bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro and in vivo Behaviour of Biodegradable and Injectable PLA/PGA Copolymers Related to Different Matrices
Authors: Tschon M. , Fini M. , Giavaresi G. , Torricelli P. , Rimondini L. , Ambrosio L. , Giardino R.
Published: January 2018

This study comparatively investigates the in vitro and in vivo behavior of injectable polymeric materials for the treatment of bone defects. The tested materials were three injectable and biodegradable PLA/PGA 50/50 copolymers dispersed in different matrices: Fisograft-gel (GEL) was dispersed in an aqueous matrix of poly-ethyl-glycole (PEG); Slurry2 (SL2) was dispersed in an aqueous matrix of PEG and dextran; and Slurry6 (SL6) was dispersed in a 3% agarose matrix. The biological characterization of these materials was studied by in vitro and in vivo tests: the in vitro test assessed the cellular response in terms of viability, differentiation and synthetic activity, while the in vivo test evaluated the healing capacity of bone defects treated with these biomaterials. GEL and SL2 induced a similar response for viability and differentiation of MG63 osteoblast-like cells after a 7-day culture, while SL6 caused a higher production of both interleukin-6 and type I collagen. Since the results showed that the materials were biocompatible and not cytotoxic in vitro, the in vivo study was carried out: materials were implanted, under general anesthesia, in critical size defects of rabbit femoral condyles; after 4 and 12 weeks, the healing rates and the quality of the regenerated bone were histomorphometrically calculated. The SL2-treated defects healed better at 12 weeks with a more similar microarchitecture of the newly formed bone to normal bone in comparison with other materials, as demonstrated by bone volume fraction and trabecular thickness values.
Experimental Validation of Numerical Simulations: A Comparison of Computational Fluid Dynamics and the Oil Film Method
Authors: Stoiber M. , Grasl C. , Pirker S. , Huber L. , Gittler P. , Schima H.
Published: January 2018

Background

Today Computational Fluid Dynamics (CFD) is used for simulating flow in many applications. The quality of the results, however, depends on various factors, like grid quality, boundary conditions and the computational model of the fluid. For this reason, it is important to validate the performed computation with experimental results. In this work, a comparison of numerical simulation with the oil film method was performed for two cardiovascular applications.

Methods

The investigations were conducted at various geometries, such as a bended cannula tubing, an impeller of a magnetically levitated rotary blood pump and tips of inflow cannulas. The oil film for the experimental validation was composed of black oil color and varnish. In the numerical simulation, color abrasion was displayed with a special post-processing tool by means of wall-attached pathlines.

Results

With the proper choice of numerical parameters, the computer simulations and the oil film method demonstrated good correlation. Improper generation of the simulation grid did lead to divergent results between the numerical simulation and the experiment. For the pump impeller as well as for the inflow cannulas, the calculation and the experiment showed similar flow patterns with backflow and stall zones.

Conclusion

The oil film method represents a fast and simple approach to help validate numerical simulations of fluid flow. The experimentally generated near wall flow patterns can be easily compared with the solution of the CFD analysis.
β2-Microglobulin Removal and Plasma Albumin Levels with High Cut-off Hemodialysis
Authors: Haase M. , Bellomo R. , Baldwin I. , Haase-Fielitz A. , Fealy N. , Morgera S. , Goehl H. , Storr M. , Boyce N. , Neumayer H.-H.
Published: January 2018

Purpose.

β2-microglobulin (β2MG) is pivotal to the pathogenesis of dialysis-related amyloidosis. We compared the effects of high cut-off hemodialysis (HCO-HD) with those of standard high-flux hemodialysis (HF-HD) regarding the concentration and clearance of β2MG and albumin.

Design.

We enrolled ten patients with acute renal failure in a double-blind, cross-over, randomized controlled trial.

Procedures

Each patient received four hours of HCO-HD (estimated in vivo cutoff 50–60 kDa) and four hours of HF-HD (estimated in vivo cutoff 15–20 kDa) in random order. Statistical methods and outcome measures: As data lacked normal distribution, we used non-parametric statistical analysis. Plasma and dialysate concentrations of β2MG and albumin were measured at baseline and after four hours of each study treatment.

Main findings.

We found significantly greater diffusive β2MG clearances for HCO-HD compared to HF-HD (at the start: 71.8 ml/min vs. 5.1 ml/min; P=0.008 and at the end: 68.8 ml/min vs. 5.7 ml/min; P=0.008). We found a reduction in plasma β2MG concentrations of -31.6% during HCO-HD compared to an increase by 25.7% during HF-HD; P=0.008. At baseline (HCO-HD: 26.0 g/L vs. HF-HD: 26.5 g/L), and at the end of both treatments, plasma albumin concentrations were comparable (HCO-HD: 25.5 g/L vs. HF-HD: 26.5 g/L; P=0.25). During HCO-HD, albumin clearance was 1.9 ml/min at the start and decreased significantly to 0.8 ml/min at the end; P=0.008. HF-HD had an albumin clearance of 0.01 ml/min.

Conclusions.

HCO-HD was more effective in decreasing plasma β2MG concentrations than standard HF-HD and did not reduce plasma albumin levels. Further studies of HCO-HD in the treatment of dialysis-related β2MG accumulation appear warranted. ( ClinicalTrials.gov number, NCT00333593 [ ClinicalTrials.gov ]) (Int J Artif Organs 2007; 30: 385–92)
Plasma Filtration on Mediators of Thrombotic Microangiopathy: An in Vitro Study
Authors: Peng Z. Y. , Kiss J. E. , Cortese-Hassett A. , Carcillo J. A. , Nguyen T. C. , Kellum J. A.
Published: January 2018

Objectives.

Sepsis-induced thrombotic microangiopathy is successfully treated by plasma exchange therapy However, certain putative mediators of thrombotic microangiopathy may not be removed by plasma filtration.

Methods.

We conducted an in vitro study to determine whether plasma filtration can remove ultra-large von Willebrand factor (ULvWF) multimers and other mediators. In separate experiments, human umbilical venous endothelial cell (HUVEC) supernatant enriched with ULvWF or human whole blood was passed through a therapeutic plasma exchange (TPE 2000, PRISMA) filter and samples were taken for measurement of ULvWF, vWF ristocetin cofactor, vWF antigen and PAI-1.

Results.

The sieving coefficients for vWF and PAI-1 were above 0.9. The ULvWF was gradually eliminated, and nearly disappeared after four circulations.

Conclusion.

The TPE 2000 filter can directly remove potential mediators of sepsis-induced thrombotic microangiopathy.
Possible Role of Milky Spots in Mesothelial Transplantation
Authors: Sacchi G. , Di Paolo N. , Venezia F. , Rossi A. , Nicolai G. , Garosi G.
Published: January 2018

Milky spots are very small omental organs, in contact with peritoneal membrane, devoid of capsule and consisting of macrophages, lymphocytes and a few plasma cells supported by blood and lymphatic vessels. The exact role of these particular organs is still not clear, but they are similar to lymphatic structures and it is clear that they play a role in peritoneal infection and abdominal tumors.

Peritoneal dialysis seems to activate the milky spots changing their morphology. The authors try to formulate some hypotheses on the role played by these little omental organs during autologous mesothelial transplant.
The Potential of Mesothelial Cells in Tissue Engineering and Regenerative Medicine Applications
Authors: Herrick S.E. , Mutsaers S.E.
Published: January 2018

Injury to the serosa through injurious agents such as radiation, surgery, infection and disease results in the loss of the protective surface mesothelium and often leads to fibrous adhesion formation. Mechanisms that increase the rate of mesothialisation are therefore actively being investigated in order to reduce the formation of adhesions. These include intraperitoneal delivery of cultured mesothelial cells as well as administration of factors that are known to increase mesothelial proliferation and migration. An exciting alternative that has only recently received attention, is the possible role of mesothelial progenitor cells in the repair and regeneration of denuded serosal areas. Accumulating evidence suggests that such a population exists and under certain conditions is able to form a number of defined cell types indicating a degree of plasticity. Such properties may explain the extensive use of mesothelial cells in various tissue engineering applications including the development of vascular conduits and peripheral nerve replacements. It is likely that with the rapid explosion in the fields of tissue engineering and regenerative medicine, a greater understanding of the potential of mesothelial progenitor cells to repair, replace and possibly regenerate damaged or defective tissue will be uncovered.
Cardiorenal Syndrome at Different Stages of Chronic Kidney Disease
Authors: Tsagalis G. , Zerefos S. , Zerefos N.
Published: January 2018

The central concept of the cardiorenal syndrome (CRS) is that the heart and the kidney should be regarded not solely as individual organs but rather as a dipole with multiple interconnections. The interplay between the heart and the kidney seems complex and multifactorial: cardiac output, regulation of extracellular volume, blood pressure and renal sodium handling are the major parameters that determine the crosstalk between the 2 organs. These basic parameters are controlled through mediators (renin-angiotensin system, endothelin) and the relevant antagonists (natriuretic peptides). Recently, it has been shown that the nitric oxide / reactive oxygen species balance, sympathetic nervous system activation and the presence of systemic inflammation aggravate atherosclerosis, promote structural alterations in left ventricular geometry and favor progression of renal disease. Although the prevalence of the CRS is high, major clinical trials for heart failure have only partially addressed this issue. The present review tries to dissect the role of various components of the CRS in a way that could potentially facilitate the implementation of specific therapeutic strategies. The multiple factors that participate in the pathogenesis of this syndrome are studied in detail in an effort to better understand this syndrome and address effectively its various components, since a holistic approach could (ideally) alter the syndrome's course and hence ameliorate the prognosis of the CRS. (Int J Artif Organs 2007; 30: 564–76)
Clearance of Levofloxacin by an in Vitro Model of Continuous Venovenous Hemodialysis (CVVHD)
Authors: Siewert S. , Drewelow B. , Mueller S.C.
Published: January 2018

Information about the elimination and the adequate dosing of levofloxacin during renal replacement therapy is scarce. The aim of this study was to characterize in vitro the elimination of levofloxacin during continuous venovenous hemodialysis (CVVHD) and to investigate whether the CVVHD clearances of creatinine and urea are correlated with the levofloxacin clearance in order to facilitate dosage adjustments. An in vitro model of CVVHD was established using five dialyzer membranes at varying dialysate flow rates applied in the clinical setting (8, 16, 25, 33 and 41 ml/min). Plasma and dialysate samples were drawn for determination of levofloxacin, creatinine and urea concentrations to evaluate clearances by CVVHD.

During CVVHD, the clearance of levofloxacin varied between 9.02 and 33.30 ml/min, depending on the chosen setup. Positive correlations (p<0.001) were received for: dialysate flow rate (QD) and creatinine/urea clearances (R>0.93); QD and levofloxacin clearance (R 0.59–0.71); levofloxacin and creatinine clearance (R 0.69–0.75); and levofloxacin and urea clearance (R 0.56–0.75) as well. When dosing critically ill patients, therefore, extracorporeal as well as total clearance of levofloxacin should be considered.
Integration of Blood Volume, Blood Pressure, Heart Rate and Bioimpedance Monitoring for the Achievement of Optimal Dry Body Weight during Chronic Hemodialysis
Authors: Bonello M. , House A.A. , Cruz D. , Asuman Y. , Andrikos E. , Petras D. , Strazzabosco M. , Ronco F. , Brendolan A. , Crepaldi C. , Nalesso F. , Ronco C.
Published: January 2018

Background

Achieving optimal dry body weight in hemodialysis is challenging. Clinical assessment alone is inadequate, and methods such as bioimpedance monitoring may be impractical for every patient treatment. Continuous blood volume monitoring, blood pressure and heart rate variability inform clinical decision-making, but integrated use of multiple methodologies to achieve dry weight and understand patient factors has not yet been described.

Methods

Nineteen chronic hemodialysis patients underwent thrice-weekly treatments for two weeks. Baseline hydration status and target weight were determined by bioimpedance. During subsequent treatments, ultrafiltration was adjusted and relative blood volume, blood pressure and pulse were recorded non-invasively Bioimpedance was repeated to assess hydration. Response of variables to progressive change in weight was assessed and selected patients underwent additional autonomic function testing.

Results

Four distinct hemodynamic patterns emerged. Profile A: 4 patients demonstrated overhydration at baseline. With decreasing target, pulse and blood pressure remained stable while blood volume and bioimpedance demonstrated achievement of dry weight. Profile B: 8 patients demonstrated overhydration at baseline. With decreasing target, blood pressure remained stable while pulse increased. Profile C: 5 patients were overhydrated, but as weight decreased, blood pressure became unstable and heart rate failed to compensate. Further testing confirmed autonomic dysfunction. Profile D: 2 patients were dehydrated, and with increasing target demonstrated stable pulse and pressure, while blood volume and bioimpedance revealed achievement of dry weight.

Conclusions

Integrating existing non-invasive, continuous monitoring during hemodialysis enabled achievement of dry weight and identified distinct profiles of the patients, some with autonomic dysfunction. This strategy may contribute to achieving optimum dry weight while improving cardiovascular tolerability of hemodialysis.
Uterine Myometrium as a Cell Patch as an Alternative Graft for Transplantation to Infarcted Cardiac Myocardium: A Preliminary Study
Authors: Taheri S.A. , Yeh J. , Batt R.E. , Fang Y. , Ashraf H. , Heffner R. , Nemes B. , Naughton J.
Published: January 2018

Purpose

Currently, only a small fraction of patients are able to receive reperfusion therapy for myocardial infarctions. We hypothesize that myometrial cell patch transplantation could be an alternative approach for the treatment of myocardial infarction.

Design

We performed a preliminary study to determine the feasibility of this novel therapeutic approach in a rabbit model.

Procedures

Six adult female New Zealand rabbits were used. Myocardial infarction was induced by left anterior descending artery ligation. A segment of uterus was removed via a laparotomy incision, and this uterine segment was transplanted as an autologous graft over the infarcted myocardium, which was then reinforced by greater omentum.

Statistical methods and outcome measures

Hemodynamic measurements and histological studies. Main findings: All uterine myometrial patches survived in the test animals. Fluoroscopic hemodynamic measurements were made for ejection fractions at 8 weeks after the application of the uterine patch. Histological study demonstrated well-healed myometrial-myocardium junctions with minimum scar tissue. Angiogenesis occurred in the transplanted myometrium. Connexin 43 expression was demonstrated in the transplanted patches.

Conclusion

Our noncontrolled preliminary rabbit experiments indicate that patches of uterine myometrium reinforced by greater omentum can be used as autologous transplant therapy for infracted myocardium. This is an innovative technique that could lead to future treatment for individuals who may suffer from an infarcted myocardium and may not be eligible for traditional reperfusion therapy.
Neurophysiological Assessment of the Electrostimulation Procedures Used in Stroke Patients during Rehabilitation
Authors: Lisiński P. , Huber J. , Samborski W. , Witkowska A.
Published: January 2018

The aim of this study was to evaluate the effectiveness of the associated electrotherapeutical and kinesiotherapeutical treatment in patients after ischemic stroke (N=24), mainly by means of neurophysiological tests. All patients underwent the same 20 days of neurorehabilitation procedures. Particular attention was paid to three-stage modified electrotherapy procedures such as: oververtebral functional electrical stimulation (FES), transcutaneous electrical nerve stimulation (TENS) and the alternate neuromuscular functional electrical stimulation (NMFES) of antagonistic muscles of the wrist and the ankle (N=16). Electrotherapy was supplemented with kinesiotherapeutic (mainly PNF) procedures acting as an amplifier. Clinical assessment included muscle tension (Ashworth's scale), muscle force (Lovett's scale) and reflex scoring at wrist and ankle. However, the effectiveness of the procedures was measured by the assessment of results in complex and repetitive, bilaterally performed global electromyography (EMG) and electroneurography (ENG; M-wave studies). The statistical analysis obtained from results in clinical and neurophysiological examinations suggested that the dorsiflexion of wrist and ankle was improved in the majority of patients who took part in this study. EMG and ENG examinations showed that 20 days of therapy improved both activity in muscle motor units on the more paralyzed side (mainly within upper extremities) and to a lesser degree in the transmission of efferent impulses within motor fibers of nerves. The results obtained suggest that patients after ischemic strokes never show an isolated unilateral disability in motor functions.

No definite similarities between the results of clinical and neurophysiological studies were found, which may suggest greater accuracy of the neurophysiological evaluation.
Prevention of Cardiac Surgery-Associated Acute Kidney Injury
Authors: Schetz M. , Bove T. , Morelli A. , Mankad S. , Ronco C. , Kellum J.A.
Published: January 2018

Numerous strategies have been evaluated to prevent early CSA-AKI. Although correction of hemodynamic problems is paramount, there are no clinical studies that compare different hemodynamic management or monitoring strategies with regard to their effect on kidney function. Pharmacologic strategies including diuretics, different classes of vasodilators and drugs with anti-inflammatory effects such as N-acetyl-cysteine, do not appear to be effective. Most of the studies are underpowered and use physiological rather than clinical endpoints. Further trials are warranted with fenoldopam and nesiritide (rhBNP). Observational and underpowered randomized studies show beneficial renal effects of off-pump technique and avoidance of aortic manipulation. There is very limited evidence for preoperative fluid loading and preemptive RRT. Potentially nephrotoxic agents should be used with caution in patients at risk of CSA-AKI. Tranexamic acid or aminocaproic acid should be preferred over aprotinin. No pharmacologic intervention has been adequately tested in the prevention of late CSA-AKI. A single-center study, including a predominance of patients after cardiac surgery, showed a decrease of kidney injury with tight glycemic control.
Residual of Bacterial Dna in Hemodialyzers: The Proof of Subclinical Infection Sustaining Chronic Inflammation
Authors: De Cal M. , Cazzavillan S. , Rassu M. , Ronco C.
Published: January 2018

Background and purpose

Inflammation and infection seem to be important causes of morbidity and mortality in Chronic Kidney Disease (CKD) patients. Subclinical infections have been proposed as an important cause of inflammatory syndrome but to date this hypothesis remains speculative. In this investigation, we developed a method for molecular detection of the presence of bacterial DNA in a population of chronic kidney disease patients in order to correlate molecular data with the degree and level of inflammation and to evaluate the usefulness of the method in the diagnosis of subclinical infection.

Design

The study was divided into two phases: the study of a population of 81 CKD patients for prevalence and level of inflammation and infection; and the molecular evaluation of a subgroup of 38 patients without evident clinical causes of inflammation for molecular evaluation of subclinical infection.

Results

Patients hemoculture negative turned out positive for the presence of bacterial DNA when molecular methods were used. We found a trend of correlation with the presence of bacterial DNA and the increase in hs-CRP, IL-6 and oxidative stress (AOPP) levels and a reduction in MFI DR+. Hemodialyzer membranes seem to have properties that are “sticky” to bacteria/bacterial DNA and work as concentrators. Moreover our data suggest that DNA can traverse hemodialysis membranes.

Conclusions

Molecular methods have turned out to be far more sensitive than standard methods in detecting subclinical infection. The presence of bacterial DNA seems to influence the variation of some parameters of inflammation and immunity. Apart from the limitations and pitfalls, a molecular method could be useful for the screening of subclinical infection and diagnosis of sepsis when the hemoculture is negative. The identification of the microorganism involved, however, must be done with species-specific primers. These results are preliminary and more investigations will have to be performed in order to confirm our results.
Vascular Endothelial Growth Factor in Dialysate in Relation to Intensity of Peritoneal Inflammation
Authors: Pawlaczyk K. , Polubinska A. , Numata M. , Nakayama M. , Pecoits-Filho R. , Czekalski S. , Lindholm B. , Breborowicz A.
Published: January 2018

Background

Peritoneal inflammation may induce changes in peritoneal microvessels, including neoangiogenesis/vasculogenesis, leading to increased peritoneal solute transport rate (PSTR) and loss of ultrafiltration capacity. We hypothesized that an inflammatory reaction in the peritoneal cavity during peritonitis induces increased synthesis of vascular endothelial growth factor (VEGF). We therefore studied the relationship between peritoneal inflammation markers, VEGF, and transport of fluid and solutes in rats during acute peritoneal inflammation induced by lipopolysaccharide (LPS) added to standard glucose-based dialysis solution.

Methods

Under ether anesthesia, male Wistar rats were injected intraperitoneally with 30 mL Dianeal 3.86% without (Control; n=6) or with LPS (μg/mL): 0.001 (LPS 0.001; n=6), 0.01 (LPS 0.01; n=7), 0.1 (LPS 0.1; n=7), 1.0 (LPS 1.0; n=8). After 8 hours, dialysate volume (IPV), peritoneal solute transport rate (PSTR) and dialysate cell count (DCC) were measured and effluent samples were collected.

Results

LPS i.p. resulted in increased PSTR and decreased IPV (p<0.005). DCC (cells/μL) and the neutrophil/macrophage ratio were higher for all LPS concentrations compared to the control group. After 8 hours, LPS-exposed rats had significantly higher dialysate levels of all investigated cytokines (TNF-α, MCP-1 and IL-10) than the control group. Addition of LPS resulted in increased dialysate VEGF concentrations (pg/mL) (LPS 0.001, 28.2±5.9; LPS 0.01, 38.9±11.6; LPS 0.1, 43.0±5.9; LPS 1.0, 46.6±11.3; Control, 14.5±9.8; p<0.0005 for all LPS vs. Control).

Conclusions

The infusion of Dianeal 3.86% with different doses of LPS induced a strong acute intraperitoneal inflammatory reaction with increased DCC and cytokine levels, resulting in increased peritoneal solute transport and decreased IPV LPS induced a dose-dependent parallel increase of the intraperitoneal concentrations of MCP-1, IL-10 and TNF-α, as well as of VEGF. These results suggest that intraperitoneal VEGF synthesis is induced in response to inflammation, and that this may be an important component in the process leading to peritoneal transport alterations.
The Management of Viral Hepatitis in CKD Patients: An Unresolved Problem
Authors: Molino C. , Fabbian F. , Cozzolino M. , Longhini C.
Published: January 2018

Chronic kidney disease (CKD) patients in dialysis (HD) show peculiar, atypical features of clinical presentation and diseases (cardiovascular, metabolic, hematologic). This is also true for viral hepatitis infections, for which CKD patients represent an important risk group. In the past, hepatitis B virus (HBV) was the major cause of viral hepatitis in end-stage renal disease (ESRD). However, the introduction of a rigorous infection-control strategy, routine screening of patients and staff for hepatitis B serologic markers, vaccination of susceptible patients and staff, use of separate rooms and dedicated machines for HD of HbsAg-positive patients have all led to a decline in the spread of HBV infection in dialysis. Despite the prevalence of the antibody-hepatitis C virus (HCV), there has been a marked decrease in HD patients; after the introduction of routine screening for HCV and the use of erythropoietin, its occurrence ranges from 5% to 25% in the United States, with a prevalence of 6.8% in Europe. In CKD and in HD patients, the presence of HBV and HCV is an independent and significant risk factor for death and this risk may be at least partially attributed to chronic liver disease with its attendant complications. Liver disease can progress with modest hepatic inflammation and prominent fibrosis; the natural history of viral hepatitis in these patients is dependent on the immune dysfunction typical of kidney disease. Despite recent advances in antiviral therapy, there are still many uncertainties in regards to the efficacy and long-term outcomes of treatment with antiviral agents.
Enhancement of Osteogenesis by Concanavalin a in Human Bone Marrow Mesenchymal Stem Cell Cultures
Authors: Sekiya K. , Nishimura M. , Suehiro F. , Nishimura H. , Hamada T. , Kato Y.
Published: January 2018

This study investigates concanavalin A (ConA) as a novel factor that may enhance osteogenesis of mesenchymal stem cells (MSCs) in vitro. Various factors, such as cytokine bone morphogenetic protein-2 (BMP-2), have been studied for their possible promotion of MSC osteogenesis in vivo and in vitro. However, the factor that might be safer, more effective, and less expensive than these has not been determined. We therefore cultured human MSCs in osteogenic medium in the presence or absence of ConA, and used calcium assays to compare the effects of ConA and BMP-2 on MSC calcification. We also used enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) to evaluate the expression levels of bone-specific markers. ConA and BMP-2 enhanced calcification with comparable effectiveness. The combination of ConA and BMP-2 further enhanced calcification slightly but significantly. ConA also increased osteocalcin and BMP-2 protein levels in MSC culture medium. Furthermore, ConA increased osteocalcin, RUNX2, BMP-2, BMP-4, and BMP-6 mRNA expression levels. However, the gene expression pattern of ConA-stimulated MSCs was different from that of MSCs stimulated by BMP-2. Together, these results suggest that ConA and BMP-2 enhance MSC osteogenesis via different pathways. ConA-induced bone formation in MSC cultures may be useful in regenerative medicine or tissue engineering in clinical studies, as well as in basic research on bone formation.
Combination of Sodium Thiosulphate, Cinacalcet, and Paricalcitol in the Treatment of Calciphylaxis with Hyperparathyroidism
Authors: Kyritsis I. , Gombou A. , Griveas I. , Agroyannis I. , Retsa K. , Agroyannis B.
Published: January 2018

Calciphylaxis (calcific uremic arteriolopathy) is a severe complication of hemodialysis characterized by subcutaneous calcification of the small arteries and tissue necrosis. Our case report is focused on a woman receiving hemodialysis (HD) with diabetes mellitus for 20 years and severe secondary hyperparathyroidism, who presented painful subcutaneous nodules, skin necrosis and ulcerations. As the treatment of calciphylaxis is mainly empirical and controversial, we decided to administer cinacalcet with paricalcitol for the control of hyperparathyroidism and sodium thiosulfate to improve the calcification of the arterioles. Two months after the start of the therapy, parathyroid hormone (PTH) decreased significantly and the skin lesions nearly disappeared. Thus, we believe that the combination of sodium thiosulfate with cinacalcet and paracalcitol is effective for the treatment of calciphylaxis with secondary hyperparathyroidism.
Still Stuck in the Slime
Authors: Arciola C. R.
Published: January 2018

The role of biofilm in implant infections and the genetic control of its production are still giving rise to great interest and controversial new results are continuing to emerge from widespread investigations. Bacteria embedded in biofilms are more resistant to most antibiotics. Hypotheses regarding the mechanisms of antibiotic multi-resistance in biofilm are brought to light, including the onset of persister cells during the attachment of bacteria to implant surfaces.

This 2008 special issue “Focus on Implant Infections”, presents new strategies for combating biofilm infections, such as the use of staphylococcal quorum-sensing inhibitors or the “bioelectric effect”: the phenomenon by which electric current can enhance the activity of some antimicrobial agents against bacteria in biofilms. (Int J Artif Organs 2008; 31: 749–51)
Bioelectric Effect and Bacterial Biofilms. a Systematic Review
Authors: Del Pozo J. L. , Rouse M. S. , Patel R.
Published: January 2018

Bacteria growing in biofilms cause a wide range of human infections. Biofilm bacteria are resistant to antimicrobics at levels 500 to 5,000 times higher than those needed to kill non-biofilm bacteria. In vitro experiments have shown that electric current can enhance the activity of some antimicrobial agents against certain bacteria in biofilms; this has been termed the “bioelectric effect”. Direct electrical current has already been safely used in humans for fracture healing. Application of direct electric current with antimicrobial chemotherapy in humans could theoretically abrogate the need to remove the device in device-related infections, a procedure associated with substantial morbidity and cost. In this article, we review what has been described in the literature with regards to the bioelectric effect. (Int J Artif Organs 2008; 31: 786–95)
The Extracellular Polymer Substance of Pseudomonas Aeruginosa: Too slippery for Neutrophils to Migrate On?
Authors: HÄnsch G. M. , Brenner-Weiss G. , Prior B. , Wagner C. , Obst U.
Published: January 2018

Purpose

Biofilm formation is increasingly recognized as the cause of persistent infections and there is evidence that P. aeruginosa organized into biofilms are quite resistant toward host defence mechanisms, particularly against an attack by polymorphonuclear neutrophils (PMN). Apparently, the migration of PMN through the biofilms is impaired, and thus the bactericidal activity remains highly localized. The aim of this study was to directly investigate the interaction of PMN with the biofilm and the extracted extracellular polymeric substance (EPS) of P. aeruginosa.

Material and Methods

Chemotaxis and random migration of PMN through P. aeruginosa biofilms was tested, as was their migration through and along the EPS.

Results

We found that the EPS and mature biofilms, but not immature or developing ones, reduced the chemotactic migration of PMN. On EPS, rather than immobilize the cells, their random, spontaneous migration was enhanced.

Conclusion

We propose that on EPS, the PMN lose their capacity to sense the direction and just slide over the EPS in a disoriented manner. (Int J Artif Organs 2008; 31: 796–803)
Prevention of Infections Associated with Vascular Catheters
Authors: Darouiche R. O.
Published: January 2018

The expanding use of vascular catheters has increased the need to prevent hazardous infectious complications. Since bloodstream infection is the most common serious complication of indwelling vascular catheters, the proof that a potentially preventive approach is truly protective against clinical infection requires a significant reduction in the incidence of this infectious complication. Although catheter colonization is a prelude to infection, most colonized catheters do not result in catheter-related infection and, therefore, a mere reduction in catheter colonization does not, in and by itself, confirm protection against clinical infection. Adherence to optimal infection control guidelines is the primary measure for preventing infection, but in most instances the level of adherence to guidelines drops subsequent to the initial surge that follows the institutional adoption of educational programs. This explains the need to assess the potential clinical protection afforded by anti-infective technologies. In addition to improving patient care, a clinically protective anti-infective approach can also bring tremendous cost savings. (Int J Artif Organs 2008; 31: 810–19)
Catheter-Related Bacteremia in Hemodialysis Patients: The Role of the Central Venous Catheter in Prevention and Therapy
Authors: Troidle L. , Finkelstein F. O.
Published: January 2018

Infections are a leading cause of morbidity and mortality in patients with end-stage renal disease. Infections in hemodialysis patients are strongly associated with the use of an indwelling central venous catheter. S. aureus, coagulase-negative staphylococci and Gram-negative rods account for the majority of these infections. The outcome of catheter-related bacteremia depends on appropriate antibiotic therapy and management of the hemodialysis catheter. Most studies note that there is no difference in outcome if the catheter is changed over a guidewire in addition to antibiotic therapy or if the catheter is completely removed and reinserted at a later date. However, bacteremia with certain organisms, particularly S. aureus, is associated with complications. Thus, the data suggests that the catheter needs to be promptly removed in patients developing S. aureus bacteremia. Bacterial biofilm likely has a critical role in the pathogenesis of these infections. Numerous in vitro and in vivo studies have demonstrated both a reduction in infection rate with the use of antibiotic catheter locks as well as a reduction in the production of or eradication of bacterial biofilm. Future studies ought to target, firstly, a reduction in the reliance on central venous catheters; and secondly, the formulation of practical strategies to reduce patient risk for developing catheter-related bacteremia. (Int J Artif Organs 2008; 31: 827–33)
Effects of Coupled Plasma Filtration Adsorption on Immune Function of Patients with Multiple Organ Dysfunction Syndrome
Authors: Mao H.-J. , Yu S. , Yu X.-B. , Zhang B. , Zhang L. , Xu X.-R. , Wang X.-Y. , Xing C.-Y.
Published: January 2018

Objective

To investigate the effects of coupled plasma filtration adsorption (CPFA) on the immune function of patients with multiple organ dysfunction syndrome (MODS).

Methods

This study was a prospective, pilot, before-and-after self-crossover, clinical trial. Seven patients diagnosed with MODS and severe infection were randomly allocated to both 10 hours of CPFA and 10 hours of high-volume hemofiltration (HVHF) with a 12-hour interval and in random order. Serum concentrations of 7 cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1Ra), and soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) were measured during each treatment. The HLA-DR expression by the blood monocytes and the TNF-α production by the patients’ blood (both spontaneous and lipopolysaccharide stimulated) were tested before and after the treatment. TNF-α production of normal human monocytes (THP-1 cells) incubated in vitro with the patient plasma was also measured.

Results

During CPFA, the fall in serum TNF-α and rise in serum IL-1Ra coincided with the rise in ratios of sTNFR2/TNF-α and IL-1Ra/IL-1β (p<0.05), which were different from those seen within HVHF (p<0.05). HLA-DR expression increased after CPFA (84.32% ± 4.63% vs. 73.65% ± 11.52%, p=0.037), but there was no change after HVHF (p>0.05). Spontaneous and lipopolysaccharide-induced TNF-α production increased over time with CPFA (p=0.038, p=0.034, respectively), but did not change with HVHF (p>0.05). Patient plasma suppressed the production of TNF-α by cultured normal monocytes. This effect decreased over time with CPFA (p=0.041), but there was no effect with HVHF (p>0.05).

Conclusions

CPFA was superior to HVHF in increasing the ratios of antiinflammatory to proinflammatory mediators, improving antigen presentation ability, and restoring leukocyte responsiveness. These findings suggest a potential role for CPFA in the treatment of MODS.
Pathogenesis of Secondary Hyperparathyroidism
Authors: Cozzolino Mario , Pasho Sabina , Fallabrino Giuditta , Olivi Laura , Gallieni Maurizio , Brancaccio Diego
Published: January 2018

Chronic renal failure is the primary cause of secondary hyperparathyroidism (SHPT). Patients with mineral metabolism disorders commonly present with low serum calcium levels, hyperphosphatemia, and calcitriol deficiency. In normal renal function subjects, parathyroid cells have a low turnover and rarely undergo mitoses. In uremic conditions, however, parathyroid glands become hyperplasic and leave quiescence. During the last ten years, new molecular mechanisms have been investigated to better understand the pathogenesis of SHPT: the emerging role of the Calcium Sensing Receptor (CaSR); the importance of the parathyroid expression of the Vitamin D receptor (VDR); the growing evidence on the central role of the Fibroblast Growth Factor 23 (FGF-23). In contrast, the discovery of a parathyroid phosphate sensor or receptor has yet to be made.
New Aliphatic Glycerophosphoryl-Containing Polyurethanes: Synthesis, Platelet Adhesion and Elution Cytotoxicity Studies
Authors: Acetti Daniela , D'arrigo Paola , Giordano Carmen , Macchi Piero , Servi Stefano , Tessaro Davide
Published: January 2018

In this study new poly(ether)urethanes (PEUs) based on aliphatic diisocyanates were synthesized with phospholipid-like residues as chain extenders. The primary objective was to prepare new polyurethanes from diisocyanates that are less toxic than the aromatic ones widely used in medical-grade polyurethanes, in order to investigate the effect of the different aromatic or aliphatic hard segment content on the final properties of the materials. Some glycerophospho residues were simultaneously introduced to enhance the hemocompatibility of these materials. Polymers were prepared by a conventional two-step solution polymerization procedure using hexamethylene diisocyanate (HDI) and dodecametilendiisocyanate (DDI) and poly(1,4-butanediol) with molecular weight 1000 to form prepolymers, which were subsequently polymerized with 1-glycerophosphorylcholine (1-GPC) or glycerophosphorylserine (GPS) to act as chain extenders. The reference polymers bearing 1,4-butandiol (BD) were also synthesized. The polymers obtained were characterized by Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (1H NMR), and differential scanning calorimetry (DSC). The hemocompatibility of synthesized segmented polyurethanes was preliminarily investigated by platelet-rich plasma contact studies and related scanning electron microscopy (SEM) photographs as well as by cell viability assay after cell exposure to material elutions to assess the effect of any toxic leachables coming out from the samples. Two of the polymers gave interesting results, suggesting the desirability of further investigation into their possible use in biomedical devices.
Preventive Effect of α-Tocopherol and Glycyrrhizin against Platelet-Neutrophil Complex Formation Induced by Hemodialysis Membranes
Authors: Takeshita Kana , Susuki Chie , Itoh Saotomo , Tsuji Tsutomu
Published: January 2018

Background

The intradialytic activation of leukocytes is a major cause of hemodialysis (HD)-associated complications. Contact between blood and HD membranes frequently induces the formation of microaggregates composed of activated platelets and leukocytes, causing leukocyte activation that includes the generation of reactive oxygen species (ROS). This complex formation is mediated primarily by the interaction between P-selectin on activated platelets and its counter-ligands on leukocytes.

Objective

We examined the preventive effects of α-tocopherol and glycyrrhizin in vitro against platelet-neutrophil microaggregate formation and neutrophil ROS production induced by HD membranes.

Methods and Results

Microaggregate formation induced by the incubation of heparinized whole blood with polysulfone (PS) HD membranes was effectively inhibited by α-tocopherol and glycyrrhizin. α-Tocopherol, but not glycyrrhizin, was found to inhibit PS membrane-induced P-selectin expression on the platelet surface; however, glycyrrhizin did inhibit both the formation of neutrophil-platelet microaggregates induced by adenosine diphosphate (ADP) and the adhesion of HL60 leukemic cells to P-selectin-expressing Chinese hamster ovary (CHO) cells, suggesting that glycyrrhizin acts as a competitive inhibitor of P-selectin-mediated cell adhesion. Finally, these compounds almost completely abrogated PS membrane-induced and platelet-dependent ROS production by neutrophils.

Conclusions

These results suggest that α-tocopherol and glycyrrhizin may function as preventive agents of HD-associated leukocyte activation though the modulation of platelet-leukocyte interaction.
Dynamic Modeling and Identification of an Axial Flow Ventricular Assist Device
Authors: Moscato Francesco , Danieli Guido A. , Schima Heinrich
Published: January 2018

An accurate characterization of the hemodynamic behavior of ventricular assist devices (VADs) is of paramount importance for proper modeling of the heart-pump interaction and the validation of control strategies. This paper describes an advanced test bench, which is able to generate complex hydraulic loads, and a procedure to characterize rotary blood pump performance in a pulsatile environment. Special focus was laid on model parameter identifiability in the frequency domain and the correlation between dynamic and steady-state models.

Twelve combinations of different flow/head/speed signals, which covered the clinical VAD working conditions, were generated for the pump characterization. Root mean square error (RMSE) between predicted and measured flow was used to evaluate the VAD model. The found parameters were then validated with broadband random signals.

In the experiments the optimization process always successfully converged. Even in the most demanding dynamic conditions the RMSE was 7.4 ml/sec and the absolute error never exceeded 24.9 ml/sec. Validity ranges for the identified VAD model were: flow 0–180 ml/sec; head 0–120 mmHg; speed 7.5–12.5 krpm.

In conclusion, a universal test bench and a characterization procedure to describe the hydrodynamic properties of rotary blood pumps were established. For a particular pump, a reliable mathematical model was identified that correctly reproduced the relationship between instantaneous VAD flow, head and impeller speed.
Ovine Models for Chronic Heart Failure
Authors: Geens Jefh , Trenson Sander , Rega Filip R. , Verbeken Erik K. , Meyns Bart P.
Published: January 2018

Purpose

Testing and optimizing of surgical therapies for chronic heart failure (CHF) requires large animal models. CHF has been induced in several large animal species. Sheep have modest body mass increase and demonstrate docile behavior and are therefore a preferred species in research on surgical therapies for CHF.

Methods

A literature search for existing ovine CHF models was performed, using search terms “sheep” and “heart failure”. Relevant secondary references were traced.

Results

Rapid ventricular pacing produces rapid-onset CHF. Its severity ranges from moderate left ventricular failure to severe biventricular failure, depending on length and frequency of pacing. Its counterpart in human CHF is tachycardia-induced HF, since it is reversible upon cessation of pacing. Myocardial damage models include CHF induced by cardiototoxic drugs and ischemia. Ischemia-based models include coronary microembolization, occlusion and ischemia/reperfusion models. The microembolization model is relevant to diabetic cardiomyopathy. Coronary occlusion models exhibit variable functional impairment, some with aneurysm formation, and some with mitral valve regurgitation, depending on occlusion localization. They are relevant to CHF following non-reperfused myocardial infarction. Coronary occlusion/reperfusion models are relevant to the occurrence of human CHF despite coronary artery recanalization. Pressure overload of left and right ventricle is induced by aortic and pulmonary artery banding, respectively. Hypertrophy precedes CHF, as in patients with valve stenosis and hypertension. Volume overload is induced by valve damage or shunt creation. Atrioventricular valve regurgitation is the most important clinical counterpart.

Conclusion

Several ovine CHF models exist. Since they exhibit important cardiac pathology differences, the choice of model should be based on the specific experimental question.
Heterotypic Cell-Cell Interaction on Micropatterned Surfaces
Authors: Lamponi Stefania , Canio Clara Dl , Barbucci Rolando
Published: January 2018

Purpose

The aim of this paper was to study the influence of chemical and topographical signals on cell behavior and to obtain a heterotypic cell-cell interaction on microstructured domains.

Methods

The polysaccharide hyaluronic acid (Hyal) was photoimmobilized on glass surfaces in order to obtain a pattern with squares and rectangles of different dimensions and chemistry. The microstructured surfaces were characterized by Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). The behavior of Human Coronary Artery Endothelial Cells (HCAEC) and human tumoral dermal fibroblasts (C54) was investigated on these micropatterned surfaces by adhesion studies. Moreover, heterotypic interaction among C54 and HCAEC adherent on patterned surfaces was evaluated by time-lapse video microscopy.

Results

Surface analysis revealed the presence of a pattern consisting of alternating glass and Hyal microstructures whose dimensions decreased from the center to the edge of the sample. Neither HCAEC nor C54 adhered to the immobilized Hyal but both adapted their shape to the different sizes of the glass squares and rectangles. The number of adherent cells depended on the dimensions of both the glass domains and the nuclei of the cells. Co-cultured C54 on HCAEC patterned surfaces showed a heterotypic cell-cell interaction in the same chemical and topographic domain.

Conclusions

A heterotypic cell-cell interaction occurred in the same chemical and topographic micro-domains but in narrow areas only. Moreover, the number of cells adhering to the glass domains and cell morphology depended on the dimensions of both adhesive areas and cell nuclei.
Suicide and Fratricide in Bacterial Biofilms
Authors: Thomas Vinai Chittezham , Hancock Lynn E.
Published: January 2018

Bacterial autolysis has recently been identified as a key mechanism that regulates different phases of biofilm development including microcolony formation and dispersal. However such autolytic measures are limited to a subfraction of cells within the entire biofilm population. Here we speculate on the role biofilm heterogeneity plays in limiting autolysis within biofilms and further describe the molecular regulation of suicidal and fratricidal mechanisms in biofilm development of Staphylococcus aureus and Enterococcus faecalis.