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https://www.readbyqxmd.com/read/28320145/vision-loss-in-tuberculous-meningitis
#1
REVIEW
Ravindra Kumar Garg, Hardeep Singh Malhotra, Neeraj Kumar, Ravi Uniyal
Vision loss is a disabling complication of tuberculous meningitis. Approximately, 15% of survivors are either completely or partially blind. All structures of the visual pathway may be affected in tuberculous meningitis. Optic nerve and optic chiasma are most frequently and dominantly affected. Thick-gelatinous exudates lying over the base of brain, are the pathological hallmark of tuberculous meningitis and are responsible for almost all of its major complications, including vision loss. Strangulation of optic nerves and optic chiasma by the exudates, compression over optic chiasma by the dilated third ventricle, raised intracranial pressure, endarteritis, shunt failure, bacterial invasion of optic nerves and drug-induced optic nerve damage are important reasons that are considered responsible for vision loss...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319812/exploring-sequence-space-harnessing-chemical-and-biological-diversity-towards-new-peptide-leads
#2
REVIEW
Richard Obexer, Louise J Walport, Hiroaki Suga
From their early roots in natural products, peptides now represent an expanding class of novel drugs. Their modular structures make them ideal candidates for pooled library screening approaches. Key technologies for library generation and screening, such as SICLOPPS, phage display and mRNA display, give unparalleled access to tight binding peptides. Through combination with genetic code reprogramming and chemical modifications, access to more natural product-like libraries, spanning non-canonical peptide space, is readily achievable...
March 17, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28319380/evaluation-and-characterization-of-trk-kinase-inhibitors-for-the-treatment-of-pain-reliable-binding-affinity-predictions-from-theory-and-computation
#3
Shunzhou Wan, Agastya P Bhati, Sarah Skerratt, Kiyoyuki Omoto, Veerabahu Shanmugasundaram, Sharan K Bagal, Peter Vivian Coveney
Optimisation of ligand binding affinity to the target protein of interest is a primary objective in small-molecule drug discovery. Until now, the prediction of binding affinities by computational methods has not been widely applied in the drug discovery process, mainly due to its lack of accuracy and reproducibility, as well as the long turnaround times required to obtain results. Herein, we report on a collaborative study that compares tropomyosin receptor kinase A (TrkA) binding affinity predictions using two recently formulated fast computational approaches - namely ESMACS (Enhanced Sampling of Molecular dynamics with Approximation of Continuum Solvent) and TIES (Thermodynamic Integration with Enhanced Sampling) - to experimentally derived TrkA binding affinities for a set of Pfizer pan-Trk compounds...
March 20, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28318778/stenotrophomonas-maltophilia-healthcare-associated-infections-identification-of-two-main-pathogenic-genetic-backgrounds
#4
C Corlouer, B Lamy, M Desroches, J Ramos-Vivas, E Mehiri-Zghal, O Lemenand, J-M Delarbre, J-W Decousser
BACKGROUND: Stenotrophomonas maltophilia is an opportunistic multi-drug-resistant bacterium responsible for healthcare-associated infections. Strategies for in-hospital infection control and management of carriers and environmental reservoirs remain controversial. AIM: To determine the population structure of S. maltophilia strains in hospitalized infected patients and to identify putative highly pathogenic subpopulations that require upgraded infection control measures...
February 9, 2017: Journal of Hospital Infection
https://www.readbyqxmd.com/read/28318570/rapid-diagnosis-of-tuberculosis-detection-of-drug-resistance-mechanisms
#5
Jesús Viñuelas-Bayón, María Asunción Vitoria, Sofía Samper
Tuberculosis is still a serious public health problem, with 10.8 million new cases and 1.8 million deaths worldwide in 2015. The diversity among members of the Mycobacterium tuberculosis complex, the causal agent of tuberculosis, is conducive to the design of different methods for rapid diagnosis. Mutations in the genes involved in resistance mechanisms enable the bacteria to elude the treatment. We have reviewed the methods for the rapid diagnosis of M. tuberculosis complex and the detection of susceptibility to drugs, both of which are necessary to prevent the onset of new resistance and to establish early, appropriate treatment...
March 15, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/28317962/-phsio1-5-8-10-12-as-nanoreactors-for-non-enzymatic-introduction-of-ortho-meta-or-para-hydroxyl-groups-to-aromatic-molecules
#6
Mozhgan Bahrami, Xingwen Zhang, Morteza Ehsani, Yousef Jahani, Richard M Laine
Traditional electrophilic bromination follows long established "rules": electron-withdrawing substituents cause bromination selective for meta positions, whereas electron-donating substituents favor ortho and para bromination. In contrast, in the [PhSiO1.5]8,10,12 silsesquioxanes, the cages act as bulky, electron withdrawing groups equivalent to CF3; yet bromination under mild conditions, without a catalyst, greatly favors ortho substitution. Surprisingly, ICl iodination without a catalyst favors (>90%) para substitution [p-IC6H4SiO1...
March 20, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28317799/a-first-insight-into-the-genetic-diversity-of-mycobacterium-tuberculosis-in-veracruz-mexico
#7
Raquel Almaraz-Velasco, Daniela Munro-Rojas, Javier Fuentes-Domínguez, Raquel Muñiz-Salazar, Maria Angélica Ibarra-Estela, Alma Delia Guevara-Méndez, Rosa Icela Chaparro-Martinez, Monserrat Perez-Navarro, Roberto Zenteno-Cuevas
OBJECTIVE/BACKGROUND: Tuberculosis (TB) remains one of the most important infectious diseases. Although Mexico is one of the Latin American countries with the largest contribution to these statistics, there are few reports that describe the genotypic characteristics of TB. The aim of this study was to use the MIRU-VNTR-24 loci to analyze the genetic diversity of M. tuberculosis circulating in the state of Veracruz, Mexico. METHODS: Here, we analyze by MIRU-VNTR-24 loci 80 clinical isolates from individuals with confirmed TB from Veracruz México, also clinical and epidemiological variables were recovered and analyzed...
January 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28317101/recent-advances-in-small-molecule-and-biological-therapeutic-approaches-in-the-treatment-of-psoriasis
#8
Jackson G Turbeville, Nupur U Patel, Leah A Cardwell, Elias Oussedik, Steven R Feldman
New treatments continue to be developed for psoriasis. In this review, we aim to summarize the results of the major published studies on biologic and small molecule drugs for the treatment of psoriasis. We emphasize the safety, efficacy, and tolerability of these treatment options. A review of the MEDLINE database was conducted for each class of medication. Randomized controlled trials were identified for each medication; data on efficacy, safety, and tolerability was reviewed. Biologic and small molecule treatment options are more effective than placebo, although there were few head-to-head trials to assess relative efficacy between biologics and small molecule treatments...
March 20, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28316253/predominance-of-hepatitis-b-virus-genotype-a-among-treated-hiv-infected-patients-experiencing-high-hbv-drug-resistance-in-nairobi-kenya
#9
Sepha Nyatichi Mabeya, Caroline Wangari Ngugi, Raphael W Lihana, Samoel Ashimosi Khamadi, Anthony Kebira Nyamache
HBV/HIV coinfections are becoming common with information on HBV genetic diversity and drug resistance still remaining elusive. To evaluate the HBV genetic diversity and drug resistance associated mutations among drug experienced HIV patients, the genetic analysis of the partial HBV-pol-reverse trancriptase gene was successfully sequenced from 13 samples. Analysis of the sequences showed that all (13) the sequences belonged to genotype A. Nucleos(t)ide drug resistance mutations were found in six (6) patients...
March 19, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28316009/safety-assessment-of-commensal-enterococci-from-dogs
#10
Ivana Kubašová, Viola Strompfová, Andrea Lauková
Enterococci form a complex, diverse, and very important group of bacteria from the technological and food safety aspect, or from the health-improving aspect as probiotics. Generally, enterococci are considered to be of low pathogenic potential, which is associated mostly with clinical strains. In these strains, production of virulence factors as well as resistance to many antimicrobial drugs could complicate treatment of nosocomial infections. Because there is a lack of information on incidence of these attributes in animal commensal enterococci, we screened 160 strains originating from feces of clinically healthy dogs in Eastern Slovakia (n = 105)...
March 18, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/28315874/multiple-drug-hypersensitivity
#11
Werner J Pichler, Yuttana Srinoulprasert, James Yun, Oliver Hausmann
Multiple drug hypersensitivity (MDH) is a syndrome that develops as a consequence of massive T-cell stimulations and is characterized by long-lasting drug hypersensitivity reactions (DHR) to different drugs. The initial symptoms are mostly severe exanthems or drug rash with eosinophilia and systemic symptoms (DRESS). Subsequent symptoms due to another drug often appear in the following weeks, overlapping with the first DHR, or months to years later after resolution of the initial presentation. The second DHR includes exanthema, erythroderma, DRESS, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hepatitis, and agranulocytosis...
March 18, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28315700/exploiting-the-aglycon-promiscuity-of-glycosyltransferase-bs-yjic-from-bacillus-subtilis-and-its-application-in-synthesis-of-glycosides
#12
Longhai Dai, Jiao Li, Peiyuan Yao, Yueming Zhu, Yan Men, Yan Zeng, Jiangang Yang, Yuanxia Sun
Glycosylation is a prominent biological mechanism for structural and functional diversity of natural products. Uridine diphosphate-dependent glycosyltransferases with aglycon promiscuity are generally recognised as effective biocatalysts for glycodiversification of natural products for practical applications. In this study, the aglycon promiscuity of glycosyltransferase Bs-YjiC from Bacillus subtilis 168 was explored. Bs-YjiC, with uridine diphosphate glucose (UDPG) as sugar donor, exhibited robust capabilities to glycosylate 19 structurally diverse types of drug-like scaffolds with regio- and stereospecificities and form O-, N- and S-linkage glycosides...
March 15, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28315483/functional-proteomic-analysis-of-corticosteroid-pharmacodynamics-in-rat-liver-relationship-to-hepatic-stress-signaling-energy-regulation-and-drug-metabolism
#13
Vivaswath S Ayyar, Richard R Almon, Debra C DuBois, Siddharth Sukumaran, Jun Qu, William J Jusko
Corticosteroids (CS) are anti-inflammatory agents that cause extensive pharmacogenomic and proteomic changes in multiple tissues. An understanding of the proteome-wide effects of CS in liver and its relationships to altered hepatic and systemic physiology remains incomplete. Here, we report the application of a functional pharmacoproteomic approach to gain integrated insight into the complex nature of CS responses in liver in vivo. An in-depth functional analysis was performed using rich pharmacodynamic (temporal-based) proteomic data measured over 66h in rat liver following a single dose of methylprednisolone (MPL)...
March 14, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28315359/antibodies-and-associates-partners-in-targeted-drug-delivery
#14
REVIEW
Patrick J Kennedy, Carla Oliveira, Pedro L Granja, Bruno Sarmento
Monoclonal antibodies (mAbs) are well established in the clinic due to their specificity and affinity to a diverse array of biochemical targets. More recently, mAbs are being exploited as targeting agents in modern drug delivery systems, aiming to bypass normal host tissue and to accumulate a therapeutic agent to a specific tissue or cell for enhanced pharmacology. At sizes ranging from ~10-100nm, antibody-based bioconjugates have opened up a whole new realm of clinical possibilities with several platforms emerging on the market...
March 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28314853/activation-of-the-orphan-g-protein-coupled-receptor-gpr27-by-surrogate-ligands-promotes-%C3%AE-arrestin-2-recruitment
#15
Nadine Dupuis, Celine Laschet, Delphine Franssen, Martyna Szpakowska, Julie Gilissen, Pierre Geubelle, Arvind Soni, Anne-Simone Parent, Bernard Pirotte, Andy Chevigne, Jean-Claude Twizere, Julien Hanson
G protein-coupled receptors are the most important drug targets for human diseases. An important number of them remain devoid of confirmed ligands. GPR27 is one of these orphan receptors, characterized by a high level of conservation among vertebrates and a predominant expression in the central nervous system. In addition, it has recently been linked to insulin secretion. However, the absence of endogenous or surrogate ligands for GPR27 complicates the examination of its biological function. Our aim was to validate GPR27 signaling pathways and therefore we sought to screen a diversity oriented synthesis library to identify GPR27-specific surrogate agonists...
March 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28314467/association-between-copayment-medication-adherence-and-outcomes-in-the-management-of-patients-with-diabetes-and-heart-failure
#16
REVIEW
George Gourzoulidis, Georgia Kourlaba, Panagiotis Stafylas, Gregory Giamouzis, John Parissis, Nikolaos Maniadakis
OBJECTIVE: To determine the association between copayment, medication adherence and outcomes in patients with Heart failure (HF) and Diabetes Mellitus (DM). METHODS: PubMed, Scopus and Cochrane databases were searched using combinations of four sets of key words for: drug cost sharing; resource use, health and economic outcomes; medication adherence; and chronic disease. RESULTS: Thirty eight studies were included in the review. Concerning the direct effect of copayment changes on outcomes, the scarcity and diversity of data, does not allow us to reach a clear conclusion, although there is some evidence indicating that higher copayments may result in poorer health and economic outcomes...
February 28, 2017: Health Policy
https://www.readbyqxmd.com/read/28314457/transitional-age-lesbian-gay-bisexual-transgender-and-questioning-youth-issues-of-diversity-integrated-identities-and-mental-health
#17
REVIEW
Scott M Rodgers
Although most LGBTQ youth become healthy young adults, they often face considerable stress over the course of their lives because of bullying, victimization, and overt/covert discrimination. Families, educational and religious institutions, health care professionals, and communities help shape the experience of LGBTQ transitional age youth. LGBTQ youth have higher rates of depression, suicide, anxiety, posttraumatic stress disorder, alcohol and drug use, and preventable sexually transmitted diseases. When best practice guidelines are followed and key stakeholders take action to support LGBTQ youth, health disparities begin to disappear...
April 2017: Child and Adolescent Psychiatric Clinics of North America
https://www.readbyqxmd.com/read/28314411/small-molecule-inhibition-of-interleukin-1-receptor-associated-kinase-4-irak4
#18
N E Genung, K M Guckian
In recent years, interleukin-1 receptor-associated kinase 4, IRAK4, has become an attractive target for many medicinal chemistry programmes. Target inhibition is of potential therapeutic value in areas including autoimmune disorders, cancer, inflammatory diseases, and possibly neurodegenerative diseases. Results from high-throughput screening efforts have led, in conjunction with structure-based drug design, to the identification of highly potent and selective small molecule IRAK4 inhibitors from many diverse chemical series...
2017: Progress in Medicinal Chemistry
https://www.readbyqxmd.com/read/28314118/in-vitro-assay-development-and-hts-of-small-molecule-human-abad-17%C3%AE-hsd10-inhibitors-as-therapeutics-in-alzheimer-s-disease
#19
Laura Aitken, Gemma Baillie, Andrew Pannifer, Angus Morrison, Philip S Jones, Terry K Smith, Stuart P McElroy, Frank J Gunn-Moore
A major hallmark of Alzheimer's disease (AD) is the formation of neurotoxic aggregates composed of the amyloid-β peptide (Aβ). Aβ has been recognized to interact with numerous proteins, resulting in pathological changes to the metabolism of patients with AD. One such mitochondrial metabolic enzyme is amyloid-binding alcohol dehydrogenase (ABAD), where altered enzyme function caused by the Aβ-ABAD interaction is known to cause mitochondrial distress and cytotoxic effects, providing a feasible therapeutic target for AD drug development...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28306751/peptidomic-and-transcriptomic-profiling-of-four-distinct-spider-venoms
#20
Vera Oldrati, Dominique Koua, Pierre-Marie Allard, Nicolas Hulo, Miriam Arrell, Wolfgang Nentwig, Frédérique Lisacek, Jean-Luc Wolfender, Lucia Kuhn-Nentwig, Reto Stöcklin
Venom based research is exploited to find novel candidates for the development of innovative pharmacological tools, drug candidates and new ingredients for cosmetic and agrochemical industries. Moreover, venomics, as a well-established approach in systems biology, helps to elucidate the genetic mechanisms of the production of such a great molecular biodiversity. Today the advances made in the proteomics, transcriptomics and bioinformatics fields, favor venomics, allowing the in depth study of complex matrices and the elucidation even of minor compounds present in minute biological samples...
2017: PloS One
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