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Pharmacology and physiology

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https://www.readbyqxmd.com/read/28534468/effect-of-wearing-a-telemetry-jacket-on-behavioral-and-physiologic-parameters-of-dogs-in-the-open%C3%A2-field-test
#1
Richard E Fish, Melanie L Foster, Margaret E Gruen, Barbara L Sherman, David C Dorman
Safety pharmacology studies in dogs often integrate behavioral assessments made using video recording with physiologicmeasurements collected by telemetry. However, whether merely wearing the telemetry vest affects canine behavior and otherparameters has not been evaluated. This pilot study assessed the effect of a telemetry vest on behavioral and physiologic responses to an environmental stressor, the sounds of a thunderstorm, in Labrador retrievers. Dogs were assigned to one of 2 experimental groups (Vest and No-Vest, n = 8 dogs per group) by using a matched pairs design, with a previously determined,sound-associated anxiety score as the blocking variable...
May 22, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28534084/the-emerging-link-between-o-glcnacylation-and-neurological-disorders
#2
REVIEW
Xiaofeng Ma, He Li, Yating He, Junwei Hao
O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is involved in the regulation of many cellular cascades and neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In the brain, the expression of O-GlcNAcylation is notably heightened, as is that of O-linked N-acetylglucosaminyltransferase (OGT) and β-N-acetylglucosaminidase (OGA), the presence of which is prominent in many regions of neurological importance. Most importantly, O-GlcNAcylation is believed to contribute to the normal functioning of neurons; conversely, its dysregulation participates in the pathogenesis of neurological disorders...
May 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28533176/the-mouse-thermoregulatory-system-its-impact-on-translating-biomedical-data-to-humans
#3
REVIEW
Christopher J Gordon
The laboratory mouse has become the predominant test species in biomedical research. The number of papers that translate or extrapolate data from mouse to human has grown exponentially since the year 2000. There are many physiological and anatomical factors to consider in the process of extrapolating data from one species to another. Body temperature is, of course, a critical determinant in extrapolation because it has a direct impact on metabolism, cardiovascular function, drug efficacy, pharmacokinetics of toxins and drugs, and many other effects...
May 19, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28530645/myc-dependent-oxidative-metabolism-regulates-osteoclastogenesis-via-nuclear-receptor-err%C3%AE
#4
Seyeon Bae, Min Joon Lee, Se Hwan Mun, Eugenia G Giannopoulou, Vladimir Yong-Gonzalez, Justin R Cross, Koichi Murata, Vincent Giguère, Marjolein van der Meulen, Kyung-Hyun Park-Min
Osteoporosis is a metabolic bone disorder associated with compromised bone strength and an increased risk of fracture. Inhibition of the differentiation of bone-resorbing osteoclasts is an effective strategy for the treatment of osteoporosis. Prior work by our laboratory and others has shown that MYC promotes osteoclastogenesis in vitro, but the underlying mechanisms are not well understood. In addition, the in vivo importance of osteoclast-expressed MYC in physiological and pathological bone loss is not known...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28529316/pharmacological-modulation-of-autophagy-therapeutic-potential-and-persisting-obstacles
#5
REVIEW
Lorenzo Galluzzi, José Manuel Bravo-San Pedro, Beth Levine, Douglas R Green, Guido Kroemer
Autophagy is central to the maintenance of organismal homeostasis in both physiological and pathological situations. Accordingly, alterations in autophagy have been linked to clinically relevant conditions as diverse as cancer, neurodegeneration and cardiac disorders. Throughout the past decade, autophagy has attracted considerable attention as a target for the development of novel therapeutics. However, such efforts have not yet generated clinically viable interventions. In this Review, we discuss the therapeutic potential of autophagy modulators, analyse the obstacles that have limited their development and propose strategies that may unlock the full therapeutic potential of autophagy modulation in the clinic...
May 19, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28529128/role-of-gper-in-the-activation-of-endothelial-nitric-oxide-synthase
#6
Natalie C Fredette, Matthias R Meyer, Eric R Prossnitz
Estrogens are potent regulators of vascular tone, yet underlying receptor- and ligand-specific signaling pathways remain poorly characterized. The primary physiological estrogen 17β-estradiol (E2), a non-selective agonist of classical nuclear estrogen receptors (ERα and ERβ) as well as the G protein-coupled estrogen receptor (GPER), stimulates formation of the vasodilator nitric oxide (NO) in endothelial cells. Here, we studied the contribution of GPER signaling in E2-dependent activation of endothelial NO formation and subsequent vasodilation...
May 18, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28528673/acid-sensing-ion-channel-pharmacology-past-present-and-future-%C3%A2
#7
Lachlan D Rash
pH is one of the most strictly controlled parameters in mammalian physiology. An extracellular pH of ~7.4 is crucial for normal physiological processes, and perturbations to this have profound effects on cell function. Acidic microenvironments occur in many physiological and pathological conditions, including inflammation, bone remodeling, ischemia, trauma, and intense synaptic activity. Cells exposed to these conditions respond in different ways, from tumor cells that thrive to neurons that are either suppressed or hyperactivated, often fatally...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28528672/physiology-and-pharmacology-of-ryanodine-receptor-calcium-release-channels
#8
Angela F Dulhunty, Philip G Board, Nicole A Beard, Marco G Casarotto
Ryanodine receptor (RyR) ion channels are essential for skeletal and cardiac muscle function. Their knockout leads to perinatal death from respiratory and cardiac failure. Acquired changes or mutations in the protein cause debilitating skeletal myopathy and cardiac arrhythmia which can be deadly. Knowledge of the pharmacology of RyR channels is central to developing effective and specific treatments of these myopathies. The ion channel is a >2.2MDa homotetamer with distinct structural and functional characteristics giving rise to a myriad of regulatory sites that are potential therapeutic targets...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28528670/glycine-receptor-drug-discovery
#9
Joseph W Lynch, Yan Zhang, Sahil Talwar, Argel Estrada-Mondragon
Postsynaptic glycine receptor (GlyR) chloride channels mediate inhibitory neurotransmission in the spinal cord and brain stem, although presynaptic and extrasynaptic GlyRs are expressed more widely throughout the brain. In humans, GlyRs are assembled as homo- or heteromeric pentamers of α1-3 and β subunits. GlyR malfunctions have been linked to a range of neurological disorders including hyperekplexia, temporal lobe epilepsy, autism, breathing disorders, and chronic inflammatory pain. Although it is possible that GlyRs may eventually be clinically targeted for a variety of neurological disorders, most research to date has focused on developing GlyR-targeted treatments for chronic pain...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28528666/role-of-nonneuronal-trpv4-signaling-in-inflammatory-processes
#10
Pradeep Rajasekhar, Daniel P Poole, Nicholas A Veldhuis
Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28528665/gabaa-receptors-and-the-diversity-in-their-structure-and-pharmacology
#11
Han Chow Chua, Mary Chebib
GABAA receptors (GABAARs) are a class of ligand-gated ion channels with high physiological and therapeutic significance. In the brain, these pentameric receptors occur with diverse subunit composition, which confers highly complex pharmacology to this receptor class. An impressive range of clinically used therapeutics are known to bind to distinct sites found on GABAARs to modulate receptor function. Numerous experimental approaches have been used over the years to elucidate the binding sites of these drugs, but unequivocal identification is challenging due to subtype- and ligand-dependent pharmacology...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28527568/evolution-of-nuclear-receptors-and-ligand-signaling-toward-a-soft-key-lock-model
#12
Guillaume Holzer, Gabriel V Markov, Vincent Laudet
Nuclear receptors (NRs) are a family of ligand-regulated transcription factors that modulate a wide variety of physiological functions in a ligand-dependent manner. The first NRs were discovered as receptors of well-known hormones such as 17β-estradiol, corticosteroids, or thyroid hormones. In these cases a direct activation of the receptor transcriptional activity by a very specific ligand, with nanomolar affinity, was demonstrated, providing a strong conceptual framework to understand the mechanism of action of these hormones...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28526710/gbt1118-a-potent-allosteric-modifier-of-hemoglobin-oxygen-affinity-increases-tolerance-to-severe-hypoxia-in-mice
#13
Kobina Dufu, Ozlem Yalcin, Eilleen Sy Ao-Ieong, Athiwat Hutchaleelala, Qing Xu, Zhe Li, Nicholas Vlahakis, Donna Oksenberg, Josh Lehrer-Graiwer, Pedro Cabrales
Adaptation to hypoxia requires compensatory mechanisms that affect oxygen (O2) transport and utilization. Decreased hemoglobin (Hb)-O2 affinity is considered part of the physiological adaptive process to chronic hypoxia. This manuscript explores the hypothesis that increased Hb-O2 affinity can complement acute physiological responses to hypoxia by increasing O2 uptake and delivery when compared to normal Hb-O2 affinity during acute severe hypoxia. To test this hypothesis, mice Hb-O2 affinity was increased via oral administration of 70 or 140 mg/kg GBT1118...
May 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28526706/cardiac-hyporesponsiveness-in-severe-sepsis-is-associated-with-nitric-oxide-dependent-activation-of-g-protein-receptor-kinase
#14
Daniela Dal-Secco, Silvia DalBó, Natalia E S Lautherbach, Fábio N Gava, Mara Rubia Nunes Celes, Patricia Oliveira Benedet, Adriana H Souza, Juliana Akinaga, Vanessa Lima, Katiussia P Silva, Luiz Ricardo A Kiguti, Marcos A Rossi, Isis do Carmo Kettelhut, André Sampaio Pupo, Fernando Queiroz Cunha, Jamil Assreuy
G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS-2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP)...
May 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28526693/a-simple-laboratory-exercise-with-rat-isolated-esophagus-and-stomach-fundus-to-reveal-functional-differences-between-striated-and-smooth-muscle-cells
#15
Francisco José Batista-Lima, Kalinne Kelly Lima Gadelha, Daniel Maia Oliveira, Thiago Brasileiro Vasconcelos, Teresinha Silva Brito, Pedro Jorge Caldas Magalhães
This study describes an undergraduate student laboratory activity using isolated preparations from rat gastrointestinal tissues that possess contractile profiles typically exhibited by striated and smooth muscle cells. While students are introduced to an ex vivo methodology, they can compare differences in trace experiments, twitch aspects, phasic and tonic properties, force-frequency relationships, and pharmacological responsiveness of esophageal (striated) and fundic (smooth muscle) segments. Muscle strips were subjected to electrical field stimulation (EFS) applied by platinum electrodes immersed in the physiological solution...
June 1, 2017: Advances in Physiology Education
https://www.readbyqxmd.com/read/28526162/pharmacologic-considerations-of-anesthetic-agents-in-pediatric-patients-a-comprehensive-review
#16
REVIEW
Alan D Kaye, Charles J Fox, Ira W Padnos, Ken P Ehrhardt, James H Diaz, Elyse M Cornett, Debbie Chandler, Sudipta Sen, Shilpadevi Patil
Acute pain in the pediatric population has important differences in terms of biology, intrapopulation variation, and epidemiology. Discussion as to the pharmacologic considerations of anesthetic agents, such as induction agents, neuromuscular blockers, opioids, local anesthetics, and adjuvant agents, is presented in this article. Special considerations and concerns, such as risk for propofol infusion syndrome and adverse potential side effects of anesthesia agents, are discussed. Anesthesiologists managing pediatric patients need to have a firm understanding of physiologic and pharmacologic differences compared with the adult population...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28526146/perioperative-pharmacologic-considerations-in-obesity
#17
REVIEW
Simon Willis, Gregory J Bordelon, Maunak V Rana
Obesity has increased in incidence worldwide. Along with the increased number of obese patients, comorbid conditions are also more prevalent in this population. Obesity leads to changes in the physiology of patients along with an altered response to pharmacologic therapy. Vigilant perioperative physicians must be aware of the unique characteristics of administered agents in order to appropriately provide anesthetic care for obese patients. Because of the variability in tissue content in obese patients and changes in pharmacokinetic modeling, a one-size-fits-all approach is not justified and a more sophisticated and prudent approach is indicated...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28525544/bistability-causality-and-complexity-in-cortical-networks-an-in-vitro-perturbational-study
#18
Mattia D'Andola, Beatriz Rebollo, Adenauer G Casali, Julia F Weinert, Andrea Pigorini, Rosa Villa, Marcello Massimini, Maria V Sanchez-Vives
Measuring the spatiotemporal complexity of cortical responses to direct perturbations provides a reliable index of the brain's capacity for consciousness in humans under both physiological and pathological conditions. Upon loss of consciousness, the complex pattern of causal interactions observed during wakefulness collapses into a stereotypical slow wave, suggesting that cortical bistability may play a role. Bistability is mainly expressed in the form of slow oscillations, a default pattern of activity that emerges from cortical networks in conditions of functional or anatomical disconnection...
May 19, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28520591/stem-cell-therapy-and-its-potential-role-in-pituitary-disorders
#19
Montserrat Lara-Velazquez, Akinduro O Oluwaseun, Ronald Reimer, Whitney W Woodmansee, Alfredo Quinones-Hinojosa
PURPOSE OF REVIEW: The pituitary gland is one of the key components of the endocrine system. Congenital or acquired alterations can mediate destruction of cells in the gland leading to hormonal dysfunction. Even though pharmacological treatment for pituitary disorders is available, exogenous hormone replacement is neither curative nor sustainable. Thus, alternative therapies to optimize management and improve quality of life are desired. RECENT FINDINGS: An alternative modality to re-establish pituitary function is to promote endocrine cell regeneration through stem cells that can be obtained from the pituitary parenchyma or pluripotent cells...
May 16, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28515690/brain-renin-angiotensin-system-and-microglial-polarization-implications-for-aging-and-neurodegeneration
#20
REVIEW
Jose L Labandeira-Garcia, Ana I Rodríguez-Perez, Pablo Garrido-Gil, Jannette Rodriguez-Pallares, Jose L Lanciego, Maria J Guerra
Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS) on microglial polarization are less known...
2017: Frontiers in Aging Neuroscience
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