IntroductionOur objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy.MethodsIn an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx), and osteoprotegerin). We assessed renal function by estimated creatinine clearance, plasma cystatin C, and urinary levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL). The changes from baseline in BMD and renal and bone biomarkers were compared across study arms.ResultsOf 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27 patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated patients we observed significant reductions from baseline in hip and lumbar spine BMD at week 24 (−1.8% and −2.5%) and week 48 (−2.1% and −2.1%), whereas BMD was stable in patients in the ABC/3TC arm. The changes from baseline in BMD were significantly different between study arms. All bone turnover biomarkers except osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but early changes did not predict subsequent loss of BMD. Renal function parameters were similar between study arms although a small increase in NGAL was detected among TDF-treated patients.ConclusionSwitching to TDF/FTC-based therapy led to decreases in BMD and increases in bone turnover markers compared with ABC/3TC-based treatment. No major difference in renal function was observed.Trial registrationClinicaltrials.gov NCT00647244
In a double-blind cross-over study of 33 marksmen (standard pistol, 25 m) the adrenergic beta 1-receptor blocker, metoprolol, was compared to placebo. Metoprolol obviously improved the pistol shooting performance compared with placebo. Shooting improved by 13.4% of possible improvement (i.e., 600 points minus actual points obtained) as an average (SE = 4%, 2P less than 0.002). The most skilled athletes demonstrated the clearest metoprolol improvement. We found no correlation between the shooting improvement and changes in the cardiovascular variables (i.e., changes of heart rate and systolic blood pressure) and no correlation to the estimated maximum O2 uptake. The shooting improvement is an effect of metoprolol on hand tremor. Emotional increase of heart rate and systolic blood pressure seem to be a beta 1-receptor phenomenon.
BackgroundOur objective was to evaluate and compare the effect of abacavir on levels of biomarkers associated with cardiovascular risk.MethodsIn an open-label randomized trial, HIV-infected patients were randomized 1:1 to switch from zidovudine/lamivudine to abacavir/lamivudine or tenofovir/emtricitabine. In the present analysis, we measured levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), E-selectin, and myeloperoxidase (MPO) at baseline and 4, 12, and 48 weeks after randomization. D-dimer and fasting lipids were measured at baseline and weeks 12 and 48. Levels of biomarkers at all time points and changes from baseline were compared across study arms using Wilcoxon rank sum test.ResultsOf 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. Levels of E-selectin (P = 0.004) and sVCAM-1 (P = 0.041) increased transiently from baseline to week 4 in the abacavir arm compared with the tenofovir arm, but no long-term increases were detected. We found no significant differences between study arms in the levels or changes in the levels of sICAM-1, MPO, d-dimer, IL-6, or hs-CRP. Levels of total cholesterol and high density lipoprotein (HDL) increased in the abacavir arm relative to the tenofovir arm, but no difference was found in total cholesterol/HDL ratio.ConclusionIn patients randomized to abacavir-based HIV-treatment transient increases were seen in the plasma levels of E-selectin and sVCAM-1 compared with treatment with tenofovir, but no difference between study arms was found in other biomarkers associated with endothelial dysfunction, inflammation, or coagulation. The clinical significance of these findings is uncertain.Trial RegestrationClinicaltrials.gov identifier: NCT00647244.
The purpose of this study was to evaluate the role of endogenous opiates in modulating physical performance during dynamic exercise in conscious man. The plasma concentration of fl-endorphin (BEP) and of adrenocorticotropic hormone (ACTH) along with muscle pain (McGuill Pain Questionnaire) were assessed in 17 trained, male runners before and after running the longest possible distance within 12 min (i.e., the Cooper test). Each runner participated twice in the test (double-blind cross-over design), with a 1-week interval-with or without an injection of the opiate antagonist naloxone (0.8 mg i.v.). The average (SEM) distance reached was 3,198 (45) m in the naloxone test and 3,240 (38) m in the placebo test. The BEP increased significantly during the tests by a factor of 4.1 on naloxone and by 2.8 on placebo (from the normal resting averages of 1.7 and 2.1 pmol/l, respectively). The ACTH also increased significantly by a factor of 2.0 on naloxone and 2.5 on placebo (from the normal resting averages of l 9.3 and 16.8 pmol/l, respectively). There were no significant differences between the naloxone and the placebo test with respect to the increments of BEP or ACTH by exercise. However, the perception of muscle pain was enhanced with naloxone. The increased perception of pain did not decrease the athletes ability to perform in terms of the distance run. We conclude that endogenous opiates are involved in the perception of pain associated with exhaustive exercise and may subserve psychological rather than physiological functions during exercise.
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