Dual endothelin-converting enzyme/neutral endopeptidase blockade in rats with D-galactosamine-induced liver failure

Secondary activation of the endothelin system is thought to be involved in toxic liver injury. This study tested the hypothesis that dual endothelin-converting enzyme / neutral endopeptidase blockade might be able to attenuate acute toxic liver injury

Renal phenotype of Et-1 transgenic mice is modulated by androgens

<p>Abstract</p> <p>Introduction</p> <p>Activation of the endothelin (ET) system promotes inflammation and fibrosis in various tissues including the kidney. Male ET-1 transgenic mice are characterized by chronic kidney inflammation and renal scarring. We hypothesized that this renal phenotype might be modulated by androgens. Thus the aim of our study was to elucidate the impact of gonadectomy in ET-1 transgenic mice on kidney function and morphology.</p> <p>Methods</p> <p>Male ET-1 transgenic mice at the age of 10 weeks were randomly allocated to the following groups: normal ET transgenic mice (ET; n = 17) and ET transgenic mice that underwent castration (ET+cas; n = 12). Study duration was 9 months. Creatinine clearance and protein excretion was monitored. At study end animals were sacrificed and kidneys were harvested for histology/immunhistochemistry.</p> <p>Results</p> <p>Castration significantly ameliorated glomerulosclerosis in ET-1 transgenic mice (ET glomerulosclerosis-score: 3.0 ± 0.17 vs ET+cas: 2.4 ± 0.17; p < 0.05) as well as renal perivascular fibrosis (ET fibrosis-score: 3.0 ± 0.14 vs ET+cas: 2.2 ± 0.14; p < 0.05). However, interstitial fibrosis and media/lumenratio of renal arteries remained unaffected by castration. Regarding inflammation, castration significantly reduced the number of CD4-positive cells in renal tissue of ET-1 transgenic mice (ET CD4-positive cells/10000 cells: 355 ± 72 vs ET+cas: 147 ± 28; p < 0.05). Renal tissue contents of CD8 positive cells as well as of macrophages were not affected by castration. Regarding kidney function castration significantly reduced proteinuria in ET-1 transgenic mice whereas creatinine clearance did not differ between study groups.</p> <p>Conclusion</p> <p>Our study demonstrates that the renal histopathological phenotype in male ET-1 transgenic mice with regard to glomerulosclerosis, proteinuria, perivascular fibrosis and immune cell immigration is ameliorated by castration. We thus conclude that the effects of ET-1 overexpression on renal tissue injury are modulated by androgens.</p

Resolution and enhancement in nanoantenna-based fluorescence microscopy

Single gold nanoparticles can act as nanoantennas for enhancing the fluorescence of emitters in their near-fields. Here we present experimental and theoretical studies of scanning antenna-based fluorescence microscopy as a function of the diameter of the gold nanoparticle. We examine the interplay between fluorescence enhancement and spatial resolution and discuss the requirements for deciphering single molecules in a dense sample. Resolutions better than 20 nm and fluorescence enhancement up to 30 times are demonstrated experimentally. By accounting for the tip shaft and the sample interface in finite-difference time-domain calculations, we explain why the measured fluorescence enhancements are higher in the presence of an interface than the values predicted for a homogeneous environment.Comment: 10 pages, 3 figures. accepted for publication in Nano Letter

Einfluss von N-Düngermenge und Nitrifikationshemmung auf die direkten N2O-Emissionen eines gemüsebaulich genutzten Ackerbodens

Lachgas (N2O) ist ein klimarelevantes Spurengas, es trägt zum Ozonabbau in der Stratosphäre sowie zu 8% am anthropogenen Treibhauseffekt bei und stammt zum Großteil aus landwirtschaftlich genutzten Böden. Ziel dieser Studie war die Ermittlung belastbarer annueller Daten zur N2O-Freisetzung aus gemüsebaulich genutzten Ackerböden Mitteleuropas, d.h. aus einer Gegend mit ausgeprägten Frost-Tau-Zyklen. Ferner sollte das Potential zur Minderung der direkten N2O-Emissionen untersucht werden. Hierzu wurde sowohl eine reduzierte Düngung als auch der Zusatz eines Nitrifikationshemmstoffs getestet. Die Beiträge von N-Dünger und Ernterückständen an den untersuchten Emissionen wurden mittels 15N-markiertem Dünger ermittelt. Die Emissionsfaktoren der verschiedenen Düngerstufen lagen zwischen 0,9 und 1,7. Durch Düngerreduktion bzw. Zusatz von Nitrifikationshemmstoff wurde bei konstantem Ertrag die N2O-Freisetzung um 24 bzw 43% reduziert. Die Blumenkohlernterückstände verursachten 21% der Jahresemissionen und sorgten für hohe Winteremissionen, während Tau-Peaks kaum ausgeprägt waren

Efficient coupling of photons to a single molecule and the observation of its resonance fluorescence

Single dye molecules at cryogenic temperatures display many spectroscopic phenomena known from free atoms and are thus promising candidates for fundamental quantum optical studies. However, the existing techniques for the detection of single molecules have either sacrificed the information on the coherence of the excited state or have been inefficient. Here we show that these problems can be addressed by focusing the excitation light near to the absorption cross section of a molecule. Our detection scheme allows us to explore resonance fluorescence over 9 orders of magnitude of excitation intensity and to separate its coherent and incoherent parts. In the strong excitation regime, we demonstrate the first observation of the Mollow triplet from a single solid-state emitter. Under weak excitation we report the detection of a single molecule with an incident power as faint as 150 attoWatt, paving the way for studying nonlinear effects with only a few photons.Comment: 6 figure

Renal Effects of the Novel Selective Adenosine A1 Receptor Blocker SLV329 in Experimental Liver Cirrhosis in Rats

Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A1 receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A1 receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (−36.5%, p<0.05), especially in those receiving furosemide (−41.9%, p<0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A1 receptor antagonists are clinically beneficial at different stages of liver cirrhosis

Pathophysiology of the endothelin system - lessons from genetically manipulated animal models

Shortly after discovery of ET-1 in 1988, the entire endothelin system was characterized. The endothelin system consists of the three peptides ET-1, ET-2 and ET-3, their G-protein-coupled receptors endothelin receptor A and B (ETRA and ETRB) and the two endothelin-converting enzymes (ECE-1 and ECE-2). Genetically modified animal models are an important tool in biomedical research. Here we describe the key findings obtained from genetically modified animal models either over-expressing compounds of the ET system or lacking these compounds (knockout mice). Results from the different transgenic and knockout models disclose that the ET system plays a major role in embryonic development. Two ET system-dependent neural crest-driven developmental pathways become obvious: one of them being an ET-1/ETAR axis, responsible for cardio-renal function and development as well as cranial development; the other seems to be an ET-3/ETBR mediated signalling pathway. Mutations within this axis are associated with disruptions in epidermal melanocytes and enteric neurons. These findings led to the discovery of similar findings in humans with Hirschsprung disease. In adult life the ET system is most important in the cardiovascular system and plays a role in fibrotic remodelling of the heart, lung and kidney as well as in the regulation of water and salt excretion

A 20-year prospective study of mortality and causes of death among hospitalized opioid addicts in Oslo

<p>Abstract</p> <p>Background</p> <p>To study mortality rate and causes of death among all hospitalized opioid addicts treated for self-poisoning or admitted for voluntary detoxification in Oslo between 1980 and 1981, and to compare their mortality to that of the general population.</p> <p>Methods</p> <p>A prospective cohort study was conducted on 185 opioid addicts from all medical departments in Oslo who were treated for either self-poisoning (<it>n </it>= 93, 1980), voluntary detoxification (<it>n </it>= 75, 1980/1981) or both (<it>n </it>= 17). Their median age was 24 years; with a range from 16 to 41, and 53% were males. All deaths that had occurred by the end of 2000 were identified from the Central Population Register. Causes of death were obtained from Statistics Norway. Standardized mortality ratios (SMRs) were computed for mortality, in general, and in particular, for different causes of death.</p> <p>Results</p> <p>During a period of 20 years, 70 opioid addicts died (37.8%), with a standardized mortality ratio (SMR) equal to 23.6 (95% CI, 18.7–29.9). The SMR remained high during the whole period, ranging from 32.4 in the first five-year period, to 13.4 in the last five-year period. There were no significant differences in SMR between self-poisonings and those admitted for voluntarily detoxification. The registered causes of death were accidents (11.4%), suicide (7.1%), cancer (4.3%), cardiovascular disease (2.9%), other violent deaths (2.9%), other diseases (71.4%). Among the 50 deaths classified as other diseases, the category "drug dependence" was listed in the vast majority of cases (37 deaths, 52.9% of the total). SMRs increased significantly for all causes of death, with the other diseases group having the highest SMR; 65.8 (95% CI, 49.9–86.9). The SMR was 5.4 (95% CI, 1.3–21.5) for cardiovascular diseases, and 4.3 (95% CI, 1.4–13.5) for cancer. The SMR was 13.2 (95% CI, 6.6–26.4) for accidents, 10.7 (95% CI, 4.5–25.8) for suicides, and 28.6 (95% CI, 7.1–114.4) for other violent deaths.</p> <p>Conclusion</p> <p>The risk of death among opioid addicts was significantly higher for all causes of death compared with the general population, implying a poor prognosis over a 20-year period for this young patient group.</p