The international journal of biochemistry & cell biology
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Sepsis is the systematic response to infection. In septic patients who develop severe disease, excessive inflammation damages the lungs, liver, kidneys, and cardiovascular system, leading to multiple organ failure and an associated high mortality rate. Sepsis is the leading cause of death in the intensive care unit. ⋯ Impairment of critical organs is closely associated with infiltration of activated neutrophils into those tissues as well as increased activation of endothelial, epithelial, and macrophage populations within the organs to produce a deregulated, overly aggressive inflammatory response. New pharmacological advances hold promise in improving survival from this multi-systemic disorder. Increasing understanding of the signal transduction pathways of inflammatory cells involved in the disease suggests that targeting specific kinases and transcriptional regulatory mechanisms may prove improve outcome from sepsis.
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Int. J. Biochem. Cell Biol. · Dec 2002
The role of oxidised regenerated cellulose/collagen in wound repair: effects in vitro on fibroblast biology and in vivo in a model of compromised healing.
Irrespective of underlying chronic wound pathology, delayed wound healing is normally characterised by impaired new tissue formation at the site of injury. It is thought that this impairment reflects both a reduced capacity to synthesize new tissue and the antagonistic activities of high levels of proteinases within the chronic wound environment. Historically, wound dressings have largely been passive devices that offer the wound interim barrier function and establish a moist healing environment. ⋯ In vivo studies considered the closure and histological characteristics of diabetic wounds treated with ORC/collagen compared to those of wounds given standard treatment on both diabetic and non-diabetic mice. ORC/collagen was found to significantly accelerate diabetic wound closure and result in a measurable improvement in the histological appearance of wound tissues. As the diabetic mouse is a recognised model of impaired healing, which may share some characteristics of human chronic wounds, the results of this in vivo study, taken together with those relating the positive effects of ORC/collagen in vitro, may predict the beneficial use of this device in the clinical setting.
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Int. J. Biochem. Cell Biol. · Oct 2001
Transforming growth factor beta1 mediates hypopigmentation of B16 mouse melanoma cells by inhibition of melanin formation and melanosome maturation.
Transforming growth factor-beta1 (TGFbeta1) downregulates tyrosinase in B16 melanoma cells by decreasing gene expression and the intracellular half-life of the enzyme, but does not block tyrosinase stimulation by alpha-melanocyte stimulating hormone (alphaMSH). In the presence of both agents, the enzymatic activity is intermediate between the one of cells treated with either agent alone. Here we show that TGFbeta1 equally inhibits the melanogenic activities of melan-a melanocytes and B16 melanoma cells, thus validating the B16 model. ⋯ TGFbeta1 increased the percentage of stage III melanosomes. This trend was even more marked in cells treated with alphaMSH and TGFbeta1. The accumulation of incompletely melanized melanosomes is consistent with the inhibition of melanin formation activity by TGFbeta1 and with its hypopigmenting effect.
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Int. J. Biochem. Cell Biol. · Oct 1997
G proteins and regulation of pyruvate dehydrogenase activity by insulin in human circulating lymphocytes.
Pertussis toxin (PT) catalyzes ADP-ribosylation of G protein alpha subunits, thus preventing their role as transducers of external signals targeting metabolic pathways. In vitro, in human circulating lymphocytes insulin at physiological concentrations (5 microU/ml) determines sharp activation of pyruvate dehydrogenase (PDH), the rate limiting enzyme in glucose oxidative breakdown. This study evaluates whether the above-described effects of insulin over PDH are mediated through G proteins. ⋯ In circulating lymphocytes exposed to PT alone, or in combination with insulin, PDH activity falls significantly below basal values (P < 0.001); PT-9K instead has no effect on basal or on insulin-stimulated PDH activity. ADP-ribosylation of a plasma membrane component with apparent molecular mass (42 kDa) comparable to that of the Gi (inhibitory) protein alpha subunit takes place in cells exposed to PT but not in those exposed to PT-9K. In human circulating lymphocytes Gi proteins or Gi protein-like components appear to be involved in preserving basal PDH activity as well as in the mechanism by which insulin exerts its control over PDH.