Preventive strategies in endothelin-induced renal failure

Preventive strategies in endothelin-induced renal failure. The endothelial vasoconstrictor endothelin (ET) can induce acute renal failure when fibrinolysis and vasodilatory prostanoids (PGs) are inhibited. This study compares therapeutic agents preventing ET-induced acute renal failure in anesthetized female pigs. We investigated the effect of four ET boli (1.5 μg/kg, i.v.) after pretreatment with indomethacin (2mg/kg) and ε-aminocaproicacid (100 + 50mg/kg) alone (controls, group 1) or during additional nifedipine (10 μg/kg/h; group 2), hirudin (0.5mg/kg; group 3), or enalapril (2 × 0.15mg; group 4) on coagulation, PGs, and renal function. The ET-induced blood pressure increase was lower in groups 2 to 4 (lowest in group 3, P < 0.05). PG synthesis was blocked in all groups. The initial hypercoagulability (controls) resulted in disseminated intravascular coagulation that was prevented by hirudin and was attenuated in groups 2 and 4. At the end of the experiment, creatinine clearance was significantly (P < 0.05) decreased. The recovery of renal function two hours after the last ET bolus was most pronounced in the hirudin group. All therapeutic drugs attenuated ET-induced impairment of renal function. Hirudin seems to be the most potent protective drug. Prevention of further ET release evoked by ET-mediated secretion of thrombin might explain this. These results suggest three important pathways for ET's hemodynamic and renal effects

Effects of endothelin on hemodynamics, prostaglandins, blood coagulation and renal function

Effects of endothelin on hemodynamics, prostaglandins, blood coagulation and renal function. The interaction of the endogenous vasoconstrictors endothelin (ET), angiotensin II (Ang II) and catecholamines with the kallikrein-kinin-, prostaglandin and renin-aldosterone systems in the pathogenesis of acute renal failure (ARF) is still to be defined. In 18 anesthesized pigs the influence of i.v. bolus applications of ET (2 µg/kg), Ang II (10 µg/kg) and norepinephrine (NE; 20 µg/kg) on hemodynamics, plasmatic coagulation and fibrinolysis system, prostaglandins and renal function was studied. ET induced a biphasic change in blood pressure, starting with an initial short-lasting reduction followed by a long-lasting elevation of systolic and diastolic blood pressure. Endothelin bolus resulted in a significant increase of 6-keto-PGF1α, PGE2 and TXB2 plasma levels (P < 0.05 against preinjection values), whereas prostaglandins remained unchanged in the Ang II and NE groups. There was a distinct correlation between the plasma ET and 6-keto-PGF1α levels (r = 0.82). In contrast to Ang II or NE, ET induced a shortening of the activated partial thromboplastin time (aPTT) and increase of antithrombin III levels (ATIII), fibrin monomers (FM), prekallikrein (PKK) and factor VIII activity at the beginning. Finally a pronounced decrease of ATIII, FM and PKK occurred, indicating a consumptive coagulopathy. At the end of the experiment, elevated plasma renin activity and pCO2, significantly decreased creatinine clearance, blood pH, pO2, base excess, HCO3-, oxygen saturation (P < 0.01), a distinct glomerular proteinuria, and a final anuria were observated. These results reveal that ET activates the plasmatic coagulation system and induces an ARF accompanied by impairment of pulmonary function. Its coagulation activating and renal vasoconstrictive effects may be important pathophysiological factors, especially when the counteractive release of vasodilatator and antiaggregatory prostacyclin or NO is impaired

Anaphylactoid reactions during hemodialysis in sheep are ACE inhibitor dose-dependent and mediated by bradykinin

Anaphylactoid reactions during hemodialysis in sheep are ACE inhibitor dose-dependent and mediated by bradykinin. Anaphylactoid reactions (AR) have been attributed to the generation of bradykinin (BK) when AN69 membranes are used together with angiotensin converting enzyme (ACE) inhibitors during hemodialysis. However, conclusive evidence for the involvement of the BK as the mediator of these AR is still lacking. This study examined the degree of contact activation in an animal model caused by three PAN membranes—AN69, PAN DX, and SPAN—and the effects of different doses of the ACE inhibitor enalapril (ENA) and the BK B2-receptor antagonist icatibant on AR during hemodialysis. Six sheep were dialyzed for one hour with or without ENA pre-treatment using the different membranes in random order. Severe AR were observed only during hemodialysis with AN69 dialyzers together with ENA pre-treatment; the severity of AR increased with the ENA dose. Mild hypotension was noted during hemodialysis with AN69 without ACE inhibition and with PAN DX and 20 mg ENA. Compared to pre-dialysis values, maximum generation of BK after blood passage through the dialyzer was found at five minutes: 73-fold (AN69 without ENA), 161-fold (AN69 with 10 mg ENA), 97-fold (AN69 with 20 mg ENA), 108-fold (AN69 with 30 mg ENA), 154-fold (AN69 with 30 mg ENA and 0.1 mg/kg icatibant), 18-fold (PAN DX without ENA), and 42-fold (PAN DX with 20 mg ENA). Elevated BK levels in arterial blood were detected during hemodialysis with AN69 membranes even without ACE inhibition (2.5-fold); pre-treatment with 20 mg ENA further increased arterial BK concentrations (4-fold). Furthermore, a marked decline of prekallikrein and high molecular weight kininogen concentrations was noted for both AN69 and PAN DX membranes. Anaphylactoid reactions during hemodialysis were completely prevented by icatibant even after pre-treatment with ENA and in the presence of high BK concentrations. Concentrations of prekallikrein, high molecular weight kininogen, and BK remained unchanged and no AR were observed during hemodialysis with SPAN and pre-treatment with 20 mg ENA. Our findings confirm that AR during hemodialysis with the negatively charged AN69 membrane are mediated by BK, since they can be prevented by the BK B2-receptor antagonist icatibant

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Interventional Decentralized Telemonitoring: Bridging the Gap Between Patient's Device and Physician's Needs in Well Selected Indications

Telemedicine comprises different concepts aiming to close a spatial distance between practitioner, medical staff and patient. It's functionality can include mere data transmission but extend as well to triggering alarms or enable consultation and therapy suggestions. A special form of telemedicinal application is interventional decentralized telemonitoring. Here practitioner-patient communication is characterized by telemedicinial data collection driven therapy-control and -optimization. To identify feasible indications for the employment of telemonitoring a detailed definition of communicated parameters, alarm rules and algorithms of intervention are required as well as a benefit-cost analysis. The quality of the telemedical application is determined by the medical quality of the resulting actions

Merkmale und Entstehungsgründe des Innovationsimperativs

Schulz-Schaeffer I, Egbert S. Merkmale und Entstehungsgründe des Innovationsimperativs. In: Windeler A, Schulz-Schaeffer I, Seibt D, eds. Innovationsgesellschaft. Befunde und Ausblick. Wiesbaden: Springer VS; In Press

Reintroduction and stock enhancement of European weatherfish (

A stocking program for the endangered European weatherfish (Misgurnus fossilis L.) was conducted in the German federal states of Rhineland-Palatinate and Hesse, southwest Germany. An initial monitoring enabled to identify local broodstock and to assess habitats regarding their ecological suitability for reintroduction. In a second step, broodstock were caught for artificial propagation and cultured fry were released in previously selected river sectors. Furthermore, reintroduction sectors were biannually monitored to assess stocking success. Within the study period (2014–2016), a total number of approximately 83,500 juveniles were stocked in three river sectors for reintroduction and approximately 85,000 juveniles were stocked in four other river sectors to strengthen existing populations. During the post-release monitoring, 45 individuals were recaptured in two sectors. The documented short-term reintroduction success (i.e. survival of released individuals) indicates appropriateness of the selected stocking strategy. Furthermore, the provided course of action might be transferred to further states or countries and thereby contribute to weatherfish conservation at larger scales

Reintroduction and stock enhancement of European weatherfish (Misgurnus fossilis L.) in Rhineland-Palatinate and Hesse, Germany

A stocking program for the endangered European weatherfish (Misgurnus fossilis L.) was conducted in the German federal states of Rhineland-Palatinate and Hesse, southwest Germany. An initial monitoring enabled to identify local broodstock and to assess habitats regarding their ecological suitability for reintroduction. In a second step, broodstock were caught for artificial propagation and cultured fry were released in previously selected river sectors. Furthermore, reintroduction sectors were biannually monitored to assess stocking success. Within the study period (2014–2016), a total number of approximately 83,500 juveniles were stocked in three river sectors for reintroduction and approximately 85,000 juveniles were stocked in four other river sectors to strengthen existing populations. During the post-release monitoring, 45 individuals were recaptured in two sectors. The documented short-term reintroduction success (i.e. survival of released individuals) indicates appropriateness of the selected stocking strategy. Furthermore, the provided course of action might be transferred to further states or countries and thereby contribute to weatherfish conservation at larger scales

Body weight telemetry is useful to reduce interdialytic weight gain in patients with end-stage renal failure on hemodialysis

Abstract Lacking compliance with liquid intake restrictions is one of the major problems in patients on hemodialysis and causes an increased mortality. In 120 patients on hemodialysis with an average interdialytic weight gain (IWG) exceeding 1.5 kg on at least 2 days during the 4 weeks preceding the intervention, the effect of telemetric body weight measurement (TBWM) on IWG, ultrafiltration rate, and blood pressure was evaluated over a period of 3 months. Patients of the telemetric group (TG) were supplied with automatic scales, which transferred the weight via telemetry on a daily basis. In the case of IWG of more than 0.75 kg/24 h, a telephonic contact was made as required, and in the case of an IWG of more than 1.5 kg, telephonic contacting was obligatory along with the advice of a liquid intake restriction to 0.5 L/day until the next dialysis. The patients of the control group (CG) received standard treatment without telemetric monitoring. We examined specific data of the second interdialytic interval (IDI2) and the average within 1 week. The average difference of IWG between TG and CG was not significant before the start of the study but 0.2 kg (p=0.027) (IDI2)/0.27kg (p=0.001) (WP) at the end of the study, respectively. The average difference in the ultrafiltration rate within 1 week was 19.0 mL/h (p=0.282) (IDI2)/8.2 mL/h (p=0.409) before the start of the study but 28.4 mL/h (p=0.122) (IDI2)/30.9 mL/h (p=0.004) at the end of the study, respectively. Thus, TBWM is a feasible method for optimizing the IWG and reducing the ultrafiltration rate