URO-Telegramm

Ohne Zusammenfassung     

Do we need to consider inflammatory markers when we treat atherosclerotic disease?

This review considers the value of monitoring inflammatory markers as a guide to selecting appropriate drugs in patients at high risk of cardiovascular disease (CVD). Clinical and experimental studies investigated inflammation in patients with acute coronary syndromes (ACS), stable coronary artery disease (CAD) and diabetes mellitus (DM) or metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD) or systemic autoimmune diseases (SAD). Evidence suggests that in these high risk groups inflammation plays a role in the extent and severity of atherosclerosis. Simple inflammatory markers (e.g. C-reactive protein and fibrinogen) can be monitored cost effectively and may influence the selection of drugs that can normalize both traditional CVD risk factors and inflammation. However, this concept requires proof in appropriately designed trials that include clinically relevant end points.     

Tumor necrosis factor-alpha downregulates protein S secretion in human microvascular and umbilical vein endothelial cells but not in the HepG- 2 hepatoma cell line

Protein S deficiency, which is associated with thrombosis, can either be inherited or acquired. Recently, we reported that a decrease in free protein S was observed in 19 of 25 persons with HIV/AIDS. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been reported to be elevated in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients and has been shown to induce a procoagulant state on the surface of endothelial cells. We report here that recombinant TNF-alpha (rTNF-alpha) downregulated protein S synthesis in the SV-40T transfected human microvascular endothelial cell line (HMEC-1) model system by approximately 70% and in primary human umbilical vein and dermal microvascular endothelial cell cultures by approximately 50%. Using the HMEC-1 model, Northern blot analysis showed a decrease in protein S RNA at 24 hours that was corroborated by Western blot analysis and enzyme- linked immunosorbent assay (ELISA) quantification. Evidence supporting the specificity of the TNF-alpha effect included the following: (1) TNF- alpha down-regulation of protein S was completely blocked by TNF neutralizing antibody; (2) the effect was transient, and protein S was restored to near normal levels after TNF was removed from cell cultures; (3) an antibody directed to the TNF RI (55-kD receptor) was shown to mimic the action of TNF-alpha on HMEC-1 cells; and (4) other proinflammatory cytokines, interleukin (IL)-1, IL-6, and TGF-beta, had no effect on protein S secretion. However, TNF-alpha showed no regulatory control over protein S synthesis in the human hepatocellular carcinoma cell line HepG-2. We suggest that TNF-alpha downregulation of protein S may be a mechanism for localized procoagulant activity and thrombosis recently reported in some AIDS patients with associated protein S deficiency.     

Association of drinking pattern and alcohol beverage type with the prevalence of metabolic syndrome, diabetes, coronary heart disease, stroke, and peripheral arterial disease in a Mediterranean cohort

The purpose of this study was to investigate the relationship between alcohol consumption and the prevalence of the metabolic syndrome (MetS), type 2 diabetes mellitus (DM), coronary heart disease (CHD), stroke, peripheral arterial disease (PAD), and overall cardiovascular disease (CVD) in a Mediterranean cohort. It consisted of a cross-sectional analysis of a representative sample of Greek adults (n = 4,153) classified as never, occasional, mild, moderate, or heavy drinkers. Cases with overt CHD, stroke, or PAD were recorded. In our population, 17% were never, 23% occasional, 27% mild, 24% moderate, and 9% heavy drinkers. Moderate alcohol consumption was associated with a lower trend for the prevalence of the MetS (P = .0001), DM (P < .0001), CHD (P = .0002), PAD (P = .005), and overall CVD (P = .001) but not stroke compared with no alcohol use. Heavy drinking was associated with an increase in the prevalence of all of these disease states. Wine consumption was associated with a slightly better effect than beer or spirits consumption on the prevalence of total CVD, and beer consumption was associated with a better effect than spirits consumption. Alcohol intake was positively related with body weight, high-density lipoprotein cholesterol levels, and hypertension. Moderate alcohol consumption is associated with a lower prevalence of the MetS, DM, PAD, CHD, and overall CVD but not stroke compared with no alcohol use in a Mediterranean population. Heavy drinking was associated with an increase in the prevalence of all of these disease states. Advice on alcohol consumption should probably mainly aim at reducing heavy drinking.     

Atenolol: differences in mode of action compared with other antihypertensives. An opportunity to identify features that influence outcome?

The beneficial effect of antihypertensive treatment on the risk of major vascular events is well established. Several trials comparing older and newer drugs in the treatment of primary hypertension suggested that it is the blood pressure achieved, rather than choice of the drug that determines most of the primary outcomes. Beta-blockers have been widely used to treat hypertension and are still recommended as first-line drugs in guidelines. However, recent meta-analyses of trials (either placebo-controlled or using drug comparisons) involving atenolol (a popular beta-blocker), have cast doubt on the suitability of atenolol as a first-line antihypertensive drug. We consider the mechanisms which might be responsible for the inferiority of atenolol in preventing vascular morbidity and mortality in patients with primary hypertension. This knowledge may help design drugs that are not only more effective in achieving blood pressure targets but that also markedly decrease vascular events.     

Pheochromocytoma: an update on genetics and management

Pheochromocytomas (PHEOs) are rare neoplasms that produce catecholamines and usually arise from the adrenal medulla and are considered to be an adrenal paraganglioma (PGL). Closely related tumors of extraadrenal sympathetic and parasympathetic paraganglia are classified as extraadrenal PGLs. Most PHEOs are sporadic, but a significant percentage (approximately 25%) may be found in patients with germline mutations of genes predisposing to the development of von Hippel-Lindau disease, neurofibromatosis 1, multiple endocrine neoplasia type 1 (MEN1) and 2 (MEN2), and the PGL/PHEOs syndrome, based on the described mutations of the genes for succinate dehydrogenase subunit D (SDHD), B (SDHB), and C (SDHC). As one out of four PHEOs turns out to be a hereditary clinical entity, screening for genetic alterations is important, as it provides useful information for a rational diagnostic approach and management. This review discusses the genetics, the pathophysiology of hypertension, the clinical picture, the biochemical and imaging diagnosis, and the preferred therapeutic approach for PGLs/PHEOs. Furthermore, it emphasizes the need for genetic testing in cases with apparently sporadic PHEOs.