Einfluss antihypertensiver Medikamente auf die Endothelfunktion

Zusammenfassung: Bei Patienten mit arterieller Hypertonie liegt eine Endotheldysfunktion vor. Eine reduzierte Verfügbarkeit von gefäßerweiterndem Stickstoffmonoxid (NO) sowie ein Überschuss an vasokonstriktiven Substanzen (z.B. Endothelin oder Angiotensin II) sind als Ursache der gestörten endothelabhängigen Vasodilatation anzusehen. Das Vorhandensein einer Endotheldysfunktion korreliert mit kardiovaskulären Ereignissen und hat auch prognostische Bedeutung. Die Reduktion des Blutdrucks per se ist nicht ausreichend, um die Endothelfunktion zu verbessern. Die verschiedenen Substanzklassen der Antihypertensiva beeinflussen die Gefäßfunktion in unterschiedlicher Art und Weis

Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671]

BACKGROUND: Acute respiratory tract infections (ARTI) are among the most frequent reasons for consultations in primary care. Although predominantly viral in origin, ARTI often lead to the prescription of antibiotics for ambulatory patients, mainly because it is difficult to distinguish between viral and bacterial infections. Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance. A novel approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases. The aim of this trial is to compare a ProCT-guided antibiotic therapy with a standard approach based on evidence-based guidelines for patients with ARTI in primary care. METHODS/DESIGN: This is a randomised controlled trial in primary care with an open intervention. Adult patients judged by their general practitioner (GP) to need antibiotics for ARTI are randomised in equal numbers either to standard antibiotic therapy or to ProCT-guided antibiotic therapy. Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial. Exclusion criteria for patients are antibiotic use in the previous 28 days, psychiatric disorders or inability to give written informed consent, not being fluent in German, severe immunosuppression, intravenous drug use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation. The primary endpoint is days with restrictions from ARTI within 14 days after randomisation. Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days, days off work and days with side-effects from medication within 14 days, and relapse rate from the infection within 28 days after randomisation. DISCUSSION: We aim to include 600 patients from 50 general practices in the Northwest of Switzerland. Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age, proportion of female physicians, specialisation, years of postgraduate training and years in private practice

Das Endocannabinoid-System

Das Endocannabinoidsystem ist ein physiologisches System, welches unter anderem für die Kontrolle des Energiegleichgewichtes, den Glukose- und Lipidmetabolismus sowie für die Regulation des Körpergewichtes verantwortlich ist. Die Endocannabinoid- Rezeptoren sind sowohl im zentralen Nervensystem als auch in der Peripherie verteilt. Durch verschiedene Studien wird belegt, dass ein hyperaktives Endocannabinoidsystem für die Entwicklung verschiedener kardialer und metabolischer Risikofaktoren von Bedeutung ist. Die medikamentöse Blockierung des Cannabinoid-1- Rezeptors kann einen neuen Ansatz zur Beeinflussung von kardiometabolischer Risikofaktoren darstellen

Einfluss antihypertensiver Medikamente auf die Endothelfunktion

Bei Patienten mit arterieller Hypertonie liegt eine Endotheldysfunktion vor. Eine reduzierte Verfügbarkeit von gefäßerweiterndem Stickstoffmonoxid (NO) sowie ein Überschuss an vasokonstriktiven Substanzen (z.B. Endothelin oder Angiotensin II) sind als Ursache der gestörten endothelabhängigen Vasodilatation anzusehen. Das Vorhandensein einer Endotheldysfunktion korreliert mit kardiovaskulären Ereignissen und hat auch prognostische Bedeutung. Die Reduktion des Blutdrucks per se ist nicht ausreichend, um die Endothelfunktion zu verbessern. Die verschiedenen Substanzklassen der Antihypertensiva beeinflussen die Gefäßfunktion in unterschiedlicher Art und Weis

Retention modeling and method development in hydrophilic interaction chromatography

In the present study, the possibility of retention modeling in the HILIC mode was investigated, testing several different literature relationships over a wide range of different analytical conditions (column chemistries and mobile phase pH) and using analytes possessing diverse physico-chemical properties. Furthermore, it was investigated how the retention prediction depends on the number of isocratic or gradient trial or initial scouting runs. The most promising set of scouting runs seems to be a combination of three isocratic runs (95, 90 and 70%ACN) and one gradient run (95 to 65%ACN in 10min), as the average prediction errors were lower than using six equally spaced isocratic runs and because it is common in Method development (MD) to perform at least one scouting gradient run in the screening step to find out the best column, temperature and pH conditions. Overall, the retention predictions were much less accurate in HILIC than what is usually experienced in RPLC. This has severe implications for MD, as it restricts the use of commercial software packages that require the simulation of the retention of every peak in the chromatogram. To overcome this problem, the recently proposed predictive elution window shifting and stretching (PEWS2) approach can be used. In this computer-assisted MD strategy, only an (approximate) prediction of the retention of the first and the last peak in the chromatogram is required to conduct a well-targeted trial-and-error search, with suggested search conditions uniformly covering the entire possible search and elution space. This strategy was used to optimize the separation of three representative pharmaceutical mixtures possessing diverse physico-chemical properties (pteridins, saccharides and cocktail of drugs/metabolites). All problems could be successfully handled in less than 2.5h of instrument time (including equilibration). © 2014 Elsevier B.V

Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis

BACKGROUND: The excess in cardiovascular risk in patients with rheumatoid arthritis provides a strong rationale for early therapeutical interventions. In view of the similarities between atherosclerosis and rheumatoid arthritis and the proven benefit of angiotensin-converting enzyme inhibitors in atherosclerotic vascular disease, it was the aim of the present study to delineate the impact of ramipril on endothelial function as well as on markers of inflammation and oxidative stress in patients with rheumatoid arthritis. METHODS AND RESULTS: Eleven patients with rheumatoid arthritis were included in this randomized, double-blind, crossover study to receive ramipril in an uptitration design (2.5 to 10 mg) for 8 weeks followed by placebo, or vice versa, on top of standard antiinflammatory therapy. Endothelial function assessed by flow-mediated dilation of the brachial artery, markers of inflammation and oxidative stress, and disease activity were investigated at baseline and after each treatment period. Endothelial function assessed by flow-mediated dilation increased from 2.85+/-1.49% to 4.00+/-1.81% (P=0.017) after 8 weeks of therapy with ramipril but did not change with placebo (from 2.85+/-1.49% to 2.84+/-2.47%; P=0.88). Although systolic blood pressure and heart rate remained unaltered, diastolic blood pressure decreased slightly from 78+/-7 to 74+/-6 mm Hg (P=0.03). Tumor necrosis factor-alpha showed a significant inverse correlation with flow-mediated dilation (r=-0.408, P=0.02), and CD40 significantly decreased after ramipril therapy (P=0.049). CONCLUSIONS: Angiotensin-converting enzyme inhibition with 10 mg/d ramipril for 8 weeks on top of current antiinflammatory treatment markedly improved endothelial function in patients with rheumatoid arthritis. This finding suggests that angiotensin-converting enzyme inhibition may provide a novel strategy to prevent cardiovascular events in these patients

Acetaminophen increases blood pressure in patients with coronary artery disease

BACKGROUND: Because traditional nonsteroidal antiinflammatory drugs are associated with increased risk for acute cardiovascular events, current guidelines recommend acetaminophen as the first-line analgesic of choice on the assumption of its greater cardiovascular safety. Data from randomized clinical trials prospectively addressing cardiovascular safety of acetaminophen, however, are still lacking, particularly in patients at increased cardiovascular risk. Hence, the aim of this study was to evaluate the safety of acetaminophen in patients with coronary artery disease. METHODS AND RESULTS: The 33 patients with coronary artery disease included in this randomized, double-blind, placebo-controlled, crossover study received acetaminophen (1 g TID) on top of standard cardiovascular therapy for 2 weeks. Ambulatory blood pressure, heart rate, endothelium-dependent and -independent vasodilatation, platelet function, endothelial progenitor cells, markers of the renin-angiotensin system, inflammation, and oxidative stress were determined at baseline and after each treatment period. Treatment with acetaminophen resulted in a significant increase in mean systolic (from 122.4±11.9 to 125.3±12.0 mm Hg P=0.02 versus placebo) and diastolic (from 73.2±6.9 to 75.4±7.9 mm Hg P=0.02 versus placebo) ambulatory blood pressures. On the other hand, heart rate, endothelial function, early endothelial progenitor cells, and platelet function did not change. CONCLUSIONS: This study demonstrates for the first time that acetaminophen induces a significant increase in ambulatory blood pressure in patients with coronary artery disease. Thus, the use of acetaminophen should be evaluated as rigorously as traditional nonsteroidal antiinflammatory drugs and cyclooxygenase-2 inhibitors, particularly in patients at increased cardiovascular risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00534651

Possibilities and Limitations of Computer-Assisted Method Development in HILIC: A Case Study

peer reviewedIn the present study, we investigated the possibilities and limitations of computer-assisted method development (CAMD) for the HILIC separation optimization of a mixture of 13 isomeric hydroxy- and aminobenzoic acids on a ZIC-HILIC column. The isocratically obtained Neue and Kuss retention parameters enabled the accurate gradient retention modeling for peaks eluting well within the gradient (mean error of 2.7 %). The prediction errors for peaks eluting at the end of the gradient could be reduced from 8.8 to 6.1 % by implementing the isocratic regime after the gradient into the expression for the gradient retention factor. The prediction of the corresponding peak widths improved significantly for certain compounds and gradient profiles using individual gradient N values for each compound compared to employing a single N value for all compounds and gradient profiles. Two gradient optimization strategies (constructing the Rs map based on individual retention modeling and predictive elution stretching and shifting, PEWS2) resulted in a reasonable separation of the challenging mixture of 13 isomeric hydroxy- and aminobenzoic acids on the ZIC-HILIC column. Overall, the optimization was limited by the steep decrease in N (dropping to the isocratic N value) and corresponding increase in peak width when increasing the gradient time. The discrimination factors d0 were used to assess the resolution between peaks varying widely in height. The best separation was found to be obtained via the PEWS2 approach. Both the individual retention modeling and PEWS2 strategies corresponded to a total instrument time less than 12 h (including equilibration). Finally, it was found that the salt concentration had a significant effect on both the retention and the peak shape of the compounds, resulting in a small “solution domain” at 10 mM. Coupled columns with higher efficiencies are suggested to improve the resolution and robustness of the separation. © 2016 Springer-Verlag Berlin Heidelber