Undernutrition is commonly associated with chronic disease in children and the elderly. Overnutrition is also, but less commonly, associated with chronic illness. In most diseases malnutrition arises because energy intake does not match energy output. Traditionally, the focus of research has been on abnormalities in energy expenditure, in the belief that these factors were the main determinants of energy imbalance. Recent studies using the doubly-labelled-water method to measure total energy expenditure, combined with more complex study design, have suggested an alternative conclusion. In many chronic diseases patient behaviour, and particularly energy intake, is responsible for energy imbalance and malnutrition. Energy balance studies have therefore provided a useful foundation for the design of strategies aimed at preventing or managing chronic malnutrition. However, modifying patient behaviour is an ambitious undertaking which may not be within the scope of existing clinical nutrition services. A number of non-traditional models of managing chronic malnutrition in children and the elderly are promising. Increasing recognition of the value of systematic review will also provide improved strategies for prevention and management of chronic malnutrition.

Insulin resistance develops as a response to virtually all types of surgical stress. There is an increasing body of evidence that suggests that insulin resistance in surgical stress is not beneficial for outcome. A recent large study in intensive-care patients showed that aggressive treatment of insulin resistance using intravenous insulin reduced mortality and morbidity substantially. Similarly, in burn patients, intensive insulin and glucose treatment has been shown to improve N economy and enhance skin-graft healing. In surgical patients insulin resistance has been characterized in some detail, and has been shown to have many similarities with metabolic changes seen in patients with type 2 diabetes. This finding may be important since insulin resistance has been shown to be one independent factor that influences length of stay. When patients about to undergo elective surgery have been treated with glucose intravenously or a carbohydrate-rich drink instead of overnight fasting, insulin resistance was reduced by about half. A small meta-analysis showed that when post-operative insulin resistance was reduced by preoperative carbohydrates, length of hospital stay was shortened. Overnight intravenous glucose at high doses improved post-operative N economy. This type of treatment has also been shown repeatedly to reduce cardiac complications after open-heart surgery. Furthermore, if the carbohydrates are given as a drink pre-operatively, pre-operative thirst, hunger and anxiety are markedly reduced. In summary, preventing or treating insulin resistance in surgical stress influences outcome. Fasting overnight is not an optimal way to prepare patients for elective surgery. Instead, pre-operative carbohydrates have clinical benefits.

General anaesthesia causes hypothermia due to decreased metabolic rate and impaired thermoregulation. Many warming devices are in use to prevent heat loss, but little attention has been paid to stimulating the body's own heat generation. All nutrients raise energy expenditure, and the highest thermic effect is ascribed to amino acids and proteins, 30–40% in the awake state. Amino acids infused during general anaesthesia exert a thermic effect that is enhanced compared with that in the awake state. At awakening from anaesthesia, post-operative hypothermia may be prevented without shivering. The tissues involved and the mechanisms by which nutrients stimulate heat production are still not completely understood. However, these findings support the existence of an inhibitory action normally exerted by central thermosensors, in order to maintain oxidative metabolism within certain limits, to prevent hyperthermia. During anaesthesia central thermosensors are silenced and, hence, amino acid thermogenesis is exaggerated. The amino acid-induced heat generation during anaesthesia predominantly occurs in extra-splanchnic tissues, most probably in skeletal muscle. It may reflect an increased protein turnover, as both protein breakdown and synthesis are energy-consuming processes known to generate heat. Possibly, amino acid infusion provides substrates, otherwise mobilized from the body's own tissues, needed for wound healing and immunological function. However, other cellular mechanisms may also contribute to this non-shivering thermogenesis.

The n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoicacid (DHA) are found in high proportions in oily fish and fish oils. The n-3 PUFA are structurally and functionally distinct from the n-6 PUFA. Typically, human inflammatory cells contain high proportions of the n-6 PUFA arachidonic acid and low proportions of n-3 PUFA. The significance of this difference is that arachidonic acid is the precursor of 2-series prostaglandins and 4-series leukotrienes, which are highly-active mediators of inflammation. Feeding fish oil results in partial replacement of arachidonic acid in inflammatory cell membranes by EPA. This change leads to decreased production of arachidonic acid-derived mediators. This response alone is a potentially beneficial anti-inflammatory effect of n-3 PUFA. However, n-3 PUFA have a number of other effects which might occur downstream of altered eicosanoid production or might be independent of this activity. For example, animal and human studies have shown that dietary fish oil results in suppressed production of pro-inflammatory cytokines and can decrease adhesion molecule expression. These effects occur at the level of altered gene expression. This action might come about through antagonism of the effects of arachidonic acid-derived mediators or through more direct actions on the intracellular signalling pathways which lead to activation of transcription factors such as nuclear factor kappa B (NFêB). Recent studies have shown that n-3 PUFA can down regulate the activity of the nuclear transcription factor NFêB. Fish oil feeding has been shown to ameliorate the symptoms in some animal models of chronic inflammatory disease and to protect against the effects of endotoxin and similar inflammatory challenges. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some patients with asthma, supporting the idea that the n-3 PUFA in fish oil are antiinflammatory. There are indications that inclusion of n-3 PUFA in enteral and parenteral formulas might be beneficial to patients in intensive care or post-surgery.

Home parenteral nutrition is required by patients with intestinal disease such that they are unable to maintain nutritional status or fluid volume without this treatment. A Managed Clinical Network has been established in Scotland. The aims of this multi-professional group are to ensure equity of access and that patients are managed according to nationally-agreed evidence-based procedures and protocols. The Clinical Standards Board for Scotland has provided support in preparing a quality-assurance framework to which the network must adhere.

Peroxisome proliferator-activated receptor (PPAR) α represents an important member of the nuclear hormone receptor superfamily that can be activated by a variety of natural fatty acids, some of their metabolites and by commonly-used anti-lipidaemic drugs. We recently demonstrated PPARα expression in T lymphocytes, where it controls the initiation of transcription of T-box expressed in T-cells (T-bet) independent of added agonist. T-bet is an activation-inducible transcription factor regulator of interleukin 2 (suppression) and interferon γ (stimulation) synthesis. A suppressed ability to produce interleukin 2 and an enhanced production of interferon γ occurs in activated T-cells from PPARα-/- mice, as well as in T-cells from wild-type aged animals whose lymphocytes express lowered basal levels of PPARα. The dysregulated expression and/or function of cytokines, glucocorticoids or leptin that occurs with advanced age could all be responsible for the reduced expression of PPARα. Dietary supplementation of aged mice with vitamin E, or supplementation with known agonists of PPARα, was associated with elevation of lymphocyte expression of this nuclear hormone receptor, restoration of control over T-bet expression and elimination of the dysregulated production of interleukin 2 and interferon γ following lymphocyte activation. Interleukin 2 and interferon γ play very important roles in the initiation and/or regulation of immune, inflammatory and autoimmune disease states. Thus, the mechanisms that control the timing, magnitude and duration of specific cytokine production by activated T lymphocytes need clarification before appropriate nutritional or therapeutic strategies can be devised to treat disease conditions where cytokine expression and/or activities are deemed to be dysregulated and responsible.

Dietary fatty acids have numerous effects on cellular function, many of which are achieved by altering the expression of genes. The present paper reviews recent data on the mechanisms by which fatty acids influence DNA transcription, and focus specifically on the importance of three transcription factors: peroxisome proliferator-activated receptor α; liver X receptor α; sterol regulatory element-binding protein 1c. These data indicate that fatty acids induce or inhibit the mRNA expression of a variety of different genes by acting both as agonists and as antagonists for nuclear hormone receptors.

Previous work has demonstrated that, besides its effects on Ca and bone metabolism, the active form of cholecalciferol, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), possesses pronounced immunomodulatory effects. In non-obese diabetic (NOD) mice primary (before disease onset), secondary (after insulitis but before diabetes onset) as well as tertiary (after transplantation of syngeneic islets) prevention of diabetes was demonstrated with 1,25(OH)2D3 and its chemically-manufactured non-hypercalcaemic analogues. 1,25(OH)2D3 exerts its immune effects both at the level of the T lymphocyte (shift in cytokine profile from T-helper (Th)1 to Th2, enhanced sensitivity to apoptosis-inducing signals) as well as at the level of the antigen-presenting cell (reduced antigen presentation, reduced production of Th1-promoting cytokines, reduced expression of co-stimulatory molecules). Also, physiologically, 1,25(OH)2D3 is believed to have a role in the immune system by serving as a negative feedback signal, limiting the mounted immune reaction. To test the clinical applicability of 1,25(OH)2D3 as treatment for type 1 diabetes in genetically-at-risk young children, we tested whether short-term early-life intervention with cholecalciferol or non-hypercalcaemic analogues of 1,25(OH)2D3 could prevent diabetes in NOD mice. Significant protection of pancreatic β cells against autoimmune destruction was observed in analogue-treated and especially in cholecalciferol-treated NOD mice as compared with controls (P < 0.005). This short-term early-life intervention was, however, not able to protect the mice from developing diabetes during their lifetime. Possible solutions are longer or combined treatments with other immunomodulators that have synergistic effects with 1,25(OH)2D3 and its analogues.

Although the clinical benefits of dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) has been recognised for a number of years, the molecular mechanisms by which particular PUFA affect metabolism of cells within the synovial joint tissues are not understood. This study set out to investigate how n-3 PUFA and other classes of fatty acids affect both degradative and inflammatory aspects of metabolism of articular cartilage chondrocytes using an in vitro model of cartilage degradation. Using well-established culture models, cartilage explants from normal bovine and human osteoarthritic cartilage were supplemented with either n-3 or n-6 PUFA, and cultures were subsequently treated with interleukin 1 to initiate catabolic processes that mimic cartilage degradation in arthritis. Results show that supplementation specifically with n-3 PUFA, but not n-6 PUFA, causes a decrease in both degradative and inflammatory aspects of chondrocyte metabolism, whilst having no effect on the normal tissue homeostasis. Collectively, our data provide evidence supporting dietary supplementation of n-3 PUFA, which in turn may have a beneficial effect of slowing and reducing inflammation in the pathogenesis of degenerative joint diseases in man.

The aim of the present paper is to briefly review the literature relating to clinical studies of the use of polyunsaturated long-chain fatty acids in the treatment of inflammatory bowel diseases ( IBD) such as ulcerative colitis and Crohn's disease. The reasons for the discrepancies in the findings could be related to the different study designs, different treatments, overlapping of treatment effects, as well as the variety of treatment formulations and doses used, which have led to results that are, in certain instances, very difficult to explain. Emphasis on a treatment formulation which reduces the incidence of side effects, together with careful selection of patients and experimental design, seems to be associated with benefits, and these studies point to the therapeutic potential for these lipids in the therapy of IBD. It is possible that these fatty acids act by reducing low-grade active inflammation rather than by preventing reinitiation of the inflammatory process from a truly quiescent state. Whether this treatment is applicable to all IBD patients has not been fully elucidated. Nevertheless, taken together, all these studies suggest the effectiveness of these new therapeutic approaches, not only when conventional treatment fails or when it is not possible to treat chronically, but also, in some instances, as first choice.

Vitamin A is necessary for normal differentiation of epithelial tissues, the visual process and reproduction, and is vital for the optimal maintenance and functioning of the innate and adaptive immune system. Vitamin A deficiency is one of the most profuse nutritional deficiencies worldwide. It is associated with increased susceptibility to infectious diseases in both man and animal models. Vitamin A also has a role as an anti-inflammatory agent. Supplementation with vitamin A has been found to be beneficial in a number of inflammatory conditions, including skin disorders such as acne vulgaris, broncho-pulmonary dysplasia and some forms of precancerous and cancer states. The present review suggests that vitamin A deficiency induces inflammation and aggravates existing inflammatory states. Supplementation with vitamin A in selected cases could ameliorate inflammation. The two main mechanisms which appear to be involved in the prevention of disease are the effects of vitamin A on the immune system and the effect on epithelial integrity.