Fluorescence-supported lymphography and extended pelvic lymph node dissection in robot-assisted radical prostatectomy: a prospective, randomized trial.

Purpose: To demonstrate the benefits of fluorescence-supported extended pelvic lymph node dissection (ePLND) compared to regular ePLND in robot-assisted radical prostatectomy.

Methods: 120 patients with intermediate- or high-risk prostate cancer were prospectively randomized (1:1): in the intervention group, indocyanine green (ICG) was injected transrectally into the prostate before docking of the robot. In both groups, ePLND was performed including additional dissection of fluorescent lymph nodes (LN) in the ICG group.

Postoperative patient comfort in suprapubic drainage versus transurethral catheterization following robot-assisted radical prostatectomy: a prospective randomized clinical trial.

Purpose: To evaluate the impact of the type of urinary diversion (suprapubic vs. transurethral catheterization) on patients' postoperative pain after radical prostatectomy, development of bacteriuria and long-term functional results.

Methods: A randomized, prospective clinical trial was performed including 160 patients who underwent robot-assisted radical prostatectomy after randomization into two groups: intraoperatively, a transurethral catheter (control group) or an additional suprapubic tube (with removal of the transurethral catheter in the morning of postoperative day 1; intervention group) was placed.

Birthweight and fetal glycosylated hemoglobin at birth in newborns carrying the GLUT1 XbaI gene polymorphism.

Background: Low birthweight is an independent risk factor of glucose intolerance and type 2 diabetes in later life. Genetically determined insulin resistance and subsequently impaired glucose uptake might explain both reduced fetal growth and elevated blood glucose. The glucose transporter 1 (GLUT1) plays an important role for fetal glucose uptake as well as for maternal-fetal glucose transfer, and it has been associated with insulin resistance in adults.

Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.

Objectives: The effects of AT1 receptor blocker, telmisartan, and the ACE inhibitor, ramipril, were tested head-to head and in combination on stroke prevention in hypertensive rats and on potential neuroprotection in acute cerebral ischemia in normotensive rats.

Methods: Prevention study: Stroke-prone spontaneously hypertensive rats (SHR-SP) were subjected to high salt and randomly assigned to 4 groups: (1) untreated (NaCl, n = 24), (2) telmisartan (T; n = 27), (3) ramipril (R; n = 27) and (4) telmisartan + ramipril (T+R; n = 26). Drug doses were selected to keep blood pressure (BP) at 150 mmHg in all groups.

Activation of the bumetanide-sensitive Na+,K+,2Cl- cotransporter (NKCC2) is facilitated by Tamm-Horsfall protein in a chloride-sensitive manner.

Active transport of NaCl across thick ascending limb (TAL) epithelium is accomplished by Na(+),K(+),2Cl(-) cotransporter (NKCC2). The activity of NKCC2 is determined by vasopressin (AVP) or intracellular chloride concentration and includes its amino-terminal phosphorylation. Co-expressed Tamm-Horsfall protein (THP) has been proposed to interact with NKCC2.

Nitric oxide-independent stimulation of soluble guanylate cyclase reduces organ damage in experimental low-renin and high-renin models.

Objectives: The nitric oxide-soluble guanylate cyclase (sGC)-cGMP signal transduction pathway is impaired in different cardiovascular diseases, including pulmonary hypertension, heart failure and arterial hypertension. Riociguat is a novel stimulator of soluble guanylate cyclase (sGC). However, little is known about the effects of sGC stimulators in experimental models of hypertension.

Does endothelin B receptor deficiency ameliorate the induction of peritoneal fibrosis in experimental peritoneal dialysis?

Background: Peritoneal fibrosis is a serious complication of peritoneal dialysis (PD); however, the mechanisms are poorly understood. The endothelin system exhibits potent pro-fibrotic properties and is known to be stimulated in peritoneal fibrosis. Thus, our study aimed at elucidating the impact of the endothelin B (ETB) receptor on peritoneal membrane thickening by means of an ETB-deficient rat model (ETB(-)(/)(-)) in experimental PD.

Cardio-renal effects of the A1 adenosine receptor antagonist SLV320 in patients with heart failure.

Background: Blocking the tubuloglomerular feedback mechanism with adenosine A1 receptor antagonists seems to improve diuresis and sodium excretion without compromising the glomerular filtration rate in patients with heart failure. However, the direct cardiac effects of this compound class have not been investigated to date.

Methods And Results: In total, 111 patients (109 men and 2 women) received a 1-hour infusion of 5, 10, and 15 mg SLV320, an adenosine A1 receptor antagonist, placebo, or 40 mg furosemide.

Fetal sex determines the impact of maternal PROGINS progesterone receptor polymorphism on maternal physiology during pregnancy.

Background: Recent evidence from very rare human diseases suggests that variation in the fetal genome can modify maternal physiology during pregnancy. Here, we tested the hypothesis that fetal sex as a major genetic variant of the fetal genome may affect maternal physiology during pregnancy in genetically susceptible pregnant women.

Methods: We analyzed the impact of fetal sex on maternal physiology during pregnancy in relationship with the maternal PROGINS progesterone receptor gene polymorphism.

The renin-angiotensin system and the third mechanism of renal blood flow autoregulation.

Autoregulation of renal blood flow comprises three mechanisms: the myogenic response (MR), the tubuloglomerular feedback (TGF), and a third mechanism (3M). The nature of 3M is unknown; it may be related to hypotensive resetting of autoregulation that probably relies on pressure-dependent stimulation of the renin-angiotensin system (RAS). Thus we used a normotensive angiotensin II clamp in anesthetized rats and studied autoregulation 1) by slow ramp-shaped reductions in renal perfusion pressure (RPP) followed by ramp-shaped RPP restorations and 2) by means of the step response technique: after 30 s of either total or partial suprarenal aortic occlusion, a step increase in RPP was made and the response of renal vascular conductance analyzed to assess the mechanisms' strength and initial direction (vasodilation or constriction).

Models of cardiovascular disease: measurement of antihypertensive activity in the conscious rat (SHR, DOCA-salt, and Goldblatt hypertension models).

The protocols described in this unit are used to assess the effects of new chemical entities on hypertension in conscious rats. In the spontaneously hypertensive rat (SHR) model, the results obtained with the reference compounds clonidine, prazosin, propranolol, and captopril are provided for illustration. All compounds demonstrate antihypertensive activity, with captopril and prazosin being the least and the most active, respectively.

Gender-dependent impact of risk factors for cardiovascular and non-cardiovascular mortality in end-stage renal disease patients on haemodialysis.

We investigated whether mortality risk factors are gender dependent in haemodialysis patients. Patients (n = 230; 118 women, 112 men) on haemodialysis were followed for 52 months to assess the incidence of death due to cardiovascular or non-cardiovascular causes. Survival was compared by Cox regression analysis using age, diabetes, pre-existing coronary disease, troponin T and C-reactive protein as covariates.

The beta-lactam antibiotic, ceftriaxone, dramatically improves survival, increases glutamate uptake and induces neurotrophins in stroke.

Objective: Ceftriaxone has been reported to reduce neuronal damage in amyotrophic lateral sclerosis and in an in-vitro model of neuronal ischaemia through increased expression and activity of the glutamate transporter, GLT1. We tested the effects of ceftriaxone on mortality, neurological outcome, and infarct size in experimental stroke in rats and looked for underlying mechanisms.

Methods: Male normotensive Wistar rats received ceftriaxone (200 mg/kg intraperitoneal) as a single injection 90 min after middle cerebral artery occlusion (90 min with reperfusion).

Urinary protein profiling with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry in ETB receptor-deficient rats.

The pathways leading to salt-sensitive hypertension and renal damage in rescued ETB receptor-deficient (ETBRd) rats are still unknown. The objective of the study was therefore to identify modifications of urinary peptide and protein expression in ETBRd rats (n = 9) and wild-type controls (n = 6) using SDS - polyacrylamide gel electrophoresis (SDS-PAGE) and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology. Glomerular filtration rate, glomerulosclerosis, and tubulointerstitial fibrosis did not differ between the groups.

Pulmonary fibrosis in L-NAME-treated mice is dependent on an activated endothelin system.

Activation of the endothelin (ET) system promotes vasoconstriction, inflammation, and fibrosis in various tissues, including the lung. Therefore, ET-1 transgenic mice overexpressing ET-1 develop pulmonary fibrosis in a slow, age-dependent manner. In vivo, NO is the most important counterregulatory mediator of the ET system and decreases ET-1 promoter activity.

Lack of iNOS impairs endothelial function in endothelin-1 transgenic mice.

Background: Endothelin-1 (ET-1) is one of the most potent biologic vasoconstrictors. Nevertheless, transgenic mice overexpressing ET-1 exhibit normal blood pressure. We hypothesized that in states of ET-1 overproduction, the lack of counterregulatory mediators such as nitric oxide (NO), produced by the inducible NO synthase (iNOS), may critically impair endothelial function and may result in blood pressure elevation.

Viscosity of contrast media perturbs renal hemodynamics.

Contrast-induced nephropathy is a common cause of acute renal failure, and the mechanisms underlying this injury are not completely understood. We sought to determine how physicochemical properties of contrast media may contribute to kidney damage in rats. We administered contrast media of equivalent iodine concentrations but differing physiocochemical properties: the high-osmolality iopromide was compared to the high-viscosity iodixanol.

Impact of maternal angiotensinogen M235T polymorphism and angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure, protein excretion and fetal outcome in pregnancy.

Objective: To test the hypothesis that genetically determined alterations of the renin-angiotensin system are associated with hypertensive disorders in pregnancy.

Methods: A genetic association study was conducted at the obstetrics department of the Charité university hospital, Berlin, Germany. A total of 1068 Caucasian women were consecutively included after delivery and genotyped for the angiotensinogen M235T polymorphism and the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism.

Cell-type specific interaction of endothelin and the nitric oxide system: pattern of prepro-ET-1 expression in kidneys of L-NAME treated prepro-ET-1 promoter-lacZ-transgenic mice.

Nitric oxide (NO) and endothelin-1 (ET-1) are known to play a major role in renal and vascular pathophysiology and exhibit a close interaction with ET-1, stimulating NO production; NO in turn inhibits ET-1 expression. Our objectives were (1) to establish a novel transgenic mouse model facilitating ET-1 expression assessment in vivo, (2) to validate this model by assessing prepro-ET-1 promoter activity in mice embryos by means of our novel model and comparing expression sites to well-established data on ET-1 in fetal development and (3) to investigate renal ET-NO interaction by assessing prepro-ET-1 promoter activity in different structures of the renal cortex in the setting of blocked NO synthases via L-NAME administration. We established transgenic mice carrying a lacZ reporter gene under control of the human prepro-ET-1 gene promoter sequence (8 kb of 5' sequences).

Soluble CD154 is a unique predictor of nonfatal and fatal atherothrombotic events in patients who have end-stage renal disease and are on hemodialysis.

Cardiovascular mortality is remarkably high in patients who are on hemodialysis. Soluble CD154 (sCD154), a protein that belongs to the TNF receptor superfamily, has been implicated in the pathogenesis of atheromatous plaque destabilization and thrombotic events. The predictive value of sCD154 as a marker for clinical outcome in patients with ESRD was investigated.

Fetal and maternal peroxisome proliferator-activated receptor gamma2 Pro12Ala does not influence birth weight.

The association between the peroxisome proliferator-activated receptor (PPAR)gamma2 Pro12Ala polymorphism and insulin resistance is reported to depend on low birth weight. Low birth weight itself has been linked to type 2 diabetes and cardiovascular diseases in adulthood. We assessed whether the PPARgamma2 Pro12Ala polymorphism determines body size at birth and whether metabolic differences between the genotypes are already detectable in the newborn.

Low birth weight, a risk factor for cardiovascular diseases in later life, is already associated with elevated fetal glycosylated hemoglobin at birth.

Background: It remains unclear whether the association between low birth weight and insulin resistance in adulthood has its origin in utero or whether it develops later in life depending on predisposition and exogenous factors.

Methods And Results: Total glycosylated hemoglobin (TGH) was quantified at delivery in 1295 mother/child pairs serving as a surrogate of maternal and fetal glycemia. Multivariable regression analysis considering gestational age at delivery, the child's sex, maternal body mass index, and smoking during pregnancy revealed that an increase in TGH by 1% in the child was significantly associated with a mean birth weight reduction of 135 g (P<0.

NO-independent activation of soluble guanylate cyclase prevents disease progression in rats with 5/6 nephrectomy.

1. Chronic renal disease is associated with oxidative stress, reduced nitric oxide (NO) availability and soluble guanylate cyclase (sGC) dysfunction. Recently, we discovered BAY 58-2667, a compound activating heme-deficient or oxidized sGC in a NO-independent manner.

Impact of genetic variation of tumor necrosis factor-alpha on gestational hypertension.

Background: The mechanisms responsible for the pathogeneses of gestational hypertension and preeclampsia are unclear. Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory Th(1)-type cytokine. TNFA gene is located in the human leukocyte antigen (HLA) class III region of the major histocompatibility complex (MHC) on chromosome 6.

Impact of genes related to immune tolerance and inflammation (tumour necrosis factor-alpha, interleukin-6) on blood pressure, protein excretion and oedema in pregnancy.

Objective: To test the hypothesis that genetically determined alterations of maternal immune tolerance to a foetal semi-allograft are important for the pathogenesis of hypertensive disorders in pregnancy.

Design: A genetic association study was performed to analyse the impact of genetic polymorphisms known to be involved in immune tolerance on markers of pre-eclampsia.

Setting: The study was conducted at the Obstetrics Department of the Charité University Hospital, Berlin, Germany.