A biophysical analysis on the arm stroke efficiency in front crawl swimming : comparing methods and determining the main performance predictors

Purpose: to compare different methods to assess the arm stroke efficiency ( ηF ), when swimming front crawl using the arms only on the Measurement of Active Drag System (MAD System) and in a free-swimming condition, and to identify biophysical adaptations to swimming on the MAD System and the main biophysical predictors of maximal swimming speed in the 200 m front crawl using the arms only ( v200m ). Methods: fourteen swimmers performed twice a 5 × 200 m incremental trial swimming the front crawl stroke using the arms only, once swimming freely, and once swimming on the MAD System. The total metabolic power was assessed in both conditions. The biomechanical parameters were obtained from video analysis and force data recorded on the MAD System. The ηF was calculated using: (i) direct measures of mechanical and metabolic power (power-based method); (ii) forward speed/hand speed ratio (speed-based method), and (iii) the simplified paddle-wheel model. Results: both methods to assess ηF on the MAD System differed (p < 0.001) from the expected values for this condition ( ηF = 1), with the speed-based method providing the closest values ( ηF ~0.96). In the free-swimming condition, the power-based ( ηF ~0.75), speed-based ( ηF ~0.62), and paddle-wheel ( ηF ~0.39) efficiencies were significantly different (p < 0.001). Although all methods provided values within the limits of agreement, the speed-based method provided the closest values to the “actual efficiency”. The main biophysical predictors of v200m were included in two models: biomechanical (R2 = 0.98) and physiological (R2 = 0.98). Conclusions: our results suggest that the speed-based method provides the closest values to the “actual ηF ” and confirm that swimming performance depends on the balance of biomechanical and bioenergetic parameter

Allopurinol Reduces the Lethality Associated with Acute Renal Failure Induced by Crotalus durissus terrificus Snake Venom: Comparison with Probenecid

In Brazil, among registered snake bites, those by the genus Crotalus originate the highest mortality rate. The rattlesnake Crotalus durissus terrificus is the most frequently implicated in these accidents. The kidney is a particularly vulnerable organ to the venom of this rattlesnake. In fact, the most serious complication of Crotalus snake bite is the renal dysfunction, and among the fatal cases of Crotalus bites in Brazil 5% are patients treated with antivenom. The hyperuricemia has been observed in human accidents with snake venoms, but this parameter has not received any special attention as a relevant factor in the etiology of renal dysfunction caused by these venoms. This study examined the effects of treatments with low-cost and low-risk uricostatic (allopurinol) and uricosuric (probenecid) drugs on the envenomation by C. d. terrificus, showing that allopurinol and probenecid mitigated certain nephrotoxic effects, as well as the survival of envenomed mice was improved through the effects of allopurinol on reduction of oxidative stress and intracellular formation of uric acid. This new knowledge provides consistent evidences linking uric acid with the renal dysfunction induced by rattlesnake bites and that the allopurinol deserves to be clinically evaluated as an approach complementary to anti-snake venom serotherapy

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

The Interrelationship between Leukotriene B4 and Leukotriene-A4-Hydrolase in Collagen/Adjuvant-Induced Arthritis in Rats

This study aimed to check the involvement of lipid mediator leukotriene (LT) B4 and the activity of LTA4 hydrolase (LTA4H) in the development of arthritis induced in rats by collagen and adjuvant (CIA). High-performance liquid chromatography (HPLC) and enzyme immunoassay (EIA) were used for measurements of LTB4 and LTA4H in plasma, synovial fluid (SF), soluble (SO), and solubilized membrane-bound fraction (MB) from synovial tissue (ST) and peripheral blood mononuclear cells (PBMCs) of CIA-arthritic and CIA-resistant. EIA process is simple, clean, and rapid and offered advantages over HPLC, showing that in SF and MB-PBMCs of CIA-arthritic and CIA-resistant, and in MB-ST of CIA-resistant, LTB4 and LTA4H were altered in parallel and were positively related. In the plasma and SO-ST and SO-PBMCs of CIA-arthritic and CIA-resistant, and in MB-ST of CIA-arthritic, this pattern was not found. The primordial role played by LTA4H in the biosynthesis of LTB4 was confirmed together with the existence of alternative steps that regulate LTB4 without participation of LTA4H. The involvement of compartmentalized and coupled changes of LTB4 and LTA4H in the resistance and development of arthritis in CIA model was demonstrated for the first time

Histopathological features of renal samples.

<p>Slides of hematoxilin-eosin stained sagittal sections from representative kidneys of mice treated with: <b>I</b> and <b>II</b>: vehicle (control); see normal appearance of Bowman's capsule (<b>BC</b>), glomerulus (<b>G</b>), macula densa (<b>DM</b>) and distal tubule (<b>DT</b>); <b>III</b>, <b>IV</b> and <b>V</b>: <i>C. d. terrificus</i> venom; the most frequently changes detected were edema (<b>*</b>), fibrosis (<b>1</b>) with cell influx (<b>2</b>), and tubular necrosis with tubules markedly dilated and cellular debris in the lumen (<b>3</b>, <b>4</b>) and in the brush border (<b>BB</b>). Treatments of envenomed with allopurinol or probenecid acted indistinguishably to ameliorate the frequency and the intensity of detectable histological changes comparatively with untreated envenomed mice. Bars = 100 µm.</p

Schematic diagram depicting mechanisms and hypothetical actions of allopurinol and probenecid in <i>vCdt</i> nephrotoxicity.

<p>ARF induced by <i>vCdt</i> occurs through indirect and direct actions leading to lethality. Direct actions of <i>vCdt</i> generate hyperuricemia and renal oxidative stress. Uric acid has direct intracellular pro-oxidative effects. Allopurinol and probenecid restore uricemia and renal oxidative stress caused by <i>vCdt</i>. These beneficial effects must be, in part, exerted through a reduction of intracellular deposit of urate, as a consequence of the reduction of uric acid formation due to the inhibition of xanthine oxidase (allopurinol) or an inhibition of an organic anion transport exchanger that blocks the entry of uric acid into the cells (probenecid). Allopurinol, but not probenecid, protects against the lethality caused by <i>vCdt</i>. This differential protective effect of allopurinol is not related to the blocking of xanthine oxidase-associated oxidants, but it is likely related to the blocking of oxidant effects of increased production of uric acid in the intracellular environment more than the entry of uric acid into the cells.</p

Effects of treatments on renal function parameters in the urine.

<p>Mice treated with vehicle (control), allopurinol (NL), probenecid (PB) and <i>Crotalus durissus terrificus</i> venom (<i>vCdt</i>) followed by NL (<i>vCdt</i>+NL) or PB (<i>vCdt</i>+PB) after 2 h. Values are means ± SEM of pooled animals, 16 (control), 9 (NL), 10 (PB), 12 (<i>vCdt</i>), 22 (<i>vCdt</i>+NL) and 12 (<i>vCdt</i>+PB) in triplicates. Comparison of the same parameter among groups: ANOVA (Osmolality, p<0.0001; Creatinine, p<0.0009; Uric acid, p<0.005; Urea, p = 0.06; Protein, p<0.001). Post hoc Student-Newman-Keuls (different letters over the bars indicate statistical differences: osmolality and creatinine, p<0.01; uric acid and protein, p<0.05).</p

Effects of treatments on hematocrit and renal function parameters in the blood plasma.

<p>Mice treated with vehicle (control), allopurinol (NL), probenecid (PB) and <i>Crotalus durissus terrificus</i> venom (<i>vCdt</i>) followed by NL (<i>vCdt</i>+NL) or PB (<i>vCdt</i>+PB) after 2 h. Values are means ± SEM. Number of animals in parentheses. Comparison of the same parameter among groups: ANOVA (Hematocrit, p = 0.1807; Osmolality, p = 0.3577; Creatinine, p<0.006; Uric acid, p<0.0001; Urea, p<0.003; Protein, p<0.0001). Post hoc Student-Newman-Keuls (different letters over the bars indicate statistical differences: creatinine and urea, p<0.05; uric acid and protein, p<0.01).</p