Gastrointestinal distress, such as diarrhoea, cramping, vomiting, nausea and gastric pain are common among athletes during training and competition. The mechanisms that cause these symptoms are not fully understood. The stress of heat and oxidative damage during exercise causes disruption to intestinal epithelial cell tight junction proteins resulting in increased permeability to luminal endotoxins. The endotoxin moves into the blood stream leading to a systemic immune response. Tight junction integrity is altered by the phosphoylation state of the proteins occludin and claudins, and may be regulated by the type of exercise performed. Prolonged exercise and high-intensity exercise lead to an increase in key phosphorylation enzymes that ultimately cause tight junction dysfunction, but the mechanisms are different. The purpose of this review is to (1) explain the function and physiology of tight junction regulation, (2) discuss the effects of prolonged and high-intensity exercise on tight junction permeability leading to gastrointestinal distress and (3) review agents that may increase or decrease tight junction integrity during exercise.

The objectives of this study are threefold: 1) to assess whether 7 days of oral glutamine (GLN) supplementation reduces exercise-induced intestinal permeability; 2) whether supplementation prevents the proinflammatory response; and 3) whether these changes are associated with upregulation of the heat shock response. On separate occasions, eight human subjects participated in baseline testing and in GLN and placebo (PLA) supplementation trials, followed by a 60-min treadmill run. Intestinal permeability was higher in the PLA trial compared with baseline and GLN trials (0.0604 ± 0.047 vs. 0.0218 ± 0.008 and 0.0272 ± 0.007, respectively; P < 0.05). IκBα expression in peripheral blood mononuclear cells was higher 240 min after exercise in the GLN trial compared with the PLA trial (1.411 ± 0.523 vs. 0.9839 ± 0.343, respectively; P < 0.05). In vitro using the intestinal epithelial cell line Caco-2, we measured effects of GLN supplementation (0, 4, and 6 mM) on heat-induced (37° or 41.8°C) heat shock protein 70 (HSP70), heat shock factor-1 (HSF-1), and occludin expression. HSF-1 and HSP70 levels increased in 6 mM supplementation at 41°C compared with 0 mM at 41°C (1.785 ± 0.495 vs. 0.6681 ± 0.290, and 1.973 ± 0.325 vs. 1.133 ± 0.129, respectively; P < 0.05). Occludin levels increased after 4 mM supplementation at 41°C and 6 mM at 41°C compared with 0 mM at 41°C (1.236 ± 0.219 and 1.849 ± 0.564 vs. 0.7434 ± 0.027, respectively; P < 0.001). GLN supplementation prevented exercise-induced permeability, possibly through HSF-1 activation.

Autophagy is a lysosome degradation pathway through which damaged organelles and macromolecules are degraded within the cell. A decrease in activity of the autophagic process has been linked to several age-associated pathologies, including triglyceride accumulation, mitochondrial dysfunction, muscle degeneration, and cardiac malfunction. Here, we examined the differences in the autophagic response using autophagy-inducer rapamycin (Rapa) in peripheral blood mononuclear cells (PBMCs) from young (21.8 ± 1.9 years) and old (64.0 ± 3.7 years) individuals. Furthermore, we tested the interplay between the heat shock response and autophagy systems. Our results showed a significant increase in LC3-II protein expression in response to Rapa treatment in young but not in old individuals. This was associated with a decreased response in MAP1LC3B mRNA levels, but not SQSTM1/p62. Furthermore, HSPA1A mRNA was upregulated only in young individuals, despite no differences in HSP70 protein expression. The combined findings suggest a suppressed autophagic response following Rapa treatment in older individuals.

The purpose of this study was to query healthcare practitioners (HCPs) who treat firefighter injuries to identify risk factors and mechanisms associated with musculoskeletal injuries during exercise. A phenomenological design was utilized to understand the experiences of HCPs while treating firefighters’ musculoskeletal injuries due to exercise. Semi-structured interviews were conducted with 14 HCPs. Two interviews were pilot-tested with HCPs to ensure reliability and validity. Interviews were transcribed and uploaded to a qualitative analysis software program. Although the study inquired about injuries incurred by any exercise modality (e.g., endurance and resistance training), injuries induced during resistance training were prominent among HCPs as resistance training emerged as a primary exercise injury mechanism. HCPs indicated that the back and shoulder were prevalent anatomical exercise injury locations. Risk factors for exercise injuries included age, immobility, movement proficiency, and factors associated with fatigue. Exercise injury mechanisms included poor resistance training technique and overexertion. These findings could guide exercise program design, use of movement assessments, and the identification of other countermeasures to decrease the risk of resistance training exercise injuries among firefighters.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease that is atherogenic. Decreased arterial distensibility (AD) is a risk factor for cardiovascular disease, and this precursor may be associated with SLE. Accordingly, we tested the hypothesis that patients with SLE will have significantly (p < 0.05) decreased AD when compared to normal, healthy age, and gender matched controls. Noninvasive, high resolution ultrasound was performed on 30 patients with chronic SLE and 16 age and gender matched controls. All were female. Maximum systolic and minimum diastolic diameters (mm) and intima-media thickness (IMT, mm) in the right common carotid artery were measured from M-mode images. In vitro arterial models were used for quality control. With a single, blinded observer, the 95% confidence levels for accuracy and precision for noninvasive systolic and diastolic tonometric arm blood pressures (SBP, DBP) and carotid sonographic diameters were ~5 mmHg and ~0.10 mm, respectively. Derived measurements for strain (%), stiffness (units), and AD (units) were determined by published arterial mechanical models and algorithms. Results (mean/standard deviation) were as follows: (patients/controls; # =p<0.05) Age 39/11, 35/11 years; SBP 130/20, 117/8# mmHg; DBP 82/11, 74/9# mmHg; strain 11/4, 11/4 %; stiffness 19/10, 17/11 units; IMT 0.44/0.08, 0.41/0.06 mm; AD 3.10/1.49, 3.30/1.63 units. There were no statistically significant differences (p<0.05) in measurements of AD and IMT in the common carotid artery between relatively young SLE patients and well matched controls.

INTRODUCTION: Aging is associated with an accumulation of damaged aberrant macromolecules. Autophagy is the process that contributes to the maintenance of cellular homeostasis through degradation and subsequent recycling of damaged proteins and organelles and may be coordinated by the heat shock response. In this pilot study, we tested the hypothesis that aging reduces the heat shock and autophagy responses to heat shock in human peripheral blood mononuclear cells (PBMC). METHODS: Four young control (21.25 ± 1.5 years, 3 male, 1 female) and four older subjects (63 ± 2.9 years, 2 male, 2 female) participated in this study. PBMCs were isolated from whole blood and cells were analyzed for baseline levels of LC3‐II and HSP70 proteins. In subsequent studies, PBMCs collected from young and older subjects were exposed to 1 h heat incubation at 42°C, and HSP70 and LC3‐II expression were measured by Western blot analysis and normalized to β‐actin. Densitometric values (mean ± standard deviation) for baseline and heat shock studies are reported. RESULTS: Surprisingly, the PBMCs from older subjects had a higher (p < .01) baseline level, 0.64 ± 0.14, of LC3‐II than the younger subjects, 0.07 ± 0.14. An increase (p < .05) in heat shock protein (HSP70) from baseline levels of 0.03 ± 0.07 to 1.77 ± 1.32 following heat shock was found in young subjects, but not older subjects. No within or between group differences were found in LC3‐II following heat shock. CONCLUSIONS: Contrary to findings in animals, our results suggest that autophagy is increased, not decreased with aging in humans. This increased baseline level may partially compensate for the compromised ability to upregulate HSP70 and stimulate autophagy after a heat stress exposure.