bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of HES on the Filtration Properties of Capillary Membrane Plasmaseparation
Authors: Haltern C. , Unger J.K. , Dohmen B. , Gressner A.M. , Rossaint R.
Published: January 2018

Plasmaseparation is a treatment under discussion for critically ill patients, especially in sepsis and multiorgan failure. These patients receive a variety of different fluid substitutes, including hydroxyethylstarch (HES). HES is known to influence rheological properties, but nothing is known about the possible interactions between HES and the plamaseparation procedure. We used an in vitro plasmaseparation circuit with heparinized porcine blood. Before priming the system, 2 liters of blood were supplemented by adding 100 ml of either NaCl 0.9% or HES (n=6 in each group). We monitored the transmembrane (TMP) and the filtration pressure (PF) and measured free plasma hemoglobin (free Hb) and platelet counts before and after the two hours plasmaseparation procedure. The final transmembrane pressure was significantly higher with HES substitution. In the HES group we found negative filtration pressures from the very beginning with a significant further decrease toward the end of the experiments. A significant increase in free Hb and decrease in platelet counts were noted only in the HES group. Volume substitution with HES leads to impaired filtration properties and deteriorated hemocompatibility in in vitro plasmaseparation. Further studies have yet to evaluate whether or not the effects described also occur under clinical conditions.
Osseointegration of Sandblasted or Anodised Hydrothermally-Treated Titanium Implants: Mechanical, Histomorphometric and Bone Hardness Measurements
Authors: Giavaresi G. , Fini M. , Chiesa R. , Rimondini L. , Rondelli G. , Borsari V. , Martini L. , Aldini N. Nicoli , Guzzardella G.A. , Giardino R.
Published: January 2018

The improvement of the implant-bone interface is still an open problem in the long-term mechanical stability of cementless fixed implants. Mechanical, histomorphometric and bone hardness measurements were performed in sheep femoral cortical bone implants at 8 and 12 weeks from surgery to compare in vivo the osseointegration of titanium screws (Ø 3.5 mm × 7 mm length) with two different surface treatments: sandblasting with 70–100 μm HA followed by acid etching with HNO3 (Group A) and Ca-P anodization followed by a hydrothermal treatment (Group B). No significant differences were found for maximum push-out force and interfacial strength between groups at both experimental times. No significant difference was observed for Bone Ingrowth between groups at both experimental times, while the Affinity Index of Group B was significantly higher (7.5%, p<0.05) and lower (10.2%, p<0.05) than that of Group A at 8 and 12 weeks, respectively. Finally, a significant increase in bone microhardness measured within 200 μm from the interface and inside the thread depth of Group A was observed between the two experimental times (p<0.05). In conclusion, present findings show that osseointegration may be accelerated by adequate surface roughness and bioactive ceramic coating such as current tested treatments which enhance bone interlocking and mineralization.
Hemodynamic Comparison of Two Different Pediatric Aortic Cannulas
Authors: De Wachter D. , De Somer F. , Verdonck P.
Published: January 2018

Any extracorporeal blood treatment requires an adequate and safe connection to the circulation. For cardiopulmonary bypass procedures, aortic and venous cannulas are utilized. However, the performance of these cannulas is not only dependent on their size (diameter), but also on their complete geometric design.

In this paper two aortic cannula designs are evaluated hemodynamically for two different sizes (8, 10 Fr) both with aqueous fluids and with blood. Using the novel concept of equivalent diameter, a new performance parameter, and the theory of dynamic similarity the results obtained with different fluids can be compared. Data points of one cannula can be fitted to a parabolic equation.

There is a significant performance difference between the two 8 Fr cannulas. The 10 Fr cannulas differ non-significantly except when water is used. Equivalent diameters obtained with water in the turbulent region are significantly higher than those obtained with fluids that have a higher viscosity (blood and aqueous glycerine mixture). The latter fluids have comparable viscosities and render an equal equivalent diameter. The coefficients of their proper parabolic fit lines can easily be recalculated into each other.

This provides a simple method to quickly determine pressure drops in cannulas in the operating room.
Closed, Phosphorylcholine-Coated Circuit and Reduction of Systemic Heparinization for Cardiopulmonary Bypass: The Intraoperative ECMO Concept
Authors: Ranucci M. , Pazzaglia A. , Isgrò G. , Cazzaniga A. , Ditta A. , Boncilli A. , Cotza M. , Carboni G. , Brozzi S. , Bonifazi C.
Published: January 2018

Cardiopulmonary bypass with heparin-bonded circuits reduces systemic heparinization which is associated to a better clinical outcome in cardiac operations. In the present study, a novel biocompatible treatment, based on a phosphorylcholine coating without heparin, has been used to reduce systemic heparinization during cardiopulmonary bypass. Sixty patients underwent coronary revascularization with a fully phosphorylcholine-coated circuit. The circuit was entirely closed; suctions from the field were separated during the cardiopulmonary bypass time. A low systemic heparinization protocol based on half the loading dose of heparin (150 lU/kg) and a target activated clotting time of 320 seconds was applied. No thrombus formation inside the extracorporeal circulation circuit occurred; in-hospital mortality was absent. One patient (1.6%) had a postoperative myocardial infarction and 2 (3.3%) were surgically revised due to bleeding. Homologous blood transfusion rate was 11.6%, postoperative bleeding was 310 ± 136 ml. If compared to patients treated with heparin-coated circuits and low systemic heparinization, these patients have better platelet count preservation and lower postoperative bleeding. The low thrombogenicity of phosphorylcholine-treated surfaces, despite the absence of surface-immobilized heparin, allows a safe reduction of systemic heparinization in the setting of an ECMO-like intraoperative cardiopulmonary - bypass. This intraoperative ECMO approach offers promising results in terms of clinical outcome after coronary revascularization operations.
Treatment of Acute Liver Failure in Pigs Reduces Hepatocyte Function in a Bioartificial Liver Support System
Authors: Abrahamse S.L. , Van De Kerkhove M.-P. , Sosef M.N. , Hartman R. , Chamuleau R.A.F.M. , Van Gulik T.M.
Published: January 2018

Several different types of bioartificial liver (BAL) support systems have been developed to bridge patients suffering from acute liver failure (ALF) to transplantation or liver regeneration. In this study we assessed the effects of ALF plasma on hepatocyte function in the BAL system that has been developed in our center. Pigs (40–60 kg) were anaesthetised and a total hepatectomy was performed. Cells were isolated from the resected livers and were transferred to the bioreactor of the BAL system. Twenty hours after cell isolation, hepatocytes in the BAL were tested for cell viability and functional activity by using a recirculating test medium in which assessment of LDH leakage, ammonia clearance, urea synthesis, 7-ethoxycoumarin O-deethylase (ECOD) activity and pseudocholine esterase production was performed. Subsequently, two groups were studied. In one group (I, n=5), the cell-loaded bioreactor was used to treat the donor pig, rendered anhepatic, for 24 hours. In the second group (II, n=5) the bioreactor was cultured for 24 h and served as a control. After 24 hours treatment or culturing, the cell viability count and functional activity tests were repeated. The results show that hepatocytes in the BAL remained viable after 24 h treatment of anhepatic pigs, as shown by the LDH release and pseudocholine esterase production. However, metabolic functions such as ammonia clearance, ECOD and urea synthesis were reduced after 24 h exposure of hepatocytes to autologous ALF plasma, whereas these functions were unaltered after 24 h culturing of the cells in the bioreactor.
Biologic Liver Support: Optimal Cell Source and Mass
Authors: Morsiani E. , Brogli M. , Galavotti D. , Pazzi P. , Puviani A.C. , Azzena G.F.
Published: January 2018

Hepatic support is indicated in acute liver failure (ALF) patients to foster liver regeneration, or until a liver becomes available for orthotopic liver transplantation (OLT), in primary non function of the transplanted liver, and hopefully in chronic liver disease patients affected by ALF episodes, in whom OLT is not a therapeutic option. The concept of bioartificial liver (BAL) is based on the assumption that only the hepatocytes can perform the whole spectrum of biotransformation functions, which are needed to prevent hepatic encephalopathy, coma and cerebral edema. Among others, two important issues are related to BAL development: 1) the choice of the cellular component; 2) the cell mass needed to perform an adequate BAL treatment. Primary hepatocytes, of human or animal origin, should be considered the first choice because they express highly differentiated functions. Accordingly, a minimal cell mass corresponding to 10% of a human adult liver, i.e. 150 grams of freshly isolated, ≥90% viable hepatocytes should be used. When 4 °C cold-stored or cryopreserved hepatocytes are used, the cellular mass should be increased because of a drop in cell viability and function. In case of hepatoma-derived cells, cultured cell lines or engineered cells, an adequate functional cell mass should be used, expressing metabolic and biotransformation activities comparable to those of primary hepatocytes. Finally, the use of porcine hepatocytes or other animal cells in BAL devices should be presently directed only to ALF patients as a bridge treatment to OLT, because of potential transmission of animal retrovirus and prions which may potentially cause major pandemics..
Primary Human Liver Cells as Source for Modular Extracorporeal Liver Support - a Preliminary Report
Authors: Sauer I.M. , Zeilinger K. , Obermayer N. , Pless G. , Grünwald A. , Pascher A. , Mieder T. , Roth S. , Goetz M. , Kardassis D. , Mas A. , Neuhaus P. , Gerlach J.C.
Published: January 2018

Cell-based extracorporeal liver support is an option to assist or replace the failing organ until regeneration or until transplantation can be performed. The use of porcine cells or tumor cell lines is controversial. Primary human liver cells, obtained from explanted organs found to be unsuitable for transplantation, are a desirable cell source as they perform human metabolism and regulation. The Modular Extracorporeal Liver Support (MELS) concept combines different extracorporeal therapy units, tailored to suit the individual and intra-individual clinical needs of the patient. A multi-compartment bioreactor (CellModule) is loaded with human liver cells obtained by 5-step collagenase liver perfusion. A cell mass of 400 g – 600 g enables the clinical application of a liver lobe equivalent hybrid organ. A detoxification module enables single pass albumin-dialysis via a standard high-flux dialysis filter, and continuous venovenuous hemodiafiltration may be included if required. Cells from 54 human livers have been isolated (donor age: 56 ± 13 years, liver weight: 1862 ± 556 g resulting in a viability of 55.0 ± 15.9%). These grafts were not suitable for LTx, due to steatosis (54%), cirrhosis (15%), fibrosis (9%), and other reasons (22%). Out of 36 prepared bioreactors, 10 were clinically used to treat 8 patients with liver failure. The overall treatment time was 7–144 hours. No adverse events were observed. Initial clinical applications of the bioreactor evidenced the technical feasibility and safety of the system.
The Heart-Pump Interaction: Effects of a Microaxial Blood Pump
Authors: Stoliński J. , Rosenbaum C. , Flameng W. , Meyns B.
Published: January 2018

Background:

When we use rotary blood pumps as an assist device, an interaction takes place between the pump performance and the native heart function (native heart influences pump performance and vice versa). The interaction between native heart and rotary blood pump can be useful to predict recovery of the failing heart.

Methods:

The rotary blood pumps used were microaxial catheter-mounted pumps with an external diameter of 6.4mm (Impella, Aachen, Germany). The pump-heart interaction was studied in five juvenile sheep with a mean body weight of 68.5 ± 8.7 kg. The pumps were introduced via the left carotid artery and placed in transvalvular aortic position. Recorded parameters were pump speed (rpm), generated flow (L/min) and differential pressure (mm Hg) obtained at high frequency rate of data recordings (25 sets of data per second). This allowed continuous analysis of the pump performance during cardiac cycle. Under clinical conditions the interaction was studied in a 60-year-old male, in whom the device was applied due to postcardiotomy heart failure after myocardial infarction.

Results:

Heart-pump interaction was analyzed based on pump flow differential pressure. This relationship, analyzed continuously during cardiac cycle, presents as a loop. The dynamic contribution of the heart to the flow generated by the pump leads to continuous fluctuation in the pressure head and the creation of hysteresis. The improved function of the failing heart under clinical conditions after seven days of mechanical support was expressed by: increased hysteresis of the loop caused by increased gradient of flow generated during cardiac cycle, a more pronounced ventricular ejection phase that indicates more dynamic heart contribution to the generated flow, and finally increased gradient of the differential pressure during cardiac cycle, caused predominantly by increased aortic pressure and decreased left ventricle pressure during diastolic phase.

Conclusions:

The heart-pump interaction based on the pump flow-differential pressure relationship can be useful in predicting the possibility to wean the patient from the device.
Plasma Carnitine Profile during Chronic Renal Anemia Treatment with Recombinant Human Erythropoietin
Authors: Dębska-Ślizień A. , Owczarzak A. , Kunicka D. , Łysiak-Szydłowska W. , Rutkowski B.
Published: January 2018

Recombinant human erythropoietin (epoetin) is widely used for correction of anaemia in patients with chronic renal disease and its efficacy has been confirmed in numerous studies. Disturbances in carnitine metabolism may also contribute to the development of renal anaemia. Although increases in erythrocyte count (RBC) and changes in RBC metabolism during L-carnitine administration have been observed, supplementation with L-carnitine in anaemic hemodialysis patients is not routine.

The aim of our study was to determine the influence of epoetin on hematological parameters and plasma carnitine profile in anaemic hemodialysis patients. 36 hemodialysis patients (22 men, 14 female, aged from 17 to 64 years, mean 43) and 30 healthy volunteers (12 men, 18 female, aged from 25 to 65 years, mean 40) were studied. Epoetin (Eprex, Janssen-Cilag) was administered subcutaneously for twelve months with the starting dose 2000 IU three times per week (range from 75 to 133, mean 102±21 IU/kg/week). The target hemoglobin (Hb) range at the time of the study was between 10–11 g/dL. Laboratory markers of hematological response, carnitine and iron status, were measured before epoetin administration and then controlled every three months. During epoetin treatment a significant increase in Hb concentration was observed (100% of patients responded to epoetin). In the third and six month of epoetin treatment, along with a significant increase in mean reticulocyte count and the highest increment of RBC count and Hb levels, probably due to increased erythropoiesis, a significant, transient decrease of mean total and free plasma carnitine levels was observed.

This may suggest the utilisation of carnitine by a new RBC population. It also indicates that there is a need for L-carnitine in carnitine deficient maintenance hemodialysis patients particularily during erythropoiesis induced by epoetin treatment.
Development of a Vibratory Microinjection Method
Authors: Miyawaki F. , Arai Y. , Morisaki T. , Ahmed S. , Omata S. , Fukui Y.
Published: January 2018

To reduce cellular damage by pronuclear microinjection and nuclear transfer, we have recently developed a vibratory microinjection method. A micropipette was fixed to a piezoelectric ceramic with a resonance frequency of 70 kHz. When this micropipette was vibrated, it easily entered a mouse-fertilized egg without any sharp depression of the cell body, whereas a sharp, deep depression at the insertion site was observed when the micropipette was not vibrated. A depression rate defined as a rate of a depth of depression over an original cell diameter was utilized as an index of cellular deformation. The depression rates with and without vibration were 11.1 ± 5.2% (N = 24) and 40.4 ± 8.8% (N = 16), respectively (P < 0.0001, Student's t-test). In conclusion, the vibratory microinjection method is a new, useful option for gene transfer because it resulted in much less cellular deformation, therefore implicating less cellular damage.
Use of Octreotide to Treat Prolonged Sulfonylurea-induced Hypoglycemia in a Patient with Chronic Renal Failure
Authors: Nzerue C.M. , Thomas J. , Volcy J. , Edeki T.
Published: January 2018

A diabetic patient with chronic renal failure who developed recurrent and prolonged episodes of hypoglycemia associated with use of sulfonylurea agent is presented here. This patient was hospitalized with neuroglycopenic symptoms of hypoglycemia that persisted in spite of large doses of parenteral glucose replacement. On administration of somatostatin analogue octreotide, hypoglycemia resolved and, blood glucose levels were maintained even after cessation of parenteral glucose. The patient received 2 subcutaneous doses of octreotide 12 hours apart, and made a complete recovery. Our experience suggests that use of octerotide to treat refractory or prolonged sulfonylurea-included hypoglycemia in renal failure patients is safe and effective; large prospective studies would be needed to validate these findings.
Perifusion Model for Detoxification of Drugs in a Bioartificial Liver
Authors: Park Y.G. , Son Y.-S. , Ryu H.-W.
Published: January 2018

Detoxification of a drug in a bioartificial liver (BAL) during an in vitro experiment was theoretically carried out based on a perifusion model. The detoxification capacity assay, the rates of disappearance of the chemicals such as flow-limited and enzyme-limited drugs in the BAL system could be defined from models of hepatic perfusion-elimination relationships. When the flow-limited drug administrated under a quasi-equilibrium condition, a two-compartment model for the concentration behavior of the drug was introduced and compared with a one-compartment model. For both models, equations involving hepatic drug clearance and various pharmacokinetic parameters were derived under initial bolus loading and constant-rate infusion plus bolus loading conditions. The concentration of enzyme-limited drug in the BAL decreased linearly with time in contrast with the concentration profile of the flow-limited drug followed by exponential functions. The perifusion model offers a quantitative understanding of the elimination kinetics of chemicals such as flow-limited and enzyme-limited drugs in a bioartificial liver and a comparison between the BAL and human liver.
Autologous Cardiomyocyte Transplantation Using a Biodegradable Polymer Scaffold
Authors: Kim W.G. , Park J.K. , Moon H.K. , Roh J.R.
Published: January 2018

Background

To achieve a more reliable way of transplanting cardiomyocytes, we conducted an autologous cardiomyocyte transplantation using a biodegradable scaffold, instead of a syringe injection, as a vehicle for transporting cells in an ovine myocardial infarction model.

Materials and Methods

A myocardial infarction was created in sheep using sequential ligation of the homonymous artery and its diagonal branch. Autologous cardiomyocytes from the right ventricular infundibulum were cultured and seeded onto a biodegradable polymer scaffold. Three months after creating myocardial infarction, the two animals were re-anesthetized and cardiomyocyte-seeded scaffolds were implanted in the infarcted area. The animals were kept alive for a further month, and then sacrificed for postmortem heart examinations. Light microscopic analysis and an immunohistochemical study for myoglobin were performed.

Results

On postmortem gross examinations, the polymer scaffolds were visible in the background of well-demarcated thin-walled anteroseptal myocardial infarcts. Microscopic analysis showed abundant myoglobin-stained cells between the fiber strands of the polymer scaffolds. However, there is a possibility that some of these cells might have been giant cells reacting to foreign material.

Conclusion

The transplantation of cultured autologous cardiomyocytes into an infarct region using a biodegradable scaffold instead of syringe injection provides another promising option for cardiomyocyte transplantation, which warrants further study.
Peritoneal Catheter Exit-Site Infections: Predisposing Factors, Prevention and Treatment
Authors: Thodis E. , Passadakis P. , Ossareh S. , Panagoutsos S. , Vargemezis V. , Oreopoulos D.G.
Published: January 2018

Catheter-related infections, exit-site-tunnel infections and peritonitis remain the Achilles heel of peritoneal dialysis. Although the overall incidence of peritoneal-dialysis-related infectious complications has been reduced since the introduction of the Y-set and double bag system, approximately one-fifth of peritonitis episodes are associated with catheter exit-site and tunnel infections. Since its development in 1968, the Tenckhoff catheter has become one of the most widely used peritoneal catheters, and many have proposed that a number of modifications have made it a better choice. Controversies concerning the effect on exit-site infections of catheter(s) with one or two cuffs, with straight, coiled, Swan-Neck, or other modifications led to the randomized controlled studies that are reviewed in this paper. Several studies have confirmed that mupirocin, applied at the exit-site as part of regular exit-site care, reduces the risk of S. aureus exit-site and tunnel infections. Recently, the emergence on a world-wide basis of mupirocin-resistant S. aureus (MuRSA) in peritoneal dialysis patients has brought this prophylactic strategy into question. However the low frequency of resistant organisms after four years of mupirocin prophylaxis suggests that we can continue its use with annual surveillance.

Once established, exit-site infections may respond to appropriate treatment, but if not the only option may be catheter removal and replacement.

Although peritonitis risk has decreased over the past decade, mainly due to improvements in connection technology, exit-site and tunnel infections have not (1, 2). An exit-site infection that does not respond to treatment may lead to tunnel infection and to persistent peritonitis, which may require catheter removal and occasionally discontinuation of the peritoneal dialysis. Therefore it is important to be familiar with these factors that predispose to exit-site infection and to know how to prevent and to treat such infections. This review will discuss factors that predispose to catheter-related exit-site infections, techniques of exit-site care, and ways to prevent exit-site infection, with emphasis on S. aureus infections and their treatment (3, 4).
Clinical Application of Sodium Profiling in the Treatment of Intradialytic Hypotension
Authors: Colì L. , Ursino M. , Donati G. , Cianciolo G. , Soverini M.L. , Baraldi O. , La Manna G. , Feliciangeli G. , Scolari M.P. , Stefoni S.
Published: January 2018

Background

Intradialytic hypotension is mainly induced by the removal of extracellular sodium during dialysis, which impairs intravascular fluid refilling and reduces blood volume. To counter this complication we tested a new kind of profiled hemodialysis (PHD) consisting of the intradialytic modulation of dialysate sodium concentration according to individual profiles set up using a new mathematical model for intradialytic solutes and water kinetics. The clinical aim of this PHD is to stabilize blood pressure maintaining higher blood volume values than standard dialysis treatments. We clinically validated PHD in comparison with constant dialysate sodium dialysis (CHD).

Methods

Twenty hypotensive dialysis patients underwent one PHD and one CHD session maintaining the same dialysis length, sodium mass removal and body weight decrease. A new mathematical model was used to define both the dialysate sodium profiles for PHD and the constant dialysate sodium for CHD. Percent blood volume variation (Crit-line), mean blood pressure, heart rate, cardiac output (Doppler-echocardiography) were monitored intradialitically.

Results

Cardiovascular stability improved on PHD as compared with CHD sessions; blood volume and cardiac output during PHD showed a lower decrease than on CHD, the differences statistically significant (from 30' and 60' respectively). Mean blood pressure was, at all time intervals, more stable on PHD than on CHD and was accompanied, on PHD, by a lower heart rate increase (differences statistically significant).

Conclusions

This study shows that PHD performed using dialysate sodium profiles elaborated by our mathematical model obtains, in hypotensive patients, a higher hemodynamic intradialytic stability than CHD, probably due to a higher stabilization of blood volume.
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.
Tailoring Biomaterial Compatibility: In Vivo Tissue Response versus in Vitro Cell Behavior
Authors: Mattioli-Belmonte M. , Giavaresi G. , Biagini G. , Virgili L. , Giacomini M. , Fini M. , Giantomassi F. , Natali D. , Torricelli P. , Giardino R.
Published: January 2018

Biocompatibility relies essentially on surface phenomena, represented by cell-cell, cell-material and material (polymer)-protein interactions. An in vivo and in vitro experimental investigation was carried out on the biomaterials of two different classes with a good potential for in situ utilisation. Non-resorbable (Polypyrrole, Polyaniline, Polyimide) and resorbable (PLLA-PDXO-PLLA) materials for tissue engineering were studied for their overall tissue tolerance and cellular interactions. These non-resorbable polymers conceived for biosensor applications and implantable drug-delivery systems are intrinsically conductive. The PLLA-PDXO-PLLA triblock copolymer showed interesting tensile properties for bone and cartilage tissue engineering due to the presence of 1,5-dioxepan-2-one. In vitro and in vivo parallel studies showed an interesting correspondence: a) the cells in contact with the resorbable material that appeared to be capable of migratory-regenerative aspects in vitro exhibited good compatibility in vivo; whereas b) the non-resorbable materials, which are designed to remain in situ in vivo, were seen to have the potential to represent an adverse factor (inflammation, fibrotic reactions) that correlated with some aspects of cell behaviour in vitro.
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.
A Modified Equivalent Annulus Model for the Hollow Fiber Hemodialyzer
Authors: Liao Z. , Klein E. , Poh C.K. , Huang Z. , Hardy P.A. , Morti S. , Clark W.R. , Gao D.
Published: January 2018

Experimental approaches to optimize hollow fiber hemodialyzer design are expensive and time-consuming. Computer modeling is an effective way to study mass transfer in the hemodialyzer because a substantial reduction in experimental time and cost can be achieved. This paper presents a two-dimensional modified “equivalent annulus” model, which employs Navier-Stokes (N-S) equations to describe blood and dialysate flow, and Kedem-Katchalsky (K-K) equations to calculate transmembrane flow. N-S equations and K-K equations must be coupled together in the process of computing. The corresponding experiments were designed to validate this model, and experimental results agreed well with numerical results. The distribution of velocity, pressure and solute concentration were investigated in detail, presenting a clear insight into dialyzer mass transfer. This model can be applied to help optimize hemodialyzer design.
Development of Co-Culture System of Hepatocytes with Bone Marrow Cells for Expression and Maintenance of Hepatic Functions
Authors: Murakami S. , Ijima H. , Ono T. , Kawakami K.
Published: January 2018

In this study, a co-culture system of hepatocytes and bone marrow cells (BMCs) was developed and characterized for the expression and maintenance of ammonia metabolism and albumin secretion activities. A culture medium supplemented with epidermal growth factor, insulin, L-proline, hydrocortisone and 20 % (v/v) heat-inactivated fetal bovine serum was developed. In addition to adhesive bone marrow cells, the co-existence of non-adhesive bone marrow cells was effective in expressing liver-specific functions for at least 3 weeks. On the other hand, experiments with Transwell in which cultured cells were separated by a semi-permeable membrane, suggested that soluble factors secreted by BMCs are the key components in the functional enhancement of cells. Furthermore, direct contact between hepatocytes and BMCs enhanced the formation of spheroids and the expression of liver specific functions. These results indicate that this co-culture system is promising in, for example, bioartificial liver, regenerative medicine, and liver function simulator applications.
Proposal for a Quantitative Description of Blood Spiral Flow in Medical Devices
Authors: Grigioni M. , Daniele C. , Morbiducci U. , Del Gaudio C. , D'Avenio G. , Balducci A. , Barbaro V.
Published: January 2018

The association between specific blood flow patterns and blood behaviour through medical devices suggests that a Lagrangian study may be a useful instrument for the evaluation of the thrombogenic and/or hemolytic potential of certain devices' geometries and biomaterials. In this study a description of blood particle trajectories in terms of their spiral contents is proposed; such a mathematical description for blood spiral flow, computed along several pathlines, is tested for a quantitative determination of the spiralled motion of blood flow into two three-dimensional numerical models, having different design characteristics, of venous cannula inserted in a vessel. As the influence of vortical flow conditions have been observed to have both beneficial and detrimental influence on blood behaviour in terms of blood-device interaction, of the degradation of its components, and of the efficiency of mass-exchange (in red cells oxygenation and plasma filtration, for example), the herein proposed method for the description of spiral laminar motion may be a helpful instrument to build up a tool to investigate, for example, the existence of correlations between level of spiral flow and geometry (as in the present investigated test case), rather than the effects of blood-surface contact. The results obtained in this test case investigation, confirm the effectiveness of the proposed function for a quantitative analysis of spiral flow in medical devices.
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.
LDL-apheresis in Acute Anterior Ischemic Optic Neuropathy
Authors: Ramunni A. , Giancipoli G. , Saracino A. , Guerriero S. , Saliani M.T. , Gentile M.C. , Sborgia C. , Coratelli P.
Published: January 2018

Acute anterior ischemic optic neuropathy (AION) is a disabling disease which impairs visual function. Standard treatment is unable to affect the outcome and the visual damage persists. We describe the case of a 64-year-old patient affected by AION, whose only known risk factor was hypercholesterolemia. After a first onset of involvement of the right eye (RE), the patient presented four weeks later with an analogous episode affecting the left eye (LE). Since standard treatment, started at involvement of the RE, had not yielded any beneficial effect, the patient underwent three sessions of LDL apheresis. The scotomatous portion of the visual field reduced even after the first session, there was further improvement after the third, and after six months the condition remained stable. Corrected vision improved from 2/10 to 6/10 after the third session. LDL cholesterol and fibrinogen decresade after the third session from 239 mg/dL to 31 mg/dL and from 289 mg/dL to 92 mg/dL, respectively. In conclusion, thanks to its effect of antagonizing hemorheologic disorders of the ocular microcirculation, LDL apheresis seems to be an efficacious treatment of AION, especially in patients suffering from hypercholesterolemia.
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.