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https://www.readbyqxmd.com/read/28915221/metformin-exerts-beneficial-effects-in-hemorrhagic-shock-in-an-ampk%C3%AE-1-independent-manner
#1
Paul Kim, Giovanna Piraino, Michael O'Connor, Paul W Hake, Vivian Wolfe, Patrick Lahni, Basilia Zingarelli
Despite therapeutic advances in hemorrhagic shock, mortality from multiple organ failure remains high. AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Two catalytic subunits, α1 and α2, have been identified, with α1 subunit largely expressed in major organs. Here, we hypothesized that genetic deficiency of AMPKα1 worsens hemorrhage-induced multiple organ failure. We also investigated whether treatment with metformin, a clinically used drug for metabolic homeostasis, affords beneficial effects...
September 14, 2017: Shock
https://www.readbyqxmd.com/read/28899928/treatment-of-hypertension-by-increasing-impaired-endothelial-trpv4-kca2-3-interaction
#2
Dongxu He, Qiongxi Pan, Zhen Chen, Chunyuan Sun, Peng Zhang, Aiqin Mao, Yaodan Zhu, Hongjuan Li, Chunxiao Lu, Mingxu Xie, Yin Zhou, Daoming Shen, Chunlei Tang, Zhenyu Yang, Jian Jin, Xiaoqiang Yao, Bernd Nilius, Xin Ma
The currently available antihypertensive agents have undesirable adverse effects due to systemically altering target activity including receptors, channels, and enzymes. These effects, such as loss of potassium ions induced by diuretics, bronchospasm by beta-blockers, constipation by Ca(2+) channel blockers, and dry cough by ACEI, lead to non-compliance with therapies (Moser, 1990). Here, based on new hypertension mechanisms, we explored a new antihypertensive approach. We report that transient receptor potential vanilloid 4 (TRPV4) interacts with Ca(2+)-activated potassium channel 3 (KCa2...
September 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28844424/analysis-of-proarrhythmic-potential-of-an-atypical-antipsychotic-drug-paliperidone-in-the-halothane-anesthetized-dogs
#3
Koki Chiba, Takeshi Wada, Yuji Nakamura, Xin Cao, Mihoko Hagiwara-Nagasawa, Hiroko Izumi-Nakaseko, Kentaro Ando, Koichiro Tanaka, Atsuhiko T Naito, Atsushi Sugiyama
Fatal cases with the use of atypical antipsychotic drug paliperidone have been reported; however, there was no clinical report describing paliperidone-induced torsade de pointes. In this study we assessed its electropharmacological effects together with its proarrhythmic potential in intravenous doses of 0.03, 0.3 and 3 mg/kg using the halothane-anesthetized dogs (n = 5), which could provide approximately 2, 20 and 200 times higher peak plasma drug concentrations than its therapeutic level, respectively...
August 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28833562/randomized-placebo-controlled-trial-of-ads-5102-amantadine-extended-release-capsules-for-levodopa-induced-dyskinesia-in-parkinson-s-disease-ease-lid-3
#4
Wolfgang Oertel, Karla Eggert, Rajesh Pahwa, Caroline M Tanner, Robert A Hauser, Claudia Trenkwalder, Reinhard Ehret, Jean Philippe Azulay, Stuart Isaacson, Larissa Felt, Mary Jean Stempien
BACKGROUND: The treatment of levodopa-induced dyskinesia in Parkinson's disease (PD) is an unmet need with no approved drug therapy. OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of 274 mg ADS-5102 (amantadine) extended-release capsules (equivalent to 340-mg amantadine HCl) for levodopa-induced dyskinesia in a randomized controlled trial. METHODS: PD patients with ≥1 hour of troublesome dyskinesia and at least mild functional impact were randomized to placebo or ADS-5102 once daily at bedtime for 13 weeks...
August 21, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28805574/nonmotor-symptoms-in-vascular-and-other-secondary-parkinsonism
#5
Oleg S Levin, Achcha Sh Chimagomedova, Natalia A Skripkina, Elena A Lyashenko, Olga V Babkina
Vascular parkinsonism (VP) is a relatively frequent variant of secondary parkinsonism caused by ischemic or hemorrhagic lesions of basal ganglia, midbrain, or their links with frontal cortex. According to different investigations, various forms of cerebrovascular disease cause 1%-15% of parkinsonism cases. Nonmotor symptoms are frequently found in VP and may negatively influence on quality of life. However, nonmotor symptoms such as hallucinations, orthostatic hypotension, REM-sleep behavior disorder, and anosmia are rarely revealed in VP, which may be noted to another diagnosis or mixed pathology...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28740895/using-low-dose-radiation-to-potentiate-the-effect-of-induction-chemotherapy-in-head-and-neck-cancer-results-of-a-prospective-phase-2-trial
#6
Susanne M Arnold, Mahesh Kudrimoti, Emily V Dressler, John F Gleason, Natalie L Silver, William F Regine, Joseph Valentino
PURPOSE: Low-dose fractionated radiation therapy (LDFRT) induces effective cell killing through hyperradiation sensitivity and potentiates effects of chemotherapy. We report our second investigation of LDFRT as a potentiator of the chemotherapeutic effect of induction carboplatin and paclitaxel in locally advanced squamous cell cancer of the head and neck (SCCHN). EXPERIMENTAL DESIGN: Two cycles of induction therapy were given every 21 days: paclitaxel (75 mg/m(2)) on days 1, 8, and 15; carboplatin (area under the curve 6) day 1; and LDFRT 50 cGy fractions (2 each on days 1, 2, 8, and 15)...
October 2016: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/28702139/ramipril-associated-cholestasis-in-the-setting-of-recurrent-drug-induced-liver-injury
#7
David Forner, Tasha Kulai, Thomas Arnason, Steven E Gruchy, Magnus MacLeod
Aim: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used to treat hypertension. Although generally well tolerated, the adverse effects of ACEIs include hypotension, cough, acute kidney injury and hyperkalemia. Rare reports of ACEI-induced hepatotoxicity have been described, most notably a cholestatic pattern of injury related to captopril. A 67-year-old male presented to the emergency department with a three-week history of jaundice, pruritis and weakness. Eight weeks before, he began taking ramipril and clopidogrel...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28684143/what-s-new-in-clinical-obstetric-anesthesia-in-2015
#8
REVIEW
P E Hess
Each calendar year the Society for Obstetric Anesthesia and Perinatology invites an individual to conduct a review of the medical literature, identifying clinically relevant publications of interest to the obstetric anesthesia provider. This report of that effort covers the publications from 2015 and includes the categories of anesthesia and analgesia, complications of neuraxial procedures, and the effects of anesthesia on the fetus. Neuraxial procedures represent the foundation of obstetric anesthesia; advances in anesthesia and analgesia include novel modes of administration, and refinements in care of the medically complex patient...
March 18, 2017: International Journal of Obstetric Anesthesia
https://www.readbyqxmd.com/read/28669088/vasovagal-syncope-with-asystole-the-role-of-cardiac-pacing
#9
REVIEW
Michele Brignole, Marco Tomaino, Alessio Gargaro
Whereas cardiac pacing has a very limited role overall in patients with vasovagal syncope (VVS), there are three reasons which support pacing efficacy in tilt-induced asystolic VVS. These are: (1) contrary to mixed and vasodepressor forms, an asystolic tilt response is specific, i.e., diagnostic, of VVS and is unlikely to occur in control patients without history of syncope and in patients with cardiac syncope; (2) contrary to mixed and vasodepressor forms, an asystolic tilt response predicts a similar asystolic event during prolonged ECG monitoring with a positive predictive value of 86%; (3) the available evidence from trials supports the efficacy of dual-chamber pacing with a low recurrence rate of syncope after pacing ranging from 6% up to 23% during 3 years of follow-up...
August 2017: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
https://www.readbyqxmd.com/read/28666833/ludwigia-octovalvis-extract-improves-glycemic-control-and-memory-performance-in-diabetic-mice
#10
Wei-Sheng Lin, Jung-Hsin Lo, Jo-Hsuan Yang, Hao-Wei Wang, Shou-Zen Fan, Jui-Hung Yen, Pei-Yu Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Ludwigia octovalvis (Jacq.) P.H. Raven (Onagraceae) extracts have historically been consumed as a healthful drink for treating various conditions, including edema, nephritis, hypotension and diabetes. AIM OF THE STUDY: We have previously shown that Ludwigia octovalvis extract (LOE) can significantly extend lifespan and improve age-related memory deficits in Drosophila melanogaster through activating AMP-activated protein kinase (AMPK)...
June 27, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28625302/pharmacogenetics-in-obstetric-anesthesia
#11
REVIEW
Ruth Landau, Richard Smiley
The 21st century has been billed as the era of "precision/personalized medicine." Genetic investigation of clinical syndromes may guide therapy as well as reveal previously unknown biological or pharmacological pathways that may result in novel drug therapies. Several clinical issues in obstetrics and obstetric anesthesiology have been targets for genetic investigations. These include evaluation of the genetic effects on preterm labor and the progression of labor, spinal anesthesia-induced hypotension and the response to medications used to treat hypotension, and the effect of gene variants on pain and analgesic responses...
March 2017: Best Practice & Research. Clinical Anaesthesiology
https://www.readbyqxmd.com/read/28602247/different-clinical-features-of-anaphylaxis-according-to-cause-and-risk-factors-for-severe-reactions
#12
Sang-Yoon Kim, Min-Hye Kim, Young-Joo Cho
BACKGROUND: Anaphylaxis is a life-threatening allergic reaction. Several studies reported different anaphylactic reactions according to the causative substances. However, a comparison of anaphylaxis for each cause has not been done. This study was conducted to identify common causes of anaphylaxis, characteristics of anaphylactic reaction for each cause and to analyze the factors related to the severity of the reaction. METHODS: Medical records of patients who visited the emergency room of Ewha Womans University Mokdong Hospital from March 2003 to April 2016 and diagnosed with anaphylactic shock were retrospectively reviewed...
June 8, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28590439/reclassifying-anaphylaxis-to-neuromuscular-blocking-agents-based-on-the-presumed-patho-mechanism-ige-mediated-pharmacological-adverse-reaction-or-innate-hypersensitivity
#13
REVIEW
David Spoerl, Haig Nigolian, Christoph Czarnetzki, Thomas Harr
Approximately 60% of perioperative anaphylactic reactions are thought to be immunoglobulin IgE mediated, whereas 40% are thought to be non-IgE mediated hypersensitivity reactions (both considered non-dose-related type B adverse drug reactions). In both cases, symptoms are elicited by mast cell degranulation. Also, pharmacological reactions to drugs (type A, dose-related) may sometimes mimic symptoms triggered by mast cell degranulation. In case of hypotension, bronchospasm, or urticarial rash due to mast cell degranulation, identification of the responsible mechanism is complicated...
June 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28588484/akrinor-tm-a-cafedrine-theodrenaline-mixture-20-1-increases-force-of-contraction-of-human-atrial-myocardium-but-does-not-constrict-internal-mammary-artery-in-vitro
#14
Benjamin Kloth, Simon Pecha, Eileen Moritz, Yvonne Schneeberger, Klaus-Dieter Söhren, Edzard Schwedhelm, Hermann Reichenspurner, Thomas Eschenhagen, Rainer H Böger, Torsten Christ, Sebastian N Stehr
Background: Intraoperative hypotension is a common problem and direct or indirect sympathomimetic drugs are frequently needed to stabilize blood pressure. Akrinor(TM) consists of the direct and the indirect sympathomimetic noradrenaline and norephedrine. Both substances are covalently bound to the phosphodiesterase (PDE) inhibitor theophylline, yielding theodrenaline and cafedrine, respectively. We investigated pharmacodynamic effects of Akrinor(TM) and its constituents on contractile force and tension in human atrial trabeculae and internal A...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28572638/mitochondrial-targeting-by-dichloroacetate-improves-outcome-following-hemorrhagic-shock
#15
Kumar Subramani, Sumin Lu, Marie Warren, Xiaogang Chu, Haroldo A Toque, R William Caldwell, Michael P Diamond, Raghavan Raju
Hemorrhagic shock is a leading cause of death in people under the age of 45 and accounts for almost half of trauma-related deaths. In order to develop a treatment strategy based on potentiating mitochondrial function, we investigated the effect of the orphan drug dichloroacetate (DCA) on survival in an animal model of hemorrhagic shock in the absence of fluid resuscitation. Hemorrhagic shock was induced in rats by withdrawing 60% of the blood volume and maintaining a hypotensive state. The studies demonstrated prolonged survival of rats subjected to hemorrhagic injury (HI) when treated with DCA...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28564654/high-dose-cannabidiol-induced-hypotension-after-global-hypoxia-ischemia-in-piglets
#16
Håvard T Garberg, Rønnaug Solberg, Jon Barlinn, Jose Martinez-Orgado, Else-Marit Løberg, Ola Didrik Saugstad
BACKGROUND: Cannabidiol (CBD) is considered a promising neuroprotectant after perinatal hypoxia-ischemia (HI). We have previously studied the effects of CBD 1 mg/kg in the early phase after global HI in piglets. In contrast to prior studies, we found no evidence of neuroprotection and hypothesized that higher doses might be required to demonstrate efficacy in this animal model. OBJECTIVE: To assess the safety and potential neuroprotective effects of high-dose CBD...
2017: Neonatology
https://www.readbyqxmd.com/read/28541755/epinephrine-but-not-vasopressin-attenuates-the-airway-response-to-anaphylactic-shock-in-rats
#17
Feng Zheng, Ruxandra Copotoiu, Charles Tacquard, Bruno Demoulin, Jean Marc Malinovsky, Bruno Levy, Dan Longrois, Grégoire Barthel, Paul Michel Mertes, François Marchal, Silvia Demoulin-Alexikova, Olivier Collange
PURPOSE: The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall. AIM OF THE STUDY: To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS...
April 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28539561/predictors-of-mortality-rehospitalization-for-syncope-and-cardiovascular-events-in-patients-with-cardiovascular-syncope
#18
Tatsuya Onuki, Makoto Shoji, Yuya Nakamura, Ko Ogawa, Akinori Ochi, Koichiro Inokuchi, Shiro Kawasaki, Yoshimi Onishi, Yoshimasa Onuma, Yumi Munetsugu, Miwa Kikuchi, Hiroyuki Ito, Yoshino Minoura, Norikazu Watanabe, Taro Adachi, Mitsuharu Kawamura, Taku Asano, Kaoru Tanno, Youichi Kobayashi
BACKGROUND: Predictors of poor outcomes remain unknown for cardiovascular syncope patients after discharge.Methods and Results:We reviewed the medical records of consecutive patients admitted to hospital with cardiovascular syncope. We then performed Cox stepwise logistic regression analysis to identify significant independent factors for death, rehospitalization for syncope, and cardiovascular events. The study group was 206 patients with cardiovascular syncope. Of them, bradycardia was diagnosed in 50%, tachycardia in 27%, and structural disease in 23%...
May 25, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28501080/intravenous-contrast-induced-nephropathy-the-rise-and-fall-of-a-threatening-idea
#19
REVIEW
Lyndon Luk, Jonathan Steinman, Jeffrey H Newhouse
Contrast-induced nephropathy (CIN) has been considered to be a cause of renal failure for over 50 years, but careful review of past and recent studies reveals the risks of CIN to be overestimated. Older studies frequently cited the use of high-osmolality contrast media, which have since been replaced by low-osmolality contrast media, which have lower risks for nephropathy. In addition, literature regarding CIN typically describes the incidence following cardiac angiography, whereas the risk of CIN from intravenous injection is much lower...
May 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/28489728/novel-adjunct-drugs-reverse-endothelial-glycocalyx-damage-after-hemorrhagic-shock-in-rats
#20
Ivo P Torres Filho, Luciana N Torres, Christi Salgado, Michael A Dubick
INTRODUCTION: There is interest in the small-volume therapeutic use of adjunct drugs for treating hemorrhagic shock (HS). However, critical information is only partially available on mechanisms of action of promising compounds such as adenosine-lidocaine-Magnesium (ALM), beta-hydroxybutyrate plus melatonin (BHB/M), and poloxamer 188 (P-188). Therefore, we tested the hypothesis that these adjuncts would reverse HS-induced damage to microvascular endothelial glycocalyx and hemodynamics...
May 9, 2017: Shock
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