Browsing by Subject "Albumins"
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- ItemOpen AccessAlbumin metabolism following partial hepatectomy in the rat(1980) Lloyd, Elwyn Allden; Saunders, Stuart JIn the work reported here the author set out to investigate five aspects of albumin metabolism following partial hepatectomy in the rat. 1. The plasma albumin levels following partial hepatectomy. 2. The effect of partial hepatectomy on the albumin synthesis rate. 3. The effect of supplementary amino acids on the albumin synthesis rate following partial hepatectomy. 4. The effect of hydrocortisone on the albumin synthesis rate following partial hepatectomy. 5. The effect of partial hepatectomy on the albumin catabolic rate.
- ItemOpen AccessEvaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting(Public Library of Science, 2013) Selden, Clare; Spearman, Catherine Wendy; Kahn, Delawir; Miller, Malcolm; Figaji, Anthony; Erro, Eloy; Bundy, James; Massie, Isobel; Chalmers, Sherri-Ann; Arendse, HiramLiver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4-6×10 10 cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell group, human proteins accumulated in pigs' plasma. Delivery of biomass using a short-term cold-chain enabled transport and use without loss of function over 3days. Thus, a fluidised-bed bioreactor containing alginate-encapsulated HepG2cell-spheroids improved important parameters of acute liver failure in pigs. The system can readily be up-scaled and transported to point-of-use justifying development at clinical scale.
- ItemOpen AccessPolymorphisms in the non-muscle myosin heavy chain gene (MYH9) are associated with lower glomerular filtration rate in mixed ancestry diabetic subjects from South Africa(Public Library of Science, 2012) Matsha, Tandi Edith; Masconi, Katya; Yako, Yandiswa Yolanda; Hassan, Mogamat Shafick; Macharia, Muiriri; Erasmus, Rajiv Timothy; Kengne, Andre PascalObjective: Though single nucleotide polymorphisms (SNPs) in the non-muscle myosin gene (MYH9) have been reported to explain most of the excess risk of nondiabetic chronic kidney disease (CKD), in African-Americans, some studies have also shown associations with diabetic end-stage renal disease. We investigated the association of MYH9 SNPs with renal traits in a mixed-ancestry South African population prone to diabetes. Research Design and METHODS: Three SNPs known to be associated with CKD (rs4821480, rs5756152 and rs12107) were genotyped using Taqman assay in 716 adults (198 with diabetes) from the Bellville-South community, Cape Town. Glomerular filtration rate was estimated (eGFR) and urinary albumin/creatinine ratio (ACR) assessed. Multivariable regressions were used to relate the SNPs with renal traits. RESULTS: Mean age was 53.6 years, with the expected differences observed in characteristics by diabetic status. Significant associations were found between rs575152 and serum creatinine, and eGFR in the total population, and in diabetic participants (all p≤0.003), but not in non-diabetics (all p≥0.16), with significant interactions by diabetes status (interaction-p≤0.009). The association with ACR was borderline in diabetic participants (p = 0.05) and non-significant in non-diabetics (p = 0.85), with significant interaction (interaction p = 0.02). rs12107 was associated with fasting-, 2-hour glucose and HbA1c in diabetic participants only (interaction-p≤0.003), but not with renal traits. CONCLUSION: MYH9 SNPs were associated with renal traits only in diabetic participants in this population. Our findings and other studies suggest that MYH9 may have a broader genetic risk effect on kidney diseases.
- ItemOpen AccessSome factors regulating albumin catabolism and synthesis(1968) Hoffenberg, Raymond; Brock, J FHypoalbuminaemia is an essential accompaniment of protein malnutrition. Yet the level of plasma albumin is usually regarded as a relatively crude reflection of a patient's nutritional status, reduction occurring only after prolonged or severe inadequacy of dietary protein. Brock recognized that a marginal degree of hypoalbuminaemia might be evidence of impending or early deficiency, and suggested that minor grades of "protein subnutrition" could conceivably exist with serum albumin levels still within the normal range. The work reported in this thesis developed originally out of an attempt to explore this possibility, and to characterize some of the changes in albumin metabolism that followed mild or early experimental protein deprivation in man and rabbits. Dynamic studies using albumin labelled with radioactive iodine revealed evidence of early adaptational changes, possibly occurring before alteration in the plasma albumin levels. While these studies shed some light on the response of albumin metabolism to experimental depletion, they failed to provide the hoped-for means by which subclinical protein malnutrition could be detected. From this work, however, it was but a short conceptual jump to the general problem of albumin homeostasis, a consideration of which forms the basis of this thesis. The first approach was a study of changes in albumin synthesis and catabolism in rabbits following limitation of dietary protein intake. Adaptive responses were then investigated in animals, provided with normal protein diets, after protein depletion induced by an alternative method - plasmapheresis - and, finally, after intravenous infusion of albumin solutions. Based on these and reported results, a tentative hypothesis has been adduced to account for the body's adaptation to variation in the plasma albumin pool, brought about by experimental manipulation or occurring spontaneously in disease.