bluuebunny/crossref_metadata_2025 huggingface dataset:
Biophysical Studies on the Correction of Uremic Human Serum Albumin Binding Defects by In Vitro Charcoal Adsorption Treatment
Authors: Nikolaev V. , Sarnatskaya V. , von Appen K. , Ivanov A. , Rotellar E. , Haspar M. , Klinkmann H.
Published: November 2008

Abstract:Spectrofluorimetry, flow microcalorimetry, and differential scanning microcalorimetry (DSMC) were used to study the conformation, binding function, and ligand loading of uremic albumin obtained from the blood plasma of 2 end‐stage renal disease (ESRD) patients before and after charcoal plasma treatment at different pH values (3.0–9.0). The spectrofluorimetric patterns of conformational N‐F transition at low pH (4.2–3.5) are practically identical for both samples of uremic human serum albumin (HSA) and control HSA from healthy donors. After the charcoal treatment at pH 3.0 and 4.0, the enthalpies of complexing on uremic HSA with bromsulfa‐lein and sodium dodecylsulfate approach that of donor HSA. The binding affinity of uremic HSA for sodium octanoate, phenol red, and salicylic acid following low pH charcoal treatment even exceed those of donor HSA.

At the same time the charcoal treatment of uremic plasma at neutral and alkaline pH does not notably improve the binding characteristics of isolated HSA. Adsorption at low pH values completely restores the tryptophan fluorescence spectrum position of uremic albumin and improves the thermodynamic characteristics of its melting process. Using DSMC data, it can nevertheless be concluded that some conformational changes or a certain amount of high‐affinity bound endogenous ligands still remain after low pH uremic HSA purification. The latter conclusion requires additional improvements of adsorption treatment of uremic plasma.
Ex Vivo Phase 1 Evaluation of the DeBakey/NASA Axial Flow Ventricular Assist Device
Authors: Kawahito Koji , Damm George , Benkowski Robert , Aber Gregory , Bacak James , Tasai Kimitaka , Shimono Takatsugu , Takatani Setsuo , Nosé Yukihiko , Noon George P. , DeBakey Michael E.
Published: November 2008

Abstract: A small ventricular assist device intended for long‐term implantation has been developed by a cooperative effort between the Baylor College of Medicine and the NASA/Johnson Space Center. To date, in vitro tests have been performed to address hemolysis and pump performance issues. In this Phase 1 study, we assessed the durability and atraumatic features aiming for 2 day implantation. Eight pumps were implanted in 2 calves as paracorporeal left ventricular assist devices. The pump running times ranged from 18 to 203 h (78.1 ± 23.7; mean ± SEM). All the pump implantations were terminated because of thrombus formation. Plasma‐free hemoglobin levels were below 13.7 mg/dl, except for 1 case complicated by inflow cannula obstruction. The pump speed was maintained between 10,100 and 11,400 rpm. Pump outputs were from 3.6 to 5.2 L/min. The electrical power required by the system ranged between 9 and 12 W. Clinically there was no detectable organ dysfunction noted, and postmortem evaluation demonstrated no pump related adverse effects in either calf except for small kidney infarctions. Thrombus deposition was observed mainly at the hub portions and the flow straightener.
A Physical Analog of the Failing Left Ventricle for In Vitro Studies of Mechanical Wall Actuation
Authors: Melvin David B. , Schima Heinz , Losert Udo M. , Stohr Hans , Siegl Helga , Huber Leopold , Glos David L. , Wolner Ernst
Published: November 2008

Abstract: Mechanical repowering of a failing heart with devices or skeletal muscle could circumvent blood‐pump lining problems. Requirements are complex: indefinite support with preservation of valve competence and coronary flow, avoidance of wall coaptation, and allowance of both rapid low impedance refilling and independent left and right pressures. An accurate in vitro physical failing‐heart analog could facilitate the choice and screening of surgical and engineering approaches in mock circulation experiments. Prosthetic models, transplant recipient hearts, normal animal hearts, existing in vivo animal failure models, and failing cadaver hearts all have serious limitations. One hundred and four excised porcine hearts were dilated and fixed by three iterative protocols. Geometric and passive mechanical parameters were assessed and compared with targets expected for an end‐stage failing heart. For Protocol 3, Subgroup 2 (reinforcing valve support, dilatation by compliant ventricular balloon, and ethyl alcohol fixation), the left ventricular shape and capacity (ellipsoid, 201–377 ml/500 g of heart weight), passive valve function, wall flexural rigidity (Et3 range 0.101‐0.331 Nm), and refilling mechanics (99 ± 17.46 ml during 200–400 ms at ≤ 10 mm Hg transmural gradient) were all within goal criteria.
The Effect of the Impeller‐Driver Magnetic Coupling Distance on Hemolysis in a Compact Centrifugal Pump
Authors: Nakazawa Tadashi , Makinouchi Kenzo , Takami Yoshiyuki , Glueck Julie , Takatani Setsuo , Nosé Yukihiko
Published: November 2008

Abstract: Blood trauma is one of the important performance parameters of centrifugal pumps. To investigate the blood trauma induced by these pumps, in vitro hemolysis tests have become an important procedure and are increasingly used for pump development and comparisons. The Baylor compact eccentric inlet port (C1E) centrifugal blood pump was developed as a long‐term centrifugal ventricular assist device (VAD) as well as a cardiopulmonary bypass pump (CPB). The Baylor C1E pump incorporates a seal‐less design with a blood stagnation‐free structure. This pump can provide flows of 5 L/min against 350 mm Hg of total pressure head at 2,600 revolutions per minute. The pump impeller is magnetically coupled to the driver magnet in a seal‐less manner. The latest hemolysis study revealed that hemolysis may be affected by the gap distance between the driver and the impeller magnet. The purpose of this study was to verify the effect of the magnetic coupling distance on the normalized index of hemolysis (NIH) with the C1E model and to obtain an optimal gap distance. The NIH value was clearly decreased by alteration of the magnetic coupling distance from 7.7 to 9.7 mm in CPB and left ventricular assist device (LVAD) conditions. The NIH, when using the pump as an LVAD condition, was reduced to a level of 0.0056 from 0.095 when the magnetic coupling distance was extended. The same results were also obtained when the pumps were used in a CPB condition. The magnetic coupling distance is an important factor for the C1E model in terms of hemolysis. Different coupling forces effect the bearings and impeller stability. These results suggest that an optimal driving condition with a proper magnetic coupling and an optimal force between the impeller and driver is necessary to develop an atraumatic centrifugal pump.
Effect of an Acidic Pyruvate‐based Peritoneal Dialysis Solution on the pH of a Residual Peritoneal Dialysate Fluid
Authors: Ing T.S. , Yang M.L. , Yang V.L. , Wong F.K.M. , Cheng Y.L. , Guddeti S.R. , Yu at A.W.
Published: November 2008

Abstract: An acidic (pH 5.2) pyruvate‐based peritoneal dialysis solution or an equally acidic lactate‐based counterpart was added to a residual fluid (i.e., peritoneal effluent) obtained from each of 6 continuous ambulatory peritoneal dialysis patients. It was found that the residual fluids were able to raise the pH of the resultant residual fluid/peritoneal dialysis solution mixture to a higher level in the case of the pyruvate‐based solution than in the case of the lactate‐based one. Key Words: Acidic‐Pyruvate‐Lactate‐Peritoneal dialysis solution‐Residual fluid‐pH.
Low–Density Lipoprotein Hemoperfusion Using a Modified Polyacrylate Adsorber: In Vitro, Ex Vivo, and First Clinical Results
Authors: Bosch Thomas
Published: November 2008

Abstract: Current lipid apheresis techniques can remove low–density lipoprotein (LDL) cholesterol only from plasma, i.e., a primary cell–plasma separation step is mandatory. This article describes in vitro, ex vivo, and clinical results using a new LDL adsorber compatible with human whole blood. It consists of modified polyacrylate, the negative charges of which can interact with the positively charged protein B moiety of LDL, thus retaining these particles on the surface of the adsorber. After the efficacy and selectivity of LDL removal had been demonstrated in vitro and ex vivo, a clinical pilot study corroborated these results. Thus, treating 60 ml of blood per kilogram of body weight in a single session, LDL hemoperfusion reduced LDL cholesterol by 50%, lipoprotein (a) by 17%, and triglycerides by 19% in 6 hy–percholesterolemic patients. High–density lipoprotein cholesterol recovery amounted to 97%. In conclusion, LDL hemoperfusion holds great promise for the future.
Low–Density Lipoprotein Removal Methods by Membranes and Future Perspectives
Authors: Matsuda Yukihiro , Malchesky Paul S. , Nose Yukihiko
Published: November 2008

Abstract:Since the application by Thompson et al. in 1975 of plasma exchange for the treatment of 2 patients with familial hyperlipidemia, plasma purification techniques for selective low–density lipoprotein (LDL) removal (i.e., LDL apheresis) have been developed and adopted for the management of this disease. Thermofil–tration is one of the LDL apheresis systems that utilizes membrane techniques developed by Nose and Malchesky's group in 1985. This article reviews its rationale, in vitro studies, animal studies, and clinical investigation. Thermofiltration effectively and selectively removes LDL cholesterol while retaining in the plasma physiologically important macromolecules such as albumin and high–density lipoprotein (HDL) cholesterol. Based on the global view of the treatment of atherosclerosis by LDL apheresis, membrane techniques are as effective, safe, and simpler to apply than other methods. Additionally, these methods are effective for the removal of lipoprotein (a) and fibrinogen; thus, they can address the needs in these application areas.
Can We Develop a Nonpulsatile Permanent Rotary Blood Pump? Yes, We Can.
Authors: Nosé Yukihiko , Kawahito Koji , Nakazawa Tadashi
Published: November 2008

Abstract For many years, it was thought that nonpulsatile perfusion produced physiological and circulatory abnormalities. Since 1977, Yukihiko Nosé and his colleagues have challenged this misconception. Toward that end, they did show that if a 20% higher blood flow uses more than that required for a pulsatile blood pump, then there would be no circulatory or physiological abnormalities. These experimental findings confirm that there is no difference in clinical outcome using either a pulsatile or nonpulsatile blood pump. Furthermore, the nonpulsatile rotary blood pump demonstrates efficient and reliable performance in various clinical situations. The nonpulsatile blood pump is a simple and reliable design that is manufactured easily and that has several desirable features. There is no need to incorporate heart valves, which are the most thrombogenic and blood trauma‐inducing component. A continuous flow pump does not require a large orifice inflow conduit and proves to be easier to implant in patients with minimal damage to the myocardium. There is no need to incorporate a compliance volume‐shifting device, which is essential for a pulsatile blood pump. The nonpulsatile device is a continuous blood pumping system; therefore, the control system is simpler and more reliable than that of a pulsatile pump. Because of the rotary blood pump's structure, only one moving part is necessary for the blood‐pumping motion. By using durable components for this moving part, a durable system becomes possible. Because the electrical motor operates continuously, the on‐and‐off motion required for a pulsatile pump is not necessary; therefore, it is a more efficient and durable system. Thus, this group is working on the development of a nonpulsatile blood pump as a permanently implantable assist device. To achieve this goal, it is necessary to incorporate seven features into the system: small size, atraumatic features, antithrombogenic features, antiinfection features, a simple and durable design, and low energy requirement with easy controllability.
Can We Develop a Permanent Pulsatile Rotary Blood Pump? Yes, We Can.
Authors: Poirier Victor L.
Published: November 2008

Abstract Active U.S. participation in the development of artificial heart technology began in 1966 with the award of six contracts. Since that beginning, and continuing to this day, we have been asking the same question, “Can we develop a system to take the place of a natural heart?” There are four formidable barriers that must be overcome before success can be achieved: technological development (Can the system perform as designed?); economic challenges (Can we finance the development?); regulatory hurdles (Can we get it approved for general use?); and acceptance (Will it be used, and will society accept it for what it is?). After 30 years, all but the last barrier has been overcome.
Development of a Pivot Bearing Supported Sealless Centrifugal Pump for Ventricular Assist
Authors: Nakazawa Tadashi , Makinouchi Kenzo , Ohara Yasuhisa , Ohtsubo Satoshi , Kawahito Koji , Tasai Kimitaka , Shimono Takatugu , Benkowski Robert , Damm George , Takami Yoshiyuki , Glueck Julie , Noon George P. , Nosé Yukihiko
Published: November 2008

Abstract Since 1991, in our laboratory, a pivot bearing‐supported, sealless, centrifugal pump has been developed as an implantable ventricular assist device (VAD). For this application, the configuration of the total pump system should be relatively small. The C1E3 pump developed for this purpose was anatomically compatible with the small‐sized patient population. To evaluate an‐tithrombogenicity, ex vivo 2‐week screening studies were conducted instead of studies involving an intracorpore‐ally implanted VADs using calves. Five paracorporeal LVAD studies were performed using calves for longer than 2 weeks. The activated clotting time (ACT) was maintained at approximately 250 s using heparin. All of the devices demonstrated trouble‐free performances over 2 weeks. Among these 5 studies, 3 implantations were subjected to 1‐month system validation studies. There were no device‐induced thrombus formations inside the pump housing, and plasma‐free hemoglobin levels in calves were within the normal range throughout the experiment (35, 34, and 31 days). There were no incidents of system malfunction. Subsequently, the mass production model was fabricated and yielded a normalized index of hemolysis of 0.0014, which was comparable to that of clinically available pumps. The wear life of the impeller bearings was estimated at longer than 8 years. In the next series of in vivo studies, an implantable model of the C1E3 pump will be fabricated for longer term implantation. The pump‐actuator will be implanted inside the body; thus the design calls for substituting plastic for metallic parts.
Study of Secondary Flow in Centrifugal Blood Pumps Using a Flow Visualization Method with a High‐Speed Video Camera
Authors: Sakuma Ichiro , Fukui Yasuhiro , Dohi Takeyoshi
Published: November 2008

Abstract Four pump models with different vane configurations were evaluated with flow visualization techniques using a high‐speed video camera. These models also were evaluated through in vivo hemolysis tests using bovine blood. The impeller having the greatest fluid velocity relative to the impeller, the largest velocity variance, and the most irregular local flow patterns in the flow passage caused the most hemolysis. Even if the pumps were operated at almost the same speed (rpm) at the same output, the impeller showing more irregular flow patterns had a statistically greater rate of hemolysis. This fact confirms that the existence of local irregular flow patterns in a centrifugal blood pump deteriorates its hemolytic performance. Thus, to optimize the design of the pump, it is very important to examine the secondary flow patterns in the centrifugal blood pump in detail using flow visualization with a high‐speed video camera.
Estimating Mechanical Blood Trauma in a Centrifugal Blood Pump: Laser Doppler Anemometer Measurements of the Mean Velocity Field
Authors: Pinotti Marcos , Paone Nicola
Published: November 2008

Abstract A laser Doppler anemometer (LDA) was used to obtain the mean velocity and the Reynolds stress fields in the inner channels of a well‐known centrifugal vaneless pump (Bio‐pump). Effects of the excessive flow resistance against which an occlusive pump operates in some surgical situations, such as cardiopulmonary bypass, are illustrated. The velocity vector field obtained from LDA measurements reveals that the constraint‐forced vortex provides pumping action in a restricted area in the core of the pump. In such situations, recirculating zones dominate the flow and consequently increase the damage to blood cells and raise the risk of thrombus formation in the device. Reynolds normal and shear stress fields were obtained in the entry flow for the channel formed by two rotating cones to illustrate the effects of flow disturbances on the potential for blood cell damage.
Relationship Between Pump Speed Design and Hemolysis in an Axial Flow Blood Pump
Authors: Anai Hirofumi , Wakisaka Yoshinari , Nakatani Takeshi , Taenaka Yoshiyuki , Takano Hisateru , Hadama Tetsuo
Published: November 2008

Abstract

In an attempt to reduce the hemolysis caused by axial flow blood pumps, we investigated whether the specific speed should be kept within the standard engineering range or whether pump speed should be minimized, thus making the specific speed beyond the standard range. Four pumps with 11.8 mm diameter impellers were designed to accommodate a flow of 5 L/min and a head of 100 mm Hg. The pumps were tested at 4 speeds: A, 14,000; B, 18,000; C, 22,000; and D, 26,000 rpm. Pump performance data were obtained, and the maximum point of total pump efficiency was found for each pump. The maximum efficiencies were A, 50%; B, 58%; C, 52%; and D, 53%. The specific speed of each pump recorded at the maximum efficiency point was calculated as A, 899; B, 954; C, 1,218; and D, 1,951 rpm. Hemolytic tests were performed with fresh goat blood in a closed, mock‐loop circuit. Hemolytic indexes were A, 0.036; B, 0.22; C, 0.35; and D, 0.66. We have concluded that decreased hemolysis is correlated with a lower pump speed and that the specific speed for the lowest pump speed is less than the standard range. Having a specific speed outside the standard range was not correlated with reduced total pump efficiency.
Effects of Surface Roughness on Mechanical Hemolysis
Authors: Umezu Mitsuo , Yamada Takashi , Fujimasu Hiromi , Fujimoto Tetsuo , Ranawake Manoja , Nogawa Atsuhiko , Kijima Toshihiko
Published: November 2008

Abstract Previous in vitro hemolysis test results showed that an inlet taper or a round corner in the leading edge of a stenotic connector played an important role in the reduction of hemolysis. However, computational fluid dynamics (CFD) analysis of these results indicated that the shear rate and hemolysis level were not always related to each other. Then, further research was performed, focusing on the effects of surface roughness on hemolysis. The results thus far can be summarized as threefold. First, the rate of hemolysis occurring at an abrupt change in the stenotic section was different if the longitudinal length of the stenosis was changed. The level of plasma‐free hemoglobin after 6 h of circulation was decreased from 280 mg/dl to 70 mg/dl when the longitudinal length was shortened from 15 mm to 1 mm. Second, a comparison of hemolysis rates in identical stenotic connectors with differing surface roughness (Ra = 0.45 and 1.35 u.m) revealed that a smooth surface achieved as much as an 80% reduction in the rate of hemolysis. Third, the in vitro hemolysis results obtained were further defined through CFD analysis.
Controller for an Axial Flow Blood Pump
Authors: Konishi Hiroaki , Antaki James F. , Amin Devin V. , Boston J.R. , Kerrigan John P. , Mandarino William A. , Litwak Philip , Yamazaki Kenji , Macha Mahender , Butler Kenneth C. , Borovetz Harvey S. , Kormos Robert L.
Published: November 2008

Abstract: A rotary blood pump inherently provides only one noninvasive “observable‘” parameter (motor current) and allows for only one “controllable” parameter (pump speed). To maintain the systemic circulation properly, the pump speed must be controlled to sustain appropriate outlet Hows and perfusion pressure while preventing pulmonary damage caused by extremes in preload. Steady‐state data were collected at repeated intervals during chronic trials of the Nimbus AxiPump (Nimbus, Inc., Rancho Cordova, California, U.S.A.) in sheep (n = 7) and calves (n = 12). For each data set, the pump speed was increased at increments of 500 rpm until left ventricular and left atrial emptying was observed by left atrial pressure diminishing to zero. The effect of decreasing preload was evaluated perioperatively by inferior vena cava occlusion at a constant pump speed. Fourier analysis established a relationship between changes in the pump preload and the power spectra of the pump current waveform. Based on these results, a control method was devised to avoid ventricular collapse and maintain the preload within a physiologic range. The objective of this controller is the minimization of the second and third harmonic of the periodic current waveform. This method is intended to provide a noninvasive regulation of the pump by eliminating the need for extraneous transducers.
Coronary Microcirculation During Left Heart Bypass with a Centrifugal Pump
Authors: Hata Mitsumasa , Shiono M. , Orime Y. , Nakata K. , Sezai A. , Yamada H. , Saito T. , Sezai Y.
Published: November 2008

Abstract: To estimate coronary microcirculation during left heart bypass (LHB), we performed an experimental comparison study of LHB and intraaortic balloon pumping (1ABP). LHB was performed with a BioMedicus BP‐80 pump supporting half of the flow of cardiac output whereas the IABP was pumped in a 1:1 mode for cardiogenic shock in a swine model. Coronary circulations were analyzed by electromagnetic flowmeter, pulsed Doppler velocimeter, and laser Doppler flowmeter. Left ventricular end‐diastolic pressure (LVEDP) was reduced significantly by LHB. Although there was no significant difference in epicardial flow between the LHB and IABP groups, endocardial flow was increased significantly by LHB. In the LHB group, the systolic reverse wave of the coronary velocity called a myocardial invalid circulation was reduced remarkably. There was a significant inverse correlation between endocardial flow and LVEDP. These results suggested that LHB was more effective for myocardial microcirculation than was IABP.
Clinical Comparative Study of Cardiopulmonary Bypass with Nikkiso and BioMedicus Centrifugal Pumps
Authors: Ohtsubo Satoshi , Tayama Eiki , Short David , Noon George P. , Nose Yukihiko
Published: November 2008

Abstract: The Nikkiso centrifugal pump was evaluated in elective adult open heard surgery in comparison with the BioMedicus pump. Ten patients using the Nikkiso pump (Group N), and 10 patients using the BioMedicus pump (Group B) were examined for (or to determine) hemato‐biologic parameters and patient outcome data as well as pump controllability. During cardiopulmonary bypass (CPB), both pumps maintained systemic perfusion satisfactorily without any mechanical adverse event. Rotation speed of the Nikkiso centrifugal pump (3,580 ± 100 rpm) was significantly higher than that of the BioMedicus pump (3,170 ± 100 rpm; p < 0.05) whereas changes in free plasma hemoglobin, platelet count, blood urea nitrogen, and creatinine levels showed no significant differences between the two groups. Urine output in Group N for 30 min after the initiation of CPB (7.10 ± 1.50 ml/kg/h) was significantly higher than that in Group B (3.23 ± 0.46 ml/kg/h; p < 0.05). Patient outcome data were similar in both groups, such as duration of intensive care unit stay, hospital stay, postoperative intubation time, amount of postoperative bleeding, and amount of blood transfused. These equivalent results with the BioMedicus pump suggested that the Nikkiso pump can be used in open heart surgery as a reliable and atraumatic CPB pump.
Experiences of Postcardiotomy Assist: Pneumatic Ventricular Assist Device or Venoarterial Bypass with Percutaneous Cardiopulmonary Support
Authors: Orime Yukihiko , Shindo Shoji , Shiono Motomi , Hata Hiroaki , Yagi Shinya , Tsukamoto Saeki , Okumura Haruhiko , Sezai Yukiyasu
Published: November 2008

Abstract: From October 1982 to the present, 16 patients have been supported by a pneumatic ventricular assist device (VAD). Since April 1990, we have introduced a venoarterial bypass (VAB) with percutaneous cardiopulmonary support (PCPS) system. This PCPS system was used in 12 patients. The long‐term survival rate of PCPS cases (41%) was much better than that of VAD cases (19%). The main cause of death in VAD cases was multiple organ failure (MOF). Although VAB was initiated more recently than VAD, the duration on support was longer in the VAD group than in the VAB group. Because of the longer support duration and the presence of many patients with MOF, coagulopathy deteriorated more readily in the VAD group than in the VAB group. In the case of postcardiotomy cardiopulmonary bypass weaning or low‐output syndrome (LOS), the VAB with PCPS system should be applied first under intraaortic balloon pumping assist because of its simplicity and low cost. Thereafter, VAD should be applied in cases refractory to VAB support.
Dilemma of Membrane Biocompatibility and Reuse
Authors: Klinkmann H. , Grassmann A. , Vienken J.
Published: November 2008

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.
The Significance of Adhesion Molecules in Nephrology
Authors: Burkhardt Klaus , Hillebrand Günther , Bösnecker Angela , Land Walter , Gurland Hans‐Jürgen
Published: November 2008

Abstract: Our knowledge of adhesion molecules has exploded over the last 5 years and has swamped most fields of medicine including nephrology. This is not surprising because adhesion molecules play a pivotal role in all aspects of cell to cell contact. Thus, they are involved in important issues, such as fetal development, in any kind of inflammatory or immune response including allograft rejection, as well as thrombus formation, and in tumor growth and metastasis (1–3). This short overview briefly reports some aspects of the biology of relevant adhesion molecules and their significance in inflammatory kidney diseases and in hemodialysis and renal allograft rejection. Finally, new therapeutic opportunities that arise by blocking adhesion molecule function are discussed.
Rifampicin Carrying Poly (D, L‐Lactide)/Poly(Ethylene Glycol) Microspheres: Loading and Release
Authors: Clelikkaya Erhan , DenkbasL Emir Baki , PisLkin Erhan
Published: November 2008

Abstract: The aim of this study is to prepare rifampicinloaded poly (d, l‐lactide)/poly(ethylene glycol) (PDLLA/PEG) copolymer microspheres as an injectable drug delivery system. PDLLA homopolymers with three different molecular weights (9,760, 14,540, and 23,050 daltons) were synthesized and then transesterified with PEG (with a molecular weight of approximately 3,300‐4,000 daltons). By changing the ratio of PEG to PDLLA, block copolymers with different chain structures were synthesized. PDLLA and PDLLA/PEG microspheres in the size range of 2–10 μm were prepared by a modified solvent evaporation technique with the use of methylene chloride as the solvent and methyl cellulose as the emulsifier within the aqueous dispersion medium. Rifampicin was loaded within the microspheres during particle formation. Effects of the solvent/polymer and drug/polymer ratios, PDLLA molecular weight, and PEG content on drug loading and release were investigated. High drug loadings up to 100 mg rifampicin/g polymer were achieved. Both size and drug loadings were decreased by an increase in the solvent/polymer ratio and PEG content and by a decrease in the drug/polymer ratio and PDLLA molecular weight. High release rates were observed in the first 5 days after which constant and slow release rates were noted. Drug release was decreased by a decrease in the solvent/polymer ratio and PEG content and by an increase in the drug/polymer ratio and PDLLA molecular weight.
Efficacy of the Chitosan Posttreatment in Calcification Prevention of the Glutaraldehyde‐Treated Porcine Aortic Noncoronary Cusp Implanted in the Right Ventricular Outflow Tract in Dogs
Authors: Kuribayashi Ryosei , Chanda Jyotirmay , Abe Tadaaki
Published: November 2008

Abstract: Calcific tissue failure results in poor performance of the bioprosthetic heart valve. Chitosan post‐treatment has been shown to be effective in calcification prevention of the glutaraldehyde‐treated bovine pericardium when implanted subdermally in rats for 12 weeks. The present study investigated the effectiveness of the chitosan posttreatment in prevention of calcification of the glutaraldehyde‐treated porcine aortic noncoronary cusp 5 months after implantation in the right ventricular outflow tract (RVOT) in mongrel dogs. Either 0.625% glutaraldehyde‐treated (Group 1, n = 6) or glutaralde‐hyde‐chitosan‐treated (Group 2, n = 6) porcine aortic noncoronary cusp with the aortic wall was sewn to the RVOT. Gross histological observations showed moderate calcification of the glutaraldehyde‐treated cusps, but no calcification was noticed in the glutaraldehyde‐chitosan‐treated grafts at 5 months. This was confirmed by results of quantitative analyses for calcium in half of each ex‐planted cusp with aortic wall. The calcium content of the 0.625% glutaraldehyde‐treated cusps (Ca, 40.6 ± 24.9 mg/g dry wt) was significantly (p < 0.01) higher than that of glutaraldehyde‐chitosan‐treated cusps (Ca, 1.3 ± 0.29 mg/g dry wt). These findings suggest that chitosan post‐treatment is effective in complete calcium mitigation of the glutaraldehyde‐treated porcine aortic noncoronary cusps implanted in the RVOT in dogs.
Changes in Platelet, Granulocyte, and Complement Activation During Cardiopulmonary Bypass Using Heparin‐coated Equipment
Authors: Fukutomi Masaaki , Kobayashi Shuichi , Niwaya Kazuo , Hamada Yoshihiro , Kitamura Soichiro
Published: November 2008

Abstract: The effects of heparin‐coated cardiopulmonary bypass (CPB) systems on platelet, granulocyte, and complement activation were investigated during cardiopulmonary bypass. Thirty patients underwent coronary artery bypass surgery with a heparin‐coated (Carmeda Bio‐Active Surface, CBAS, Medtronic, U.S.A.) CPB system (HC group, n = 10), a heparin‐coated oxygenator and uncoated CPB circuit (HO group, n = 10), or an uncoated system (UC group, n = 10). In the HO group, plasma C3a (1667 ± 632 ng/ml) and C4a (1088 ± 319 ng/ml) concentrations were significantly (p < 0.05) lower than in the UC group (2846 ± 1045 ng/ml and 1494 ± 480 ng/ml, respectively) 10 min after the administration of protamine, but there were no significant differences in the platelet or granulocyte counts. In the HC group, granulocyte elastase concentrations 120 min after the onset of CPB (365 ± 177 μg/L) and 10 min after the administration of protamine (676 ± 314 μg/L) were significantly (p < 0.05) lower than in the other 2 groups (820 ± 341 and 893 ± 303 μg/L and 1365 ± 595 and 1,258 ± 622 μg/L). In addition, the increase in the plasma C3a concentration in the HC group 60 (p < 0.05) and 120 min after the onset of CPB (p < 0.05) was significantly less than in the other 2 groups. The C3a and C4a concentrations 10 min after the administration of protamine were significantly (p < 0.005 and p < 0.05) less in the HC group than in the UC group. Platelet counts 10 min after the administration of protamine were significantly higher (p < 0.05) and plasma β‐throm‐boglobulin concentrations during CPB were significantly lower in the HC group than in the other 2 groups 5 (p < 0.05), 60, and 120 min (p < 0.005) after the onset of CPB. Postoperative blood loss during the first 12 h in the HC group was significantly (p < 0.05) less than that in the UC group. The heparin‐coated oxygenator and uncoated CPB circuit reduced complement activation but demonstrated no significant effects on the platelet and granulocyte systems. However, the heparin‐coated CPB circuit (with all components making blood contact) reduced platelet, granulocyte, and complement activation and significantly reduced postoperative blood loss. Therefore, heparin coating of CPB systems improves biocompatibility.
Extracting 1/f Fluctuation from the Arterial Blood Pressure of an Artificial Heart
Authors: Yambe Tomoyuki , Nanka Shun‐suke , Naganuma Shigeru , Kobayashi Shin‐ichi , Nitta Shin‐ichi , Fukuju Takeo , Miura Makoto , Uchida Naoki , Tabayashi Kouichi , Tanaka Akira , Takayasu Misako , Abe Kenichi , Takayasu Hideki , Yoshizawa Makoto , Takeda Hiroshi
Published: November 2008

Abstract: We have studied the fluctuations of an artificial circulation for the analysis of the physiological aspects; however, the conventionally used fast Fourier transform (FFT) method cannot separate harmonic oscillations, such as respiratory and Mayer waves, from the 1/f fluctuation, which has been thought to represent underlying fractal dynamics. Fractal structure was shown in the strange attractor with chaotic dynamics, which is thought to be a flexible and intelligent system. In this study, the coarse‐graining spectral analyzing (CGSA) method was utilized to quantitatively evaluate the proportion of the 1/f fluctuation in the total power in the frequency domain and to analyze artificial circulation in the whole system. We implanted two pneumatically actuated ventricular assist devices as biventricular bypasses (BVBs) in chronic animal experiments using 4 healthy adult goats. To compare the natural and prosthetic circulation of each experimental animal, the BVB‐type complete prosthetic circulation model with electrically induced ventricular fibrillation was adopted. All hemodynamic parameters of natural and prosthetic circulation were recorded under awake conditions and calculated with the use of a personal computer. With the use of the CGSA method, time‐series data of the hemodynamics were analyzed and fractal percentages, extracting the 1/f fluctuation from a given time series, were calculated. Fractal percentages of the arterial blood pressure were 85.8 ± 10.7% and 82.0 ± 7.3% with natural and artificial circulation, respectively (not significant [NS]). 1/f fluctuation showed the characteristics of being fractal in a time series. The fractal structure showed robustness and error resistance in nonlinear dynamics. Therefore, our results suggest that the circulatory regulatory system of the artificial heart may have desirable characteristics such as error resistance.
Feasibility of an Air Motor‐Driven Centrifugal Blood‐Pumping System
Authors: Forbes Scott J. , Akula Jayaram , Smith William A.
Published: November 2008

Abstract: The use of cardiopulmonary bypass (CPB) is extending out of the cardiac surgery operating room into new venues. The long‐term goal of this project is the development of a completely disposable temporary‐use CPB system that could be economically distributed to all of the units where it might be needed. Centrifugal blood pumps have demonstrated successful and widespread use. However, they are not as widely available as might be desired because they require a large and expensive console. An inexpensive, small, lightweight, disposable unit, in contrast, could be widely distributed for emergency care of patients and would be logistically practical for patient transportation between the presenting institution and a major cardiac care facility equipped for definitive treatment. An air motor might be an approach to such a device. The current research project underway at the University of Akron in conjunction with the Cleveland Clinic Foundation has focused on the following key feasibility issues: air consumption, air motor noise, and sealing the rotating shaft. Prototypes have been constructed from commercially available vane and turbine motors. Early studies have demonstrated favorable results with regard to air consumption and shaft sealing and directions for handling air motor noise.
Bacterial Challenge of NISSHO Ultrafilter ETF 609: Results of In Vitro Testing
Authors: Krautzig S. , Lonnemann G. , Shaldon S. , Koch KM.
Published: November 2008

Abstract: In hemodialysis, a certain degree of bacterial contamination on the dialysate side is a regular finding. Concern has been growing that this contamination may lead to a chronic inflammatory response in the patient. Ultrafiltration of dialysate can be used to reduce bacterial content and levels of cytokine‐inducing substances upstream of the patient's dialyzer. The aim of this study was to test in vitro the rejection capacity of a polysulfone hollow‐fiber ultrafilter (ETF 609, NISSHO Co., Osaka, Japan) challenged with bacterial filtrates derived from Pseudomonus aeruginosa PA 103. Results showed a reduction of interleukin‐Iβ‐inducing activity (measured on peripheral blood mononuclear cells) from 5,035 ± 394 pg/ml prefilter to nondetectable levels postfilter and endotoxin levels (limulus amebocyte lysate assay) of 4,167 ± 1,079 versus 12 ± 2 pg/ml, respectively. In conclusion, ultrafiltration of dialysate with the polysulfone ultrafilter ETF 609 leads to a potent reduction of cytokine‐inducing activity.
The Human Genome Efforts and the cDNA Project
Authors: Matsubara Kenichi
Published: November 2008

Abstract: Molecular biology has been moving swiftly toward clarifying the entire genome of organisms, including human. The human genome efforts that promote this transaction are characterized by the large‐scale, high throughput production of data about the structure of the genome of the molecular level and its computer‐assisted management. In addition, functional analyses of the genome have become important for decoding the entire genetic information carried in the human genome. In the functional analyses of the genome, the large‐scale collection of partial cDNA sequences, the cDNA project, is becoming important, because it allows researchers to register genes active in any given tissue, on one hand, and, on the other hand, it allows for quantitative description of gene activities in tissues. Tissue‐specific or stage‐specific genes can be discovered by comparing expression profiles from different tissues or from a tissue at different stages of development, respectively.
Selective Immunomodulation: Utilization of CD29/VLA Molecules
Authors: Morimoto Chikao , Sato Toshiya , Tachibana Kouichi
Published: November 2008

Abstract: Accumulating evidence suggests that the VLA/ CD29 molecule plays an important role in T‐cell costim‐ulation, and CD4 + CD29/VLA + memory T cells play a key role in induction of CD8 killer effector T cells which are considered to be a major population involved in graft rejection. To target limited elements of the T‐lymphocyte population, we have described the preparation of a bi‐specific antibody‐toxin conjugate designed to target CD4 + CD29 + memory T cells. We also showed that the solid‐phase crosslinking of VLA‐4 by the antibody against this molecule or by its ligand, the CS‐1 region of fibronectin, stimulates tyrosine phosphorylation of 140, 120‐105, 80‐70, 60‐55, 50, and 45 kilodalton proteins. In addition, we identified the ppl40 protein as PLCγ, ppl20 protein as ppl25FAK, pp70 and pp50 proteins as paxillin, and pp60‐55 proteins as pp59fyn and pp56lck, and pp45 as MAP kinase, respectively. Moreover, we demonstrated that ppl25FAK is directly associated with paxillin. The paxillin binding domain of ppl25FAK is homologous to the paxillin binding domain of vinculin. Mutations in the conserved amino acid residues between ppl25FAK and vinculin result in the loss of paxillin‐binding activity. Because VLA/CD29 is preferentially expressed on CD4 memory T cells, the above described system will be used to develop a novel drug design for providing selective immunosuppression useful for organ transplantation. Key Words: Immunomodulation–Graft rejection– Transplantation.
Non‐Major Histocompatibility Complex Antigen Class I‐Regulatory Molecule for Cytotoxicity by Natural Killer Cells
Authors: Kamiguchi Kenjiro , Takashima Satoru , Tamura Yasuaki , Cho Joon Moon , Torigoe Toshihiko , Takahashi Shuji , Sato Noriyuki , Kikuchi Kokichi
Published: November 2008

Abstract: The mechanism of the cytotoxicity by natural killer (NK) cells is not known. It is speculated that there exist several positively regulated and negatively regulated target molecules expressed on the target cell surface. Although one of the latter is considered to be major histocompatibility complex antigen (MHC) class I, in this study we described a novel non‐MHC class 1 molecule that may negatively regulate the NK cytotoxicity. This antigen is defined by monoclonal antibody Cho‐1 and is composed of noncovalently associated antigens that are 40 and 200 kilodaltons in molecular size. The expression of this antigen is reduced along with the cell growth induced by growth factors and/or oncogenes. Thus, Cho‐1‐defined antigen appears to be involved as one of the resistant molecules in the cytotoxic mechanism of NK cells.
Human Peripheral Blood Lymphocyte‐Reconstituted, Severe Combined Immunodeficient Mice as a Model for Porcine Islet Xenograft Rejection in Humans
Authors: Shiroki Ryoichi , Nazirrudin Bashoo , Hoshinaga Kiyotaka , Naide Yorio , Scharp David W. , Mohanakumar T.
Published: November 2008

Abstract: Previously we established human peripheral blood lymphocyte‐reconstituted severe combined immunodeficiency (SCID) (hu‐PBL‐SCID) mice as a model for human islet allograft rejection. The function of xenografted hu‐PBL was confirmed to reject human allois‐lets in hu‐PBL‐SCID mice. In this study, we modified this model as a porcine islet xenograft to study porcine islet rejection in humans. Chimeric mice were used as the recipients of porcine islets to reveal the mechanisms of xenograft rejection in humans. SCID mice were reconstituted with 30 times 106 of hu‐PBL initially, and 10 times 106 of antihuman CD3‐primed PBL was injected intraperitoneally 2 days later as a booster. An additional booster injection provided greater possibility (86.7%, n = 15) of chimera establishment as well as a higher human immunoglobulin concentration in SCID mice than the single injection group. In an in vitro assay, sera from hu‐PBL‐SCID mice were found to recognize porcine islets by FACS staining. In an in vivo study, immunofluorescent analysis of a frozen section showed that human immunoglobulins adhered to the xenografted porcine islet under the kidney capsule of hu‐PBL‐SCID mice. Although no mouse immunoglobulins were detected on sections, mouse complement (C3) was shown to adhere to the xenografted porcine islet. Thus, hu‐PBL‐SCID mice provide a useful model for investigating the real‐life situation of porcine islet xenograft rejection in humans.
Selective Inhibition of Resistance to Hemopoietic Allografts But Not Rejection to a Natural Killer Cell Sensitive Tumor in Transgenic Mice for Granulocyte Colony Stimulating Factor
Authors: Kokai Yasuo , Kimura Hiromitsu , Matsuura Akihiro , Fujimoto Junichiro
Published: November 2008

Abstract: Transplanted allogeneic marrow grafts often fail to engraft in a lethally irradiated host. Resistance to hemopoietic allograft is a complexed phenomenon involving multiple components. To study the involvement of a hemopoietic cytokine, which was known to play a role for stem cell function, we established lines of mice that were transgenic for human granulocyte colony‐stimulating factor (hG‐CSF). Elevated and constitutive expression was found in sera (1,041 ± 242 pg/ml) of these transgenic mice regardless of their sexes and ages. Strong neutrophilic granulocytosis correlated with the elevated G‐CSF activity in transgenic mice but not in littermate controls, establishing a functional expression of this cytokine. In lethally irradiated mice transgenic for G‐CSF, infusion of fully allogeneic marrow cells induced donor‐derived spleen colony. Growth of hemopoietic allografts appeared to be similar to those of syngeneic marrow cells, which indicates inhibition of resistance for allogeneic marrow grafts. Because of a positive correlation, involvement of natural killer (NK) cells in resistance of transplanted allografts has been suggested. Inocula of NK‐sensitive lymphoma cells were, however, vigorously rejected in the G‐CSF‐transgenic mice. This observation indicates that G‐CSF may play a role in engraftment of transplanted allogeneic marrow grafts and may represent a component of mechanisms of hemopoietic resistance. Furthermore, this result may be an indication that allore‐sistance and NK cells use different mechanisms to resist each target.
Evidence of Direct Recognition Subset in Xeno‐reactive Helper T Cells
Authors: Hirota Toshio , Hirose Hajime , Iwata Hisashi , Bando Michiya , Mori Yoshio , Senga Shoshi , Onitsuka Atsuyoshi , Hamaoka Toshiyuki , Fujiwara Hiromi
Published: November 2008

Abstract: There are two functional subsets of alloreactive helper T cells: one recognizes the alloantigens on self‐antigen‐presenting cells (APCs), and the other recognizes the alloantigens on alio‐APCs. In this study, we analyzed which specific Th cells have a possible effect on concor‐dant‐xenograft rejection responses and how Th cells recognize xeno‐antigens. In the proliferative response stimulated with spleen cells obtained from rats (r‐SPC), mouse T cells (m‐Tc) were not inhibited by GK1.5 (CD4) or 2.43 (CD8) antibodies. In a xeno‐mixed lymphocyte reaction, m‐Tc that included APC (APC(+)) proliferated when stimulated with r‐SPC APC(+) or APC(‐). In contrast, B6 T cell APC(‐) proliferated only when stimulated with r‐APC(+)SPC but not when stimulated with APC(‐). The m‐Tc lines responded to F344 SPC APC(+) but not to SPC APC(‐); however, the m‐Tc line did not respond to SPC from another rat strain. We hypothesize that both CD4+ Th and CD8+ Th are included in the concordant xeno‐reactive Th; there are both xeno‐APC‐restricted Th and self‐APC‐restricted Th; and xeno‐APC‐restricted Th recognizes xeno‐major histocompatibility complexes.