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Pharmacology and physiology

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https://www.readbyqxmd.com/read/29793210/polypharmacological-profile-of-1-2-dihydro-2-oxo-pyridine-3-carboxamides-in-the-endocannabinoid-system
#1
Andrea Chicca, Chiara Arena, Simone Bertini, Francesca Gado, Elena Ciaglia, Mario Abate, Maria Digiacomo, Margherita Lapillo, Giulio Poli, Maurizio Bifulco, Marco Macchia, Tiziano Tuccinardi, Jürg Gertsch, Clementina Manera
The endocannabinoid system (ECS) represents one of the major neuromodulatory systems involved in different physiological and pathological processes. Multi-target compounds exert their activities by acting via multiple mechanisms of action and represent a promising pharmacological modulation of the ECS. In this work we report 4-substituted and 4,5-disubstituted 1,2-dihydro-2-oxo-pyridine-3-carboxamide derivatives with a broad spectrum of affinity and functional activity towards both cannabinoid receptors and additional effects on the main components of the ECS...
May 14, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29792024/metabotropic-glutamate-receptors-in-alcohol-use-disorder-physiology-plasticity-and-promising-pharmacotherapies
#2
Max E Joffe, Samuel W Centanni, Anel A Jaramillo, Danny G Winder, P Jeffrey Conn
Developing efficacious treatments for alcohol use disorder (AUD) has proven difficult. The insidious nature of the disease necessitates a deep understanding of its underlying biology as well as innovative approaches to ameliorate ethanol-related pathophysiology. Excessive ethanol-seeking and relapse are generated by long-term changes to membrane properties, synaptic physiology, and plasticity throughout the limbic system and associated brain structures. Each of these factors can be modulated by metabotropic glutamate (mGlu) receptors, a diverse set of G protein-coupled receptors highly expressed throughout the central nervous system...
May 23, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29789529/inhibiting-p38-mapk-alpha-rescues-axonal-retrograde-transport-defects-in-a-mouse-model-of-als
#3
Katherine L Gibbs, Bernadett Kalmar, Elena R Rhymes, Alexander D Fellows, Mahmood Ahmed, Paul Whiting, Ceri H Davies, Linda Greensmith, Giampietro Schiavo
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the degeneration of upper and lower motor neurons. Defects in axonal transport have been observed pre-symptomatically in the SOD1G93A mouse model of ALS, and have been proposed to play a role in motor neuron degeneration as well as in other pathologies of the nervous system, such as Alzheimer's disease and hereditary neuropathies. In this study, we screen a library of small-molecule kinase inhibitors towards the identification of pharmacological enhancers of the axonal retrograde transport of signalling endosomes, which might be used to normalise the rate of this process in diseased neurons...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29786646/metabolic-reprogramming-by-3-iodothyronamine-t1am-a-new-perspective-to-reverse-obesity-through-co-regulation-of-sirtuin-4-and-6-expression
#4
Fariba M Assadi-Porter, Hannah Reiland, Martina Sabatini, Leonardo Lorenzini, Vittoria Carnicelli, Micheal Rogowski, Ebru S Selen Alpergin, Marco Tonelli, Sandra Ghelardoni, Alessandro Saba, Riccardo Zucchi, Grazia Chiellini
Obesity is a complex disease associated with environmental and genetic factors. 3-Iodothyronamine (T1AM) has revealed great potential as an effective weight loss drug. We used metabolomics and associated transcriptional gene and protein expression analysis to investigate the tissue specific metabolic reprogramming effects of subchronic T1AM treatment at two pharmacological daily doses (10 and 25 mg/kg) on targeted metabolic pathways. Multi-analytical results indicated that T1AM at 25 mg/kg can act as a novel master regulator of both glucose and lipid metabolism in mice through sirtuin-mediated pathways...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29785199/physical-exercise-for-parkinson-s-disease-clinical-and-experimental-evidence
#5
REVIEW
Alessandro Oliveira de Carvalho, Alberto Souza Sá Filho, Eric Murillo-Rodriguez, Nuno Barbosa Rocha, Mauro Giovanni Carta, Sergio Machado
Background: National projections about the increase in the elderly population over 60 years bring with it an increase in the number of people affected by Parkinson's Disease (PD), making it an important public health problem. Therefore, the establishment of effective strategies for intervention in people with PD needs to be more clearly investigated. Objective: The study aimed to report the effectiveness of exercise on functional capacity and neurobiological mechanisms in people with PD...
2018: Clinical Practice and Epidemiology in Mental Health: CP & EMH
https://www.readbyqxmd.com/read/29783840/discovery-of-melanocortin-ligands-via-a-double-simultaneous-substitution-strategy-based-on-the-ac-his-dphe-arg-trp-nh-2-template
#6
Aleksandar Todorovic, Cody J Lensing, Jerry Ryan Holder, Joseph W Scott, Nicholas B Sorensen, Carrie Haskell-Luevano
The melanocortin system regulates an array of diverse physiological functions including pigmentation, feeding behavior, energy homeostasis, cardiovascular regulation, sexual function, and steroidogenesis. Endogenous melanocortin agonist ligands all possess the minimal messaging tetrapeptide sequence His-Phe-Arg-Trp. Based on this endogenous sequence, the Ac-His1-DPhe2-Arg3-Trp4-NH2 tetrapeptide has previously been shown to be a useful scaffold when utilizing traditional positional scanning approaches to modify activity at the various melanocortin receptors (MC1-5R)...
May 21, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29783282/sustained-conduction-of-vasomotor-responses-in-rat-mesenteric-arteries-in-a-two-compartment-in-vitro-setup
#7
Teresa Palao, Angela van Weert, Anne de Leeuw, Judith de Vos, Erik N T P Bakker, Ed van Bavel
AIM: Conduction of vasomotor responses may contribute to long-term regulation of resistance artery function and structure. Most previous studies have addressed conduction of vasoactivity only during very brief stimulations. We developed a novel setup that allows the local pharmacological stimulation of arteries in vitro for extended periods of time, and studied the conduction of vasomotor responses in rat mesenteric arteries under those conditions. METHODS: The new in vitro set up was based on the pressure myograph...
May 21, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29782843/role-of-nutritional-vitamin-d-in-osteoporosis-treatment
#8
REVIEW
Yi-Chou Hou, Chia-Chao Wu, Min-Tser Liao, Jia-Fwu Shyu, Chi-Feng Hung, Tzung-Hai Yen, Chien-Lin Lu, Kuo-Cheng Lu
Osteoporosis is a systemic skeletal disorder characterized by a decrease in bone mass and microarchitectural deterioration of bone tissue. The World Health Organization has defined osteoporosis as a decrease in bone mass (50%) and bony quality (50%). Vitamin D, a steroid hormone, is crucial for skeletal health and in mineral metabolism. Its direct action on osteoblasts and osteoclasts and interaction with nonskeletal tissues help in maintaining a balance between bone turnover and bone growth. Vitamin D affects the activity of osteoblasts, osteoclasts, and osteocytes, suggesting that it affects bone formation, bone resorption, and bone quality...
May 18, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29782651/pharmacokinetic-and-metabolism-studies-of-bavachinin-through-ultra-high-performance-liquid-chromatography-coupled-with-electrospray-ionization-tandem-mass-spectrometry
#9
Jun Qian, Fan Xie, Yanhong Shi, Jinhang Li, Liuqiang Zhang, Yiming Li, Fujiang Guo, Rui Wang
Bavachinin (BVC), one of the main bioactive prenylated flavonoids derived from Psoralea corylifolia Linn, has a wide variety of pharmacological effects, such as antiangiogenic, antitumour, antiallergic, anti-inflammatory, and antibacterial activities, especially as a pan-peroxisome proliferator-activated receptors (PPARs) agonist. A rapid and sensitive method for quantifying BVC in rat plasma was developed and validated through ultra-high-performance liquid chromatography coupled with electrospray-ionization tandem mass spectrometry...
May 21, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29782001/a-simple-and-reproducible-method-to-prepare-membrane-samples-from-freshly-isolated-rat-brain-microvessels
#10
Hrvoje Brzica, Wazir Abdullahi, Bianca G Reilly, Patrick T Ronaldson
The blood-brain barrier (BBB) is a dynamic barrier tissue that responds to various pathophysiological and pharmacological stimuli. Such changes resulting from these stimuli can greatly modulate drug delivery to the brain and, by extension, cause considerable challenges in the treatment of central nervous system (CNS) diseases. Many BBB changes that affect pharmacotherapy, involve proteins that are localized and expressed at the level of endothelial cells. Indeed, such knowledge on BBB physiology in health and disease has sparked considerable interest in the study of these membrane proteins...
May 7, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29778216/nitric-oxide-signalling-in-yeast
#11
Rika I Astuti, Ryo Nasuno, Hiroshi Takagi
Nitric oxide (NO) is a cellular signalling molecule widely conserved among organisms, including microorganisms such as bacteria, yeasts, and fungi, and higher eukaryotes such as plants and mammals. NO is mainly produced by the activities of NO synthase (NOS) or nitrite reductase (NIR). There are several NO detoxification systems, including NO dioxygenase (NOD) and S-nitrosoglutathione reductase (GSNOR). NO homeostasis, based on the balance between NO synthesis and degradation, is important for regulating its physiological functions, since an excess of NO causes nitrosative stress due to the high reactivity of NO and NO-derived compounds...
2018: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/29775644/redox-signal-mediated-trpm2-promotes-ang-ii-induced-adipocyte-insulin-resistance-via-ca-2-dependent-camkii-jnk-cascade
#12
Min Gao, Yu Du, Jing-Wen Xie, Jing Xue, Yi-Ting Wang, Li Qin, Ming-Ming Ma, Yong-Bo Tang, Xiao-Yan Li
BACKGROUND AND OBJECTIVE: Redox-sensitive transient receptor potential melastatin 2 (TRPM2) is a Ca2+ -permeable, nonselective cation channel which plays a crucial role in various physiological processes. However, little is known whether TRPM2 is involved in adipocyte dysfunction during hypertension. In the present study, we determined the role of TRPM2 in angiotensin II (Ang II)-induced insulin resistance in adipocytes and the underlying mechanisms. METHODS: Ang II-induced adipocyte insulin resistant model was conducted...
May 15, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29774530/cardiomyocyte-programmed-necrosis-mitochondria-death-receptor-and-beyond
#13
REVIEW
Junxia Zhang, Dairu Liu, Mao Zhang, Yan Zhang
Excessive death of cardiac myocytes leads to multiple cardiac diseases, including myocardial infarction, arrhythmia, heart failure and sudden cardiac death. For the last several decades, most work on cell death has focused on apoptosis, which is generally considered as the only form of regulated cell death, whereas necrosis has been regarded to be an unregulated process. Recent findings reveal that necrosis also occurs in a regulated manner and that it is closely related to the physiology and pathophysiology of multiple organs, including the heart...
May 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29773053/editorial-new-mechanisms-of-gi-ulceration-healing-physiology-pharmacology-pathology
#14
EDITORIAL
Predrag Sikiric
No abstract text is available yet for this article.
May 17, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29772453/the-roles-of-cypa-and-cd147-in-cardiac-remodelling
#15
REVIEW
Hongyan Su, Yi Yang
Cyclophilin A (CyPA), an abundantly expressed protein belonging to the immunophilin family, is involved in a variety of physiological and pathological activities together with its extracellular receptor, CD147. Many studies have provided compelling evidence supporting critical roles of CyPA in immune and infectious diseases and malignant tumours. Recent studies have revealed that both CyPA and CD147 strongly promote cardiovascular inflammation, myocardial ischaemia-reperfusion injury, and myocardial remodelling processes...
May 14, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29770207/recent-advances-in-bioreactors-for-cell-based-therapies
#16
REVIEW
Makeda Stephenson, Warren Grayson
Bioreactors have become indispensable tools in the cell-based therapy industry. Various forms of bioreactors are used to maintain well-controlled microenvironments to regulate cell growth, differentiation, and tissue development. They are essential for providing standardized, reproducible cell-based products for regenerative medicine applications or to establish physiologically relevant in vitro models for testing of pharmacologic agents. In this review, we discuss three main classes of bioreactors: cell expansion bioreactors, tissue engineering bioreactors, and lab-on-a-chip systems...
2018: F1000Research
https://www.readbyqxmd.com/read/29767351/evaluating-the-methods-used-for-measuring-cerebral-blood-flow-at-rest-and-during-exercise-in-humans
#17
REVIEW
Michael M Tymko, Philip N Ainslie, Kurt J Smith
The first accounts of measuring cerebral blood flow (CBF) in humans were made by Angelo Mosso in ~1880, who recorded brain pulsations in patients with skull defects. In 1890, Charles Roy and Charles Sherrington determined in animals that brain pulsations-assessed via a similar method used by Mosso-were altered during a variety of stimuli including sensory nerve stimulation, asphyxia, and pharmacological interventions. Between 1880 and 1944, measurements for CBF were typically relied on skull abnormalities in humans...
May 16, 2018: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/29767077/strategies-and-challenges-to-increase-the-precision-in-feeding-zinc-to-monogastric-livestock
#18
REVIEW
Daniel Brugger, Wilhelm M Windisch
Practical diets for monogastric livestock must be supplemented with zinc (Zn) due to their high contents of antagonistic substances like phytates. Current feeding recommendations include quite generous safety margins because of uncertainties regarding the gross Zn requirements under varying rearing conditions. Furthermore, the use of pharmacological Zn doses to stabilise animal performance and wellbeing is widespread. Taken together, modern diets for pigs and poultry contain considerably more Zn than necessary to meet animal requirements, which is associated with concerns related to the environment as well as animal and consumer safety...
June 2017: Animal nutrition
https://www.readbyqxmd.com/read/29762383/starch-tolerance-and-the-short-bowel
#19
Jan de Laffolie, Hassan Y Naim, Silvia Rudloff, Klaus-Peter Zimmer
Short bowel syndrome with intestinal failure is a rare disease with a massive impairment in quality of life, requiring a multidisciplinary team approach to medical, surgical, and nutritional therapy. Current pharmacological and surgical therapeutic options are limited; an important cornerstone is enteral and parenteral nutrition. The changed physiology of carbohydrate digestion plays a major role in the adaptation process and can be a target for specific enteral nutrition interventions. An important prognostic factor is the preservation of at least portions of the colon in continuity with small bowel...
June 2018: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29762011/strategies-toward-organic-carbon-monoxide-prodrugs
#20
Xingyue Ji, Binghe Wang
Carbon monoxide is widely acknowledged as an important gasotransmitter in the mammalian system with importance on par with that of nitric oxide. It has also been firmly established as a potential therapeutic agent with a wide range of indications including organ transplantation, cancer, bacterial infection, and inflammation-related conditions such as colitis and sepsis. One major issue in developing CO based therapeutics is its delivery in a pharmaceutically acceptable form. Currently, there are generally five forms of deliveries: inhaled CO, photosensitive CO-releasing molecules, encapsulated CO, CO dissolved in drinks, and molecules that would release CO under physiological conditions without the need for light...
May 15, 2018: Accounts of Chemical Research
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