Dialysis solution containing hyaluronan: Effect on peritoneal permeability and inflammation in rats

Dialysis solution containing hyaluronan: Effect on peritoneal permeability and inflammation in rats.BackgroundHyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks.MethodsWistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86%; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment.ResultsAfter four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46% lower for albumin, P < 0.001; 33% lower for total protein, P < 0.001). The total drained volume after a four hour dwell was 29% higher in the HA group compared with the control (P < 0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 ± 6.7 vs. 22.8 ± 9.5%, P < 0.01) and lower levels of the cytokines, tumor necrosis factor-α (11.2 ± 14.7 vs. 42.3 ± 35.3 pg/mL, P < 0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 ± 86.5 vs. 402.4 ± 258.3 pg/mL, P < 0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48%, P < 0.01) than tissue from control animals.ConclusionsThe addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis

Thrombin inhibitory activity of some polyphenolic compounds

Thrombin, also known as an active plasma coagulation factor II, belongs to the family of serine proteases and plays a crucial role in blood coagulation process. The process of thrombin generation is the central event of the hemostatic process and regulates blood coagulant activity. For this reason, thrombin inhibition is key to successful novel antithrombotic pharmacotherapy. The aim of our present study was to examine the effects of the well-known polyphenolic compounds on the activity of thrombin, by characterization of its interaction with selected polyphenols using different biochemical methods and biosensor BIAcore analyses. Only six compounds, cyanidin, quercetin, silybin, cyanin, (+)-catechin and (−)-epicatechin, of all examined in this study polyphenols caused the inhibition of thrombin amidolytic activity. But only three of the six compounds (cyanidin, quercetin and silybin) changed thrombin proteolytic activity. BIAcore analyses demonstrated that cyanidin and quercetin caused a strong response in the interaction with immobilized thrombin, while cyanin and (−)-epicatechin induced a low response. Lineweaver–Burk curves show that used polyphenol aglycones act as competitive thrombin inhibitors. Our results suggest that polyphenolic compounds might be potential structural bases and source to find and project nature-based, safe, orally bioavailable direct thrombin inhibitors.This work was supported by Grant 545/485 and Grant 506/810 from the University of Lodz

Rare variants in BNC2 are implicated in autosomal-dominant congenital lower urinary-tract obstruction

Congenital lower urinary-tract obstruction (LUTO) is caused by anatomical blockage of the bladder outflow tract or by functional impairment of urinary voiding. About three out of 10,000 pregnancies are affected. Although several monogenic causes of functional obstruction have been defined, it is unknown whether congenital LUTO caused by anatomical blockage has a monogenic cause. Exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853(∗)]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage

Profiling and imaging of forensic evidence – a pan-European forensic round robin study part 1: document forgery

The forensic scenario, on which the round robin study was based, simulated a suspected intentional manipulation of a real estate rental agreement consisting of a total of three pages. The aims of this study were to (i) establish the amount and reliability of information extractable from a single type of evidence and to (ii) provide suggestions on the most suitable combination of compatible techniques for a multi-modal imaging approach to forgery detection. To address these aims, seventeen laboratories from sixteen countries were invited to answer the following tasks questions: (i) which printing technique was used? (ii) were the three pages printed with the same printer? (iii) were the three pages made from the same paper? (iv) were the three pages originally stapled? (v) were the headings and signatures written with the same ink? and (vi) were headings and signatures of the same age on all pages? The methods used were classified into the following categories: Optical spectroscopy, including multispectral imaging, smartphone mapping, UV-luminescence and LIBS; Infrared spectroscopy, including Raman and FTIR (micro-)spectroscopy; X-ray spectroscopy, including SEM-EDX, PIXE and XPS; Mass spectrometry, including ICPMS, SIMS, MALDI and LDIMS; Electrostatic imaging, as well as non-imaging methods, such as non-multimodal visual inspection, (micro-)spectroscopy, physical testing and thin layer chromatography. The performance of the techniques was evaluated as the proportion of discriminated sample pairs to all possible sample pairs. For the undiscriminated sample pairs, a distinction was made between undecidability and false positive claims. It was found that none of the methods used were able to solve all tasks completely and/or correctly and that certain methods were a priori judged unsuitable by the laboratories for some tasks. Correct results were generally achieved for the discrimination of printer toners, whereas incorrect results in the discrimination of inks. For the discrimination of paper, solid state analytical methods proved to be superior to mass spectrometric methods. None of the participating laboratories deemed addressing ink age feasible. It was concluded that correct forensic statements can only be achieved by the complementary application of different methods and that the classical approach of round robin studies to send standardised subsamples to the participants is not feasible for a true multimodal approach if the techniques are not available at one location

Ramipril and Risk of Hyperkalemia in Chronic Hemodialysis Patients

Angiotensin converting enzyme (ACE) inhibitors provide well known cardiorenal-protective benefits added to antihypertensive effects in chronic renal disease. These agents are underused in management of patients receiving hemodialysis (HD) because of common concern of hyperkalemia. However, few studies have investigated effect of renin angiotensin aldosterone system (RAAS) blockade on serum potassium in hemodialysis patients. We assessed the safety of ramipril in patients on maintenance HD. We enrolled 28 adult end stage renal disease (ESRD) patients treated by maintenance HD and prescribed them ramipril in doses of 1.25 to 5 mg per day. They underwent serum potassium concentration measurements before ramipril introduction and in 1 to 3 months afterwards. No significant increase in kalemia was found. Results of our study encourage the use of ACE inhibitors in chronically hemodialyzed patients, but close potassium monitoring is mandatory

Static optimization electrical drive with induction motor for limited torque control

Przeprowadzono optymalizację statyczną wektorowego układu sterowania częstotliwościowego silnikiem indukcyjnym klatkowym. Celem optymalizacji jest określenie wartości modułu strumienia skojarzonego z wirnikiem, zapewniającego maksymalną graniczną wartość momentu elektromagnetycznego silnika. Wyznaczono wartość modułu strumienia skojarzonego z wirnikiem w przypadku ograniczenia realnej wartości strumienia głównego silnika. Określono właściwości dynamiczne sterowania momentem elektromagnetycznym w przypadku stabilizacji na "optymalnym" poziomie wartości strumienia skojarzonego z wirnikiem. Do przeprowadzenia optymalizacji wykorzystano obwodowy model silnika o nieliniowych parametrach.In the paper optimal value of rotor flux, which ensures the maximum value of electromagnetic torque of the motor, was calculated. The permissible rate of electromagnetic moment change for the case when follow-up stator current regulation systems operating in the sliding motion are employed was determined on the basis of the above analysis. An analysis of the drive system with a 5.5 kW motor working with the maximum value of the torque was carried out. The variability of motor parameters with respect to the function of electromagnetic states was accounted for the motor model

Determination of basic energy parameters of a drive system containing an induction motor operating under extreme dynamic overload conditions

Przeprowadzono analizę parametrów energetycznych układu napędowego prądu przemiennego z silnikiem indukcyjnym klatkowym pracującym w trybie ekstremalnych przeciążeń momentem elektromagnetycznym. Silnik zasilany jest z zespołu przekształtników AC-DC-AC składającego się z wejściowego aktywnego prostownika z modulacją szerokości impulsów, obwodu prądu stałego i wyjściowego falownika zasilającego silnik indukcyjny. Tranzystorowe przekształtniki wejściowy i wyjściowy wykonane są w postaci trójpoziomowego układu falownika napięcia z diodami poziomującymi połączonymi z punktem neutralnym (NPC). Wyznaczono podstawowe straty statyczne i dynamiczne w falowniku trójpoziomowym i silniku indukcyjnym pracujących w trybie ekstremalnych przeciążeń dynamicznych.There has been made in the paper the analysis of energy parameters of an AC drive system containing an induction squirrel-cage motor operating under extreme conditions of overload with an electromagnetic moment. The motor has been supplied from a set of the AC-DC-AC converters consisting of an input active rectifier with a PDM (pulse-width modulation), a DC circuit and an output inverter to supply the induction motor. The input and output transistor converters have been made in the form of a three-level voltage converter with clamping diodes connected to a neutral point (NPC). There have been determined the basic static and dynamic losses in the three-level converter and the induction motor which operates under extreme dynamic overload conditions

Analysis of influence of AC drive system on a network in case of asymmetry of a supply circuit

Przeprowadzono analizę działania układu napędowego prądu przemiennego składającego się z silnika indukcyjnego klatkowego zasilanego z falownika napięcia z modulacją szerokości impulsów - MSI i zasilanego z sieci poprzez sześciopulsowy prostownik diodowy. Celem pracy jest wyznaczenie i analiza wejściowych prądów przekształtnika pobieranych z sieci zasilającej w przypadku niesymetrii napięć i parametrów sieci zasilającej. Opracowano model zastępczy układu "sieć - prostownik - falownik - silnik indukcyjny" dla ustalonego stanu pracy. Przeprowadzono modelowanie matematyczne i wyznaczono prądy sieci zasilającej dla układu napędowego z silnikiem o mocy 2,2 kW dla różnych wartości niesymetrii napięcia zasilającego.The analyses of operation of an AC drive system including an induction squirrel-cage motor supplied from a voltage inverter with pulse-width modulation (PDM) as well as from a network by means of a six-pulse diode rectifier, have been made. The work aims at determination and analysis of the input currents of a converter consumed from a power network in case of asymmetry of voltages and parameters of this network. An equivalent model of a system: "network - rectifier - inverter - induction motor" has been developed for a steady state of operation. A mathematical modelling has been made and the currents of the drive system including a motor of 2.2 kW for various values of asymmetry of supply voltage have been determined