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Pharmacology & Therapeutics

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https://www.readbyqxmd.com/read/28642119/targeting-inflammation-for-the-treatment-of-alcoholic-liver-disease
#1
REVIEW
Ming-Jiang Xu, Zhou Zhou, Richard Parker, Bin Gao
Alcoholic liver disease (ALD) is a leading cause of chronic liver disease with a wide spectrum of manifestations including simple steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Liver injury in ALD is caused by chronic inflammation, which has been actively investigated as a therapeutic target for the treatment of ALD for over the last four decades. In this review, we summarize a wide variety of inflammatory mediators that have been shown to contribute to the pathogenesis of ALD, and discuss the therapeutic potential of these mediators for the treatment of ALD...
June 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28642118/current-state-of-the-art-for-cardiac-arrhythmia-gene-therapy
#2
REVIEW
J Kevin Donahue
Cardiac arrhythmias are a leading cause of morbidity and mortality. Currently available therapeutic options lack sufficient efficacy and safety. Gene therapy has been proposed for treatment of cardiac arrhythmias. This review will discuss the current state of development for arrhythmia gene therapy. So far, all published studies are short-term, proof-of-concept animal studies. Potential replacement of cardiac pacemakers has been shown for combination gene therapy using the HCN2 gene and either the gene for adenylate cyclase, the skeletal muscle isoform of the sodium channel, or a dominant negative mutant of the potassium channel responsible for resting membrane potential...
June 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28642117/soluble-epoxide-hydrolase-as-a-therapeutic-target-for-pain-inflammatory-and-neurodegenerative-diseases
#3
REVIEW
Karen M Wagner, Cindy B McReynolds, William K Schmidt, Bruce D Hammock
Eicosanoids are biologically active lipid signaling molecules derived from polyunsaturated fatty acids. Many of the actions of eicosanoid metabolites formed by cyclooxygenase and lipoxygenase enzymes have been characterized, however, the epoxy-fatty acids (EpFAs) formed by cytochrome P450 enzymes are newly described by comparison. The EpFA metabolites modulate a diverse set of physiologic functions that include inflammation and nociception among others. Regulation of EpFAs occurs primarily via release, biosynthesis and enzymatic transformation by the soluble epoxide hydrolase (sEH)...
June 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28642116/contrast-induced-nephropathy-basic-concepts-pathophysiological-implications-and-prevention-strategies
#4
REVIEW
Charalampos Mamoulakis, Konstantinos Tsarouhas, Irini Fragkiadoulaki, Ioannis Heretis, Martin F Wilks, Demetrios A Spandidos, Christina Tsitsimpikou, Aristides Tsatsakis
Contrast-induced nephropathy (CIN) is reversible acute renal failure observed following administration of iodinated contrast media (CM) during angiographic or other medical procedures such as urography. There are various mechanisms through which CM develop their nephrotoxic effects, including oxidative stress and apoptosis. CIN is a real-life, albeit not very rare, entity. Exact pathophysiology remains obscure and no standard diagnostic criteria apply. The Acute Kidney Injury Network criteria was recently employed but its incidence/clinical significance warrants further clarification based on recent methodological advancements, because most published studies to date were contaminated by bias...
June 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28642115/anti-tnf%C3%AE-therapy-in-inflammatory-lung-diseases-bn
#5
REVIEW
Rama Malaviya, Jeffrey D Laskin, Debra L Laskin
Increased levels of tumor necrosis factor (TNF) α have been linked to a number of pulmonary inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sarcoidosis, and interstitial pulmonary fibrosis (IPF). TNFα plays multiple roles in disease pathology by inducing an accumulation of inflammatory cells, stimulating the generation of inflammatory mediators, and causing oxidative and nitrosative stress, airway hyperresponsiveness and tissue remodeling...
June 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28583800/analysis-of-natural-product-regulation-of-cannabinoid-receptors-in-the-treatment-of-human-disease
#6
REVIEW
S Badal, K N Smith, R Rajnarayanan
The organized tightly regulated signaling relays engaged by the cannabinoid receptors (CBs) and their ligands, G proteins and other effectors, together constitute the endocannabinoid system (ECS). This system governs many biological functions including cell proliferation, regulation of ion transport and neuronal messaging. This review will firstly examine the physiology of the ECS, briefly discussing some anomalies in the relay of the ECS signaling as these are consequently linked to maladies of global concern including neurological disorders, cardiovascular disease and cancer...
June 2, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28579388/targeting-cysteine-proteases-in-trypanosomatid-disease-drug-discovery
#7
REVIEW
Leonardo G Ferreira, Adriano D Andricopulo
Chagas disease and human African trypanosomiasis are endemic conditions in Latin America and Africa, respectively, for which no effective and safe therapy is available. Efforts in drug discovery have focused on several enzymes from these protozoans, among which cysteine proteases have been validated as molecular targets for pharmacological intervention. These enzymes are expressed during the entire life cycle of trypanosomatid parasites and are essential to many biological processes, including infectivity to the human host...
June 1, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28579387/treatment-advances-in-small-cell-lung-cancer-sclc
#8
REVIEW
Saiama N Waqar, Daniel Morgensztern
Small cell lung cancer (SCLC) is an aggressive tumor characterized by rapid doubling time and high propensity for early development of disseminated disease. Although most patients respond to initial therapy with a platinum doublet, the majority of those with limited stage and virtually all patients with metastatic disease eventually develop tumor progression for which there are limited treatment options. There have been no recent changes in the treatment of SCLC, with platinum plus etoposide and topotecan as the standard first-line and second-line respectively, neither showing survival benefit over the combination of cyclophosphamide, doxorubicin and vincristine, which was developed in the 1970s...
June 1, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28579386/microrna-and-chronic-pain-from-mechanisms-to-therapeutic-potential
#9
REVIEW
María José López-González, Marc Landry, Alexandre Favereaux
Chronic pain is a major public health issue with an incidence of 20-25% worldwide that can take different forms like neuropathic, cancer-related or inflammatory pain. Chronic pain often limits patients in their daily activities leading to despair. Thus, the goal of treatments is to relieve pain sufficiently to enable patients to go back to a normal life. Unfortunately, few patients with chronic pain obtain complete relief from the analgesics that are currently available. It is thus of prime importance to get a better understanding of chronic pain mechanisms to design new therapeutic strategies and pain-killers...
June 1, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28564583/fibroblast-growth-factors-fgfs-in-cancer-fgf-traps-as-a-new-therapeutic-approach
#10
REVIEW
Marco Presta, Paola Chiodelli, Arianna Giacomini, Marco Rusnati, Roberto Ronca
Originally characterized as angiogenic factors, fibroblast growth factors (FGFs) are pleiotropic factors that exert autocrine and paracrine functions on tumor and stromal cells. Thus, they may represent key players in the complex crosstalk among angiogenesis, inflammation, tumor growth, and drug resistance, all contributing to tumor progression. Given the multiple activities of FGFs, inhibitors of the FGF/FGFR system may act as "two compartment" targeting drugs able to exert a deep impact on the growth of FGF/FGFR-driven tumors...
May 28, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28551025/cytochrome-p450-derived-eicosanoids-and-heart-function
#11
REVIEW
K Lockhart Jamieson, Tomoko Endo, Ahmed M Darwesh, Victor Samokhvalov, John M Seubert
The cytochrome P450 monooxygenase system (CYP) is a multigene superfamily of enzymes, which are important in the metabolism foreign and endogenous compounds. CYP isoforms metabolize a number of n-3 and n-6 polyunsaturated fatty acids (PUFA), including linoleic acid (18:2n6, LA), arachidonic acid (20:4n6, AA), ecosapentaenoic acid (20:5n3, EPA) and docosahexaenoic acid (22:6n3, DHA) into bioactive lipid mediators, termed eicosanoids. CYP-derived eicosanoids have numerous effects toward physiological and pathophysiological events within the body, which depends on the type, quantity and timing of metabolites produced...
May 24, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28549597/prolactin-receptor-targeting-in-breast-and-prostate-cancers-new-insights-into-an-old-challenge
#12
REVIEW
Vincent Goffin
In the era of precision medicine, the identification of new targets is a constant challenge to improve cancer therapy. Preclinical investigations, epidemiological studies and analyses of tissue specimens from patients strongly support the contribution of prolactin receptor (PRLR) signaling to breast and prostate tumorigenesis and cancer progression. Although a clear causative link with mutations of the genes encoding prolactin or its receptor is lacking, increased PRLR signaling in these cancers can be assessed by the overexpression of cognate proteins and is often confirmed by over-activation of downstream signaling effectors...
May 23, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28549596/emerging-roles-of-the-cxcl12-cxcr4-axis-in-pancreatic-cancer-progression-and-therapy
#13
REVIEW
Richard L Sleightholm, Beth K Neilsen, Jing Li, Maria M Steele, Rakesh K Singh, Michael A Hollingsworth, David Oupicky
Chemokine networks regulate a variety of cellular, physiological, and immune processes. These normal functions can become appropriated by cancer cells to facilitate a more hospitable niche for aberrant cells by enhancing growth, proliferation, and metastasis. This is especially true in pancreatic cancer, where chemokine signaling is a vital component in the development of the supportive tumor microenvironment and the signaling between the cancer cells and surrounding stromal cells. Although expression patterns vary among cancer types, the chemokine receptor CXCR4 has been implicated in nearly every major malignancy and plays a prominent role in pancreatic cancer development and progression...
May 23, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28546081/targeting-nuclear-receptors-for-the-treatment-of-fatty-liver-disease
#14
REVIEW
Naoki Tanaka, Toshifumi Aoyama, Shioko Kimura, Frank J Gonzalez
Ligand-activated nuclear receptors, including peroxisome proliferator-activated receptor alpha (PPARα), pregnane X receptor, and constitutive androstane receptor, were first identified as key regulators of the responses against chemical toxicants. However, numerous studies using mouse disease models and human samples have revealed critical roles for these receptors and others, such as PPARβ/δ, PPARγ, farnesoid X receptor (FXR), and liver X receptor (LXR), in maintaining nutrient/energy homeostasis in part through modulation of the gut-liver-adipose axis...
May 23, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28546083/mechanisms-of-tolerance-and-potential-therapeutic-interventions-in-alopecia-areata
#15
REVIEW
Gabriel Skogberg, Sonya Jackson, Annika Åstrand
This review aims to address the mechanisms of compromised immune tolerance contributing to the development and maintenance of Alopecia Areata (AA). Our goal is to also highlight future treatment opportunities and therapeutics that will safely and efficiently restore hair growth and maintain patients in remission. AA is a presumptive autoimmune disorder that coincides and genetically clusters to several other autoimmune diseases. In this review, we pay attention to the learnings from the mechanistic research and drug development in these other autoimmune conditions...
May 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28546082/targeting-gpnmb-with-glembatumumab-vedotin-current-developments-and-future-opportunities-for-the-treatment-of-cancer
#16
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/28529069/cholinergic-modulation-of-the-immune-system-presents-new-approaches-for-treating-inflammation
#17
REVIEW
Donald B Hoover
The nervous system and immune system have broad and overlapping distributions in the body, and interactions of these ubiquitous systems are central to the field of neuroimmunology. Over the past two decades, there has been explosive growth in our understanding of neuroanatomical, cellular, and molecular mechanisms that mediate central modulation of immune functions through the autonomic nervous system. A major catalyst for growth in this field was the discovery that vagal nerve stimulation (VNS) caused a prominent attenuation of the systemic inflammatory response evoked by endotoxin in experimental animals...
May 18, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28529068/adverse-outcome-pathways-application-to-enhance-mechanistic-understanding-of-neurotoxicity
#18
REVIEW
Anna Bal-Price, M E Bette Meek
Recent developments have prompted the transition of empirically based testing of late stage toxicity in animals for a range of different endpoints including neurotoxicity to more efficient and predictive mechanistically based approaches with greater emphasis on measurable key events early in the progression of disease. The adverse outcome pathway (AOP) has been proposed as a simplified organizational construct to contribute to this transition by linking molecular initiating events and earlier (more predictive) key events at lower levels of biological organization to disease outcomes...
May 18, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28527921/drug-induced-fatal-arrhythmias-acquired-long-qt-and-brugada-syndromes
#19
REVIEW
Isik Turker, Tomohiko Ai, Hideki Itoh, Minoru Horie
Since the early 1990s, the concept of primary "inherited" arrhythmia syndromes or ion channelopathies has evolved rapidly as a result of revolutionary progresses made in molecular genetics. Alterations in genes coding for membrane proteins such as ion channels or their associated proteins responsible for the generation of cardiac action potentials (AP) have been shown to cause specific malfunctions which eventually lead to cardiac arrhythmias. These arrhythmic disorders include congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, progressive cardiac conduction disease, etc...
May 17, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28527920/emerging-bronchoscopic-treatments-for-chronic-obstructive-pulmonary-disease
#20
REVIEW
Wouter H van Geffen, Huib A M Kerstjens, Dirk-Jan Slebos
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by pathophysiological factors including airflow limitation, hyperinflation and reduced gas exchange. Treatment consists of lifestyle changes, lung rehabilitation and pharmacological therapies such as long acting beta-2-agonists (LABA) and long acting muscarinic antagonists (LAMA). More recently bronchoscopic treatments are emerging for COPD. Among them endobronchial valves(EBV) and endobronchial coils (EBC), next to endobronchial stents, sclerosing agents, targeted lung denervation and liquid nitrogen metered cryospray...
May 17, 2017: Pharmacology & Therapeutics
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