and physiological barriers. Additionally, its overexpression has been implicated in multidrug resistance in chemotherapy of multiple cancers. Here, we describe the development of a high content imaging-based screening assay for MRP1 activity...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28245739/the-conundrum-of-feline-trichomonosis
#17
Jody L Gookin, Katherine Hanrahan, Michael G Levy
Practical relevance: Trichomonosis of the large intestine of the cat was described as a cause of chronic diarrhea over 20 years ago. The trichomonad was identified as Tritrichomonas foetus, with a genotype that is distinct from venereal T foetus of cattle. Clinical challenges: Despite multiple means for diagnosis of the infection, including light microscopy, protozoal culture and PCR amplification using species-specific primers, tests with even greater sensitivity are needed. Feline trichomonosis is resistant to all commonly used antiprotozoal drugs...
March 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/28235673/laquinimod-enhances-central-nervous-system-barrier-functions
#18
Fred Lühder, Hania Kebir, Francesca Odoardi, Tanja Litke, Maike Sonneck, Jorge Ivan Alvarez, Jan Winchenbach, Nadine Eckert, Liat Hayardeny, Ella Sorani, Dmitri Lodygin, Alexander Flügel, Alexandre Prat
Laquinimod is currently being tested as a therapeutic drug in multiple sclerosis. However, its exact mechanism of action is still under investigation. Tracking of fluorescently-tagged encephalitogenic T cells during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, revealed that laquinimod significantly reduces the invasion of pathogenic effector T cells into the CNS tissue. T-cell activation, differentiation and amplification within secondary lymphoid organs after immunization with myelin antigen, their migratory capacity and re-activation within the nervous tissue were either only mildly affected or remained unchanged...
June 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28223391/evaluation-of-para-aminosalicylic-acid-pas-as-a-substrate-of-multiple-solute-carrier-slc-uptake-transporters-and-possible-drug-interactions-with-nsaids-in-vitro
#19
Md Masud Parvez, Ho Jung Shin, Jin Ah Jung, Jae-Gook Shin
para-Aminosalicylic acid (PAS) is a second-line anti-tuberculosis drug used to treat multidrug-resistant and extensively drug-resistant tuberculosis for more than 60 years. Renal secretion and glomerular filtration are the major pathways for elimination of PAS. We comprehensively studied PAS transport by using cell lines that overexpressed various transporters, and found that PAS acts as a novel substrate of organic anionic polypeptide (OATP1B1), organic cationic transporters (OCT1 and OCT2), and organic anion transporters (OAT1 and OAT3) but not a substrate of any ATP-binding cassette (ABC) transporters...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28198682/molecular-epidemiology-and-antimicrobial-resistance-phenotypes-of-acinetobacter-baumannii-isolated-from-patients-in-three-hospitals-in-southern-vietnam
#20
Nguyen Tuan Anh, Tran Vu Thieu Nga, Huynh Minh Tuan, Nguyen Si Tuan, Dao Minh Y, Nguyen Van Vinh Chau, Stephen Baker, Ho Huynh Thuy Duong
Multidrug resistance in the nosocomial pathogen Acinetobacter baumannii limits therapeutic options and impacts on clinical care. Resistance against carbapenems, a group of last-resort antimicrobials for treating multidrug-resistant (MDR) A. baumannii infections, is associated with the expression (and over-expression) of carbapenemases encoded by the blaOXA genes. The aim of this study was to determine the prevalence of antimicrobial-resistant A. baumannii associated with infection in three hospitals in southern Vietnam and to characterize the genetic determinants associated with resistance against carbapenems...
January 2017: Journal of Medical Microbiology
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