The international journal of biochemistry & cell biology
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Int. J. Biochem. Cell Biol. · Oct 2005
ReviewInsulin-like growth factor-1 and muscle wasting in chronic heart failure.
Chronic heart failure is a clinical syndrome of cardiac origin, which affects various organ systems. It is associated with metabolic abnormalities leading to a catabolic syndrome in advanced stages of the disease. As in several other chronic diseases, skeletal muscle dysfunction and structural muscle abnormalities result in progressive muscle wasting and cachexia. ⋯ This suppression occurs in the presence of normal serum levels of insulin-like growth factor-1. In addition to catabolic effects of proinflammatory cytokines, these recent findings are consistent with reduced anabolism involving altered local insulin-like growth factor-1 levels in progressive muscle atrophy in chronic heart failure. This article describes local effects of insulin-like growth factor-1 on skeletal muscle function and morphology, its role in stem cell recruitment and muscle regeneration as well as its regulation in circumstances of muscle inflammation and wasting.
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Hepatorenal syndrome (HRS) is a major complication of patients with cirrhosis, with the annual incidence in patients with ascites being approximately 8% []. This syndrome develops in the latest phase of the disease and there is now evidence that it is an important determinant of patient survival. Many aspects of HRS are, however, still poorly understood. ⋯ Intrarenal mechanisms are also important and require prolonged improvement in circulatory function to be deactivated. Long-term administration of intravenous albumin and vasoconstrictors or the correction of portal hypertension with a transjugular intrahepatic portacaval shunt are effective in the treatment of HRS. They also appear to improve survival and may serve as a bridge to liver transplantation, which is the treatment of choice in these patients.
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Int. J. Biochem. Cell Biol. · Apr 2004
ReviewStem cell-based approaches to solving the problem of tissue supply for islet transplantation in type 1 diabetes.
Type 1 diabetes is a debilitating condition, affecting millions worldwide, that is characterized by the autoimmune destruction of insulin-producing pancreatic islets of Langerhans. Although exogenous insulin administration has traditionally been the mode of treatment for this disease, recent advancements in the transplantation of donor-derived insulin-producing cells have provided new hope for a cure. However, in order for islet transplantation to become a widely used technique, an alternative source of cells must be identified to supplement the limited supply currently available from cadaveric donor organs. ⋯ The potential for the differentiation of embryonic stem (ES) cells to islet phenotype is discussed, as well as the possibility of identifying and exploiting a pancreatic progenitor/stem cell from the adult pancreas. The possibility of creating new islets from adult stem cells derived from other tissues, or directly form other terminally differentiated cell types is also addressed. Finally, a model for the isolation and maturation of islets from the neonatal porcine pancreas is discussed as evidence for the existence of an islet precursor cell in the pancreas.
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Int. J. Biochem. Cell Biol. · Jul 2003
ReviewAlpha(1)-antitrypsin deficiency, liver disease and emphysema.
alpha(1)-Antitrypsin is a member of the serine proteinase inhibitor (serpin) superfamily and a potent inhibitor of neutrophil elastase. The most important deficiency variant of alpha(1)-antitrypsin arises from the Z mutation (Glu342Lys). This mutation perturbs the protein's tertiary structure to promote a precise, sequential intermolecular linkage that results in polymer formation. ⋯ Thus, the Z alpha(1)-antitrypsin homozygote is predisposed to developing early onset basal, panacinar emphysema. In this review, we summarise the current understanding of the pathobiology of alpha(1)-antitrypsin deficiency and the associated liver cirrhosis and emphysema. We show how this knowledge has led to the development of novel therapeutic approaches to treat this condition.
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Int. J. Biochem. Cell Biol. · Jan 2003
ReviewPathological aspects of apoptosis in severe sepsis and shock?
Today, despite the application of contemporary operative/pharmacological approaches in the treatment of the critically ill trauma/surgery patient, we are still faced with a high incidence of patients who develop sepsis and subsequent multiple organ failure. This review attempts to summarize data gathered over the last few years, from both experimental and patient settings, that not only documents the presence of apoptosis, but begins to define its contribution to the pathology of sepsis and shock, which in turn precipitate organ injury/damage.