Physiological Reports最新文献

Type 2 diabetes mellitus is characterized by a low cardiac energy status (PCr/ATP ratio), but it is unknown whether this also applies to prediabetes. Since PCr/ATP is correlated with elevated free fatty acids (FFA), a potentially lower PCr/ATP might be secondary to elevated FFA. To investigate this, we determined PCr/ATP and FFA levels in volunteers with prediabetes at two time-points during the day. Eight male volunteers with prediabetes underwent a MRI/MRS scan to determine left ventricular ejection fraction (LVEF) and PCr/ATP ratio at 7 am and at 5 pm. For reference, these results were compared to eight non-insulin resistant overweight or obese volunteers. Myocardial energy status was lower in the volunteers with prediabetes (PCr/ATP 1.03 ± 0.08) compared to non-insulin resistant overweight or obese volunteers (PCr/ATP 1.22 ± 0.04, p < 0.05), but FFA were not significantly different between groups. LVEF was similar in the volunteers with prediabetes compared to healthy overweight and obese volunteers (p = 0.23). Volunteers with prediabetes have a lower myocardial energy status in the morning compared to healthy overweight and obese volunteers, while cardiac function remained normal. In addition, no differences between morning and evening measurements of cardiac energy status and function were found.

We manipulated baseline peripheral arterial stiffness via changes in local arterial pressure with different limb positions to test the hypothesis that the magnitude of decrease in arterial stiffness post exercise/compression would be less when baseline stiffness is higher with the arm below the heart. Brachial-radial pulse wave velocity (PWV) was measured with tonometers in 19 healthy volunteers before and after 5 min of rhythmic handgrip exercise or passive forearm compressions with the arm positioned below or above the heart. Brachial-radial PWV was reduced 5 min after handgrip exercise below (10.4 ± 2.6 to 8.7 ± 2.2 m/s) and above (6.4 ± 1.3 to 5.3 ± 1.0 m/s) the heart, with no difference between positions (p > 0.05). PWV was also reduced 5 min after passive compressions with the arm below (10.8 ± 2.0 to 9.8 ± 2.1 m/s) and above (7.5 ± 1.4 to 5.7 ± 1.1 m/s), with no difference between positions (p > 0.05). Changes in local arterial pressure associated with arm position resulted in differences in baseline PWV but did not affect the magnitude of reduction in PWV with exercise or compressions. Reductions in peripheral arterial stiffness observed after rhythmic handgrip exercise and passive compressions were independent of baseline arterial stiffness.

The dispersion of the tidal volume and of the breathing frequency have been used to diagnose dysfunctional breathing during cardio-pulmonary exercise testing. No validated methods to objectively describe this dispersion exist. We aimed to validate such a method. We used simulations based on real-life parameters. Moving standard deviation (MSD) and residuals from locally estimated scatterplot smoothing (LOESS) were evaluated. The precision and the bias of each tested method at rest and during exercise simulations, with and without sighs, were measured. For LOESS, a 2nd degree polynomial was used, and different spans were tested (LOESS₁, LOESS_0.75, and LOESS_0.5). For MSD, different number of points used for the calculation were tested (MSD₇, MSD₁₁, MSD₁₅, and MSD19). The LOESS method was globally more precise, had less bias, and was less influenced by the trend as compared to MSD in almost all simulations except for extremely low dispersion combined with extreme trends. LOESS_0.75 had intermediate bias and precision between LOESS_0.5 and LOESS₁ in all simulations. LOESS_0.75 is a method that combines high precision, low bias, and low influenceability of trends. It could be considered as the method of choice to evaluate the dispersion of breathing parameters during cardiopulmonary exercise testing.

Muscle function declines with age. Since the primary energy source for contraction is aerobic, this study investigated age-related changes in muscle oxygenation dynamics to: characterize PO₂ transients during rest-work transitions, identify age-specific differences in oxygen delivery/utilization balance, and examine the relationship between interstitial and arterial oxygen tension (PO₂). Interstitial PO₂ was measured with a high-resolution stroboscopic phosphorescence quenching technique to map intra-contractile dynamics during changes in muscle activity-rest-to-work (RtW) and work-to-rest (WtR) in rats aged three (young) and 23 (old) months. RtW (τ_w) and WtR (τ_r) PO₂ transitions had lag periods and mono-exponential time constants. In young muscles, lag was 4 s, τ_w = 9.0 ± 3.7 s, and τ_r = 15.4 ± 3.9 s. For old, lag was also 4 s with increases to τ_w = 15.9 ± 3.5 s and τ_r = 41.4 ± 8.3 s. Resting PO₂'s were higher for young than for old (66.7 ± 13.7 vs. 60.2 ± 13.0 mmHg; p < 0.05). Work reduced PO₂ with a greater effect on old (42.5 ± 14.0 vs. 28.3 ± 16.5 mmHg; p < 0.05). Intra-contractile measurements revealed a spike in PO₂ (11 mmHg amplitude for >200 ms), which was absent in old. Further, sustained exercise in young showed a rising trend in PO₂, while old remained at nadir. The missing PO₂ spike in aged muscle contributes to reduced PO₂ during work and may explain age-related loss of endurance.

Urinary incontinence increases with age, reducing the elderly quality of life. Understanding its mechanisms and developing treatments are urgent tasks. While healthy striated muscle maintains homeostasis through mitophagy, aging is thought to reduce autophagy activity. This study aimed to detect abnormal mitochondrial accumulation in the rhabdosphincter using transmission electron microscopy (TEM). We collected the rhabdosphincter samples from seven patients undergoing cystectomy and used the rectus abdominis as controls. Both tissues were examined with Hematoxylin and eosin (HE) staining and TEM. ImageJ software was used to measure the mitochondrial area, perimeter, and luminance. HE staining revealed that the rhabdosphincter had fewer muscle fibers and more stromal tissue than the rectus abdominis. TEM images showed more gaps in muscle bundles and signs of mitochondrial damage, vacuolation, and swelling in the rhabdosphincter. Quantitative analysis revealed a larger average mitochondrial area (0.21 μm² vs. 0.063 μm², p < 0.01), longer perimeter (1.83 μm vs. 0.94 μm, p < 0.01) and higher luminance (156.6 vs. 90.2, p < 0.01) than those of the rectus abdominis. The rhabdosphincter of elderly individuals showed significant mitochondrial morphological abnormalities, with increased swelling and vacuolation.

Although mitochondrial alterations are implicated in cardiac pathologies, sex-specific changes following chronic stress and ischemia-reperfusion injury are poorly characterized. Male and female Wistar rats underwent chronic restraint stress (CRS) for 4 weeks versus controls, whereafter ex vivo hearts were subjected to regional ischemia and reperfusion. Post-reperfusion hearts were dissected into ischemia-reperfused and non-ischemic regions with high-resolution mitochondrial respirometry, and oxidative stress assays performed. CRS males displayed increased routine and fatty acid β-oxidation respiration in non-ischemic tissues but lowered ETF-linked LEAK contributions to overall electron transfer system capacity ratios in ischemia-reperfused regions versus controls. CRS males exhibited lowered superoxide dismutase activity and increased lipid peroxidation in well-perfused regions versus controls. Female CRS hearts showed attenuated ETF-linked LEAK respiration and increased lipid peroxidation versus controls in non-ischemic tissue but a lowered RE ratio (measure of mitochondrial coupling) with ischemia-reperfusion. Our findings highlight the heart's sexually dimorphic response to chronic stress and ischemic injury, with female hearts showing oxidative damage in non-ischemic tissues together with relatively intact mitochondrial function in ischemia-reperfused tissues.

The potential role of dark chocolate (DC) in enhancing exercise performance remains underexplored. While DC has been associated with various health benefits, its specific impact on endurance performance, particularly VO_2max, has not been conclusively established. This meta-analysis examined the effect of DC on VO_2max in healthy individuals using PRISMA guidelines. Following the application of inclusion and exclusion criteria, five randomized controlled trials (RCTs) involving 144 participants were included, with VO_2max as the primary outcome. The meta-analysis revealed no significant effect of DC on VO_2max (SMD = 0.14, 95% CI: -0.16 to 0.44, p = 0.36). Heterogeneity among the studies was low (Q-value = 3.34, I² = 0.00, p = 0.50), and sensitivity analysis confirmed the robustness of the findings, as excluding individual studies did not alter the results (SMD = 0.14, 95% CI: -0.16 to 0.44, p = 0.36). In conclusion, this meta-analysis suggests that DC consumption does not significantly improve VO_2max in healthy individuals. Future research should explore the effects of DC on other aspects of exercise performance, as well as its long-term impact, to better understand its potential role in athletic and health-related outcomes.

Intestinal tuft cells have recently been the focus of many studies due to their function in chemosensation and type 2 immunity in human gastrointestinal diseases. This study investigated the impact of acute tuft cell loss on intestinal physiological function. Tuft cell deletion was induced in DCLK1-IRES-GFP-CreERT2/+;Rosa-DTA (DCLK1-DTA) mice by a single tamoxifen injection, concomitant with littermate controls. Transient deletion of intestinal and biliary tuft cells was maximal on day 4 and recovered by day 7 post tamoxifen. DCLK1-DTA mice presented with significantly shortened small intestinal length and greater body weight loss by day 4. The activity of Na⁺-dependent glucose transporter 1 (SGLT1) and cystic fibrosis transmembrane regulator (CFTR) was reduced. Correlated with tuft cell reduction, the frequency of cholecystokinin (CCK)⁺ enteroendocrine and intermediate secretory cells, which co-express Paneth and goblet cell markers, was increased. In the lamina propria, fewer mast cells and leukocytes were found in the Day 4 DCLK1-DTA mice compared to controls. Ablation of tuft cells may induce nutrient malabsorption through alterations in epithelial cell proliferation and differentiation, along with changes in the mucosal defense response. These observations identify a new role for tuft cells in regulating intestinal absorption and mucosal regeneration.

Inflammatory molecules originating from an inflamed gut can promote systemic inflammation. We studied how acute intestinal injury affects the kidneys and the kallikrein-kinin system in mice with dextran sodium sulfate (DSS)-induced colitis. Seven-week-old male BALB/c mice were treated with 5% DSS for 7 days and either sacrificed immediately (DSS7, n = 6) or given fresh water for 4 more days (DSS11, n = 6). Untreated mice (n = 6) served as controls. Colitis and kidney damage was assessed using histochemical and immunohistochemical staining, ELISA, and RT-qPCR. Markers of kidney injury correlated with markers of colitis. Colitis increased albuminuria, reduced kidney weight, and induced transcription of lipocalin 2, kidney injury molecule-1, and interleukin-1beta, as well as increased immunostaining signal of c-Jun and NF-κB p65 in the kidneys. Colitis caused strong induction of colonic kininogen 2 transcription and bradykinin receptor B1-positive cells in the disrupted mucosa. In the kidney, colitis induced localization of tubular bradykinin receptor B2 to the nuclear envelope and increased kininogen 2 transcription. Disruption of the intestinal barrier by DSS promotes markers of kidney injury and inflammation, and the degree of kidney injury correlates with the severity of colitis. Colitis is associated with increased expression of kallikrein-kinin components in both the colon and kidneys.

This study aimed to evaluate discordance, binary classification, and model fit between race-predicted and race-neutral spirometry prediction equations. Spirometry data from 9506 patients (18-95 years old) self-identifying as White, Black, or Hispanic were analyzed, focusing on the lower limit of normal (LLN). Best-fit prediction equations were developed from 3771 patients with normal spirometry, using Bayesian Information Criterion (BIC) to compare models with and without race as a covariate. Results showed that including race as a covariate improved model fit, reducing BIC by at least ten units compared to Race-Neutral equations. Discordance between race-specific and race-neutral equations for detecting airway obstruction and restrictive spirometry patterns ranged from 4% to 13%. Using race-neutral equations resulted in false discovery rates (FDR) of 14% for Hispanics and 45% for Blacks and false negative rates (FNR) of 21% for Hispanics and 27% for Blacks in diagnosing airway obstruction. These findings indicate that removing race as a covariate in spirometry equations increases FDR and FNR, leading to higher misclassification rates. The 4%-13% discordance in interpreting airway obstruction and restrictive patterns has significant clinical implications, underscoring the need for careful consideration in developing spirometry reference equations.