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anesthetic pharmacology

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https://www.readbyqxmd.com/read/28333442/photoaffinity-ligand-for-the-inhalational-anesthetic-sevoflurane-allows-mechanistic-insight-into-potassium-channel-modulation
#1
Kellie A Woll, Wesley Peng, Qiansheng Liang, Lianteng Zhi, Jack A Jacobs, Lina Maciunas, Natarajan Bhanu, Benjamin A Garcia, Manuel Covarrubias, Patrick J Loll, William P Dailey, Roderic G Eckenhoff
Sevoflurane is a commonly used inhaled general anesthetic. Despite this, its mechanism of action remains largely elusive. Compared to other anesthetics, sevoflurane exhibits distinct functional activity. In particular, sevoflurane is a positive modulator of voltage-gated Shaker-related potassium channels (Kv1.x), which are key regulators of action potentials. Here, we report the synthesis and validation of azisevoflurane, a photoaffinity ligand for the direct identification of sevoflurane binding sites in the Kv1...
March 23, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28331287/does-remifentanil-attenuate-renal-ischemia-reperfusion-injury-better-than-dexmedetomidine-in-rat-kidney
#2
E Erkılıç, E Kesimci, F Alaybeyoğlu, I Kılınç, R Tural, A Yazgan, T Gümüş, A Sepici Dinçel, E G Dumlu, O Kanbak
BACKGROUND: Ischemia-reperfusion (I/R) injury is a common cause of patient morbidity and mortality in the perioperative period. Patients undergoing long-lasting, abdominal, and urogenital surgeries with risk factors such as advanced age, peripheral artery disease, diabetes mellitus, renovascular disease, and congestive heart failure are candidates for acute kidney injury (AKI) due to impaired renal perfusion and decreased functional renal reserve. Pharmacological agents with multiple functions and anti-oxidative and anti-inflammation properties may be promising preventative strategies for AKI...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28330964/thermoregulatory-inversion-a-novel-thermoregulatory-paradigm
#3
Domenico Tupone, Georgina Cano, Shaun F Morrison
To maintain core body temperature in mammals, the normal CNS thermoregulatory reflex networks produce an increase in brown adipose tissue (BAT) thermogenesis in response to skin cooling, and an inhibition of the sympathetic outflow to BAT during skin rewarming. In contrast, these normal thermoregulatory reflexes appear to be inverted in hibernation/torpor: thermogenesis is inhibited during exposure to a cold environment, allowing dramatic reductions in core temperature and metabolism, and thermogenesis is activated during skin rewarming, contributing to a return of normal body temperature...
March 22, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28328862/postoperative-analgesia-comparing-levobupivacaine-and-ropivacaine-for-brachial-plexus-block-a-randomized-prospective-trial
#4
Kunitaro Watanabe, Joho Tokumine, Alan Kawarai Lefor, Kumi Moriyama, Hideaki Sakamoto, Tetsuo Inoue, Tomoko Yorozu
BACKGROUND: On a pharmacologic basis, levobupivacaine is expected to last longer than ropivacaine. However, most reports of these anesthetics for brachial plexus block do not suggest a difference in analgesic effect. The aim of this study is to compare the postoperative analgesic effects of levobupivacaine and ropivacaine when used for treating ultrasound-guided brachial plexus block. METHODS: A total of 62 patients undergoing orthopedic surgery procedures were prospectively enrolled and randomized to receive levobupivacaine (group L, N = 31) or ropivacaine (group R, N = 31)...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28325748/halogenated-ether-alcohol-and-alkane-anesthetics-activate-task-3-tandem-pore-potassium-channels-likely-through-a-common-mechanism
#5
Anita Luethy, James D Boghosian, Rithu Srikantha, Joseph Cotten
TASK-3 (KCNK9) tandem pore potassium channel function is activated by halogenated anesthetics through binding at a putative anesthetic binding cavity. To understand pharmacological requirements for TASK-3 activation, we studied the concentration-response of TASK-3 to several anesthetics (isoflurane, desflurane, sevoflurane, halothane, α-chloralose, 2,2,2-trichloroethanol(TCE), and chloral hydrate), to ethanol, and to a panel of halogenated methanes and alcohols. We used mutagenesis to probe the anesthetic binding cavity as observed in a TASK-3 homology model...
March 21, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28315459/dynamic-reorganization-of-intrinsic-functional-networks-in-the-mouse-brain
#6
Joanes Grandjean, Maria Giulia Preti, Thomas Aw Bolton, Michaela Buerge, Erich Seifritz, Christopher R Pryce, Dimitri Van De Ville, Markus Rudin
Functional connectivity (FC) derived from resting-state functional magnetic resonance imaging (rs-fMRI) allows for the integrative study of neuronal processes at a macroscopic level. The majority of studies to date have assumed stationary interactions between brain regions, without considering the dynamic aspects of network organization. Only recently has the latter received increased attention, predominantly in human studies. Applying dynamic FC (dFC) analysis to mice is attractive given the relative simplicity of the mouse brain and the possibility to explore mechanisms underlying network dynamics using pharmacological, environmental or genetic interventions...
March 14, 2017: NeuroImage
https://www.readbyqxmd.com/read/28301327/high-resolution-respiratory-inductive-plethysmography-in-rats-validation-in-anesthetized-conditions
#7
Timothe Flenet, Julie Fontecave-Jallon, Pierre-Yves Gumery, Charles Eynard, Francois Boucher, Pierre Baconnier, Stephane Tanguy
Respiratory monitoring is often required in experimental physiological and pharmacological studies in rodents. Currently, the mostly used techniques are direct measurement of airflow on intubated animals and whole body plethysmography. Although the reliability of these methods has been broadly demonstrated, they also have several drawbacks such as invasiveness, high cost of use or confinement of the animals. Respiratory Inductive Plethysmography (RIP) is a non-invasive technique already used in medium-sized mammals that has not yet been evaluated in small rodents...
March 16, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28298749/perioperative-considerations-and-management-of-patients-receiving-anticoagulants
#8
REVIEW
Safiya Imtiaz Shaikh, R Vasantha Kumari, Ganapati Hegade, M Marutheesh
Anticoagulants remain the primary strategy for the prevention and treatment of thrombosis. Unfractionated heparin, low molecular weight heparin (LMWH), fondaparinux, and warfarin have been studied and employed extensively with direct thrombin inhibitors typically reserved for patients with complications or those requiring interventions. Novel oral anticoagulants have emerged from clinical development and are expected to replace older agents with their ease to use and more favorable pharmacodynamic profiles...
January 2017: Anesthesia, Essays and Researches
https://www.readbyqxmd.com/read/28296541/pharmacological-modulators-of-autophagy-activate-a-parallel-noncanonical-pathway-driving-unconventional-lc3-lipidation
#9
Elise Jacquin, Stéphanie Leclerc-Mercier, Celine Judon, Emmanuelle Blanchard, Sylvie Fraitag, Oliver Florey
The modulation of canonical macroautophagy/autophagy for therapeutic benefit is an emerging strategy of medical and pharmaceutical interest. Many drugs act to inhibit autophagic flux by targeting lysosome function, while others were developed to activate the pathway. Here, we report the surprising finding that many therapeutically relevant autophagy modulators with lysosomotropic and ionophore properties, classified as inhibitors of canonical autophagy, are also capable of activating a parallel noncanonical autophagy pathway that drives MAP1LC3/LC3 lipidation on endolysosomal membranes...
February 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28293172/ethanol-modulates-the-spontaneous-complex-spike-waveform-of-cerebellar-purkinje-cells-recorded-in-vivo-in-mice
#10
Guang-Jian Zhang, Mao-Cheng Wu, Jin-Di Shi, Yin-Hua Xu, Chun-Ping Chu, Song-Biao Cui, De-Lai Qiu
Cerebellar Purkinje cells (PCs) are sensitive to ethanol, but the effect of ethanol on spontaneous complex spike (CS) activity in these cells in vivo is currently unknown. Here, we investigated the effect of ethanol on spontaneous CS activity in PCs in urethane-anesthetized mice using in vivo patch-clamp recordings and pharmacological manipulation. Ethanol (300 mM) induced a decrease in the CS-evoked pause in simple spike (SS) firing and in the amplitude of the afterhyperpolarization (AHP) under current clamp conditions...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28288780/neuroprotective-effects-of-gabaergic-phenols-correlated-with-their-pharmacological-and-antioxidant-properties
#11
Leticia Delgado-Marín, Mariela Sánchez-Borzone, Daniel A García
AIMS: Various investigations have demonstrated the protective capacity of general anesthetics as neuroprotective agents. The effects of propofol against ischemia are known to reside in its antioxidant properties and its GABAergic activity. Other aromatic alcohols have also been reported as able to protect neurons against oxidative damage. The aim of this work is to evaluate the potential neuroprotective effect of some phenols, structurally analogues of propofol, with proven GABAergic activity...
March 10, 2017: Life Sciences
https://www.readbyqxmd.com/read/28285409/pharmacological-blockade-of-small-conductance-ca-2-activated-k-channels-by-ica-reduces-arrhythmic-load-in-rats-with-acute-myocardial-infarction
#12
Laura A Hundahl, Stefan M Sattler, Lasse Skibsbye, Jonas G Diness, Jacob Tfelt-Hansen, Thomas Jespersen
Acute myocardial infarction (AMI) with development of ventricular fibrillation (VF) is a common cause of sudden cardiac death (SCD). At present, no pharmacological treatment has successfully been able to prevent VF in the acute stage of AMI. This study investigates the antiarrhythmic effect of inhibiting small conductance Ca(2+)-activated K(+) (SK) channels using the pore blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) in AMI rats. Acute coronary ligation was performed in 26 anesthetized rats, and ECG, monophasic action potentials (MAPs), and ventricular effective refractory period (vERP) were recorded...
March 11, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28284817/differential-effects-of-gaseous-versus-injectable-anesthetics-on-changes-in-regional-cerebral-blood-flow-and-metabolism-induced-by-l-dopa-in-a-rat-model-of-parkinson-s-disease
#13
Zisis Bimpisidis, Carl M Öberg, Natallia Maslava, M Angela Cenci, Cornelia Lundblad
Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [(14)C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [(14)C]-deoxyglucose) with a highly sensitive autoradiographic method...
March 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28269275/development-of-a-brain-monitoring-system-for-multimodality-investigation-in-awake-rats
#14
Kanokwan Limnuson, Raj K Narayan, Amrit Chiluwal, Chad Bouton, Ping Wang, Chunyan Li
Multimodal brain monitoring is an important approach to gain insight into brain function, modulation, and pathology. We have developed a unique micromachined neural probe capable of real-time continuous monitoring of multiple physiological, biochemical and electrophysiological variables. However, to date, it has only been used in anesthetized animals due to a lack of an appropriate interface for awake animals. We have developed a versatile headstage for recording the small neural signal and bridging the sensors to the remote sensing units for multimodal brain monitoring in awake rats...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28268237/effect-of-a-bicyclic-pyrimidine-derivative-krp-103-a-novel-selective-tachykinin-nk1-receptor-antagonist-on-bladder-function-in-guinea-pigs
#15
Asao Tanioka, Takashi Deguchi
We evaluated the pharmacological characteristics of KRP-103, chemically named as ((2-(4-acetylpiperazin-1-yl)-6-[3,5-bis(trifluorometheyl)-phenylmethyl]-4- (2-methylphenyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one), and its effects on lower urinary tract function in guinea pigs. In radioligand binding assay, KRP-103 showed higher selectivity for human NK1 receptor (hNK1R) than for human NK2 receptor (hNK2R) and human NK3 receptor (hNK3R) (Ki for hNK1R, hNK2R and hNK3R=0.126 nM, > 10 000 nM and > 10 000 nM)...
March 7, 2017: Drug Research
https://www.readbyqxmd.com/read/28267676/contrasting-regulation-of-catecholamine-neurotransmission-in-the-behaving-brain-pharmacological-insights-from-an-electrochemical-perspective
#16
REVIEW
Megan E Fox, R Mark Wightman
Catecholamine neurotransmission plays a key role in regulating a variety of behavioral and physiologic processes, and its dysregulation is implicated in both neurodegenerative and neuropsychiatric disorders. Over the last four decades, in vivo electrochemistry has enabled the discovery of contrasting catecholamine regulation in the brain. These rapid and spatially resolved measurements have been conducted in brain slices, and in anesthetized and freely behaving animals. In this review, we describe the methods enabling in vivo measurements of dopamine and norepinephrine, and subsequent findings regarding their release and regulation in intact animals...
January 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28237801/inactivation-of-the-medial-mammillary-nucleus-attenuates-theta-rhythm-activity-in-the-hippocampus-in-urethane-anesthetized-rats
#17
Witold Żakowski, Łukasz Braszka, Piotr Zawistowski, Jolanta Orzeł-Gryglewska, Edyta Jurkowlaniec
Although the importance of the mammillary body for memory and learning processes is well known, its exact role has remained vague. The fact, that many neurons in one nucleus of the mammillary body in rats, i.e. the medial mammillary nucleus (MM), fires according with hippocampal theta rhythm, makes this structure crucial for a theta rhythm signaling in so-called extended hippocampal system. These neurons are driven by descending projections from the hippocampal formation, but it is still unknown whether the mammillary body only conveys theta rhythm or may also modulate it...
February 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28227509/development-of-a-brain-monitoring-system-for-multimodality-investigation-in-awake-rats
#18
Kanokwan Limnuson, Raj K Narayan, Amrit Chiluwal, Chad Bouton, Ping Wang, Chunyan Li, Kanokwan Limnuson, Raj K Narayan, Amrit Chiluwal, Chad Bouton, Ping Wang, Chunyan Li, Chunyan Li, Ping Wang, Kanokwan Limnuson, Amrit Chiluwal, Raj K Narayan, Chad Bouton
Multimodal brain monitoring is an important approach to gain insight into brain function, modulation, and pathology. We have developed a unique micromachined neural probe capable of real-time continuous monitoring of multiple physiological, biochemical and electrophysiological variables. However, to date, it has only been used in anesthetized animals due to a lack of an appropriate interface for awake animals. We have developed a versatile headstage for recording the small neural signal and bridging the sensors to the remote sensing units for multimodal brain monitoring in awake rats...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28223123/proarrhythmia-liability-assessment-and-the-comprehensive-in-vitro-proarrhythmia-assay-cipa-an-industry-survey-on-current-practice
#19
Simon Authier, Michael K Pugsley, John E Koerner, Bernard Fermini, William S Redfern, Jean-Pierre Valentin, Hugo M Vargas, Derek J Leishman, Krystle Correll, Michael J Curtis
INTRODUCTION: The Safety Pharmacology Society (SPS) has conducted a survey of its membership to identify industry practices related to testing considered in the Comprehensive In vitro Proarrhythmia Assay (CiPA). METHODS: Survey topics included nonclinical approaches to address proarrhythmia issues, conduct of in silico studies, in vitro ion channel testing methods used, drugs used as positive controls during the conduct of cardiac ion channel studies, types of arrhythmias observed in non-clinical studies and use of the anticipated CiPA ion channel assay...
February 20, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28215996/morphological-and-behavioral-responses-of-zebrafish-after-24h-of-ketamine-embryonic-exposure
#20
Luís M Félix, Cindy Serafim, Maria J Martins, Ana M Valentim, Luís M Antunes, Manuela Matos, Ana M Coimbra
Ketamine, one anesthetic used as an illicit drug, has been detected both in freshwater and marine ecosystems. However, knowledge of its impact on aquatic life is still limited. This study aimed to test its effects in zebrafish embryos by analyzing its time- and dose-dependent developmental toxicity and long-term behavioral changes. The 24h-LC50 was calculated from percent survival using probit analysis. Based on the 24h-LC50 (94.4mgL(-1)), embryos (2hour post-fertilization - hpf) were divided into four groups, including control, and exposed for 24h to ketamine concentrations of 50, 70 or 90mgL(-1)...
February 17, 2017: Toxicology and Applied Pharmacology
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