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.

Extracellular and cellular Hsp72 differ as biomarkers in acute exercise/environmental stress and recovery.

Stress-inducible Hsp72 is a potential biomarker to track risk of exertional heat illness during exercise/environmental stress. Characterization of extracellular (eHsp72) vs cellular Hsp72 (iHsp72) responses is required to define the appropriate use of Hsp72 as a reliable biomarker. In each of four repeat visits, participants (n = 6 men, 4 trials; total n = 24): (a) passively dehydrated overnight, (b) exercised (2 h) with no fluid in a hot, humid environmental chamber, (c) rested and rehydrated (1 h), (d) maximally exercised for 0.5 h, and (e) returned after 24 h of at-home recovery and rehydration. We measured rectal temperature, hydration status (% body mass loss, urine markers, serum osmolality), and Hsp72 (ELISA, flow cytometry. eHsp72 (circulating) and iHsp72 (CD3+ PBMCs) correlated (P < 0.05) with markers of heat, exercise, and dehydration stresses. eHsp72 immediately post-exercise (>15% above baseline, P < 0.05) decreased back to baseline levels by 1 h post-exercise, but iHsp72 expression continued to rise and remained elevated 24 h post-exercise (~2.5-fold baseline, P < 0.05). These data suggest that in addition to the classic physiological biomarkers of exercise heat stress, using cellular Hsp72 as an indicator of lasting effects of stress into recovery may be most appropriate for determining long-term effects of stress on risk for exertional heat illness.

Assessment of hydration biomarkers including salivary osmolality during passive and active dehydration.

BACKGROUND/OBJECTIVES: Hydration state can be assessed via body mass change (BMΔ), serum and urine osmolality (Sosm, Uosm), urine-specific gravity (Usg) and urine volume (Uvol). As no hydration index has been shown to be valid in all circumstances, value exists in exploring novel biomarkers such as salivary osmolality (Vosm). Utilizing acute BMΔ as the reference standard, this research examined the efficacy of Sosm, Vosm, Uosm, Uvol and Usg, during passive (PAS) and active (ACT) heat exposure. SUBJECTS/METHODS: Twenty-three healthy men (age, 22±3 years; mass, 77.3±12.8 kg; height, 179.9±8.8cm; body fat, 10.6±4.5%) completed two randomized 5-h dehydration trials (36±1 °C). During PAS, subjects sat quietly, and during ACT, participants cycled at 68±6% maximal heart rate. Investigators measured all biomarkers at each 1% BMΔ. RESULTS: Average mass loss during PAS was 1.4±0.3%, and 4.1±0.7% during ACT. Significant between-treatment differences at -1% BMΔ were observed for Sosm (PAS, 296±4; ACT, 301±4 mOsm/kg) and Uosm (PAS, 895±207; ACT, 661±192 mOsm/kg). During PAS, only Uosm, Uvol and Usg increased significantly (-1 and -2% BMΔ versus baseline). During ACT, Vosm most effectively diagnosed dehydration 2% (sensitivity=86%; specificity=91%), followed by Sosm (sensitivity=83%; specificity=83%). Reference change values were validated for Sosm, Usg and BMΔ. CONCLUSIONS: The efficacy of indices to detect dehydration 2% differed across treatments. At rest (PAS), only urinary indices increased in concert with body water loss. During exercise (ACT), Sosm and Vosm exhibited the highest sensitivity and specificity. Sosm, Usg and BMΔ exhibited validity in serial measurements. These findings indicate hydration biomarkers should be selected by considering daily activities.

Evaluation of Uosm:Posm ratio as a hydration biomarker in free-living, healthy young women.

BACKGROUND/OBJECTIVES: Urinary and plasma indices are utilized to assess whole-body water balance in healthy adults, whereas the urine-to-plasma osmolality ratio (Uosm:Posm) rarely is. To explore the efficacy of Uosm:Posm as a hydration biomarker, diet records of 120 college women were analyzed (beverage water+food water=total fluid intake (TFI); 5 days) to identify habitual high-volume (HIGH) and low-volume (LOW) drinkers. SUBJECTS/METHODS: The experimental protocol first involved two ad libitum baseline days for HIGH (TFI, 3.21 l per 24 h; n=14) and LOW (TFI, 1.64 l per 24 h; n=14). During a controlled intervention (days 3-6), mineral water was the only beverage; HIGH consumed less than baseline (TFI, 2.00 l per 24 h), and LOW consumed more than baseline (TFI, 3.50 l per 24 h). During ad libitum recovery (day 7), TFI were 3.17 and 1.71 l per 24 h for HIGH and LOW, respectively. Duplicate Uosm (24 h collection) and Posm (morning) samples were analyzed on all days via freezing point depression osmometry. RESULTS: In the evaluation of relative water excess (Uosm:Posm<1.0), 11/13 values occurred for HIGH on days 1, 2 and 7; for LOW, 28/29 occurred on intervention days 3-6. Chi-squared analysis indicated that the treatment and Uosm:Posm were significantly associated (χ(2)1:0.001=23.5, P<0.001). Statistical regression analyses detected a strong, significant relationship between renal free-water clearance (FWC) and Uosm:Posm (r(2)=0.86, P<0.00001); this was not true for FWC and Posm (r(2)=0.00, P=0.40) because Posm values were stable across 7 days. CONCLUSIONS: These findings support the use of Uosm:Posm as a hydration biomarker.

Interpreting common hydration biomarkers on the basis of solute and water excretion.

BACKGROUND/OBJECTIVES: This investigation evaluated 12 hydration biomarkers, to determine which represent 24-h whole-body water balance (that is, measured as water retention or clearance (WR-C) by the kidneys). SUBJECTS/METHODS: Healthy males (n=59; body mass, 75.1±7.9 kg; height, 178±6 cm; age, 22±3 years; body mass index, 23.9±2.4 kg/m(2)) met with a registered dietitian each morning (days 1-11) to optimize completeness and accuracy of food and fluid records, then went about ordinary daily activities. These men visited the laboratory for blood samples and collected all urine produced on days 1, 3, 6, 9 and 12. The reference standard (WR-C) was calculated using 24-h urine volume, 24-h urine osmolality, and serum osmolality (single morning venous sample). RESULTS: Statistical regression analyses indicated that, among the 12 hydration biomarkers, only 24-h urine osmolality (r(2)=0.60, P<0.0001) and 24-h urine specific gravity (r(2)=0.52, P<0.0001) strongly predicted WR-C. The 24-h fluid intake, 24-h body mass change, 24-h urine color and 24-h urine volume were weak (P>0.05) predictors of WR-C, similar to serum osmolality and other single measurements (range of r(2) values, 0.19-0.0001). CONCLUSIONS: These observations of healthy, active young men demonstrate that WR-C is strongly related to the 24-h concentration of urine, which in turn reflects the excretion of total solids in the diet. Although morning urine assessments provided information about a single time point, 24-h urine osmolality and 24-h urine specific gravity were the best predictors of 24-h body water balance.

Effects of oral rehydration and external cooling on physiology, perception, and performance in hot, dry climates.

Only limited research evaluates possible benefits of combined drinking and external cooling (by pouring cold water over the body) during exercise. Therefore, this study examined cold water drinking and external cooling on physiological, perceptual, and performance variables in hot, dry environments. Ten male runners completed four trials of walking 90 min at 30% VO(2max) followed by running a 5-km time trial in 33 ± 1 °C and 30 ± 4% relative humidity. Trials examined no intervention (CON), oral rehydration (OR), external cooling (EC), and oral rehydration plus external cooling (OR + EC). Investigators measured rectal temperature, skin temperatures, heart rate, thirst, thermal sensation, and ratings of perceived exertion (RPE). Oral rehydration (OR and OR + EC) significantly lowered heart rate (P < 0.001) and thirst (P < 0.001) compared with nondrinking (CON and EC) during low-intensity exercise. External cooling (EC and OR + EC) significantly reduced chest and thigh temperature (P < 0.001), thermal sensation (P < 0.001), and RPE (P = 0.041) compared with non-external cooling (CON and OR) during low-intensity exercise. Performance exhibited no differences (CON = 23.86 ± 4.57 min, OR = 22.74 ± 3.20 min, EC = 22.96 ± 3.11 min, OR + EC = 22.64 ± 3.73 min, P = 0.379). Independent of OR, pouring cold water on the body benefited skin temperature, thermal sensation, and RPE during low-intensity exercise in hot, dry conditions but failed to influence high-intensity performance.

Mutations in SID2, a novel gene in Saccharomyces cerevisiae, cause synthetic lethality with sic1 deletion and may cause a defect during S phase.

SIC1 encodes a nonessential B-type cyclin/CDK inhibitor that functions at the G1/S transition and the exit from mitosis. To understand more completely the regulation of these transitions, mutations causing synthetic lethality with sic1 Delta were isolated. In this screen, we identified a novel gene, SID2, which encodes an essential protein that appears to be required for DNA replication or repair. sid2-1 sic1 Delta strains and sid2-21 temperature-sensitive strains arrest preanaphase as large-budded cells with a single nucleus, a short spindle, and an approximately 2C DNA content. RAD9, which is necessary for the DNA damage checkpoint, is required for the preanaphase arrest of sid2-1 sic1 Delta cells. Analysis of chromosomes in mutant sid2-21 cells by field inversion gel electrophoresis suggests the presence of replication forks and bubbles at the arrest. Deleting the two S phase cyclins, CLB5 and CLB6, substantially suppresses the sid2-1 sic1 Delta inviability, while stabilizing Clb5 protein exacerbates the defects of sid2-1 sic1 Delta cells. In synchronized sid2-1 mutant strains, the onset of replication appears normal, but completion of DNA synthesis is delayed. sid2-1 mutants are sensitive to hydroxyurea indicating that sid2-1 cells may suffer DNA damage that, when combined with additional insult, leads to a decrease in viability. Consistent with this hypothesis, sid2-1 rad9 cells are dead or very slow growing even when SIC1 is expressed.