Betulinic Acid Exerts Cytoprotective Activity on Zika Virus-Infected Neural Progenitor Cells.

Zika virus (ZIKV), a member of the Flaviviridae family, was brought into the spotlight due to its widespread and increased pathogenicity, including Guillain-Barré syndrome and microcephaly. Neural progenitor cells (NPCs), which are multipotent cells capable of differentiating into the major neural phenotypes, are very susceptible to ZIKV infection. Given the complications of ZIKV infection and potential harm to public health, effective treatment options are urgently needed. Betulinic acid (BA), an abundant terpenoid of the lupane group, displays several biological activities, including neuroprotective effects. Here we demonstrate that Sox2+ NPCs, which are highly susceptible to ZIKV when compared to their neuronal counterparts, are protected against ZIKV-induced cell death when treated with BA. Similarly, the population of Sox2+ and Casp3+ NPCs found in ZIKV-infected cerebral organoids was significantly higher in the presence of BA than in untreated controls. Moreover, well-preserved structures were found in BA-treated organoids in contrast to ZIKV-infected controls. Bioinformatics analysis indicated Akt pathway activation by BA treatment. This was confirmed by phosphorylated Akt analysis, both in BA-treated NPCs and brain organoids, as shown by immunoblotting and immunofluorescence analyses, respectively. Taken together, these data suggest a neuroprotective role of BA in ZIKV-infected NPCs.

Calf Muscle Oxygen Saturation during 6-Minute Walk Test and Its Relationship with Walking Impairment in Symptomatic Peripheral Artery Disease.

BACKGROUND: Impaired microcirculation is associated with poor walking capacity in symptomatic peripheral artery disease (PAD) patients during treadmill test; however, this test does not simulate the efforts of daily walking of these patients. Thus, the aim of the study was to describe the microcirculation responses during a 6-minute walk test (6MWT) and to analyze the relationship between microcirculation indicators and walking impairment in symptomatic PAD patients. METHODS: Thirty-four patients were included (mean age = 67.6 ± 11.2 years). Their clinical characteristics were collected, and they performed a 6MWT, in which the initial claudication distance (ICD) and total walking distance (TWD) were recorded. During and after the 6MWT, calf muscle oxygen saturation (StO2) parameters were monitored continuously to measure microcirculation behavior. The association between calf muscle StO2 parameters and walking impairment were analyzed by Pearson or Spearman correlations. RESULTS: Walking impairment was not associated with any StO2 parameters during exercise. In contrast, after 6MWT, recovery time of StO2 (r = -0.472, P = 0.008) and recovery time to maximal StO2 (r = -0.402, P = 0.019) were negatively correlated with ICD. Furthermore, the distance walked under claudication symptoms (ΔTWD-ICD) was positively correlated with recovery time to maximal StO2 (r = 0.347, P = 0.048). CONCLUSIONS: In symptomatic PAD patients, shorter ICD values during a 6MWT are associated with a delayed recovery in calf muscle StO2 after exercise. Calf muscle StO2 parameters decrease subtly during 6MWT, suggesting that the degree of ischemia in the calf muscle during ground walking, simulating efforts of the daily walking, is relatively low.

Effects of Resistance Training on Cardiovascular Function in Patients With Peripheral Artery Disease: A Randomized Controlled Trial.

Gomes, APF, Correia, MA, Soares, AHG, Cucato, GG, Lima, AHRA, Cavalcante, BR, Sobral-Filho, DC, and Ritti-Dias, RM. Effects of resistance training on cardiovascular function in patients with peripheral artery disease: A randomized controlled trial. J Strength Cond Res 32(4): 1072-1080, 2018-The aim of this study was to analyze the effects of resistance training on cardiovascular function of patients with peripheral artery disease (PAD). In total, 30 patients with PAD were invited to participate in this randomized controlled trial, randomly allocated to a control (n = 15, 66 ± 2 years; stretching and relaxation exercises) or resistance training group (n = 15, 60 ± 3 years; 3 sets of 10 repetitions of 8 whole-body exercises, with a 2-minute interval between sets). Resting and 24-hour blood pressure (BP), cardiac output, systemic vascular resistance, and autonomic variables were obtained before and after 12 weeks of intervention. A blinded investigator performed all analyses. After 12 weeks of intervention there was maintenance of resting systolic, diastolic, and mean BP (p > 0.18), cardiac output (p = 0.46), and systemic vascular resistance (p = 0.55) in both groups. There was a time effect reduction in heart rate (p = 0.02), accompanied by changes in cardiac autonomic modulation (p = 0.03). There were no changes in 24-hour systolic, diastolic, and mean BP, heart rate, or rate pressure product (p > 0.05). The BP variability decreased in systolic (asleep, p = 0.003), diastolic (24 hours and awake, p = 0.001), and mean (24 hours and asleep, p < 0.02) only in the resistance training (RT) group. Twelve weeks of RT did not change resting and 24-hour BP, or their hemodynamic and autonomic determinants in patients with PAD; however, there were decreases in BP variability, indicating that it could be considered as an alternative to reducing cardiovascular risk in patients with PAD.

Effects of active recovery on autonomic and haemodynamic responses after aerobic exercise.

The aim of this study was to examine the effect of active recovery on autonomic and haemodynamic responses after exercise in healthy adults. Nineteen healthy young male individuals underwent two experimental sessions: exercise with active recovery (AR) and exercise with passive recovery (PR). The exercise sessions comprised three phases: warm-up (5 min), exercise phase (cycle ergometer, 30 min, intensity between 60 and 70% of the heart rate reserve) and recovery (5 min). In the AR, the subjects remained cycling in the recovery phase at intensity between 30% and 35% of heart rate reserve, while in the PR, the subjects stopped the exercise after finishing the exercise phase. Blood pressure and heart rate were measured before and over the 30 min after the interventions. There were no differences for systolic and diastolic blood pressures, heart rate and rate pressure product between active and passive recovery sessions. Also, all heart rate variability parameters changed similarly after exercise with passive or active recovery sessions. In summary, exercise with active recovery does not affect the autonomic and haemodynamic responses after moderate-intensity aerobic exercise in healthy young male individuals.

Are the barriers for physical activity practice equal for all peripheral artery disease patients?

OBJECTIVE: To investigate barriers to physical activity related to the sociodemographic comorbidities and clinical variables of patients with intermittent claudication. DESIGN: Cross-sectional study. SETTING: Ambulatory care. PARTICIPANTS: The medical histories of patients (N=145) aged ≥50 years with intermittent claudication were examined. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sociodemographic data (sex, race, level of education, socioeconomic status, marital status), comorbidities (overweight, hypertension, dyslipidemia, diabetes, currently smoking, heart disease), and clinical variables (initial claudication distance, total walking distance, ankle-brachial index). Information on personal and environmental barriers was obtained by questionnaire. RESULTS: Low economic status was most associated with "being afraid of falling" (odd ratios [OR]=2.22; 95% confidence interval [CI], 1.08-4.54). Low education level was most associated with "lack of street pedestrian crossing" (OR=3.34; 95% CI, 1.48-7.52). Diabetes was associated with lack of energy (OR=3.38; 95% CI, 1.68-6.79) and other medical conditions (eg, arthritis, angina) (OR=3.44; 95% CI, 1.65-7.16). Ankle brachial index was associated with "some difficulty in getting to a place where physical activity can be performed" (OR=2.75; 95% CI, 1.22-6.21). Walking capacity was strongly associated with barriers relating to leg pain (OR=7.39; 95% CI, 1.66-32.88). CONCLUSIONS: Older patients, those with a low education level, patients with diabetes, low ankle brachial index, and those with a lower walking capacity are more likely to experience barriers to physical activity.