Hypertonie und Bewegung

Physical exercise is of paramount therapeutic importance in nonpharmacological interventions of arterial hypertension. The extent and the effects of exercise on blood pressure lowering are analyzed according to the actual literature. Suitable and nonsuitable activities are considered. Dynamic isotonic endurance training is more effective than static isometric exercise. A rather low or moderate extent of endurance training lowers the systolic and diastolic blood pressure by approximately 5-11 mmHg and 3-8 mmHg, respectively. This effect of exercise can be achieved besides the favorable effects on other cardiovascular risk factors. Intensity of exercise should be monitored by the heart rate. The mean intensity should not exceed 70% of the maximal heart rate. An initial ergometry might be suitable for the planning of training recommendations.     

Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation

Single nucleotide polymorphisms (SNPs) of the NOD2/CARD15 gene resulting in a diminished nuclear factor-kappaB (NF-kappaB) response to bacterial cell wall products have been associated with an increased incidence of Crohn disease. To assess a possible contribution of NOD2/CARD15 mutations to graft-versus-host disease (GvHD) and complications following allogeneic stem cell transplantation, we retrospectively typed DNA from donor/recipient pairs in 169 consecutive patients receiving transplants from related or unrelated donors. Mutated alleles were observed in 21% of patients and in 14% of donors. Cumulative incidence of 1-year, transplant-related mortality rose from 20% in donor/recipient pairs without mutated SNPs to 49% in pairs with recipient mutations (P =.03) and 59% in pairs with donor mutations (P <.005), and was highest in 12 pairs with mutated alleles in both donor and recipients (83%; P <.001). Similar associations were observed for severe overall and severe gastrointestinal GvHD. The impact of NOD2/CARD15 mutations was more prominent for HLA-identical sibling transplantations but was also observed in unrelated donor transplantation. Mutations proved to be independent risk factors for transplant-related mortality. Our findings indicate a major role of monocyte/macrophage dysfunction in the pathophysiology of GvHD and strongly suggest a future risk assessment or even donor selection through NOD2/CARD15 typing.     

Efficacy of epoetin alfa administered every 2 weeks to maintain hemoglobin and quality of life in anemic HIV-infected patients

Anemia, a common hematological abnormality in HIV, contributes to decreased quality of life (QOL). This study assessed once-every-2-week epoetin alfa on maintaining QOL and hemoglobin (Hb) in anemic HIV-infected patients in a 24-week, open-label, multicenter study. HIV-infected patients (Hb < or =12 g/dl) received epoetin alfa 40,000 units subcutaneously once weekly, until reaching Hb > or =13 g/dl. Patients then entered a maintenance phase (MP), in which epoetin alfa was administered every other week or at longer intervals. The trial objectives were to determine if QOL, as measured by the Medical Outcomes Study-HIV (MOS-HIV) general health perceptions (GHP) domain and Hb, was maintained. Safety was also assessed. A total of 292 patients were enrolled (72% on HAART). Mean baseline laboratory values were Hb = 10.8 g/dl, CD4(+) count = 280 cells/microl, and HIV RNA = 51,867 copies/ml. In all, 81% of patients reached Hb > or =13 g/dl and 92% reached Hb > or =12 g/dl. QOL was maintained from the beginning (GHP = 44.2 points) to the end of MP (GHP = 43.4 points) with every other week or longer dosing. Mean Hb at the beginning of MP was 13.4 +/- 0.5 g/dl and was 12.8 +/- 1.4 g/dl at study end. Epoetin alfa was well tolerated; adverse events were consistent with those reported in previous studies of epoetin alfa in HIV-infected patients. Although the clinical approach tested in this study is not consistent with current prescribing recommendations, the results confirm the efficacy of prolonged dosing intervals (every 2-4 weeks) in maintaining optimal Hb levels and QOL in anemic HIV-infected patients.     

Ablation of atrial fibrillation

Atrial fibrillation (AF) is a common arrhythmia, affecting an estimated 2 million people in the United States and its prevalence increases with age, reaching 10% in those > or = 80 years. AF confers a four- to fivefold increased risk of stroke compared to the general population and has been associated with a doubling of all-cause mortality. During the past decade, limited success rates of drug treatment stimulated an exploration of interventional treatment options for AF. As our knowledge on initiating triggers and perpetuating substrate of AF expanded, different potentially curative catheter ablation techniques have been developed. In this article we review the current patient selection criteria, methods, and the results of the catheter ablation of atrial fibrillation.     

Effect of segmental Le Fort I osteotomy on maxillary tooth type-related pulpal blood-flow characteristics

Laser Doppler flowmetry (LDF) is a noninvasive method to assess pulpal blood-flow (PBF). Osteotomies may have segment-related losses of pulpal sensibility. OBJECTIVES: To determine the effect of segmental Le Fort I osteotomy on tooth-type related PBF values. MATERIALS AND METHODS: In 12 volunteers, maxillary incisors, canines, and premolars were investigated bilaterally by LDF to assess local PBF values before and after surgery. Perfusion units (PU) were in 3 sessions, on the day before surgery and at 4 and 56 days after osteotomy. RESULTS: Measurements before surgery were significantly higher than at 4 days after surgery for the canine (P <.01) and for the overall PBF values (P <.01). At 4 days assessment, PBF values of tooth types adjacent to vertical osteotomy cuts showed a significant decrease for the lateral incisors (P <.05), canines, and first premolars (P <.05), with no significant differences between the preoperative and postoperative values for tooth types not adjacent to vertical osteotomy cuts (P <.05). CONCLUSIONS: Segmental Le Fort I osteotomy induced a short-term and long-term decrease in maxillary PBF values of tooth types adjacent to vertical osteotomy cuts.     

Effect on blood pressure of lumiracoxib versus ibuprofen in patients with osteoarthritis and controlled hypertension: a randomized trial

OBJECTIVES: Nonsteroidal anti-inflammatory drugs vary in their impact on blood pressure and the effect of lumiracoxib 100 mg once daily has not been studied previously. To examine whether lumiracoxib 100 mg once daily would result in lower 24-h mean systolic ambulatory blood pressure than ibuprofen 600 mg three times daily in osteoarthritis patients with controlled hypertension, a 4-week, randomized, double-blind, parallel-group study was conducted in 79 centres in nine countries. METHODS: Hypertensive osteoarthritis patients of 50 years at least whose office blood pressure was less than 140/90 mmHg on stable antihypertensive treatment were randomized to lumiracoxib (n = 394) 100 mg once daily or ibuprofen 600 mg three times daily (n = 393) and 24-h ambulatory blood pressure monitoring was performed at baseline and end of study. The primary outcome measure was a comparison of the change in 24-h mean systolic ambulatory blood pressure from baseline to week 4. Secondary analyses included other blood pressure-related endpoints and efficacy (pain) measurements. RESULTS: Compared with baseline, the 24-h mean systolic ambulatory blood pressure (least square mean) decreased in lumiracoxib-treated patients (-2.7 mmHg) and increased in ibuprofen-treated patients (+2.2 mmHg) at 4 weeks, estimated difference -5.0 mmHg (95% confidence interval -6.1 to -3.8) in favour of lumiracoxib. The 24-h mean diastolic ambulatory blood pressure changes were -1.5 mmHg (lumiracoxib), +0.5 mmHg (ibuprofen), difference -2.0 mmHg (95% confidence interval -2.7 to -1.3). Efficacy results were comparable. CONCLUSIONS: Treatment with lumiracoxib 100 mg once daily resulted in clinically significant lower blood pressure compared with ibuprofen 600 mg three times daily in osteoarthritis patients with well controlled hypertension.     

Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel by NADPH oxidase 4

Physiological sensing of O(2) tension (partial O(2) pressure, pO(2)) plays an important role in some mammalian cellular systems, but striated muscle generally is not considered to be among them. Here we describe a molecular mechanism in skeletal muscle that acutely couples changes in pO(2) to altered calcium release through the ryanodine receptor-Ca(2+)-release channel (RyR1). Reactive oxygen species are generated in proportion to pO(2) by NADPH oxidase 4 (Nox4) in the sarcoplasmic reticulum, and the consequent oxidation of a small set of RyR1 cysteine thiols results in increased RyR1 activity and Ca(2+) release in isolated sarcoplasmic reticulum and in cultured myofibers and enhanced contractility of intact muscle. Thus, Nox4 is an O(2) sensor in skeletal muscle, and O(2)-coupled hydrogen peroxide production by Nox4 governs the redox state of regulatory RyR1 thiols and thereby governs muscle performance. These findings reveal a molecular mechanism for O(2)-based signaling by an NADPH oxidase and demonstrate a physiological role for oxidative modification of RyR1.     

Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation

Considerable evidence indicates that the general blockade of protein synthesis prevents both the initial consolidation and the postretrieval reconsolidation of long-term memories. These findings come largely from studies of drugs that block ribosomal function, so as to globally interfere with both cap-dependent and -independent forms of translation. Here we show that intra-amygdala microinfusions of 4EGI-1, a small molecule inhibitor of cap-dependent translation that selectively disrupts the interaction between eukaryotic initiation factors (eIF) 4E and 4G, attenuates fear memory consolidation but not reconsolidation. Using a combination of behavioral and biochemical techniques, we provide both in vitro and in vivo evidence that the eIF4E-eIF4G complex is more stringently required for plasticity induced by initial learning than for that triggered by reactivation of an existing memory.     

Osteopontin is an activator of human adipose tissue macrophages and directly affects adipocyte function

Osteopontin (OPN) is highly up-regulated in adipose tissue in human and murine obesity and has been recently shown to be functionally involved in the pathogenesis of obesity-induced adipose tissue inflammation and associated insulin resistance in mice. OPN is a protein with multiple functions and acts as a chemokine and an inflammatory cytokine through a variety of different receptors (CD44, integrins). It is expressed in many cell types including adipose tissue macrophages (ATM). However, the target cells of OPN action in obese adipose tissue are still elusive. Here, we investigated expression of OPN receptors and the impact of OPN on ATM, adipocytes, and other cells of human adipose tissue. We found broad expression of OPN receptors in different adipose tissue cell types including adipocytes. OPN stimulated inflammatory signaling pathways and secretion of cytokines in model macrophages as well as isolated human ATM. Moreover, OPN impaired differentiation and insulin sensitivity of primary adipocytes as determined by peroxisomal proliferator-activated receptor-γ and adiponectin gene expression and insulin-stimulated glucose uptake. Furthermore, OPN induced inflammatory signaling in human adipocytes. In conclusion, OPN activates ATM and interferes with adipocyte function. Thus these data underline the potential of OPN as a therapeutic target for obesity-induced complications.