12.15 Effect of Anti-Hypertensive Treatment on Circulating Endothelial Progenitor Cells in Patients with Mild Essential Hypertension

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Role of heme oxygenase in modulating endothelial function in mesenteric small resistance arteries of spontaneously hypertensive rats.

It has been proposed that endothelial dysfunction is due to the excessive degradation of nitric oxide (NO) by oxidative stress. The enzyme heme-oxygenase (HO) seems to exert a protective effect on oxidative stress in the vasculature, both in animal models and in humans. The objective of this study is to evaluate the effects of inhibition or activation of HO on endothelial function in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). Six SHR were treated with cobalt protoporphyrin IX 50 mg/Kg (CoPP), an activator of HO; six SHR with stannous mesoporphyrin 30 mg/Kg (SnMP), an inhibitor of HO, and six SHR with saline. As controls, six Wistar-Kyoto rats (WKY) were treated with CoPP, six WKY with SnMP, and six WKY with saline. Drugs were injected in the peritoneum once a week for 2 weeks. Systolic blood pressure (SBP) was measured (tail cuff method) before and after treatment. Mesenteric small resistance arteries were mounted on a micromyograph. Endothelial function was evaluated as a cumulative concentration-response curve to acetylcholine (ACH), before and after pre-incubation with N(G)-methyl-L-arginine (L-NMMA, inhibitor of NO synthase), and to bradykinin (BK). In SHR treatment with CoPP, improved ACH-and BK-induced vasodilatation (ANOVA p < 0.001) and this improvement was abolished by L-NMMA (ANOVA p < 0.001). SnMP was devoid of effects on endothelial function. In WKY, both activation and inhibition of HO did not substantially affect endothelium-mediated vasodilatation. The stimulation of HO seems to induce an improvement of endothelial dysfunction in SHR by possibly reducing oxidative stress and increasing NO availability

Risk of hyperkalemia in patients with moderate chronic kidney disease initiating angiotensin converting enzyme inhibitors or angiotensin receptor blockers : a randomized study

Background: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are renoprotective but both may increase serum potassium concentrations in patients with chronic kidney disease (CKD). The proportion of affected patients, the optimum follow-up period and whether there are differences between drugs in the development of this complication remain to be scertained. Methods: In a randomized, double-blind, phase IV, controlled, crossover study we recruited 30 patients with stage 3 CKD under restrictive eligibility criteria and strict dietary control. With the exception of withdrawals, each patient was treated with olmesartan and enalapril separately for 3 months each, with a 1-week wash-out period between treatments. Patients were clinically assessed on 10 occasions via measurements of serum and urine samples. We used the Cochran-Mantel-Haenszel statistics for comparison of categorical data between groups. Comparisons were also made using independent two-sample t-tests and Welch's t-test. Analysis of variance (ANOVA) was performed when necessary. We used either a Mann-Whitney or Kruskal-Wallis test if the distribution was not normal or the variance not homogeneous. Results: Enalapril and olmesartan increased serum potassium levels similarly (0.3 mmol/L and 0.24 mmol/L respectively). The percentage of patients presenting hyperkalemia higher than 5 mmol/L did not differ between treatments: 37% for olmesartan and 40% for enalapril. The mean e-GFR ranged 46.3 to 48.59 ml/mint/1.73 m2 in those treated with olmesartan and 46.8 to 48.3 ml/mint/1.73 m2 in those with enalapril and remained unchanged at the end of the study. The decreases in microalbuminuria were also similar (23% in olmesartan and 29% in enalapril patients) in the 4 weeks time point. The percentage of patients presenting hyperkalemia, even after a two month period, did not differ between treatments. There were no appreciable changes in sodium and potassium urinary excretion. Conclusions: Disturbances in potassium balance upon treatment with either olmesartan or enalapril are frequent and without differences between groups. The follow-up of these patients should include control of potassium levels, at least after the first week and the first and second month after initiating treatment

Bridging consent: from toll bridges to lift bridges?

<p>Abstract</p> <p>Background</p> <p>The ability to share human biological samples, associated data and results across disease-specific and population-based human research biobanks is becoming increasingly important for research into disease development and translation. Although informed consent often does not anticipate such cross-domain sharing, it is important to examine its plausibility. The purpose of this study was to explore the feasibility of bridging consent between disease-specific and population-based research. Comparative analyses of 1) current ethical and legal frameworks governing consent and 2) informed consent models found in disease-specific and population-based research were conducted.</p> <p>Discussion</p> <p>Ethical and legal frameworks governing consent dissuade cross-domain data sharing. Paradoxically, analysis of consent models for disease-specific and population-based research reveals such a high degree of similarity that bridging consent could be possible if additional information regarding bridging was incorporated into consent forms. We submit that bridging of consent could be supported if current trends endorsing a new interpretation of consent are adopted. To illustrate this we sketch potential bridging consent scenarios.</p> <p>Summary</p> <p>A bridging consent, respectful of the spirit of initial consent, is feasible and would require only small changes to the content of consents currently being used. Under a bridging consent approach, the initial data and samples collection can serve an identified research project as well as contribute to the creation of a resource for a range of other projects.</p

Sharing data for future research-engaging participants' views about data governance beyond the original project:a DIRECT Study

Purpose: Biomedical data governance strategies should ensure that data are collected, stored, and used ethically and lawfully. However, research participants’ preferences for how data should be governed is least studied. The Diabetes Research on Patient Stratification (DIRECT) project collected substantial amounts of health and genetic information from patients at risk of, and with type II diabetes. We conducted a survey to understand participants’ future data governance preferences. Results will inform the postproject data governance strategy. Methods: A survey was distributed in Denmark, Sweden, The Netherlands, and the United Kingdom. Results: In total 855 surveys were returned. Ninety-seven percent were supportive of sharing data postproject, and 90% were happy to share data with universities, and 56% with commercial companies. The top three priorities for data sharing were highly secure database, DIRECT researchers to monitor data used by other researchers, and researchers cannot identify participants. Respondents frequently suggested that a postproject Data Access Committee should involve a DIRECT researcher, diabetes clinician, patient representative, and a DIRECT participant. Conclusion: Preferences of how data should be governed, and what data could be shared and with whom varied between countries. Researchers are considered as key custodians of participant data. Engaging participants aids in designing governance to support their choices