Biomedical subjects

Kenneth C H Fearon

Publications and source records attributed to Kenneth C H Fearon.

6 recordsLinked to original sources

PubMed2004

Modulation of the liver export protein synthetic response to feeding by an n-3 fatty-acid-enriched nutritional supplement is associated with anabolism in cachectic cancer patients.

The acute-phase protein response is associated with accelerated weight loss and shortened survival in cancer. This may be due to hepatic protein synthesis increasing demand for amino acids. An n -3 fatty-acid-enriched nutritional supplement will moderate aspects of cachexia in cancer patients. The present study examined the effect of such a supplement on hepatic synthesis of albumin and fibrinogen. Albumin and fibrinogen synthesis were measured in the fed and fasting state in eight weight-losing patients with pancreatic cancer by an intravenous flooding dose technique. Tracer incorporation into proteins was measured by GC/MS. Patients were restudied after 3 weeks of oral supplement enriched with fish oil (providing 2510 kJ/day and 2 g of eicosapentaenoic acid/day). At baseline, all patients were losing weight (median, 2.4 kg/month). After 3 weeks of consumption of the fish-oil-enriched nutritional supplement, patients' weight stabilized (median change, +1 kg; P = 0.01). At baseline, albumin and fibrinogen synthesis rates were stimulated in the fed compared with the fasting state [14.2 compared with 11.3 g/day (29% rise; P = 0.01) and 4.5 compared with 3.3 g/day (38% rise; P = 0.01) respectively]. After 3 weeks of the supplement, this stimulation in the fed state was no longer observed for albumin and was reduced for fibrinogen [11.2 compared with 10.5 g/day (3% rise; P = 0.21) and 3.7 compared with 2.9 g/day (17% rise; P = 0.01) respectively]. After 3 weeks, the combined albumin plus fibrinogen synthetic rate tended to fall in the fasting state (14.7 compared with 12.3 g/day; P = 0.09) and was significantly reduced in the fed state (18.7 compared with 14.6 g/day; P = 0.01). Modulation of hepatic export protein synthesis with feeding may have contributed to the net whole-body anabolism observed with administration of the n -3 fatty-acid-enriched oral supplement.

Aged↗

PubMed2004

Renal metabolism of amino acids: its role in interorgan amino acid exchange.

The kidneys play a role in the synthesis and interorgan exchange of several amino acids. The quantitative importance of renal amino acid metabolism in the body is not, however, clear. We review here the role of the kidney in the interorgan exchange of amino acids, with emphasis on quantitative aspects. We reviewed relevant literature by using a computerized literature search (PubMed) and checking relevant references from the identified articles. Our own data are discussed in the context of the literature. The kidney takes up glutamine and metabolizes it to ammonia. This process is sensitive to pH and serves to maintain acid-base homeostasis and to excrete nitrogen. In this way, the metabolism of renal glutamine and ammonia is complementary to hepatic urea synthesis. Citrulline, derived from intestinal glutamine breakdown, is converted to arginine by the kidney. Renal phenylalanine uptake is followed by stoichiometric tyrosine release, and glycine uptake is accompanied by serine release. Certain administered oligopeptides (eg, glutamine dipeptides) are converted by the kidneys to their constituent components before they can be used in metabolic processes. The kidneys play an important role in the interorgan exchange of amino acids. Quantitatively, for several important amino acids, the kidneys are as important as the gut in intermediary metabolism. The kidneys may be crucial "mediators" of the beneficial effects of specialized, disease-specific feeding solutions such as those enriched in glutamine dipeptides.

Amino Acids↗

PubMed2003

The nutritional management of surgical patients: enhanced recovery after surgery.

Malnutrition has long been recognised as a risk factor for post-operative morbidity and mortality. Traditional metabolic and nutritional care of patients undergoing major elective surgery has emphasised pre-operative fasting and re-introduction of oral nutrition 3-5 d after surgery. Attempts to attenuate the consequent nutritional deficit and to influence post-operative morbidity and mortality have included parenteral, enteral and oral sip feeding. Recent studies have emphasised that an enhanced rate of recovery can be achieved by a multi-modal approach focused on modulating the metabolic status of the patient before (e.g. carbohydrate and fluid loading), during (e.g. epidural anaesthesia) and after (e.g. early oral feeding) surgery. Using such an approach preliminary results on patients undergoing elective colo-rectal surgery indicate a significant reduction in hospital stay (traditional care, n 48, median stay 10 d v. enhanced recovery programme, n 33, median stay 7d; P<0.01) can be achieved. Such findings emphasise the potential role of multi-modal care programmes in the promotion of early recovery from major surgical trauma.

Humans↗

PubMed2003

Eicosapentaenoic acid perturbs signalling via the NFkappaB transcriptional pathway in pancreatic tumour cells.

In addition to various roles in membrane structure and metabolism, polyunsaturated fatty acids have effects on signal transduction and on the regulation of gene expression. Eicosapentaenoic acid (EPA) is an omega-3 fatty acid which is known to induce cell cycle arrest and apoptosis in pancreatic tumour cells. NFkappaB is a key transcription factor regulating genes involved in the immune response and has been implicated in apoptotic pathways. In this study we investigated the effect of eicosapentanoic acid on the NFkappaB pathway in pancreatic tumour cells. The pancreatic cell line MIA PaCa2 was incubated in the presence of the fatty acids EPA (n-3), arachidonic acid (AA, n-6) or oleic acid (OA, n-9) before pulsing with TNF to provide a kinetic assessment of NFkappaB activation and IkappaBalpha degradation. Pre-incubation of pancreatic cells with EPA or AA for 2 h before pulsing with TNF preserved IkappaBalpha but did not prevent NFkappaB activation. Indeed, NFkappaB activation was prolonged after exposure to EPA. N-acetyl-L-cysteine did not influence the effect of EPA on TNF-stimulated IkappaBalpha degradation. These results suggest that the omega-3 fatty acid EPA perturbs the NFkappaB pathway by a novel mechanism. This mechanism may be important in delineating alternative pathways to NFkappaB activation.

Acetylcysteine↗

PubMed2002

Cancer cachexia.

Cancer cachexia is a complex, multifactorial syndrome that results from a reduction in food intake, a variety of metabolic abnormalities (including hypermetabolism) or more often a combination of the two. Multiple mediator pathways including pro-inflammatory cytokines, neuroendocrine hormones and tumour-specific factors are involved. Therapy requires a multi-model approach that addresses both reduced food intake and metabolic change. Combination treatments such as nutritional support plus metabolic/inflammation modulation promise improved functional capacity and quality of life.

Cachexia↗

PubMed2002

Eicosanoid-dependent cancer cachexia and wasting.

The reversal of catabolic processes remains a significant challenge related, in part, to their complexity and our incomplete understanding of the mechanisms involved. The eicosanoids are key players in the inflammatory process and have been implicated in the process of cancer cachexia. They are unsaturated C20 fatty acids which can be separated into two main groups: the lipoxygenase products including leukotrienes and lipoxins, and the prostanoids including prostaglandins, prostacyclin and thromboxane. This review examines the biology of the eicosanoids and the evidence of a role for the eicosanoids in cancer cachexia and wasting.

Animals↗