A Single Dose of Ibuprofen Impacts IL-10 Response to 164-km Road Cycling in the Heat.

Purpose: The purpose was to determine the effect of a single-dose prophylactic ibuprofen use before a 164-km road cycling event in high ambient temperature on the circulating cytokine and leukocyte responses. Methods: Twenty-three men (53 ± 8 y, 172.0 ± 22.0 cm, 85.1 ± 12.8 kg, 19.6 ± 4.4% body fat) completed a 164-km self-paced recreational road cycling event in a hot, humid, sunny environment (WBGT = 29.0 ± 2.9°C) after consuming 600 mg of ibuprofen (n = 13) or a placebo (n = 10). Blood samples were obtained one to two hours before (PRE) and immediately after (POST) the event, and analyzed for concentrations of circulating cytokines interleukins (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, GM-CSF, IFN-γ, and TNF-α and leukocytes (total leukocytes, granulocytes, monocytes, and lymphocytes). Results: Event completion time was 400.2 ± 74.8 min. Concentrations of all cytokines (except IL-1ß, IL-2, IL-5, IL-12, GM-CSF, and IFN-γ) and of all leukocyte subsets increased from PRE to POST. Ibuprofen ingestion attenuated the increase in IL-10 (86% increase with Ibuprofen; 270% increase with placebo). Conclusions: Consuming 600 mg of Ibuprofen prior to a 164-km road cycling event in a hot-humid environment attenuates exercise-induced increases in the concentration of the anti-inflammatory cytokine IL-10, but does not alter the effect of the exercise event on concentrations of other circulating cytokines or leukocyte subset concentrations.

Enhancement of pressure perturbations in ablation due to kinetic magnetized transport effects under direct-drive inertial confinement fusion relevant conditions.

We present kinetic two-dimensional Vlasov-Fokker-Planck simulations, including both self-consistent magnetic fields and ablating ion outflow, of a planar ablating foil subject to nonuniform laser irradiation. Even for small Hall parameters (ωτ_{ei}≲0.05) self-generated magnetic fields are sufficient to invert and enhance pressure perturbations. The mode inversion is caused by a combination of the Nernst advection of the magnetic field and the Righi-Leduc heat flux. Nonlocal effects modify these processes. The mechanism is robust under plasma conditions tested; it is amplitude independent and occurs for a broad spectrum of perturbation wavelengths, λ_{p}=10-100µm. The ablating plasma response to a dynamically evolving speckle pattern perturbation, analogous to an optically smoothed beam, is also simulated. Similar to the single-mode case, self-generated magnetic fields increase the degree of nonuniformity at the ablation surface by up to an order of magnitude and are found to preferentially enhance lower modes due to the resistive damping of high mode number magnetic fields.

Consumption of a high-fat meal was associated with an increase in monocyte adhesion molecules, scavenger receptors, and Propensity to Form Foam Cells.

BACKGROUND: Macrophage-derived foam cells are the predominant component of arterial plaques in the early stages of atherosclerosis. One factor that poses a major risk for plaque development is high levels of plasma low-density lipoprotein (LDL) as a result of a high-fat meal. In order to better understand how an individuals' diet affects arterial plaque deposition via the process of foam cell formation, we measured the acute circulating monocyte activity response after consuming a high-fat meal (85% of daily fat allowance). MATERIALS AND METHODS: Venous blood samples from 17 participants were acquired on a FlowSight. Samples were analyzed to identify nonclassical (CD14+/16+) and classical (CD14+/16-) monocytes. We measured monocyte concentration, adhesion molecule expression, CD36 expression, and oxidized LDL (oxLDL) endocytosis for preprandial 1, 3, and 5 h postprandial. RESULTS: Consuming a high-fat meal caused increases in oxLDL uptake, adhesion molecule expression, and CD36 expression in both classical and nonclassical monocytes, with the nonclassical monocytes responding with larger increases than the classical monocytes. CONCLUSION: These results suggest that consumption of a high-fat meal increased the potential of monocytes to become foam cells, and implicates nonclassical monocytes as having greater potential than classical monocytes to become foam cells. © 2016 International Clinical Cytometry Society.

Effects of exercise mode and participant sex on measures of anaerobic capacity.

AIM: The purpose of this study was to compare values of maximal accumulated oxygen deficit (MAOD; a measure of anaerobic capacity) and peak post-exercise blood lactate concentration ([lactate]; a reflection of glycolytic contribution) in running and cycling, in women and men. METHODS: One hundred and nineteen women and 104 men performed an exhaustive treadmill test of ~5 min duration; 106 women and 110 men performed an exhaustive cycle ergometer test of ~5 min duration. Oxygen demands for the exhaustive exercise tests were estimated by extrapolation from steady state VO2 values. For running, an upwardly curvilinear relationship between demand and speed (i.e., with demand a function of speed1.05) was used. For cycling, a linear relationship between demand and work rate was used. RESULTS: The MAOD was 22% higher (P<0.01) in running than in cycling, and 32% higher (P<0.01) in men than in women. Peak [lactate] was 8% higher (P<0.01) in running, and 23% higher (P<0.01) in men. The VO2max was 10% higher (P<0.01) in running, and 14% higher (P<0.01) in men. CONCLUSION: These results indicate that some of the differences between running and cycling, which affect MAOD, do not similarly affect VO2max or peak [lactate]. It is possible that greater lactate removal by the upper body musculature during running permits the greater anaerobic capacity in running, and explains the relatively small difference in blood [lactate] in running compared to cycling.

Relationship between speed and time in running.

The purpose of this study was to evaluate the effect of using different mathematical models to describe the relationship between treadmill running speed and time to exhaustion. All models generated a value for an aerobic parameter (critical speed; S (critical)). 35 university students performed 5-7 constant-speed 0%-slope treadmill tests at speeds that elicited exhaustion in ∼3 min to ∼10 min. Speed and time data were fitted using 3 models: (1) a 2-parameter hyperbolic model; (2) a 3-parameter hyperbolic model; and (3) a hybrid 3-parameter hyperbolic+exponential model. The 2-parameter model generated values for S (critical) (mean (± SD): 186 ± 33 m·min (-1)) and anaerobic distance capacity (ADC; 251 ± 122 m) with a high level of statistical certainty (i.e., with small SEEs). The 3-parameter models generated parameter estimates that were unrealistic in magnitude and/or associated with large SEEs and little statistical certainty. Therefore, it was concluded that, for the range of exercise durations used in the present study, the 2-parameter model is preferred because it provides a parsimonious description of the relationship between velocity and time to fatigue, and it produces parameters of known physiological significance, with excellent confidence.

The development of a new three-step protocol to determine the efficacy of disinfectant wipes on surfaces contaminated with Staphylococcus aureus.

We developed a three-step protocol to quantify the efficacy of disinfectant wipes, their ability to remove and prevent microbial transfer from surfaces and their overall antimicrobial activity. Meticillin-resistant (MRSA) or -susceptible (MSSA) Staphylococcus aureus (6-7 log(10)cfu) were inoculated onto stainless steel discs with or without organic load and dried. Grapefruit extract-containing test wipes and unmedicated control wipes were used. In step 1, wipes were mechanically rotated against surfaces for 10s at 60rpm, exerting a weight of 100+/-5g. Bacterial removal was assessed by transferring the steel discs to neutraliser, resuspending and counting remaining bacteria. In step 2, bacterial transfer from wipes was assessed by eight consecutive mechanical adpression transfers to agar/neutraliser plates. Step 3 was the measurement of antimicrobial activity by direct inoculation of the wipes for 10s followed by neutralisation and enumeration. Test wipes achieved a significantly higher bacterial cell removal than control wipes on all surfaces (P<0.05). The low bactericidal activity of the wipes (<1 log(10) reduction when directly inoculated) and the subsequent survival of bacteria on the wipes, however, led to repeated microbial transfer when initially high contamination levels were present. There were no differences between MRSA and MSSA in removal, transfer or antimicrobial activity. The three-step method is a useful tool for developing future guidelines to assess the ability of wipes to disinfect surfaces.

VO2 response profiles in severe intensity exercise.

AIM: VO2peak can be achieved over the range of intensities that define the severe intensity domain. The purpose of this study was to help characterize the VO2 response during constant-load exercise in this domain. METHODS: Twelve participants performed cycle ergometer tests at 267+/-52 W, 238+/-45 W, and 216+/-37 W, which were individually selected to elicit VO2peak and to cause fatigue in 3 min, 5 min, and 7 min, respectively. RESULTS: Times to fatigue were 201+/-16 s, 301+/-20 s, and 448+/-51 s, respectively. VO2 responded faster at higher work rates, with VO2peak reached after 154+/-25 s, 193+/-35 s, and 206+/-24 s, respectively. Extrapolation of the times to reach VO2peak revealed that 300 W was the highest power, and 151 s was the shortest time, for which VO2peak could be elicited. TheVO2 response was described using a three-component model. Exercise intensity did not affect the speed of the primary response, with time constants of 22+/-3 s, 23+/-4 s, and 23+/-4 s, respectively. However, the size of the primary phase was greater at higher intensities, with amplitudes of 1,798+/-200 mlxmin-1, 1,739+/-267 mlxmin-1, and 1,677+/-254 mlxmin-1, respectively. The amplitude of the slow component was correspondingly smaller at higher intensities. Extrapolation of the slow component amplitudes revealed that 299 W was the highest intensity, and 152(-1)53 s was the shortest time, for which a slow component would be engendered. CONCLUSION: VO2peak is attained faster at higher intensities because the amplitude of the primary response is greater, not because the response is faster. There is a slow component to the VO2 response at all intensities within the severe domain, but not at higher intensities, in the extreme domain, where fatigue occurs before VO2peak can be elicited.

Point-of-care controls for nosocomial legionellosis combined with chlorine dioxide potable water decontamination: a two-year survey at a Welsh teaching hospital.

This study reports a two-year programme of attempted eradication of Legionella colonization in the potable water supply of a 1000-bed tertiary care teaching hospital in Wales. There was a simultaneous, point-of-care, sterile-water-only policy for all intensive care units (ICU) and bone marrow and renal transplant units in order to prevent acquisition of nosocomial Legionnaires' disease. The programme was initiated following a case of nosocomial pneumonia caused by Legionella pneumophila serogroup 1-Bellingham-like genotype A on the cardiac ICU. The case occurred 14 days after mitral and aortic valve replacement surgery. Clinical and epidemiological investigations implicated aspiration of hospital potable water as the mechanism of infection. Despite interventions with chlorine dioxide costing over 25000 UK pounds per annum, Legionella has remained persistently present in significant numbers (up to 20000 colony forming units/L) and with little reduction in the number of positive sites. Two further cases of nosocomial disease occurred over the following two-year period; in one case, aspiration of tap water was implicated again, and in the other case, instillation of contaminated water into the right main bronchus via a misplaced nasogastric tube was implicated. These cases arose because of inadvertent non-compliance with the sterile-water-only policy in high-risk locations. Enhanced clinical surveillance over the same two-year period detected no other cases of nosocomial disease. This study suggests that attempts at eradication of Legionella spp. from complex water systems may not be a cost-effective measure for prevention of nosocomial infections, and to the best of our knowledge is the first study from the UK to suggest that the introduction of a sterile-water-only policy for ICUs and other high-risk units may be a more cost-effective approach.

Relationships and significance of lactate minimum, critical velocity, heart rate deflection and 3 000 m track-tests for running.

AIM: The running velocities associated to lactate minimum (V(lm)), heart rate deflection (V(HRd)), critical velocity (CV), 3.000 m (V(3000)) and 10 000 m performance (V10km) were compared. Additionally the ability of V(lm) and V(HRd) on identifying sustainable velocities was investigated. METHODS: Twenty runners (28.5+/-5.9 y) performed 1) 3,000 m running test for V3000; 2) an all-out 500 m sprint followed by 6x800 m incremental bouts with blood lactate ([lac]) measurements for V(lm); 3) a continuous velocity-incremented test with heart rate measurements at each 200 m for V(HRd); 4) participants attempted to 30 min of endurance test both at V(lm)(ETV(lm)) and V(HRd)(ETV(HRd)). Additionally, the distance-time and velocity-1/time relationships produced CV by 2 (500 m and 3 000 m) or 3 predictive trials (500 m, 3,000 m and distance reached before exhaustion during ETV(HRd)), and a 10 km race was recorded for V10km. RESULTS: The CV identified by different methods did not differ to each other. The results (m.min(-1)) revealed that V(lm) (281+/-14.8)

The relationship between power and time to fatigue in cycle ergometer exercise.

The purpose of this study was to evaluate three critical power (P (critical)) models. Ten university students performed tests that elicited fatigue in > 2 min to approximately 10 min. Power and time data were fit to a 2-parameter hyperbolic model, a 3-parameter hyperbolic model, and a 3-parameter exponential model. Models described the power-time relationship well (R (2) > or = 0.995). However, P (critical) (209 +/- 51 W; SEE: 20 +/- 47 W) and the time constant (198 +/- 87 s; SEE: 103 +/- 246 W) from the exponential model have no obvious meaning. The 2-parameter model produced P (critical) (187 +/- 38 W) and anaerobic work capacity (20.4 +/- 9.0 kJ) that have known physiological meaning, with excellent confidence (SEE: 2 +/- 2 W and 1.0 +/- 1.0 kJ, respectively). Addition of a maximal power parameter to the 2-parameter model did not improve description of the relationship, and the third parameter was superfluous. The 2-parameter model was preferred because, for the range of exercise durations used in this study, it describes the power-relationship adequately and in a most parsimonious fashion.

Induction of redox instability of bovine myoglobin by adduction with 4-hydroxy-2-nonenal.

The redox stability of myoglobin (Mb) is compromised by many factors, including lipid oxidation and its products. 4-Hydroxy-2-nonenal (HNE) is an alpha,beta-unsaturated aldehyde derived from the oxidation of omega-6 polyunsaturated fatty acids and is highly reactive and cytotoxic. Our objective was to study potential binding of HNE to Mb and determine how it affects redox stability. OxyMb (0.15 mM) was incubated with HNE (1 mM) at 4, 25, and 37 degrees C at pH 7.4 or 5.6. Samples were analyzed for MetMb formation and by Western blot analyses, LC-MS, LC-MS-MS, circular dichroism (CD), and differential scanning calorimetry (DSC). MetMb formation increased with increasing temperature and was greater at pH 5.6 than at pH 7.4 (P < 0.05). At 37 degrees C, HNE accelerated oxidation at pH 7.4 but not at pH 5.6 (P < 0.05). At both 25 and 4 degrees C, HNE accelerated oxidation at pH 7.4 and 5.6 (P < 0.05). LC-MS revealed the covalent binding of HNE to Mb at both pH values via Michael addition, while Western blot analysis indicated that HNE was bound to histidine (HIS) residues. LC-MS-MS identified six histidine residues of Mb that were readily adducted by HNE, including the proximal (HIS 93) and distal (HIS 64) histidine associated with the heme group. Secondary structure differences between control Mb and Mb incubated with HNE were not detected by CD. However, DSC revealed a decreased T(m) for Mb reacted with HNE at pH 7.4, indicating Mb tertiary structure was altered in a manner consistent with destabilization. These results suggest that HNE accelerates bovine skeletal muscle OxyMb oxidation in vitro by covalent modification at histidine residues.

Clinical significance of the emergence of bacterial resistance in the hospital environment.

Antibiotic resistance is an increasing threat in hospitals and both morbidity and mortality from infections are greater when caused by drug-resistant organisms. Whilst hospitals are universally blamed for this increase, there is an insufficient appreciation of external sources of resistance, such as when patients are admitted to hospitals from long-term care facilities in the community. The use of antibiotics in family practice and animal husbandry has also been linked to drug resistance being encountered in the hospital setting. Justifiable hospital antibiotic use, which can be life saving, may lead to 'collateral damage' with the emergence of resistance in non-target bacteria in the bowel, for example, with subsequent spread by cross-infection. At a management level, antibiotic resistance can have a significant impact on the ability of hospitals to maintain services since cohorting of patients and ward closures from outbreaks add to continuing bed shortages and waiting lists. Hospital laboratories must review their standard operating procedures since some resistance mechanisms may be missed by current methods of antibiotic susceptibility testing. With increasing public concern from press reports of 'multiresistant Staphylococcus aureus killer virus' and other drug-resistant organisms, there will inevitably be a push by national authorities for more surveillance data on antibiotic resistance; however, the cost-effectiveness of different surveillance strategies should be considered. Clinical governance and risk management are dominant themes in the National Health Service and hospital hygiene and antibiotic resistance are likely to feature prominently in audits related to these themes in the near future.

Clinical significance of the emergence of bacterial resistance in the hospital environment.

Antibiotic resistance is an increasing threat in hospitals and both morbidity and mortality from infections are greater when caused by drug-resistant organisms. Whilst hospitals are universally blamed for this increase, there is an insufficient appreciation of external sources of resistance, such as when patients are admitted to hospitals from long-term care facilities in the community. The use of antibiotics in family practice and animal husbandry has also been linked to drug resistance being encountered in the hospital setting. Justifiable hospital antibiotic use, which can be life saving, may lead to 'collateral damage' with the emergence of resistance in non-target bacteria in the bowel, for example, with subsequent spread by cross-infection. At a management level, antibiotic resistance can have a significant impact on the ability of hospitals to maintain services since cohorting of patients and ward closures from outbreaks add to continuing bed shortages and waiting lists. Hospital laboratories must review their standard operating procedures since some resistance mechanisms may be missed by current methods of antibiotic susceptibility testing. With increasing public concern from press reports of 'multiresistant Staphylococcus aureus killer virus' and other drug-resistant organisms, there will inevitably be a push by national authorities for more surveillance data on antibiotic resistance; however, the cost-effectiveness of different surveillance strategies should be considered. Clinical governance and risk management are dominant themes in the National Health Service and hospital hygiene and antibiotic resistance are likely to feature prominently in audits related to these themes in the near future.

The VO(2) response at the onset of severe intensity exercise.

Fourteen participants achieved a peak VO(2) of 2573 +/- 738 ml á min-1 in approximately 3 1/2-min cycle ergometer tests. However, in the first 45 s of exercise, formal description of the phase II of the V(O)2 response indicated that the V(O)2 was projecting toward a value of 3451 +/- 1599 ml x min(-1), well above the peak VO(2)peak and not different from the predicted O(2) demand of 3389 +/- 800 ml x min(-1). We conclude that, at the onset of exercise in the severe intensity domain, VO(2) is initially driven toward the O(2) demand, and then is limited by the achievable VO(2) (VO(2peak)).

Characterization of urinary metabolites of testosterone, methyltestosterone, mibolerone and boldebone in greyhound dogs.

Androgenic steroids are used in female greyhound dogs to prevent the onset of estrus; moreover, these steroids also have potent anabolic activity. As anabolic steroids increase muscle mass and aggression in animals, the excessive use of these agents in racing greyhounds gives an unfair performance advantage to treated dogs. The biotransformation of most anabolic steroids has not been determined in greyhound dogs. The objective of the present study was to identify the urinary metabolites of testosterone, methyltestosterone, mibolerone, and boldenone in greyhound dogs. These steroids were administered orally (1 mg/kg) to either male or female greyhound dogs and urine samples were collected pre-administration and at 2, 4, 8, 12, 24, 72, and 96 h post-administration. Urine extracts were analyzed by high-performance liquid chromatography/mass spectrometry (HPLC/MS) to identify major metabolites and to determine their urinary excretion profiles. Major urinary metabolites, primarily glucuronide, conjugated and free, were detected for the selected steroids. Sulfate conjugation did not appear to be a major pathway for steroid metabolism and excretion in the greyhound dog. Phase I biotransformation was also evaluated using greyhound dog liver microsomes from untreated dogs. The identification of several in vivo steroid metabolites generated in this study will be useful in detecting these steroids in urine samples submitted for drug screening.

Drug metabolism: in vitro biotransformation of anabolic steroids in canines.

Forensic drug testing of anabolic steroids in racing animals is required because of the potential for steroid abuse. Often when the metabolic products of an administered compound have not been identified, the analysis and verification of the administered compound is difficult. The objective of this study was to qualitatively identify the in vitro phase I biotransformation products of anabolic steroids that have a high potential for abuse in canines. The investigated steroids included testosterone, methyltestosterone, mibolerone and boldenone. Steroid biotransformation products were generated using beagle liver microsomes and analysed by high performance liquid chromatography (HPLC)/mass spectrometry (MS) with an electrospray ionization source. Characterization of steroid metabolites was based on HPLC retention, UV and mass spectra. The major testosterone metabolites were identified as androstenedione and 6beta- and 16alpha-hydroxytestosterone. 6beta-Hydroxymethyltestosterone was identified as a major metabolite in the methyltestosterone microsomal incubations. Several mibolerone metabolites were identified as monohydroxylated mibolerones as well as an oxidized mibolerone metabolite. Boldenone metabolites were identified as monohydroxylated boldenones, oxidized boldenone, and testosterone. This information should assist in the determination of anabolic steroid use in canines through the correlation of the urinary metabolites to the administered drug.

Development of analytical methods for the detection of metaraminol in the horse.

Aramine (metaraminol bitartrate) has been found in the possession of horse trainers and veterinarians who have been investigated for possible inappropriate drug administration to racing horses. Metaraminol (3-hydroxyphenylisopropanolamine) is a sympathomimetic amine that directly and indirectly affects adrenergic receptors, with alpha effects being predominant. Because it has the potential to affect the performance of a racing horse, its use is prohibited. In the present study, methods for the detection of metaraminol were developed. Metaraminol was found to be extracted with poor recovery (< 50%) from aqueous solutions by routine basic extraction or cation exchange/reversed-phase solid-phase extraction techniques. However, an extractive acetylation method gave good (> 90%) recovery of metaraminol from aqueous samples. Sequential urine samples collected from horses administered metaraminol intramuscularly at 0.02, 0.10, and 0.23 mg/kg were extracted by the developed extractive acetylation procedure and analyzed by gas chromatography-mass spectrometry (GC-MS) in full-scan and selected ion monitoring modes. Norphenylephrine was used as an internal standard for quantitative analysis. The maximum concentration of metaraminol occurred between 1 and 2 h postadministration. Metaraminol was detected in the 0.23 mg/kg administration urine for 24 h postadministration. Metaraminol was detected for the 0.10 and 0.02 mg/kg doses for approximately 8 h postadministration. No apparent biotransformation products were observed in a reaction mixture of metaraminol and horse liver microsomal reaction mixture. Comparison of gas chromatograms of the extracts of the postadministration urine samples with those of the pre-administration samples failed to reveal any exogenous compound other than metaraminol.

Reversed-phase liquid chromatographic separation of complex samples by optimizing temperature and gradient time I. Peak capacity limitations.

The separation of samples that contain more than 15 to 20 analytes (n > 15-20) is typically difficult and usually requires gradient elution. We have examined the reversed-phase liquid chromatographic separation of 24 samples with 8 < or = n < or = 48 as a function of temperature T and gradient time tG. The required peak capacity was determined for each sample, after selecting T and tG for optimum selectivity and maximum sample resolution. Comparison of these results with estimates of the maximum possible peak capacity in reversed-phase gradient elution was used to quantify the maximum value of n for some required sample resolution (when T and tG have been optimized). These results were also compared with literature studies of similar isocratic separations as a function of ternary-solvent mobile phase composition, where the proportions of methanol (MeOH), tetrahydrofuran (THF) and water were varied simultaneously. This in turn provides information on the relative effectiveness of these two different method development procedures (optimization of T and tG vs. % MeOH and % THF) for changing selectivity and achieving maximum resolution.