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Ischemic tolerance

Wojciech Kosmala, Aleksandra Rojek, Monika Przewlocka-Kosmala, Leah Wright, Andrzej Mysiak, Thomas H Marwick
BACKGROUND: Impaired functional capacity is a hallmark of patients with heart failure with preserved ejection fraction (HFpEF). Despite the association of HFpEF with reduced myocardial compliance attributed to fibrosis, spironolactone has not been shown to alter outcomes-perhaps reflecting the heterogeneity of underlying pathological mechanisms. OBJECTIVES: The authors sought to identify improvement in exercise capacity with spironolactone in the subset of patients with HFpEF with exercise-induced increase in ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') reflecting elevation of left ventricular (LV) filling pressure...
October 25, 2016: Journal of the American College of Cardiology
Yoshihiro Kokubo
Hypertension is one of the strongest risk factor for cardiovascular disease. Recently, accumulating evidence also indicates that hypertension has been linked with non-cardiovascular diseases including dementia, cancer, oral health diseases and so on. In general, elderly individuals tend to have multiple diseases as getting older. Preventing of hypertension is also benefit for other diseases.In the Hisayama Study, hypertension increased the risk of vascular dementia, but were not associated with an increased risk of Alzheimer disease, and that subjects with hypertension in midlife and normotension and hypertension in late-life increased risks of incident vascular dementia...
September 2016: Journal of Hypertension
Kendra M Cherry-Allen, Jeff M Gidday, Jin-Moo Lee, Tamara Hershey, Catherine E Lang
The authors tested whether 2 doses of remote limb ischemic conditioning (RLIC), induced via blood pressure cuff inflation, enhanced motor and cognitive learning to an equal extent, and explored a panel of blood biomarkers of RLIC. Thirty-two young adults were randomized to 3 groups and underwent a 7-day protocol of RLIC/sham followed by motor and cognitive training, with follow-up. Both RLIC groups had greater motor learning and a trend toward greater cognitive learning compared with the sham group. RLIC at the lower inflation pressure was as effective as RLIC with the higher inflation pressure...
October 12, 2016: Journal of Motor Behavior
Peter H Jones, Harold E Bays, Umesh Chaudhari, Robert Pordy, Christelle Lorenzato, Kathryn Miller, Jennifer G Robinson
Previous individual trials of alirocumab (a PCSK9 monoclonal antibody) showed significant low-density lipoprotein cholesterol reductions with overall treatment-emergent adverse event (TEAE) rates comparable with controls. This analysis evaluated safety data from 14 trials (4 phase 2 and 10 phase 3, 8 to 104 weeks; n = 5,234), in 2 pools according to control (placebo/ezetimibe). Overall, 3,340 patients received alirocumab (4,029 patient-years' exposure), 1,276 received placebo, and 618 received ezetimibe. Incidence of deaths, serious TEAEs, discontinuations because of TEAEs, and overall TEAEs were similar between alirocumab and control groups...
September 14, 2016: American Journal of Cardiology
Gian Marco Rosa, Daniele Bianco, Alberto Valbusa, Laura Massobrio, Francesco Chiarella, Claudio Brunelli
After acute coronary syndromes (ACS), the so-called dual antiplatelet therapy (DAPT), which usually consists of low-dose of aspirin in combination with a thienopyridine (clopidogrel, prasugrel) or with a cyclopentyltriazolopyrimidine (ticagrelor), reduces the risk of ischemic events. Ticagrelor, un particular, is an effective drug as it isn' a prodrug, doesn't require metabolic activation and demonstrates a rapid onset and faster offset of action. Areas covered: This article evaluates the pharmacokinetics, efficacy, safety and tolerability of ticagrelor during DAPT after ACS and its potential use beyond the canonical twelve months after PCI...
October 7, 2016: Expert Opinion on Drug Metabolism & Toxicology
Daniel O'Dea, Jacqueline Whetteckey, Naitee Ting
INTRODUCTION: In the pivotal RE-LY trial, dabigatran etexilate (DE) at the dose of 150-mg twice daily (BID), significantly reduced total stroke and ischemic stroke compared with warfarin in patients with non-valvular atrial fibrillation (NVAF), while the 110-mg BID dose had efficacy equivalent to warfarin, and major bleeds were significantly reduced. Both DE regimens were generally well tolerated; however, approximately 4% of the patients discontinued treatment with DE due to gastrointestinal (GI) discomfort...
October 5, 2016: Cardiology and Therapy
P P Tregub, N A Malinovskaya, V P Kulikov, A B Salmina, M E Nagibaeva, A S Zabrodina, G E Gertsog, S K Antonova
We compared the intensity of apoptosis in the peri-infarction area of the brain after isolated and combined exposure to hypoxia and hypercapnia prior to focal ischemic stroke modeling. Hypoxia and hypercapnia reduced the number of TUNEL-positive cells in the peri-infarction area, and their combination was most effective in comparison with effects of isolated exposures. The maximum neuroprotective effect of combined exposure to hypoxia and hypercapnia in comparison with isolated exposures was determined by inhibition of apoptosis in the peri-infarction zone...
September 2016: Bulletin of Experimental Biology and Medicine
Petra Bonova, Miroslava Nemethova, Milina Matiasova, Martin Bona, Miroslav Gottlieb
Ischemic tolerance (IT) has gained attention as an attractive strategy for improving stroke outcome. Recently, it was shown that signal responsible for rapid IT induction (tolerance induction factor- TIF) is transmitted via circulating blood. In the present paper, we have hypothesized about the role of the blood cell compartment in TIF production. We used hind limb ischemia to generate TIF as a rapid preconditioning against transient middle cerebral artery occlusion (MCAO). The essential properties of protein synthesis inhibitors actinomycin D and cycloheximide were utilized to obtain the following results: 1...
October 5, 2016: European Journal of Neuroscience
Tony Chung Tung Lo, Stephen Tung Yeung, Sujin Lee, Kira Skavinski, Solomon Liao
OBJECTIVE: Ehlers-Danlos syndrome frequently causes acute and chronic pain because of joint subluxations and dislocations secondary to hypermobility. Current treatments for pain related to Ehlers-Danlos syndrome and central pain syndrome are inadequate. This case report discusses the therapeutic use of ketamine intravenous infusion as an alternative. CASE REPORT: A 27-year-old Caucasian female with a history of Ehlers-Danlos syndrome and spinal cord ischemic myelopathy resulting in central pain syndrome, presented with severe generalized body pain refractory to multiple pharmacological interventions...
2016: Journal of Pain Research
Hee Jun Kim, Gee Su Yang, Joel D Greenspan, Katherine D Downton, Kathleen A Griffith, Cynthia L Renn, Meg Johantgen, Susan G Dorsey
Our objective was to describe the racial and ethnic differences in experimental pain sensitivity. Four databases (PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO) were searched for studies examining racial/ethnic differences in experimental pain sensitivity. Thermal-heat, cold-pressor, pressure, ischemic, mechanical cutaneous, electrical, and chemical experimental pain modalities were assessed. Risk of bias was assessed using the Agency for Healthcare Research and Quality guideline...
September 24, 2016: Pain
Étienne Ojardias, Oscar Azeo, Diana Rimaud, Pascal Giraux
OBJECTIVE: Transcortical direct current stimulation (tDCS) is an emerging technique in the rehabilitation of hemiplegic patients after stroke, and has been mainly evaluated for the upper limb. The feasibility and tolerance of the use of repeated stimulations on the lower limb motor cortex require a clinical evaluation. OBSERVATIONS: A 72-year-old patient, who suffered from a first ischemic stroke in the left middle cerebral artery area, on July 2015, was admitted, 6 months post-stroke, to the PRM outpatient clinic of the university hospital of Saint-Étienne, for a motor training program combined with iterative tDCS stimulations...
September 2016: Annals of Physical and Rehabilitation Medicine
C Michael Gibson, Serge Korjian, Pierluigi Tricoci, Yazan Daaboul, John H Alexander, Philippe G Steg, A Michael Lincoff, John J P Kastelein, Roxana Mehran, Denise D'Andrea, Bela Merkely, Maciej Zarebinski, Ton Oude Ophius, Robert A Harrington
BACKGROUND: Despite aggressive pharmacotherapy and stenting, there is a residual risk of major adverse cardiovascular events among patients with acute coronary syndrome. High-density lipoprotein (HDL) has been a major target for secondary acute coronary syndrome prevention; however, a better understanding of the physiologic function of HDL has demonstrated that a high cholesterol efflux capacity, rather than high HDL concentrations alone, may be critical to improving outcomes. CSL112, a reconstituted, infusible human apolipoprotein A-I, has been demonstrated to increase cholesterol efflux capacity and to have a protective effect in experimental models of atherosclerotic cardiovascular disease...
October 2016: American Heart Journal
R Polignano, C Baggiore, F Falciani, U Restelli, N Troisi, S Michelagnoli, G Panigada, S Tatini, A Farina, G Landini
OBJECTIVE: Intravenous iloprost is an important option in the treatment of ischemic disease of the lower limbs; however, the administration of therapy is frequently compromised because of the need for long cycles of infusion in a hospital setting. The aim of the study is to evaluate the efficacy, safety, feasibility, and the economic impact of infusion therapy in the outpatient setting. PATIENTS AND METHODS: Twenty-four consecutive patients were treated with iloprost at their homes where they were administered a slow rate of infusion for 24 hours a day, during 9...
September 2016: European Review for Medical and Pharmacological Sciences
Yoshihiro Kokubo
Hypertension is one of the strongest risk factor for cardiovascular disease. Recently, accumulating evidence also indicates that hypertension has been linked with non-cardiovascular diseases including dementia, cancer, oral health diseases and so on. In general, elderly individuals tend to have multiple diseases as getting older. Preventing of hypertension is also benefit for other diseases.In the Hisayama Study, hypertension increased the risk of vascular dementia, but were not associated with an increased risk of Alzheimer disease, and that subjects with hypertension in midlife and normotension and hypertension in late-life increased risks of incident vascular dementia...
September 2016: Journal of Hypertension
S Wolf, N Hainz, A Beckmann, C Maack, M D Menger, T Tschernig, C Meier
Perinatal hypoxia is a critical complication during delivery and is mostly studied in animal models of postnatal hypoxic-ischemic brain injury. We here studied the effects of postnatal hypoxic-ischemic brain injury in two different sub-strains of C57BL/6 mice, i.e. C57BL/6J and C57BL/6N mice. These two sub-strains show different metabolic properties, for instance an impaired glucose tolerance in C57BL/6J mice. Genetically, this was linked to differences in their nicotinamide nucleotide transhydrogenase (Nnt) genes: In C57BL/6J mice, exons 7-11 of the Nnt gene are deleted, resulting in the absence of functional Nnt protein...
November 1, 2016: Brain Research
Angela E Rankine-Mullings, Courtney R Little, Marvin E Reid, Deanne P Soares, Carolyn Taylor-Bryan, Jennifer M Knight-Madden, Susan E Stuber, Asha V Badaloo, Karen Aldred, Margaret E Wisdom-Phipps, Teresa Latham, Russell E Ware
BACKGROUND: Cerebral vasculopathy in sickle cell anemia (SCA) begins in childhood and features intracranial arterial stenosis with high risk of ischemic stroke. Stroke risk can be reduced by transcranial doppler (TCD) screening and chronic transfusion therapy; however, this approach is impractical in many developing countries. Accumulating evidence supports the use of hydroxyurea for the prevention and treatment of cerebrovascular disease in children with SCA. Recently we reported that hydroxyurea significantly reduced the conversion from conditional TCD velocities to abnormal velocities; whether hydroxyurea can be used for children with newly diagnosed severe cerebrovascular disease in place of starting transfusion therapy remains unknown...
September 12, 2016: JMIR Research Protocols
Nicolas Melis, Isabelle Rubera, Marc Cougnon, Sébastien Giraud, Baharia Mograbi, Amine Belaid, Didier F Pisani, Stephan M Huber, Sandra Lacas-Gervais, Konstantina Fragaki, Nicolas Blondeau, Paul Vigne, Christian Frelin, Thierry Hauet, Christophe Duranton, Michel Tauc
The eukaryotic initiation factor 5A (eIF5A), which is highly conserved throughout evolution, has the unique characteristic of post-translational activation through hypusination. This modification is catalyzed by two enzymatic steps involving deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Notably, eIF5A may be involved in regulating the lifespan of Drosophila during long-term hypoxia. Therefore, we investigated the possibility of a link between eIF5A hypusination and cellular resistance to hypoxia/anoxia...
September 9, 2016: Journal of the American Society of Nephrology: JASN
Vesa Anttila, Henri Haapanen, Fredrik Yannopoulos, Johanna Herajärvi, Tuomas Anttila, Tatu Juvonen
In remote ischemic preconditioning (RIPC) short periods of non-lethal ischemia followed by reperfusion of tissue or organ prepare remote tissue or organ to resist a subsequent more severe ischemia-reperfusion injury. The signaling mechanism of RIPC can be humoral communication, neuronal stimulation, systemic modification of circulating immune cells, and activation of hypoxia inducible genes. Despite promising evidence from experimental studies, the clinical effects of RIPC have been controversial. Heterogeneity of inclusion and exclusion criteria and confounding factors such as comedication, anesthesia, comorbidities, and other risk factors may have influenced the efficacy of RIPC...
September 5, 2016: Scandinavian Cardiovascular Journal: SCJ
Zubair Ali, Muhammad Daniyal, Ismailov S I, Khan Usmanghani, Safila Naveed
Type 2 diabetes mellitus (T2D) is a chronic metabolic disease regarded as insulin resistance and progressive failure of β cells. Beta cells secretagogues are useful to reach satisfactory glycemic control. Glimepiride is a second-generation sulfonylurea excites pancreatic beta cells to discharge insulin. Glimepiride may be safer to use in patients with cardiovascular disease due to lack of destructive effects on ischemic preconditioning. It is effective in dropping fasting plasma glucose (FPG), postprandial glucose and glycated hemoglobin levels and is a useful and cost-effective option treatment for the management of T2D...
July 2016: Pakistan Journal of Pharmaceutical Sciences
P P Tregub, V P Kulikov, Yu G Motin, M E Nagibaeva, A S Zabrodina
We studied the expression of chaperone GRP-78 and transcription factor NF-kB during the development of ischemic tolerance of the brain after combined and isolated exposure to hypoxia and hypercapnia. Combined exposure to hypoxia and hypercapnia maximally increased the expression of chaperone GRP-78 and transcription factor NF-kB, while the formation of ischemia-induced tolerance under conditions of hypercapnic hypoxia can be associated with activation of adaptive stress mechanisms in the endoplasmic reticulum...
August 2016: Bulletin of Experimental Biology and Medicine
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