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Antibiotics Pharmacology

Tamasen Hayward, Alexander Young, Abigail Jiang, Erica J Crespi, Allison B Coffin
Aminoglycoside antibiotics have potent antibacterial properties but cause hearing loss in up to 25% of patients. These drugs are commonly administered in patients with high glucocorticoid stress hormone levels and can be combined with exogenous glucocorticoid treatment. However, the interaction of stress and aminoglycoside-induced hearing loss has not been fully explored. In this study, we investigated the effect of the glucocorticoid stress hormone cortisol on hair cells in the zebrafish lateral line as an important step toward understanding how physiological stressors modulate hair cell survival...
March 6, 2019: Hearing Research
Mark J Taylor, Thomas W von Geldern, Louise Ford, Marc P Hübner, Kennan Marsh, Kelly L Johnston, Hanna T Sjoberg, Sabine Specht, Nicolas Pionnier, Hayley E Tyrer, Rachel H Clare, Darren A N Cook, Emma Murphy, Andrew Steven, John Archer, Dominique Bloemker, Franziska Lenz, Marianne Koschel, Alexandra Ehrens, Haelly M Metuge, Valerinne C Chunda, Patrick W Ndongmo Chounna, Abdel J Njouendou, Fanny F Fombad, Robert Carr, Howard E Morton, Ghaith Aljayyoussi, Achim Hoerauf, Samuel Wanji, Dale J Kempf, Joseph D Turner, Stephen A Ward
There is an urgent global need for a safe macrofilaricide drug to accelerate elimination of the neglected tropical diseases onchocerciasis and lymphatic filariasis. From an anti-infective compound library, the macrolide veterinary antibiotic, tylosin A, was identified as a hit against Wolbachia This bacterial endosymbiont is required for filarial worm viability and fertility and is a validated target for macrofilaricidal drugs. Medicinal chemistry was undertaken to develop tylosin A analogs with improved oral bioavailability...
March 13, 2019: Science Translational Medicine
Tri Wangrangsimakul, Rachel C Greer, Chulapong Chanta, Supalert Nedsuwan, Stuart D Blacksell, Nicholas P J Day, Daniel H Paris
BACKGROUND: Scrub typhus, caused by Orientia tsutsugamushi, is a major cause of acute febrile illness in children in the rural tropics. METHODS: We recruited 60 febrile pediatric patients with a positive scrub typhus rapid diagnostic test result and 40 healthy controls from Chiang Rai Province in northern Thailand. Diagnosis was confirmed by the detection of (1) O. tsutsugamushi-specific DNA in blood or eschar samples with a polymerase chain reaction assay, (2) a fourfold rise in immunoglobulin M (IgM) titer to ≥1:3200 in paired plasma samples with an indirect immunofluorescence assay (IFA), or (3) a single IgM titer of ≥1:3200 in an acute plasma sample with an IFA...
March 13, 2019: Journal of the Pediatric Infectious Diseases Society
S Gaduzo, V McGovern, J Roberts, J E Scullion, D Singh
While single-inhaler triple therapy (SITT) devices were not available when the Global Initiative for Chronic Obstructive Lung Disease strategy and National Institute for Health and Care Excellence guidelines were developed, two devices are now available in the UK. This paper offers practical, patient-focused advice to optimize placement of SITT in the management of COPD. A survey of UK health care professionals (HCPs) identified issues around, and attitudes toward, SITT, which informed a multidisciplinary expert panel's discussions...
2019: International Journal of Chronic Obstructive Pulmonary Disease
Rachel F Eyler, Kristina Shvets
Antimicrobial pharmacology and its effect on prescribing is quite complex. Selecting an antibiotic that will optimally treat an infection while minimizing adverse effects and the development of resistance is only the first step, as one must also consider the patient's individual pharmacokinetic alterations and the pharmacodynamic properties of the drug when prescribing it as well. Patients with CKD may have alterations in their protein binding, volumes of distribution, kidney clearance, and nonrenal clearance that necessitates antibiotic dose adjustments to prevent the development of toxicity...
March 12, 2019: Clinical Journal of the American Society of Nephrology: CJASN
Tomoya Uchimura, Daisy S Nakamura, Eric M Link, Yoshihiko Noguchi, Satoshi Ōmura, Toshiaki Sunazuka, David J Greenblatt, Li Zeng
Osteoarthritis (OA) is a prevalent disease characterized by chronic joint degeneration and low-grade localized inflammation. There is no available treatment to delay OA progression. We report that in human primary articular chondrocytes, erythromycin, a well-known macrolide antibiotic, had the ability to inhibit pro-inflammatory cytokine Interleukin 1β (IL-1β)-induced catabolic gene expression and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Furthermore, erythromycin inhibited monosodium iodoacetate (MIA)-induced joint inflammation and cartilage matrix destruction in mice, an arthritis model that reflects the inflammatory and cartilage matrix loss aspects of OA...
March 9, 2019: Biochemical Pharmacology
Tian-Xin Cong, Dan Hao, Xiang Wen, Xiao-Hua Li, Gu He, Xian Jiang
Acne vulgaris is a cutaneous chronic inflammatory disorder with complex pathogenesis. Four factors play vital roles in acne pathophysiology: hyperseborrhea and dysseborrhea, altered keratinization of the pilosebaceous duct, Cutibacterium acnes (C. acnes) and inflammation. The main hormones responsible for the development of acne vulgaris include androgens, insulin and insulin-like growth factor-1. Other factors involved in this process are corticotropin-releasing hormone, α-melanocyte-stimulating hormone and substance P...
March 11, 2019: Archives of Dermatological Research
Rodrigo M Burgos, Keith A Rodvold
Fosfomycin is a bactericidal antibiotic available since the 1970s whose intravenous formulation has been available in many countries outside the USA. Given the rise in drug resistant bacteria, its introduction into the US market has become a necessity for addressing these organisms. This review provides an overview of the microbiology, clinical pharmacology and initial clinical experiences of the intravenous fosfomycin product (ZTI-01) that is undergoing clinical development in the USA for the treatment of complicated urinary tract infections and acute pyelonephritis...
March 11, 2019: Future Microbiology
John W Frew, Jason E Hawkes, James G Krueger
Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin, manifesting in chronic, recurrent painful pustules, nodules, boils and purulent draining abscesses. Our current understanding of the pathogenesis of the disease is incomplete. This review aims to identify available treatment options in HS and discuss the pharmacological mechanisms through which such agents function. Identifying common pathways may inform our understanding of the pathogenesis of HS as well as identify future therapeutic targets...
2019: Therapeutic Advances in Chronic Disease
Edward Pajarillo, Asha Rizor, Jayden Lee, Michael Aschner, Eunsook Lee
Glutamate is the primary excitatory neurotransmitter in the central nervous system (CNS) that initiates a rapid signal transmission in the synapse before its re-uptake into the surrounding glia, specifically astrocytes. The astrocytic glutamate transporters, glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) and their human homologs excitatory amino acid transporter 1 (EAAT1) and 2 (EAAT2), respectively, are the major transporters that take up synaptic glutamate to maintain its optimal extracellular levels, thus preventing its accumulation in the synaptic cleft and the ensuing excitotoxicity...
March 6, 2019: Neuropharmacology
Di Du, Chia-Hua Chang, Yumeng Wang, Pan Tong, Wai Kin Chan, Yulun Chiu, Bo Peng, Lin Tan, John N Weinstein, Philip L Lorenzi
MOTIVATION: The concept of synergy between two agents, over a century old, is important to the fields of biology, chemistry, pharmacology, and medicine. A key step in drug combination analysis is the selection of an additivity model to identify combination effects including synergy, additivity, and antagonism. Existing methods for identifying and interpreting those combination effects have limitations. RESULTS: We present here a computational framework, termed Response Envelope Analysis (REA), that makes use of 3-D response surfaces formed by generalized Loewe Additivity and Bliss Independence models of interaction to evaluate drug combination effects...
March 9, 2019: Bioinformatics
Vikas Yadav, Puneet Talwar
Increasing development costs and higher failure rate in clinical trials has reduced the repertoire of newer drugs in the market for clinical use. The most appropriate approach to end the search for newer drugs is "Repositioning", as it requires less time and money to explore new indication of existing drug or failed drug. In the past, several drugs have been repositioned for different indication but the full potential remains unharnessed. With rise in cancer prevalence and treatment costs, it is imperative to search for newer drugs and the use of repositioning approach may help us...
March 2019: Biomedicine & Pharmacotherapy
Chongming Wu, Yu Tian, Jiaqi Yu, Rong Zhang, Xiaopo Zhang, Peng Guo
BACKGROUND: The gut microbiota plays a key role in the maintenance of human health and mediates the beneficial effects of natural products including polyphenols. Previous studies have demonstrated that the polyphenol-rich Pandanus tectorius fruit extract (PTF) was effective in ameliorating high-fat diet (HFD)-induced hyperlipidaemia, and polyphenols can significantly change the structure of the gut microbiota. PURPOSE: In this study, we assessed whether the modulation of the gut microbiota plays a key role in the PTF-induced anti-hyperlipidaemic effects...
February 18, 2019: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Hamed Memariani, Mojtaba Memariani, Mohammad Shahidi-Dadras, Soheila Nasiri, Maziar Mohammad Akhavan, Hamideh Moravvej
The emergence of antibiotic-resistant bacteria, dubbed superbugs, together with relative stagnation in developing efficient antibiotics has led to enormous health and economic problems, necessitating the need for discovering and developing novel antimicrobial agents. In this respect, animal venoms represent a rich repertoire of pharmacologically active components. As a major component in the venom of European honeybee Apis mellifera, melittin has a great potential in medical applications. In this mini-review, we summarize a multitude of studies on anti-bacterial effects of melittin against planktonic and biofilm-embedded bacteria...
March 1, 2019: Applied Microbiology and Biotechnology
Robert Silasi, Ravi Shankar Keshari, Cristina Lupu, Walter Janse Van Rensburg, Hala Chaaban, Girija Regmi, Aleksandr Shamanaev, Joseph J Shatzel, Cristina Puy, Christina U Lorentz, Erik I Tucker, David Gailani, András Gruber, Owen J T McCarty, Florea Lupu
Staphylococcus aureus infections can produce systemic bacteremia and inflammation in humans, which may progress to severe sepsis or septic shock, even with appropriate antibiotic treatment. Sepsis may be associated with disseminated intravascular coagulation and consumptive coagulopathy. In some types of mouse infection models, the plasma coagulation protein factor XI (FXI) contributes to the pathogenesis of sepsis. We hypothesize that FXI also contributes to the pathogenesis of sepsis in primates, and that pharmacological interference with FXI will alter the outcome of Staphylococcus aureus -induced lethality in a baboon model...
February 26, 2019: Blood Advances
Kai-Uwe Lewandrowski
Objective: The objective of this study is to analyze incidence, estimate cost savings, and evaluate best management practices of complications resulting from outpatient transforaminal endoscopic decompression surgery for lumbar foraminal and lateral recess stenosis performed in an ambulatory surgery center. Background: Endoscopic spinal surgery is gaining popularity for the treatment of lumbar disc herniations. Recent advances in surgical techniques allow for endoscopically assisted bony decompression for neurogenic claudication symptoms due to spinal stenosis...
January 2019: International Journal of Spine Surgery
Jen-Chung Ko, Jyh-Cheng Chen, Tzu-Ying Chen, Ting-Chuan Yen, Peng-Fang Ma, Yuan-Cheng Lin, Chia-Hung Wu, Yi-Shuan Peng, Hao-Yu Zheng, Yun-Wei Lin
Salinomycin is a polyether ionophore antibiotic having anti-tumorigenic property in various types of cancer. Elevated thymidine phosphorylase (TP) levels, a key enzyme in the pyrimidine nucleoside salvage pathway, are associated with an aggressive disease phenotype and poor prognoses. Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. In this study, we report whether Hsp90 inhibitor 17-AAG could enhance salinomycin-induced cytotoxicity in NSCLC cells through modulating TP expression in two non-small-cell lung cancer (NSCLC) cell lines, A549 and H1975...
February 20, 2019: Toxicology
John van den Anker, Karel Allegaert
Rational medicine use in neonates implies the prescription and administration of age-appropriate drug formulations, selecting the most efficacious and safe dose, all based on accurate information on the drug and its indications in neonates. This review illustrates that important uncertainties still exist concerning the different aspects ( when, what, how ) of rational antibiotic use in neonates. Decisions when to prescribe antibiotics are still not based on robust decision tools. Choices ( what ) on empiric antibiotic regimens should depend on the anticipated pathogens, and the available information on the efficacy and safety of these drugs...
February 16, 2019: Healthcare (Basel, Switzerland)
Genzhu Wang, Jing Pang, Xinxin Hu, Tongying Nie, Xi Lu, Xue Li, Xiukun Wang, Yun Lu, Xinyi Yang, Jiandong Jiang, Congran Li, Yan Q Xiong, Xuefu You
BACKGROUND: Antibiotic-resistant H. pylori was increasingly found in infected individuals, which resulted in treatment failure and required alternative therapeutic strategies. Daphnetin, a coumarin-derivative compound, has multiple pharmacological activities. METHODS: The mechanism of daphnetin on H. pylori was investigated focusing on its effect on cell morphologies, transcription of genes related to virulence, adhesion, and cytotoxicity to human gastric epithelial (GES-1) cell line...
February 15, 2019: International Journal of Molecular Sciences
Eric R Coon, Ricardo A Quinonez, Daniel J Morgan, Sanket S Dhruva, Timmy Ho, Nathan Money, Alan R Schroeder
Importance: Efforts to combat medical overuse have gained traction in recent years, but success has been intermittent and shortcomings have been recognized. A commitment to a strong evidence base is needed to more broadly engage clinicians and reduce overuse. Observations: A structured MEDLINE search and a manual review of tables of contents from selected high-impact journals was performed to identify original research published in 2017 relevant to pediatric overuse...
February 18, 2019: JAMA Pediatrics
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