Inorganic nitrate benefits contrast-induced nephropathy after coronary angiography for acute coronary syndromes: the NITRATE-CIN trial.

BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality following coronary angiographic procedures in high-risk patients and remains a significant unmet need. In pre-clinical studies inorganic nitrate, which is chemically reduced in vivo to nitric oxide, is renoprotective but this observation is yet to be translated clinically. In this study, the efficacy of inorganic nitrate in the prevention of CIN in high-risk patients presenting with acute coronary syndromes (ACS) is reported. METHODS: NITRATE-CIN is a double-blind, randomized, single-centre, placebo-controlled trial assessing efficacy of inorganic nitrate in CIN prevention in at-risk patients presenting with ACS. Patients were randomized 1:1 to once daily potassium nitrate (12 mmol) or placebo (potassium chloride) capsules for 5 days. The primary endpoint was CIN (KDIGO criteria). Secondary outcomes included kidney function [estimated glomerular filtration rate (eGFR)] at 3 months, rates of procedural myocardial infarction, and major adverse cardiac events (MACE) at 12 months. This study is registered with ClinicalTrials.gov: NCT03627130. RESULTS: Over 3 years, 640 patients were randomized with a median follow-up of 1.0 years, 319 received inorganic nitrate with 321 received placebo. The mean age of trial participants was 71.0 years, with 73.3% male and 75.2% Caucasian; 45.9% had diabetes, 56.0% had chronic kidney disease (eGFR <60 mL/min) and the mean Mehran score of the population was 10. Inorganic nitrate treatment significantly reduced CIN rates (9.1%) vs. placebo (30.5%, P < .001). This difference persisted after adjustment for baseline creatinine and diabetes status (odds ratio 0.21, 95% confidence interval 0.13-0.34). Secondary outcomes were improved with inorganic nitrate, with lower rates of procedural myocardial infarction (2.7% vs. 12.5%, P = .003), improved 3-month renal function (between-group change in eGFR 5.17, 95% CI 2.94-7.39) and reduced 1-year MACE (9.1% vs. 18.1%, P = .001) vs. placebo. CONCLUSIONS: In patients at risk of renal injury undergoing coronary angiography for ACS, a short (5 day) course of once-daily inorganic nitrate reduced CIN, improved kidney outcomes at 3 months, and MACE events at 1 year compared to placebo.

NITRATE-CIN Study: Protocol of a Randomized (1:1) Single-Center, UK, Double-Blind Placebo-Controlled Trial Testing the Effect of Inorganic Nitrate on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography for Acute Coronary Syndromes.

BACKGROUND: Contrast-induced nephropathy (CIN), an acute kidney injury resulting from the administration of intravascular iodinated contrast media, is a significant cause of morbidity/mortality following coronary angiographic procedures in high-risk patients. Despite preventative measures intended to mitigate the risk of CIN, there remains a need for novel effective treatments. Evidence suggests that delivery of nitric oxide (NO) through chemical reduction of inorganic nitrate to NO may offer a novel therapeutic strategy to reduce CIN and thus preserve long term renal function. DESIGN: The NITRATE-CIN trial is a single-center, randomized, double-blind placebo-controlled trial, which plans to recruit 640 patients presenting with acute coronary syndromes (ACS) who are at risk of CIN. Patients will be randomized to either inorganic nitrate therapy (capsules containing 12 mmol KNO3) or placebo capsules containing potassium chloride (KCl) daily for 5 days. The primary endpoint is development of CIN using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. A key secondary endpoint is renal function over a 3-month follow-up period. Additional secondary endpoints include serum renal biomarkers (e.g. neutrophil gelatinase-associated lipocalin) at 6 h, 48 h and 3 months following administration of contrast. Cost-effectiveness of inorganic nitrate therapy will also be evaluated. SUMMARY: This study is designed to investigate the hypothesis that inorganic nitrate treatment decreases the rate of CIN as part of semi-emergent coronary angiography for ACS. Inorganic nitrate is a simple and easy to administer intervention that may prove useful in prevention of CIN in at-risk patients undergoing coronary angiographic procedures.

EndoPil: A Magnetically Actuated Swallowable Capsule for Weight Management: Development and Trials.

Intragastric balloons (IGBs), by occupying the stomach space and prolonging satiety, is a promising method to treat obesity and consequently improves its associated comorbidities, e.g. coronary heart disease, diabetes, and cancer. However, existing IGBs are often tethered with tubes for gas or liquid delivery or require endoscopic assistance for device delivery or removal, which are usually uncomfortable, costly, and may cause complications. This paper presents a novel tetherless, magnetically actuated capsule (EndoPil) which can deploy an IGB inside the stomach after being swallowed and being activated by an external magnet. The external magnet attracts a small magnet inside the EndoPil to open a valve, triggering the chemical reaction of citric acid and potassium bicarbonate to produce carbon dioxide gas, which inflates a biocompatible balloon (around 120 mL). A prototype, 13 mm in diameter and 35 mm in length, was developed. Simulations and bench-top tests were conducted to test the force capability of the magnetic actuation mechanism, the required force to activate the valve, and the repeatability of balloon inflation. Experiments on animal and human were successfully conducted to demonstrate the safety and feasibility of inflating a balloon inside the stomach by an external magnet.

Effects of high potassium iodate intake on iodine metabolism and antioxidant capacity in rats.

BACKGROUND: KIO3 and KI are the most common salt iodization agents. Coincidentally, iodine exists naturally in high-iodine drinking water in the form of iodide (I-) or iodate (IO3-). As an oxidizing substance, IO3- should be reduced to I- before it can be effectively used by the thyroid. However, there is a lack of systematic studies on the metabolic process of high dose KIO3in vivo. METHODS: The iodine metabolism processes in the thyroid and serum of rats after high KIO3 intake were determined using high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC/ICP-MS) and arsenic cerium catalytic spectrophotometry. The changes of redox activity in the serum, thyroid, liver, and kidneys were observed by detecting total antioxidative activity (TAA). RESULTS: High doses of IO3- were completely reduced to I-in vivo within 0.5 h. The level of organic bound iodine in the serum was stable, while the organic bound iodine in the thyroid increased to a plateau after intake of high-dose KIO3. The levels of total iodine and I- in serum and thyroid increased quickly, then all decreased after reaching the maximum absorption peak, and I- had two absorption peaks in serum. The thyroid blocking dose of I- was 0.5 mg/kg in rat. Additionally, high KIO3 intake did not influence the TAA in serum and other tissues. CONCLUSION: The body is able to reduce and utilize high doses of KIO3 ingested through the digestive tract. The metabolism of high KIO3in vivo is characterized by two absorption process of I- in serum and the thyroid blocking effect. Moreover, a single intake of high-dose KIO3 does not affect TAA in vivo. The results suggest that such excess IO3- may have be reduced in the digestive tract before I- enters the blood.

Hypokalemic paralysis as an initial presentation of Sjogren syndrome.

Sjogren syndrome (SS) is a systemic autoimmune disorder with predominant exocrine gland involvement leading to sicca symptoms. Among extraglandular manifestations, renal disease is the most common. Tubular interstitial nephritis and renal tubular acidosis (RTA) are the common presentations. Mild hypokalemia associated with distal RTA is common in SS, however, severe hypokalemia causing paralysis is unusual. We report the case of a 26-year-old female who presented with hypokalemic paralysis. On evaluation, distal RTA was diagnosed. Further evaluation showed positive SS-a/SS-b antibodies in high titer, which confirms the diagnosis of primary SS. Our report illustrates that SS is a rare but important cause of hypokalemic paralysis.

Résumé syndrome de Sjogren (SS) est une maladie auto-immune systémique avec une atteinte prédominante des glandes exocrines entraînant des symptômes de sicca. Parmi manifestations extraglandulaires, la maladie rénale est la plus courante. La néphrite interstitielle tubulaire et l'acidose tubulaire rénale (RTA) sont les présentations. Une hypokaliémie légère associée à un RTA distal est courante dans les SS, cependant, une hypokaliémie sévère provoquant une paralysie est inhabituelle. Nous rapportons le cas d'une femme de 26 ans qui présentait une paralysie hypokaliémique. À l'évaluation, un RTA distal a été diagnostiqué. Plus loin l'évaluation a montré des anticorps SS-a / SS-b positifs à titre élevé, ce qui confirme le diagnostic de SS primaire. Notre rapport montre que SS est un cause rare mais importante de paralysie hypokaliémique.

Retrospective study of the efficacy of oral potassium supplementation in cats with kidney disease.

OBJECTIVES: The aim of this study was to assess the effect of three oral potassium supplements (potassium gluconate tablets [PGT], potassium gluconate granules [PGG] and potassium citrate granules [PCG]) on hypokalemia and serum bicarbonate in cats with chronic kidney disease (CKD). METHODS: Medical records (2006-2016) were retrospectively searched for cats that had been prescribed an oral potassium supplement for management of their CKD-associated hypokalemia. For inclusion, laboratory work had to be available at the time of hypokalemia diagnosis, and at recheck within 1-6 weeks. Treatment response was defined in three ways: any increase in potassium, an increase in potassium to within the normal reference interval, and an increase to >4 mEq/l. RESULTS: Thirty-seven cats met inclusion criteria (16 PGT, 11 PGG, 10 PCG). Dosing ranged from 0.21 to 1.6 mEq/kg/day for PGT, from 0.25 to 1.48 mEq/kg/day for PGG and from 0.04 to 1.34 mEq/kg/day for PCG. After supplementation, 36/37 cats had an increase in potassium, 34/37 increased to within the reference interval and 24/37 had an increase in potassium to >4 mEq/l. There was a statistically significant difference in serum potassium post-supplementation for all three treatments: PGT (P = 0.0001), PGG (P = 0.001) and PCG (P = 0.002). There was a positive correlation between PGT dose and change in potassium concentration (P = 0.04), but there was no significant correlation for PGG or PCG. In cats that had data available, serum bicarbonate increased >2 mEq/l in 1/6 PGT, 1/6 PGG and 3/4 PCG cats. CONCLUSIONS AND RELEVANCE: All three potassium supplements were effective in treating hypokalemia secondary to CKD in the majority of cats despite variable dosing. Data were limited to assess the alkalinizing effect and prospective studies are needed.

Acute ulceronecrotic adverse reaction to potassium hydroxide 5% solution in the treatment of molluscum contagiosum.

Molluscum contagiosum is a common childhood condition, and although it is self-limited, treatments are often prescribed. Several medications are available, but there is no consensus regarding the optimal choice in the pediatric population. We report a child who underwent potassium hydroxide 5% treatment resulting in superficial diffuse erosions caused by the inappropriate application. This underlines the importance of parent education before use of this medication with well-known caustic properties.

Potassium phosphate and potassium carbonate administration by feed or drinking water improved broiler performance, bone strength, digestive phosphatase activity and phosphorus digestibility under induced heat stress conditions.

Potassium phosphate (K2HPO4) and potassium carbonate (K2CO3) administration by feed or water were evaluated on broiler performance, bone strength, alkaline phosphatase activity (ALP), and phosphorus digestibility under heat stress and high chloride condition. Experimental groups include control; 15 cc/kg K2HPO4; 30 cc/kg K2HPO4; 15 cc/l K2HPO4; and 3.7 g/kg K2CO3. Body weight (BW), feed and water consumption, plasma potassium, phosphorus, and calcium concentration along with plasma and digestive ALP and intestinal digesta pH were measured during the trial. Tibia ash, calcium and phosphorus content, and breaking strength were measured on days 21 and 42 and phosphorus digestibility on day 36 of age. As a result of this, study feed and water consumption was increased by supplementation of the feed or water with K2HPO4 (P ≤ 0.001). K2HPO4 increased body weight at 42 days of age (P ≤ 0.001). Tibia ash and phosphorus content was increased by K2HPO4 supplementation (P ≤ 0.004; P ≤ 0.003). K2CO3 did increased tibia ash but not changed tibia phosphorus content significantly. Tibia shear force, shear energy, extension, and length were improved by K2HPO4 administration at 42 days of age (P ≤ 0.001). Administration of either feed or water with K2HPO4 increased plasma potassium, phosphorus, and calcium concentration at 21 days of age, whereas K2CO3 reduced plasma potassium at 21 days of age (P ≤ 0.05). Plasma ALP reduced by addition of 15 cc K2HPO4 and K2CO3 to diets at 42 days of age, whereas digestive ALP was increased by inclusion of K2HPO4 and not by K2CO3. Supplementation of either feed or water with K2HPO4 increased phosphorus digestibility, whereas K2CO3 reduced phosphorus digestibility (P ≤ 0.003). Jejunum and ileum pH was reduced by K2HPO4 or by K2CO3 at 21 and 42 days of age (P ≤ 0.006; (P ≤ 0.05). Over all, results of current study revealed that K2HPO4 can be a suitable potassium salt choice instead of KCL in hot weather conditions especially when the water or diet contains high levels of chloride.

Cardioplegia defibrillation of circulatory and metabolic phase ventricular fibrillation in a swine model.

INTRODUCTION: We previously found potassium cardioplegia followed by rapid calcium reversal (Kplegia) can achieve defibrillation in a swine model of electrical phase of ventricular fibrillation (VF) comparable to standard care. HYPOTHESIS: Exploring 3 possible potassium dose and timing protocols, we hypothesize Kplegia may benefit resuscitation of longer duration untreated VF. METHODS: Three separate blinded randomized placebo-controlled trials were performed with electrically-induced VF untreated for durations of 6, 9, and 12min in a swine model. Experimental groups received infusion of 1 or 2 boluses of intravenous (IV) potassium followed by a single calcium reversal bolus. Potassium was replaced by saline in the control groups. Outcomes included: amplitude spectrum area (AMSA) during VF, resulting rhythms, number of defibrillations, return of spontaneous circulation (ROSC), and hemodynamics for 1h post ROSC. Binomial and interval data outcomes were compared with exact statistics. Serial interval data were assessed with mixed regression models. RESULTS: Twelve, 12, and 8 animals were included at 6, 9, and 12min VF durations for a total of 32. ROSC was achieved in: 4/6 Kplegia and 3/6 control animals in the 6min protocol, (p=1.00), 4/6 Kplegia and 2/6 control animals in the 9min protocol,(p=0.57), and 0/5 Kplegia and 1/3 control animals in the 12min protocol,(p=0.38). Two of 8 Kplegia animals achieved ROSC with chemical defibrillation alone. CONCLUSIONS: The majority of animals achieved ROSC after up to 9min of untreated VF arrest using K plegia protocols. K plegia requires further optimization for both peripheral IV and intraosseous infusion, and to assess for superiority over standard care. Institutional Animal Care and Use Committee protocol #15127224.

Nanoporous CD-MOF particles with uniform and inhalable size for pulmonary delivery of budesonide.

It is essential to optimize a carrier of dry powder inhalation (DPI) for the aerodynamic deposition in vitro to achieve pulmonary delivery of drug molecules in vivo. In this study, neutralized nanoporous γ-cyclodextrin metal-organic framework (CD-MOF) crystals with cubic morphology and uniform inhalation size were developed and modified as a DPI carrier for budesonide (BUD). Cholesterol (CHO) and leucine (LEU)-poloxamer were used to modify the CD-MOF powder for the improvement of flowability and particle aerodynamic behaviour, for which the particle size distribution, Carr's index and in vitro pulmonary deposition were assessed. Compared to CD-MOF or LEU-CD-MOF-BUD, CHO-CD-MOF had a superior mass median aerodynamic diameter (4.35 ±â€¯0.04 µm) and inhalable performance (fine particle fraction of 30.60 ±â€¯0.76%), which were maintained after budesonide loading (4.47 ±â€¯0.30 µm, 24.95 ±â€¯4.33%). The crystallinity, cytotoxicity and in vivo deposition of drug loaded samples (CHO-CD-MOF-BUD) were then investigated by powder X-ray diffraction (PXRD), cell viability study, in vivo fluorescence imaging and pharmacokinetic studies in rats. The characteristic PXRD crystallinity peaks of budesonide disappeared after being loaded into CHO-CD-MOF, potentially indicating the molecular incorporation of budesonide into the pores of CD-MOF. The cell viability of A549 cell was more than 90% for CHO-CD-MOF-BUD as a result of the good biocompatibility of CD-MOF. When Rhodamine B was carried by the DPI particles, the fluorescence signal at the lung tissue was markedly improved after cholesterol modification compared with CD-MOF, whilst the bioavailability of CHO-CD-MOF-BUD in rat was equivalent with that of the commercial product of Pulmicort Turbuhaler. Therefore, the CD-MOF powders modified by cholesterol can be used as a promising inhalable carrier for pulmonary delivery of drugs with small dose.

Cardiac sympathetic innervation scintigraphy with 123I-meta-iodobenzylguanidine. Basis, protocols and clinical applications in Cardiology. / Gammagrafía de inervación simpática cardiaca con 123I-metayodobencilguanidina. Fundamento, protocolos y aplicaciones clínicas en Cardiología.

Imaging of cardiac sympathetic innervation is only possible by nuclear cardiology techniques and its assessment is key in the evaluation of and decision-making for patients with cardiac sympathetic impairment. This review includes the basis of cardiac sympathetic scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG), recommended protocols, patient preparation, image acquisition and quantification, reproducibility, dosimetry, etc., and also the clinical indications for cardiac patients, mainly with regard to heart failure, arrhythmia, coronary artery disease, cardiotoxicity, including its contribution to establishing the indication for and monitoring the response to implantable cardiac devices, pharmacological treatment, heart transplantation and other.

Acute interaction between oral glucose (75 g as Lucozade) and inorganic nitrate: Decreased insulin clearance, but lack of blood pressure-lowering.

AIMS: Dietary inorganic nitrate (NO3- ) lowers peripheral blood pressure (BP) in healthy volunteers, but lacks such effect in individuals with, or at risk of, type 2 diabetes mellitus (T2DM). Whilst this is commonly assumed to be a consequence of chronic hyperglycaemia/hyperinsulinaemia, we hypothesized that acute physiological elevations in plasma [glucose]/[insulin] blunt the haemodynamic responses to NO3- , a pertinent question for carbohydrate-rich Western diets. METHODS: We conducted an acute, randomized, placebo-controlled, double-blind, crossover study on the haemodynamic and metabolic effects of potassium nitrate (8 or 24 mmol KNO3 ) vs. potassium chloride (KCl; placebo) administered 1 hour prior to an oral glucose tolerance test in 33 healthy volunteers. RESULTS: Compared to placebo, there were no significant differences in systolic or diastolic BP (P = 0.27 and P = 0.30 on ANOVA, respectively) with KNO3 , nor in pulse wave velocity or central systolic BP (P = 0.99 and P = 0.54 on ANOVA, respectively). Whilst there were significant elevations from baseline for plasma [glucose] and [C-peptide], no differences between interventions were observed. A significant increase in plasma [insulin] was observed with KNO3 vs. KCl (n = 33; P = 0.014 on ANOVA) with the effect driven by the high-dose cohort (24 mmol, n = 13; P < 0.001 on ANOVA; at T = 0.75 h mean difference 210.4 pmol/L (95% CI 28.5 to 392.3), P = 0.012). CONCLUSIONS: In healthy adults, acute physiological elevations of plasma [glucose] and [insulin] result in a lack of BP-lowering with dietary nitrate. The increase in plasma [insulin] without a corresponding change in [C-peptide] or [glucose] suggests that high-dose NO3- decreases insulin clearance. A likely mechanism is via NO-dependent inhibition of insulin-degrading enzyme.

Impact of Crystalloid or Albumin Priming of the Heart-Lung Machine on Inhospital Outcome after Coronary Artery Bypass Surgery.

BACKGROUND: Crystalloid priming is a cost-effective, free from immunological reactions, and independent from human plasma delivery. However, there is some debate on the negative impact of low plasma colloid pressure and higher incidence of systemic inflammatory response syndrome (SIRS). The aim of the study was to rule out any adverse effects of crystalloid priming on the postoperative outcome. METHODS: We investigated 520 consecutive patients, including emergencies, who had isolated on-pump coronary artery bypass grafting in 2009 by retrospective analysis in our clinic. Crystalloid priming (n = 294) was introduced as an alternative to albumin (n = 226). Reviewing patient charts and IT-based data generated a dataset of perioperative parameters. RESULTS: There were no differences with respect to demographical data and preexisting comorbidities between both groups. Despite equal perfusion times, more volume had to be substituted during extracorporeal circulation following crystalloid priming. However, this did not influence the inhospital outcomes. According to the definition of the "Sepsis-3 Guidelines," the incidence of SIRS was similar. There was no difference in the need for a vasopressor treatment, and only transient higher serum lactate levels were found in the crystalloid group. The incidence of neurologic and organ-related adverse events, as well as 30-day mortality was comparable. CONCLUSION: The use of crystalloid priming is safe in coronary artery bypass grafting surgery in adults. However, there might be a greater need for crystalloid fluids during surgery.

Low-Volume Cardioplegia and Myocardial Protection in Coronary Artery Bypass Graft Surgery.

We studied myocardial protection during coronary artery bypass graft surgery using low-volume cardioplegia (Cardioplexol) and minimal extracorporeal circulation (MECC) for different types of coronary artery diseases. In total, 426 consecutive patients were included and divided into four groups: those with left main stem stenosis (n = 45), those with three-vessel disease (n = 200), those with both (n = 141), and those with neither (n = 40). The peak postoperative myocardial markers and 30-day mortality were analyzed. Both myocardial markers and 30-day mortality were significantly elevated in patients with isolated main stem stenosis. We conclude that the use of low-volume cardioplegia and MECC is safe. However, patients with underlying isolated left main stem stenosis might be less protected.

Comparative Effects of Blood and Crystalloid Cardioplegia on Cellular Injury and Oxidative Stress in Cardiovascular Surgery.

PURPOSE: The purpose of this study was to evaluate the effect of different cardioplegic solutions on endothelial integrity and oxidative stress in cardiovascular surgery. METHODS: In this randomized prospective study, after ethics approval and informed consent, 60 surgical patients were included. Patients undergoing coronary bypass surgery were randomized into two groups as warm blood cardioplegia (n = 30) and cold crystalloid cardioplegia (n = 30) following the cross-clamping. Measurements were performed at three time points: before induction of anesthesia (T1), at admission to intensive care unit (ICU) (T2) and at the 24th postoperative hour (T3). Besides biochemical routine hemodynamic monitoring, patients were assessed for the sialic acid (SA), ischemic-modified albumin (IMA), advanced oxide protein products (AOPPs), total thiol (SH), and free hemoglobin (fHb) level. RESULTS: Neither crystalloid nor blood cardioplegia led to significant changes in the AOPPs, T-SH, and SA level (p >0.05). Crystalloid cardioplegia, however, increased IMA level compared to both baseline (p <0.01) and blood cardioplegia group (p <0.05). fHb levels were transiently increased in both groups at the second-time point (p <0.001). fHb level was lower in the crystalloid group compared to that in the other group (p <0.05) at T2. CONCLUSION: Cardioplegia type creates similar effects on glycocalyx integrity. However, myocardial protection could be provided with warm blood cardioplegia.

Chronic Ingestion of Sodium and Potassium Bicarbonate, with Potassium, Magnesium and Calcium Citrate Improves Anaerobic Performance in Elite Soccer Players.

Anaerobic power and anaerobic capacity significantly influence performance in many sport disciplines. These include prolonged sprints in athletics, swimming, or cycling, and other high intensity intermittent sports, such as soccer or basketball. Considering the association of exercise-induced acidosis and fatigue, the ingestion of potential buffering agents such as sodium bicarbonate, has been suggested to attenuate metabolic acidosis and improve anaerobic performance. Since elite soccer players cover from 200 to 350 m while sprinting, performing 40⁻60 all out sprints during a game, it seems that repeated sprint ability in soccer players is among the key components of success. In our experiment, we evaluated the effectiveness of chronic supplementation with sodium and potassium bicarbonate, fortified with minerals, on speed and speed endurance in elite soccer players. Twenty-six soccer players participated in the study. The subjects were randomly divided into two groups. The experimental group was supplemented with sodium bi-carbonate and potassium di-carbonate fortified with minerals, while the control group received a placebo. The athletes were tested at baseline and after nine days of supplementation. Anaerobic performance was evaluated by the Repeated Anaerobic Sprint Test (RAST) protocol which involved 6 × 30 m max sprints, separated by 10 s of active recovery. Resting, post ingestion and post exercise concentrations of HCO3- and blood pH were measured as well as lactate concentration. The current investigation demonstrated a significant increase in RAST performance of elite soccer players supplemented with sodium and potassium bicarbonate along with calcium phosphate, potassium citrate, and magnesium citrate ingested twice a day over a nine-day training period. The improvements in anaerobic performance were caused by increased resting blood pH and bicarbonate levels.

WITHDRAWN: Iodine supplementation for preventing iodine deficiency disorders in children.

BACKGROUND: Iodine deficiency is the main cause of potentially preventable mental retardation in childhood, as well as causing goitre and hypothyroidism in people of all ages. It is still prevalent in large parts of the world. OBJECTIVES: To assess the effects of iodine supplementation overall, and of different forms and dosages of iodine supplementation separately, in the prevention of iodine deficiency disorders in children. SEARCH METHODS: The Cochrane Library, MEDLINE, EMBASE and reference lists, databases of ongoing trials and the Internet were searched. SELECTION CRITERIA: We included randomised controlled trials and prospective controlled trials not using randomisation of iodine supplementation in children living in areas of iodine deficiency. DATA COLLECTION AND ANALYSIS: Two reviewers did the initial data selection and quality assessment of trials independently. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarised the data in a narrative format. MAIN RESULTS: Twenty-six prospective controlled trials were related to our question, assessing a total of 29613 children. Twenty of them were classified as being of low quality, six of moderate quality. Most studies used iodised oil as a supplement, but other supplements were also used. The intervention groups were compared to a non-supplemented control group, different doses or different forms of iodine supplementation.There was a clear tendency towards goitre reduction with iodine supplementation; this was significant in several studies. Significant differences in physical development were not seen, except in one study. Results for differences in cognitive and psychomotor measures were mixed, with only few studies showing a positive intervention effect. One study suggested that infant mortality was lowered after iodine supplementation.Most studies showed a significant increase in urinary iodine excretion and levels recommended by the WHO were reached in most cases after supplementation. Thyroid-stimulating hormone (TSH) levels were significantly reduced in one study. In 1.8% of the children investigated, adverse effects were found, most of them were minor and transient. AUTHORS' CONCLUSIONS: Despite most of the included studies being of low quality, the results suggest that iodine supplementation, especially iodised oil, is an effective means of decreasing goitre rates and improving iodine status in children. Indications of positive effects on physical and mental development and mortality were seen, although results were not always significant. Adverse effects were generally minor and transient. Insufficient evidence was available on non-oil supplements. High quality controlled studies investigating relevant long term outcome measures are needed to address the question of the best form of iodine supplementation in different population groups and settings.

Humic acid and enzymes inclusion in canola-based diets generate different responses in growth performance, protein utilization dynamics, and hemato-biochemical parameters in broiler chickens.

The current study was conducted to investigate the effect of a humic acid and enzymes on growth performance, protein utilization, and blood parameters in broilers fed canola-based diets. Canola meal (CM) is characterized as low protein compared to soybean meal. Two-hundred-twenty broiler chickens were randomly allotted to the following 5 dietary treatments: 1. Control (commercial broiler diet); 2. CM (17.5% canola meal inclusion); 3. CMEnz (CM + 0.3 g/kg enzymes [Axtra XAP]); 4. CMPh (CM + 1.5% potassium humate, PH) and 5. CMEnzPh (CM + 1.5% PH + 0.3 g/kg Axtra XAP). Each treatment was replicated 4 times with each pen holding 11 birds as the experimental unit. The feeding trial was conducted over a grower (15 to 28 d) and a finisher phase (29 to 42 d). Diet did not affect (P > 0.05) feed intake across either grower or finisher phase but affected average daily gain (ADG) in the grower phase. In the grower phase, broilers fed CM had the highest ADG (71± 1.08 g/d), while the control (63.75 ± 1.08 g/d) had the lowest. However, control chickens had the highest feed conversion ratio (FCR) (1.65), while those fed CM (1.47) had the lowest. Diet significantly affected total white blood cell and white blood cell differential, which were consistently high in broilers fed CMEnzPh. With regard to serum metabolites, CM had the highest levels (P < 0.05) of aspartate aminotransferase (AST) (406.86 ± 38.07 IU/L), while CMEnzPh (254.17 ± 41.11 IU/L) had the lowest levels. Additionally, broilers fed CMPh had the highest (P < 0.05) serum sodium content (150.57 ± 0.69 mmol/l). Overall, canola meal, in the presence of enzymes and humic acid, was shown to have great potential as an alternative replacement of soybean meal in broiler diets. The findings from the study can, therefore, contribute to the design of low-cost canola-based feed formulations that will improve growth performance and health status in poultry farming systems in the future.

Pilot Study Examining the Influence of Potassium Bicarbonate Supplementation on Nitrogen Balance and Whole-Body Ammonia and Urea Turnover Following Short-Term Energy Restriction in Older Men.

With aging there is a chronic low-grade metabolic-acidosis that may exacerbate negative protein balance during weight loss. The objective of this randomized pilot study was to assess the impact of 90 mmol∙day-1 potassium bicarbonate (KHCO3) versus a placebo (PLA) on 24-h urinary net acid excretion (NAE), nitrogen balance (NBAL), and whole-body ammonia and urea turnover following short-term diet-induced weight loss. Sixteen (KHCO3; n = 8, PLA; n = 8) older (64 ± 4 years) overweight (BMI: 28.5 ± 2.1 kg∙day-1) men completed a 35-day controlled feeding study, with a 7-day weight-maintenance phase followed by a 28-day 30% energy-restriction phase. KHCO3 or PLA supplementation began during energy restriction. NAE, NBAL, and whole-body ammonia and urea turnover (15N-glycine) were measured at the end of the weight-maintenance and energy-restriction phases. Following energy restriction, NAE was -9.8 ± 27.8 mmol∙day-1 in KHCO3 and 43.9 ± 27.8 mmol∙day-1 in PLA (p < 0.05). No significant group or time differences were observed in NBAL or ammonia and urea turnover. Ammonia synthesis and breakdown tended (p = 0.09) to be higher in KHCO3 vs. PLA following energy restriction, and NAE was inversely associated (r = -0.522; p < 0.05) with urea synthesis in all subjects. This pilot study suggests some benefit may exist with KHCO3 supplementation following energy restriction as lower NAE indicated higher urea synthesis.

Discrete physiological effects of beetroot juice and potassium nitrate supplementation following 4-wk sprint interval training.

The physiological and exercise performance adaptations to sprint interval training (SIT) may be modified by dietary nitrate ([Formula: see text]) supplementation. However, it is possible that different types of [Formula: see text] supplementation evoke divergent physiological and performance adaptations to SIT. The purpose of this study was to compare the effects of 4-wk SIT with and without concurrent dietary [Formula: see text] supplementation administered as either [Formula: see text]-rich beetroot juice (BR) or potassium [Formula: see text] (KNO3). Thirty recreationally active subjects completed a battery of exercise tests before and after a 4-wk intervention in which they were allocated to one of three groups: 1) SIT undertaken without dietary [Formula: see text] supplementation (SIT); 2) SIT accompanied by concurrent BR supplementation (SIT + BR); or 3) SIT accompanied by concurrent KNO3 supplementation (SIT + KNO3). During severe-intensity exercise, V̇o2peak and time to task failure were improved to a greater extent with SIT + BR than SIT and SIT + KNO3 ( P < 0.05). There was also a greater reduction in the accumulation of muscle lactate at 3 min of severe-intensity exercise in SIT + BR compared with SIT + KNO3 ( P < 0.05). Plasma [Formula: see text] concentration fell to a greater extent during severe-intensity exercise in SIT + BR compared with SIT and SIT + KNO3 ( P < 0.05). There were no differences between groups in the reduction in the muscle phosphocreatine recovery time constant from pre- to postintervention ( P > 0.05). These findings indicate that 4-wk SIT with concurrent BR supplementation results in greater exercise capacity adaptations compared with SIT alone and SIT with concurrent KNO3 supplementation. This may be the result of greater NO-mediated signaling in SIT + BR compared with SIT + KNO3. NEW & NOTEWORTHY We compared the influence of different forms of dietary nitrate supplementation on the physiological and performance adaptations to sprint interval training (SIT). Compared with SIT alone, supplementation with nitrate-rich beetroot juice, but not potassium [Formula: see text], enhanced some physiological adaptations to training.