bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitumor Necrosis Factor Antibodies Reduce Hepatic Steatosis During Total Parenteral Nutrition and Bowel Rest in the Rat
Authors: Pappo Itzhak , Bercovier Herve , Berry Elliot , Gallilly Ruth , Feigin Elad , Freund Herbert R.
Published: May 2008

Background: In previous studies, we demonstrated the overgrowth of gram‐negative bacteria in the gut and an enhanced release of tumor necrosis factor (TNF) by peritoneal macrophages, suggesting that endotoxin, TNF, or both, may act as hepatotoxins to produce hepatic steatosis during total parenteral nutrition (TPN) and bowel rest. The present study attempts to better define the role of each of these two mediators. The first part examines the LD50 for various doses of endotoxin in TPN‐treated rats compared with free‐feeding and free‐feeding saline‐infused rats. In the second part we repeatedly administered anti‐TNF monoclonal antibodies to rats subjected to TPN and bowel rest. Methods: In the first set of experiments, 87 male Sabra rats were randomized into three groups: free‐feeding, nfused with normal saline, and infused with TPN. On day 7 of, he experiment, all rats received an IV injection of endotoxin at various doses (1.5, 2.5, 5.0, 7.5, and 10 mg/kg). The LD50 in the three groups and at the various doses of lipopolysaccharide ested was determined at 24 hours postinjection. In the second set of experiments, 38 male Sabra rats were randomized into three groups: infused with normal saline and fed rat food ad libitum, infused with TPN, and infused with TPN but also receiving monoclonal antibodies against TNF. Results: Lower endotoxin doses were required to achieve LD50 in the two IV‐infused groups (2.5 to 5.0 mg/kg) compared with the free‐feeding group (7.5 mg/kg) (p <.03). These findings suggest a moderate increase in susceptibility to the lethal effect of endotoxin in IV‐treated rats. The total hepatic fat and triglyceride levels, which were markedly increased in TPN rats, were significantly reduced by using anti‐TNF antibodies. Enhanced TNF production by peritoneal macrophages during TPN was completely eliminated by anti‐TNF antibodies, probably the result of suppressed TNF production. Conclusions: The continuous translocation of endotoxin from gram‐negative bacterial overgrowth in the gut during TPN and bowel rest results in enhanced release of TNF by macrophages. TNF causes hepatic dysfunction, portrayed in the present experimental model as hepatic steatosis. TPN‐induced hepatic steatosis was significantly reduced by the administration of monoclonal antibodies against TNF‐α. (Journal of Parenteral and Enteral Nutrition 19:80–82, 1995)
Ventricular Muscle and Lung Protein Synthesis In Vivo in Response to Fasting, Refeeding, and Nutrient Supply by Oral and Parenteral Routes
Authors: Preedy Victor R. , Garlick Peter J.
Published: May 2008

Background: Fasting and other catabolic states are characterized by reductions in the rate of protein synthesis. Most studies have investigated tissues such as skeletal muscle or liver, but impairments in the biochemistry of cardiovascular tissues also contribute to enhanced morbidity. The objectives of the present study were (1) to determine the response of protein synthesis in the heart and lung of young rats to overnight fasting; and (2) to determine whether protein synthesis could be ameliorated or modulated by refeeding or provision of enteral or parenteral nutrition. Methods: Fractional rates of protein synthesis (ie, the percentage of tissue protein renewed each day, ks) were measured in vivo in the ventricular muscle and lungs of young male Wistar rats (body weight, 100 to 130 g) with a “flooding” dose of L‐[43H]phenylalanine. Rats were fed ad libitum or fasted overnight. Fasted rats were subjected to various treatments. Results: When nutrient supply in fasted rats recommenced by refeeding for 1 hour, there were small but significant increases in the rates of ventricular protein synthesis, although the infusion of amino acids and glucose for 1 hour had no significant effect. Increases in ventricular k s were also obtained when amino acids were infused for 6 hours. Infusion of glucose alone for 6 hours did not cause a significant increase in ventricular k s . The effect of infusing a mixture of glucose plus amino acids for 6 hours was similar to the effects of amino acids alone. In all instances, ventricular k s in rats infused with amino acid for 6 hours did not attain rates observed in fed rats. k s was reduced in the lung after overnight fasting but was unresponsive to refeeding or to acute or chronic provision of amino acids and glucose by either IV or oral routes. Measurements also suggested that changes in neither insulin nor glucagon per se were responsible for the amino acid‐induced increases in heart protein synthesis. However, acute treatment of rats with anti‐insulin serum reduced rates of ventricular k s below values observed in fed rats. Anti‐insulin serum also increased lung k s Conclusions: It was concluded that rates of heart protein synthesis could be increased by the chronic provision (ie, 6 hours) of nutrients by oral or IV routes. In contrast, the lung was insensitive to these treatments. The observations have important implications for clinical situations, which are characterized by diminished cardiopulmonary protein synthesis. (Journal of Parenteral and Enteral Nutrition 19:107–113, 1995)
Insulin‐like Growth Factor‐I Prevents Gut Atrophy and Maintains Intestinal Integrity in Septic Rats
Authors: Chen Kai , Okuma Toshitada , Okamura Kenji , Tabira Yoichi , Kaneko Hirofumi , Miyauchi Yoshimasa
Published: May 2008

Background: The effects of insulin‐like growth factor‐I (IGF‐I) on gut metabolism, structure, and barrier function as well as its general anabolic effects were investigated in septic rats. Methods: Thirty‐three male Wistar rats that underwent cecal ligation were randomly divided into one of the following two groups: (1) received only total parenteral nutrition(control group) or (2) received total parenteral nutrition with IGF‐I (IGF group) at a dose of 4 mg/kg/d for 3 days. Results: During the 3‐day period, the body weight of rats in the IGF group increased significantly over that of rats in the control group (17.1 ± 2.6 vs 5.8 ± 4.6 g, p <.01). The total and free IGF‐I plasma concentrations were significantly higher in the IGF group than in the control group. The cumulative nitrogen balance was significantly more positive for the IGF group (423.9 ± 24.3 mg of nitrogen) than for the control group (290.8 ± 26.0 mg of nitrogen). The weights of thymus, spleen, and kidneys were significantly increased in the IGF group compared with weights in the control group. Treatment with IGF‐I improved the gut mucosal weight in all regions of the gut examined, including duodenum, jejunum, ileum, and colon. Histologic and biochemical analyses of the jejunum showed greater villus height and crypt depth and higher mucosal DNA and protein content in the IGF group. The arterial concentration of endotoxin was not significantly different between the two groups, whereas its level in portal blood was significantly lower in the IGF group (23.2 ± 9.9 pg/mL) than in the control group (95.5 ± 37.9 pg/mL), an indication that IGF‐I treatment decreased the amount of endotoxin that traversed the gut barrier. Conclusions: These results indicate that IGF‐I can improve gut metabolism and reduce mucosal atrophy and that it may play a role in maintaining the gut barrier function in sepsis. (Journal of Parenteral and Enteral Nutrition 19:119–124, 1995)
Effects of Free Glycerol Contained in Intravenous Fat Emulsion on Plasma Triglyceride Determination
Authors: Howdieshell Thomas R. , Bhalla Niti , Dipiro Joseph T. , Kuske Terrence , Baisden Robert
Published: May 2008

Background: Plasma triglyceride analyses to evaluate the clearance of IV fat emulsion are necessary in patients receiving parenteral nutrition. Enzymatic kits for triglyceride analysis measure the glycerol that is hydrolyzed from triglyceride. This study investigates the effect of fat emulsion free glycerol on plasma triglyceride determination. Methods: Venous blood from fasting volunteers (n = 10) was drawn into tubes containing EDTA and was centrifuged to separate the plasma. An IV fat emulsion containing 2.25% glycerol was added to plasma samples to create serial dilutions ranging from 0.049% to 0.245% fmal lipid concentration. Total triglyceride and free glycerol concentrations were determined in each dilution and control sample. The free glycerol concentration was subtracted from the total triglyceride concentration to yield a true triglyceride value. Results: Increasing concentrations of fat emulsion added to donor plasma produced increases in total triglyceride and free glycerol concentrations. The increase in free glycerol concentration produced significant concentration‐related differences between total and true triglyceride concentrations. Conclusions: The total triglyceride level overestimated the true triglyceride concentration due to fat emulsion free glycerol. To assure reliable triglyceride results in patients receiving fat emulsion, blanking for free glycerol should be considered. (Journal of Parenteral and Enteral Nutrition 19:125–126, 1995)
Fasting‐Induced Reduction of Intestinal Reperfusion Injury
Authors: Langkamp‐Henken Bobbi , Kudsk Kenneth A. , Proctor Kenneth G.
Published: May 2008

Background: Fasting is associated with significant structural, functional, and metabolic alterations in the intestinal mucosa. Before abdominal surgery, patients are usually fasted the night before surgery or for a longer period of time if chronic illness is present. The splanchnic organs may experience varying degrees of ischemia/reperfusion as blood vessels are occluded during the various manipulations. Methods: To study whether fasting alters intestinal reperfusion injury, rats were fasted for 0 to 2 days, and the mesenteric artery was occluded for 30 minutes and then reperfused for 1 hour. Mucosal atrophy was quantitated by measuring jejunal villus height and crypt depth, and mucosal injury was quantitated by measuring jejunal villus width to villus height and mucosal integrity. To determine whether any effect of fasting on reperfusion injury was due to the absence of luminal nutrients or to a systemic nutrient deficiency, rats were fed parenterally for 7 days before ischemia/reperfusion. Results: A 1‐day fast produced significant mucosal atrophy. Reperfusion in the O‐day and 1‐day fasted animals produced mucosal injury and additional mucosal atrophy. After a 2‐day fast, there was no mucosal injury or mucosal atrophy other than that produced by fasting alone. Parenteral feeding before ischemia/reperfusion did not prevent ischemia/reperfusion induced mucosal atrophy and injury. Conclusions: The protective effect of a 2‐day fast before intestinal ischemia/reperfusion cannot be attributed to the physical and chemical absence of food within the intestinal lumen. (Journal of Parenteral and Enteral Nutrition 19:127–132, 1995)
Adjuvant Recombinant Human Growth Hormone Normalizes Plasma Amino Acids in Parenterally Fed Trauma Patients
Authors: Jeevanandam Malayappa , Ali Mohammed R. , Holaday Nancy J. , Petersen Scott R.
Published: May 2008

Background: The addition of an anabolic stimulant during intensive nutrition therapy in trauma patients seems to be a reasonable adjuvant for minimizing muscle‐mass erosion. The plasma free amino acid pattern is the mirror of the net amino acid metabolism, and we have measured the progressive changes resulting from recombinant human growth hormone therapy in trauma victims during nutritional repletion in the early catabolic flow phase of injury. Methods: In 20 severely injured (injury severity scale = 31 ± 2), highly catabolic, and hypermetabolic adult multiple‐trauma patients, we have measured the fasting (day 0) plasma amino acid levels (48 to 60 hours after injury before starting the nutrition therapy) and their progressive changes during 7 days of IV nutrition support (total parenteral nutrition, 1.1 × resting energy expenditure calories, 250 mg of nitrogen per kilogram per day) with or without adjuvant recombinant human growth hormone. Group H (n = 10) randomly received daily recombinant human growth hormone (0.15 mg of Somatropin per kilogram per day) and Group C (n = 10) received the vehicle of infusion. Results: Hypoaminoacidemia of trauma is normalized by infusion of recombinant human growth hormone, which indicates its anabolic nature, and this is confirmed in the cumulative nitrogen balance (‐281 ± 139 mg of nitrogen per kilogram per 7 days compared with ‐809 ± 151 mg of nitrogen per kilogram per 7 days without recombinant human growth hormone; p ≤.005). This improved nitrogen retention is also reflected in the significantly low blood urea nitrogen levels in the recombinant human growth hormone group, which represents the efficient utilization of the infused amino acids for synthesis of proteins. Elevated plasma insulin‐like growth factor‐1 levels in Group H compared with those in Group C may also account for this altered amino acid metabolism. Conclusions: Recombinant human growth hormone treatment in combination with conventional total parenteral nutrition in the immediate posttraumatic period improved nitrogen metabolism and normalized the plasma free amino acid levels. (Journal of Parenteral and Enteral Nutrition 19:137–144, 1995)
Intravenous Albumin and Nutrition Support: Going for the Quick Fix
Authors: Koretz Ronald L.
Published: May 2008

Background: IV albumin has been advocated as adjunctive therapy for hypoalbuminemic patients who are receiving nutrition support. This discussion will critically consider the rationale for this recommendation as well as the evidence available in the medical literature. Methods: The medical literature was reviewed. Results: Randomized controlled trials have shown that IV albumin improves serum albumin levels. However such therapy does not improve clinical outcome in patients receiving parenteral nutrition. Although no trials exist that test the hypothesis in hypoalbuminemic patients receiving enteral nutrition, the purported “supportive evidence” in the medical literature is actually weak and contradictory. IV albumin does have some associated toxicity, and it is expensive. Conclusions: There is reason to believe that IV albumin is not effective in improving the clinical outcome of hypoalbuminemic patients who are receiving nutrition support. Until more compelling data become available, it is not reasonable to adopt a policy of routinely correcting the hypoalbuminemia in this way. In fact, hypoalbuminemia may be a manifestation of a serious disease state rather than a marker of deficient protein stores. (Journal of Parenteral and Enteral Nutrition 19:166–171, 1995)
Gastroesophageal Reflux During Gastrostomy Feeding R. M. COBEN, A. WEINTRAUB, A. J. DIMARINO JR, ET AL Journal of Parenteral and Enteral Nutrition 106:13–18, 1994
Authors: Hamaoui Elie
Published: May 2008

To investigate the pathophysiology of aspiration pneumonia in patients fed via gastrostomy tube, the authors measured lower esophageal sphincter pressure in 10 patients1 before and 24 hours after percutaneous endoscopic gastrostomy tube placement and also during bolus vs continuous feeding.2 In five of these patients, gastroesophageal reflux scintigrams were obtained (using technetium‐99‐labeled feeding) comparing bolus and continuous feeding. Bolus feeding consisted of 250 mL of Jevity, an isotonic formula (310 mOsm/kg), followed by 100 mL of water, all given within 20 seconds; continuous feeding consisted of the same formula infused at 80 mL/h without added water. Lower esophageal sphincter pressure was measured continuously during the 15 minutes immediately after a feeding bolus and for another 15 minutes after initiation of continuous feeding 2 hours later. The scintigrams were obtained every 10 seconds during similar 15‐minute periods. Basal lower esophageal sphincter pressure was not affected by percutaneous endoscopic gastrostomy tube placement or by continuous intragastric feeding. In contrast, bolus feeding was associated with marked relaxation of the lower esophageal sphincter to incompetent levels (16.6 ± 4.6 mm Hg to 2.1 ± 2.0 mm Hg, p <.001). The scintigrams revealed gastroesophageal reflux to the sternal notch after bolus infusion but not during continuous feeding. The authors concluded that gastroesophageal reflux associated with lower esophageal sphincter relaxation occurs in response to bolus feeding but not in response to continuous feeding, presumably a result of gastric distention by the bolus. Continuous feeding is therefore recommended for reducing the risk of aspiration pneumonia.
Effects of Deoxycholic Acid and Butyrate on Mucosal Prostaglandin E2 Release and Cell Proliferation in the Human Sigmoid Colon
Authors: Bartram Hans‐Peter , Scheppach Wolfgang , Englert Stefan , Dusel Gerda , Richter Astrid , Richter Frank , Kasper Heinrich
Published: May 2008

Background: A high‐fat, low‐fiber diet resulting in increased excretion of fecal secondary bile acids is regarded as a major risk factor for colon cancer. Incubation of human colonic biopsies with the secondary bile acid deoxycholic acid (DCA) leads to hyperproliferation with expansion of the proliferative zone, ie, a biomarker of increased cancer risk. Antiproliferative effects on various colon cancer cell lines, however, were reported for butyrate (BUT), a fermentation product of dietary fiber. Methods: In the following in vitro study we incubated biopsies from the normal sigmoid colon of 12 patients (age 55.8 ± 3.6 years) with 5 μM DCA or a combination of 5 μM DCA plus 10 mM BUT (DCA/BUT) and determined epithelial proliferation by bromodeoxyuridine immunohistochemistry. As a possible mediator for the DCA effects on colonic cell proliferation, mucosal prostaglandin E2 (PGE2) release into the incubation medium was measured by 125I‐PGE2 radioimmunoassay. Results: Incubation with DCA alone revealed a significantly higher labeling index for the whole crypt (.17 vs.11, p <.01) and for the upper 40% of the crypt (.05 vs.01, p <.01) compared with DCA/BUT. Mucosal PGE2 release during DCA/BUT incubation showed a trend toward lower values compared with DCA incubation (357.07 vs 434.29 pg/mg per hour; p =.07). Conclusion: The results indicate a normalization of DCA‐induced hyperproliferation of colonic epithelium by butyrate that is not clearly mediated by PGE2. Considering that nutrition affects the luminal concentrations of DCA and butyrate, our findings may have implications for colonic carcinogenesis. (Journal of Parenteral and Enteral Nutrition 19:182–186, 1995)
Interrelation of Intracellular Proteases With Total Parenteral Nutrition‐Induced Gut Mucosal Atrophy and Increase of Mucosal Macromolecular Transmission in Rats
Authors: Kishibuchi Masanori , Tsujinaka Toshimasa , Jima Shohei , Yano Masahiko , Ebisui Chikara , Kan Kazuomi , Morimoto Takashi , Mori Takesada
Published: May 2008

Total parenteral nutrition (TPN) is known to induce mucosal atrophy and to increase macromolecular transmission of the small intestine. The potential participation of various proteases in that process was investigated. Male Wistar rats were randomly divided into two groups: the TPN group (n = 11) received a standard TPN (250 kcal/kg per day, 1.78 g nitrogen/kg per day) and the FED group (n = 10) received a standard rat food for 1 week. This was followed by an examination of gut macromolecular transmission of fluorescein isothiocyanate dextran 70,000 (FITC‐dextran) after intragastric injection and of the activities of gut mucosal cathepsins B, H, and L and of proteasome. Mucosal wet weight and protein content decreased significantly by TPN for 1 week. In both groups, the activities of all proteases in the ileum were significantly greater than in the jejunum. In the TPN group, cathepsin L and H activities in the ileum, and cathepsin B activity in both the jejunum and the ileum, were greater than those in the FED group. The portal concentration of FITC‐dextran was higher than arterial and venous concentrations in the both groups. In the TPN group, the portal FITC‐dextran concentration increased significantly compared with the FED group. In conclusion, active proteolysis is not associated with TPN‐induced mucosal atrophy. Cathepsins activities in the ileum increase as a result of TPN. Interrelationship is implicated between increase of lysosomal protease activity and the deterioration of the intestinal barrier function, which permits macromolecular transmission. (Journal of Parenteral and Enteral Nutrition 19:187–192, 1995)
Effect of Enteral and Parenteral Nutrition on Amino Acid Levels in Cancer Patients
Authors: Pearlstone David B. , Lee Jong‐Inn , Alexander Richard H. , Chang Tsung‐Hung , Brennan Murray F. , Burt Michael
Published: May 2008

Background: The syndrome of cancer cachexia can have a significant impact on response to therapy as well as on survival in cancer patients. Therapies directed at metabolic perturbations in cachectic patients are dependent on nutritional repletion and maintenance of adequate amino acid substrate levels. This study compares the ability of oral feeding, enteral nutrition, and total parenteral nutrition to alter plasma amino acid levels in cancer patients. Methods: Patients with esophageal cancer were stratified by weight loss. Patients with < 20% weight loss were randomized to continue an ad libitum oral diet (group I) or to receive total parenteral nutrition (group II) for 2 weeks; patients with > 20% weight loss were randomized to receive either enteral nutrition (group III) or total parenteral nutrition (group IV) for 2 weeks. Plasma amino acid levels were measured before the study and again after 2 weeks of nutrition support. Results: Before therapy, there was no difference between the groups in total or essential amino acid levels; however, patients in all groups had significantly lower total amino acid levels compared with those of normal controls. After 2 weeks of treatment, patients in groups I and III showed no difference in individual, essential, or total amino acid levels. However, patients in groups II and IV showed significant increases in a number of individual amino acids as well as in essential and total amino acid levels after 2 weeks of TPN. Conclusions: Patients with esophageal cancer demonstrated significant alterations in amino acid profiles compared with those of normal controls. Total parenteral nutrition was superior to ad libitum oral feeding and jejunostomy feeding in repleting plasma amino acid levels. (Journal of Parenteral and Enteral Nutrition 19:204–208, 1995)
Influence of Casein and Casein Hydrolysate Diets on Nutritional Recovery of Starved Rats
Authors: Boza Julio , Martinez Olga , Baro Luis , Suarez Maria Dolores , Gil Angel
Published: May 2008

Background: The aim of this study was to compare the effects of two diets, which differed in their protein source (casein and casein hydrolysate), on the nutritional recovery and intestinal repair of undernourished rats at weaning after a 3‐day fasting period. Profound alterations in gut structure and signs of malnutrition appeared after the starvation period. Methods: The casein hydrolysate was prepared by enzymatic hydrolysis and ultrafiltration. Rats were refed the casein‐based or the casein hydrolysate‐based diet for 96 hours. Normal‐fed male Wistar rats at weaning were given the casein diet for 7 days and were used as controls. Liver acetylcholinesterase, glutamate dehydrogenase activities, serum amino acid profiles, jejunal oligosaccharidases, alkaline phosphatase, and leucine aminopeptidase activities were studied. Intestinal permeability to intact proteins was also tested by using ovalbumin and measuring its concentration in serum. Results: Intestinal and liver enzyme activities and serum amino acid profiles reached normal values after 96 hours of refeeding, regardless of the diet used. Glutamate dehydrogenase activity remained higher in both diet groups. Intestinal permeability to ovalbumin remained significantly increased only in the group refed the casein diet. Conclusions: Our results show that 4 days of refeeding are sufficient for complete intestinal recovery after fasting, provided the dietary protein source is a casein hydrolysate. We suggest that patients with malnutrition or malabsorption syndrome should be fed formula composed of enzymatic protein hydrolysates (because of their low antigenicity) rather than enteral formulas composed of intact proteins. (Journal of Parenteral and Enteral Nutrition 19 :216–221, 1995)
Metabolic Effects of Arginine in a Healthy Elderly Population
Authors: Hurson Moira , Regan Mark C. , Kirk Stephen J. , Wasserkrug Hannah L. , Barbul Adrian
Published: May 2008

Recently there has been much interest in the use of arginine to stimulate immune responses and to promote wound healing. In the present study, the effect of an oral supplementation with arginine on the metabolism of 45 healthy, nonsmoking, elderly volunteers was investigated. Subjects were divided into two groups that received either arginine aspartate (17 g free arginine) (n = 30) or a placebo (n = 15). The supplements were taken for a period of 14 days. Dietary intake of food was not controlled. Blood chemistry, lipid profiles, and as an index of nutritional status, serum insulin‐like growth factor‐1 levels and nitrogen balance were compared before and after supplementation. Two weeks of arginine supplementation led to a significant elevation of serum insulin‐like growth factor concentrations and an improved and positive nitrogen balance (2.0 ± 0.41 g N) when compared with controls (0.11 ± 0.47 g N; p = 0.0114). In addition the arginine‐supplemented group demonstrated a decreased total serum cholesterol with a reduction in the low‐density lipoprotein but not the high‐density lipoprotein fraction resulting in a increase in the ratio of low‐ to high‐density lipoprotein fraction. No adverse effects were observed at this dosage of arginine. The data suggest that oral arginine supplementation may be used safely in elderly humans. (Journal of Parenteral and Enteral Nutrition 19:227–230, 1995)
Altered Mental Function During Intravenous Infusion of Recombinant Human Insulin‐Like Growth Factor 1
Authors: Fouque Denis , Tayek John A. , Kopple Joel D.
Published: May 2008

Recombinant human insulin‐like growth factor‐1 (rhIGF‐1) is currently used experimentally to treat patients with insulin‐resistant diabetes mellitus, impaired growth, protein malnutrition, and osteoporosis. We report here the case of a marked transient alteration in consciousness in a healthy 22‐year‐old man who was given an IV infusion of a relatively low dose of rhIGF‐1 for 1 hour. This individual developed the sudden onset of dizziness, nausea, coldness, air hunger, and pallor. He became unresponsive to simple questions and experienced diaphoresis, a feeling of warmth, and paresthesias. Although there was a mild fall in heart rate and blood pressure, these hemodynamic effects did not appear sufficient to cause the altered mentation. There were no changes in serum glucose, phosphorus, or potassium that could seem to account for these events. This individual recovered completely several minutes after stopping the rhIGF‐1 infusion. (Journal of Parenteral and Enteral Nutrition 19:231–233, 1995)
Review: Nitric Oxide, Sepsis, and Arginine Metabolism
Authors: Kelly Edward , Morris Sidney M. , Billiar Timothy R.
Published: May 2008

Nitric oxide is one of the most versatile molecules produced by mammalian cells. Its role in sepsis and inflammation has been the subject of intense investigation since its discovery as a cell product in 1987. The role of arginine in sepsis and trauma has also received considerable attention, but most of the earlier studies on arginine preceded the studies on nitric oxide and the discovery that arginine serves as the nitrogen donor for nitric oxide synthesis. This review will explore the role that nitric oxide plays in sepsis and the effects of arginine metabolism on nitric oxide synthesis. (Journal of Parenteral and Enteral Nutrition 19:234–238, 1995)
Percutaneous Endoscopic Gastrojejunostomy: A Dual Center Safety and Efficacy Trial
Authors: Delegge Mark H. , Duckworth P. Frederick , Mchenry Lee , Foxx‐Orenstein Amy , Craig Robert M. , Kirby Donald F.
Published: May 2008

Although jejunal tube placement through a percutaneous endoscopic gastrostomy (PEG) has not been proven to be preferable to PEG feeding, it would be theoretically advantageous for those patients prone to gastrointestinal aspiration. However, reliable placement of a small bowel feeding tube through a PEG has been technically difficult. We have previously reported successful placement of a percutaneous endoscopic gastrojejunostomy (PEG/J) with minimal complications. These results are in contrast to other series that report technical difficulty, frequent tube dysfunction and gastric aspiration. We describe an over‐the‐wire PEG/J technique performed by multiple operators at two medical centers. Gastrostomy tube placement was successful in 94% of patients. Initial placement of the jejunal tube was successful in 88% of patients. Second attempts were 100% successful. The average procedure time was 36 minutes. The distal duodenal and jejunal placement of the jejunal tube resulted in no episodes of gastroduodenal reflux. Complications included jejunal tube migration (6%), clogging (18%), and unintentional removal (11%). The majority of patients were ultimately converted to either oral or intragastric feedings. We conclude that the PEG/J system is a reliable, reproducible method of small bowel feeding and is associated with no episodes of tube feeding reflux when the jejunal tube is positioned in the distal duodenum or beyond. Furthermore, it provides a temporary nutritional bridge for those patients who are later transitioned to either PEG or oral feeding. (Journal of Parenteral and Enteral Nutrition 19:239–243, 1995)
Intraoperative Placement of the Nasoenteric Feeding Tube: A Practical Alternative?
Authors: Jensen Gordon L. , Sporay George , Whitmire Susan , Taraszewski Robert , Reed Mary J.
Published: May 2008

Background: The provision of early postoperative enteral feeding may be enhanced by the placement of enteral feeding access during celiotomy, but surgeons are often reluctant to pursue this option because of the extra effort required. Methods: We conducted a retrospective review of our 2‐year experience with 60 sequential intraoperative nasoenteric feeding‐tube placements and included data on demographics, diagnosis, surgery, type of feeding tube, formula, tolerance, and complications. Our surgeons placed intraoperative nasoenteric feeding tubes at their discretion in a variety of subjects who were undergoing elective or urgent celiotomies. Results: The surgeries largely involved the upper gastrointestinal tract, and feeding‐tube placements were readily accomplished. The majority of patients received enteral feedings within 3 postoperative days and achieved feeding rates of 50 mL/h or greater. The average duration of feeding‐tube use was 1 week, accounting for 399 feeding days overall. There were no serious complications attributable to feeding‐tube placement or use, but inadvertent tube removal by patients or staff was a limitation. Conclusions: Intraoperative placement of the nasoenteric feeding tube may be a reasonable option for treating the surgical patient at nutritional risk who faces a limited course of impaired oral intake postoperatively. (Journal of Parenteral and Enteral Nutrition 19:244–247, 1995)
Down‐Regulation of Albumin Synthesis in the Rat by Human Recombinant Interleukin‐1β or Turpentine and the Response to Nutrients
Authors: Ballmer Peter E. , Mcnurlan Margaret A. , Grant Ian , Garlick Peter J.
Published: May 2008

Background: Inflammatory stimuli and provision of nutrients are important factors regulating both total liver protein synthesis and albumin synthesis. Methods: The influence of interleukin‐1β or turpentine injection and a 2‐hour infusion of a hypocaloric mixture of glucose and amino acids on the synthesis of total liver protein and albumin was investigated in rats. Total liver protein synthesis was measured by an IV flooding dose of L‐[2,63H]phenylalanine and albumin synthesis was determined from the labeling of immunoprecipitated albumin and expressed both as a fraction of total liver protein synthesis and as an absolute rate. Results: Interleukin‐1β or turpentine injection stimulated total liver protein synthesis compared with controls, whereas albumin synthesis, both as a fraction of total liver protein synthesis and as an absolute synthesis rate, decreased. In control animals, the 2‐hour IV infusion with glucose and amino acids resulted in a significant increase of total liver protein synthesis. Albumin synthesis as a fraction of total liver protein synthesis was not altered, but increased when expressed as an absolute rate in control animals. However, interleukin‐1β or turpentine injection abolished this response of albumin synthesis to nutrient supply. Conclusions: Total liver protein synthesis increases under inflammatory conditions and remains responsive to nutrient supply. In contrast, albumin synthesis decreases under the same conditions and does not seem to be responsive to short‐term IV nutrients. (Journal of Parenteral and Enteral Nutrition 19:266–271, 1995)
Intestinal Amino Acid Content in Critically III Patients
Authors: Ahlman Bo , Ljungqvist Olle , Persson Bo , Bindslev Lars , Wernerman Jan
Published: May 2008

Background: The purpose of the study was to determine the concentrations of free amino acids and the total protein content of the human intestinal mucosa during critical illness. Methods: The free amino acid and protein concentrations in endoscopically obtained biopsy specimens from the duodenum and the distal colonic segments were determined on 19 critically ill patients. The free amino acids were separated by ion exchange chromatography and detected by fluorescence, and the protein content was quantified by the method of Lowry. Results: In general, the typical amino acid pattern of the intestinal mucosa was seen, with very high levels of taurine, aspartate and glutamic acid. The main difference, as compared to a reference series of healthy subjects, was the elevated glutamine concentration of the duodenal mucosa. This amino acid was unaltered in the descending colon and depressed in the rectum. At the same time, the glutamatic acid concentrations were unaltered, suggesting that the degradation of glutamine was not increased in the septic state of the majority of the patients studied. Phenylalanine and the two branched‐chain amino acids, valine and leucine, were elevated in the duodenal mucosa, and in the colonic mucosa, methionine and phenylalanine were elevated; otherwise, all the other individual amino acids were unaltered or depressed. Conclusions: The alterations seen in mucosal free amino acid and protein concentrations in connection with critical illness are different in many respects and contrast with the findings seen after starvation or moderate surgical trauma. (Journal of Parenteral and Enteral Nutrition 19:272–278, 1995)
Is Muscle Protein Turnover Regulated by Intracellular Glutamine During Sepsis?
Authors: Fang C.H. , James J.H. , Fischer J.E. , Hasselgren P.O.
Published: May 2008

Background: Low muscle glutamine levels during sepsis are associated with reduced protein synthesis and elevated protein breakdown, in particular myofibrillar protein breakdown. It is not known if this is a causal or coincidental relationship. We tested the hypothesis that muscle protein turnover rates are directly regulated by glutamine. Methods: Paired extensor digitorum longus muscles from nonseptic (sham‐operated) and septic rats (16 hours after cecal ligation and puncture) were incubated in the absence or presence of 15 mmol glutamine/L. The effect of glutamine was tested in unsupplemented medium or in medium containing 1 mU/mL of insulin or a mixture of amino acids at normal plasma concentrations. Protein synthesis was measured as incorporation of 14C‐phenylalanine into protein; total and myofibrillar protein breakdown was determined by measuring tyrosine and 3‐methylhistidine, respectively. Results: Muscles accumulated intracellular glutamine well above normal concentrations in the presence of 15 mmol glutamine/L. In spite of this, protein synthesis was not affected by glutamine, neither when muscles were incubated in unsupplemented medium nor in medium containing insulin or amino acid mixture. Total protein breakdown was not influenced by glutamine when muscles were incubated in unsupplemented medium or with insulin but was reduced by glutamine in the presence of an amino acid mixture. Myofibrillar protein breakdown was unaffected by glutamine in unsupplemented medium and in medium containing insulin but was increased by glutamine in the presence of amino acid mixture. Conclusion: Reduced muscle protein synthesis and increased myofibrillar protein breakdown during sepsis are probably not caused by the low intracellular glutamine levels noticed in this condition. (Journal of Parenteral and Enteral Nutrition 19:279–285, 1995)
Spinal Osteomyelitis After TPN Catheter‐Induced Septicemia
Authors: Corso Francesca A. , Shaul Donald B. , Wolfe Bruce M.
Published: May 2008

Osteomyelitis of the spine is a well‐recognized delayed manifestation of septicemia but has not been recognized as a complication of total parenteral nutrition. We report five cases of spinal osteomyelitis that were clinically recognized 1 to 13 months after total parenteral nutrition catheter‐induced septicemia. Radiographic evidence of osteomyelitis was seen in all five patients. In three patients, culture of bony aspirates was positive for the same organism as from the blood. In one case, the diagnosis was established by histology, and in one the diagnosis was based on radiographic and radionuclide evidence of osteomyelitis. The organism responsible was Staphylococcus aureus in two cases, Candida albicans in another two cases and C tropicalis in one case. The septic episode that preceded osteomyelitis was treated with systemic antibiotics and catheter removal in four patients, and antibiotics without catheter removal in one patient. Nevertheless, osteomyelitis occurred, requiring bracing or operative debridement as well as prolonged antibiotic therapy. Spinal osteomyelitis may occur as a delayed manifestation of total parenteral nutrition catheter‐induced septicemia. Prompt and effective treatment of septicemia is indicated but may not always be sufficient. Clinical suspicion is the key to the correct and early diagnosis of osteomyelitis and therefore to adequate treatment. (Journal of Parenteral and Enteral Nutrition 19:291—295, 1995)
Growth Hormone, Glutamine, and a Modified Diet Enhance Nutrient Absorption in Patients With Severe Short Bowel Syndrome
Authors: Byrne Theresa A. , Morrissey Thomas B. , Nattakom Thomas V. , Ziegler Thomas R. , Wilmore Douglas W.
Published: May 2008

Background: Massive loss of intestinal surface area results in the short bowel syndrome characterized by malabsorption of fluid, electrolytes, and other nutrients. Although the remaining bowel undergoes morphological and functional adaptation, often these changes are inadequate to support the individual by enteral feedings, and parenteral nutrition is required to prevent dehydration, electrolyte disturbances, and malnutrition. Substances such as growth hormone, glutamine, and fiber exert bowel‐specific trophic effects and either directly or indirectly influence nutrient absorption. This study was undertaken to determine whether the co‐administration of exogenous growth hormone, supplemental glutamine, and a modified fiber‐containing diet could enhance nutrient absorption in patients who had undergone massive intestinal resection. Methods: Ten patients (5 men, 5 women, aged 43 ± 4 years) with short bowel syndrome were studied 6 ± 1 years after surgical resection. All patients were admitted to the Clinical Research Center for a 28‐day period; the first week served as a control period when nutritional (enteral and parenteral) and medical management simulated usual home therapy. Thereafter, eight patients received exogenous growth hormone, supplemental glutamine, and a modified high‐carbohydrate, high‐fiber diet. Two patients were treated with the modified diet alone. The efficiency of net nutrient absorption (percent absorbed) for total calories, protein, fat, carbohydrate, water, and sodium was calculated from the measured nutrient intake and stool losses. Results: Three weeks of treatment with growth hormone, glutamine, and a modified diet increased total caloric absorption from 60.1 ± 6.0% to 74.3 ± 5.0% (p ≤.003), protein absorption from 48.8 ± 4.8% to 63.0 ± 5.4% (p ≤.006), and carbohydrate absorption from 60.0 ± 9.8% to 81.5 ± 5.3% (p ≤.02). Fat absorption did not change (61.0 ± 5.3% to 60.3 ± 7.9%, p = NS). Water and sodium absorption increased from 45.7 ± 6.7% to 65.0 ± 7.3% (p ≤.002) and from 49.0 ± 9.8% to 69.6 ± 6.5% (p ≤.04), respectively. These absorptive changes resulted in a decrease in stool output (1,783 ± 414 g/d control period vs 1,308 ± 404 g/d third week of treatment, p ≤.05). Treatment with diet alone did not influence nutrient absorption or stool output. Conclusions: The combined administration of growth hormone, glutamine, and a modified diet enhanced nutrient absorption from the remnant bowel after massive intestinal resection. These changes occurred in a group of patients that had previously failed to adapt to the provision of enteral nutrients. This therapy may offer an alternative to long‐term dependence on total parenteral nutrition for patients with severe short bowel syndrome. (Journal of Parenteral and Enteral Nutrition 19:296–302, 1995)
The Depression of Hepatic Drug Conjugation Reactions in Rats After Lipid‐Free Total Parenteral Nutrition Administered via the Portal Vein
Authors: Raftogianis Rebecca B. , Franklin Michael R. , Galinsky Raymond E.
Published: May 2008

Background: Total parenteral nutrition provides nutrition support in patients who are unable to eat. Long‐term parenteral nutrition is accompanied by alterations in gut and liver function including changes in drug metabolism. This study examined the effects of lipid‐free total parenteral nutrition in rats on (1) the overall elimination pharmacokinetics of acetaminophen, (2) changes in sulfation and glucuronidation pathways during acetaminophen elimination, and (3) hepatic drug metabolizing enzyme activities determined in vitro. Methods: Chronic indwelling catheters were implanted in the aorta, inferior vena cava, and portal vein of adult male Sprague‐Dawley rats. Total parenteral nutrition, consisting of 25% dextrose, 5% amino acids, electrolytes, and vitamins, was infused via the portal vein for up to 14 days. Acetaminophen pharmacokinetics were characterized in vivo and selected drug metabolizing enzyme activities were determined in vitro. Results: Parenteral nutrition for 10 days decreased the total clearance of acetaminophen by 23% (from 11.5 ± 1.4 to 8.9 ± 1.4 mL/min per kg; p <.05) and decreased the formation clearance to acetaminophen sulfate (from 6.2 ± 0.4 to 3.9 ± 0.5 mL/min per kg; p <.05). Parenteral nutrition decreased microsomal cytochrome P450 concentration (47%), p‐nitroanisole demethylase activity (68%) and p‐nitrophenol UDP‐glucuronosyltransferase activity (58%). Cytosolic glutathione‐S‐transferase activity towards 1‐chloro‐2,4‐dinitrobenzene decreased 29%. Sulfotransferase activity towards p‐nitrophenol and acetaminophen was decreased 48% and 25%, respectively. Conclusion: Lipid‐free, total parenteral nutrition depresses drug conjugative metabolism in rats. The magnitude of this effect in humans remains to be investigated. (Journal of Parenteral and Enteral Nutrition 19:303–309, 1995)
Manganese Deposition in the Brain During Long‐Term Total Parenteral Nutrition
Authors: Ono Jiro , Harada Koushi , Kodaka Ryuhei , Sakurai Kosuke , Tajiri Hitoshi , Takagi Yoji , Nagai Toshisaburo , Harada Tokuzo , Nihei Akio , Okada Akira , Okada Shintaro
Published: May 2008

Background: Manganese deposition was suspected in a pediatric patient who received long‐term total parenteral nutrition. T1‐weighted magnetic resonance images revealed high intensity areas in the globus pallidus. This study was designed to clarify if these abnormal findings were related to manganese deposition and clinical neurological manifestations. Methods: Whole‐blood manganese concentrations were measured during manganese supplementation to total parenteral nutrition and after 5 months without manganese. Magnetic resonance images were also examined on each occasion and compared with the blood level of manganese. Results: The whole‐blood manganese level during supplementation was 135 μg/L (normal range 14.6 ± 4.7 μg/L), whereas the level was 20 μg/L after a manganese‐free period of 5 months. Accompanied with normalization of manganese level, abnormal high intensity lesions in the globus pallidus on T1‐weighted images also disappeared. No neurological manifestation related to the high manganese level was recognized. Conclusions: It is probable that the high manganese level was elicited by manganese supplementation to total parenteral nutrition. This high manganese condition was confirmed by the measurement of whole‐blood manganese level, which was associated with the abnormal high intensity lesions on T1‐weighted magnetic resonance images. (Journal of Parenteral and Enteral Nutrition 19:310–312, 1995)
Effect of Different Combinations of Dietary Additives on Bacterial Translocation and Survival in Gut‐Derived Sepsis
Authors: Gennari Roberto , Alexander J. Wesley , Eaves‐Pyles Tonyia
Published: May 2008

Background: Dietary arginine, glutamine, and fish oil each have been shown to improve resistance to infection. The purpose of this study was to assess the potential benefit of different combinations and amounts of these components on bacterial translocation and related mortality during gut‐derived sepsis. Methods: Balb/c mice were fed for 10 days with an AIN‐76A diet supplemented with different combinations and percentages of arginine, glutamine, glycine, fish oil, and medium‐chain triglycerides. Controls were fed a complete AIN‐76A diet or chow. After 10 days of feeding, all animals were transfused. On day 15, the animals were gavaged with 1010 111In‐radiolabeled or unlabeled Escherichia coli and given a 30% burn injury. Animals gavaged with unlabeled bacteria were observed for survival (n = 317). Groups that showed the best survival as well as control groups were gavaged with labeled bacteria and killed 4 hours postburn (n = 60) for harvest of mesenteric lymph nodes, liver and spleen. Results: Mice fed diets enriched with 5% fish oil + 2% arginine, 2% arginine + 2% glutamine, or 5% fish oil + 2% glutamine had higher survival than control groups. The animals fed fish oil + glutamine had significantly reduced translocation to the liver and spleen. Animals fed arginine + glutamine had an enhanced ability to kill translocated organisms in the liver compared with other groups. Fish oil + arginine improved both barrier function and microbial killing. Conclusions: Feeding with arginine + glutamine, fish oil + arginine, or fish oil + glutamine supplemented diets positively affects the outcome in a gut‐derived sepsis model. (Journal of Parenteral and Enteral Nutrition 19:319–325, 1995)