The Effects of Ethanol on the Heart: Alcoholic Cardiomyopathy

Alcoholic-dilated Cardiomyopathy (ACM) is the most prevalent form of ethanol-induced heart damage. Ethanol induces ACM in a dose-dependent manner, independently of nutrition, vitamin, or electrolyte disturbances. It has synergistic effects with other heart risk factors. ACM produces a progressive reduction in myocardial contractility and heart chamber dilatation, leading to heart failure episodes and arrhythmias. Pathologically, ethanol induces myocytolysis, apoptosis, and necrosis of myocytes, with repair mechanisms causing hypertrophy and interstitial fibrosis. Myocyte ethanol targets include changes in membrane composition, receptors, ion channels, intracellular [Ca2+] transients, and structural proteins, and disrupt sarcomere contractility. Cardiac remodeling tries to compensate for this damage, establishing a balance between aggression and defense mechanisms. The final process of ACM is the result of dosage and individual predisposition. The ACM prognosis depends on the degree of persistent ethanol intake. Abstinence is the preferred goal, although controlled drinking may still improve cardiac function. New strategies are addressed to decrease myocyte hypertrophy and interstitial fibrosis and try to improve myocyte regeneration, minimizing ethanol-related cardiac damage. Growth factors and cardiomyokines are relevant molecules that may modify this process. Cardiac transplantation is the final measure in end-stage ACM but is limited to those subjects able to achieve abstinence

Central sensitization: a pathogenic mechanism in complex undefined diseases

There is a common perception that complex undefined diseases manifested with diverse combination of symptoms and a difficult clinical diagnosis have a possible common physiological mechanism of disease production. Physical or cognitive fatigue, widespread pain without arthritis, sleep, mood and autonomic disturbances as well as multiple intolerance involving drug, food, chemical agents, electromagnetic fields or other environmental factors may be included in this category. Along last three decades, the existence of central sensitivity as a well established common pathogenic mechanism involved in abnormal symptom development emerged in diverse areas as pain, fatigue, food and environmental intolerance, as well as in the global chronic disease epidemic. The common fact of all of these disorders is a deregulation of the central control mechanisms at the limbic brain system. This may relate to amplification of pain and fatigue perception and disturbance of environmental tolerance and control of circadian rhythms and mood. This deregulation causes amplification of central somatosensory perception, but also a decrease of nociceptive inhibitory outputs. The final result is a chronic condition with central hyperexcitability and systemic disabling symptoms highly difficult to manage. This article comments on the current significance to evaluate central sensitization symptoms and to consider these mechanisms in the development of complex diseases, as well as in the global chronic disease epidemic. We propose to include central sensitization to structuring a multidisciplinary concept addressed to improve scientific comprehension and clinical management of these diseases, as wee as future research directions on this field

New Treatment Strategies for Alcohol-Induced Heart Damage.

High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis. In addition, ethanol decreases myocyte protective and repair mechanisms and their regeneration. Although there are diverse different strategies to directly target alcohol-induced heart damage, they are partially effective, and can only be used as support medication in a multidisciplinary approach. Alcohol abstinence is the preferred goal, but control drinking is useful in alcohol-addicted subjects not able to abstain. Correction of nutrition, ionic and vitamin deficiencies and control of alcohol-related systemic organ damage are compulsory. Recently, several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK inhibitors) and new cardiomyokines such as FGF21 have been described to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms, and they are promising agents in this field. New potential therapeutic targets aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may improve myocyte regeneration. However, these strategies are not yet approved for clinical use

Síndromes de sensibilización central: hacia la estructuración de un concepto multidisciplinar.

Article en el que es discuteix el concepte de sensibilització central, les malaties que hi són incloses i la seva utilitat pràctica per al maneig del conjunt d'aquesta simptomatologia. Es fa més émfasi en la Fibromiàlgia,Síndrome de Fatiga Crónica i la Sensibiltiat Química Múltiple. S'aborda el tema des d'un vessant multidisciplinar

Insulin-Like growth-factor 1 myocardial expression decreases in chronic alcohol consumption

Background Chronic alcohol ingestion may cause severe biochemical and pathophysiological derangements to skeletal muscle. Unfortunately, these alcohol-induced events may also prime skeletal muscle for worsened, delayed, or possibly incomplete repair following acute injury. As alcoholics may be at increased risk for skeletal muscle injury, our goals were to identify the effects of chronic alcohol ingestion on components of skeletal muscle regeneration. To accomplish this, age- and gender-matched C57Bl/6 mice were provided normal drinking water or water that contained 20% alcohol (v/v) for 18-20 wk. Subgroups of mice were injected with a 1.2% barium chloride (BaCl2) solution into the tibialis anterior (TA) muscle to initiate degeneration and regeneration processes. Body weights and voluntary wheel running distances were recorded during the course of recovery. Muscles were harvested at 2, 7 or 14 days post-injection and assessed for markers of inflammation and oxidant stress, fiber cross-sectional areas, levels of growth and fibrotic factors, and fibrosis. Results Body weights of injured, alcohol-fed mice were reduced during the first week of recovery. These mice also ran significantly shorter distances over the two weeks following injury compared to uninjured, alcoholics. Injured TA muscles from alcohol-fed mice had increased TNFα and IL6 gene levels compared to controls 2 days after injury. Total protein oxidant stress and alterations to glutathione homeostasis were also evident at 7 and 14 days after injury. Ciliary neurotrophic factor (CNTF) induction was delayed in injured muscles from alcohol-fed mice which may explain, in part, why fiber cross-sectional area failed to normalize 14 days following injury. Gene levels of TGFβ1 were induced early following injury before normalizing in muscle from alcohol-fed mice compared to controls. However, TGFβ1 protein content was consistently elevated in injured muscle regardless of diet. Fibrosis was increased in injured, muscle from alcohol-fed mice at 7 and 14 days of recovery compared to injured controls. Conclusions Chronic alcohol ingestion appears to delay the normal regenerative response following significant skeletal muscle injury. This is evidenced by reduced cross-sectional areas of regenerated fibers, increased fibrosis, and altered temporal expression of well-described growth and fibrotic factors

Asistencia urgente a pacientes con infección por el virus de la inmunodeficiencia humana: un problema que crece

La asistencia médica a pacientes con infección por el virus de la inmunodeficiencia humana (VIH) es habitualmente compleja debido a las características peculiares de esta enfermedad y al gran número de complicaciones infecciosas, metabólicas, neurológicas y en general, de todo tipo que presentan 1.3. Estos factores y la potencial gravedad que pueden representar, hace que con frecuencia estos pacientes soliciten asistencia médica en régimen urgente. La atención urgente a este colectivo de pacientes está poco organizada a nivel sanitario en nuestro país, ya que no se ha creado un dispositivo de asistencia sanitaria específica y la atención ambulatoria que reciben es claramente insuficiente

Situaciones estresantes asociadas a la presentación del síndrome de fatiga crónica.

Chronic Fatigue Syndrome (CFS) is a complex and multifactorial disease. Stressful situations experienced could be related to the presentation of the disease. Few studies have determined which factors could trigger CFS. The main objective of this study was to explore the stressful situations which can be associated with CFS presentation. METHODS: Retrospective observational case-control study with CFS diagnosed patients according to the Fukuda's criteria. Controls were matched to cases by sex, age and educational level with a 1:1 ratio. Participants aged between 18 and 75 years from the province of Lleida. Information was obtained through personal questionnaires. The measure of association was the odds ratio. RESULTS: In total, 77 cases and 77 controls were included. Association found between stressful life events and presentation of disease were pregnancy ORa=31.7 (CI95%:2.2-456.7), spousal abuse ORa= 10.2 (CI95%:1.2-88.4) and mobbing ORa=6.9 (CI95%:1.3-36.9), eating disorders=7.5 (CI95%:1.3-42.1), car accident ORa=5.5 (CI95%:1.7-17 9), economic problems ORa=5.1 (CI95%:2.1-12.6) and changes in sleep habits ORa=2.8 (CI95%:1.1-7.5). CONCLUSIONS: Stressful life events as pregnancy, spousal abuse, mobbing, eating disorders, car accident, economic problems and changes in sleep habits felt by those affected must be taken into consideration when compiling background information related to the onset of Chronic Fatigue Syndrome. Adequate identification of these stressful life events in risk people could contribute to early diagnosis of Chronic Fatigue Syndrome

Decreased myocardial Titin expression in chronic alcoholic cardiomyopathy

Aims: Cardiomyopathy (CMP) with a reduced ejection fraction develops in a dose-28 dependent manner in one- third of subjects with a long-term history of heavy daily alcohol consumption. Ethanol alters heart transduction signals including excitation- contraction sarcomeric coupling, causing diastolic and systolic left-ventricular (LV) dysfunction. Titin is a giant structural sarcomeric filament macro protein involved in contractile heart function and contributes to cardiac myocyte elastic recoil, a key factor for diastolic LV filling. We evaluated whether titin expression is affected by chronic high-dose ethanol 35 consumption in alcoholic CMP. Methods and Results: We analyzed a total of 30 heart samples from human organ 37 donors: 20 from high alcohol consumers (10 without CMP and 10 with CMP) and 10 healthy controls. Patient evaluation comprised daily and lifetime ethanol consumption, chest X ray, 2-D echocardiography and LV histology. CMP was assessed by functional 40 and histological criteria. Titin activity was evaluated by specific immunohistochemical 41 (IHC) and transcript expression (rtPCR) assays. Titin IHC expression was clearly present in sarcomere areas of myocytes. Compared to healthy donors (82.58±3.36), alcohol consumers showed a significantly lower cardiac titin expression (71.29±3.16; 13.67±3.83% decrease; p=0.04), being significantly lower in alcohol consumers with CMP (62.31±4.18; 24.54±5.06% decrease, p<0.0009), compared to both their counter-parts without CMP (80.27±2.62; 2.80±3.17% decrease 47 vs. controls; p<0.0030 vs. alcoholic CMP). Titin transcript levels confirmed similar patterns of expression

Down-regulation of adhesion molecules and other inflammatory biomarkers after moderate wine consumption in healthy women: a randomized trial

Background: Moderate alcohol consumption is cardioprotective. The mechanism for this beneficial effect might be reduced inflammatory responses, as suggested by prospective studies and small clinical trials in men. No studies have evaluated the antiinflammatory effects of wine in women. Objective: We investigated whether low-dose intake of white and red wines has differential effects on inflammatory markers in women. Design: In a crossover study, we randomly assigned 35 healthy women to two 4-wk periods of 20 g ethanol/d as white or red wine, preceded by two 4-wk washout periods. Before and after interventions, we measured serum lipids, circulating inflammatory biomarkers, cellular adhesion molecules (CAMs), and adhesion of monocytes to stimulated endothelial cells. Results: HDL cholesterol increased, and the serum concentrations of high-sensitivity C-reactive protein, intercellular adhesion molecule-1, CD40L, and interleukin-6 decreased after either wine (P< 0.01, all). Vascular CAM-1 and E-selectin decreased (P <0.01) only after red wine. CAM expression by mononuclear cells was blunted after either wine, with a greater suppressant effect of red wine. Enhanced adhesion of monocytes to stimulated endothelial cells was reduced by 51% (95% CI:-57%,-45%) after white wine and by 89% (95% CI: -96%, -82%) after red wine (P <0.01 for between-wine differences). Conclusions: Moderate wine consumption is associated with beneficial effects on various inflammatory pathways related to endothelial activation in women. Probably because of its higher polyphenol content, red wine shows superior antiinflammatory effects than does white wine. Reducing low-grade inflammation and endothelial activation may be another potential mechanism by which alcoholic beverages exert their cardioprotective effect

Prospective cohort study for assessment of integrated care with a triple aim approach: hospital at home as use case

Background: Applicability of comprehensive assessment of integrated care services in real world settings is an unmet need. To this end, a Triple Aim evaluation of Hospital at Home (HaH), as use case, was done. As ancillary aim, we explored use of the approach for monitoring the impact of adoption of integrated care at health system level in Catalonia (Spain). Methods: Prospective cohort study over one year period, 2017-2018, comparing hospital avoidance (HaH-HA) with conventional hospitalization (UC) using propensity score matching. Participants were after the first episode directly admitted to HaH-HA or the corresponding control group. Triple Aim assessment using multiple criteria decision analysis (MCDA) was done. Moreover, applicability of a Triple Aim approach at health system level was explored using registry data. Results: HaH-HA depicted lower: i) Emergency Room Department (ER) visits (p < .001), ii) Unplanned re-admissions (p = .012); and iii) costs (p < .001) than UC. The weighted aggregation of the standardized values of each of the eight outcomes, weighted by the opinions of the stakeholder groups considered in the MCDA: i) enjoyment of life; ii) resilience; iii) physical functioning; iv) continuity of care; v) psychological wellbeing; (vi) social relationships & participation; (vii) person-centeredness; and (viii) costs, indicated better performance of HaH-HA than UC (p < .05). Actionable factors for Triple Aim assessment of the health system with a population-health approach were identified. Conclusions: We confirmed health value generation of HaH-HA. The study identified actionable factors to enhance applicability of Triple Aim assessment at health system level for monitoring the impact of adoption of integrated care. Registration: ClinicalTrials.gov (26/04/2017; NCT03130283). Keywords: Chronic care, Health Delivery Assessment, Health Services Research, Hospital at Home, Implementation Science, Multiple Criteria Decision Analysis, Triple Ai