A protocol update for the Selenium Treatment and Chagasic Cardiomyopathy (STCC) trial.

Several studies evaluating clinical forms of chronic Chagas disease show that about one-third of patients present cardiac involvement. Heart failure, sudden death and cardioembolic stroke are the main mechanisms of death in Chagas heart disease. The impact of specific etiologic treatment on the prognosis of patients with chronic Chagas heart disease is very limited regardless of the presence or absence of heart failure. Patients with symptomatic Chagas heart disease present serum selenium (Se) levels lower than patients without Chagas heart disease. Moreover, Se supplementation in animal models showed promising results. The aim of this trial is to estimate the effect of Se treatment on prevention of heart disease progression in patients with Chagas cardiomyopathy. However, we had to introduce some protocol modifications in order to keep trial feasibility, as follows: the primary outcome was restricted to left ventricular ejection fraction as a continuous variable, excluding disease progression; the follow-up period was decreased from 5 years to 1 year, an adjustment that might increase the participation rate of our study; the superior age limit was increased from 65 to 75 years; and diabetes mellitus was no longer considered an exclusion criterion. All of these protocol modifications were extensively debated by the research team enrolled in the design, recruitment and conduction of the clinical trial to guarantee a high scientific quality. TRIAL REGISTRATION: Clinical Trials.gov, NCT00875173 . Registered on 20 October 2008.

Long-Term Excessive Selenium Supplementation Induces Hypertension in Rats.

Selenium (Se) is an essential trace element involved in several biological pathways, naturally found in rocks, soils, and food. Even though the daily requirement of Se is achieved through a balanced diet, the use of Se supplements has been frequent. Due to the risk of toxic effects of having Se in excess, supplementation is still under debate. The aim was to evaluate the effects of long-term Se supplementation upon systolic blood pressure (SBP) and redox status of rats exposed to sodium selenite. Male Wistar rats were exposed to 2 and 6 mg/L of sodium selenite in drinking water for 85 days. SBP and body weight were evaluated weekly; oxidative stress biomarkers were measured in blood or plasma; and Se levels were assessed in blood, plasma, kidney, and liver. Se supplementation (2 and 6 mg/L) induced significant increase in the SBP in rats from the 42nd day until the end of the study. This increase on SBP was not associated with significant changes in oxidative stress biomarkers. A significant increase in Se levels was found in whole blood, kidney, and liver from both groups of rats receiving Se supplementation when compared to control. Although the exact mechanisms underlying this augment in SBP are not clear, they are potentially related to other Se biological routes besides the synthesis of selenoproteins, such as GSH-Px. Due to the negative effects upon blood pressure, precautionary measures are advised, since the selling of supplements does not require a medical prescription.

Pharmaconutrition with selenium in critically ill patients: what do we know?

Selenium is a component of selenoproteins with antioxidant, anti-inflammatory, and immunomodulatory properties. Systemic inflammatory response syndrome (SIRS), multiorgan dysfunction (MOD), and multiorgan failure (MOF) are associated with an early reduction in plasma selenium and glutathione peroxidase activity (GPx), and both parameters correlate inversely with the severity of illness and outcomes. Several randomized clinical trials (RCTs) evaluated selenium therapy as monotherapy or in antioxidant cocktails in intensive care unit (ICU) patient populations, and more recently several meta-analyses suggested benefits with selenium therapy in the most seriously ill patients. However, the largest RCT on pharmaconutrition with glutamine and antioxidants, the REducing Deaths due to Oxidative Stress (REDOXS) Study, was unable to find any improvement in clinical outcomes with antioxidants provided by the enteral and parenteral route and suggested harm in patients with renal dysfunction. Subsequently, the MetaPlus study demonstrated increased mortality in medical patients when provided extra glutamine and selenium enterally. The treatment effect of selenium may be dependent on the dose, the route of administration, and whether administered with other nutrients and the patient population studied. Currently, there are few small studies evaluating the pharmacokinetic profile of intravenous (IV) selenium in SIRS, and therefore more data are necessary, particularly in patients with MOD, including those with renal dysfunction. According to current knowledge, high-dose pentahydrate sodium selenite could be given as an IV bolus injection (1000-2000 µg), which causes transient pro-oxidant, cytotoxic, and anti-inflammatory effects, and then followed by a continuous infusion of 1000-1600 µg/d for up to 10-14 days. Nonetheless, the optimum dose and efficacy still remain controversial and need to be definitively established.

Selenium Treatment and Chagasic Cardiopathy (STCC): study protocol for a double-blind randomized controlled trial.

BACKGROUND: Heart disease progression occurs in 30% of patients with chronic Trypanosoma cruzi infection. Supplementation with selenium (Se) in animal model of T. cruzi infection produced promising results. There is evidence that patients with Chagas heart disease have lower Se levels than healthy individuals and patients with T. cruzi infection without of cardiac disease. The aim of this investigation is to estimate the effect of Se treatment on prevention of heart disease progression in patients with chagasic cardiopathy. METHODS: The Selenium Treatment and Chagasic Cardiopathy trial is a superiority, double-blind, placebo-controlled, randomized clinical trial. The eligibility criteria are as follows: (1) a Chagas disease diagnosis confirmed by serology; (2) segmental, mild or moderate global left ventricular systolic dysfunction; and (3) age between 18 and 65 years. The exclusion criteria are as follows: (1) pregnancy, (2) diabetes mellitus, (3) tobacco use, (4) alcohol abuse, (5) evidence of nonchagasic heart disease, (6) depression, (7) dysphagia with evidence of food residues in the esophagus, (8) dysphagia with weight loss higher than 15% of usual weight in the last four months and/or (9) conditions that may result in low protocol adherence. The intervention will be 100 µg of sodium selenite once daily for 365 consecutive days compared to placebo. The following are the primary outcomes to be measured: (1) the trajectories of the left ventricular ejection fraction in the follow-up period; (2) reduction of heart disease progression rates, with progression defined as a 10% decrease in left ventricular ejection fraction; and (3) rate of hospital admissions attributable to dysrhythmia, heart failure or stroke due to Chagas disease. One hundred thirty patients will be randomly allocated into either the intervention or placebo group at a ratio of 1:1. The sequence allocation concealment and blinding were planned to be conducted with the strategy of numbered boxes. Both patients and health-care providers will remain blinded to the intervention groups during the 5 years of follow-up. DISCUSSION: If Se treatment reduces the progression of Chagas cardiopathy, the inclusion of this micronutrient in the daily diet can improve the therapeutic regimen for this neglected tropical disease at low cost. TRIAL REGISTRATION: Clinical Trials.gov ID: NCT00875173 (registered 20 October 20 2008).

SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX-trial): study design of an international multicenter randomized double-blinded controlled trial of high dose sodium-selenite administration in high-risk cardiac surgical patients.

BACKGROUND: Cardiac surgery has been shown to result in a significant decrease of the antioxidant selenium, which is associated with the development of multiorgan dysfunction and increased mortality. Thus, a large-scale study is needed to investigate the effect of perioperative selenium supplementation on the occurrence of postoperative organ dysfunction. METHODS/DESIGN: We plan a prospective, randomized double-blind, multicenter controlled trial, which will be conducted in North and South America and in Europe. In this trial we will include 1,400 high-risk patients, who are most likely to benefit from selenium supplementation. This includes patients scheduled for non-emergent combined and/or complex procedures, or with a predicted operative mortality of ≥ 5% according to the EuroSCORE II. Eligible patients will be randomly assigned to either the treatment group (bolus infusion of 2,000 µg sodium selenite immediately prior to surgery, followed by an additional dosage of 2,000 µg at ICU admission, and a further daily supplementation of 1,000 µg up to 10 days or ICU discharge) or to the control group (placebo administration at the same time points).The primary endpoint of this study is a composite of 'persistent organ dysfunction' (POD) and/or death within 30 days from surgery (POD + death). POD is defined as any need for life-sustaining therapies (mechanical ventilation, vasopressor therapy, mechanical circulatory support, continuous renal replacement therapy, or new intermittent hemodialysis) at any time within 30 days from surgery. DISCUSSION: The SUSTAIN-CSX™ study is a multicenter trial to investigate the effect of a perioperative high dosage sodium selenite supplementation in high-risk cardiac surgical patients. TRIAL REGISTRATION: This trial was registered at Clinicaltrials.gov (identifier: NCT02002247) on 28 November 2013.

Comparação da eficiência dos caldos de enriquecimento seletivo no isolamento de Salmonella Dublin / Comparison of the efficiency of selective enrichment broths for Salmonella Dublin isolation

The aim of this study was to compare three different selective enrichment broths: Rappaport-Vassiliadis (RV), selenite cystine (SC) and Muller-Kauffmann tetrathionate (MKT) for Salmonella Dublin isolation from faecal samples of calf experimentally infected. The bacteriological procedure involved pre-enrichment stages in Hajna-GN broth (only for the samples inoculated in RV broth), selective enrichment, culture in modified brilliant green agar (BGA), presumptive biochemistry tests (using triple-sugar-iron agar and lysine-agar) and slide agglutination test with poli-O and poli-H Salmonella antiserum. The effects of enrichment temperatures using RV broth were also evaluated (37ºC and 42ºC). SC broth was significantly more efficient in the isolation of Salmonella Dublin (P<0,05), whereas RV broth incubated at 42ºC had a lower efficiency in the microbiological isolation.(AU)

Comparação da eficiência dos caldos de enriquecimento seletivo no isolamento de Salmonella Dublin / Comparison of the efficiency of selective enrichment broths for Salmonella Dublin isolation

The aim of this study was to compare three different selective enrichment broths: Rappaport-Vassiliadis (RV), selenite cystine (SC) and Muller-Kauffmann tetrathionate (MKT) for Salmonella Dublin isolation from faecal samples of calf experimentally infected. The bacteriological procedure involved pre-enrichment stages in Hajna-GN broth (only for the samples inoculated in RV broth), selective enrichment, culture in modified brilliant green agar (BGA), presumptive biochemistry tests (using triple-sugar-iron agar and lysine-agar) and slide agglutination test with poli-O and poli-H Salmonella antiserum. The effects of enrichment temperatures using RV broth were also evaluated (37ºC and 42ºC). SC broth was significantly more efficient in the isolation of Salmonella Dublin (P<0,05), whereas RV broth incubated at 42ºC had a lower efficiency in the microbiological isolation.