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Pharmacology and physiology

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https://www.readbyqxmd.com/read/28803917/sca1-cells-from-the-heart-possess-a-molecular-circadian-clock-and-display-circadian-oscillations-in-cellular-functions
#1
Bastiaan C Du Pré, Evelyne J Demkes, Dries A M Feyen, Pieterjan Dierickx, Sandra Crnko, Bart J M Kok, Joost P G Sluijter, Pieter A Doevendans, Marc A Vos, Toon A B Van Veen, Linda W Van Laake
Stem cell antigen 1-positive (SCA1(+)) cells (SPCs) have been investigated in cell-based cardiac repair and pharmacological research, although improved cardiac function after injection has been variable and the mode of action remains unclear. Circadian (24-hr) rhythms are biorhythms regulated by molecular clocks that play an important role in (patho)physiology. Here, we describe (1) the presence of a molecular circadian clock in SPCs and (2) circadian rhythmicity in SPC function. We isolated SPCs from human fetal heart and found that these cells possess a molecular clock based on typical oscillations in core clock components BMAL1 and CRY1...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28802647/pharmacological-modulation-of-acid-sensing-ion-channels-1a-and-3-by-amiloride-and-2-guanidine-4-methylquinazoline-gmq
#2
Thomas Besson, Eric Lingueglia, Miguel Salinas
Acid-Sensing Ion Channels (ASICs) are cation channels activated by extracellular acidification that emerge as potential pharmacological targets in pain and other neurological disorders. Here, we compare the pharmacological modulation of ASIC1a and ASIC3 channels by amiloride and 2-guanidine-4-methylquinazoline (GMQ), two compounds commonly used for their in vitro and in vivo investigation. We analyzed the effect of amiloride on the pH-dependent activation and inactivation, the relative influence of the extracellular domain and the transmembrane/cytosolic domains on the effect of amiloride and GMQ using chimeras between ASIC1a and ASIC3, and how these compounds potentiate the physiologically relevant ASIC3 sustained window current...
August 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28802231/phytochemical-properties-and-pharmacological-effects-of-quercus-ilex-l-aqueous-extract-on-gastrointestinal-physiological-parameters-in-vitro-and-in-vivo
#3
Kaïs Rtibi, Imen Hammami, Slimen Selmi, Dhekra Grami, Hichem Sebai, Mohamed Amri, Lamjed Marzouki
INTRODUCTION: Several research studies have reported on the pharmacological relevance of the medicinal plants used for treating various gastrointestinal disorders and controlling the dietary glucose uptake in the intestinal tract. METHODS: Male rats were used to investigate the pharmacological effects of green oak acorn aqueous extract (GOAE) on gastrointestinal physiological parameters in vivo and in vitro. In this respect, the gastro-intestinal motility and hypersecretion essays were evaluated using a simple test meal (10% charcoal in 5% gum arabic) and castor oil induced diarrhea...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28801825/intractable-constipation-in-the-elderly
#4
REVIEW
Noemi Baffy, Amy E Foxx-Orenstein, Lucinda A Harris, Susan Sterler
Chronic constipation is a common gastrointestinal disorder disproportionately affecting the elderly. Immobility, polypharmacy, and physiologic changes contribute to its increased prevalence in this population. Unidentified and undertreated constipation leads to a significant negative impact on quality of life and an increase in healthcare spending. Careful physical examination and exploration of the clinical history can unmask primary and secondary forms of constipation, guiding diagnostic and therapeutic considerations...
August 11, 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28801643/the-role-of-pge2-in-alveolar-epithelial-and-lung-microvascular-endothelial-crosstalk
#5
Thomas Bärnthaler, Jovana Maric, Wolfgang Platzer, Viktoria Konya, Anna Theiler, Carina Hasenöhrl, Benjamin Gottschalk, Sandra Trautmann, Yannick Schreiber, Wolfgang F Graier, Rudolf Schicho, Gunther Marsche, Andrea Olschewski, Dominique Thomas, Rufina Schuligoi, Akos Heinemann
Disruption of the blood-air barrier, which is formed by lung microvascular endothelial and alveolar epithelial cells, is a hallmark of acute lung injury. It was shown that alveolar epithelial cells release an unidentified soluble factor that enhances the barrier function of lung microvascular endothelial cells. In this study we reveal that primarily prostaglandin (PG) E2 accounts for this endothelial barrier-promoting activity. Conditioned media from alveolar epithelial cells (primary ATI-like cells) collected from BALB/c mice and A549 cells increased the electrical resistance of pulmonary human microvascular endothelial cells, respectively...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28799512/modulation-of-gabaa-receptors-in-the-treatment-of-epilepsy
#6
Eleonora Palma, Gabriele Ruffolo, Pierangelo Cifelli, Cristina Roseti, Erwin A van Vliet, Eleonora Aronica
BACKGROUND: A variety of evidence suggested that an imbalance in excitatory and inhibitory neurotransmission could be one of the pathophysiological mechanisms underlying the occurrence and progression of seizures. Understanding the causes of this imbalance may provide essential insight into the basic mechanisms of epilepsy and may uncover novel targets for future drug therapies. Accordingly, GABA is the most important inhibitory neurotransmitter in the CNS and its receptors (e.g., GABAARs) can still be relevant targets of new antiepileptic drugs (AEDs)...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28798199/human-cerebral-blood-flow-control-during-hypoxia-focus-on-chronic-pulmonary-obstructive-disease-copd-and-obstructive-sleep-apnea-osa
#7
Andrew E Beaudin, Sara E Hartmann, Matiram Pun, Marc J Poulin
The brain is a vital organ that relies on a constant and adequate blood flow to match oxygen and glucose delivery with the local metabolic demands of active neurons. Thus, exquisite regulation of cerebral blood flow (CBF) is particularly important under hypoxic conditions to prevent a detrimental decrease in the partial pressure of oxygen within the brain tissues. Cerebrovascular sensitivity to hypoxia, assessed as the change in CBF during a hypoxic challenge, represents the capacity of cerebral vessels to respond to, and compensate for, a reduced oxygen supply, and has been shown to be impaired or blunted in a number of conditions...
August 10, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28797116/calcium-imaging-with-genetically-encoded-sensor-case12-facile-analysis-of-%C3%AE-7-%C3%AE-9-nachr-mutants
#8
Irina Shelukhina, Ekaterina Spirova, Denis Kudryavtsev, Lucy Ojomoko, Markus Werner, Christoph Methfessel, Michael Hollmann, Victor Tsetlin
Elucidation of the structural basis of pharmacological differences for highly homologous α7 and α9 nicotinic acetylcholine receptors (nAChRs) may shed light on their involvement in different physiological functions and diseases. Combination of site-directed mutagenesis and electrophysiology is a powerful tool to pinpoint the key amino-acid residues in the receptor ligand-binding site, but for α7 and α9 nAChRs it is complicated by their poor expression and fast desensitization. Here, we probed the ligand-binding properties of α7/α9 nAChR mutants by a proposed simple and fast calcium imaging method...
2017: PloS One
https://www.readbyqxmd.com/read/28794102/optogenetics-and-pharmacogenetics-principles-and-applications
#9
Jingwei Jiang, Huxing Cui, Kamal Rahmouni
Remote and selective spatiotemporal control of the activity of neurons to regulate behavior and physiological functions has been a long-sought goal in system neuroscience. Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin and archaerhodopsins) from the bacteria has made it possible to utilize light to artificially modulate neuronal activity, namely optogenetics. Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G-protein coupled receptors which can be activated by otherwise inert drug-like small molecules such as the Designer Receptors Exclusively Activated by Designer Drug (DREADD) - a form of chemogenetics...
August 9, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28794065/vasa-recta-pericyte-density-is-negatively-associated-with-vascular-congestion-in-the-renal-medulla-following-ischemia-reperfusion-in-rats
#10
G Ryan Crislip, Paul M O'Connor, Qingqing Wei, Jennifer C Sullivan
Recent evidence suggests that a greater density of pericytes in renal cadaveric allografts is associated with better recovery following transplant. The physiological mechanism(s) through which pericyte density may be beneficial is not well understood. The goal of this study was to test the hypothesis that lower medullary pericyte density is associated with greater renal injury following ischemia reperfusion (IR) in a rat model, providing a basis for future studies to better understand pericytes in a pathological environment...
August 9, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28792489/l-phenylalanine-modulates-gut-hormone-release-and-glucose-tolerance-and-suppresses-food-intake-through-the-calcium-sensing-receptor-in-rodents
#11
A Alamshah, E Spreckley, M Norton, J S Kinsey-Jones, A Amin, A Ramgulam, Y Cao, R Johnson, K Saleh, E Akalestou, Z Malik, N Gonzalez-Abuin, A Jomard, R Amarsi, A Moolla, P R Sargent, G W Gray, S R Bloom, K G Murphy
OBJECTIVE: High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which HPDs exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may have a role in appetite regulation and satiety. We investigated the effects of l-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents. METHODS: We investigated the effects of the aromatic amino-acid and calcium-sensing receptor (CaSR) agonist l-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal (GI) hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo...
July 13, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28790177/phosphorylation-of-the-fus-low-complexity-domain-disrupts-phase-separation-aggregation-and-toxicity
#12
Zachary Monahan, Veronica H Ryan, Abigail M Janke, Kathleen A Burke, Shannon N Rhoads, Gül H Zerze, Robert O'Meally, Gregory L Dignon, Alexander E Conicella, Wenwei Zheng, Robert B Best, Robert N Cole, Jeetain Mittal, Frank Shewmaker, Nicolas L Fawzi
Neuronal inclusions of aggregated RNA-binding protein fused in sarcoma (FUS) are hallmarks of ALS and frontotemporal dementia subtypes. Intriguingly, FUS's nearly uncharged, aggregation-prone, yeast prion-like, low sequence-complexity domain (LC) is known to be targeted for phosphorylation. Here we map in vitro and in-cell phosphorylation sites across FUS LC We show that both phosphorylation and phosphomimetic variants reduce its aggregation-prone/prion-like character, disrupting FUS phase separation in the presence of RNA or salt and reducing FUS propensity to aggregate...
August 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28783174/lysine-specific-demethylase-lsd1-regulates-autophagy-in-neuroblastoma-through-sesn2-dependent-pathway
#13
S Ambrosio, C D Saccà, S Amente, S Paladino, L Lania, B Majello
Autophagy is a physiological process, important for recycling of macromolecules and maintenance of cellular homeostasis. Defective autophagy is associated with tumorigenesis and has a causative role in chemotherapy resistance in leukemia and in solid cancers. Here, we report that autophagy is regulated by the lysine-specific demethylase LSD1/KDM1A, an epigenetic marker whose overexpression is a feature of malignant neoplasia with an instrumental role in cancer development. In the present study, we determine that two different LSD1 inhibitors (TCP and SP2509) as well as selective ablation of LSD1 expression promote autophagy in neuroblastoma cells...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28782783/poly-%C3%AE%C2%B5-caprolactone-nanocapsule-carriers-with-sustained-drug-release-single-dose-for-long-term-glaucoma-treatment
#14
Chih-Hung Lee, Yu-Jia Li, Chih-Ching Huang, Jui-Yang Lai
Glaucoma is an eye-related disease accompanied by highly elevated intraocular pressure (IOP), which causes damage to the optic nerve and results in vision loss and even blindness. Although the treatment of glaucoma with eye drops may reduce the IOP, eye drops have some limitations, such as poor patient compliance and short duration. To develop drug carriers that facilitate the sustained and long-term release of drugs for glaucoma therapy, we synthesized poly(ε-caprolactone) nanoparticles (PCL NPs) capable of loading pilocarpine, a widely used drug for the treatment of dry eye and glaucoma...
August 7, 2017: Nanoscale
https://www.readbyqxmd.com/read/28781041/advancements-in-evidence-based-anesthesia-of-exotic-animals
#15
REVIEW
Julie A Balko, Sathya K Chinnadurai
Anesthesia and sedation of pet nondomestic species are often necessary for both invasive and noninvasive procedures. Even minimally invasive procedures can be stressful for small prey species that are not domesticated or acclimated to human contact and restraint. Recent advancements in evidence-based practice will continue to improve the field based on scientifically sound best practices and rely less on anecdotal recommendations. This article focuses on new scientific literature that has been published in the past 5 years...
September 2017: Veterinary Clinics of North America. Exotic Animal Practice
https://www.readbyqxmd.com/read/28775329/transient-ingrowth-of-lymphatic-vessels-into-the-physiologically-avascular-cornea-regulates-corneal-edema-and-transparency
#16
Deniz Hos, Anne Bukowiecki, Jens Horstmann, Felix Bock, Franziska Bucher, Ludwig M Heindl, Sebastian Siebelmann, Philipp Steven, Reza Dana, Sabine A Eming, Claus Cursiefen
Lymphangiogenesis is essential for fluid homeostasis in vascularized tissues. In the normally avascular cornea, however, pathological lymphangiogenesis mediates diseases like corneal transplant rejection, dry eye disease, and allergy. So far, a physiological role for lymphangiogenesis in a primarily avascular site such as the cornea has not been described. Using a mouse model of perforating corneal injury that causes acute and severe fluid accumulation in the cornea, we show that lymphatics transiently and selectively invade the cornea and regulate the resolution of corneal edema...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28771714/multifunctional-curcumin-mediate-multitherapeutic-effects
#17
Adeeb Shehzad, Munibah Qureshi, Muhammad Nabeel Anwar, Young Sup Lee
Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases...
August 3, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28771275/latency-transition-of-plasminogen-activator-inhibitor-type-1-is-evolutionarily-conserved
#18
Agnieszka Jendroszek, Malene S Sønnichsen, Andrés C Muñoz, Kato Leyman, Anni Christensen, Steen Vang Petersen, Tobias Wang, Christian Bendixen, Frank Panitz, Peter A Andreasen, Jan K Jensen
Plasminogen activator inhibitor type 1 (PAI-1) is a central regulator of fibrinolysis and tissue remodelling. PAI-1 belongs to the serpin superfamily and unlike other inhibitory serpins undergoes a spontaneous inactivation process under physiological conditions, termed latency transition. During latency transition the solvent exposed reactive centre loop is inserted into the central β-sheet A of the molecule, and is no longer accessible to reaction with the protease. More than three decades of research on mammalian PAI-1 has not been able to clarify the evolutionary advantage and physiological relevance of latency transition...
August 3, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28771229/autophagy-couteracts-weight-gain-lipotoxicity-and-pancreatic-%C3%AE-cell-death-upon-hypercaloric-pro-diabetic-regimens
#19
Álvaro F Fernández, Clea Bárcena, Gemma G Martínez-García, Isaac Tamargo-Gómez, María F Suárez, Federico Pietrocola, Francesca Castoldi, Lorena Esteban, Elena Sierra-Filardi, Patricia Boya, Carlos López-Otín, Guido Kroemer, Guillermo Mariño
In the last years, autophagy has been revealed as an essential pathway for multiple biological processes and physiological functions. As a catabolic route, autophagy regulation by nutrient availability has been evolutionarily conserved from yeast to mammals. On one hand, autophagy induction by starvation is associated with a significant loss in body weight in mice. Here, we demonstrate that both genetic and pharmacological inhibition of the autophagy process compromise weight loss induced by starvation. Moreover, autophagic potential also impacts on weight gain induced by distinct hypercaloric regimens...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28770650/osteoblast-as-a-target-of-anti-osteoporotic-treatment
#20
Addolorata Corrado, Eliana Rita Sanpaolo, Silvana Di Bello, Francesco Paolo Cantatore
Osteoblasts are mesenchymal cells that play a key role in maintaining bone homeostasis; they are responsible for the production of extracellular matrix proteins, regulation of matrix mineralization, control of bone remodeling and regulate osteoclast differentiation. Osteoblasts have an essential role in the pathogenesis of many bone diseases, particularly osteoporosis. For many decades, the main current available treatments for osteoporosis have been represented by anti-resorptive drugs, such as bisphosphonates, which act mainly by inhibiting osteoclasts maturation, proliferation and activity; nevertheless, in recent years much attention has been paid on anabolic aspects of osteoporosis treatment...
August 3, 2017: Postgraduate Medicine
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