The effects of hydration status on markers of oxidative and cellular stress during prolonged exercise in hyperthermic environments

The relationships between hyperthermia, dehydration and oxidative stress have been thoroughly studied  separately within the literature both in vitro and in vivo. However, no in vivo attempts have been made to  manipulate the hydration status of individuals to investigate the resulting changes in oxidative and cellular stress during and after exercise in hyperthermic conditions and what effect these changes may have on  exercise performance.The purpose of the first experiment was to investigate the effects of exercise-induced dehydration with and without hyperthermia on oxidative stress. Seven healthy male trained cyclists (mean ± SD) age: 36 ± 6 yrs, height: 177.4 ± 6.5 cm, weight: 72.8 ± 7.0 kg, and power output (PO) at lactate threshold (LT): 199.3 ± 19.0 Watts (W) completed 90 min cycling exercise at 95% LT followed by a 5 km time trial (TT) in four conditions: 1) euhydration in a warm environment (EU-W, control), 2) dehydration in a warm environment (DE-W), 3) euhydration in a thermoneutral environment (EU-T), and 4) dehydration in a thermoneutral environment (DE-T) (W: 33.9 ± 0.9°C; T: 23.0 ± 1.0°C). Whole blood oxidised glutathione (GSSG) increased significantly post exercise in dehydration trials only (DE-W: p < 0.01, DE-T: p = 0.03), and while not significant, whole blood total glutathione (TGSH) and plasma thiobarbituric acid reactive substances (TBARS) tended to increase post exercise in dehydration trials (p = 0.08 for both). Intracellular monocyte heat shock protein 72 (HSP72) concentration was increased (p = 0.01) while intracellular lymphocyte HSP32 concentration was decreased for all trials (p = 0.02). Exercise-induced dehydration led to an increase in GSSG concentration while maintenance of euhydration attenuated these increases regardless of environmental condition. Additionally, evidence of increased cellular stress (measured via HSP) was found during all trials independent of body mass loss and environment. Finally, total distance covered during 90 min and PO during both 90 min and 5 km TT performance were reduced during only the DE-W trial, likely a result of combined cellular stress, hyperthermia and dehydration. These findings highlight the importance of fluid consumption during exercise to attenuate thermal and oxidative stress during prolonged exercise in the heat.The purpose of the second experiment was to investigate the effect of prolonged exercise-induced dehydration with and without hyperthermia on cellular and oxidative stress markers in untrained individuals, to serve as a comparison to the results of the first experimental chapter. Seven untrained male university students (mean ± SD) age: 21 ± 3 yrs, height: 181.1 ± 9.2 cm, weight: 76.8 ± 8.8 kg, and PO at LT 100.0 ± 13.0 W, who were unacclimatised to heat, participated in this study. Subjects completed the same experimental protocol as outlined in experimental chapter one, in warm (33.9 ± 1.0°C) and thermoneutral (22.9 ± 1.0°C) environments. Whole blood GSSG increased an average of 32% (p < 0.01) as a result of prolonged exercise, however unlike the trained subjects of experiment one, there was no effect of body mass loss on GSSG (p = 0.63). Similarly, intracellular monocyte HSP72 concentration increased 14% (p < 0.01) as a result of prolonged cycling regardless of body mass loss and environmental heat stress, analogous to subjects in experiment one. While there were no significant changes as a result of hydration or environment, a relationship was found between GSSG concentration and body mass loss (r2 = 0.5, p = 0.05), while HSP72 was correlated with body temperature and levels of heat storage (r2 = 0.5, p = 0.01). Similar to the trained individuals in experiment one, PO during the 90 min (7%, p < 0.01) and TT (14%, p < 0.01) were decreased while thermoregulation was impaired during DE-W only. These results demonstrate the increased level of stress in untrained subjects as a result of exercise and highlight the importance of participation in recommended physical activity to aid in positive cellular adaptations leading to superior antioxidant defences to aid in disease prevention.In light of the findings from the first experimental chapter that dehydration can significantly influence oxidative stress in trained subjects, the purpose of the third experimental chapter was to compare pre-exercise hyperhydration with plain water (W) or water with glycerol (G) to no hyperhydration (C) on markers of oxidative stress prior to and after a 90 min TT. Seven trained male cyclists and triathletes (age: 28 ± 8 yrs, height: 178.4 ± 7.8 cm, and mass: 73.2 ± 9.6 kg) covered as much distance as possible during a 90 min cycle after G, W or C. Blood was collected pre ingestion (PRE), post ingestion/pre exercise (PI), immediately post exercise (PE) and 1 hour post exercise (1HR) and analysed for whole blood TGSH, GSSG, and plasma levels of lipid hydroperoxides (LOOH) and protein carbonyls (PC). TGSH concentration increased post exercise in W and C (p < 0.01) while PC concentration increased post exercise during C only (p = 0.03). Additionally, GSSG concentration was greater PI and PE in C compared to G (p = 0.05, and p < 0.01, respectively), likely due to the inferior amount of fluid retained during C compared to the G and W trials. Therefore, it appears that both pre exercise hyperhydration with ad libitum fluid ingestion during exercise is sufficient to attenuate rises in exercise-induced oxidative stress.The novel findings presented in this thesis indicate fluid ingestion plays a vital role in providing cellular protection from oxidative stress. These results suggest that individuals participating in prolonged exercise should consume adequate fluid during exercise to avoid dehydration, matching fluid intake with body mass loss. Additionally, individuals who wish to hyperhydrate prior to exercise may enhance their ability to delay dehydration and thus enhance their cellular protection from oxidative stress

End-of-life priorities of older adults with terminal illness and caregivers: A qualitative consultation

Abstract Background As older adults approach the end‐of‐life (EOL), many are faced with complex decisions including whether to use medical advances to prolong life. Limited information exists on the priorities of older adults at the EOL. Objective This study aimed to explore patient and family experiences and identify factors deemed important to quality EOL care. Method A descriptive qualitative study involving three focus group discussions (n = 18) and six in‐depth interviews with older adults suffering from either a terminal condition and/or caregivers were conducted in NSW, Australia. Data were analysed thematically. Results Seven major themes were identified as follows: quality as a priority, sense of control, life on hold, need for health system support, being at home, talking about death and competent and caring health professionals. An underpinning priority throughout the seven themes was knowing and adhering to patient's wishes. Conclusion Our study highlights that to better adhere to EOL patient's wishes a reorganization of care needs is required. The readiness of the health system to cater for this expectation is questionable as real choices may not be available in acute hospital settings. With an ageing population, a reorganization of care which influences the way we manage terminal patients is required

The physiological stress response to anaerobic exercise is altered following sodium bicarbonate supplementation

Sodium bicarbonate (NaHCO3) is a nutritional aid that is proposed to enhance performance by reducing the state of exercise induced acidosis, however research is currently equivocal. Despite this, most research still focuses on its effects upon performance, and not whether the reduced acidosis impacts upon any other factors related to exercise. There is some research to suggest that such a reduction in [H+] can attenuate a number of physiological stress pathways such as stress hormones (1, 4), heat shock protein 72 (HSP72) and oxidative stress (3), suggesting a potential role in exercise recovery. However there are some limitations with this previous research as work intensities were not controlled for, hence making comparisons between treatments difficult. Also limited markers of stress were measured despite the physiological stress response being multi-faceted. The aim of this study was to examine whether the ingestion of NaHCO3 would influence the expression of several markers of stress measured simultaneously, following a work controlled anaerobic exercise

Exercising in the Fasted State Reduced 24-Hour Energy Intake in Active Male Adults

The effect of fasting prior to morning exercise on 24-hour energy intake was examined using a randomized, counterbalanced design. Participants (12 active, white males, 20.8±3.0 years old, VO2max:   59.1±5.7 mL/kg/min) fasted (NoBK) or received breakfast (BK) and then ran for 60 minutes at 60%  VO2max. All food was weighed and measured for 24 hours. Measures of blood glucose and hunger were collected at 5 time points. Respiratory quotient (RQ) was measured during exercise. Generalized linear mixed models and paired sample t-tests examined differences between the conditions. Total 24-hour (BK: 19172±4542 kJ versus NoBK: 15312±4513 kJ; p<0.001) and evening (BK: 12265±4278 kJ versus NoBK: 10833±4065; p=0.039) energy intake and RQ (BK: 0.90±0.03 versus NoBK: 0.86±0.03; p<0.001) were significantly higher in BK than NoBK. Blood glucose was significantly higher in BK than NoBK before exercise (5.2±0.7 versus 4.5±0.6 mmol/L; p=0.025). Hunger was significantly lower for BK than NoBK before exercise, after exercise, and before lunch. Blood glucose and hunger were not associated with energy intake. Fasting before morning exercise decreased 24-hour energy intake and increased fat oxidation during exercise. Completing exercise in the morning in the fasted state may have implications for weight management

Transplant Recipients and Anal Neoplasia Study: Design, Methods, and Participant Characteristics of a Prevalence Study

Kidney recipients have anal cancer rates 3 times higher than the general population in Australia and New Zealand. High-risk human papillomavirus (HPV) genotypes are implicated in the majority of anal cancers. Establishing the epidemiology of anal HPV infection and precursors of anal cancer in transplant recipient populations is 1 consideration in any potential screening program. The Transplant and Anal Neoplasia Study is a cross-sectional study of the prevalence of anal cytological abnormalities and HPV deoxyribonucleic acid in kidney transplant recipients, as well as evaluating the acceptability of an anal cancer screening intervention. The study aims to recruit 100 kidney transplant recipients, older than 18 years, in Australia. Transplant recipients at- tending for a protocol biopsy at 3 and 12 months and annually posttransplant are approached to participate. Participants undergo an anal swab, which is then analyzed using liquid-based cytological examination and tested for the detection of 37 anogenital HPV deoxyribonucleic acid genotypes. Participants also complete a demographic and behavioral questionnaire that covers sexual be- havior, history of anal symptoms, and possible anal cancer risk factors. Associations will be tested using multiple regression anal- ysis. Recruitment for the study began in 2015 and is ongoing. To date, 96 (77%) of 125 kidney transplant recipients approached have consented to the study. The mean age is 48 (median, 47 y; range, 20–76 y), 59% are male, and Northwest European (58%) represented the largest ethnic group. No participants self-identified as Aboriginal or Torres Strait Islander. High consent rates and positive qualitative results suggest that a larger screening program may be well received by kidney transplant recipients, with in- creased resources and some modification to the timing of approach. Further results of the study will inform the possible implemen- tation of a larger screening trial for prevention of anal cancers in kidney and other solid organ transplant recipients

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against &gt;100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

The Effect of Water Immersion during Exercise on Cerebral Blood Flow

Introduction: Regular exercise induces recurrent increases in cerebrovascular perfusion. In peripheral arteries, such episodic increases in perfusion are responsible for improvement in arterial function and health. We examined the hypothesis that exercise during immersion augments cerebral blood flow velocity compared with intensity-matched land-based exercise. Methods: Fifteen normotensive participants were recruited (26 ± 4 yr, 24.3 ± 1.9 kg·m−2). We continuously assessed mean arterial blood pressure, HR, stroke volume, oxygen consumption, and blood flow velocities through the middle and posterior cerebral arteries before, during, and after 20-min bouts of water- and land-based stepping exercise of matched intensity. The order in which the exercise conditions were performed was randomized between subjects. Water-based exercise was performed in 30°C water to the level of the right atrium. Results: The water- and land-based exercise bouts were closely matched for oxygen consumption (13.3 mL·kg−1·min−1 (95% confidence interval (CI), 12.2–14.6) vs 13.5 mL·kg−1·min−1 (95% CI, 12.1–14.8), P = 0.89) and HR (95 bpm (95% CI, 90–101) vs 96 bpm (95% CI, 91–102), P = 0.65). Compared with land-based exercise, water-based exercise induced an increase in middle cerebral artery blood flow velocity (74 cm·s−1 (95% CI, 66–81) vs 67 cm·s−1 (95% CI, 60–74) P < 0.001), posterior cerebral artery blood flow velocity (47 cm·s−1 (95% CI, 40–53) vs 43 cm·s−1 (95% CI, 37–49), P < 0.001), mean arterial blood pressure (106 mm Hg (95% CI, 100–111) vs 101 mm Hg (95% CI, 95–106), P < 0.001), and partial pressure of expired CO2 (P ≤ 0.001). Conclusions: Our findings suggest that water-based exercise augments cerebral blood flow, relative to land-based exercise of similar intensity, in healthy humans

Dynamic displacement of normal and detached semicircular canal cupula

© 2009 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in JARO - Journal of the Association for Research in Otolaryngology 10 (2009): 497-509, doi:10.1007/s10162-009-0174-y.The dynamic displacement of the semicircular canal cupula and modulation of afferent nerve discharge were measured simultaneously in response to physiological stimuli in vivo. The adaptation time constant(s) of normal cupulae in response to step stimuli averaged 36 s, corresponding to a mechanical lower corner frequency for sinusoidal stimuli of 0.0044 Hz. For stimuli equivalent to 40–200 deg/s of angular head velocity, the displacement gain of the central region of the cupula averaged 53 nm per deg/s. Afferents adapted more rapidly than the cupula, demonstrating the presence of a relaxation process that contributes significantly to the neural representation of angular head motions by the discharge patterns of canal afferent neurons. We also investigated changes in time constants of the cupula and afferents following detachment of the cupula at its apex—mechanical detachment that occurs in response to excessive transcupular endolymph pressure. Detached cupulae exhibited sharply reduced adaptation time constants (300 ms–3 s, n = 3) and can be explained by endolymph flowing rapidly over the apex of the cupula. Partially detached cupulae reattached and normal afferent discharge patterns were recovered 5–7 h following detachment. This regeneration process may have relevance to the recovery of semicircular canal function following head trauma.Financial support was provided by the NIDCD R01 DC06685 (Rabbitt) and NASA GSRP 56000135 & NSF IGERT DGE- 9987616 (Breneman)