Sensitivity of SARS‐CoV‐2 to different temperatures

This study was designed to investigate the sensitivity of SARS‐CoV‐2 to different temperatures, to provide basic data and a scientific basis for the control of COVID‐19 epidemic. The virus was dispersed in 1 mL basal DMEM medium at a final concentration of 10^3.2 TCID₅₀/mL and then incubated at 4, 22, 30, 35, 37, 38, 39 and 40°C for up to 5 days. The infectivity of residual virus was titrated using the Vero E6 cell line. The results showed that the virus remained viable for 5 days at 4°C, and for 1 day only at 22 and 30°C. We found that the infectivity of the virus was completely lost after less than 12 hours at 37, 38 and 39°C, while at 40°C, the inactivation time of the virus was rapidly reduced to 6 hours. We show that SARS‐CoV‐2 is sensitive to heat, is more stable at lower temperatures than higher temperature, remains viable for longer at lower temperatures, and loses viability rapidly at higher temperatures.     

Cooling Capacity of Transpulmonary Cooling and Cold-Water Immersion After Exercise-Induced Hyperthermia

ContextCold-water immersion (CWI) may not be feasible in some remote settings, prompting the identification of alternative cooling methods as adjunct treatment modalities for exertional heat stroke (EHS).ObjectiveTo determine the differences in cooling capacities between CWI and the inhalation of cooled air.DesignRandomized controlled clinical trial.SettingLaboratory.Patients or Other ParticipantsA total of 12 recreationally active participants (7 men, 5 women; age = 26 ± 4 years, height = 170.6 ± 10.1 cm, mass = 76.0 ± 18.0 kg, body fat = 18.5% ± 9.7%, peak oxygen uptake = 42.7 ± 8.9 mL·kg⁻¹·min⁻¹).Intervention(s)After exercise in a hot environment (40°C and 40% relative humidity), participants were randomized to 3 cooling conditions: cooling during passive rest (PASS; control), CWI, and the Polar Breeze thermal rehabilitation machine (PB) with which participants inspired cooled air (22.2°C ± 1.0°C).Main Outcome Measure(s)Rectal temperature (T_REC) and heart rate were continuously measured throughout cooling until T_REC reached 38.25°C.ResultsCooling rates during CWI (0.18°C·min⁻¹ ± 0.06°C·min⁻¹) were greater than those during PASS (mean difference [95% CI] of 0.16°C·min⁻¹ [0.13°C·min⁻¹, 0.19°C·min⁻¹]; P < .001) and PB (0.15°C·min⁻¹ [0.12°C·min⁻¹, 0.16°C·min⁻¹]; P < .001). Elapsed time to reach a T_REC of 38.25°C was also faster with CWI (9.71 ± 3.30 minutes) than PASS (−58.1 minutes [−77.1, −39.9 minutes]; P < .001) and PB (−46.8 minutes [−65.5, −28.2 minutes]; P < .001). Differences in cooling rates and time to reach a T_REC of 38.25°C between PASS and PB were not different (P > .05).ConclusionsTranspulmonary cooling via cooled-air inhalation did not promote an optimal cooling rate (>0.15°C·min⁻¹) for the successful treatment of EHS. In remote settings where EHS is a risk, access and use of treatment methods via CWI or cold-water dousing are imperative to ensuring survival.Trial RegistryClinicalTrials.gov (NCT0419026).     

Movement Technique and Standing Balance After Graded Exercise-Induced Dehydration

ContextHypohydration has been shown to alter neuromuscular function. However, the longevity of these impairments remains unclear.ObjectiveTo examine the effects of graded exercise-induced dehydration on neuromuscular control 24 hours after exercise-induced hypohydration.DesignCrossover study.SettingLaboratory.Patients or Other ParticipantsA total of 23 men (age = 21 ± 2 years, height = 179.8 ± 6.4 cm, mass = 75.24 ± 7.93 kg, maximal oxygen uptake [VO₂max] = 51.7 ± 5.5 mL·kg⁻¹·min⁻¹, body fat = 14.2% ± 4.6%).Intervention(s)Participants completed 3 randomized exercise trials: euhydrated arrival plus fluid replacement (EUR), euhydrated arrival plus no fluid (EUD), and hypohydrated arrival plus no fluid (HYD) in hot conditions (ambient temperature = 35.2°C ± 0.6°C, relative humidity = 31.3% ± 2.5%). Each trial consisted of 180 minutes of exercise (six 30-minute cycles: 8 minutes at 40% VO₂max; 8 minutes, 60% VO₂max; 8 minutes, 40% VO₂max; 6 minutes, passive rest) followed by 60 minutes of passive recovery.Main Outcome Measure(s)We used the Landing Error Scoring System and Balance Error Scoring System (BESS) to measure movement technique and postural control at pre-exercise, postexercise and passive rest (POST_EX), and 24 hours postexercise (POST₂₄). Differences were assessed using separate mixed-design (trial × time) repeated-measures analyses of variance.ResultsThe magnitude of hypohydration at POST_EX was different among EUR, EUD, and HYD trials (0.2% ± 1%, 3.5% ± 1%, and 5% ± 0.9%, respectively; P < .05). We observed no differences in Landing Error Scoring System scores at pre-exercise (2.9 ± 1.6, 3.0 ± 2.1, 3.0 ± 2.0), POST_EX (3.3 ± 1.5, 3.0 ± 2.0, 3.1 ± 1.9), or POST₂₄ (3.3 ± 1.9, 3.2 ± 1.4, 3.3 ± 1.6) among the EUD, EUR, and HYD trials, respectively (P = .90). Hydration status did not affect BESS scores (P = .11), but BESS scores at POST_EX (10.4 ± 1.1) were greater than at POST₂₄ (7.7 ± 0.9; P = .03).ConclusionsWhereas exercise-induced dehydration up to 5% body mass did not impair movement technique or postural control 24 hours after a prolonged bout of exercise in a hot environment, postural control was impaired at 60 minutes after prolonged exercise in the heat. Consideration of the length of recovery time between bouts of exercise in hot environments is warranted.     

Hypertension is associated with greater heat exchange during exercise recovery in a hot environment

Individuals with systemic arterial hypertension have a higher risk of heat-related complications. Thus, the aim of this study was to examine the thermoregulatory responses of hypertensive subjects during recovery from moderate-intensity exercise performed in the heat. A total of eight essential hypertensive (H) and eight normotensive (N) male subjects (age=46.5±1.3 and 45.6±1.4 years, body mass index=25.8±0.8 and 25.6±0.6 kg/m², mean arterial pressure=98.0±2.8 and 86.0±2.3 mmHg, respectively) rested for 30 min, performed 1 h of treadmill exercise at 50% of maximal oxygen consumption, and rested for 1 h after exercise in an environmental chamber at 38°C and 60% relative humidity. Skin and core temperatures were measured to calculate heat exchange parameters. Mean arterial pressure was higher in the hypertensive than in the normotensive subjects throughout the experiment (P<0.05, unpaired t-test). The hypertensive subjects stored less heat (H=-24.23±3.99 W·m⁻² vs N=-13.63±2.24 W·m⁻², P=0.03, unpaired t-test), experienced greater variations in body temperature (H=-0.62±0.05°C vsN=-0.35±0.12°C, P=0.03, unpaired t-test), and had more evaporated sweat (H=-106.1±4.59 W·m⁻² vs N=-91.15±3.24 W·m⁻², P=0.01, unpaired t-test) than the normotensive subjects during the period of recovery from exercise. In conclusion, essential hypertensive subjects showed greater sweat evaporation and increased heat dissipation and body cooling relative to normotensive subjects during recovery from moderate-intensity exercise performed in hot conditions.     

Quantitative T cell subsets profile in peripheral blood from patients with idiopathic inflammatory myopathies: tilting the balance towards proinflammatory and pro-apoptotic subsets

The role of T cells in idiopathic inflammatory myopathies (IIM) is not yet clear. Some alterations in certain subsets have been reported in inflamed muscle cells. However, a broad quantitative assessment of peripheral T cell subsets has not been evaluated. The aim of this study was to address the quantitative profile of potential pathogenic T cell subsets, namely follicular helper T cells (Tfh), T helper type 17 (Th17), CD28^null and regulatory T cells (T_regs) in peripheral blood from IIM patients. Thirty IIM patients and 30 age- and gender-matched healthy donors were included. Peripheral blood mononuclear cells were isolated. T cell subsets were evaluated by flow cytometry, as follows: Tfh (CD4⁺CXCR5⁺) and its subsets Tfh1 (CXCR3⁺CCR6⁻), Tfh2 (CXCR3⁻CCR6⁻), Tfh17 (CXCR3⁻CCR6⁺), Th17 (CD4⁺IL17A⁺), CD28^null (CD4⁺CD28⁻CD244⁺) and T_regs (CD4⁺CD25^highforkhead box protein 3 (FoxP3⁺); CD8⁺CD25^highFoxP3⁺). Percentage, absolute numbers and mean fluorescence intensity were analysed. We found increased numbers of total Tfh cells (28 ± 8·16 versus 6·64 ± 1·29, P = 0·031) in IIM patients when compared to healthy controls. Moreover, this increment was dependent upon Tfh2 and Tfh17 (Tfh2:9·49 ± 2·19 versus 1·66 ± 0·46, P = 0·005; Tfh17 9·48 ± 2·83 versus 1·18 ± 0·21, P = 0·014). Also, IIM patients showed higher numbers of Th17 cells (30·25 ± 6·49 versus 13·46 ± 2·95, P = 0·031) as well as decreased number of T_regs (5·98 ± 1·61 versus 30·82 ± 8·38, P = 0·009). We also found an expansion of CD28^null cells (162·88 ± 32·29 versus 64 ± 17·35, P = 0·015). Our data suggest that IIM patients are characterized by an expansion of peripheral proinflammatory T cells, such as Tfh and Th17, as well as pro-apoptotic CD28 null cells and a deficiency of suppressor populations of T_regs (CD4⁺ and CD8⁺).     

Increased numbers of CD5+ B cells and T cell receptor (TCR) γδ+ T cells are associated with younger age of onset in rheumatoid arthritis (RA)

Patients presenting with RA before the age of 45 years (younger onset) are known to have more aggressive disease compared with patients presenting after the age of 65 years (older onset). Coordinated expansion of circulating CD5⁺ B cell and TCR γδ⁺ T cell levels has been reported in patients with RA. This study assesses the peripheral blood levels of these two cell types in RA patients with younger and older onset of disease. CD5⁺ B cell levels were significantly elevated in the younger onset RA group (26·6 ± 4·5%) compared with the older onset RA group (14·2 ± 1·2%; P <0·01). TCR γδ⁺ T cell levels were also significantly raised in the young patients (4·0 ± 0·9%) compared with elderly patients (1·6 ± 0·2%; P <0·01). T cell levels (CD3⁺) were similar in both groups (young 66·4 ± 3·3%; old 74·3 ± 3·4% (mean ± s.e.m.); NS). Total B cell levels (CD19⁺) were also similar in these groups (7·7 ± 0·7% versus 8·9 ± 1·8%; NS). A significant positive correlation was observed between the CD5⁻ B and TCR γδ⁺ T cell types in the patients (r = 0·72, P <0.05). Compared with age-matched normal controls, the younger onset patients had similar CD5⁺ B cell and TCR γδ⁺ T cell levels to the elderly controls (CD5⁺ B cells 30·2 ± 3·0%; TCR γδ⁺ T cells 3·0 ± 0·8%). Conversely, older onset RA patients had CD5⁺ B cell levels similar to the young controls (12·3 ± 1·9%). Spontaneous in vitro synthesis of immunoglobulins (IgM, IgA and IgG) and rheumatoid factors (IgM and IgA isotypes) were not significantly different in both patient groups. The coordinate expansion of circulating CD5⁺ B cells and γδ⁺ T cells seen in patients with RA presenting before 45 years of age and not after 65 years of age may suggest a potential role for these cells in more aggressive disease states.     

NLRP3 inflammasome is essential for the development of chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is now recognized as an inflammatory disease and the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome was speculated to participate into its pathophysiological process, however, a direct role of NLRP3 has yet to be clearly shown. Method: COPD model was established by tobacco inhalation, COPD modeling and NLRP3 knockout mice were treated with similar dose and duration of tobacco inhalation for 12 months, the lung function, lung damage and immune responses were evaluated between control, wild type COPD and NLRP3 knock out C57B1/6 mice. Results: 10 months after tobacco inhalation, the respiratory system resistance indexes of COPD mice was significantly higher than that of control and NLRP3 knockout mice (2.8 ± 0.5 vs. 1.2 ± 0.3 and 1.3 ± 0.1 cm H₂O ml^-1 s^-1, P < 0.05); the respiratory system compliance indexes of COPD was significantly lower than that of control and NLRP3 knockout mice (0.31 ± 0.02 vs. 0.43 ± 0.04, and 0.39 ± 0.01 ml/cm H₂O); the NLRP3 knockout mice displayed no distinguishable pathological damage in the lung. Of the broncho-alveolar lavage fluid (BALF), the concentration of IL-1 and IL-18 of the COPD were significantly higher than that of control and NLRP3 knockout mice (IL-1: 286.8 ± 1.7 vs. 23.8 ± 2.1 and 24.2 ± 1.3 pg/mL, P < 0.05; IL-18: 104.5 ± 4.2 vs. 12.6 ± 2.1 and 15.7 ± 2.8 pg/mL, P < 0.05); the total numbers of macrophages, eosinophils, lymphocyte and neutrophil of control, COPD and NLRP3 knockout mice were 2.3 ± 0.4, 0.5 ± 0.2, 10.3 ± 3.4 and 2.8 ± 2.7; 8.7 ± 1.1, 12.5 ± 1.1, 45.3 ± 3.3 and 29.2 ± 4.2; and 3.2 ± 0.7, 1.8 ± 0.4, 18.1 ± 1.1 and 12.8 ± 3.4 × 10⁴ mL, respectively; the rates of NLRP3 positive macrophages in the BALF of control, COPD and NLRP3 knockout mice were 5.0 ± 1.0%, 78.1 ± 9.2% and 2.0 ± 0.9%, respectively. Conclusion: NLRP3 inflammasome is essential for the development of COPD and blockade of NLRP3 might be a possible therapeutic strategy for COPD.     

Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H₂S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H₂S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg⁻¹·day⁻¹, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H₂S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H₂S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein⁻¹·h⁻¹) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H₂S formation.     

Hepatitis B virus DNA stability in plasma samples under short-term storage at 42°C

We evaluated the stability of hepatitis B virus (HBV) DNA in plasma samples stored at 42°C for external quality assessment (EQA) panels of viral load. To assess the stability of plasma samples containing different concentrations of HBV DNA, serial dilutions of HBV-infected samples with a viral load of 6.40 log₍₁₀₎ IU/mL were made to yield viral loads of 5, 4, and 3 log₍₁₀₎ IU/mL. These were incubated at 42°C for up to 7 days and then frozen at -70°C. Viral load testing for HBV DNA was performed for all samples using COBAS^¯ AmpliPrep/COBAS^¯ TaqMan^¯ HBV Test (v.2.0, Roche, Switzerland). Results were compared with fresh frozen plasma samples as a benchmark to establish acceptable measurements on the days following sample collection. Although the results of this study demonstrated a decrease in HBV DNA viral load ranging from 0.005 to 0.30 log₍₁₀₎ IU/mL after storage at 42°C for up to 7 days, these values did not exceed 0.5 log₍₁₀₎, which is the estimated intra-assay variation for molecular tests. Thus, the insignificant decrease in viral load suggests that shipment of HBV in plasma samples at temperatures of up to 42°C is permissible if they are frozen within 7 days.     

Mammary and whole animal metabolism of glucose and fatty acids in fasting lactating goats

1. Measurements were made of milk yield, mammary blood flow and mammary arteriovenous differences during the measurement of substrate entry rate by the isotope dilution method using [U-¹⁴C]glucose, acetate, palmitate, stearate or oleate in conscious lactating goats after 24 hr starvation.2. As previously reported, in fasting, milk yield fell to 40 ± 3·4 (S.E.)%, lactose secretion to 31 ± 3·4%, milk fat secretion to 81 ± 6·7% and mammary blood flow fell to 53 ± 7·5% of the values before fasting. Mammary O₂ uptake was only 45 ± 5% of the mean value in fed animals and there were marked falls in the uptakes of glucose, acetate and triglycerides, a smaller fall in β-hydroxybutyrate uptake, and a large increase in free fatty acid uptake.3. Glucose was found to enter the circulation of the fasting animal at 1-1·6 mg/min/kg body wt. (entry rate) and it gave rise to 3-5% of the total CO₂. The udder took up 10·7-16·1 mg/min/kg of tissue and 8-10% of mammary CO₂ was derived from glucose, although only 5-10% was oxidized. Mammary uptake accounted for 35-43% of the total glucose entering the circulation.4. In the whole animal acetate entry rate was 1-1·4 mg/min/kg and 9-10% of total CO₂ was derived from it. The udder used 0·8-2·4 mg/min/kg of tissue and 9-13% of mammary CO₂ was derived from acetate, 46-79% of that taken up being oxidized. Mammary uptake accounted for only 2-6% of the total acetate entry rate. Negligible quantities of isotope were found in milk fatty acids and there was a fall in the proportion of milk fatty acids of chain length up to C₁₄ which in fed animals are synthesized from acetate and β-hydroxybutyrate.5. Palmitate, stearate and oleate entered the circulation as free fatty acids at 0·94-6·8 mg/min/kg and 6-9% of total CO₂ was derived from each. The udder took up 3·0-5·7 mg/min/kg of tissue and 4-8% of mammary CO₂ was derived from each acid. In the udder 8 and 5·5% of stearate and oleate were oxidized and 25% of palmitate. Mammary uptake of stearate was 31·5% of the total entry rate, palmitate 1%, and oleate 7·5%. Only long chain milk fatty acids were labelled.6. During fasting the mammary R.Q. was 0·85 ± 0·045 compared with a value in fed animals of 1·24 ± 0·02, when the udder is synthesizing fatty acids from acetate. The total mammary uptake of lipid precursors was only 74% of the rate of milk fat secretion and there was an 18% shrinkage in empty udder volume, suggesting the use of endogenous mammary tissue substrates.     

The Effect of Cadmium Pretreatment on the Nephrotoxic Action and Kidney Uptake of Mercury in Male and Female Rats

Pretreatment of female rats with cadmium (2 × 2·46 mg Cd²⁺/kg as CdCl₂) protected them against the nephrotoxic effect of Hg²⁺ (0·5, 1·0 and 1·5 mg/kg as HgCl₂) given 6 days after the second dose of Cd²⁺. Male rats were more sensitive than females to HgCl₂ and were protected by the Cd²⁺ pretreatment against only 0·5 mg Hg²⁺/kg.Protection by Cd²⁺ was not associated with decreased accumulation of Hg²⁺ in the kidneys; on the contrary, uptake was increased by Cd²⁺ and, at the two higher dose levels, was greater in the kidney of the less sensitive female rat than in the male. Also, in control female rats the renal burden of Hg²⁺ seemed to be independent of the dose within the range 0·5-1·5 mg Hg²⁺/kg, whereas the tubular damage was dose dependent.     

Circulating lymphocyte subpopulations in Hashimoto thyroiditis

Peripheral blood and T and B lymphocytes and [¹²⁵I]thyroglobulin-binding lymphocytes were investigated in twenty-two euthyroid Hashimoto thyroiditis patients and in twenty-two age- and sex-matched normal subjects. Although the total lymphocyte count in Hashimoto patients (mean±SEM = 1226±187/mm³) was lower than in normal subjects (1603±156/mm³) this difference was not statistically significant. There was, however, a statistically significant reduction in the proportion of circulating T lymphocytes in the Hashimoto patients (mean±SEM = 57·4±2·5%) as assessed by the sheep red-cell rosette method when compared with the normal controls (mean±SEM = 66·7±1·8%). The proportion of B lymphocytes in the peripheral blood as assessed by indirect immunofluorescence, was not significantly different being 21·6±2·1% in the Hashimoto patients and 20·2±1·1% in normal subjects.

[¹²⁵I]thyroglobulin-binding lymphocytes, as assessed by autoradiography were present in the circulation of nineteen Hashimoto patients with a mean frequency of 8·37±1·15/10⁴ lymphocytes and in thirteen normal subjects with a mean of 8·84±0·93/10⁴ lymphocytes. There was no difference in the degree of [¹²⁵I]thyroglobulin binding between the two groups as determined by grain count analysis. There was no apparent correlation between age or thyroglobulin antibody titres and the frequency of [¹²⁵I]thyroglobulin-binding lymphocytes. Thyroglobulin-binding lymphocytes were increased 100-fold in a Hashimoto thyroid biopsy in comparison to the patient's peripheral blood.

     

Mild Dehydration and Cycling Performance During 5-Kilometer Hill Climbing

Context:

Hydration has been shown to be an important factor in performance; however, the effects of mild dehydration during intense cycling are not clear.

Objective:

To determine the influence of mild dehydration on cycling performance during an outdoor climbing trial in the heat (ambient temperature = 29.0°C ± 2.2°C).

Design:

Crossover study.

Setting:

Outdoor.

Patients or Other Participants:

Ten well-trained, male endurance cyclists (age = 28 ± 5 years, height = 182 ± 0.4 cm, mass = 73 ± 4 kg, maximal oxygen uptake = 56 ± 9 mL·min⁻¹·kg⁻¹, body fat = 23% ± 2%, maximal power = 354 ± 48 W).

Intervention(s):

Participants completed 1 hour of steady-state cycling with or without drinking to achieve the desired pre-exercise hydration level before 5-km hill-climbing cycling. Participants started the 5-km ride either euhydrated (EUH) or dehydrated by −1% of body mass (DEH).

Main Outcome Measure(s):

Performance time, core temperature, sweat rate, sweat sensitivity, and rating of perceived exertion (RPE).

Results:

Participants completed the 5-km ride 5.8% faster in the EUH (16.6 ± 2.3 minutes) than DEH (17.6 ± 2.9 minutes) trial (t₁ = 10.221, P = .001). Postexercise body mass was −1.4% ± 0.3% for the EUH trial and −2.2% ± 0.2% for the DEH trial (t₁ = 191.384, P < .001). Core temperature after the climb was greater during the DEH (39.2°C ± 0.3°C) than EUH (38.8°C ± 0.2°C) trial (t₁ = 8.04, P = .005). Sweat rate was lower during the DEH (0.44 ± 0.16 mg·m⁻²·s⁻¹) than EUH (0.51 ± 0.16 mg·m⁻²·s⁻¹) trial (t₈ = 2.703, P = .03). Sweat sensitivity was lower during the DEH (72.6 ± 32 g·°C⁻¹·min⁻¹) than EUH (102.6 ± 54.2 g·°C⁻¹·min⁻¹) trial (t₈ = 3.072, P = .02). Lastly, RPE after the exercise performance test was higher for the DEH (19.0 ± 1.0) than EUH (17.0 ± 1.0) participants (t₉ = −3.36, P = .008).

Conclusions:

We found mild dehydration decreased cycling performance during a 5-km outdoor hill course, probably due to greater heat strain and greater perceived intensity.Key Words: hypohydration, heat stress, hyperthermia, hydration status, exercise

Key Points

• Euhydrated athletes were faster during a 5-km, outdoor, hill-climbing course.
• Mild dehydration decreased physiologic function.
• Dehydration hindered cyclists'' ability to maintain cycling cadence.
• Mild dehydration decreased cycling performance during a 5-km, outdoor, hill-climbing course, possibly due to thermoregulatory strain and perceived exertion.

Researchers have documented well that dehydration exceeding 2% of body mass reduces exercise performance^1,2 and increases thermoregulatory strain, especially in the heat.³ Dehydration-induced hypovolemia leads to increased heart rate to maintain cardiac output.¹ Dehydration also decreases blood flow in the skin and sweat rate and increases the risk of hyperthermia when exercise is performed in a hot environment. All these physiologic responses to dehydration lead to lower aerobic capacity and exercise performance.^1,4Greater levels of dehydration result in greater reductions in aerobic exercise performance. Investigators⁵ have demonstrated that levels of dehydration of −1%, −2%, −3%, and −4% of body mass are increasingly detrimental to cardiovascular and thermoregulatory function. Similarly, researchers⁶ have shown that dehydration at −2.5% of body mass reduces exercise time to exhaustion even in a temperate environment. In addition, Cheuvront et al⁷ reported that, when cyclists performed a fixed 30-minute cycling test in a temperate environment dehydrated (DEH) at −3% of body mass, their total work production was 8% lower than their performance in a euhydrated (EUH) state. In addition, Ebert et al⁸ studied the effect of dehydration on cycling performance during hill climbing in the heat. Dehydration was induced by a 2-hour submaximal exercise bout, with low (0.4 L) or high (2.4 L) fluid intake causing a −1.3% or −3.6% reduction, respectively, in body mass. After the 2-hour exercise bout, participants mounted their own bicycles and cycled on a treadmill set at an 8% grade and a speed of 88% of each maximal aerobic power output. Time to exhaustion was 5.6 minutes shorter when participants were dehydrated.In a separate study,⁹ cyclists completed a performance test involving a fixed amount of work in a hot environment either EUH or with less than 2% dehydration. Time to completion was 6.5% (43 seconds) shorter in EUH participants (P < .05). The researchers suggested cyclists could self-select higher workloads while EUH, probably due to lower esophageal temperatures and ratings of perceived exertion (RPE).⁹ Nevertheless, some investigators have not shown a negative effect of modest dehydration (<−2% body mass) on 1-hour cycling performance in temperate environments.^10,11 Interestingly, these researchers have tested cycling performance only in a laboratory setting through an exercise-to-exhaustion or constant time protocol, but no data are available for real outdoor conditions.Investigators^12,13 have documented well that a substantial percentage of athletes start training or competing when inadequately hydrated based on high urine specific gravity (USG) values. Although this technique cannot provide a precise level of dehydration, we believe that their degree of dehydration might be just below the threshold of thirst. Thirst usually is activated when body water deficit exceeds 1% of body mass.¹⁴ Therefore, we suspect that these hypohydrated athletes might be dehydrated by approximately −1% of their body mass.Currently, few investigators have examined the effects of mild dehydration (1% of body mass loss) on cycling performance, so the physiologic responses during intense cycling remain unclear. Furthermore, no one has examined the effect of dehydration on cycling performance in outdoor conditions, especially when air flow over the skin is much higher in cycling than in a laboratory setting with a fan. Therefore, the purpose of our study was to determine the influence of mild dehydration (−1% of body mass) on cycling performance during outdoor hill climbing in the heat.     

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT₄ receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT₄ receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT₄ receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg⁻¹·day⁻¹, days 36-42), tegaserod (1 mg·kg⁻¹·day⁻¹, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT₄ receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT₄ receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.     

The effect of diameter on the electrical constants of frog skeletal muscle fibres

1. Electrical constants were determined on isolated single fibres or on fibres from bundles from frog's twitch muscles by analysing the low frequency cable properties.

2. The sarcoplasmic conductivity (G_i) was 5·9 mmho/cm at 20° C, and its temperature coefficient (Q₁₀) was 1·37.

3. The Q₁₀ of the membrane conductance (G_M) was 1·49, and that of the membrane capacity (C_M) was 1·02.

4. C_M increases with diameter (D) in an approximately linear manner: the values were 4·6 μF/cm² at D = 50 μ, and 8·5 μF/cm² at D = 130 μ.

5. G_M also increases with diameter, being 0·21 mmho/cm² at D = 50 μ and 0·37 mmho/cm² at D = 130 μ.

6. These results suggest that the transverse tubular system contributes substantially to the values of low frequency capacity and conductance measured at the surface membrane.

     

Aural Canal,Esophageal, and Rectal Temperatures During Exertional Heat Stress and the Subsequent Recovery Period

Context:

The measurement of body temperature is crucial for the initial diagnosis of exertional heat injury and for monitoring purposes during a subsequent treatment strategy. However, little information is available about how different measurements of body temperature respond during and after exertional heat stress.

Objective:

To present the temporal responses of aural canal (T_ac), esophageal (T_es), and rectal (T_re) temperatures during 2 different scenarios (S1, S2) involving exertional heat stress and a subsequent recovery period.

Design:

Randomized controlled trial.

Setting:

University research laboratory.

Patients or Other Participants:

Twenty-four healthy volunteers, with 12 (5 men, 7 women) participating in S1 and 12 (7 men, 5 women) participating in S2.

Intervention(s):

The participants exercised in the heat (42°C, 30% relative humidity) until they reached a 39.5°C cut-off criterion, which was determined by T_re in S1 and by T_es in S2. As such, participants attained different levels of hyperthermia (as determined by T_re) at the end of exercise. Participants in S1 were subsequently immersed in cold water (2°C) until T_re reached 37.5°C, and participants in S2 recovered in a temperate environment (30°C, 30% relative humidity) for 60 minutes.

Main Outcome Measure(s):

We measured T_ac, T_es, and T_re throughout both scenarios.

Results:

The T_es (S1  =  40.19 ± 0.41°C, S2  =  39.50 ± 0.02°C) was higher at the end of exercise compared with both T_ac (S1  =  39.74 ± 0.42°C, S2  =  38.89 ± 0.32°C) and T_re (S1  =  39.41 ± 0.04°C, S2  =  38.74 ± 0.28°C) (for both comparisons in each scenario, P < .001). Conversely, T_es (S1  =  36.26 ± 0.74°C, S2  =  37.36 ± 0.34°C) and T_ac (S1  =  36.48 ± 1.07°C, S2  =  36.97 ± 0.38°C) were lower compared with T_re (S1  =  37.54 ± 0.04°C, S2  =  37.78 ± 0.31°C) at the end of both scenarios (for both comparisons in each scenario, P < .001).

Conclusions:

We found that T_ac, T_es, and T_re presented different temporal responses during and after both scenarios of exertional heat stress and a subsequent recovery period. Although these results may not have direct practical implications in the field monitoring and treatment of individuals with exertional heat injury, they do quantify the extent to which these body temperature measurements differ in such scenarios.     

Postexercise Cooling Rates in 2 Cooling Jackets

Context:

Cooling jackets are a common method for removing stored heat accumulated during exercise. To date, the efficiency and practicality of different types of cooling jackets have received minimal investigation.

Objective:

To examine whether a cooling jacket containing a phase-change material (PC17) results in more rapid postexercise cooling than a gel cooling jacket and a no-jacket (control) condition.

Design:

Randomized, counterbalanced design with 3 experimental conditions.

Setting:

Participants exercised at 75% V̇o₂max workload in a hot climate chamber (temperature  =  35.0 ± 1.4°C, relative humidity  =  52 ± 4%) for 30 minutes, followed by postexercise cooling for 30 minutes in cool laboratory conditions (ambient temperature  =  24.9 ± 1.8°C, relative humidity  =  39% ± 10%).

Patients or Other Participants:

Twelve physically active men (age  =  21.3 ± 1.1 years, height  =  182.7 ± 7.1 cm, body mass  =  76.2 ± 9.5 kg, sum of 6 skinfolds  =  50.5 ± 6.9 mm, body surface area  =  1.98 ± 0.14 m², V̇o₂max  =  49.0 ± 7.0 mL·kg⁻¹·min⁻¹) participated.

Intervention(s):

Three experimental conditions, consisting of a PC17 jacket, a gel jacket, and no jacket.

Main Outcome Measure(s):

Core temperature (T_C), mean skin temperature (T_Sk), and T_C cooling rate (°C/min).

Results:

Mean peak T_C postexercise was 38.49 ± 0.42°C, 38.57 ± 0.41°C, and 38.55 ± 0.40°C for the PC17 jacket, gel jacket, and control conditions, respectively. No differences were observed in peak T_C cooling rates among the PC17 jacket (0.038 ± 0.007°C/min), gel jacket (0.040 ± 0.009°C/min), and control (0.034 ± 0.010°C/min, P > .05) conditions. Between trials, no differences were calculated for mean T_Sk cooling.

Conclusions:

Similar cooling rates for all 3 conditions indicate that there is no benefit associated with wearing the PC17 or gel jacket.     

Human erythrocyte anion permeabilities measured under conditions of net charge transfer

1. The permeability of the human erythrocyte to anions has been measured under conditions of net charge transfer: for Cl^- and HCO₃^- ions, at 37° C, this permeability is 5 orders of magnitude too small to account for the rate of the electroneutral anion exchange which is responsible for the chloride, or Hamburger, shift.

2. The method is an indirect one in which the ionophore, valinomycin, is used to increase the erythrocyte K⁺ permeability: in the absence of permeant cation externally, the rate of the resulting K⁺ efflux may be limited by the slowness of the accompanying anion efflux, allowing the true anion permeability to be estimated.

3. The average Cl^- permeability estimated in ACD-stored erythrocytes (seven experiments) and erythrocytes from fresh blood (two experiments) was 2·1 × 10^-8 cm/sec at 37° C and pH 7·4: this may also be expressed as a Cl^- conductance of about 1·0 × 10^-5 Ω^-1 cm^-2. The apparent activation energy for net efflux of Cl^- was found to be 3·9 kJ/mole (16·4 kcal/mole).

4. In fresh cells, the ratios of Cl^-, HCO₃^-, Br^- and I^- permeabilities (or conductances) were 1:0·8:1·5:5. The three halide ions follow Eisenman's Sequence I, representing a binding site of low field strength.

     

Interaction of α- and δβ0-thalassaemia: haematological features and globin chain synthesis analysis

An observation of suspected interaction of δβ⁰- and α-thalassaemia, identified through careful examination of the family, is reported. The δβ⁰-thalassaemia was of the usual type found in Sardinia, characterised by high Hb F levels and very low levels of glycine in the isolated γCB₃ peptide. The haematological findings in the double δβ⁰-/α-thalassaemia heterozygotes were: normal MCV and Hb A₂ levels, increased Hb F (11·3 to 16·8%) heterogeneously distributed in red cells, and almost balanced α/β globin chain synthesis ratios.     

Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

In cardiomyocytes, calcium (Ca²⁺) release units comprise clusters of intracellular Ca²⁺ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca²⁺ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca²⁺ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F₀), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca²⁺ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F₀, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.