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Handbook of Experimental Pharmacology

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https://www.readbyqxmd.com/read/27913889/ocular-pharmacology-of-tear-film-dry-eye-and-allergic-conjunctivitis
#1
Shilpa Gulati, Sandeep Jain
Dry Eye Disease (DED) is "a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear-film instability with potential damage to the ocular surface." DED comprises two etiologic categories: aqueous-deficient dry eye (ADDE) and evaporative dry eye (EDE). Diagnostic workup of DED should include clinical history, symptom questionnaire, fluorescein TBUT, ocular surface staining grading, Schirmer I/II, lid and meibomian pathology, meibomian expression, followed by other available tests...
December 3, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27913888/erratum-to-the-mitochondrial-permeability-transition-pore-and-atp-synthase
#2
Gisela Beutner, Kambiz N Alavian, Elizabeth A Jonas, George A Porter
No abstract text is available yet for this article.
December 3, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27900610/novel-sgc-stimulators-and-sgc-activators-for-the-treatment-of-heart-failure
#3
Stefanie Breitenstein, Lothar Roessig, Peter Sandner, Kelly S Lewis
The burden of heart failure (HF) increases worldwide with an aging population, and there is a high unmet medical need in both, heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). The nitric oxide (NO) pathway is a key regulator in the cardiovascular system and modulates vascular tone and myocardial performance. Disruption of the NO-cyclic guanosine monophosphate (cGMP) signaling axis and impaired cGMP formation by endothelial dysfunction could lead to vasotone dysregulation, vascular and ventricular stiffening, fibrosis, and hypertrophy resulting in a decline of heart as well as kidney function...
November 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27900609/dry-age-related-macular-degeneration-pharmacology
#4
Charles B Wright, Jayakrishna Ambati
Age-related macular degeneration (AMD), the most common form of irreversible blindness in the industrially developed world, can present years before a patient begins to lose vision. For most of these patients, AMD never progresses past its early stages to the advanced forms that are principally responsible for the vast majority of vision loss. Advanced AMD can manifest as either an advanced avascular form known as geographic atrophy (GA) marked by regional retinal pigment epithelium (RPE) cell death or as an advanced form known as neovascular AMD marked by the intrusion of fragile new blood vessels into the normally avascular retina...
November 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27900608/interaction-of-epac-with-non-canonical-cyclic-nucleotides
#5
Holger Rehmann
Epac1 and Epac2 are cyclic nucleotide-binding (CNB) domain containing proteins, which were originally identified as cAMP-regulated guanine nucleotide exchange factors (GEFs) for the small G-protein Rap. Therefore, Epac proteins founded next to protein kinase A (PKA) and cyclic nucleotide-regulated ion channels the third group of cAMP-responsive proteins in higher organisms. Epac proteins are involved in the regulation of several physiological processes. In particular Epac1 mediates the regulation of molecular processes underlying cell adhesion and mobility...
November 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27900607/mammalian-nucleotidyl-cyclases-and-their-nucleotide-binding-sites
#6
Stefan Dove
Mammalian membranous and soluble adenylyl cyclases (mAC, sAC) and soluble guanylyl cyclases (sGC) generate cAMP and cGMP from ATP and GTP, respectively, as substrates. mACs (nine human isoenzymes), sAC, and sGC differ in their overall structures owing to specific membrane-spanning and regulatory domains but consist of two similarly folded catalytic domains C1 and C2 with high structure-based homology between the cyclase species. Comparison of available crystal structures - VC1:IIC2 (a construct of domains C1a from dog mAC5 and C2a from rat mAC2), human sAC and sGC, mostly in complex with substrates, substrate analogs, inhibitors, metal ions, and/or modulators - reveals that especially the nucleotide binding sites are closely related...
November 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27896476/medicinal-chemistry-of-the-noncanonical-cyclic-nucleotides-ccmp-and-cump
#7
Frank Schwede, Andreas Rentsch, Hans-Gottfried Genieser
After decades of intensive research on adenosine-3',5'-cyclic monophosphate (cAMP)- and guanosine-3',5'-cyclic monophosphate (cGMP)-related second messenger systems, also the noncanonical congeners cyclic cytidine-3',5'-monophosphate (cCMP) and cyclic uridine-3',5'-monophosphate (cUMP) gained more and more interest. Until the late 1980s, only a small number of cCMP and cUMP analogs with sometimes undefined purities had been described. Moreover, most of these compounds had been rather synthesized as precursors of antitumor and antiviral nucleoside-5'-monophosphates and hence had not been tested for any second messenger activity...
November 29, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27888348/pathogenesis-of-copd-and-asthma
#8
Clive Page, Blaze O'Shaughnessy, Peter Barnes
Asthma and COPD remain two diseases of the respiratory tract with unmet medical needs. This review considers the current state of play with respect to what is known about the underlying pathogenesis of these two chronic inflammatory diseases of the lung. The review highlights why they are different conditions requiring different approaches to treatment and provides a backdrop for the subsequent chapters in this volume discussing recent advances in the pharmacology and treatment of asthma and COPD.
November 26, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27885525/histamine-h1-receptor-gene-expression-and-drug-action-of-antihistamines
#9
Hiroyuki Fukui, Hiroyuki Mizuguchi, Hisao Nemoto, Yoshiaki Kitamura, Yoshiki Kashiwada, Noriaki Takeda
The upregulation mechanism of histamine H1 receptor through the activation of protein kinase C-δ (PKCδ) and the receptor gene expression was discovered. Levels of histamine H1 receptor mRNA and IL-4 mRNA in nasal mucosa were elevated by the provocation of nasal hypersensitivity model rats. Pretreatment with antihistamines suppressed the elevation of mRNA levels. Scores of nasal symptoms were correlatively alleviated to the suppression level of mRNAs above. A correlation between scores of nasal symptoms and levels of histamine H1 receptor mRNA in the nasal mucosa was observed in patients with pollinosis...
November 25, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27885524/camp-dependent-protein-kinase-and-cgmp-dependent-protein-kinase-as-cyclic-nucleotide-effectors
#10
Robin Lorenz, Daniela Bertinetti, Friedrich W Herberg
The cAMP-dependent protein kinase (PKA) and the cGMP-dependent protein kinase (PKG) are homologous enzymes with different binding and activation specificities for cyclic nucleotides. Both enzymes harbor conserved cyclic nucleotide-binding (CNB) domains. Differences in amino acid composition of these CNB domains mediate cyclic nucleotide selectivity in PKA and PKG, respectively. Recently, the presence of the noncanonical cyclic nucleotides cCMP and cUMP in eukaryotic cells has been proven, while the existence of cellular cIMP and cXMP remains unclear...
November 25, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27878470/%C3%AE-2-agonists
#11
Charlotte K Billington, Raymond B Penn, Ian P Hall
History suggests β agonists, the cognate ligand of the β2 adrenoceptor, have been used as bronchodilators for around 5,000 years, and β agonists remain today the frontline treatment for asthma and chronic obstructive pulmonary disease (COPD). The β agonists used clinically today are the products of significant expenditure and over 100 year's intensive research aimed at minimizing side effects and enhancing therapeutic usefulness. The respiratory physician now has a therapeutic toolbox of long acting β agonists to prophylactically manage bronchoconstriction, and short acting β agonists to relieve acute exacerbations...
November 23, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27873089/gut-hormone-regulation-and-secretion-via-ffa1-and-ffa4
#12
Fiona M Gribble, Eleftheria Diakogiannaki, Frank Reimann
The digestion, absorption and utilisation of dietary triglycerides are controlled by gut hormones, released from enteroendocrine cells along the length of the gastrointestinal tract. Major players in the detection of ingested lipids are the free fatty acid receptors FFA1 and FFA4, which are highly expressed on enteroendocrine cells. These receptors are activated when free fatty acids (FFA) are absorbed across the intestinal epithelium, and provide a dynamic hormonal signal indicating that lipids are arriving in the bloodstream from the gut...
November 22, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27873088/anti-inflammatory-and-insulin-sensitizing-effects-of-free-fatty-acid-receptors
#13
Junki Miyamoto, Mayu Kasubuchi, Akira Nakajima, Ikuo Kimura
Chronic low-grade inflammation in macrophages and adipose tissues can promote the development of obesity and type 2 diabetes. Free fatty acids (FFAs) have important roles in various tissues, acting as both essential energy sources and signaling molecules. FFA receptors (FFARs) can modulate inflammation in various types of cells and tissues; however the underlying mechanisms mediating these effects are unclear. FFARs are activated by specific FFAs; for example, GPR40 and GPR120 are activated by medium and long chain FFAs, GPR41 and GPR43 are activated by short chain FFAs, and GPR84 is activated by medium-chain FFAs...
November 22, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27873087/key-questions-for-translation-of-ffa-receptors-from-pharmacology-to-medicines
#14
Arthur T Suckow, Celia P Briscoe
The identification of fatty acids as ligands for the G-protein coupled free fatty acid (FFA) receptor family over 10 years ago led to intensive chemistry efforts to find small-molecule ligands for this class of receptors. Identification of potent, selective modulators of the FFA receptors and their utility in medicine has proven challenging, in part due to their complex pharmacology. Nevertheless, ligands have been identified that are sufficient for exploring the therapeutic potential of this class of receptors in rodents and, in the case of FFA1, FFA2, FFA4, and GPR84, also in humans...
November 22, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27873086/what-we-know-and-do-not-know-about-actin
#15
Thomas D Pollard
Seven decades of research have revealed much about actin structure, assembly, regulatory proteins, and cellular functions. However, some key information is still missing, so we do not understand the mechanisms of most processes that depend on actin. This chapter summarizes our current knowledge and explains some examples of work that will be required to fill these gaps and arrive at a mechanistic understanding of actin biology.
November 22, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27864678/polymorphic-variation-in-ffa-receptors-functions-and-consequences
#16
Atsuhiko Ichimura
Overfeeding of fat can cause various metabolic disorders including obesity and type 2 diabetes (T2D). Diet provided free fatty acids (FFAs) are not only essential nutrients, but they are also recognized as signaling molecules, which stimulate various important biological functions. Recently, several G protein-coupled receptors (GPCRs), including FFA1-4, have been identified as receptors of FFAs by various physiological and pharmacological studies. FFAs exert physiological functions through these FFA receptors (FFARs) depending on carbon chain length and degree of unsaturation...
November 19, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27864677/glucocorticoids
#17
Ian M Adcock, Sharon Mumby
The most effective anti-inflammatory drugs used to treat patients with airways disease are topical glucocorticosteroids (GCs). These act on virtually all cells within the airway to suppress airway inflammation or prevent the recruitment of inflammatory cells into the airway. They also have profound effects on airway structural cells to reverse the effects of disease on their function. Glucorticosteroids act via specific receptors-the glucocorticosteroid receptor (GR)-which are a member of the nuclear receptor family...
November 19, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27864676/anti-ige-and-biologic-approaches-for-the-treatment-of-asthma
#18
Patrick D Mitchell, Amani I El-Gammal, Paul M O'Byrne
Current asthma treatments are effective for the majority of patients with mild-to-moderate disease. However, in those with more severe refractory asthma, agents other than inhaled corticosteroids and beta-agonists are needed both to better manage this group of patients and to avoid the side effects of high-dose corticosteroids and the social and personal hardship endured. Several biological pathways have been targeted over the last 20 years, and this research has resulted in pharmacological approaches to attempt to better treat patients with severe refractory asthma...
November 19, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27864675/drugs-affecting-trp-channels
#19
M A Wortley, M A Birrell, M G Belvisi
Chronic obstructive pulmonary disease (COPD) and asthma are both common respiratory diseases that are associated with airflow reduction/obstruction and pulmonary inflammation. Whilst drug therapies offer adequate symptom control for many mild to moderate asthmatic patients, severe asthmatics and COPD patients symptoms are often not controlled, and in these cases, irreversible structural damage occurs with disease progression over time. Transient receptor potential (TRP) channels, in particular TRPV1, TRPA1, TRPV4 and TRPM8, have been implicated with roles in the regulation of inflammation and autonomic nervous control of the lungs...
November 19, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27848029/pharmacologic-treatment-of-noninfectious-uveitis
#20
Jared E Knickelbein, Karen R Armbrust, Meredith Kim, H Nida Sen, Robert B Nussenblatt
Uveitis encompasses a spectrum of diseases whose common feature is intraocular inflammation, which may be infectious or noninfectious in etiology (Nussenblatt and Whitcup 2010). Infectious causes of uveitis are typically treated with appropriate antimicrobial therapy and will not be discussed in this chapter. Noninfectious uveitides are thought have an autoimmune component to their etiology and are thus treated with anti-inflammatory agents.
November 16, 2016: Handbook of Experimental Pharmacology
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