Objective

The purpose of this study was to examine the effects of aerobic exercise training (AEXT) on dipping status in pre-hypertensive and stage-1 hypertensive individuals. A secondary purpose was to evaluate whether AEXT alters oxidative stress and endothelial biomarkers correlated to dipping status.

Methods

Twenty-three subjects underwent 24-h ambulatory blood pressure monitoring at baseline and after 6 months of AEXT. AEXT consisted of training at 70% VO2max 3 days/week for 6 months. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein (LDL)-cholesterol, oxidized LDL (ox-LDL), triglycerides, urinary and plasma nitric oxide end-products, superoxide dismutase and 8-iso-PGF2α were measured before and after AEXT. Statistically, ANOVA and linear regression were used.

Results

Before and after AEXT, there were no significant differences between dippers and non-dippers in any of the biomarkers except for total cholesterol following AEXT. In a sub-analysis following AEXT, 14 subjects retained their original dipping status, five subjects changed from dippers to non-dippers and four subjects changed from non-dippers to dippers. Significant differences existed between these groups in changes in total and LDL-cholesterol, ox-LDL, 8-iso-PGF2α and % Dip.

Conclusions

Changes in cholesterol levels but not oxidative stress or endothelial biomarkers were related to changes in BP variables following AEXT in dippers and non-dippers.

Aldosterone influences the kidney’s regulation of blood pressure (BP), but aldosterone can contribute to the pathogenesis of hypertension. Blood pressure is reduced with aerobic exercise training (AEX), but the extent to which plasma aldosterone (PA) levels change is unclear. The purpose of this study was to determine whether 6 months of AEX changed PA levels, 24 h sodium (Na+) excretion and BP in prehypertensive and hypertensive subjects and whether these changes differed according to ethnicity. The study was performed in the Kinesiology Department at the University of Maryland, College Park, and 35 (22 Caucasian; 13 African American) sedentary prehypertensive and hypertensive subjects completed 6 months of AEX. Blood samples were collected under fasting and supine conditions, and PA was measured by radioimmunoassay. In total population aerobic exercise training increased maximal oxygen consumption (24 ± 0.8 versus 28 ± 1 ml kg−1 min−1, P < 0.001) and decreased PA levels (97 ± 11 versus 72 ± 6 pg ml−1, P = 0.01), body mass index (28 ± 0.5 versus 28 ± 0.5 kg m−2, P = 0.004) and weight (85 ± 2 versus 83 ± 2 kg, P = 0.003). Aerobic exercise training decreased PA levels (from 119 ± 16 to 81 ± 7 pg ml−1, P = 0.02) in the Caucasians but there was no change in BP or Na+ excretion. African American participants had no significant changes in PA levels, BP and Na+ excretion. Plasma aldosterone levels were 47% lower at baseline (P = 0.01) and 30% lower after AEX (P = 0.04) in African American participants compared with Caucasians. Baseline (P = 0.08) and final PA levels (P = 0.17) did not differ between the two groups after accounting for baseline and final intra-abdominal fat, respectively. The reduction in PA levels with AEX appeared to be driven by the change in PA levels in Caucasian participants. Fat distribution contributed to the ethnic differences in PA levels.

Background & Aims

The relationship between serum peginterferon pharmacokinetics and pharmacodynamics and the early virologic response (EVR) to peginterferon and ribavirin therapy was assessed in patients with chronic hepatitis C virus (HCV) genotype 1 infection in the Virahep-C study.

Methods

333 patients [160 African Americans (AA) and 173 Caucasian Americans (CA)] who received peginterferon alfa-2a (180 μg/wk) without a dose modification during the initial 4 weeks of therapy were analyzed. Peginterferon and 2,5-OAS serum levels were measured on days 0, 1, 2, 3, 7, 14, 28, 56, 84, and 168 of treatment. The EVR: (≥ 2 log10 decline in HCV RNA levels by week 12 of therapy) was the primary virologic endpoint.

Results

Peginterferon pharmacokinetics after the first dose were similar in AA and CA, but AA had greater peginterferon concentrations at days 1, 3, 14 and 28 (p < 0.05). AA had higher absolute serum 2,5-OAS levels on days 0, 1, 2, 3, 7, 14, 28 and 56 (p < 0.05), but the magnitude of 2,5-OAS induction during treatment relative to day 0 were similar. AA patients exhibited a smaller decline in serum HCV RNA during the first 28 days of treatment (p < 0.001) and a lower EVR (65% vs. 83%). AA and CA with EVR had significantly higher serum peginterferon concentrations and serum 2,5-OAS induction during the first 12 weeks than patients without an EVR.

Conclusion

Peginterferon alfa-2a pharmacokinetic and pharmacodynamic variability is associated with EVR in both AA and CA with HCV infection, but do not explain the racial disparity in combination treatment efficacy.

Hemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for the renal toxicity that can follow intestinal infection and hemorrhagic colitis due to E. coli. A chimeric mouse-human antibody, designated cαStx2, that has neutralizing activity in a mouse model was produced and tested in healthy adult volunteers. In this phase I dose escalation study, cαStx2 was generally well tolerated. Pharmacokinetic studies indicated that clearance was stable over the dose range of 1.0 to 10 mg/kg of body weight (0.249 ± 0.023 ml/kg/h) but was higher for the 0.1-mg/kg dose (0.540 ± 0.078 ml/kg/h), suggesting saturable elimination. A similar nonlinear trend was observed for the volume of distribution, where average values ranged from 0.064 ± 0.015 liter/kg for the 1.0- to 10-mg/kg doses and 0.043 ± 0.005 for the 0.01-mg/kg dose. The relatively small volume of distribution suggests that the antibody is limited to the vascular (plasma) compartment. The mean half-life was 165 ± 66 h, with lowest values observed for the 0.1-mg/kg dose (56.2 ± 9.7 h) and the highest values reported for the 10.0-mg/kg dose (206.4 ± 12.4 h). Future studies are needed to confirm the safety of this cαStx2, and innovative clinical trials will be required to measure its efficacy in preventing or treating HUS.