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Handbook of Experimental Pharmacology

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https://www.readbyqxmd.com/read/28101683/allergy-histamine-and-antihistamines
#1
Martin K Church
This chapter concentrates on the role in allergic disease of histamine acting on H1-receptors. It is clear that allergy has its roots in the primary parasite rejection response in which mast cell-derived histamine creates an immediate hostile environment and eosinophils are recruited for killing. This pattern is seen in allergic rhinitis where the early events of mucus production and nasal itching are primarily histamine mediated whereas nasal blockage is secondary to eosinophil infiltration and activation...
January 19, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28040850/mitochondrial-fission-in-human-diseases
#2
Madhavika N Serasinghe, Jerry E Chipuk
Mitochondria are an essential component of multicellular life - from primitive organisms, to highly complex entities like mammals. The importance of mitochondria is underlined by their plethora of well-characterized essential functions such as energy production through oxidative phosphorylation (OX-PHOS), calcium and reactive oxygen species (ROS) signaling, and regulation of apoptosis. In addition, novel roles and attributes of mitochondria are coming into focus through the recent years of mitochondrial research...
January 1, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28039543/sigma-receptors-and-alcohol-use-disorders
#3
Valentina Sabino, Pietro Cottone
Although extensive research has focused on understanding the neurobiological mechanisms underlying alcohol addiction, pharmacological treatments for alcohol use disorders are very limited and not always effective. This constraint has encouraged the search for novel pharmacological targets for alcoholism therapy. Sigma receptors were shown to mediate some of the properties of cocaine and amphetamine, which was attributed to the direct binding of psychostimulants to these receptors. More recently, the role of sigma receptors in the rewarding and reinforcing effects of alcohol was also proposed, and it was suggested that their hyperactivity may result in excessive alcohol drinking...
December 31, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28035535/the-role-of-the-gastrointestinal-microbiota-in-visceral-pain
#4
Kieran Rea, Siobhain M O'Mahony, Timothy G Dinan, John F Cryan
A growing body of preclinical and clinical evidence supports a relationship between the complexity and diversity of the microorganisms that inhabit our gut (human gastrointestinal microbiota) and health status. Under normal homeostatic conditions this microbial population helps maintain intestinal peristalsis, mucosal integrity, pH balance, immune priming and protection against invading pathogens. Furthermore, these microbes can influence centrally regulated emotional behaviour through mechanisms including microbially derived bioactive molecules (amino acid metabolites, short-chain fatty acids, neuropeptides and neurotransmitters), mucosal immune and enteroendocrine cell activation, as well as vagal nerve stimulation...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28035534/oprd1-genetic-variation-and-human-disease
#5
Richard C Crist, Toni-Kim Clarke
The OPRD1 gene encodes the delta-opioid receptor, which has multiple functions including regulating reward pathways. The gene contains more than 2,000 verified genetic variants but only 2 currently have evidence for specific functions: rs1042114 disrupts maturation of the receptor and rs569356 affects OPRD1 expression. These polymorphisms and others in the gene have been found to be associated with human diseases. The most reproducible data are associations between opioid addiction and three variants in intron 1 (rs2236861, rs2236857, and rs3766951), which have been described in a number of independent populations...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28035533/mitochondrial-cholesterol-and-the-paradox-in-cell-death
#6
Carmen García-Ruiz, Vicente Ribas, Anna Baulies, Jose C Fernández-Checa
Mitochondria are considered cholesterol-poor organelles, and obtain their cholesterol load by the action of specialized proteins involved in its delivery from extramitochondrial sources and trafficking within mitochondrial membranes. Although mitochondrial cholesterol fulfills vital physiological functions, such as the synthesis of bile acids in the liver or the formation of steroid hormones in specialized tissues, recent evidence indicates that the accumulation of cholesterol in mitochondria may be a key event in prevalent human diseases, in particular in the development of steatohepatitis (SH) and its progression to hepatocellular carcinoma (HCC)...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28035532/ghrelin-and-motilin-control-systems-in-gi-physiology-and-therapeutics
#7
Gareth J Sanger, John Broad, Brid Callaghan, John B Furness
Ghrelin and motilin are released from gastrointestinal endocrine cells during hunger, to act through G protein-coupled receptors that have closely related amino acid sequences. The actions of ghrelin are more complex than motilin because ghrelin also exists outside the GI tract, it is processed to des-acyl ghrelin which has activity, ghrelin can exist in truncated forms and retain activity, the ghrelin receptor can have constitutive activity and is subject to biased agonism and finally additional ghrelin-like and des-acyl ghrelin receptors are proposed...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28035531/neuroimmune-modulation-of-gut-function
#8
Terez Shea-Donohue, Joseph F Urban
Neuroimmune communications are facilitated by the production of neurotransmitters by immune cells and the generation of immune mediators by immune cells, which form a functional entity called the "neuroimmune synapse." There are several mechanisms that further facilitate neuroimmune interactions including the anatomic proximity between immune cells and nerves, the expression of receptors for neurotransmitters on immune cells and for immune mediators on nerves, and the receptor-mediated activation of intracellular signaling pathways that modulate nerve and immune phenotype and function...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28035530/serotonergic-mechanisms-regulating-the-gi-tract-experimental-evidence-and-therapeutic-relevance
#9
Natalie Terry, Kara Gross Margolis
Serotonin (5-hydroxytryptamine; 5-HT) is best known as a neurotransmitter critical for central nervous system (CNS) development and function. 95% of the body's serotonin, however, is produced in the intestine where it has been increasingly recognized for its hormonal, autocrine, paracrine, and endocrine actions. This chapter provides the most current knowledge of the critical autocrine and paracrine roles of 5-HT in intestinal motility and inflammation as well as its function as a hormone in osteocyte homeostasis...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28035529/hereditary-retinal-dystrophy
#10
Thomas C Hohman
As our understanding of the genetic basis for inherited retinal disease has expanded, gene therapy has advanced into clinical development. When the gene mutations associated with inherited retinal dystrophies were identified, it became possible to create animal models in which individual gene were altered to match the human mutations. The retina of these animals were then characterized to assess whether the mutated genes produced retinal phenotypes characteristic of disease-affected patients. Following the identification of a subpopulation of patients with the affected gene and the development of techniques for the viral gene transduction of retinal cells, it has become possible to deliver a copy of the normal gene into the retinal sites of the mutated genes...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28035528/delta-opioid-receptors-learning-and-motivation
#11
L P Pellissier, C N Pujol, J A J Becker, J Le Merrer
Delta opioid receptor (DOR) displays a unique, highly conserved, structure and an original pattern of distribution in the central nervous system, pointing to a distinct and specific functional role among opioid peptide receptors. Over the last 15 years, in vivo pharmacology and genetic models have allowed significant advances in the understanding of this role. In this review, we will focus on the involvement of DOR in modulating different types of hippocampal- and striatal-dependent learning processes as well as motor function, motivation, and reward...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28035527/new-and-emerging-therapies-and-targets-beta-3-agonists
#12
Lauriane Y M Michel, Jean-Luc Balligand
While crucial for the acute physiologic response to stress, the adrenergic system may become maladaptive upon prolonged stimulation in the course of development of heart failure. This has been the basis for the development of beta-blocking therapies, targeting mainly beta1-2 adrenoreceptors (B1-2AR). The third isotype, B3AR, was more recently identified in cardiac myocytes and endothelial cells from human (and many other animal species), where its distinctive coupling to nitric oxide and antioxidant pathways suggested potential protective properties that were unexploited so far...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28004291/sacubitril-valsartan-lcz696-in-heart-failure
#13
Yasser Khder, Victor Shi, John J V McMurray, Martin P Lefkowitz
It has been known since the 1990s that long-term morbidity and mortality is improved in patients with heart failure with reduced ejection fraction (HFrEF) by treatments that target the renin-angiotensin-aldosterone system (RAAS). It has also long been thought that enhancement of the activity of natriuretic peptides (NPs) could potentially benefit patients with HFrEF, but multiple attempts to realize this benefit had failed over the years - until 2014, when a large, phase III, randomized, controlled clinical trial (PARADIGM-HF) was completed comparing sacubitril/valsartan with enalapril, a well-established treatment for HFrEF...
December 22, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27999957/postoperative-ileus-pathophysiology-current-therapeutic-approaches
#14
N Stakenborg, P J Gomez-Pinilla, G E Boeckxstaens
Postoperative ileus, which develops after each abdominal surgical procedure, is an iatrogenic disorder characterized by a transient inhibition of gastrointestinal motility. Its pathophysiology is complex involving pharmacological (opioids, anesthetics), neural, and immune-mediated mechanisms. The early neural phase, triggered by activation of afferent nerves during the surgical procedure, is short lasting compared to the later inflammatory phase. The latter starts after 3-6 h and lasts several days, making it a more interesting target for treatment...
December 21, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27995392/abnormal-barrier-function-in-gastrointestinal-disorders
#15
Ricard Farré, María Vicario
There is increasing concern in identifying the mechanisms underlying the intimate control of the intestinal barrier, as deregulation of its function is strongly associated with digestive (organic and functional) and a number of non-digestive (schizophrenia, diabetes, sepsis, among others) disorders. The intestinal barrier is a complex and effective defensive functional system that operates to limit luminal antigen access to the internal milieu while maintaining nutrient and electrolyte absorption. Intestinal permeability to substances is mainly determined by the physicochemical properties of the barrier, with the epithelium, mucosal immunity, and neural activity playing a major role...
December 20, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27995391/irritable-bowel-syndrome-pathophysiology-and-current-therapeutic-approaches
#16
Michael Camilleri, Alexander C Ford
Irritable bowel syndrome (IBS) is a prevalent condition affecting 10-20% of adults in most countries; IBS results in significant morbidity and health care costs. IBS is a disorder of the brain-gut axis, and recent insights into the pathophysiological mechanisms include altered bile acid metabolism, neurohormonal regulation, immune dysfunction, alterations in the epithelial barrier, and secretory properties of the gut. There remains a significant unmet need for effective treatments, particularly for the pain component of IBS, although the introduction of drugs directed at secretion, motility, and a nonabsorbable antibiotic provides an option for the bowel dysfunction in IBS...
December 20, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27995390/the-three-decade-long-journey-in-heart-failure-drug-development
#17
Kelly S Lewis, Javed Butler, Johann Bauersachs, Peter Sandner
Heart failure is a global disease with increasing prevalence due to an aging worldwide population with increasing co-morbidities. Despite several therapeutic options available to treat HFrEF, morbidity and mortality remain high. Importantly, no approved therapies are available to treat HFpEF. This paper will briefly summarize the burden of disease, HF classification and definitions and the landmark clinical trials in both HFrEF and HFpEF. Given the increasing incidence and prevalence of HF and the high morbidity and mortality associated with this disease, continued development efforts are essential to address the unmet needs of these patients...
December 20, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27995389/equipping-physiologists-with-an-informatics-tool-chest-toward-an-integerated-mitochondrial-phenome
#18
Anders Olav Garlid, Jennifer S Polson, Keith D Garlid, Henning Hermjakob, Peipei Ping
Understanding the complex involvement of mitochondrial biology in disease development often requires the acquisition, analysis, and integration of large-scale molecular and phenotypic data. An increasing number of bioinformatics tools are currently employed to aid in mitochondrial investigations, most notably in predicting or corroborating the spatial and temporal dynamics of mitochondrial molecules, in retrieving structural data of mitochondrial components, and in aggregating as well as transforming mitochondrial centric biomedical knowledge...
December 20, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27995388/structural-insights-into-sigma1-function
#19
Andrew Kruse
Sigma1 (also known as this sigma-1 receptor) is an unusual and enigmatic transmembrane protein implicated in a diverse array of biological processes ranging from neurodegenerative disease to cancer. Despite decades of research, the molecular architecture of Sigma1 is only beginning to become clear. Recent work has established that Sigma1 is an oligomer, and crystallographic studies have now offered the first high-resolution views of its molecular structure. For the first time, these results provide a detailed framework to understand mutagenesis data and the molecular pharmacology of Sigma1 ligands...
December 20, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27995387/noncoding-rnas-in-heart-failure
#20
Seema Dangwal, Katharina Schimmel, Ariana Foinquinos, Ke Xiao, Thomas Thum
Heart failure is a major contributor to the healthcare burden and mortality worldwide. Current treatment strategies are able to slow down the transition of healthy heart into the failing one; nevertheless better understanding of the complex genetic regulation of maladaptive remodeling in the failing heart is essential for new drug discovery. Noncoding RNAs are key epigenetic regulators of cardiac gene expression and thus significantly influence cardiac homeostasis and functions.In this chapter we will discuss characteristics of noncoding RNAs, especially miRNAs, long noncoding RNAs, and circular RNAs, and review recent evidences proving their profound involvement during different stages of heart failure progression...
December 20, 2016: Handbook of Experimental Pharmacology
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