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https://www.readbyqxmd.com/read/28550735/clarithromycin-inhibits-tnf-%C3%AE-induced-muc5ac-mucin-gene-expression-via-the-mkp-1-p38mapk-dependent-pathway
#1
Said Ahmad Shah, Hajime Ishinaga, Kazuhiko Takeuchi
Clarithromycin is a 14-membered macrolide antibiotic. Low-dose, long-term macrolide therapy is effective in patients with chronic airway diseases, such as diffuse panbronchitis, chronic bronchitis, and chronic sinusitis. However, the mechanism underlying this clinical efficacy remains unclear. The dual specificity phosphatase MKP-1 (MAPK phosphatase-1), also called DUSP (dual specificity phosphatase-1), was initially identified as an in vitro ERK-specific phosphatase, but depending on the cell type, it can also dephosphorylate other members of the MAPK family, such as p38 and JNK, and thus suppress downstream signaling of these kinases...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550055/potential-drug-interactions-mediated-by-renal-organic-anion-transporter-oatp4c1
#2
Toshihiro Sato, Eikan Mishima, Nariyasu Mano, Takaaki Abe, Hiroaki Yamaguchi
OATP4C1 is an organic anion transporter expressed in the basolateral membrane of the renal proximal tubules. It plays a major role in the urinary excretion of both exogenous drugs and endogenous compounds. Our previous studies have indicated the importance of OATP4C1 in pathological and physiological conditions; however, the majority of its pharmacological characteristics remained unclear. Therefore, to provide essential information for clinical drug therapy decisions and drug development, we, in this study, attempted to clarify drug interactions mediated by OATP4C1...
May 26, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28548387/a-quantitative-systems-physiology-model-of-renal-function-and-blood-pressure-regulation-model-description
#3
K M Hallow, Y Gebremichael
Renal function plays a central role in cardiovascular, kidney, and multiple other diseases, and many existing and novel therapies act through renal mechanisms. Even with decades of accumulated knowledge of renal physiology, pathophysiology, and pharmacology, the dynamics of renal function remain difficult to understand and predict, often resulting in unexpected or counterintuitive therapy responses. Quantitative systems pharmacology modeling of renal function integrates this accumulated knowledge into a quantitative framework, allowing evaluation of competing hypotheses, identification of knowledge gaps, and generation of new experimentally testable hypotheses...
May 26, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28548108/drugging-the-pain-epigenome
#4
REVIEW
Ellen Niederberger, Eduard Resch, Michael J Parnham, Gerd Geisslinger
More than 20% of adults worldwide experience different types of chronic pain, which are frequently associated with several comorbidities and a decrease in quality of life. Several approved painkillers are available, but current analgesics are often hampered by insufficient efficacy and/or severe adverse effects. Consequently, novel strategies for safe, highly efficacious treatments are highly desirable, particularly for chronic pain. Epigenetic mechanisms such as DNA methylation, histone modifications and microRNAs (miRNAs) strongly affect the regulation of gene expression, potentially for long periods over years or even generations, and have been associated with pathophysiological pain...
May 26, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28546769/treatment-of-chronic-low-back-pain-new-approaches-on-the-horizon
#5
REVIEW
Nebojsa Nick Knezevic, Shane Mandalia, Jennifer Raasch, Ivana Knezevic, Kenneth D Candido
Back pain is the second leading cause of disability among American adults and is currently treated either with conservative therapy or interventional pain procedures. However, the question that remains is whether we, as physicians, have adequate therapeutic options to offer to the patients who suffer from chronic low back pain but fail both conservative therapy and interventional pain procedures before they consider surgical options such as discectomy, disc arthroplasty, or spinal fusion. The purpose of this article is to review the potential novel therapies that are on the horizon for the treatment of chronic low back pain...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28546755/pediatric-ventricular-assist-devices-current-challenges-and-future-prospects
#6
REVIEW
Sarah Burki, Iki Adachi
The field of mechanical circulatory support has made great strides in the preceding 2 decades. Although pediatric mechanical circulatory support has lagged behind that of adults, the gap between them is expected to close soon. The only device currently approved by the US Food and Drug Administration for use in children is the Berlin Heart EXCOR ventricular assist device (VAD). The prospective Berlin Heart Investigational Device Exemption Trial demonstrated good outcomes, such as bridge to transplantation or recovery, in ~90% of children supported with this device...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28546740/new-developments-in-managing-opioid-addiction-impact-of-a-subdermal-buprenorphine-implant
#7
REVIEW
MariaLisa Itzoe, Michael Guarnieri
Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT). For decades, oral or intravenous (IV) MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone), antagonists (naltrexone, naloxone), and combinations of the two (buprenorphine/naloxone)...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28546082/targeting-gpnmb-with-glembatumumab-vedotin-current-developments-and-future-opportunities-for-the-treatment-of-cancer
#8
REVIEW
April A N Rose, Marco Biondini, Rafael Curiel, Peter M Siegel
GPNMB has emerged as an immunomodulator and an important positive mediator of tumor progression and metastasis in numerous solid cancers. Tumor intrinsic GPNMB-mediated effects on cellular signaling, coupled with the ability of GPNMB to influence the primary tumor and metastatic microenvironments in a non-cell autonomous fashion, combine to augment malignant cancer phenotypes. In addition, GPNMB is often overexpressed in a variety of cancers, making it an attractive therapeutic target. In this regard, glembatumumab vedotin, an antibody-drug conjugate (ADC) that targets GPNMB, is currently in clinical trials as a single agent in multiple cancers...
May 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28545888/delivering-safer-immunotherapies-for-cancer
#9
Lauren Milling, Yuan Zhang, Darrell J Irvine
Cancer immunotherapy is now a powerful clinical reality, with a steady progression of new drug approvals and a massive pipeline of additional treatments in clinical and preclinical development. However, modulation of the immune system can be a double-edged sword: Drugs that activate immune effectors are prone to serious non-specific systemic inflammation and autoimmune side effects. Drug delivery technologies have an important role to play in harnessing the power of immune therapeutics while avoiding on-target/off-tumor toxicities...
May 22, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28545372/lectin-carbohydrate-interactions-implications-for-the-development-of-new-anticancer-agents
#10
Evellyne de Oliveira Figueirôa, Cassia Regina Albuquerque da Cunha, Priscilla B S Albuquerque, Raiana Apolinário de Paula, Mary Ângela Aranda-Souza, Matheus Alves da Silva, Adrielle Zagmignan, Maria G Carneiro-da-Cunha, Luís Cláudio Nascimento da Silva, Maria Tereza Dos Santos Correia
Lectins are a large group of proteins found in animals, plants, fungi, and bacteria that recognize specific carbohydrate targets and play an important role in cell recognition and communication, host-pathogen interactions, embryogenesis, and tissue development. Recently, lectins have emerged as important biomedical tools that have been used in the development of immunomodulatory, antipathogenic, and anticancer agents. Several lectins have been shown to have the ability to discriminate between normal cells and tumor cells as a result of their different glycosylation patterns...
May 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28545225/state-of-art-of-cancer-pharmacogenomics-in-latin-american-populations
#11
REVIEW
Andrés López-Cortés, Santiago Guerrero, María Ana Redal, Angel Tito Alvarado, Luis Abel Quiñones
Over the past decades, several studies have shown that tumor-related somatic and germline alterations predicts tumor prognosis, drug response and toxicity. Latin American populations present a vast geno-phenotypic diversity due to the great interethnic and interracial mixing. This genetic flow leads to the appearance of complex characteristics that allow individuals to adapt to endemic environments, such as high altitude or extreme tropical weather. These genetic changes, most of them subtle and unexplored, could establish a mutational profile to develop new pharmacogenomic therapies specific for Latin American populations...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28544857/new-treatment-directions-for-ipf-current-status-of-ongoing-and-upcoming-clinical-trials
#12
Francesco Macagno, Francesco Varone, Paolo Maria Leone, Pier-Valerio Mari, Loredana Panico, Ludovica Berardini, Luca Richeldi
The main objective of this review is to explore the wide and expanding field of new clinical trials in IPF. Recent trials have confirmed the efficacy of the approved drugs pirfenidone and nintedanib; nonetheless, the discovery of new biological pathways has opened new horizons in this field. Areas Covered: New strategies against matrix deposition are under study and so is for the role of immunity and autoimmunity. Recent advances in the use of stem cells are opening new possibilities for the recovery of damaged lung tissues...
May 25, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28544801/nanotherapeutic-systems-for-local-treatment-of-brain-tumors
#13
REVIEW
Rami Walid Chakroun, Pengcheng Zhang, Ran Lin, Paula Schiapparelli, Alfredo Quinones-Hinojosa, Honggang Cui
Malignant brain tumor, including the most common type glioblastoma, are histologically heterogeneous and invasive tumors known as the most devastating neoplasms with high morbidity and mortality. Despite multimodal treatment including surgery, radiotherapy, chemotherapy, and immunotherapy, the disease inevitably recurs and is fatal. This lack of curative options has motivated researchers to explore new treatment strategies and to develop new drug delivery systems (DDSs); however, the unique anatomical, physiological, and pathological features of brain tumors greatly limit the effectiveness of conventional chemotherapy...
May 24, 2017: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/28544782/rationale-and-design-of-amphilimus-sirolimus-eluting-stents-versus-zotarolimus-eluting-stents-in-all-comers-requiring-percutaneous-coronary-intervention-recre8-a-multicenter-randomized-clinical-trial
#14
Rik Rozemeijer, Mèra Stein, Peter Frambach, Michiel Voskuil, Adriaan O Kraaijeveld, Ramón Rodríguez-Olivares, Leo Timmers, Bruno Pereira, Saskia Z Rittersma, Pierfrancesco Agostoni, Pieter A Doevendans, Pieter R Stella
BACKGROUND: Amphilimus sirolimus-eluting stents (A-SES) represent a novel elution technology in the current era of drug-eluting stents with promising results in patients with diabetes mellitus. At present no large trial has been designed to evaluate clinical outcomes of A-SES as compared to new-generation drug-eluting stents in unselected patients. Accordingly, we designed this trial to evaluate clinical noninferiority of A-SES as compared with zotarolimus-eluting stents (ZES) in a real-world, all-comers setting...
May 22, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28544467/a-survey-on-the-beliefs-and-knowledge-of-gout-management-in-new-medical-graduates-new-south-wales-australia
#15
Matthew Terrill, John Riordan
AIM: To assess the beliefs and knowledge of gout management in new medical graduates. METHOD: A survey on gout management was sent to new medical graduates during their orientation week, New South Wales, Australia. RESULTS: Of 15 hospital networks, 11 agreed to participate. From these, 168 graduates responded (23.7% response rate). Most (81.1%) felt that gout was a serious disease, 51.2% answered that they had been taught adequately to manage acute gout, only 37...
May 25, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28544292/perioperative-adverse-events-in-patients-on-continued-anticoagulation-undergoing-photoselective-vaporisation-of-the-prostate-with-the-180-w-greenlight-lithium-triborate-laser
#16
Georgia L Knapp, Venu Chalasani, Henry H Woo
OBJECTIVES: To compare perioperative factors and adverse events (AEs) in men undergoing photoselective vaporisation of the prostate (PVP) with or without continued anticoagulation therapy. PATIENTS AND METHODS: Retrospective review of a PVP database of men treated with the 180-W lithium triborate (LBO) laser from 2010 to 2016. Of 373 men, 59 underwent PVP with continued anticoagulant therapy, which was defined as treatment with heparin, warfarin, clopidogrel, dipyridamol or new oral anticoagulant drugs...
May 2017: BJU International
https://www.readbyqxmd.com/read/28544095/phenotypic-assays-for-mycobacterium-tuberculosis-infection
#17
Ok-Ryul Song, Nathalie Deboosere, Vincent Delorme, Christophe J Queval, Gaspard Deloison, Elisabeth Werkmeister, Frank Lafont, Alain Baulard, Raffaella Iantomasi, Priscille Brodin
Tuberculosis (TB) is still a major global threat, killing more than one million persons each year. With the constant increase of Mycobacterium tuberculosis strains resistant to first- and second-line drugs, there is an urgent need for the development of new drugs to control the propagation of TB. Although screenings of small molecules on axenic M. tuberculosis cultures were successful for the identification of novel putative anti-TB drugs, new drugs in the development pipeline remains scarce. Host-directed therapy may represent an alternative for drug development against TB...
May 19, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28543695/mechanisms-and-strategies-to-overcome-resistance-to-molecularly-targeted-therapy-for-melanoma
#18
REVIEW
Su Yin Lim, Alexander M Menzies, Helen Rizos
The identification of driver mutations in melanoma has changed the field of cancer treatment. BRAF and NRAS mutations are predominant in melanoma and lead to overactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. Selective inhibitors targeting key effectors of the MAPK pathway have revolutionized the treatment of patients with advanced metastatic BRAF-mutant melanoma. However, resistance to therapy is almost universal and remains a major challenge in clinical care, with the majority of patients progressing within 1 year...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543367/successful-treatment-of-methicillin-susceptible-staphylococcus-aureus-osteomyelitis-with-oritavancin
#19
Dino J Delaportas, Sandy J Estrada, Matthew Darmelio
Staphylococcus aureus remains the most common causative pathogen in osteomyelitis. New or alternate therapies are often needed to adequately treat S. aureus infections in patients with drug allergies, treatment failures, or drug interactions. Oritavancin is a novel long-acting lipoglycopeptide approved by the Food and Drug Administration (FDA) in 2014 for the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI). With a terminal half-life of 8 to 10 days, oritavancin dosing regimens with infrequent parenteral administration now exist to treat infectious diseases such as osteomyelitis that would otherwise require daily dosing of intravenous antimicrobials for weeks; however clinical experience is lacking...
May 23, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28542953/zebrafish-tmem230a-cooperates-with-the-delta-notch-signaling-pathway-to-modulate-endothelial-cell-number-in-angiogenic-vessels
#20
Silvia Carra, Lorenzo Sangiorgio, Paride Pelucchi, Solei Cermenati, Alessandra Mezzelani, Valentina Martino, Mira Palizban, Alberto Albertini, Martin Götte, James Kehler, Gianluca Deflorian, Monica Beltrame, Antonio Giordano, Rolland Reinbold, Franco Cotelli, Gianfranco Bellipanni, Ileana Zucchi
During embryonic development, new arteries and veins form from preexisting vessels in response to specific angiogenic signals. Angiogenic signaling is complex since not all endothelial cells exposed to angiogenic signals respond equally. Some cells will be selected to become tip cells and acquire migration and proliferation capacity necessary for vessel growth while others, the stalk cells become trailer cells that stay connected with pre-existing vessels and act as a linkage to new forming vessels. Additionally, stalk and tip cells have the capacity to interchange their roles...
May 25, 2017: Journal of Cellular Physiology
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