Urinary 3-methylhistidine Research Articles

Metabolic and structural effects of insulin-like growth factor-I and high-protein diet on dystrophic hamster skeletal muscle.

In muscular dystrophy (MD) there is an imbalance between muscle protein synthesis and protein degradation, which results in a net muscle catabolism, along with muscle wasting and weakness. Using a dystrophic hamster model (BIO 53.58), we examined the chronic (8 weeks) effects of two factors that may enhance muscle protein synthesis and inhibit protein degradation, namely, insulin-like growth factor-I (rhIGF-I) and high-protein diet (HPD). Protein synthesis was determined by measuring the incorporation of 14C phenylalanine into perfused leg muscle, while protein degradation was calculated from the release of tyrosine from the same perfused muscle. Urinary 3-methylhistidine excretion was used as an indicator of myofibrillar degradation. Treatment of dystrophic hamsters with rhIGF-I, HPD, or a combination of the two for 8 weeks resulted in significant decreases in total and myofibrillar degradation when compared with untreated dystrophic animals (P < 0.05) but had minimal effects on protein synthesis. Significant morphologic improvements (P < 0.05), including a normalization and greater uniformity of muscle fibers, were also seen in rhIGF-I- and rhIGF-I + HPD-treated animals. rhIGF-I and HPD were effective in reducing the excessive proteolysis seen in dystrophic muscle, and this reduced proteolysis resulted in improvement of muscle morphology.

Dose-dependent effect of octreotide on nitrogen retention and glucose homeostasis in response to endotoxemia in parenterally fed rats.

This study compared the effect of different doses of octreotide on glucose and protein homeostasis in rats receiving concomitant lipopolysaccharide and parenteral nutrition infusions.Sixty-six male Sprague Dawley rats (185 to 220 g) were randomized to receive parenteral nutrition only (PN), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), PN plus LPS plus octreotide at 10 micrograms/kg/day (LPS + Oct 10), 100 micrograms/kg/day (LPS + Oct 100), or 1000 micrograms/kg/day (LPS + Oct 1000) for 48 hours. Prior to randomization all animals received isocaloric and isonitrogenous PN (170 kcal/kg/day as glucose and 1.1 g N/kg/day) and were kept nil per os except for water ad libitum. Nitrogen balance, urinary 3-methylhistidine/creatinine ratio, serum glucose concentration, and incidence of glycosuria were compared between groups. Serum urea nitrogen (SUN) changes were incorporated into the cumulative 48 hour nitrogen balance. ANOVA, Duncan's multiple range test, and Fisher's Exact Test were used for statistical analysis.Nitrogen balance (mg/48 hours) was significantly lower in all four groups receiving LPS +/− Oct when compared to the control group receiving PN alone. SUN (mg/dL) was significantly higher in all four groups receiving LPS +/− Oct when compared to control. There were no statistically significant differences in nitrogen balance or SUN among the four groups receiving LPS +/− Oct. The ratio of urinary 3-methylhistidine/ creatinine was significantly higher in the LPS + Oct 1000 group compared to the PN group (0.77 +/− 0.37 vs. 0.42 +/− 0.24, p < 0.05). Serum glucose concentrations and incidence of glycosuria among the five groups were not significantly different.Endotoxin significantly reduces nitrogen balance compared to controls fed PN. Octreotide does not significantly improve nitrogen retention or glucose homeostasis in endotoxemic parenterally fed rats.

Zinc repletion with organic or inorganic forms of zinc and protein turnover in marginally zinc-deficient calves.

We conducted two experiments using marginally Zn-deficient (-Zn) calves to determine which supplemental chemical form of Zn would most rapidly reverse certain Zn deficiency signs and to determine whether a change in protein turnover had occurred in Zn deficiency. In Exp. 1, 40 crossbred beef heifers were allocated by BW to four groups. The control group received 23 mg Zn/kg diet DM from ZnSO4 supplemented to the -Zn diet (17 mg Zn/kg diet DM). The three other groups received the -Zn diet. After 21 d, based on a decreased (P < .05) feed efficiency, they were deemed -Zn. Cell-mediated immune (CMI) response to phytohemagglutinin (PHA) was reduced (P < .05) but plasma and liver Zn were unaffected in the -Zn calves. Zinc was repleted by feeding iso-Zn amounts (23 mg Zn/kg diet DM) from Zn lysine, Zn methionine, or ZnSO4. At 8 h after injection of PHA, control CMI response values were similar to Zn Methionine, and Zn lysine was lower (P < .05). In Exp. 2, 10 Holstein steers were allocated by BW to two groups. One group received the -Zn diet, and the other received the +Zn diet. Urine collections were obtained from both groups of calves when the -Zn calves showed a decrease (P < .05) in feed efficiency relative to the controls and when they were repleted with 23 mg Zn/kg diet DM from ZnSO4 and their feed efficiency had returned to that of the controls. Urinary 3-methylhistidine indicated that -Zn calves had less (P < .05) daily protein degradation than the controls. Refeeding Zn to the -Zn group did not change BW or daily protein degradation. Results indicated that a marginal Zn deficiency decreased fractional accretion rate, increased (P < .05) urine excretion, and tended to increase (P < .19) Na and decrease (P < .12) K concentrations in the urine.

Quantitative urinary excretion of unmetabolised N tau-[Me-14C] methylhistidine by the common ringtail possum (Pseudocheirus peregrinus) marsupialia.

Six common ringtail possums (Pseudocheirus peregrinus) were intravenously injected with a standard dose of radioactive 3-Methylhistidine (N tau-[Me-14C]MeH). The dose was rapidly and quantitatively excreted by the possums. More than 90% of radioactivity was recovered within 3 days. Thin layer chromatography and mass spectroscopy showed that 97% of recovered radioactivity was associated with unmetabolised N tau-[Me-14C]MeH. These data satisfy two key requirements for the validity of urinary 3-Methylhistidine (N tau-3MeH) excretion as an index of muscle protein catabolism, in P. peregrinus.

Standardization of acid hydrolysis procedure for urinary 3-methylhistidine determination by high-performance liquid chromatography

The N-acetylated form of N-methylhistidine (3-methylhistidine, 3-meH), a non-invasive marker of proteolysis, accounts for 80–90% of total 3-meH excretion (acetylated+non-acetylated 3-meH) in the rat. To determine total 3-meH excretion, samples require acid hydrolysis prior to determination by high-performance liquid chromatography. This study evaluated the stability of 3-meH at various times and temperatures of hydrolysis and determined the optimal conditions for hydrolysis of samples. Increasing temperature (120°C) results in significant degradation of 3-meH with no appreciable change in concentration being noted at 80°C. Hydrolysis at 100°C for 1.5 to 4 h or 80°C for 8 to 12 h is recommended for determining total 3-meH concentrations in rat urine.

Quantitative excretion of 3-methylhistidine in urine of cats as a measure of in vivo skeletal muscle protein catabolism

The purpose of this study was to evaluate the use of urinary 3-methylhistidine excretion as an index of in vivo skeletal muscle protein degradation in cats. The criterion for validation was the rapid and quantitative excretion of an intravenously administered dose of radiolabeled 3-methylhistidine (3-methyl- 14C). Four adult cats were maintained in individual metabolism cages and allowed free access to a purified diet (43.5% protein) and water for 4 weeks. The cats were then injected intravenously with 740 kBq 3-[ 14C]methylhistidine dihydrochloride diluted in 1 mL of saline. Twenty-four-hour urine samples were collected for 7 days. Total radioactivity in each urine sample was determined by direct counting. Quench correction was determined by using an external standard. The mean (±SEM) cumulative urinary recovery of 3-[ 14C]methylhistidine from the four cats was 94.9 ±3.5% at 48 hr following radioisotope injection. The mean (±SEM) cumulative urinary recovery of radioactivity from the four cats was 103.9 ± 2.2% at 7 days following radioisotope administration. There was no detectable radioactivity found in expired CO 2 and negligible amounts (mean ± SEM: 0.6 ± 0.5%) in the feces. Chromatography of urinary amino acids and radioactive urine metabolites revealed no significant radioactivity in any other peak besides 3-methylhistidine. Acid hydrolysis of urine resulted in no increase in 3-methylhistidine content or urine, indicating that there is no significant acetylation of 3-methylhistidine in this species. On the basis of these results, 3-methylhistidine does not appear to be metabolized and should therefore be a valid index of in vivo skeletal muscle protein degradation in the cat. Urinary 3-methylhistidine excretion should be useful for studying how nutritional, hormonal, and other physiological or pathological factors cause losses or gains in skeletal muscle protein in this species.

Estimation of 3-methylhistidine production in pigs by compartmental analysis.

Direct in vivo methodology is not available to accurately evaluate muscle turnover in pigs. Urinary 3-methylhistidine (3MH) excretion, which is used as an in vivo marker of muscle protein breakdown in humans and cattle, is not a valid indicator for pigs. The present study proposes that data from a single bolus dose of 3-[methyl-2H3]methylhistidine tracer can mathematically describe 3MH metabolism in pigs. Plasma concentration of the tracer is described by a linear time-invariant three-compartment model by using the SAAM/CONSAM computer modeling program. The model defines masses and fluxes of 3MH within the pigs and, in particular, the intracellular de novo production of 3MH, which should reflect muscle proteolysis. The de novo production of 3MH as calculated by the model was 621 mumol/d, corresponding to a fractional breakdown rate of 2.28%/d, which is similar to values reported by using indirect methodology. These data also suggest that certain model compartments may be indicators of body muscle mass (mass of compartment 3, r = .59, P = .006). The mathematical model developed does not depend on urine collections and can be used to assess changes in muscle proteolysis in vivo.

Perioperative Changes in Body Composition and Metabolism in Patients with Colorectal Cancer according to Tumor Stage

Background: Reports about the influence of curative and palliative tumor resection on metabolism and resting energy expenditure (REE) in colorectal carcinoma are controversial. This study deals with a group of patients with colorectal cancer of all tumor stages undergoing surgery for the primary. Special attention was attributed to the question whether perioperative changes of REE and body composition depend on tumor stage. Patients and Methods: In a prospective study 32 colorectal cancer patients undergoing surgery were investigated in order to compare nutritional status, body composition and metabolism according to tumor stage. In 18 patients with UICC tumor stages I-III the tumors could be completely removed and in 14 patients with stage IV there was persisting tumor mass as liver metastases after resection of the primary. 10 days pre- and post-operatively bioelectrical body impedance analysis (B.I.A.), indirect calori-metry as well as serum and urine analysis were performed. Results: According to tumor stages no significant inter-group difference was observed in body mass index and preoperative weight loss. Significant increase of extracellular/body cell mass ratio indicating an increase of extracellular mass and decrease of body cell mass was preoperatively found in patients with metastatic colorectal cancer. Correlation between the percentage of preoperative weight loss and extracellular/body cell mass ratio was found in patients with tumor stages I-III. Preoperatively, resting energy expenditure, substrate oxidation rates, serum albumin and trans-ferrin as well as urine 3-methylhistidine excretion were without significant differences between the two groups. After resection of the primary no shift towards hypermetabolism was found in patients with unresected metastases compared to those with complete tumor removal. Taking into account the effects of the surgical trauma itself, postoperatively a further increase of extracellular mass and decrease of body cell mass was observed. These changes led to significantly higher ratios of extracellular/body cell mass and resting energy expenditure/body cell mass in patients with metastatic disease. Resting energy expenditure, substrate oxidation rates, serum albumin and transferrin and urine 3-methylhistidine excretion did not reveal significant inter-group differences postoperatively. Conclusion: No difference in body mass index, resting energy expenditure, protein oxidation and 3-methylhistidine urinary excretion can be found in patients with colorectal cancer without and with liver metastases before and after resection of the primary. However, there are indicators for a perioperative higher decrease of body cell mass in patients with liver metastases and palliative resection of the primary. This might be partially attributed to peripheral protein mobilization and protein retention and synthesis by the tumor itself.

Phenotypic and functional characterization of intrahepatic natural killer and macrophages in viral chronic hepatitis (VCH): [formula omitted]. Liver Unit, Molecular Biology Unit∗, and Pathology Service#, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain

14 severely burned patients were randomly assigned to receive one of three nasogastric feeds commencing after the resuscitation period and continuing for 15 days. Group A received a feed with a high leucine content (31% of protein as branched chain amino-acids, BCAA). Group B received a similar feed to Group A but 65% of the leucine was replaced by alpha-ketoisocaproate (KIC). Group C received a whole protein feed (16% of the protein content as BCAA), and acted as a control group. Targeted energy intake was twice the calculated Basal Metabolic Rate (BMR).Group A had significantly reduced urinary 3-methylhistidine (3-MEH) and serum urea, compared with the control group. Serum total protein, albumin and transferrin and apparent nitrogen balance were not significantly different. Group B's results did not vary significantly from controls.Leucine enrichment reduces muscle protein breakdown benefiting burn patients fed enterally when compared to a standard feed, whereas KIC enrichment does not.

Inhibitory effects of cadmium ion on extracellular Ca-independent contraction of rat aorta

Administration of clenbuterol to rats in the drinking water over a 4 day period increased incorporation of [3H]leucine into muscle protein and caused a slight reduction in urinary 3-methylhistidine but did not result in an increase in body or muscle weight. However, both urinary and liver taurine were significantly reduced at the highest dose of clenbuterol (2 mg · kg−1 · day−1). Serum creatine kinase, muscle isoenzyme (CK-MM) was raised and single muscle fibre injury was observed in the soleus muscle in animals treated with the middle dose (0.2 mg · kg−1 · day−1) and highest dose (2 mg · kg−1 · day−1). The reduction in the body pool of taurine caused by clenbuterol is of concern as taurine has been shown to have protective properties.

The biochemical effects of clenbuterol: with particular reference to taurine and muscle damage

Administration of clenbuterol to rats in the drinking water over a 4 day period increased incorporation of [ 3H]leucine into muscle protein and caused a slight reduction in urinary 3-methylhistidine but did not result in an increase in body or muscle weight. However, both urinary and liver taurine were significantly reduced at the highest dose of clenbuterol (2 mg · kg −1 · day −1). Serum creatine kinase, muscle isoenzyme (CK-MM) was raised and single muscle fibre injury was observed in the soleus muscle in animals treated with the middle dose (0.2 mg · kg −1 · day −1) and highest dose (2 mg · kg −1 · day −1). The reduction in the body pool of taurine caused by clenbuterol is of concern as taurine has been shown to have protective properties.

A compartmental model of 3-methylhistidine metabolism in humans

Urinary 3-methylhistidine (3MH) excretion has been proposed as a noninvasive in vivo marker of muscle protein breakdown, but such analysis requires quantitative collection of urine and yields few details about the metabolism of 3MH. In this study, we propose that data from a single bolus dose of tracer and serial blood samples over 72 h can be described by a kinetic model that defines 3MH metabolism in humans. Plasma concentration of the tracer was described by a linear time-invariant three-compartment model. The model defines masses and fluxes of 3MH within the subjects and, in particular, the intracellular de novo production of 3MH. The de novo production of 3MH as calculated by the model was not different from that calculated via the traditional collection of urinary 3MH (3.09 vs 2.57 mumol.kg-1.day-1, respectively; P > 0.30). These data indicate that 3MH production can be measured by a compartmental model that can be used to measure muscle proteolysis without quantitative urine collections.

Study of hypocaloric peripheral parenteral nutrition in postoperative patients (Europan project)

The objective of this study is to ascertain whether or not the supply of a low-calorieamino acids (AA) parenteral solution is useful in postoperative patients, by assessing a series of parameters that indicate nutritional status. 75 postoperative patients who met at least 2 of the 3 criteria: 1) albumin less than 3 g/dl; 2)prealbumin less than 21 mg/dl; 3) body weight less than 95% of ideal weight, were studied. Patients were divided into 4 groups: control group, 15 patients receiving conventional infusion therapy; group I, 20 patients receiving glucose + AA; group II, 20 patients receiving glycerol + AA; and group III, 20 patients receiving sorbitol-xylitol + AA. The most significant findings were a prompt recovery of short half-life proteins (prealbumin and retinol binding protein), a less negative nitrogen balance, a greater decrease in urinary 3-methylhistidine and a marked increase in most AAs when hypocaloric peripheral parenteral nutrition (HPPN) was used. As regards complications, suture dehiscence occurred in a greater percentage of controlpatients than in the active therapy groups (13.3% versus 5%) and, in contrast, a greater number of cases of infusion phlebitis was observed in the HPPN groups. Clinical data were not statistically significant. We conclude that HPPN is a valid means for providing nutritional support but, at present,there are few randomized, controlled studies that show that its use is clearly beneficial.

Effects of human growth hormone in critically ill nonseptic patients

To study the effects of growth hormone administration on insulin-like growth factor I concentration, nitrogen balance, and fuel utilization, and to study its safety in critically ill nonseptic patients. Prospective, randomized, placebo-controlled trial. Medical intensive care unit of a university hospital. Eighteen critically ill nonseptic patients were studied for 8 days after admission. Growth hormone (0.1 mg/kg/day) or placebo was administered as a continuous intravenous infusion on the second, third, and fourth days after admission. The study period was 8 days. Plasma hormone concentrations were measured every 6 hrs and average daily values were calculated. The 24-hr urinary nitrogen and 3-methylhistidine excretion were measured. Indirect calorimetry was used to calculate fuel utilization. Insulin-like growth factor I concentrations increased in the treatment group from subnormal to normal values and remained increased despite discontinuation of growth hormone treatment (p = .02). Nitrogen balance differed between the groups upon admission: growth hormone group (3.9 +/- 4.1 g/day) vs. controls (13.8 +/- 5.4 g/day), but improved with growth hormone. This finding appeared independent of the imbalance between the groups. The 3-methylhistidine excretion was not different between the groups and did not change during growth hormone administration. Free fatty acids and glycerol concentrations increased during growth hormone treatment, but calculated fuel utilization did not change. During growth hormone treatment, insulin concentrations increased, due to the increased administration of insulin necessary for glycemic control. Side effects other than hyperglycemia were not observed. Growth hormone administration in a heterogeneous group of critically ill nonseptic patients resulted in normalization of insulin-like growth factor I levels, even after cessation of growth hormone treatment. Nitrogen balance improved, but this change was transient. Hence, growth hormone affects nitrogen balance, probably partly independent of insulin-like growth factor I.

Myofibrillar protein synthesis in young and old human subjects after three months of resistance training

Muscle protein synthesis is slower in healthy older men and women than in young adults, but whether this results from relative disuse rather than aging is unclear. The present study was done to examine rates of myofibrillar protein synthesis before and after a 3-mo progressive resistance exercise program in young and old men and women. Protein synthesis was determined by incorporation of the tracer L-[1-13C]leucine into myofibrillar proteins obtained from the vastus lateralis muscle by needle biopsy. Before exercise, mean fractional myofibrillar synthesis was 33% slower (P < 0.01) in nine older subjects (62-72 yr old, 5 men and 4 women) than in 9 young subjects (22-31 yr old, 5 men and 4 women). Initial strength, as determined by three-repetition-maximum tests, was significantly less in the older group. Strength and training weights increased similarly in young and old groups, when expressed in relation to baseline values. Posttraining myofibrillar synthesis was determined on the day after the final training session. There was not a significant change in fractional myofibrillar synthesis in either the young or the old group after training, and the rate in the older group remained 27% slower (P < 0.05). Whole body protein turnover increased approximately 10% only in the younger group, and 24-h urinary 3-methylhistidine excretion (an index of myofibrillar proteolysis) was not significantly affected by training. These data suggest that the slower myofibrillar synthesis rate in older subjects cannot be explained by disuse.

Insulin, Cortisol and Thyroid Hormones Modulate Maternal Protein Status and Milk Production and Composition in Humans

AbstractThe partitioning of dietary and endogenous nutrients during lactation is not well understood. To examine associations between plasma hormone and substrate profiles and indices of either maternal body protein metabolism or lactational performance, we measured plasma insulin, cortisol, prolactin, thyroxine, triiodothyronine, individual amino acid, blood urea nitrogen, and prealbumin concentrations in lactating and nulliparous women in the postabsorptive state. We related these measurements to the subjects' nitrogen balance, urinary 3-methylhistidine excretion, [1-13C]leucine metabolism and milk production. Insulin concentrations showed significant positive relationships with nitrogen balance and prealbumin concentrations; cortisol levels showed a significant negative relationship with nitrogen balance and a significant positive relationship with leucine incorporation into protein. Thyroid hormone concentrations showed significant positive relationships with urinary 3-methylhistidine excretion, leucine incorporation into protein, and milk production. Proline concentrations were associated positively with nitrogen balance and negatively with leucine incorporation into protein, whereas glutamate-glutamine concentrations showed positive associations with leucine oxidation and milk nitrogen concentrations. We propose that insulin and cortisol modulate the channeling of nutrients between anabolic and anti-anabolic aspects of maternal body protein metabolism, whereas thyroid hormones and cortisol modulate nutrient partitioning toward milk production and visceral protein synthesis. We suggest that some nonessential amino acids (proline, glutamate-glutamine) may become limiting during lactation because of their unique contributions to milk protein synthesis

Biochemical assessment of nutritional status in patients with chronic obstructive pulmonary disease and acute respiratory failure on admission to an intensive care unit

Although chronic obstructive pulmonary disease (COPD) is associated with weight loss and malnutrition, there is a paucity of relevant data on COPD patients with acute respiratory failure (ARF). We studied 30 consecutive patients on the day of admission to our intensive care unit for ARF. In addition to a clinical work-up, the following biochemical parameters were determined: markers of nutritional status (albumin — ALB, transferrin — TRF, transthyretin — TTR, retinol binding protein — RBP, fibronectin), inflammation (C-reactive protein — CRP, α 1 glycoprotein acid — α 1GPA) and catabolism (plasma phenylalanine — PHE, urinary 3-methylhistidine — 3-MH). Values were expressed as mean ± SD and compared to those of 10 healthy subjects matched for age. COPD-ARF patients had a poor protein status (ALB = 30 ± 5 vs 42 ± 3 g.l −1; TTR = 118 ± 75 vs 251 ± 43 mg.l −1; RBP = 23 ± 12 vs 46 ± 8 mg.l −1; p < 0.001), were hypercatabolic ( 3-MH Cr = 31 ± 12 vs 22 ± 7 μmol.mmol Cr −1 ; PHE = 62 ± 27 vs 46 ± 10 μmol.l −1; p < 0.001) and inflamed (CRP = 68 ± 50 vs 12 ± 5 mg.l −1; α 1GPA = 1.2 ± 0.4 vs 0.5 ± 0.1 g.l −1; p < 0.001). Severity of the disease correlated with short half-life proteins and protein catabolism markers but not with inflammation markers. Considering ALB, TTR, RBP, the 3- MH Cr ratio and PHE values, the 30 COPD patients fell into 3 groups: chronic malnutrition (n = 7), acute malnutrition (n = 2), and acute + chronic malnutrition (n = 18). 3 patients had normal nutritional status. We conclude that an assessment of nutritional status at admission to intensive care units could contribute towards a rapid formulation of specific nutritional therapy.

Glutamine-supplemented parenteral nutrition improves gut mucosa integrity and function in endotoxemic rats.

The effects of glutamine-supplemented parenteral nutrition on protein metabolism, small intestinal mucosal metabolism, morphology, and barrier function were studied in endotoxin-treated rats. Forty-six male Wistar rats were randomized to two groups of 23 animals each and received total parenteral nutrition solutions supplemented with either glutamine (GLN group) or glycine (GLY group) at 2% wt/vol. Endotoxemia was induced by continuous intravenous infusion of endotoxin at a dose of 2 mg/kg per day throughout the 4-day study period. The GLN group had a less-negative cumulative nitrogen balance (-14.0 +/- 132.8 mg of nitrogen in the GLN group and -86.8 +/- 161.7 mg of nitrogen in the GLY group, p < .05) and less cumulative excretion of urinary 3-methylhistidine (2910 +/- 593 nmol) than the GLY group (4447 +/- 933 nmol, p < .01). Jejunal mucosal glutaminase activity and the arterio-portal venous blood glutamine concentration differences were significantly higher in the GLN group compared with the GLY group (15.6 +/- 2.3 vs 11.1 +/- 1.9 mumol/g per minute, p < .05, and 181 +/- 52 vs 147 +/- 36 nmol/mL, p < .05, respectively). The morphology of the jejunal mucosa in the GLN group was significant for having greater mucosal weight (23.4 +/- 3.1 vs 17.6 +/- 2.5 mg/cm), villus height (445 +/- 75 vs 357 +/- 57 microns), crypt depth (197 +/- 34 vs 161 +/- 28 microns), and wall thickness (751 +/- 77 vs 648 +/- 102 microns) than the GLY group (p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrogen balance in extremely low birth weight infants with nonoliguric hyperkalemia

We measured nitrogen balance and urinary 3-methylhistidine molar ratios in 33 extremely low birth weight infants (12 with hyperkalemia and 21 without) for the first 3 days of life. Although all infants were in negative nitrogen balance during the study, there was no difference in the degree of negative nitrogen balance between the two groups. There was also no difference in the 3-methylhistidine/creatinine molar ratios, indicating that muscle protein catabolism did not differ. We conclude that it is unlikely that catabolism contributes to the development of nonoliguric hyperkalemia in extremely low birth weight infants.

Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women.

Muscle mass and function are improved in the elderly during resistance exercise training. These improvements must result from alterations in the rates of muscle protein synthesis and breakdown. We determined the rate of quadriceps muscle protein synthesis using the in vivo rate of incorporation of intravenously infused [13C]leucine into mixed-muscle protein in both young (24 yr) and elderly (63-66 yr) men and women before and at the end of 2 wk of resistance exercise training. Before training, the fractional rate of muscle protein synthesis was lower in the elderly than in the young (0.030 +/- 0.003 vs. 0.049 +/- 0.004%/h; P = 0.004) but increased (P < 0.03) to a comparable rate of muscle protein synthesis in both young (0.075 +/- 0.009%/h) and elderly subjects (0.076 +/- 0.011%/h) after 2 wk of exercise. In the elderly, muscle mass, 24-h urinary 3-methylhistidine and creatinine excretion, and whole body protein breakdown rate determined during the [13C]leucine infusion were not changed after 2 wk of exercise. These findings demonstrate that, during the initial phase of a resistance exercise training program, a marked increase in quadriceps muscle protein synthesis rate occurs in elderly and young adults without an increase in the rate of whole body protein breakdown. In the elderly, this was not accompanied by an increase in urinary 3-methylhistidine excretion, an index of myofibrillar protein breakdown.