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At least 595 records · Page 33Linked to original sources

PubMed2003

Method for monitoring alginate released in biological fluids by high-performance anion-exchange chromatography with pulsed amperometric detection.

The use of alginate-entrapped cells in cell therapy requires a method for monitoring possible released compound within biological fluids following either their implantation or inoculation in artificial organs. Oligomannuronic and oligoguluronic acids were prepared by enzymatic depolymerization with alginate lyase from Pseudomonas alginovora, characterized by high-performance anion-exchange chromatography with pulsed amperometric detection and quantitated in human, pig and rabbit blood, urine and tissue samples. The method was tested for linearity and detection limit, accuracy, intra- and inter-day precision. The limit of detection was 3 microgram/ml in both urine and plasma and 5 mg/g of tissues. The relative standard deviations (RSDs) of intra-day precision were 6.0-16.6% and 4.8-8.7% in plasma and urine, respectively; the RSDs of inter-day precision were 5.1-14.4% and 5.0-11.6% in plasma and urine, respectively. Thus, this method appears suitable for the measurement of released alginate from entrapped cells used in cell therapy.

Alginates↗

PubMed1994

Cell-binding peptides conjugated to poly(ethylene glycol) promote neural cell aggregation.

We have developed a method for promoting cell aggregation with bifunctional macromolecules synthesized by coupling cell-binding peptides to an inert, water-soluble polymer. The peptides Arg-Gly-Asp (RGD) and Tyr-Ile-Gly-Ser-Arg (YIGSR) were conjugated through their amino termini to both ends of linear poly(ethylene glycol) (PEG), producing bifunctional hybrid polymers: RGD-PEG-RGD and YIGSR-PEG-YIGSR. RGD-PEG-RGD promoted aggregation of mechanically-dissociated fetal brain cells, pheochromocytoma cells (PC12), and neuroblastoma cells maintained in rotation culture at 37 degrees C. Enhanced aggregation was noticeable within 10 minutes and became more pronounced over the next several hours: after 7-9 hours, the mean aggregate volume was up to 10 times larger than the mean volume produced in suspensions containing unmodified PEG. Similar results were obtained with YIGSR-PEG-YIGSR and PC12 cells. Enhancement in aggregation correlated with the ability of soluble RGD or YIGSR to inhibit cell adhesion to surfaces coated with laminin or fibronectin. This method for promoting aggregation may be useful for large scale culture of anchorage dependent cells, eliminating the need for microcarriers. In addition, aggregates formed by this method may be suitable for use in artificial organs or as cell transplants for tissue regeneration.

Adrenal Gland Neoplasms↗

PubMed2003

Side-chain control of beta-peptide secondary structures.

As one of the most important families of non-natural polymers with the propensity to form well-defined secondary structures, the beta-peptides are attracting increasing attention. The compounds incorporating beta-amino acid residues have found various applications in medicinal chemistry and biochemistry. The conformational pool of beta-peptides comprises several periodic folded conformations, which can be classified as helices, and nonpolar and polar strands. The latter two are prone to form pleated sheets. The numerous studies that have been performed on the side-chain dependence of the stability of the folded structures allow certain conclusions concerning the principles of design of the beta-peptide foldamers. The folding propensity is influenced by local torsional, side-chain to backbone and long-range side-chain interactions. Although beta-peptide foldamers are sensitive to solvent, the systematic choice of the side-chain pattern and spatiality allows the design of the desired specific secondary structure. The application of beta-peptide foldamers may open up new directions in the synthesis of highly organized artificial tertiary structures with biochemical functions.

Amino Acids↗

PubMed2001

Clinical long-term results of vascular prosthesis sealed with fragmented autologous adipose tissue.

Tissue engineering can improve the former limitations of artificial organs. This article reports the long-term clinical results of grafts constructed with fragmented autologous adipose tissue. We did a retrospective analysis of a series of 53 patients with lower leg ischemia that received 69 fragmented adipose tissue (FAT) grafts implantation at our institution. The mean follow-up period was 36.0 months. After 1, 2, 3, and 5 years, the primary potency rates were 85.3, 83.3, 73.8, and 67.7%, respectively. The lumen of occluded areas not only at anastomotic sites but also in areas far from the anastomotic sites was occupied by a thickened neointima, which had a great number of capillary blood vessels, elastic laminae, smooth muscle cells, fibroblasts, and collagen fibers. This type of intimal hyperplasia was a characteristic finding in the FAT grafts. From the results of this clinical trial, we conclude that the FAT grafts are acceptable as vascular prostheses for ischemic lower extremities. The intimal hyperplasia at sites far from the anastomotic lines suggested the possibility of neointima formation throughout the luminal surface of the grafts.

Adipose Tissue↗

PubMed2001

Computational fluid dynamics as a development tool for rotary blood pumps.

Computational fluid dynamics (CFD) is beginning to significantly impact the development of biomedical devices, in particular rotary cardiac assist devices. The University of Pittsburgh's McGowan Center for Artificial Organ Development has extensively used CFD as the primary tool to analyze and design a novel axial flow blood pump having a magnetically suspended rotor. The blood-contacting surfaces of the pump were developed using a design strategy based on CFD that involved closely coupling a Navier-Stokes solver to a parameterized geometry modeler and advanced mesh movement techniques. CFD-based blood damage models for shear-induced hemolysis as well as surrogate functions describing thrombosis potential were employed to help guide design improvements. This CFD-based design approach resulted in the timely development of a pump subjected to multiple geometric refinements without building expensive physical prototypes for each design iteration. A physical prototype of the final improved pump was fabricated and experimentally analyzed using particle imaging flow visualization. The CFD predicted results correlated well with the experimental data including pressure-flow (H-Q) performance and specific flow field features. It is estimated that the present CFD-based design approach shortened the overall design time frame from an order of years to months.

Computational Biology↗

PubMed2001

Assessment of hemolysis related quantities in a microaxial blood pump by computational fluid dynamics.

A computational assessment or even quantification of shear induced hemolysis in the predesign phase of artificial organs (e.g., cardiac assist devices) would largely decrease efforts and costs of design and development. In this article, a general approach of hemolysis analysis by means of computational fluid dynamics (CFD) is discussed. A validated computational model of a microaxial blood pump is used for detailed analysis of shear stress distribution. Several methods are presented that allow for a qualitative assessment of shear stress distribution and related exposure times using a Lagrangian approach and mass distribution in combination with shear stress analysis. The results show that CFD offers a convenient tool for the general assessment of shear-induced hemolysis. The determination of critical regions and an estimation of the amount of blood subject to potential damage in relation to the total mass flow are shown to be feasible. However, awareness of limitations and potential flaws in CFD based hemolysis assessments is crucial.

Computational Biology↗

PubMed2002

Atomic force microscopic observation of mechanically traumatized erythrocytes.

Erythrocytes are damaged or stimulated mechanically by artificial organs assisting in circulation. For several decades, a large number of research studies have been conducted to investigate the traumatizing phenomena due to nonphysiological flow conditions. These phenomena are thought to be the physical interaction between the cell membrane and the various fluidic conditions. To elucidate or evaluate the phenomena, however, chemical components emerging into the circulating solution, such as liberated hemoglobin or lactic dehydrogenase (LDH), have been measured as a main parameter. Naturally, the physical reaction caused on the membrane itself cannot be detailed by these parameters because they are the secondary products resulting from the mechanical membrane rupture. The aim of this study is to understand the traumatizing mechanism directly from a microbiological viewpoint. As a first step, we visualized the surface of sheep erythrocytes loaded with shear stress and measured erythrocyte surface roughness by atomic force microscopy (AFM) on a nanometer scale (10(-9) m). The constant shear rate was set at 1,800 (1/s), and the exposure time was set at 0.5, 1, and 2 h. We also measured the liberated hemoglobin concentration. As a result, it was found that the fine structure on the cell surface was changed drastically by the stress. It was also found that the surface roughness value increased with the exposure time, and correlated to the hemoglobin concentration. The visualization and the measurement of surface roughness of traumatized erythrocytes by AFM were thought to offer a new parameter for both hemolytic and subhemolytic studies.

Animals↗

PubMedDate not supplied

The Ito "Flow-Through" Centrifuge. A new device for long-term (24 hours) plasmapheresis without platelet deterioration.

An efficacious procedure for continuous plasmapheresis in long-term extracorporeal circulation has not yet been devleoped. This technique could be important in plasma exchange or cross-exchange and in artificial organ support if it could be accomplished safely using heparin as the anticoagulant. When sheep were connected to the Celltrifuge for 23 hours and administered 150 units/kg per hour heparin anticoagulant, we found gross platelet clumping in separated plasma and a 60 per cent fall in platelet count. When 120,000 units of heparin were directly injected into the centrifuge bowl at the onset of the centrifugation followed by hourly heparin administration at 500 units/kg, there was no platelet clumping but the platelet count fell to 52 per cent. Under identical conditions the Ito Flow-Through Centrifuge, a new continuous flow centrifuge with no rotating seals, was used. We found no platelet aggregates and no drop in platelet count, and there was a 100 per cent recovery of platelets in the separated plasma. Platelets sampled from arterial blood and separated plasma were found to have normal function in vitro, and responded 100 per cent to both collagen and ADP. These results indicate that the Ito Flow-Through Centrifuge can be used in plasmapheresis with heparin anticoagulation with no donor platelet loss and normal function in separated plasma.

Animals↗

PubMed2003

Have we met the expectations of heart and lung transplantation in children?

Heart transplantation in children has been a relatively common practice for more than 15 years, and lung transplantation, while in use as a therapeutic modality for a shorter period of time, has 10 years of follow-up data for review. Because they are expensive, time-consuming, labor-intensive procedures, it is reasonable to review what has transpired to evaluate the effectiveness of these procedures, not only from the standpoint of survival, but in the applicability and availability to all who need it, and successful long-term outcomes including quality of life in those who receive it. Health care expense can be justified by improved results that reach expectations in the areas of applicability, availability, and survival. The applicability issue has, in large part, been achieved in transplantation in children. The goal of comprehensive availability can be met by providing alternatives to transplantation, advancing artificial organ research, and overhauling the organ donor programs to improve organ retrieval. To better meet expectations for survival, further advances in transplant immunology and solutions to the problems of post-transplant coronary artery disease and bronchiolitis obliterans will have to occur.

Child↗

PubMedDate not supplied

Modifying the NH2 and COOH termini of aquaporin-5: effects on localization in polarized epithelial cells.

To reengineer polarized epithelial cell functions directly in situ, or ex vivo in the fabrication of an artificial organ, it is necessary to understand mechanisms that account for polarized membrane sorting. We have used the aquaporins (AQPs), a family of homotetrameric water channel proteins, as model membrane proteins for this purpose. AQP monomers contain six transmembrane-spanning domains linked by five interconnecting loops, with the NH2 and COOH termini residing in the cytosol. AQP5 is localized in the apical membranes of several different epithelia in vivo, and in stably transfected MDCK-II cells grown as a polarized monolayer. We wished to identify a structural region(s) within rat AQP5 (rAQP5) important for apical localization, and to study the MDCK-II cell localization of rAQP5s modified in either their NH2 or COOH terminus. We show that the NH2- terminal region does not play a major role in apical localization as deletion of the NH2 terminus produced a modified rAQP5 construct (AQP5-NT(del)) that was stably expressed and localized primarily to the apical membranes of MDCK-II cells. Attachment of a FLAG epitope to the NH2 terminus of AQP5 (AQP5(flag) construct) also did not perturb apical localization. In addition, we found that the exchange of NH2-terminal regions between rAQP5 and human AQP1 (hAQP1; a nonpolarized AQP isoform) produced a modified rAQP5 construct (AQP5-1NT) and a modified hAQP1 construct (AQP1-5NT), each of which localized as the parental AQP (apically, and to both apical and basolateral membranes, respectively). In contrast, we found that deletion of the COOH terminus resulted in a modified rAQP5 construct (AQP5-CT(del)) that was unstably expressed and localized to intracellular site(s) in MDCK-II cells. Substitution of the COOH terminus of AQP1 with the COOH terminus of AQP5 also produced a construct (AQP1-5CT) transiently expressed in intracellular compartment(s). However, substitution of the COOH terminus of rAQP5 with the COOH terminus of hAQP1 produced a modified rAQP5 construct (AQP5-1CT) that was stably expressed and localized to basolateral membranes, suggesting the loss of an apical targeting/retention signal from rAQP5, the gain of a basolateral targeting/retention signal from hAQP1, or a combination of these two possibilities.

Animals↗

PubMed2004

Gene and cell-based therapies for heart disease.

Heart disease remains the prevalent cause of premature death and accounts for a significant proportion of all hospital admissions. Recent developments in understanding the molecular mechanisms of myocardial disease have led to the identification of new therapeutic targets, and the availability of vectors with enhanced myocardial tropism offers the opportunity for the design of gene therapies for both protection and rescue of the myocardium. Genetic therapies have been devised to treat complex diseases such as myocardial ischemia, heart failure, and inherited myopathies in various animal models. Some of these experimental therapies have made a successful transition to clinical trial and are being considered for use in human patients. The recent isolation of endothelial and cardiomyocyte precursor cells from adult bone marrow may permit the design of strategies for repair of the damaged heart. Cell-based therapies may have potential application in neovascularization and regeneration of ischemic and infarcted myocardium, in blood vessel reconstruction, and in bioengineering of artificial organs and prostheses. We expect that advances in the field will lead to the development of safer and more efficient vectors. The advent of genomic screening technology should allow the identification of novel therapeutic targets and facilitate the detection of disease-causing polymorphisms that may lead to the design of individualized gene and cell-based therapies.

Coronary Artery Disease↗

PubMedDate not supplied

A novel method for quantifying shape deformation applied to biocompatibility testing.

Cytotoxicity tests are important for the screening and evaluation of biocompatibility of artificial organs. Morphologic changes of cells that were contacted biomaterials or biomaterial extracts indicate their toxicity. However, information on cytotoxic effects is still obtained by subjective visual inspection of microscopic samples. In this article, a novel computer assisted method is introduced. The automatic analysis of digitized micrographs is achieved in several stages: segmentation, separation, classification, and measurement. The segmentation of the image is provided by a new local adaptive thresholding technique, which adapts the threshold window sizes onto local gray level distribution and yields optimal window sizes. The actual threshold is obtained by maximizing interclass variances and minimizing intraclass variance. For the separation of connected cells, the binarized samples are cleaned from "false" markers by morphologic filtering. The subsequent separation is a two phase approach. Information levels are generated top-down by successively applying an enhanced erosion operator, which yields markers and filters noise usually evolving from multiple erosions. The converse bottom-up integration of the eroded markers is performed by successively applying an enhanced dilation operator, which reconstructs the cells and prevents merging of already separated objects. The subsequent measuring provides quantitative parameters of the distribution of size and compactness of the cells contained within the sample. The method was evaluated by L-929 fibroblasts that were in contact with 0%, 5%, and 10% concentrations of ethanol. For each concentration, 268 images of the cell populations were captured. The obtained quantitative parameters are highly correlated to the common verbal description of morphologic changes. Therefore, the proposed automatic method has several advantages compared with subjective examinations. The results allow an objective comparison of the quantification of phenomena; the subjective influence of the observer is eliminated; and the laboratory staff is relieved of time consuming routine work.

Animals↗

PubMedDate not supplied

A novel percutaneous barrier device that permits safe subcutaneous access.

Successful subcutaneous access is important for optimal management of internal artificial organs and treatment of many diseases. However, skin downgrowth and tissue infection are still significant problems in the use of devices that require long-term subcutaneous access. The authors developed a new percutaneous device that provides a unique biologic boundary with surrounding connective tissue while minimizing the risk of complications. This new percutaneous device is made of a circumferential, strong, thin, and flexible mesh collar with millimeter size holes for connecting the structure. It has two distinct functional portions: a connecting zone and a sealing line. The most important features of the structure are: 1) Connective tissue grows through the millimeter size pores of the connecting zone to form a strong bond between the device and healthy tissue. 2) The millimeter size pores of the connecting zone allow capillaries to grow through its entire surface, ensuring sufficient blood supply. 3) The tissue of the connecting zone and the device surface form a biosealed junction (sealing line). This sealing line is protected by the connecting zone and is free from external forces acting on local skin. 4) The device is generally functional immediately after surgical implantation. The subcutaneous perimeter of the functional dome contains extruded rigid rings of millimeter size holes permitting growth of subcutaneous tissue through the device. This functions as the minor connecting structure of the device. Four of five implanted rabbits have remained healthy 8 months postimplantation without antibiotic administration. The fifth rabbit died 4 months postimplantation for reasons unrelated to the device. Gross or histopathologic inspection revealed no signs of tissue injury or inflammation. Growth of healthy connective tissue was clearly observed. These results indicate this percutaneous device can provide a strong, stable, and effective connection to internal organs without bioboundary damage, skin downgrowth, or tissue infection.

Animals↗

PubMedDate not supplied

Influence of static pressure and shear rate on hemolysis of red blood cells.

The purpose of this study was to investigate the effect of multiple mechanical forces in hemolysis. Specific attention is focused on the effects of shear and pressure. An experimental apparatus consisting of a rotational viscometer, compression chamber, and heat exchanger was prepared to apply multiple mechanical forces to a blood sample. The rotational viscometer, in which bovine blood was subjected to shear rates of 0, 500, 1,000, and 1,500 s(-1), was set in the compression chamber and pressurized with an air compressor at 0, 200, 400, and 600 mm Hg. The blood temperature was maintained at 21 degrees C and 28 degrees C. Free hemoglobin at 600 mm Hg was observed to be approximately four times higher than at 0 mm Hg for a shear rate of 1,500 s(-1) (p < 0.05). The results suggest that the increase in hemolysis is strongly related to pressure when high shear rates are applied to the erythrocytes. The data acquired in this study will be helpful in the development of artificial organs, where it will facilitate the prediction of hemolysis in flow dynamics analysis, flow visualization, and computational fluid dynamics.

Blood Viscosity↗

PubMedDate not supplied

Lentiviral vector: a useful tool for transduction of human liver endothelial cells.

Endothelial cells play multiple roles in pathophysiologic processes and are increasingly being recognized as target cells of gene therapy. Lentiviral vectors derived from human immunodeficiency virus type 1 have an ability to infect both dividing and nondividing cells and currently receive a great deal of attention as an innovative tool for transduction of target cells. The purpose of the present work was to evaluate the efficacy of a lentiviral vector for transducing human liver endothelial cells (HLECs) in vitro. For the present study, a pseudotyped lentiviral vector encoding a green fluorescent protein (GFP) gene, LtV-GFP, was generated by means of FuGENE 6 method and allowed to infect HLECs. Approximately 95% of HLECs were positive for GFP expression after LtV-GFP infection at a multiplicity of infection of 10. Notably, LtV-GFP transduced HLECs had stable and long term GFP expression, showed gene expression of endothelial markers including CD 34, factor VIII, flt-1, KDR/flk-1 and HGF, and maintained in vitro angiogenic potential in a Matrigel assay to the same extent as primarily cultured HLECs. These findings provide evidence that lentivirus based gene delivery is an efficient tool for transduction of endothelial cells that could be considered for cell and gene therapies and hybrid artificial organs.

Biocompatible Materials↗

PubMed2006

Challenges in tissue engineering.

Almost 30 years have passed since a term 'tissue engineering' was created to represent a new concept that focuses on regeneration of neotissues from cells with the support of biomaterials and growth factors. This interdisciplinary engineering has attracted much attention as a new therapeutic means that may overcome the drawbacks involved in the current artificial organs and organ transplantation that have been also aiming at replacing lost or severely damaged tissues or organs. However, the tissues regenerated by this tissue engineering and widely applied to patients are still very limited, including skin, bone, cartilage, capillary and periodontal tissues. What are the reasons for such slow advances in clinical applications of tissue engineering? This article gives the brief overview on the current tissue engineering, covering the fundamentals and applications. The fundamentals of tissue engineering involve the cell sources, scaffolds for cell expansion and differentiation and carriers for growth factors. Animal and human trials are the major part of the applications. Based on these results, some critical problems to be resolved for the advances of tissue engineering are addressed from the engineering point of view, emphasizing the close collaboration between medical doctors and biomaterials scientists.

Animals↗

PubMed1980

Inbreeding in a Brazilian general hospital.

A group of 925 adult in-patients of a Brazilian general hospital was matched by race (subdivided in five groups) and age with a group of 925 of their visitors, who were taken as controls. Illiteracy increases from Whites to Blacks and is significantly more prevalent among the patients than among their respective controls. Inbreeding, on the contrary, increases from Blacks to Whites. White patients showed a significantly higher rate of inbreeding than their corresponding controls. The difference is also significant for the fraction Whites plus Light Mulattoes, but not for the other race subgroups. As regards the total, the significance is present only in a one-tailed distribution. It is concluded that the inbreeding load (if any) acting on the total of the patients is negligible; it seems significantly different from 0 only among Whites. No inbreeding effect could be verified, however, on any particular condition among the Whites. Estimates of the number of morbid equivalents per gamete (morbons) revealed values which are both significantly (among Whites and Whites plus Light Mulattoes) and non-significantly (among the other racial subgroups) different from zero. These estimates reflect the situation in the sample which has been artificially organized to contain 50% of patients.

Adult↗

PubMed1995

Model for a general mechanical blood damage prediction.

Knowledge of the correlation between mechanical loading of formed blood elements and the amount of their destruction is important for the prediction of blood trauma in artificial circulatory devices as well as in natural circulation. A hemodynamic assessment and optimization of artificial organs to minimize trauma could be undertaken in the design phase given a comprehensive mechanical blood damage model. A theory to determine blood trauma theoretically as a combination of a mechanical loading analysis and a phenomenological blood damage resistance hypothesis is presented. Arbitrary stress-time functions of blood particles predicted by flow analysis are reduced to a set of simple time functions for which the damage behavior may, in principle, be obtained from mechanical blood damage tests. A classification of those stress functions into damaging and nondamaging parts is followed by an overall trauma prediction considering cumulative effects by means of a damage accumulation hypothesis. Theoretical determination of blood destruction caused by mechanical stresses in a centrifugal pump is one possible application of the proposed theory. The strategy of hemolysis prediction is demonstrated for the Aries Medical Isoflow Pump. Irregular stress-time loading functions of particles passing the pump domain obtained by three-dimensional numerical flow simulations were reduced and classified into harmonic components. To relate these functions to their hemolytic response can only be done in a qualitative manner since blood damage behavior under transient stress loading has not been sufficiently investigated. Accurate prediction of blood trauma using the proposed theory will require detailed study of the influence of frequency and amplitude of harmonic stress loading on formed blood elements.

Blood Flow Velocity↗