Effect of structured lipid-enriched total parenteral nutrition in rats bearing yoshida sarcoma

The efficacy of structured lipid, a triacylglycerol of medium and long chain fatty acids, as an element of nutritional support therapies in cancer cachexia was investigated. Using the Yoshida sarcoma to induce cachexia, male Sprague Dawley rats (90 g) were injected subcutaneously with tumor cells (n = 17) or sterile saline (n = 16). Seven days later, rats were randomized to two intravenous diets for 3 days at 220 kcal/kg body weight/d, including 2 g nitrogen/kg body weight/d and 39% of total calories as either structured lipid or long chain triglyceride. Nitrogen balance, tumor growth rate, energy metabolism, and plasma albumin and free fatty acid levels were measured, and whole-body protein kinetics and liver, muscle, and tumor fractional protein synthetic rates were evaluated by adding (14)C-leucine to the diet during the last 4 hours of feeding. Nitrogen balance improved (P < .05) in both tumor and control rats receiving structured lipid-enriched total parenteral nutrition, and was also greater in tumor rats compared with controls. There were no differences in tumor growth or protein kinetics between diet groups. Albumin was lower (P < .05) in tumor rats, but significantly higher in both tumor and control rats given structured lipid-enriched total parenteral nutrition. Free fatty acid was significantly higher in tumor rats versus controls. Whole-body protein kinetics were similar among the four groups. Liver weight, liver weight to body weight ratio, and liver protein synthetic rate were higher in tumor rats. Also, liver weight to body weight ratio was lower in tumor and control animals given structured lipid-enriched total parenteral nutrition. Muscle protein synthetic rate was significantly lower in tumor rats, but higher in tumor and control rats given long chain triglyceride-enriched total parenteral nutrition. The nutritional benefits of structured lipid-enriched total parenteral nutrition favor support of host tissue without promoting tumor growth.     

Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis.

Creatine monohydrate (CrM) supplementation during resistance exercise training results in a greater increase in strength and fat-free mass than placebo. Whether this is solely due to an increase in intracellular water or whether there may be alterations in protein turnover is not clear at this point. We examined the effects of CrM supplementation on indexes of protein metabolism in young healthy men (n = 13) and women (n = 14). Subjects were randomly allocated to CrM (20 g/day for 5 days followed by 5 g/day for 3-4 days) or placebo (glucose polymers) and tested before and after the supplementation period under rigorous dietary and exercise controls. Muscle phosphocreatine, creatine, and total creatine were measured before and after supplementation. A primed-continuous intravenous infusion of L-[1-(13)C]leucine and mass spectrometry were used to measure mixed-muscle protein fractional synthetic rate and indexes of whole body leucine metabolism (nonoxidative leucine disposal), leucine oxidation, and plasma leucine rate of appearance. CrM supplementation increased muscle total creatine (+13.1%, P < 0.05) with a trend toward an increase in phosphocreatine (+8.8%, P = 0.09). CrM supplementation did not increase muscle fractional synthetic rate but reduced leucine oxidation (-19.6%) and plasma leucine rate of appearance (-7.5%, P < 0.05) in men, but not in women. CrM did not increase total body mass or fat-free mass. We conclude that short-term CrM supplementation may have anticatabolic actions in some proteins (in men), but CrM does not increase whole body or mixed-muscle protein synthesis.     

Light aerobic physical exercise in combination with leucine and/or glutamine-rich diet can improve the body composition and muscle protein metabolism in young tumor-bearing rats

Nutritional supplementation with some amino acids may influence host??s responses and also certain mechanism involved in tumor progression. It is known that exercise influences body weight and muscle composition. Previous findings from our group have shown that leucine has beneficial effects on protein composition in cachectic rat model as the Walker 256 tumor. The main purpose of this study was to analyze the effects of light exercise and leucine and/or glutamine-rich diet in body composition and skeletal muscle protein synthesis and degradation in young tumor-bearing rats. Walker tumor-bearing rats were subjected to light aerobic exercise (swimming 30?min/day) and fed a leucine-rich (3%) and/or glutamine-rich (4%) diet for 10?days and compared to healthy young rats. The carcasses were analyzed as total water and fat body content and lean body mass. The gastrocnemious muscles were isolated and used for determination of total protein synthesis and degradation. The chemical body composition changed with tumor growth, increasing body water and reducing body fat content and total body nitrogen. After tumor growth, the muscle protein metabolism was impaired, showing that the muscle protein synthesis was also reduced and the protein degradation process was increased in the gastrocnemius muscle of exercised rats. Although short-term exercise (10?days) alone did not produce beneficial effects that would reduce tumor damage, host protein metabolism was improved when exercise was combined with a leucine-rich diet. Only total carcass nitrogen and protein were recovered by a glutamine-rich diet. Exercise, in combination with an amino acid-rich diet, in particular, leucine, had effects beyond reducing tumoral weight such as improving protein turnover and carcass nitrogen content in the tumor-bearing host.     

Monoacetoacetin and protein metabolism during parenteral nutrition in burned rats.

The effect of intravenous infusion of monoacetoacetin (glycerol monoacetoacetate) as a non-protein energy source was evaluated in burned rats. During 3 days of parenteral nutrition, in which animals received 14 g of amino acids/kg body wt. per day exclusively (group I) or with the addition of isoenergetic amounts (523 kJ/kg per day) of dextrose (group II), a 1:1 mixture of dextrose and monoacetoacetin (group III) or monoacetoacetin (group IV), significant decreases in urinary nitrogen excretion and whole-body leucine oxidation were observed in the three groups given additional non-protein energy as compared with group I. Serum ketone bodies (acetoacetate and 3-hydroxybutyrate) were decreased in rats given dextrose, whereas glucose and insulin increased significantly. Monoacetoacetin-infused animals (group IV) had high concentrations of ketone bodies without changes in glucose and insulin, whereas animals infused with both monoacetoacetin and glucose (group III) showed intermediate values. On day 4 of nutritional support, whole-body L-leucine kinetics were measured by using a constant infusion of L-[1-14C]leucine. In comparison with group I, the addition of dextrose or monoacetoacetin produced a significant decrease in plasma leucine appearance and release from whole-body protein breakdown. Gastrocnemius-muscle protein-synthesis rates were also higher in the three groups receiving additional non-protein energy. These findings suggest that monoacetoacetin can effectively replace dextrose as an intravenous energy source in stressed rats. Both fuels are similar in decreasing weight loss, nitrogen excretion, leucine release from whole-body protein breakdown and oxidation, in spite of differences in energy substrate and insulin concentrations.     

Greater potency of IGF-I than IGF-I/BP-3 complex in catabolic parenterally fed rats

We compared the anabolic effects of recombinant human insulin-like growth factor I (rhIGF-I, 2.5 mg/kg) and equimolar amounts of rhIGF-I prebound to rhIGF binding protein-3 (rhIGF-I/BP-3) coinfused continuously with total parenteral nutrition (TPN) solution in dexamethasone (Dex, 70 microg/day ip)-treated male rats for 6 days. The four TPN groups included control, Dex, Dex + IGF-I, and Dex+IGF-I/BP-3. Pharmacokinetic analysis indicated reduced clearance of IGF-I when infused as IGF-I/BP-3 compared with free IGF-I (0.91 +/- 0.09 vs. 2.01 +/- 0.19 ml serum/min, P < 0.001) and this was associated with significantly greater serum IGF-I concentrations in the Dex+IGF-I/BP-3 group. Despite greater total serum IGF-I levels, infusion of free IGF-I produced greater anabolic responses than IGF-I/BP-3 based on body weight, nitrogen balance, and jejunal cellularity. Treatment with free IGF-I, but not IGF-I/BP-3, significantly reduced serum insulin and glucose levels that were elevated due to Dex. There were no significant differences in liver IGF-I mRNA levels between groups. Serum IGFBP-3 levels were elevated with infusion of IGF-I/BP-3 compared with IGF-I. These results indicate greater anabolic potency of IGF-I compared with IGF-I/BP-3 when administered by continuous parenteral infusion with TPN solution in catabolic rats.     

Hepatic uptake of chylomicrons and triglyceride emulsions in rats fed diets of differing fat content

The hepatic removal of plasma chylomicrons was determined for rats fed the following diets: a) containing no triglyceride, b) regular chow diet with 4.5% of its mass as lipid and, c) a corn oil-supplemented chow with triglyceride accounting for 20% of the mass. The fractional hepatic uptake of either radiolabeled chylomicrons or a triglyceride emulsion was reciprocally related to the amount of lipid in the diet. The animals receiving only carbohydrate and protein calories had the most active hepatic uptake of particulate triglyceride and were observed to have a significant decrease in the plasma concentration of the C apolipoproteins. The addition of either C-I, C-II, or C-III apoproteins to the triglyceride emulsion prior to intravenous injection produced a significantly lower hepatic triglyceride recovery of emulsions containing apoC-III. When the plasma of animals fed a fat-free diet was supplemented with human C-III-1 apolipoprotein, the distribution into the liver of either enterally administered fatty acid or parenteral triglyceride was diminished. The triglyceride content in the liver of the rats fed fat-free or corn oil-supplemented diets was significantly greater than that of the control rats and composition was somewhat similar to that of lymph triglyceride. The studies indicate an important influence of dietary lipid on both the partition of plasma triglyceride into the liver and the steady state hepatic triglyceride content.     

不同营养支持方式对进展期胃癌术后病人临床结局比较

摘要目的：研究肠内营养、肠外营养、常规补液对胃癌术后患者临床结局的影响。方法：择我院住院治疗并行外科手术治疗的胃 癌患者183 例,随机分至肠内营养组、肠外营养组、常规补液组,分别行相应的营养支持治疗,比较三组患者术前/ 后1 天及术后 8 天体重、白蛋白、淋巴细胞计数的变化及术后并发症发生情况、营养支持费用、术后住院时间、总费用。结果：常规补液组术后第 8 天体重较术前1 天明显下降;肠内、肠外营养组患者体重下降幅度均明显低于常规补液组;肠内、肠外营养组术后第8 天白蛋白 水平升高显著,且明显高于常规补液组;肠内营养组患者术后第8 天淋巴细胞明显上升,且较常规补液组有明显升高。肠外营养 组、常规补液组患者肝功能损害、血脂升高、血糖升高的发生率均明显高于肠内营养组;肠外营养组患者肝功能损害、血脂升高发 生率明显低于常规补液组;肠内营养组患者切口腹腔感染及肺部感染的发生率均明显低于常规补液组。与常规补液组相比,肠 外、内营养组患者术后住院时间均明显缩短,肠内营养组患者总费用明显偏高;与肠外营养相比,肠内营养组、常规补液组营养支 持费用明显降低,肠内营养组患者总费用显著下降,上述差异均有统计学意义（P＜0.05）。结论：胃癌术后患者行肠内营养可大大 降低术后并发症的发生,并减少患者住院费用,缩短术后住院时间。     

不同营养支持方式对进展期胃癌术后病人临床结局比较

目的：研究肠内营养、肠外营养、常规补液对胃癌术后患者临床结局的影响。方法：择我院住院治疗并行外科手术治疗的胃癌患者183例,随机分至肠内营养组、肠外营养组、常规补液组,分别行相应的营养支持治疗,比较三组患者术前／后1天及术后8天体重、白蛋白、淋巴细胞计数的变化及术后并发症发生情况、营养支持费用、术后住院时间、总费用。结果：常规补液组术后第8天体重较术前1天明显下降;肠内、肠外营养组患者体重下降幅度均明显低于常规补液组;肠内、肠外营养组术后第8天白蛋白水平升高显著,且明显高于常规补液组;肠内营养组患者术后第8天淋巴细胞明显上升,且较常规补液组有明显升高。肠外营养组、常规补液组患者肝功能损害、血脂升高、血糖升高的发生率均明显高于肠内营养组;肠外营养组患者肝功能损害、血脂升高发生率明显低于常规补液组;肠内营养组患者切口腹腔感染及肺部感染的发生率均明显低于常规补液组。与常规补液组相比,肠外、内营养组患者术后住院时间均明显缩短,肠内营养组患者总费用明显偏高;与肠外营养相比,肠内营养组、常规补液组营养支持费用明显降低,肠内营养组患者总费用显著下降,上述差异均有统计学意义（P〈O．05）。结论：胃癌术后患者行肠内营养可大大降低术后并发症的发生,并减少患者住院费用,缩短术后住院时间。     

The effect of total starvation and very low energy diet in lean men on kinetics of whole body protein and five hepatic secretory proteins

It is unclear whether the rate of weight loss, independent of magnitude, affects whole body protein metabolism and the synthesis and plasma concentrations of specific hepatic secretory proteins. We examined 1) whether lean men losing weight rapidly (starvation) show greater changes in whole body protein kinetics, synthesis, and circulating concentrations of selected hepatic secretory proteins than those losing the same amount of weight more slowly [very low energy diet (VLED)]; and 2) whether plasma concentrations and synthetic rates of these proteins are related. Whole body protein kinetics were measured using [1-(13)C]leucine in 11 lean men (6 starvation, 5 VLED). Fractional and absolute synthetic rates of HDL-apolipoprotein A1 (apoA1), retinol binding protein, transthyretin, alpha(1)-antitrypsin (alpha(1)-AT), and transferrin were measured using a prime-constant intravenous infusion of [(13)C(2)]glycine. Compared with VLED group, the starvation group showed greater increases (at a 5% weight loss) in whole body protein oxidation (P < 0.05); fractional synthetic rates of HDL-apoA1 (25.3 vs. -1.52%; P = 0.003) and retinol binding protein (30.6 vs. 7.1%; P = 0.007); absolute synthetic rates of HDL-apoA1 (7.1 vs. -3.8 mg.kg(-1).day(-1); P = 0.003) and alpha(1)-AT (17.8 vs. 3.6 mg.kg(-1).day(-1); P = 0.02); and plasma concentration of alpha(1)-AT (P = 0.025). Relationships between synthetic rates and plasma concentrations varied between the secreted proteins. It is concluded that synthetic rates of hepatic secreted proteins in lean men are more closely related to the rate than the magnitude of weight loss. Changes in concentration of these secreted proteins can occur independently of changes in synthetic rates, and vice versa.     

复方高支链氨基酸对肝硬化大鼠肝功能及营养状况的影响

将SD雄性大鼠用四氯化碳处理建立肝硬化大鼠模型,并随机分为A、B、C三组,A组大鼠给予静脉输注生理盐水,B组、C组大鼠分别给予输注等量的普通氨基酸注射液和复方高支链氨基酸注射液,分别于实验第0d、第14d测定大鼠体质量、肝功能指标及营养学指标水平。实验结束后,B、C两组大鼠体质量明显增加,与A组相比,B、C两组大鼠肝功能各指标水平显著降低,血清蛋白水平显著升高,且C组相比,B组大鼠肝功能水平与血清蛋白水平改善作用更为明显(p<0.05)。说明复方高支链氨基酸能改善肝硬化大鼠的肝功能指标,抑制血浆蛋白分解,有效控制肝硬化病症的进一步恶化。     

The effect of pyruvate or dihydroxyacetone on parenterally induced liver lipid accumulation in the rat

Orally fed pyruvate (pyr) and dihydroxyacetone (DHA) have been shown to decrease liver lipid accumulation in animal models. These compounds lessen the degree of fatty liver in ethanol-fed rats and in a genetic strain of hens predisposed to fatty liver. Total parenteral nutrition can result in liver dysfunction, including fatty infiltration of the liver. In this study, rats were assigned to either control, pyr, or DHA groups. All rats were fitted with jugular vein catheters, and following a 3-day recovery, were infused continuously for 7 days. The infusate provided adequate nutrition (including 7% kcal as fat) with 5% pyr or 5% DHA (g/liter) substituted for dextrose in the experimental groups. Plasma triglycerides were lower in the pyr groups relative to controls: 62.2 +/- 34.7 (SE) vs 96.8 +/- 44.3 mg/dl, though this was significant only at P less than 0.10. Neither pyr nor DHA decreased liver lipids. Pyr and DHA were administered intravenously in this study, and therefore passed through the heart and to peripheral tissues first. These compounds may need to be fed orally, passing via the portal system, to produce the liver lipid-lowering effects seen in other studies.     

Combined growth hormone/insulin-like growth factor I in addition to glutamine-supplemented TPN results in net protein anabolism in critical illness

Protein loss leading to reduced lean body mass is recognized to contribute to the high levels of morbidity and mortality seen in critical illness. This prospective, randomized, controlled study compared the effects of conventional parenteral nutrition (TPN), glutamine-supplemented (0.4 g.kg-1.day-1) TPN (TPNGLN), and TPNGLN with combined growth hormone (GH, 0.2 IU.kg-1.day-1) and IGF-I (160 microg.kg-1.day-1) on protein metabolism in critical illness. Nineteen mechanically ventilated subjects [64 +/- 3 yr, body mass index (BMI) 23.8 +/- 1.3, kg/m2] were initially studied in the fasting state (study 1) and subsequently after 3 days of nutritional with/without hormonal support (study 2). All had recently been admitted to the ICU and the majority were postemergency abdominal surgery (APACHE II 17.5 +/- 1.0). Protein metabolism was assessed using a primed constant infusion of [1-13C]leucine. Conventional TPN contained mixed amino acids, Intralipid, and 50% dextrose. TPNGLN, unlike TPN alone, resulted in an increase in plasma glutamine concentration ( approximately 50%, P < 0.05). Both TPN and TPNGLN decreased the rate of protein breakdown (TPN 15%, P < 0.002; TPNGLN 16%, P < 0.05), but during these treatments the patients remained in a net negative protein balance. Combined treatment with TPNGLN + GH/IGF-I increased plasma IGF-I levels (10.3 +/- 0.8 vs. 48.1 +/- 9.1 nmol/l, study 1 vs. study 2, P < 0.05), and in contrast to therapy with nutrition alone, resulted in net protein gain (-0.75 +/- 0.14 vs. 0.33 +/- 0.12 g protein.kg-1.day-1, study 1 vs. study 2, P < 0.05). Therapy with GH/IGF-I + TPNGLN, unlike nutrition alone, resulted in net positive protein balance in a group of critically ill patients.     

Quantitative analysis of metabolism of hepatic triglyceride in ethanol-treated rats.

An acute intraperitoneal injection of ethanol (0.7 or 2.1g/kg body wt.) causes the reversible, dose-dependent accumulation of hepatic triglyceride in rats. By using a pulse of [14C]palmitate injected into a tail vein, it was found that ethanol (2.1g/kg)had no effect on the flux of unesterified fatty acid of serum (4.3mumol/min per 100g body wt.). However, either dose increased the fraction of the total flux going to liver from 0.16 to0.27 as rapidly as could be measured (30s), and it remained elevated until all ethanol had been cleared from the blood. The fraction of the total radioactivity in lipids of liver that was in triglyceride increased linearly for 1 h from 30 to 50% and there was a simultaneous decrease in phospholipid from 60 to 40%. The rate of synthesis of hepatic triglyceride derived directly from unesterified fatty acid of serum was calculated by using the flux rate of unesterified fatty acid in serum, the fractional hepatic uptake of this flux, and the percentage of liver fatty acid esterified to triglyceride. This contribution is related to the total synthetic rate of hepatic triglyceride (rate of accumulation+rate of release) to determine quantitatively how much of the developing fatty liver is attributable to increased uptake of unesterfied fatty acid of serum. At the higher dose of ethanol, about half of the accumulating triglyceride is derived from this source, whereas with the lower dose of ethanol it can account for all of the build-up.     

Protein synthesis in rat lung. Measurements in vivo based on leucyl-tRNA and rapidly turning-over procollagen I.

The relationships of the specific radioactivities of leucine in serum, leucine acylated to tRNA and leucine in procollagen I, procollagen III and total protein in lungs of unanaesthetized young male rats in vivo were assessed as a function of time during constant intravenous infusion of radiolabelled leucine. The specific radioactivity of free leucine in plasma reached a steady-state plateau value within 30 min of initiation of [3H]leucine infusion. Leucine acylated to tRNA isolated from lungs had the same specific radioactivity as free serum leucine. Leucine in procollagen I rapidly achieved a specific radioactivity equal to that of serum leucine and leucyl-tRNA, indicating that serum leucine and leucyl-tRNA isolated from total lung were in rapid equilibrium with the precursor leucine pool for procollagen I synthesis. On the basis of leucyl-tRNA or free serum leucine as the precursor, half-times of fractional conversion of procollagen I and III were calculated as 9 and 38 min respectively. The incorporation of leucine into mixed lung proteins calculated from the tracer studies was 6.8 mumol/day for the first 30 min of the infusion, after which the calculated rate increased to 15.0 mumol/day. This apparent increase correlated with the appearance of rapidly labelled plasma proteins trapped in the lungs. On the basis of short infusions lasting 30 min or less, followed by vascular perfusion of the lung, the average fractional synthesis rate of mixed pulmonary proteins in young male rats was 20%/day.     

Effects of factors derived from a tumor clonal cell line on DNA synthesis of transformed and non transformed cells

Conditioned medium from neoplastic thyroid cell cultures, extracts of tumors developed by identical cells in isogeneic Fisher 344 rats and serum from those tumor-bearing animals, were tested in pulse thymidine labelled experiments on a transformed and two non transformed cell lines. Tumor extract and conditioned medium inhibited DNA synthesis. Tumor-bearing rat serum increased DNA synthesis in a cerebellar transformed cell line, but no in chick embryo fibroblasts or in aorta non transformed cells.     

The Nitric Oxide Synthase Inhibitor NG-Nitro-L-Arginine Methyl Ester Diminishes the Immunomodulatory Effects of Parental Arginine in Rats with Subacute Peritonitis

The combined treatment of parenteral arginine and the nitric oxide synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) have been shown to improve liver function and systemic inflammation in subacute peritonitic rats. Here, we investigated the effects of single and combined parenteral arginine and L-NAME treatments on leukocyte and splenocyte immunity. Male Wistar rats were subjected to cecal punctures and were intravenously given total parenteral nutrition solutions with or without arginine and/or L-NAME supplementations for 7 days. Non-surgical and sham-operated rats with no cecal puncture were given a chow diet and parenteral nutrition, respectively. Parenteral feeding elevated the white blood cell numbers and subacute peritonitis augmented the parenteral nutrition-induced alterations in the loss of body weight gain, splenomegaly, and splenocyte decreases. Parenteral arginine significantly increased the B-leukocyte level, decreased the natural killer T (NKT)-leukocyte and splenocyte levels, alleviated the loss in body weight gain and total and cytotoxic T-splenocyte levels, and attenuated the increases in plasma nitrate/nitrite and interferon-gamma production by T-splenocytes. L-NAME infusion significantly decreased NKT-leukocyte level, tumor-necrosis factor (TNF)-alpha production by T-splenocytes and macrophages, and interferon-gamma production by T-leukocytes, monocytes, and T-splenocytes, as well as increased interleukin-6 production by T-leukocytes and monocytes and nitrate/nitrite production by T-leukocytes. Combined treatment significantly decreased plasma nitrate/nitrite, the NKT-leukocyte level, and TNF-alpha production by T-splenocytes. Parenteral arginine may attenuate immune impairment and L-NAME infusion may augment leukocyte proinflammatory response, eliminate splenocyte proinflammatory and T-helper 1 responses, and diminish arginine-induced immunomodulation in combined treatment in subacute peritonitic rats.     

Effect of Starvation,Refeeding and Hydrocortisone Administration on Turnover of Myofibrillar Proteins Estimated by Urinary Excretion of Nτ-Methylhistidine in the Rat

Quantitative changes in fractional catabolic and synthetic rates of the myosin-actin pool in rat muscle under starvation and refeeding, during growth or after treatment with hydrocortisone were studied by estimating urinary excretion of N^τ-methylhistidine (3-methyl- histidine; Me-His).

Following deprivation of food, urinary Me-His output increased from 0.35 mg/day to 0.45 mg/day during first 2 day in spite of decreasing body Me-His pool. This high rate of Me-His excretion was maintained for the following 4 days of starvation and then decreased. When rats were refed a 20% casein diet after 10 days of starvation, Me-His excretion continued to decrease even after 3 days of refeeding. On the fifth day of refeeding, it began to rise progressively. During starvation, fractional catabolic rate of myosin-actin was about 3.7 %/day in comparison with 2.6 %/day of fed rats. After refeeding, the fractional catabolic rate decreased rapidly to a minimum value of 1.7 %/day on the third day. After that, it reached to a value of 2.6 %/day of fed rats. On the other hand, fractional synthetic rate of myosin-actin dropped immediately after fasting and the low rate of about 0.4 %/day was maintained during starvation period. Fractional synthetic rate recovered quickly after refeeding.

Urinary output of nitrogen and creatinine rose quickly on the first day after administration of hydrocortisone and on the second day it fell to their normal value. While Me-His excretion increased after injection of hydrocortisone up to 0.52 mg/day on the second day and this high excretion rate remained until the following day. From these results, it was shown that administration of hydrocortisone to rats enhances catabolism and reduces synthesis of myosin-actin. The results also show that the effect of this hormone on myofibrillar protein catabolism appears to last longer than its effect on nitrogen metabolism in the whole body judged from urinary nitrogen output.

Fractional rates of catabolism and synthesis of rat myosin-actin were 3.3 %/day (half- life of 21 days) and 7.2%/day, respectively, at the growth stage of 129 g body weight. These rates were 2.3 %/day (half-life of 30 days) and 2.8 %/day, respectively, at the mature stage of 363 g body weight.

Under the dietary conditions in this experiment, fractional synthetic rate changed far more dramatically than catabolic rate. This suggests that mass of muscle protein is primarily regulated by the rate of synthesis, although the rate of catabolism should not be neglected.     

Effect of intralipid infusion on lecithin:cholesterol acyltransferase and lipoprotein lipase in young rats

We compared the effects of Intralipid and dextrose infusion on plasma lecithin:cholesterol acyltransferase (LCAT), plasma lipid profiles and lipolytic activity. We used 5-week-old male Sprague-Dawley rats which were given total parenteral nutrition (TPN) with either Intralipid (3 g/kg body weight) or an equicaloric amount of 25% dextrose in the presence or absence of heparin (1 or 10 IU/ml of TPN). 40 min after the end of 4 h of infusion, plasma LCAT activity was significantly decreased (P less than 0.001), while total cholesterol and free fatty acid levels were significantly (P less than 0.05) increased in rats given Intralipid as compared to those given dextrose. We found associations (P less than 0.005) between LCAT activity and total cholesterol and between LCAT and free fatty acid levels; the coefficients of negative correlation were 0.543 and 0.607, respectively. Concomitantly to the increment in plasma total cholesterol levels, there was a decrease in the high-density lipoprotein (HDL) cholesterol fraction; the latter, which was 40% of the total plasma cholesterol in control and dextrose-infused rats, declined to 9% in rats given Intralipid. Administration of heparin during Intralipid infusion, even up to 10 IU/ml of TPN, did not affect any of these changes. After dextrose infusion, the values of all three parameters were similar to those of the control group. Plasma lipolytic activity was not significantly different between rats given infusion (Intralipid or dextrose) and controls. However, in the presence of heparin, plasma lipolytic activity increased similarly in both infused groups. These data indicate that in young rats, Intralipid infusion leads to an increase in plasma total cholesterol and free fatty acid levels, which correlates with a decrease in LCAT activity; the concurrent decrease in HDL cholesterol levels might account, in part, for the loss of LCAT activity. The administration of heparin results in an elevation of plasma lipolytic activity; however, it does not prevent the hypercholesterolemia, nor the decline in LCAT activity associated with Intralipid infusion.     

Catabolic Rate of Body Protein in Adult Rat over an Entire Period of Protein Depletion

In order to clarify the magnitude of different labile body proteins and the over-all catabolizable body protein, the catabolic rate of total body nitrogen in adult rat was measured by nitrogen balance method up to the time of death due to protein depletion.

The more labile body protein having 83.3% of fractional catabolic rate per day and occupying 2.8% of the whole body protein mainly represented the so-called protein reserves at the beginning of protein depletion. The less labile one, the remainder, namely 97.2%, having 0.79% of fractional catabolic rate almost wholly represented the exponential decrease of body protein during the first 40 days of protein depletion. Urinary and fecal nitrogen in this period showed a similar exponential decrease. In the next 40 days of the depletion, body protein decreased almost linearly giving the constant excretions of urinary and fecal nitrogen. In the last 40 days, it decreased drastically accompanied by a remarkable increase in urinary nitrogen.

After 118 days, on the average, the animals died of protein depletion at 35.7% level of the initial body nitrogen. Contributions of various organs to the total nitrogen deficit up to the time of death, were considerably different in different organs, where muscle was the greatest in total amount but with less catabolizability than the viscera, such as liver, pancreas and spleen.     

Anabolic effectiveness of nitrogenous preparations for parenteral nutrition in the presence of toxic liver damage]

The authors studied the assimilation of nitrogen preparations--moriamin S-2 and "improved" caseine hydrolysate in parenternal administration to 100 albino rats. Healthy animals and those with toxic affection of the liver induced with CCl4 were experimented upon. In healthy animals administration of nitrogen preparations led to the change of negative nitrogen balance into a positive one, normalized the content of blood and tissue amine nitrogen deranged in protein deficiency. Assimilation of nitrogen preparations fell considerably in toxic hepatitis. An 8-day parenteral nutrition failed to change the negative nitrogen balance into positive, and did not eliminate hypoproteinemia; however, it normalized the amine nitrogen concentration in the blood and tissues.