肝炎后肝硬化病人血浆氨基酸和整体蛋白质更新速率的研究

目的用稳定性检索标记的１５Ｎ－甘氨酸和１３Ｃ－亮氨酸双示踪技术研究肝炎后肝硬化病人血浆氨基酸和整体蛋白质更新速率。方法１１例正常人和１９例肝硬化加入（１２例代偿期，７例失代偿期）恒速静滴６小时示踪剂后测定血浆中标记氨基酸水平，并计算血浆中氨基酸和整体蛋白质的更新速率，合成速率和分解速率。结果肝硬化时血浆氨基酸和蛋白顶的更新速率，合成和分解速率均明显加快，分解速率大于合成速率，此现象在失代偿期尤为明显。结论肝硬化时机体氨基酸和蛋白质代谢处于高流量状态，分解速率明显高于合成速率，处于负氮平衡状态。     

Gastrectomized patients are in a state of chronic protein malnutrition analyses of 23 amino acids

BACKGROUND/AIMS: Malnutrition is one of the major postoperative complications of radical subtotal or total gastrectomy for gastric cancer. This study was conducted to clarify the nutritional consequences of radical gastrectomy with respect to protein metabolism. METHODOLOGY: To evaluate the nutritional status and the abnormalities in protein metabolism in such cases, serum concentrations of 23 amino acids were measured by high performance liquid chromatography in 40 patients who had undergone either subtotal (n = 20) or total (n = 20) gastrectomy more than 6 months prior to this analysis. RESULTS: Serum concentrations of total amino acids and nonessential amino acids were the same between gastrectomized patients and healthy controls (n = 50). However, concentrations of essential amino acids, essential amino acid/nonessential amino acid and branched-chain amino acid/total amino acid ratios were significantly lower in patient groups than in normal controls. Each essential amino acid was decreased and concentrations of glutamate and citrulline were increased in both patient groups compared with controls. The major differences between patients with subtotal and total gastrectomies included an increased ornithine and a decreased arginine concentration in patients with subtotal gastrectomy. CONCLUSIONS: These changes suggest that malabsorption of protein from the intestinal tract causes persistent proteolysis in the skeletal muscle for long periods of time after surgery in these patients and that changes in ornithine and citrulline levels may reflect more severe alterations in those with total gastrectomy.     

Branched chain amino acids in the management of chronic liver disease. Facts and fantasies

The liver plays a central role in protein and amino acid metabolism. It processes dietary amino acids and reprocesses amino acids released from muscle protein degradation. It utilises amino acids for protein synthesis and gluconeogenesis, regulates the supply of amino acids to peripheral tissues and converts excess amino acids to urea. In patients with liver disease the liver's ability to control both plasma and tissue amino acid fluxes may be seriously disturbed. The resultant changes in amino acid metabolism may be implicated in the genesis of the neuropsychiatric abnormalities and the deterioration in nutritional status commonly observed in patients with hepatic failure. Thus, on theoretical grounds, amelioration of these amino acid abnormalities might benefit patients with liver disease who have hepatic encephalopathy or are malnourished. However, there is, at present, no consensus as to the efficacy, practicality or cost-effectiveness of 'amino acid therapy' in patients with liver disease.     

REVIEW: Nutritional support for patients with cirrhosis

Nutritional support is indicated when cirrhotic patients undergo surgery becasue they are malnourished, hypercatabolic and immunocompromised. However, the choice of nutrient may be problematic as the liver itself is the central organ of protein, fat and glucose metabolism. Branched chain amino acid-enriched solution may be the choice of protein source, as it is anticatabolic and it stimulates liver regeneration. Excessive glucose is undesirable as it may suppress endogenous fat utilization, which may be the preferred pathway of metabolism after hepatectomy. Medium chain triglycerides are preferred to long chain triglycerides as they are readily utilized and are not deposited in the liver; however, the tendency of cirrhotic patients to accumulate free fatty acids and glycerol after infusion of triglycerides dictates their use intermittently. Clinical studies have shown that perioperative nutritional support is beneficial in cirrhotic patients undergoing major hepatectomy or liver transplantation. The judicious choice of nutrient, care of the catheter and a limitation of the fluid infused are all prerequisites for the efficient use of perioperative nutritional support, which is complementary to a technically perfect operation.     

Effect of insulin and plasma amino acid concentration on leucine metabolism in cirrhosis

Clinically stable patients with cirrhosis demonstrate insulin resistance with regard to glucose metabolism. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in cirrhotic patients. To examine this question, we performed paired euglycemic insulin clamp studies in combination with 14C-leucine and indirect calorimetry. In the first study insulin alone was infused, and the plasma amino acid concentration was allowed to decline. During the second study a balanced amino acid solution was infused with insulin to increase the total plasma amino acid concentration approximately twofold. Insulin-mediated glucose disposal (4.68 vs. 6.45 mg/kg-min, p less than 0.01) was significantly impaired by 30% in cirrhotic patients during both insulin clamp studies. In the postabsorptive state, cirrhotic patients manifested low plasma leucine (76 vs. 102 mumol/L) and alpha-ketoisocaproate (19 vs. 30 mumol/L) concentrations, but all parameters of leucine turnover were normal. When insulin alone was infused, the endogenous leucine flux (an index of protein degradation) declined similarly in cirrhotic patients (30.8 mumol/m2-min) and control (26.9) subjects, and this was accompanied by a similar decrease in plasma leucine concentration (31% vs. 33%). The decline in circulating leucine concentration was accompanied by a parallel decline in leucine oxidation (5.1 vs. 4.6 mumol/m2-min) and nonoxidative (28.9 vs. 26.0 mumol/m2-min) leucine disposal, which were of similar magnitude in cirrhotic patients and control subjects, respectively. In both cirrhotic patients and control subjects, combined hyperinsulinemia/hyperaminoacidemia elicited a similar stimulation of nonoxidative leucine disposal (an index of protein synthesis) and leucine oxidation while causing a greater suppression of endogenous leucine flux than observed with insulin alone. Thus the suppressive effect of insulin on protein degradation and the stimulatory effect of insulin/amino acid infusion on protein synthesis are not impaired in cirrhotic patients, demonstrating a clear-cut dissociation between the effects of insulin on protein and glucose metabolism.     

Nutritional therapy in cirrhosis

Abstract   In recent years increasing interest has been given to nutritional therapy in a variety of chronic diseases, including cirrhosis. Protein/calorie malnutrition is a common feature of advanced liver disease, and considerably affects prognosis. Hence, the need for nutritional support to provide patients with the minimum protein requirements to balance increased catabolism. Although most patients tolerate normal protein supply, in subjects with impending encephalopathy a nutritional support with branched-chain amino acids (BCAA) was suggested on the basis of neuro-pharmacological studies. A large, randomized trial has recently provided evidence that BCAA may be superior to equicaloric and equinitrogenous supplements, improving survival and retarding hepatocellular failure. Administration schedules including a late evening supplementation may be particularly helpful. Biochemical studies are providing the rationale for the beneficial effects, showing that leucine may be an important regulator of amino acid/protein metabolism.     

Amino acids and proteins in relation to the nutrition of elderly people

In this short review some aspects of body protein and amino acid metabolism during ageing in human subjects have been explored. The picture that emerges is a progressive diminution of total body protein with ageing, due largely to a decline in the size of the skeletal muscle mass. These changes are accompanied by a shift in the overall pattern of whole body protein synthesis and breakdown, with muscle mass estimated to account for about 30% of whole body protein turnover in the young adult, as compared with a lower value of 20% or less in the elderly subject. The metabolic significance and possible functional implications of this alteration in the quantitative contribution by muscle to whole body amino acid and protein dynamics have been considered. The determination of requirements for individual essential amino acids and for total protein has been discussed, and it is evident that the data are limited and often contradictory. However, elderly individuals are more likely to be influenced by various biological, environmental and social factors, the effects of which would be generally to increase protein needs above those for younger adults. Thus, in practice, the protein needs of elderly people are probably higher than for the young. The decline in energy intake, together with its possible consequences for reduced dietary protein utilization, will also tend to increase the protein need of elderly subjects, compared with that for physically more active young adults. Until more data become available, it is recommended for food planning purposes that an appropriate protein allowance could be 12-14% of the total energy intake, for mixed protein sources characteristic of the diets of industrialized countries or the more affluent sectors of populations in developing countries. Energy intake should be at a level that meets the estimates proposed by FAO/WHO/UNU for older persons. Tentative recommendations are made herein that intakes of specific indispensable (essential) amino acids, per unit of protein need, should be similar to those for the young school-age child and they should be higher than those currently judged by international authorities (i.e. FAO/WHO/UNU) to be sufficient for maintenance of protein nutritional status in the adult. In view of (i) the increasing proportion of older individuals within technically advanced populations together with the need of this group for health care and (ii) the important role played by diet and food habits in health maintenance, and in the aetiology or progression of degenerative disease, it is vitally necessary to improve upon the current state of knowledge concerning protein and amino acid metabolism and nutrition during the later phases of our lives.     

Leucine metabolism in thyrotoxicosis: plasma aminogram and 3-methylhistidine excretion before and after treatment

Previous studies have suggested increased protein catabolism and altered muscle metabolism in hyperthyroid patients. In this experiment we investigated parameters of protein and leucine metabolism before and after treatment of hyperthyroidism. While confined in a metabolic ward, patients' daily caloric intake was based on the resting energy expenditure and an allowance for 16 hours of light physical activity. We found no significant difference in plasma aminogram and urinary 3-methylhistidine excretion (an index of protein catabolism) before and after treatment. On the other hand, hyperthyroidism appeared to increase the rates of oxidation, turnover, and plasma clearance of endogenous leucine. However, only the 60% increase in the rate of leucine oxidation was statistically significant. We conclude that in spite of increased catabolism, basal levels of branched-chain amino acids are well maintained in plasma of hyperthyroid patients consuming a diet that compensates for their hypermetabolic state.     

The effects of the formula of amino acids enriched BCAA on nutritional support in traumatic patients

AIM: To investigate the formula of amino acid enriched BCAA on nutritional support in traumatic patients after operation. METHODS: 40 adult patients after moderate or large abdominal operations were enrolled in a prospective, randomly and single-blind-controlled study, and received total parenteral nutrition (TPN) with either formula of amino acid (AA group, 20 cases) or formula of amino acid enriched BCAA (BCAA group, 20 cases). From the second day after operation, total parenteral nutrition was infused to the patients in both groups with equal calorie and equal nitrogen by central or peripheral vein during more than 12 hours per day for 6 days. Meanwhile, nitrogen balance was assayed by collecting 24 hours urine for 6 days. The markers of protein metabolism were investigated such as amino acid patterns, levels of total protein, albumin, prealbumin, transferrin and fibronectin in serum. RESULTS: The positive nitrogen balance in BCAA group occurred two days earlier than that in AA group. The serum levels of total protein and albumin in BCAA group were increased more obviously than that in AA group. The concentration of valine was notably increased and the concentration of arginine was markedly decreased in BCAA group after the formula of amino acids enriched BCAA transfusion. CONCLUSION: The formula of amino acid enriched BCAA may normalize the levels of serum amino acids, reduce the proteolysis, increase the synthesis of protein, improve the nutritional status of traumatic patients after operation.     

Dietary control of protein turnover

The balance between protein synthesis and breakdown (protein turnover) regulates whole-body protein mass. The relationships between dietary changes (amount and composition of food) and protein synthesis, protein breakdown and amino acid oxidation have been explored in order to better understand adaptations of protein and amino acid metabolism. Methods for measuring protein synthesis, especially whole-body protein synthesis, can be divided into two groups: the 15N end-product method (urea and/or ammonia), and the incorporation of labelled amino acid(s) into proteins. Assumptions and limitations of the widely used two-pool model (free amino acid and protein pools) are discussed. Results obtained with different methods and for amino acids have been compared, to assess their ability to detect changes in protein synthesis rates. Methods of measuring protein breakdown have also been described briefly. Food intake affects whole-body and tissue protein turnover throughout development of animals and humans in different ways. Protein metabolism fluctuates during the 24-hour period in response to intermittent food intake. During the post-prandial period, a net whole-body protein deposition occurs. This is essentially due to increased protein synthesis. The free amino acid pool and amino acid oxidation rates also increase. Consequently, amino acids are used to a great extent as energy substrates. In contrast, a decrease in protein breakdown could enhance protein deposition. During fasting, the rates of whole-body protein synthesis are lower than those of protein breakdown. This results in protein loss, essentially because the drop in protein synthesis rate in muscle is pronounced. N balance is controlled by the amounts and composition of the diet and by changes in protein synthesis and breakdown. Increasing food intake above levels of energy equilibrium can produce growth by enhancing both the whole-body protein synthesis and breakdown rates. Below energy equilibrium, whole-body protein loss occurs because of decreased protein synthesis which becomes lower than protein breakdown. Protein synthesis rate is the main factor controlling N balance in response to alterations in food intake. Increasing dietary protein, especially the essential amino acids, involves increased rates of whole-body protein synthesis and breakdown. The improved N balance obtained by enhancing dietary non-protein energy (carbohydrate, fat) can be brought on by reducing amino acid oxidation and slightly increasing protein synthesis. The effects of dietary protein and energy on protein turnover are apparently additive.     

Interleukin-6 markedly decreases skeletal muscle protein turnover and increases nonmuscle amino acid utilization in healthy individuals

CONTEXT: IL-6 is a key modulator of immune function and suggested to be involved in skeletal muscle wasting as seen in sepsis. OBJECTIVE: Our objective was to determine the role of IL-6 in human in vivo systemic and skeletal muscle amino acid metabolism and protein turnover. SUBJECTS AND METHODS: There were 12 healthy men infused for 3 h with saline (saline, n = 6) or recombinant human IL (rhIL)-6 (n = 6). Systemic and muscle protein turnover was determined with a combination of tracer dilution methodology, primed constant infusion of L-[ring-(2)H(5)]phenylalanine, and femoral arterial-venous blood differences and m. vastus lateralis biopsies after 2-h basal, 3-h infusion, and 3 h after infusion. RESULTS: The IL-6 concentration after 30-min infusion was approximately 4 (saline) and 140 pg/ml (rhIL-6). Three-hour rhIL-6 infusion caused an approximate 50% decrease in muscle protein turnover, albeit synthesis was more suppressed than breakdown, causing a small increase in net muscle protein breakdown. Furthermore, rhIL-6 decreased arterial amino acid concentration with 20-40%, despite the increase net release from muscle. CONCLUSIONS: We demonstrated that IL-6 profoundly alters amino acid turnover. A substantial decrease in plasma amino acids was observed with a concomitant 50% decrease in muscle protein turnover, however, modest increase in net muscle degradation. We hypothesize that the profound reduction in muscle protein turnover and modest increase in net degradation are primarily caused by the reduced plasma amino acid availability and not directly mediated by IL-6.     

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??Abstract??Protein-energy malnutrition (PEM) is a common complication in peritoneal dialysis patients.The morbidity increases with the extension of the duration of dialysis.PEM seriously affect patients?? quality of life??hospitalization rate and mortality.The main factors leading to PEM are inflammation??diabetes??high peritoneal transporter and elder age of patients.The main countermeasures to prevent PEM in PD patients include nutritional support??use of amino acid peritoneal dialysis solution??improvement of micro-inflammatory state??adequate dialysis??better fluid volume control??correction of metabolic acidosis??and the protection of residual renal function.In addition??automated peritoneal dialysis (APD) has the advantage of delivering higher doses of dialysis??more exchanges??shorter dwelling time??and thus might be more effective in management of PEM in PD patients.     

Nutrition and stress

Acute illness induces major physiological responses, which favor the adaptation of the organism to stress and injury. The metabolic response plays key roles in maintenance of vital functions and promotion of the healing mechanisms. All the components of energy expenditure are modified, particularly the resting metabolism. The regulation of carbohydrate metabolism is also markedly altered. Such patients are characterized by fasting and postprandial hyperglycemia, insulin resistance, and by a stimulation of the hepatic glucose production in fasted and fed states. Lipolysis and increased fat oxidation are typically observed. Ketogenesis processes are inhibited, concurring to alter the adaptation to starvation. Protein turnover is stimulated with a preponderance of the catabolic processes, even during full nutritional support. This induces a state of resistance to feeding, leading to a progressive depletion of the fat free mass. Such progressive tissue catabolism cannot be reversed by hypercaloric nutrition or growth factors. Specific nutrients (aminoacids, micronutrients, PUFA) may offer interesting perspectives in stimulating immunity, improving the antioxidant balance or modulating the inflammatory response.     

Endothelin-1 levels in patients with Paget's disease of bone.

A locally accelerated bone turnover is the pathophysiological basis of Paget's disease of bone (PD) and may result in severe bone deformations and pain. Affected bone sites are hypervascularized. Secreted endothelial products such as endothelin-1 (ET-1), influence bone metabolism. We investigated a possible correlation between ET-1 plasma concentrations and bone metabolism in patients with PD and whether ET-1 plasma levels are regulated by i. v. bisphosphonate treatment. Plasma ET-1 levels were determined in 22 patients with PD and found to be significantly (p = 0.006) elevated (0.75 +/- 0.48 fmol/ml) compared to 19 healthy controls (0.20 +/- 0.24 fmol/ml). In a group of five patients with PD, plasma ET-1 levels were determined before and after treatment with i. v. pamidronate. On the average, ET-1 levels decreased by 21 % after pamidronate infusions (p = 0.045). The results suggest that bone metabolism in pagetic bone affects endothelial cell metabolism and may also be modulated by endothelial cell products. ET-1 plasma levels may indicate PD activity.     

Is the correlation between adequate dialysis in peritoneal dialysis and nutritional parameters mathematical or biological? Influence of residual renal function and comorbidity

The relationship between urea Kt/V and nPCR (nPNA) is partly due to a mathematical coupling and greatly depends on the residual renal function (RRF). On the other hand, albumin could be just a comorbidity marker. Our objective in this study was to verify whether dialysis dose in peritoneal dialysis (PD) is biologically related to the nutritional state measured by the mean values of several parameters not mathematically related while analyzing the influence of RRF and comorbidity (C). 101 stable PD patients, 60M and 41F with a mean age of 59.3 +/- 14.3 years, were studied and followed up every six months for a mean time of 35.8 +/- 22.3 months (8-112). The variables studied were initial comorbidity, plasma albumin, normalized protein nitrogen appearance (nPNA), lean body weight % (LBW%) and fat-free mass index (FFMI) derived from creatinine, and RRF. In every study (n = 471) the 24 hours dialysate and urine volumes were collected and the total (T), dialytic (P) and renal (R) urea KT/V and normalized creatinine clearance (CCR) were determined and compared with the nutritional parameters. When starting PD 48 patients (47.5%) had some C and 34 (33.7%) were already anuric. The correlations of nPNA with T-KT/V and T-CCR (n = 101) were r = 0.67 and 0.50 (p < 0.0005) while the correlations of LBW% with T-KT/V and T-CCR were r = 0.36 and 0.40 (p < 0.0005) respectively. The correlations of albumin with T, P and R KT/V and CCR did not reach significance. The nutritional state was better in patients with a higher RRF and albumin showed significant differences when related to morbidity. KT/V and CCR correlations with nutritional variables not mathematically related verify the hypothesis that dialysis dose is biologically associated with the nutritional state.     

A Randomized, Controlled Trial of Treatment of Alcoholic Hepatitis with Parenteral Nutrition and Oxandrolone. I. Short-Term Effects on Liver Function

The present studies were designed to provide careful measures of effects of oxandrolone, an anabolic steroid, intravenous nutritional supplementation, and the combination of these two treatments on liver functions, metabolic balances, nitrogen metabolism, and nutritional status in patients with moderate to severe alcoholic hepatitis. Of 43 patients originally recruited, 39 (19 men, 20 women) with typical clinical and laboratory features of alcoholic hepatitis (11 Child's-Pugh class B; 28 class C) were admitted to a metabolic unit and completed a 35-day three-phase protocol. Phase I was a 10-day baseline period of observation, during which routine and special quantitative tests of liver function (galactose and antipyrine metabolism), a 7-day elemental balance study, and a 15N, 13C-leucine metabolism study were done. Phase II was a 21-day treatment period during which patients were randomly assigned to receive one of four regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 L daily of 3.5% crystalline amino acids (in 5% dextrose), given by peripheral vein; or 4) a combination of oxandrolone and nutritional supplementation, along with standard therapy. Metabolic balances were repeated during phase II. Phase III was 2 or 3 days posttreatment, during which special studies of liver functions and volumes and leucine metabolism were repeated. All patients who completed phase I of study and were randomly allocated to one of the four treatment groups completed the subsequent two phases. Overall, with time, patients showed highly significant improvements in most clinical and laboratory features. For most standard laboratory tests (e.g., serum albumin, transferrin, prothrombin time) improvements were more marked in patients treated with nutritional supplementation and/or oxandrolone than in those given standard therapy alone. Liver volumes fell in all treatment groups, with greater improvement in those treated with nutritional supplementation. Improvements in galactose and antipyrine metabolism rates were significant only in those treated with nutritional supplementation or oxandrolone. Effects of treatments on metabolic balances, nitrogen metabolism, and measures of nutrition are described in this issue in a companion paper. We conclude that the addition of nutritional supplementation and oxandrolone to standard therapy of moderately severe or severe alcoholic hepatitis is well tolerated, and leads to more rapid improvement in the laboratory parameters measured.     

The role of degradation in the acute control of protein balance in adult man: failure of feeding to stimulate protein synthesis as assessed by L-[1-13C]leucin infusion

The effect of feeding on whole-body protein turnover was measured in six healthy volunteers using the essential amino acid, L-[1-13C]leucine, as a tracer for protein metabolism. Varied lengths of periods of feeding and isotope infusion produced different apparent responses to feeding. When parameters of protein turnover were estimated from 8-hour infusions, the change from post-absorptive in the first four hours to mixed feeding during the final four hours was found to produce positive leucine balance by decreasing degradation from 89.5 +/- 5.0 to 31.7 +/- 7.3 mumol leucine/kg/h (P less than .001), with no apparent change in synthesis. By contrast, when tracer was infused for 24 hours with 12 hours of feeding followed by 12 hours of fasting, the estimate of protein synthesis during feeding was 35% higher than during fasting (P less than .01). However, when tracer infusion during the 12-hour feeding/12-hour fasting protocol was limited to the last four hours of each nutritional period, the estimates of fed and fasted protein synthesis showed no significant difference, 71.3 +/- 6.5 and 66.2 +/- 5.6 respectively, while the calculated rate of protein degradation was 43% lower during feeding (P less than .002). As relatively higher levels of enrichment in plasma leucine were detected in comparable nutritional states following longer infusions, the possibility of significant recycling of label was investigated. Residual tracer was still detectable in both breath and plasma 12 hours after cessation of a 12-hour tracer infusion, supporting the conclusion that significant errors in estimates of protein turnover due to recycling of label arise with prolonged infusions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Energy metabolism in cancer patients

The presence of cachexia as defined by a series of clinical symptoms, such as anorexia, weight loss, muscular atrophy, tissue wasting, altered organ function, is frequently observed in cancer and makes a decisive contribution to morbidity and mortality. The onset of neoplastic cachexia is characterized by two events: the presence of primary or secondary anorexia and alterations of the host's intermediate metabolism. Among the most frequent metabolic alterations described in cancer patients is an absolute or relative increase in basal energy consumption with lack of adaptation to fasting. The causes of increased energy consumption in cancer patients are still not clear. Numerous studies on glucose, fat and protein metabolism induced by cancer have significantly contributed to our understanding of the phenomenon. The main alterations of the glucose metabolism are increased glucose turnover and reduced peripheral utilization, both of which probably depend on the presence of the tumour, as shown by their normalization after treatment. Increased gluconeogenesis, from lactate and from gluconeogenetic AA, is the main factor responsible for increased glucose turnover. The main alterations of the fat metabolism are increased mobilization of lipids from adipose tissues, reduced use of exogenous triglycerides and increased oxidation of free fatty acids that cannot be suppressed by glucose. The main alterations of protein metabolism are increased protein turnover with reduced synthesis and increased degradation of muscular proteins and increased hepatic protein synthesis. Knowledge of the pathogenesis of neoplastic cachexia represents a valuable aid for its effective prevention and treatment.     

Growth hormone/insulin-like growth factor 1 axis alterations contribute to disturbed protein metabolism in cirrhosis patients after hepatectomy.

BACKGROUND/AIM: Liver cirrhosis is accompanied by a fall in whole-body protein turnover and alterations of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, the influence of liver cirrhosis on the GH/IGF-1 axis in the perioperative period, and the contribution of the GH/IGF-1 axis alteration in cirrhosis to postoperative nitrogen metabolism are not known. METHODS: Plasma GH, IGF-1 and IGF binding protein 3 (IGF-BP3) levels were measured sequentially in patients undergoing hepatectomy with or without cirrhosis. Postoperative nitrogen excretion and whole-body protein turnover rate were also determined. RESULTS: Preoperative plasma IGF-1 level showed a negative correlation with indocyanine green retention rate. Cirrhosis patients undergoing hepatectomy had low IGF-1 and IGF-BP3 levels, despite extremely high GH levels in the perioperative period. Perioperative IGF-1 levels were lower in patients with postoperative complications than in those without complications. Postoperative nitrogen excretion was higher and whole-body protein turnover rate was lower in patients with cirrhosis than in those without cirrhosis. The post-operative IGF-1 level showed a positive correlation with whole-body protein turnover rate. CONCLUSIONS: Postoperative hepatic IGF-1 production may be severely disturbed in patients with cirrhosis, and the impaired IGF-1 production contributes to the suppressed postoperative protein metabolism in cirrhosis. It may be appropriate to increase plasma IGF-1 level in patients with cirrhosis to enhance postoperative protein metabolism and improve the postoperative outcome.     

Regulation of muscle protein turnover: possible implications for modifying the responses to trauma and nutrient intake

The physiological control of muscle protein balance has been reviewed. In addition to trauma, fasting and reduced activity have been shown to cause muscle protein loss through changes in synthesis and breakdown. Many of the effects of these states are mediated by alterations in the concentrations of insulin, glucagon, steroids and catecholamines. Branched-chain amino acids also appear to have specific effects in improving protein synthesis. Recently, prostaglandins have been identified as having a central role as mediators in the control of protein metabolism by many hormones and pathological states. Identification of factors which control muscle protein synthesis leads to the possibility that the metabolic response to illness and injury and its attendant muscle protein loss could be open to pharmacological manipulation. Inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs can improve muscle protein turnover, but their clinical usefulness may be limited by side-effects. Hormonal manipulation may offer the possibility of abolishing the metabolic response. For example, inhibition of adrenal secretion in surgical patients by spinal anaesthesia appears to modify many of the metabolic effects of injury. A variety of other treatments have been used to minimize the metabolic derangements of injury. Some of these have considerable potential, but as yet clinical benefits from their use have not been positively identified. It is likely that a pharmacological approach to the nutritional disorders of stress and injury will prove to be of major interest in the future.