The NAD(P)H oxidase inhibitor apocynin improves endothelial NO/superoxide balance and lowers effectively blood pressure in spontaneously hypertensive rats: comparison to calcium channel blockade

The vascular NAD(P)H oxidase contributes to endothelial dysfunction and high blood pressure in the spontaneously hypertensive rat by enhancing superoxide production. We investigated the effects of apocynin, a NAD(P)H oxidase inhibitor, on blood pressure and vascular radical and nitric oxide formation in SHR and compared its effects to the calcium channel blocker nifedipine. Apocynin (over four weeks) lowered systolic blood pressure significantly and as effectively as nifedipine. Both apocynin and nifedipine significantly reduced superoxide production. In parallel, vascular nitric oxide production and ecNOS activity was significantly increased by apocynin treatment. Therefore, apocynin may be an effective antihypertensive drug in essential hypertension.     

Role of gender and estrogen receptors in the rat aorta endothelium-dependent relaxation to red wine polyphenols

Regular intake of moderate amounts of beverages rich in polyphenols such as red wine is associated with a protective effect on the vascular system, in part, by increasing the endothelial formation of nitric oxide (NO), a major vasoprotective factor. Since estrogens are potent inducers of NO formation and polyphenols have been shown to have phytoestrogen properties, we determined whether estrogen receptors mediate the stimulatory effect of red wine polyphenols (RWPs) on the endothelial formation of NO using isolated rat aortic rings and cultured endothelial cells.RWPs caused endothelium-dependent relaxations, which were more pronounced in the aorta of female than male rats. Increased relaxations were also observed to acetylcholine but not to sodium nitroprusside. Relaxations to RWPs were abolished by nitro l-arginine and MnTMPyP, markedly reduced by polyethyleneglycol-catalase and wortmannin, and not affected by the estrogen antagonist ICI 182,780 in aortic rings from males and females. eNOS expression was higher in aortic sections of female than male rats. RWPs caused the phosphorylation of Akt and eNOS in endothelial cells, which was unaffected by ICI 182,780.Thus, RWPs cause redox-sensitive PI3-kinase/Akt-dependent NO-mediated relaxations, which are more pronounced in the aorta of female than male rats; an effect most likely due to the increased expression level of eNOS rather than activation of estrogen receptors.     

Effect of an invasive strategy on in-hospital outcome in elderly patients with non-ST-elevation myocardial infarction

Aims: We sought to investigate the impact of an invasive treatmentin elderly patients presenting with non-ST elevation myocardialinfarction (NSTEMI) in clinical practice. Methods and results: We analysed data of consecutive elderly patients (75 years)with NSTEMI who were prospectively enrolled in the German AcuteCoronary Syndromes registry between July 2000 and November 2002.Overall 1936 patients were divided into two groups: 1005 (51.9%)underwent coronary angiography and/or revascularization, 931(48.1%) received conservative treatment. In the invasive group,percutaneous coronary intervention was performed in 37.5% within48 h and in 17.6% after 48 h, whereas 9.8% underwent coronaryartery bypass grafting within the hospital stay. In-hospitaldeath (12.5 vs. 6.0%, P < 0.0001) and death/myocardial infarction(17.3 vs. 9.6%, P < 0.0001) occurred significantly less oftenin patients with invasive strategy. After adjustment of theconfounding factors in the propensity score analysis the invasivestrategy remained superior for mortality (OR 0.55, 95% CI 0.35–0.86)and death and non-fatal myocardial infarction (OR 0.51, 95%CI 0.35–0.75) and 1 year mortality (OR 0.56, 95% CI 0.38–0.81).Major bleeding complications tended to be more frequent in theinvasive group (8.8 vs. 5.8%, P = 0.07). Conclusion: In clinical practice, in elderly patients with NSTEMI, an invasivestrategy is associated with an improved in-hospital and 1 yearoutcome but a trend towards more bleeding complications.     

Expression of the Endothelin-axis in the different histologic subtypes of renal cell carcinoma: a tissue microarray analysis

Endothelin-1 and its receptors ETAR and ETBR, commonly referred to as the Endothelin-axis, are emerging to play a role in cancer. The Endothelin-axis has been shown to be involved in proliferation, angiogenesis and metastasis in various human tumours. To assess the role of the Endothelin-axis in renal cell carcinoma, we analysed its expression in archival tumour tissue of 183 patients. Representative tumour blocks were selected for constructing a tissue microarray. Paraffin sections were assessed immunohistochemically using monoclonal and polyclonal antibodies for Endothelin-1, ETAR and ETBR. Staining intensities were analysed semiquantitatively and the results were correlated with various histopathologic factors. Overexpression of Endothelin-1, ETAR and ETBR was identified in 12.8%, 84.1% and 93.3% of cases, respectively. No association with pathological tumour stage and histologic grading was found. Papillary renal cell carcinomas expressed highly significantly more Endothelin-1 than clear cell renal cell carcinomas (34.5% vs. 6.7%, p<0.001), while there was no difference between ETAR- and ETBR-expression in these histologic subtypes. However, ETAR tended to be overexpressed in the subgroup of G3-tumours (p=0.044). Studies are underway assessing the role of the Endothelin-axis and its potential use as a molecular target in renal cell carcinoma.     

A study on the ability of quaternary ammonium groups attached to a polyurethane foam wound dressing to inhibit bacterial attachment and biofilm formation

Bacterial infection of acute and chronic wounds impedes wound healing significantly. Part of this impediment is the ability of bacterial pathogens to grow in wound dressings. In this study, we examined the effectiveness of a polyurethane (PU) foam wound dressings coated with poly diallyl‐dimethylammonium chloride (pDADMAC‐PU) to inhibit the growth and biofilm development by three main wound pathogens, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, within the wound dressing. pDADMAC‐PU inhibited the growth of all three pathogens. Time‐kill curves were conducted both with and without serum to determine the killing kinetic of pDADMAC‐PU. pDADMAC‐PU killed S. aureus, A. baumannii, and P. aeruginosa. The effect of pDADMAC‐PU on biofilm development was analyzed quantitatively and qualitatively. Quantitative analysis, colony‐forming unit assay, revealed that pDADMAC‐PU dressing produced more than eight log reduction in biofilm formation by each pathogen. Visualization of the biofilms by either confocal laser scanning microscopy or scanning electron microscopy confirmed these findings. In addition, it was found that the pDADMAC‐PU‐treated foam totally inhibited migration of bacteria through the foam for all three bacterial strains. These results suggest that pDADMAC‐PU is an effective wound dressing that inhibits the growth of wound pathogens both within the wound and in the wound dressing.     

Methylene blue administration in severe systemic inflammatory response syndrome (SIRS) after thoracic surgery.

A 66-year-old male patient developed significant pleural effusion on the right side six years after coronary bypass grafting and mitral valve replacement. After pleurocentesis, hemo-pneumothorax developed and finally resulted in complete atelectasis of the right lung. Three weeks later, the patient was transferred to our department, and underwent a right lateral thoracotomy. The hematoma was removed and a complete decortication was performed. Four hours postoperatively the patient developed severe SIRS with beginning multiorgan failure. Even extremely high doses of norepinephrine could not raise the systemic vascular resistance. Single intravenous administration of methylene blue lead to significant and permanent improvement of the hemodynamic status.