bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caspase-3 and -8 Activation and Cytokine Removal with a Novel Cellulose Triacetate Super-Permeable Membrane in an in Vitro Sepsis Model
Authors: Bordoni V. , Bolgan I. , Brendolan A. , Crepaldi C. , Gastaldon F. , D'Intini V. , Pilotto L. , Inguaggiato P. , Bonello M. , Galloni E. , Everard P. , Bellomo R. , Ronco C. 
Published: January 2018

Pro-apoptotic molecules are generated during sepsis which may be responsible for alteration of organ function in sepsis. Removal of systemic apoptotic activity may affect recovery from sepsis. Current high flux membranes might not be sufficiently permeable to eliminate pro-apoptotic factors. We evaluated the elimination of pro-apoptotic factors induced by LPS in human whole blood by a super-permeable cellulose triacetate membrane (SUREFLUX FH 150, Nipro, Osaka, Japan) in comparison to a standard high flux cellulose triacetate membrane (UT 700, Nipro, Osaka, Japan) and a polyethersulfone plasmafilter (Bellco, Mirandola Italy) in an in vitro blood circulation. We spiked human whole blood with lipopolysaccharide from Escherichia coli (Serotype 026–86, 10 mg/ml), incubated it for 3 hours to allow cytokine generation and recirculated it at 300 ml/min for 3 hours. The UF line was first returned to the blood module at 10 min. After this, the UF was drained from 10 to 60 min at a rate of 1000 ml/h. Zero balance was obtained by re-infusion of bicarbonate buffered hemofiltration fluid. Apoptosis was assessed on U937 monocytes (incubated with plasma or ultrafiltrate) by fluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V flow cytometry. Caspase-3 and Caspase-8 activity was assessed on the recirculated blood monocytes by spectrophotometric methods. IL-2, IL-10 and TNFα were determined by commercially available ELISAs. Sieving coefficients and clearances were determined for the different cytokines. Caspase-3 and Caspase-8 were activated by LPS and remained either stable or increased during in vitro circulation. Apoptosis activity of U937 cells, when incubated with the ultrafiltrate, increased in parallel with arterial plasma values (for Uf: UT700=23.1%; Sureflux FH150=42.5%). However, by 60 min the apoptotic activity recorded with the ultrafiltrate was reduced to the levels of arterial plasma (for Uf: UT700=19.8%; Sureflux FH150=11.2%). Sieving coefficients in the super-permeable membrane were significantly higher for all measured cytokines in comparison to the standard high flux membrane (e.g. TNFα 0.72 vs 0.03 p<0.001) and close to the values observed for the plasmafiltration membrane. Nevertheless protein losses measured by albumin leakage were much lower with the Sureflux filter in comparison to the plasmafilter. In conclusion, pro-apoptotic factors can be eliminated by dialytic membranes with the removal rate maximized by using super high flux dialysers which may represent a compromise between hemofiltration and plasmafiltration membranes.
Effect of Lipoprotein Apheresis on Oxidative Stress and Antioxidant Status in Familial Hypercholesterolemic Patients
Authors: Kurtoglu E. , Ugur A , Gonen M. Sait , Kısakol G. 
Published: January 2018

Extracorporeal low-density lipoprotein (LDL) apheresis is an established and highly effective therapy for the patients with familial hypercholesterolemia (FH) not adequately responding to diet and drug therapy alone. This study was designed to measure the effect of lipid apheresis on oxidant and antioxidant status in a patient with FH. The levels of plasma lipid peroxidation were determined as thiobarbituric acid-reactive substances. The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were established in one subject with FH before and after lipid apheresis. The pre- and post lipid apheresis procedures witness a significant decrease in oxidative stress (p<0.05) but the erythrocyte levels of CAT, SOD and GPx were unchanged.
Modelling of Cardiovascular System: Development of a Hybrid (Numerical-Physical) Model
Authors: Ferrari G. , Kozarski M. , De Lazzari C. , Górczyńska K. , Mimmo R. , Guaragno M. , Tosti G. , Darowski M. 
Published: January 2018

Physical models of the circulation are used for research, training and for testing of implantable active and passive circulatory prosthetic and assistance devices. However, in comparison with numerical models, they are rigid and expensive. To overcome these limitations, we have developed a model of the circulation based on the merging of a lumped parameter physical model into a numerical one (producing therefore a hybrid). The physical model is limited to the barest essentials and, in this application, developed to test the principle, it is a windkessel representing the systemic arterial tree. The lumped parameters numerical model was developed in LabVIEW™ environment and represents pulmonary and systemic circulation (except the systemic arterial tree). Based on the equivalence between hydraulic and electrical circuits, this prototype was developed connecting the numerical model to an electrical circuit - the physical model. This specific solution is valid mainly educationally but permits the development of software and the verification of preliminary results without using cumbersome hydraulic circuits. The interfaces between numerical and electrical circuits are set up by a voltage controlled current generator and a voltage controlled voltage generator. The behavior of the model is analyzed based on the ventricular pressure-volume loops and on the time course of arterial and ventricular pressures and flow in different circulatory conditions. The model can represent hemodynamic relationships in different ventricular and circulatory conditions.
Clinical Efficacy of Ozonated Autohemotherapy in Hemodialyzed Patients with Intermittent Claudication: An Oxygen-Controlled Study
Authors: Biedunkiewicz B. , Tylicki L. , Nieweglowski T. , Burakowski S. , Rutkowski B. 
Published: January 2018

Background Hemodialyzed patients are particularly exposed to the development of peripheral arterial occlusive disease. Ozonotherapy is used as a therapeutic tool in the treatment of this atherosclerotic complication, but there are still no properly designed studies to show the clinical effectiveness of this approach. The aim of this study was to evaluate the influence of ozonated autohemotherapy on walking ability and the subjective clinical experience of hemodialyzed patients with peripheral arterial disease. Methods Ten subjects with intermittent claudication (Fontain II stage) received the cycle of ozonated autohemotherapy with ozone concentration of 50 μg/ml and the cycle of oxygen autohemotherapy as a control in a cross-over, single-blind manner. Pain-free distance and maximal walking distance were measured using a standardized march test on a treadmill. The efficacy of therapy was assessed subjectively by patients on a five-degree scale. Results Significant prolongation of maximal waking distance after ozonated autohemotherapy was found, as compared to the baseline (by 30.5%) and to the oxygen control (by 22.7%) (p<0.01 and p<0.03). There was also significant increase in pain-free distance after ozonated autohemotherapy, as compared to the baseline (by 71.7%) and to the oxygen control (by 62.8%) (p<0.02 and p<0.03 respectively). In a subjective assessment (questionnaires) 90% of patients reported clinical improvement relative to the baseline after ozonated autohemotherapy as compared to 40% after the oxygen-control treatment (p<0.025). Conclusion We demonstrated that ozonated autohemotherapy might prolong walking ability and attenuate subjective clinical signs of ischemia in patients with peripheral arterial disease treated regularly with hemodialysis.
Adjustment of Dry Weight in Hemodialysis Patients using Intradialytic Continuous Multifrequency Bioimpedance of the Calf
Authors: Zhu F. , Kuhlmann M.K. , Sarkar S. , Kaitwatcharachai C. , Khilnani R. , Leonard E.F. , Greenwood R. , Levin N.W. 
Published: January 2018

Background Current concepts of dry weight (DW) prescription are largely based on clinical symptoms because of the difficulty in assessing extracellular fluid volume (ECV) during dialysis. Intradialytic changes in ECV can be recorded as changes in extracellular resistance [Re] by continuous regional calf multifrequency bioimpedance spectroscopy (BIS). We hypothesized that relative changes in calf Re (Re at time ‘0’ over Re at time ‘t’ [Re-0/Re-t]) will become very small when ECV is reduced towards normal and individual dry weight is reached. Method Intradialytic continuous calf BIS was recorded repeatedly in 15 hemodialysis (HD) patients. The first measurement was performed at the prevailing clinical dry weight (CDW). Next measurements were made after post-HD body weight was gradually decreased by 0.2–0.3 kg per treatment. This procedure was iterated over several subsequent treatments until a treatment was observed where changes in Re-0/Re-t were < 1%. The weight at the end of this treatment was defined as “achieved dry weight (ADW)”. Each Re-0/Re-t curve was fitted using a Matlab program (curve fitting toolbox) to obtain the exact weight at 20 min after beginning of the flattening of the Re-0/Re-t slope (‘dry’ weight estimated from BIS, DW-BIS). Results Both mean ADW (80.5 ± 34.1 kg) and mean DW-BIS (80.6 ± 34.1) were significantly lower than CDW (81.4 ± 32.0 kg, p < 0.001), but there was no difference between ADW and DW-BIS. However, the average weight reduction from CDW to ADW (0.80 ± 0.15 kg) was significantly higher than from CDW to DW-BIS (0.66 ± 0.14 kg, p < 0.001, paired t-test). When ADW was achieved, pre-dialysis systolic blood pressure (SBP) was lower than at CDW (139.3 ± 32.5 mmHg, vs. 129.4 ± 33 mmHg, p < 0.05), post-HD SBP did not differ. The incidence of clinical symptoms of underhydration was similar at CDW (15 %) and DW-BIS (15 %), but higher at ADW (46 %). Conclusion Intradialytic continuous calf BIS allows the assessment of changes in extracellular calf resistance as an indicator of changes in extracellular fluid volume. Recording of a continuous Re-0/Re-t slope during dialysis appears to be a promising new tool for the prediction of dry weight in hemodialysis patients.
Mass Transfers in a Fluidized Bed Bioreactor using Alginate Beads for a Future Bioartificial Liver
Authors: David B. , Doré E. , Jaffrin M.Y. , Legallais C. 
Published: January 2018

Fluidized bed bioreactor with alginate beads may be an alternative to hollow fiber cartridge to host hepatocytes for bioartificial liver purposes. After the bioreactor design and the characterization of fluid mechanics, the present study was aimed at analyzing bi-directional mass transfers of calibrated species between external fluid and empty beads. Static (batch) and dynamic (fluidized bed bioreactor) experimental conditions were analyzed. A simple modelling approach permitted the definition of mass transfer coefficients. The motion of beads within the bioreactor clearly enhanced mass transfer kinetics, but did not alter the amount exchanged. The shear enhanced diffusion coefficient for VitB12 was 20 times higher in the fluidized bed bioreactor than under batch conditions, proving the efficiency of such a device.
Reduced Systemic Heparin Dose with Phosphorylcholine Coated Closed Circuit in Coronary Operations
Authors: Ranucci M. , Isgrò G. , Soro G. , Canziani A. , Menicanti L. , Frigiola A. 
Published: January 2018

In this prospective cohort study we addressed the clinical impact of a reduced anticoagulation protocol on the hospital outcome of patients undergoing coronary revascularization with cardiopulmonary bypass. 364 consecutive low to moderate risk patients scheduled for elective isolated coronary operations were admitted to the study. 184 patients (Control Group) received conventional open circuits and full systemic anticoagulation (target activated clotting time 480 seconds); 180 patients (Intraoperative ECMO group) received closed, phosphorylcholine coated circuits and a reduced systemic heparin dose (target activated clotting time 320 seconds). Patients of the Intraoperative ECMO group had less requirement for allogeneic blood products (odds ratio 0.55, 95% confidence interval 0.34–0.92, p= 0.02), a significant containment of blood loss (374 ± 278 mL vs. 463 ± 321 mL in Control group, p= 0.005) a lower postoperative peak serum creatinine levels (1.19 ± 0.48 mg/dL vs. 1.41 ± 0.94 mg/dL in Control group, p= 0.048), and a significant lower rate of severe morbidity (odds ratio 0.27, 95% confidence interval 0.09–0.81, p= 0.02). A reduction of systemic anticoagulation is feasible with a non-heparin-bonded, closed biocompatible circuit, and results in a significant improvement of the outcome of low to moderate risk coronary patients.
Inhibition of the Effect of High Glucose on the Expression of Smad in Human Peritoneal Mesothelial Cells
Authors: Yao Q. , Qian J.Q. , Lin X.H. , Lindholm B. 
Published: January 2018

Objective As high glucose (HG) concentration in peritoneal dialysis (PD) solution is thought to contribute to peritoneal fibrosis, and angiotensin II receptor blockers (ARBs) may have a key role in preventing fibrosis as they may inhibit the TGF- ß1–Smad pathway, the aims of this in vitro study were to investigate 1) if HG affects the expression of Smad in human peritoneal mesothelial cells (HPMCs) and 2) if ARB (losartan) can inhibit this effect. Methods HPMCs, obtained from non-renal patients undergoing elective abdominal surgery, were stimulated by HG solutions with different concentrations (1.5%, 2.5%, 4.25%) of dextrose and mannitol, and by solutions containing combination with dextrose and losartan. The supernatant was assayed for TGF- ß1 by ELISA and cells were collected for the analysis of Smad family by RT-PCR and Western Blot. Results 1) HG up-regulated the expression of Smad2 on both gene and protein levels, especially in 2.5% and 4.25% dextrose groups (P&0.05), and also stimulated the expression of Smad4 in 4.25% dextrose group. However, the expression of Smad3 was not affected. 2) High osmolality as such (using mannitol) did not affect the TGF-ß1-Smad signaling pathway. 3) Losartan inhibited the expression of Smad2 on the gene level but not on the protein level. 4) HG up-regulated the level of TGF- ß1 with increasing dextrose concentration, while losartan partially inhibited this effect of HG on releasing of TGF-ß1. Conclusion A high glucose solution up-regulated the expression of Smad2 and Smad4, suggesting that the TGF- ß1-Smad pathway could be involved in the fibrosis of the peritoneum during PD. As losartan inhibited the expression of Smad2 on the gene level and reduced the concentration of TGF- ß1 in our study, the results of this in vitro study suggest that the use of angiotensin II receptor blockers might represent a possible way to prevent and treat peritoneal fibrosis in PD patients. However, further studies in vivo are needed to confirm this hypothesis.
Kidney Failure Associated with Liver Transplantation or Liver Failure: The Impact of Continuous Veno-Venous Hemofiltration
Authors: Naka T. , Wan L. , Bellomo R. , Wang B. ZONG , Jones R. , Berry R. , Angus P. , Gow P. 
Published: January 2018

Background and Aims The short-term outcome of critically ill patients with kidney failure combined with severe liver failure or orthotopic liver transplantation (OLTx) is poor. We sought to test the hypothesis that, with the exclusive use of continuous veno-venous hemofilration (CVVH) with minimal heparin-anticoagulation, the short and long-term outcomes of these patients would be improved. Patients Sixty-six consecutive patients with combined liver and kidney failure Setting Intensive Care Unit of tertiary hospital Design Retrospective interrogation of prospectively collected databases Intervention Treatment of all patients with continuous veno-venous hemofiltration (CVVH) by protocol with 2L/h of ultrafiltration rate and minimal use of circuit heparinization. Retrieval of specific information on demographic, clinical, therapeutic and outcome details. Measurements and Main Results From July 1995 to April 2004, 66 patients with combined liver and renal failure received continuous veno-venous hemofiltration (CVVH). Of these, 26 received liver transplantation and 40 did not. There were no significant differences in age, APACHE II score, bilirubin, ALT, INR or albumin on admission. The average duration of CVVH was 9.5 days for OLTx patients and 5 days for non-transplanted patients (p=0.013). Heparin anticoagulation was used in only 12% of OLTx patients and 20% of non-transplanted patients. ICU mortality was 15% in OLTx patients and 63% in non-transplanted patients (p<0.0005); hospital mortality was 23% compared to 70% (p<0.001). Mean survival time at follow up was 1,120 days compared to 358 days (p<0.0001). Conclusions ARF associated with OLTx has a much better outcome than ARF without OLTx. Furthermore, management based on a conservative anticoagulation policy and CVVH as the exclusive form of renal support was associated with the best ICU, hospital and long term survival reported so far.
Fulminant Hepatic Failure and the Potential Role of Liver Dialysis
Authors: Akdogan M. , Aladag M. , Rashwan S. , Shrago S. , Warner E. , Sebastian A. , Wright H. , Nour B. , Gurakar A. 
Published: January 2018

Fulminant hepatic failure (FHF) carries a high mortality. We aimed to review the prognostic factors and explore the potential role of Liver Dialysis (LD). Fifty-two patients were reviewed. The etiologies were acetaminophen toxicity (33%), viral hepatitis (18%), autoimmune (10%), idiosyncratic drug reactions (8%), others (6%) and undetermined (25%). Patients with acetaminophen had a significantly higher survival compared to the non-acetaminophen group (p=0.04). Patients with grade 3 encephalopathy had a mortality of 68%, among 5 patients with grade IV encephalopathy, 2 survived and both had had treatment with LD. Chi-square with Fisher's exact test was used for statistical analysis. Our study confirmed that the diagnosis of non-acetaminophen induced FHF and reduced initial serum factor V level are associated with fatal outcome. Timely OLT significantly improved the survival. The role of LD in hepatic regeneration or as a bridge to OLT needs to be further studied with prospective control trials.
Physical and Computer Modelling of Blood Flow in a Systemic-to-pulmonary Shunt
Authors: Małota Z. , Nawrat Z. , Kostka P. , Mizerski J. , Nowinski K. , Waniewski J. 
Published: January 2018

The aim of this work was the application of computer and physical in vitro simulation methods for estimating surgery procedure hemodynamics. The modified Blalock-Taussig (mB-T) palliative surgical procedure is performed to increase the pulmonary blood flow in children with congenital heart defects. Such a systemic-to-pulmonary shunt yields substantial modification in the blood flow within the large blood vessels. The objective of the present study was to investigate basic characteristics of the flow, flow pattern and pressure-flow efficiency, before and after opening of the mB-T graft. Methods The model was based on the vessel geometry obtained from the Visible Human Project and included the arch of aorta, the three arteries branching from the arch, the pulmonary trunck, and the left and right pulmonary arteries. The graft was added between the left subclavian artery and the left pulmonary artery. The glass model of the vessels was produced and investigated in a physical model of the cardiovascular system with an artificial ventricular device as the blood pump. Flow rate and hydrostatic pressure were measured at the inlet to and outlets from the glass model and in a few points within the system. Laser flow visualization was also performed. Computer simulations were done using the boundary conditions from the physical model. Results The opening of the mB-T graft changed flow distribution in all branches (including inflow). A complex flow pattern with large eddies and channelling of the flow in the vicinity of the graft and within it was observed in flow visualization and in computer simulations. Because of that complexity the local measurements of hydrostatic pressure at the vessel wall could not predict the average flow rate. The reversed flow in the graft was observed during the systole. Conclusions The complex flow pattern developed in the physical model of the mB-T graft. The channelling of the flow and the formation of large eddies may yield high shear stress and modify blood properties. The rigid wall model can describe only some flow characteristics observed in vivo. Computer simulation is a very fast and accurate method which permits earlier qualification of cardiac surgeons on how to change cardiac vascular blood flow after operations.
High Volume Hemofiltration (HVHF) in Sepsis: A Comprehensive Review of Rationale, Clinical Applicability, Potential Indications and Recommendations for Future Research
Authors: Honore P. M. , Joannes-Boyau O. 
Published: January 2018

HVHF can be still seen as a potent powerful immunomodulatory treatment in sepsis. Pleiotropical properties of HVHF give this treatment the possibility to affect not only SIRS but also cardiovascular compounds, clotting and post septic-insult immunoparalysis. By this multimodal approach, HVHF can alter the sepsis network through many targets. The crucial relationship between immunological changes, hemodynamics and survival must be found in future prospective randomised studies. Circulatory cytokines are no longer valuable players except for catecholamine-resistant septic shock. Definitions are of upmost value as ultrafiltrate volume has been correlated in terms of response and survival with the type of disease (sepsis or not) and severity (catecholamine-resistant shock or not). This latter condition can be seen as the best indication for HVHF and probably even more for very high volume hemofiltration (VHVHF). More studies are needed to clarify the role of HVHF in hyperdynamic septic shock (with or without acute renal failure), sepsis and SIRS. They can be seen as potential indications up to now. Possible interferences with activated protein C deserve more attention as both treatments can be given sequentially in the same septic patient or even concomitantly.
A Technique for the Measurement of Renal ATP in a Large Animal Model of Septic Shock
Authors: May C. , Wan L. , Williams J. , Wellard M.R. , Pell G. , Jackson G. , Bellomo R. 
Published: January 2018

Background The mechanisms responsible for acute renal failure in sepsis are not understood. Measurement of tissue ATP might help to understand this process but, in the large animal, it is hampered by major technical difficulties. Objective To develop a technique to monitor ATP in the kidney of a large mammal during the induction of septic shock and then circulatory arrest. Methods Implantation of a custom-made phosphorus coil around the left kidney. Induction of septic shock by intravenous E. coli administration. Acquisition of 31P magnetic resonance (MR) spectroscopic data at 3-tesla before and during septic shock over several hours. Induction of euthanasia and measurement of the same 31P signal immediately and thirty minutes after circulatory arrest. Results Clear reproducible 31P MR spectra were obtained before and after the induction of septic shock and euthanasia. They indicated limited changes in ATP during septic shock. An expected rapid and dramatic decrease in ATP occurred with euthanasia. Conclusions It is possible to sequentially monitor renal bioenergetics in a large mammal during septic shock using an implanted custom-made phosphorus coil and 3-tesla MR technology. This technique offers a novel approach to the investigation of septic renal failure.