In this work, a mathematical modelling approach is taken to improve and optimize the designs of bioartificial liver (BAL) systems. BALs are an alternative therapy for the extremely serious condition of liver failure where liver transplant is currently the only viable option. As yet, large-scale clinical trials have not been successful enough in order for BALs to gain regulatory approval. Through the work in this report, it is envisaged that BAL design can be improved to the point where they can gain clinical acceptanceOne of the main issues in BAL design is the provision of adequate oxygen to the cell mass. To this end, a mathematical model to describe oxygen mass transport is developed based on the principle of Krogh cylinders. The results of this model are subsequently interpreted and presented in Operating Region charts, an image of a parameter space that corresponds to viable BAL designs. These charts allow several important design trends to be identified, e.g. numerous short and thin hollow fibres are favourable over fewer thicker, longer fibres. In addition, it is shown that a physiologically relevant cell number of more than 10% of the native liver cell mass can be supported in these devices under the right conditions. Subsequently the concept of the Operating Region is expanded to include zonation, a metabolic phenomenon where local oxygen tension is a primary modulator of liver cell function. It is found that zonation profiles can be well controlled and under standard conditions a plasma flow rate of 185 ml/min to the BAL would distribute the three metabolic zones evenly. Finally, the principles of the Operating Region charts and zonation are applied to three existing commercial BAL designs; the HepaMate, BLSS and ELAD systems. In each case it could be seen that the default designs of each system did not present ideal environments for liver cells. Through consideration of zonation profiles, each device design and operating parameters could be optimized to produce in vivo-like environments. In the case of the ELAD, reducing the plasma flow rate from 500 to 90 ml/min resulted in a balanced zonation profile. Overall, the work in this report has developed and detailed a series of tools that will assist a BAL designer in making judicious choices over bioreactor design and operating parameters. As a result, it is hoped that BALs can take a step forward towards clinical practice and ultimately saving lives.

Bacterial toxins have been shown to modify animal cell proteins in vivo with ADPR. Animal cells also contain endogenous enzymes that can modify proteins. Indirect evidence for the existence in vivo of rat liver proteins modified by ADPR on arginine residues has been reported previously. Presented here is direct evidence for the existence of ADP-ribosylarginine in rat liver proteins. Proteins were subjected to exhaustive protease digestion and ADP-ribosyl amino acids were isolated by boronate chromatography.

The aim of this study was to determine the levels of cadmium (Cd) and lead (Pb) in livers and kidneys of cattle slaughtered at Grootfontein abattoir in Namibia. The study design was based on the epidemiological principles to detect a single animal whose kidneys or liver contained Cd or Pb residues. The Grootfontein area of Namibia has extensive base-metal ore reserves, which were and are still extracted and processed in localities used as livestock pastures. Namibia is also an arid country which predominantly uses borehole water for livestock and human consumption. These underground water bodies share the same space as base-metal ores. The anthropogenic activities in this area under the existing geological and hydrogeological circumstances offer opportunities for Cd and Pb to enter the food chain. Entry of Cd and Pb in the food chain leads to bioaccumulation in cattle kidneys and livers to concentrations above Codex Alimentarius Commission (CAC) standards, creating a possible public health risk. The CAC withdrew the maximum limit (ML) of 1mg kg-1 Cd in bovine kidneys and liver, but it has a provisional tolerable monthly intake (PTMI) of 0.025mg kg-1 human body weight. This CAC PTMI translates to a total exposure of 1.5mg Cd for a 60kg body weight person. The CAC ML for Pb in bovine offal is 0.5mg kg-1, while its provisional tolerable weekly intake (PTWI) of 0.025mg kg-1 human body weight is under review. This investigation intended to establish if Cd and Pb in the livers and kidneys of cattle slaughtered in the study area exceeded CAC human exposure limits. Liver and kidney specimens were collected from 31 randomly sampled mature cattle (estimated over five years old based on incisor teeth examined post slaughter). The specimens were analysed at a local mine laboratory, which was the only facility available and capable of performing the tests. They were digested using wet-ashing (the oxidation procedure). All liver digestates were analysed, while one kidney analyte was insufficient. Cd and Pb were measured using flame atomic absorption spectroscopy (FAAS). The detection limit (DL), which was the minimum metal concentration FAAS could measure was 0.2mg kg-1 for Cd and 1.1mg kg-1 for Pb. The laboratory could not refine the Pb DL which was more than twice the CAC ML. All livers had Cd concentrations below 0.2mg kg-1. One discarded kidney specimen was assigned a concentration below DL for analysis purposes. The Cd concentrations in 12 kidney specimens were below 0.2mg kg-1, between 0.288 and 1.221mg kg-1 in 16 and above 1.5mg kg-1 (2.6 - 3.64mg kg-1) in 3 specimens. The mean renal Cd concentration for the population (0.71±0.96mg kg-1) was statistically lower than 1.5mg kg-1 (p <0.05). Cd was therefore shown to be a chemical hazard for consumers of kidneys and a potential environmental hazard in the study area. Pb was negative in all of the 31 liver specimens, while in all the 30 kidney specimen digestates it was detected at concentrations below 1.1mg kg,-1. This result confirmed the presence of Pb as a potential chemical hazard found in bovine kidneys. However, a more sensitive analytical method was required to assess Pb food chain and public health hazard parameters in the study area. An epidemiological investigation of the study area using geographical information systems (GIS) to explore geographical factors that could have influenced exposure to Cd and Pb was done. While proximity to operational and decommissioned mining ventures appeared to result in higher mean renal Cd concentrations, the influence was not statistically significant. Feedlot rearing also appeared to cause higher mean renal Cd concentrations but the impact was also not statistically significant. It was concluded that Cd and Pb were chemical environmental contaminants which enter the animal and human food chain in the study area. A kilogram of bovine kidney-meat from approximately one in ten cattle (9.7%) carried more than 1.5mg Cd, exceeding the recommended CAC total dietary exposure for a 60-kg man. A mathematical model was used to estimate the risk of cattle with renal Cd concentration exceeding 1.5mg kg,-1, the expected number of cattle affected and the weight of meat entering the food chain. The estimated cattle population affected monthly was 5.95%, with a range of between 5 and 11 (mean = 8±4) cattle. These cattle were estimated to yield 8 to 18 (mean 13±6) kg bovine kidney-meat per month. A WHO standard-weight man who consumes a kilogram of kidney meat in this category in a month risks exposure to Cd doses beyond the CAC PTMI. The epidemiological triad of interactions between the host (cattle), agent (Cd and Pb) and the environment (proximity to mines) was used in order to suggest risk mitigation options. Recommendations from this study included advocacy on Cd and Pb in the food chain and developing partnerships with mining entities so that risk mitigation and communication can be better coordinated. Consumers are advised to reduce their monthly intake of kidney meat as this organ tissue has higher levels that those in other bovine organs and tissues. The cattle in the study were mature breeding animals (>5 years) and it is likely that this factor increased the risk of higher levels in kidneys as temporal determinants for bioaccumulation of Cd are important. The kidneys of younger animals would thus be less likely to contain significant Cd levels. Lastly, use of mathematical modelling, to translate research findings into quantitative estimates useful for public health safety programs, is recommended. / Dissertation (MMedVet)--University of Pretoria, 2012. / Paraclinical Sciences / unrestricted

All carbohydrates metabolized in the body must first be phosphorylated, As a result of Lundgaard's (1930 ) and Lohmann's (1934) discoveries, the focal interest of muscle biochemlstry has passed from the carbohydrate molecules to the phosphorus compounds, For glucose, the first reaction is the formation of a phosphate ester, glucose-6- phosphate, D. M. Neeedham (1938) found that ATP acts as a phosphorus donor, Glucose-6-phosphate may be transformed into glucose-1-phosphate or into fructose-6-phosphate. In liver, it may be hydrolized back to free glucose and inorganic phosphorus, Bate-Smith (1948) indicated that the free phosphate must be present before any breakdown of glycogen occurs and that the breakdown of glycogen will occur to the extent that free phosphate becomes available. Analysis of total and inorganic phosphorus in the liver is a measure of how much sugar is phosphorylated, This is related to the utilization of sugar, As the liver is an organ vitally concerned with the mechanism of carbohydrate, protein, and fat metabolism, it stores , transforms, and regulates food materials, T. B, Osborne , et al. (1919) suggested that economy in nutrition during growth depends upon the correct adjustment between the proportions of protein and total energy supplied. Quo (19 55) found that total carbohydrate content of turkey livers increased slightly with the addition of sucrose to the ration, The effect of sucrose in the ration on the protein content of turkey livers has not been investigated, The purpose of this study was to determine the influence of short pre-slaughter feeding of various levels of sucrose to turkeys on total and inorganic phosphorus and protein content of turkey liver and muscle. This thesis is part of a larger project which includes the feeding of sucrose to various farm animals and poultry. This work has been 2 under investigation at Utah Agricultural Experiment Station since 1950. Weight gains, dressing percentages, liver weights, and total carbohydrate content, pH, total solids, ether extract and color of liver and muscle of the sucrose-fed-animal or bird has been determined, This thesis includes the total, inorganic, and organic phosphorus and protein values on both liver and muscle and measurement of color of liver of the sucrose-fed turkeys.

Author: Nikola Jozefčeková Title: Endoglin and liver Form: Diploma Thesis University: Charles University, Faculty of Pharmacy in Hradec Králové Degree: Pharmacy This diploma thesis concludes the available information about endoglin, its isoforms in the liver and its impact on the liver during various pathological conditions. In the first part of the thesis describes morphology and physiology of the liver, its structure, histology and metabolic functions. Second part contains an information about endoglin, its isoforms and role in TGF-β signaling complex, expression of endoglin and regulation of the expression. In the third part are described liver diseases during which is expression of endoglin changed. This part deals with the significance of endoglin as a diagnostic and prognostic marker. Endoglin (CD105, TGF-β receptor III) is a homodimeric transmembrane glycoprotein and a membrane co-receptor TGF-β with high expression in endothelial cells. Endoglin plays an important role in the vascular development. Endoglin is involved in the processes of angiogenesis, vascular homeostasis and TGF-β signalization. It affects activity of TGF-βRII, ALK1 and ALK5 receptors. Due to the interactions with TGF-β complex, modulation of activity of ALK receptors and Smads, endoglin controls fibrotic and anti-...