Juan Guillermo Gormaz

A Randomized Controlled Trial to Prevent Post-Operative Atrial Fibrillation by Antioxidant Reinforcement

OBJECTIVES This study was designed to assess whether the reinforcement of the antioxidant system, through n-3 fatty acids plus antioxidant vitamin supplementation, could reduce the incidence of post-operative atrial fibrillation. BACKGROUND Therapy to prevent post-operative atrial fibrillation remains suboptimal. Although oxidative stress plays a key role in the pathogenesis of this arrhythmia, antioxidant reinforcement has produced controversial results. METHODS A total of 203 patients scheduled for on-pump cardiac surgery were randomized to placebo or supplementation with n-3 polyunsaturated fatty acids (2 g/day) (eicosapentaenoic acid:docosahexaenoic acid ratio 1:2), vitamin C (1 g/day), and vitamin E (400 IU/day). The primary outcome was the occurrence of post-operative atrial fibrillation. Secondary outcomes were the biomarkers related to oxidative stress and inflammation. RESULTS Post-operative atrial fibrillation occurred in 10 of 103 patients (9.7%) in the supplemented group versus 32 of 100 patients (32%) in the placebo group (p < 0.001). Early after surgery, placebo patients presented with increased levels of biomarkers of inflammation and oxidative stress, which were markedly attenuated by antioxidant supplementation. The activity of catalase, superoxide dismutase, and glutathione peroxidase in atrial tissue of the supplemented patients was 24.0%, 17.1%, and 19.7% higher than the respective placebo values (p < 0.05). The atrial tissue of patients who developed atrial fibrillation showed NADPH oxidase p47-phox subunit protein and mRNA expression 38.4% and 35.7% higher, respectively, than patients in sinus rhythm (p < 0.05). CONCLUSIONS This safe, well-tolerated, and low-cost regimen, consisting of n-3 polyunsaturated fatty acids plus vitamins C and E supplementation, favorably affected post-operative atrial fibrillation, increased antioxidant potential, and attenuated oxidative stress and inflammation. (Prevention of Post-Operative Atrial Fibrillation: Pathophysiological Characterization of a Pharmacological Intervention Based on a Novel Model of Nonhypoxic Pre-Conditioning; ISRCTN45347268).

Biosynthesis and bioavailability of long-chain polyunsaturated fatty acids in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) has a high occurrence in most countries. Recent studies estimate its prevalence to be near 30% in United States, Italian and Japanese general adult populations. NAFLD commonly presents along with obesity and insulin resistance (IR), pathologies that share with NAFLD metabolic and inflammatory components. These conditions, particularly NAFLD, are associated with alterations in the bioavailability of long-chain polyunsaturated fatty acids (LCPUFAs). In the human population, the bioavailability of LCPUFAs depends both on endogenous biosynthesis and diet amount of preformed LCPUFAs. However, the lower liver LCPUFAs product/precursor ratio namely (20:5n-3+22:6n-3)/18:3n-3, 20:4n-6/18:2n-6 present in common Western diets, makes critical an adequate pathway activity to ensure minimum bioavailability of LCPUFAs in most Western populations. The key step of this biosynthesis involves Δ5 and Δ6-desaturases, whose activities are altered in NAFLD. During the disease, the presence of molecular activators of these two enzymes does not correlate with the scarce LCPUFAS biosynthesis observed. The key to this apparent contradiction, or at least part of it, could be explained on the basis of the possible sensitivity of the desaturases to oxidative stress; a metabolic condition strongly linked to inflammatory pathologies such as NAFLD, obesity and IR and that, according to latest research, not only would be consequence but also possibly a cause of these diseases. The present review is focused on the relationship between NAFLD and the bioavailability of LCPUFAs, with special reference to the role that oxidative stress could play in the modulation of the liver fatty acid desaturase activity.

Potential Role of Polyphenols in the Prevention of Cardiovascular Diseases: Molecular Bases

Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. It is widely accepted that oxidative stress plays a key role in their development and progression; hence oxidative damage might be abrogated by antioxidants. Polyphenols are phytochemicals showing extensively studied antioxidant properties in-vivo. Most representative sources of these compounds include fruits, greens, nuts, herbs, cocoa, tea and coffee. Epidemiological evidence suggests an association between the consumption of polyphenol-rich vegetables and the reduction of cardiovascular disease prevalence. This fact could be related to the anti-inflammatory, antithrombotic and vasodilatory effects of polyphenols. Even though these biological effects could be mainly attributed to the antioxidant activity of polyphenols, other pharmacological mechanisms should also be considered. The latter could comprise direct anti-inflammatory effects, modulation of intracellular signaling and gene expression, improvement of nitric oxide homeostasis, as well as platelet antiaggregation. However, it is noticeable that protocols of interventions to evaluate the properties of polyphenols have failed to show the same positive results reported from observational studies. At present, a controversy exists regarding the actual effectiveness of polyphenols in preventing cardiovascular diseases. Therefore, an improvement of the available knowledge about polyphenol pharmacokinetics, together with a better understanding of the mechanisms of action of these compounds, could be of great benefit. Thus, a rational support for the development of interventional designs could provide reliable evidence on the actual role of polyphenols in CVD prevention.

Public Health Perspectives on Aquaculture

Nearly half of all seafood consumed globally comes from aquaculture, a method of food production that has expanded rapidly in recent years. Increasing seafood consumption has been proposed as part of a strategy to combat the current non-communicable disease (NCD) pandemic, but public health, environmental, social, and production challenges related to certain types of aquaculture production must be addressed. Resolving these complicated human health and ecologic trade-offs requires systems thinking and collaboration across many fields; the One Health concept is an integrative approach that brings veterinary and human health experts together to combat zoonotic disease. We propose applying and expanding the One Health approach to facilitate collaboration among stakeholders focused on increasing consumption of seafood and expanding aquaculture production, using methods that minimize risks to public health, animal health, and ecology. This expanded application of One Health may also have relevance to other complex systems with similar trade-offs.

Novel relationships between oxidative stress and angiogenesis-related factors in sepsis: New biomarkers and therapies.

Abstract Sepsis is a systemic uncontrolled inflammatory response in the presence of an infection. It remains a major cause of morbidity and mortality in hospitalized patients. According to its severity, sepsis can progress to three different states: severe sepsis, septic shock, and multiple organ dysfunction syndrome, related to organ dysfunction and/or tissue hypoperfusion. Different processes underlie its pathophysiology; among them are oxidative stress, endothelial and mitochondrial dysfunction, and angiogenesis-related factors. However, no studies have integrated these elements in sepsis. The main difficulty in sepsis is its diagnosis. Currently, the potential of inflammatory biomarkers in septic patients remains weak. In this context, the research into new biomarkers is essential to aid with sepsis diagnosis and prognostication. Furthermore, even though the current management of severe forms of sepsis has been effective, morbimortality remains elevated. Therefore, it is essential to explore alternative approaches to therapy development. The aim of this review is to present an update of evidence supporting the role of oxidative stress and angiogenesis-related factors in the pathophysiology of the different forms of sepsis. It proposes a novel convergence between both elements in their role in the disease, and it will cover their utility as new diagnostic tools, predictors of outcome, and as novel therapeutic targets.

Amelioration of persistent left ventricular function impairment through increased plasma ascorbate levels following myocardial infarction

Purpose: Percutaneous coronary angioplasty (PCA) has been demonstrated to reduce mortality and morbidity and thereby improve the prognosis of patients undergoing acute myocardial infarctions (AMIs). However, this procedure paradoxically increases the initial damage as the result of a condition known as ‘myocardial reperfusion injury’. Oxidative stress may contribute to the mechanism of this injury. The goal of the present study was to ascertain whether high plasma ascorbate levels could ameliorate the reperfusion injuries that occur after the successful restoration of blood flow. Methods: Patients from three clinical centers of the public health system were included in the study. The groups were formed by either-sex patients with a diagnosis of ST-segment elevation myocardial infarction with an indication for primary PCA. Only the patients who presented with their first myocardial infarction were enrolled. Ascorbate was administered through an infusion given prior to the restoration of the coronary flow, which was then followed by oral treatment with vitamin C (500 mg/12 hours) plus vitamin E (400 IU/day) for 84 days. The left ventricular ejection fraction (LVEF) was determined by using cardiac magnetic resonance on days 6 and 84 following the onset of the reperfusion. In addition, the microvascular function was assessed by an angiographic evaluation using the Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade (TMPG). The results were grouped according to the plasma ascorbate concentration achieved immediately following the onset of reperfusion into either the HA group (high ascorbate, >1 mmol/l) or the LA group (low ascorbate, <1 mmol/l). The biochemical parameters were analyzed throughout the protocol. Results: The LVEF of the HA group was significantly higher than that of the LA group, values on day 84 in the HA group were 33% higher than those of the LA group. The amelioration of the LVEF was accompanied by an improvement in the microvascular dysfunction, after PCA, 95% of the patients in the HA group achieved a TMPG of 2–3, in the LA group only 79% of patients showed a TMPG of 2–3. Conclusions: These data are consistent with the protective effect of high plasma levels of ascorbate against the oxidative challenge caused by reperfusion injury in patients subjected to PCA following an AMI. Further studies are needed to elucidate the mechanism accounting for this beneficial antioxidant effect.

The population impact of obesity, sedentary lifestyle, and tobacco and alcohol consumption on the prevalence of type 2 diabetes: Analysis of a health population survey in Chile, 2010

Aim To estimate the impact of tobacco use, sedentary lifestyle, obesity and alcohol consumption on type 2 diabetes mellitus (T2DM) prevalence in the Chilean population. Methods The study-included 5,293 subjects with fasting glycaemia levels from the nationwide cross-sectional health survey in 2010, commissioned by the Ministry of Health, Chile. Crude and Adjusted Odds Ratio to T2DM and its corresponding 95% confidence interval were estimated through logistic regressions. Attributable fractions and population attributable fractions were estimated. Results T2DM prevalence was 9.5%. Sedentary lifestyles and obesity were significant risk factors for T2DM. 52,4% of T2DM could be avoided if these individuals were not obese, and at a population level, 23% of T2DM could be preventable if obesity did not exist. A 64% of T2DM is explained by sedentariness, and if people would become active, a 62,2% of the cases of diabetes could be avoided. Interpretation About 79% of T2DM cases in Chile could be prevented with cost-effective strategies focused on preventing sedentary lifestyle and obesity. It’s therefore urgent to implement evidence-based public health polices, aimed to decrease the prevalence of T2DM, by controlling its risk factors and consequently, reducing the complications from T2DM.

Effects of a novel ascorbate-based protocol on infarct size and ventricle function in acute myocardial infarction patients undergoing percutaneous coronary angioplasty

Introduction This study was designed to test the hypothesis that high-dose ascorbate prior to reperfusion followed by low chronic oral doses ameliorate myocardial reperfusion injury (MRI) in acute myocardial infarction patients subjected to primary percutaneous coronary angioplasty (PCA). Material and methods A randomized double-blind placebo-controlled and multicenter clinical trial was performed on acute myocardial infarction (AMI) patients who underwent PCA. Sodium ascorbate (320 mmol/l, n = 53) or placebo (n = 46) was infused 30 min prior to PCA. Blood samples were drawn at enrolment (M1), after balloon deflation (M2), 6–8 h after M2 (M3) and at discharge (M4). Total antioxidant capacity of plasma (ferric reducing ability of plasma – FRAP), erythrocyte reduced glutathione (GSH) and plasma ascorbate levels were determined in blood samples. Cardiac magnetic resonance (CMR) was performed at 7–15 days and 2–3 months following PCA. Ninety-nine patients were enrolled. In 67 patients, the first CMR was performed, and 40 patients completed follow-up. Results The ascorbate group showed significantly higher ascorbate and FRAP levels and a decrease in the GSH levels at M2 and M3 (p < 0.05). There were no significant differences in the infarct size, indexed end-systolic volume and ejection fraction at both CMRs. There was a significant amelioration in the decreased ejection fraction between the first and second CMR in the ascorbate group (p < 0.05). Conclusions Ascorbate given prior to reperfusion did not show a significant difference in infarct size or ejection fraction. However, it improved the change in ejection fraction determined between 7–15 days and 2–3 months. This result hints at a possible functional effect of ascorbate to ameliorate MRI.

Clinical decision making in postmastectomy radiotherapy in node negative breast cancer

For decades, postmastectomy radiotherapy (PMRT) has been recommended for node positive [N(+)] breast cancer patients; nevertheless, the beneficial effect of PMRT for treatment of node negative [N(−)] disease remains under discussion. Nowadays, the biology of breast cancer and the risk factors (RFs) for locoregional failure (LRF) must be included in the decision on whether or not to carry out PMRT. For these reasons, the present review aims to evaluate the rationale use of PMRT in N(−) patients and discuss which subgroups may further benefit from the treatment in present times where the decision must be personalised, according to the RFs of locoregional recurrence (LRR). To perform the analysis, we ponder that LRR of over 10% should be considered unacceptable due to the fact that LRRs generate great morbidity in patients. For this purpose, we consider that routine RT in these patients is not recommended, although there are subgroups of patients with high LRR, in which PMRT could be beneficial.