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Pharmacology & Therapeutics

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https://www.readbyqxmd.com/read/28529069/cholinergic-modulation-of-the-immune-system-presents-new-approaches-for-treating-inflammation
#1
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
#2
REVIEW
Anna Bal-Price, M E 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
#3
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
#4
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
https://www.readbyqxmd.com/read/28527919/mechanisms-of-the-amplifying-pathway-of-insulin-secretion-in-the-%C3%AE-cell
#5
REVIEW
Michael A Kalwat, Melanie Cobb
Pancreatic islet β cells secrete insulin in response to nutrient secretagogues, like glucose, dependent on calcium influx and nutrient metabolism. One of the most intriguing qualities of β cells is their ability to use metabolism to amplify the amount of secreted insulin independent of further alterations in intracellular calcium. Many years studying this amplifying process have shaped our current understanding of β cell stimulus-secretion coupling; yet, the exact mechanisms of amplification have been elusive...
May 17, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28527918/cytochrome-p450-eicosanoids-in-cerebrovascular-function-and-disease
#6
REVIEW
Catherine M Davis, Xuehong Liu, Nabil J Alkayed
Cytochrome P450 eicosanoids play important roles in brain function and disease through their complementary actions on cell-cell communications within the neurovascular unit (NVU) and mechanisms of brain injury. Epoxy- and hydroxyeicosanoids, respectively formed by cytochrome P450 epoxygenases and ω-hydroxylases, play opposing roles in cerebrovascular function and in pathological processes underlying neural injury, including ischemia, neuroinflammation and oxidative injury. P450 eicosanoids also contribute to cerebrovascular disease risk factors, including hypertension and diabetes...
May 17, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28461251/mitophagy-and-age-related-pathologies-development-of-new-therapeutics-by-targeting-mitochondrial-turnover
#7
REVIEW
Konstantinos Palikaras, Ioanna Daskalaki, Maria Markaki, Nektarios Tavernarakis
Mitochondria are highly dynamic and semi-autonomous organelles, essential for many fundamental cellular processes, including energy production, metabolite synthesis, ion homeostasis, lipid metabolism and initiation of apoptotic cell death. Proper mitochondrial physiology is a prerequisite for health and survival. Generation of new and removal of damaged or unwanted mitochondria are tightly controlled processes that need to be accurately coordinated for the maintenance of mitochondrial and cellular homeostasis...
April 28, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28457804/the-clinical-pharmacology-of-non-sedating-antihistamines
#8
REVIEW
Kazuhiko Yanai, Takeo Yoshikawa, Ai Yanai, Tadaho Nakamura, Tomomitsu Iida, Rob Leurs, Manabu Tashiro
We previously reported on brain H1 receptor occupancy measurements of antihistamines in human brain using [(11)C]doxepin and positron emission tomography (PET). We proposed the use of brain H1 receptor occupancy to classify antihistamines objectively into three categories of sedating, less-sedating, and non-sedating antihistamines according to their sedative effects. Non-sedating antihistamines are recommended for the treatment of allergies such as pollinosis and atopic dermatitis because of their low penetration into the central nervous system...
April 27, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28442326/inhaled-efficacious-dose-translation-from-rodent-to-human-a-retrospective-analysis-of-clinical-standards-for-respiratory-diseases
#9
REVIEW
J E Phillips
Clinical pharmacologists and toxicologists are often faced with predicting equivalent dosages for humans from biological observations in laboratory animals. Allometric scaling has been used extensively as the basis for extrapolation of drug dosage that might be expected to produce the equivalent biological effects. Allometry is the study of size and its consequences and it is based on the anatomical, physiological, and biochemical similarities between animals. In this review, retrospective analyses have been performed based on data reported in the literature in an attempt to determine the utility of allometric scaling for human dose projections from pre-clinical data for compounds that are delivered by inhalation...
April 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28438639/targeting-interleukin-17-signalling-in-cigarette-smoke-induced-lung-disease-mechanistic-concepts-and-therapeutic-opportunities
#10
REVIEW
Abraham B Roos, Martin R Stampfli
It is widely accepted that compromised lung function in chronic obstructive pulmonary disease (COPD) is, at least in part, a consequence of persistent airway inflammation caused by particles and noxious gases present in cigarette smoke and indoor air pollution from burning biomass fuel. Currently, the World Health Organization estimates that 80 million people have moderate or severe COPD worldwide. While there is a global need for effective medical treatment, current therapeutic interventions have shown limited success in preventing disease pathology and progression...
April 21, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28435091/antimicrobial-peptides-role-in-human-disease-and-potential-as-immunotherapies
#11
REVIEW
César de la Fuente-Núñez, Osmar N Silva, Timothy K Lu, Octavio Luiz Franco
Antimicrobial peptides (AMPs) have evolved through billions of years as part of our innate immune system. These agents are produced by various cells throughout the human body and play important roles in our ability to respond to infections. In this review, we outline evidence linking AMP expression with a range of inflammatory and autoimmune human diseases. Finally, we highlight the promise of endogenous AMP induction for the treatment of disease (i.e., host-directed therapy) and briefly mention the different peptide drugs that are currently undergoing clinical trials...
April 21, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28351720/estradiol-effects-on-hypothalamic-ampk-and-bat-thermogenesis-a-gateway-for-obesity-treatment
#12
REVIEW
Miguel López, Manuel Tena-Sempere
In addition to their prominent roles in the control of reproduction, estrogens are important modulators of energy balance, as evident in conditions of deficiency of estrogens, which are characterized by increased feeding and decreased energy expenditure, leading to obesity. AMP-activated protein kinase (AMPK) is a ubiquitous cellular energy gauge that is activated under conditions of low energy, increasing energy production and reducing energy wasting. Centrally, the AMPK pathway is a canonical route regulating energy homeostasis, by integrating peripheral signals, such as hormones and metabolites, with neuronal networks...
March 27, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28351719/reviving-the-guardian-of-the-genome-small-molecule-activators-of-p53
#13
REVIEW
Daniel Nguyen, Wenjuan Liao, Shelya X Zeng, Hua Lu
The tumor suppressor p53 is one of the most important proteins for protection of genomic stability and cancer prevention. Cancers often inactivate it by either mutating its gene or disabling its function. Thus, activating p53 becomes an attractive approach for the development of molecule-based anti-cancer therapy. The past decade and half have witnessed tremendous progress in this area. This essay offers readers with a grand review on this progress with updated information about small molecule activators of p53 either still at bench work or in clinical trials...
March 25, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28342824/development-of-car-t-cells-designed-to-improve-antitumor-efficacy-and-safety
#14
REVIEW
Janneke E Jaspers, Renier J Brentjens
Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are 'on-target, off-tumor' toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how optimizing the design of CAR T cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CAR T cell therapy in pre-clinical models...
March 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28336474/the-evolution-of-heart-failure-with-reduced-ejection-fraction-pharmacotherapy-what-do-we-have-and-where-are-we-going
#15
REVIEW
Ahmed Selim, Ronald Zolty, Yiannis S Chatzizisis
Cardiovascular diseases represent a leading cause of mortality and increased healthcare expenditure worldwide. Heart failure, which simply describes an inability of the heart to meet the body's needs, is the end point for many other cardiovascular conditions. The last three decades have witnessed significant efforts aiming at the discovery of treatments to improve the survival and quality of life of patients with heart failure; many were successful, while others failed. Given that most of the successes in treating heart failure were achieved in patients with reduced left ventricular ejection fraction (HFrEF), we constructed this review to look at the recent evolution of HFrEF pharmacotherapy...
March 21, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28336473/unravelling-the-complexities-of-vascular-smooth-muscle-ion-channels-fine-tuning-of-activity-by-ancillary-subunits
#16
REVIEW
Thomas A Jepps
Which ion channel is the most important for regulating vascular tone? Which one is responsible for controlling the resting membrane potential or repolarization? Which channels are recruited by different intracellular signalling pathways or change in certain vascular diseases? Many different ion channels have been identified in the vasculature over the years and claimed as future therapeutic targets. Unfortunately, several of these ion channels are not just found in the vasculature, with many of them also found to have prominent functional roles in different organs of the body, which then leads to off-target effects...
March 21, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28322974/current-modalities-in-cancer-immunotherapy-immunomodulatory-antibodies-cars-and-vaccines
#17
REVIEW
Jason Lohmueller, Olivera J Finn
Successes of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cell therapy in curing patients with otherwise lethal cancers have validated immunotherapy as a treatment for cancer and have inspired excitement for its broader potential. Most promising is the ability of each approach to eliminate bulky and advanced-stage cancers and to achieve durable cures. Despite this success, to date only a subset of cancer patients and a limited number of cancer types respond to these therapies. A major goal now is to expand the types of cancer and number of patients who can be successfully treated...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28322973/imidazoline-i2-receptors-an-update
#18
REVIEW
Jun-Xu Li
Since first introduced more than two decades ago, the research in imidazoline I2 receptors has been steadily increasing. This review provides an update on the current status of I2 receptor pharmacology. Imidazoline I2 receptors or I2 binding sites refer to several (at least four) different proteins that bind to [(3)H]-idazoxan and [(3)H]-2-BFI with high affinity. The molecular identities of the proteins remain elusive. One of the proteins (45 kD) seems to be consistent with the identity of brain creatine kinase...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28322972/potential-role-of-cyp1b1-in-the-development-and-treatment-of-metabolic-diseases
#19
REVIEW
Fei Li, Weifeng Zhu, Frank J Gonzalez
Cytochrome P450 1B1 (CYP1B1), a member of CYP450s, is expressed in liver and extrahepatic tissues carries out the metabolism of numerous xenobiotics, including the metabolic activation of polycyclic aromatic hydrocarbons. Surprisingly, CYP1B1 was also shown to be important in regulating endogenous metabolic pathways, including the metabolism of steroid hormones, fatty acids, melatonin, and vitamins. CYP1B1 and nuclear receptors including peroxisome proliferator-activated receptors (PPARs), estrogen receptor (ER), and retinoic acid receptors (RAR) contribute to the maintenance of the homeostasis of these endogenous compounds...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28322971/effects-and-mechanisms-of-compound-chinese-medicine-and-major-ingredients-on-microcirculatory-dysfunction-and-organ-injury-induced-by-ischemia-reperfusion
#20
REVIEW
Jing-Yan Han, Quan Li, Zhi-Zhong Ma, Jing-Yu Fan
Microcirculation dysfunction and organ injury after ischemia and reperfusion (I/R) result from a complex pathologic process consisting of multiple links, with metabolism impairment in the ischemia phase and oxidative stress in the reperfusion phase as initiators, and any treatment targeting a single link is insufficient to cope with this. Compound Chinese medicine (CCM) has been applied in clinics in China and some Asian nations for >2000years. Studies over the past decades revealed the protective and therapeutic effect of CCMs and major ingredients on I/R-induced microcirculatory dysfunction and tissue injury in the heart, brain, liver, intestine, and so on...
March 16, 2017: Pharmacology & Therapeutics
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