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Synthetic Function (synthetic + function)

Distribution by Scientific Domains

Medical Sciences	70%

Selected Abstracts

Non-heart-beating donor porcine livers: The adverse effect of cooling

LIVER TRANSPLANTATION, Issue 1 2005
Srikanth Reddy
Normothermic preservation has been shown to be advantageous in an experimental model of preservation of non-heart-beating donor (NHBD) livers, which have undergone significant warm ischemic injury. The logistics of clinical organ retrieval might dictate a period of cold preservation prior to warm perfusion. We have investigated the effects of a brief period of cold preservation on NHBD livers prior to normothermic preservation. Porcine livers were subjected to 60 minutes of warm ischaemia and then assigned to following groups: Group W (n = 5), normothermic preservation for 24 hours; and Group C (n = 6), cold preservation in University of Wisconsin solution for 1 hour followed by normothermic preservation for 23 hours (total preservation time, 24 hours). Synthetic function (bile production and factor V production) and cellular damage were compared on the ex vivo circuit during preservation. There was no significant difference in the synthetic function of the livers (bile production and factor V production). Markers of hepatocellular damage (alanine aminotransferase and aspartate aminotransferase release), sinusoidal endothelial cell dysfunction (hyaluronic acid), and Kupffer cell injury (,-galactosidase) were significantly higher in Group C. The histology of the livers at the end of perfusion was similar. In conclusion, a brief-period cold preservation prior to normothermic perfusion maintains the synthetic function and metabolic activity but results in significant hepatocellular damage, sinusoidal endothelial cell dysfunction, and Kupffer cell injury. Transplant studies are required to establish whether livers treated in this way are viable for transplantation. (Liver Transpl 2005;11:35,38.) [source]

Cholestasis enhances liver ischemia/reperfusion-induced coagulation activation in rats

HEPATOLOGY RESEARCH, Issue 2 2010
Jaap J. Kloek
Aim:, Cholestasis is associated with increased morbidity and mortality in patients undergoing major liver surgery. An additional risk is induced when vascular inflow occlusion is applied giving rise to liver ischemia/reperfusion (I/R) injury. The role of the coagulation system in this type of injury is elusive. The aim of the current study was to assess activation of coagulation following hepatic I/R injury in cholestatic rats. Methods:, Male Wistar rats were randomized into two groups and subjected to bile duct ligation (BDL) or sham laparotomy. After 7 days, both groups underwent 30 min partial liver ischemia. Animals were sacrificed before ischemia or after 6 h, 24 h, and 48 h reperfusion. Results:, Plasma AST and ALT levels were higher after I/R in cholestatic rats (P < 0.05). Hepatic necrosis, liver wet/dry ratio and neutrophil influx were increased in the BDL group up to 48 h reperfusion (P < 0.05). Liver synthetic function was decreased in the BDL group as reflected by prolonged prothrombin time after 6 h and 24 h reperfusion (P < 0.05). I/R in cholestatic rats resulted in a 12-fold vs. 7-fold (P < 0.01) increase in markers for thrombin generation and a 6-fold vs. 2-fold (P < 0.01) increase in fibrin degradation products (BDL vs. control, respectively). In addition, the cholestatic rats exhibited significantly decreased levels of antithrombin (AT) III and increased levels of the fibrinolytic inhibitor plasminogen activator inhibitor (PAI-1) during reperfusion. Conclusions:, Cholestasis significantly enhances I/R-induced hepatic damage and inflammation that concurs with an increased activation of coagulation and fibrinolysis. [source]

Small-Sample Equating Using a Synthetic Linking Function

JOURNAL OF EDUCATIONAL MEASUREMENT, Issue 4 2008
Sooyeon Kim
This study addressed the sampling error and linking bias that occur with small samples in a nonequivalent groups anchor test design. We proposed a linking method called the synthetic function, which is a weighted average of the identity function and a traditional equating function (in this case, the chained linear equating function). Specifically, we compared the synthetic, identity, and chained linear functions for various-sized samples from two types of national assessments. One design used a highly reliable test and an external anchor, and the other used a relatively low-reliability test and an internal anchor. The results from each of these methods were compared to the criterion equating function derived from the total samples with respect to linking bias and error. The study indicated that the synthetic functions might be a better choice than the chained linear equating method when samples are not large and, as a result, unrepresentative. [source]

Novel fibrinogen mutation ,314Thr,Pro (fibrinogen AI duPont) associated with hepatic fibrinogen storage disease and hypofibrinogenaemia

LIVER INTERNATIONAL, Issue 10 2010
Stephen O. Brennan
Abstract Mutation in fibrinogen genes may lead to quantitative or qualitative disorders that result in bleeding, thrombosis or hepatic fibrinogen storage disease. Only three mutations in the fibrinogen , gene have been identified that cause hepatic endoplasmic reticulum storage of mutant fibrinogen. To investigate the possibility of hepatic fibrinogen storage disease in a 4-year-old male with persistently elevated serum aminotransferases and preserved synthetic function except for a prolonged INR. After informed consent, liver and blood samples were obtained. Liver sections were examined by light microscopy, anti-fibrinogen immunolabelling and electron microscopy. Purified fibrinogen was analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and reverse phase high performance liquid chromatography; DNA sequencing was performed using a BigDye Terminator (v. 3.1) cycle sequencing kit. Four-year-old male with persistently elevated transaminases with an INR 1.5 but otherwise normal synthetic function. Fibrinogen activity and thrombin clotting time were abnormal at 0.47 g/L and 46 s respectively. Hepatic histological examination revealed portal inflammatory infiltrates with bridging fibrosis. Clumped eosinophilic material was observed in hepatocytes that was immunoreactive to fibrinogen antisera. Ultrastructural examination showed cytoplasmic inclusions arrayed in fingerprint-like patterns. DNA sequence analysis revealed heterozygosity for a novel ,314Thr ,Pro mutation (fibrinogen AI duPont) in the fibrinogen , gene. Protein analyses showed normal patterns of A,, B, and , chains suggesting that the variant , allele was not expressed in plasma fibrinogen. We describe only the fourth mutation to be identified, ,314Thr,Pro (fibrinogen AI duPont), giving rise to hypofibrinogenaemia and hepatic fibrinogen storage disease. [source]

Non-heart-beating donor porcine livers: The adverse effect of cooling

Synovial fibroblasts self-direct multicellular lining architecture and synthetic function in three-dimensional organ culture

ARTHRITIS & RHEUMATISM, Issue 3 2010
Hans P. Kiener
Objective To define the intrinsic capacity of fibroblast-like synoviocytes (FLS) to establish a 3-dimensional (3-D) complex synovial lining architecture characterized by the multicellular organization of the compacted synovial lining and the elaboration of synovial fluid constituents. Methods FLS were cultured in spherical extracellular matrix (ECM) micromasses for 3 weeks. The FLS micromass architecture was assessed histologically and compared with that of dermal fibroblast controls. Lubricin synthesis was measured via immunodetection. Basement membrane matrix and reticular fiber stains were performed to examine ECM organization. Primary human and mouse monocytes were prepared and cocultured with FLS in micromass to investigate cocompaction in the lining architecture. Cytokine stimuli were applied to determine the capacity for inflammatory architecture rearrangement. Results FLS, but not dermal fibroblasts, spontaneously formed a compacted lining architecture over 3 weeks in the 3-D ECM micromass organ cultures. These lining cells produced lubricin. FLS rearranged their surrounding ECM into a complex architecture resembling the synovial lining and supported the survival and cocompaction of monocyte/macrophages in the neo,lining structure. Furthermore, when stimulated by cytokines, FLS lining structures displayed features of the hyperplastic rheumatoid arthritis synovial lining. Conclusion This 3-D micromass organ culture method demonstrates that many of the phenotypic characteristics of the normal and the hyperplastic synovial lining in vivo are intrinsic functions of FLS. Moreover, FLS promote survival and cocompaction of primary monocytes in a manner remarkably similar to that of synovial lining macrophages. These findings provide new insight into inherent functions of the FLS lineage and establish a powerful in vitro method for further investigation of this lineage. [source]

In Vitro and In Vivo Evaluation of Albumin Synthesis Rate of Porcine Hepatocytes in a Flat-Plate Bioreactor

ARTIFICIAL ORGANS, Issue 7 2001
Masaya Shito
Abstract: Several configurations of extracorporeal bioartificial liver devices have been developed for the potential treatment of fulminant hepatic failure or as a bridge to liver transplantation. Recently, we developed a microchannel flat-plate bioreactor with an internal membrane oxygenator in which porcine hepatocytes are cultured as a monolayer on the bottom glass surface. In the present study, we investigated synthetic function of porcine hepatocytes in the bioreactor in both in vitro and in vivo flow circuit models. In vitro, albumin synthesis was stable in the bioreactor for up to 4 days of perfusion. In vivo, with the extracorporeal connection of the bioreactor to rat vasculature, porcine albumin was detectable for 24 h in the rat plasma. We also developed a simple mathematical model to predict the in vivo porcine albumin concentration in rat plasma. These results indicate that this configuration of a microchannel flat-plate bioreactor has potential as a liver support device and warrants further investigation. [source]

Hemoglobin regulates the metabolic and synthetic function of rat insulinoma cells cultured in a hollow fiber bioreactor

BIOTECHNOLOGY & BIOENGINEERING, Issue 3 2010
Sharon I. Gundersen
Abstract Pancreatic islet transplantation continues to benefit patients with type 1 diabetes by normalizing glucose metabolism and improving other complications of diabetes. However, islet transplantation therapy is limited by the inadequate availability of pancreatic islets. In order to address this concern, this work investigated the expansion of rat insulinoma cells (INS-1) and their ability to generate insulin in a hollow fiber bioreactor (HFB). The long-term goal of this project is to develop a bioartificial pancreas. HFBs were incubated at two different oxygenation conditions (10% and 19% O2) to determine the best scenario for O2 transport to cultured cells. Also, bovine hemoglobin (BvHb) was supplemented in the cell culture media of the HFBs in order to increase O2 transport under both oxygenation conditions. Our results show that INS-1 cells expanded under all oxygenation conditions after 2 weeks of culture, with a slightly higher cell expansion under normoxic oxygenation (19% O2) for both control HFBs and BvHb HFBs. In addition, cellular insulin production remained steady throughout the study for normoxic control HFBs and BvHb HFBs, while it increased under hypoxic oxygenation (10% O2) for both types of HFBs but to different extents. Under the two different oxygenation conditions, cellular insulin production was more uniform with time in BvHb HFBs versus control HFBs. These results, along with qRT-PCR analysis, suggest a possible dysregulation of the insulin-signaling pathway under hypoxic culture conditions. In conclusion, the HFB culture system is an environment capable of expanding insulinomas while maintaining their viability and insulin production capabilities. Biotechnol. Bioeng. 2010;107: 582,592. © 2010 Wiley Periodicals, Inc. [source]