Bacterial meningitis caused by Streptococcus pneumoniae is associated with a significant mortality rate and persisting neurologic sequelae, including sensory-motor deficits, seizures, and impairment of learning and memory. The presence of proliferating bacteria within the subarachnoid and ventricular space compartments triggers an intense inflammatory host response at killing the invading microorganism. Proinflammatory mediators released in the process, including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, were shown to contribute to the development of brain injury in bacterial meningitis. Thus, the aim of this study was to verify the levels of the TNF-alpha, IL-1beta, IL-6, and CINC-1 in the rat brain after pneumococcal meningitis. The animals underwent a magna cistern tap receiving either 10 microL of sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension at the concentration of 5x10(9) cfu/mL. The placebo group was killed immediately after the induction and the meningitis group at 0, 6, 12, 24, 48, and 96h after induction. The brains were removed followed by the isolation of the hippocampus and prefrontal cortex for determining TNF-alpha, IL-1beta, IL-6, and CINC-1 levels. In the hippocampus we found increased levels of the TNF-alpha only at 6h (p<0.01; F=3.777); CINC-1 levels increased at 6 and 24h (p<0.001; p<0.05; F=15.05); and IL-6 and IL-1beta levels were not altered. In the prefrontal cortex, the TNF-alpha levels were found to be increased only at 6h (p<0.05; F=4.921); IL-6 (p<0.05; F=11.69) and IL-1beta (p<0.001; F=132.0) levels were found to be increased only at 24h after meningitis induction; and CINC-1 levels were found to be increased at 6, 12, and 24h (p<0.01; p<0.01; p<0.01; F=16.86) after meningitis induction. Our data suggest that cytokine/chemokine levels can be putative biomarkers of brain damage in the first hours of the pneumococcal meningitis.

Brachial vascular function after acute aerobic exercise in older adults with and without type 2 diabetes Purpose: The acute exercise model provides clinical insights regarding vascular dysfunction in adults with type 2 Diabetes Mellitus (T2DM), as it uncovers abnormalities not normally present at rest. However, whether vascular responses to acute exercise in adults with T2DM are intensity-dependent, and whether response patterns differ with aging and disease, remains unknown. Thus, we examined brachial artery flow-mediated dilation (FMD) and flow-mediated slowing (FMS) of pulse wave velocity (PWV), 10 and 60-min after an acute bout of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) in middle-aged and older men with and without T2DM compared to young men without T2DM. Hypothesis: HIIE would induce a larger decrease in FMD immediately after exercise cessation compared to MICE in older men with and without T2DM. Methods: Twelve males with (57-84 yr) and without (57-76 yr) T2DM, and 12 healthy young adults (20-40 yr), completed an isocaloric acute exercise bout of HIIE, MICE, and a non-exercise condition in randomized order. FMD and FMS were evaluated and offline analyzed by the same researcher following standard guidelines. Central and peripheral arterial stiffness were measured via applanation tonometry estimates of carotid-femoral PWV (cfPWV) and carotid dorsalis pedis PWV (cdPWV), respectively. Statistical inferences were performed using linear mixed models. Results: %FMD was reduced (d= - 5.94, 95% CI: -10.50 to -1.38 %, p=0.002), whereas %FMS was increased (d= 4.55, 95% CI: 0.62 to 8.48%, p=0.01), 10-min after HIIE only in older adults with T2DM, returning to resting values 60-min into recovery. Conversely, %FMD was increased (d= 5.33, 95% CI: 0.76 to 9.89%, p=0.009) 10-min after MICE only in older adults with T2DM, while cfPWV and cdPWV remained unchanged following HIIE and MICE in all groups. There were no group differences at rest in brachial %FMD and %FMS, while cfPWV and cdPWV were higher in older adults with T2DM compared to age-matched controls (cfPWV: d= 1.94, 95% CI: 0.44 to 3.44 m. s-1, p=0.009). Conclusions: We found evidence of intensity- and disease-dependent vascular responses to acute aerobic exercise. These findings suggest that high-intensity acute exercise transiently impairs vascular function in older adults with T2DM, which may constitute an important trigger for exercise-based long-term improvements in vascular function. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Flow-mediated slowing (FMS) is a non-invasive measure of endothelial function measured through reactive hyperemia-induced changes in pulse wave velocity (PWV). FMS is suggested to mitigate known pitfalls of flow-mediated dilation (FMD) including suboptimal repeatability and high-operator dependency. However, the few single-rater studies that examined FMS repeatability have shown controversial results and used only regional measurements of PWV, which might not reflect local brachial artery stiffness responses to reactive hyperemia. We assessed the inter- and intra-rater repeatability of ultrasound-based changes in local PWV (FMS) and diameter (FMD). Twenty-four healthy male participants aged 23–75 yr, were examined on two separate days. Reactive hyperemia-induced changes in PWV were calculated using a tailored R-script. The inter- and intra-rater repeatability were tested with the intraclass correlation coefficient (ICC), coefficient of variation (CV), and the Bland-Altman plot estimates. The inter-rater repeatability of FMS (bias: -0.08%; ICC: 0.85; 95% CI: 0.65 to 0.93; CV: 11%) and FMD (bias: -0.02%; ICC: 0.98; 95% CI: 0.97 to 0.99; CV: 7%) showed overall good repeatability over different days. The intra-rater repeatability of FMD (1st rater: bias: 0.27%; ICC: 0.90; 95% CI: 0.78 to 0.96; CV: 14%; 2nd rater: bias: 0.60%; ICC: 0.85; 95% CI: 0.64 to 0.94; CV: 18%) was better than FMS (1st rater: bias: -1.03%; ICC: 0.76; 95% CI: 0.44 to 0.91; CV: 21%; 2nd rater: bias:-0.49%; ICC: 0.70; 95% CI: 0.34 to 0.80; CV: 23%) but not different between raters. Ultrasound-based local measurements of PWV deceleration reactive hyperemia were repeatable among the raters.