bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Intravenous ω‐3 and ω‐6 Fat Emulsion on Cytokine Production and Delayed Type Hypersensitivity in Burned Rats Receiving Total Parenteral Nutrition
Authors: Hayashi Naganori , Tashiro Tsuguhiko , Yamamori Hideo , Takagi Kazuya , Morishima Yuichi , Otsubo Yoshihisa , Sugiura Toshiyuki , Furukawa Katsunori , Nitta Hiroshi , Nakajima Nobuyuki , Suzuki Nobuo , Ito Isao
Published: May 2008

Background: The effects of fat emulsions containing ω‐3 and ω‐6 polyunsaturated fatty acids (PUFAs) on fatty acid profile, cytokine production, and delayed type hypersensitivity (DTH) in burned rats receiving total parenteral nutrition (TPN) were investigated. Methods: A fat emulsion containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was prepared (ω‐3 fat emulsion). Sprague‐Dawley rats were fed fat‐free chow for 2 weeks and were divided into three groups according to the contents of TPN. Groups C (n = 11) and C' (n = 14) received fat‐free TPN. Group ω6 received safflower oil emulsion containing linoleic acid (w‐6 PUFA) (n = 11). Group ω3 (n = 11) received safflower oil emulsion (19% of total caloric intake) and fat emulsion containing only EPA and DHA (1% of total calories). On day 5, all rats except for those in group C' were subjected to a 20% full‐thickness burn. Group C' did not receive burns. After 48 hours, the rats were killed. Results: The interleukin (IL)‐8 concentration was significantly 45% lower in group ω3 than in group C (p <.05). The IL‐10 concentration was significantly 15% lower in group ω3 than in group ω6 (p <.05). The IL‐6 concentration was increased in group w6 but not in group w3 when compared with group C. The IL‐6 and IL‐8 were not detected in group C'. Prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) concentrations were increased by burn injury, but there were no significant differences among the burned groups. Cell‐mediated immunity was thus significantly decreased in burned groups (groups C, ω6, and ω3; p <.01). However, the decrease of DTH was smaller in group w3 and significantly greater when compared with groups C and w6 (p <.05). Conclusions: ω‐6 PUFAs increased serum inflammatory cytokine levels in a stressed state. ω‐3 fat emulsion reduced IL‐8 and IL‐10 levels and prevented immunosuppression in burned rats that were receiving TPN. (Journal of Parenteral and Enteral Nutrition 22:363–367, 1998)
Growth Hormone Inhibits Apoptosis and Up‐Regulates Reactive Oxygen Intermediates Production by Human Polymorphonuclear Neutrophils
Authors: Matsuda Takeaki , Saito Hideaki , Inoue Tomomi , Fukatsu Kazuhiko , Han Ilsoo , Furukawa Satoshi , Ikeda Shigeo , Muto Tetsuichiro
Published: May 2008

Background: Growth hormone (GH) regulates the immune and metabolic systems; however, the effects of GH on the functions and cell death of polymorphonuclear neutrophils (PMNs) are not well understood. Therefore, this study was designed to investigate the effects of GH on PMN apoptosis, reactive oxygen intermediates (ROI) production, CD16, and Fas expression. We also investigated the effects of GH on the functions of other circulating leukocytes (ie, monocytes and lymphocytes). Methods: Venous blood was collected from healthy volunteers. Whole blood was washed and pretreated with GH (0 or 100 ng/mL) for 3 hours and then cultured for 0, 4, or 12 hours. PMNs in washed whole blood were analyzed by flow cytometry for cell death, phorbol myristate acetate‐stimulated ROI production, CD16, and Fas expression at each time point. Morphologic features also were assessed. PMN apoptosis was confirmed by chromatin staining and DNA gel electrophoresis. Results: GH inhibited PMN apoptosis at 12 hours of culture. GH enhanced ROI production by PMNs and monocytes throughout the 12‐hour culture but had no effects on CD16 expression on PMNs. Furthermore, GH decreased Fas expression on PMNs at 4 hours of culture. However, there were no effects of GH on apoptosis of monocytes or lymphocytes for the duration of this experiment. Conclusions: GH pretreatment down‐regulates Fas expression on PMNs, inhibits apoptosis, and up‐regulates ROI production. GH pretreatment also increases monocyte ROI production. Although activated PMNs have potentially harmful aspects, our results suggest that GH may improve host defense, mainly through enhancement of the PMN functional life span. (Journal of Parenteral and Enteral Nutrition 22:368–374, 1998)
Review: Glycine
Authors: Hall John C.
Published: May 2008

Glycine consists of a single carbon molecule attached to an amino and a carboxyl group. Its small size helps it to function as a flexible link in proteins and allows for the formation of helices, an extracellular signaling molecule, recognition sites on cell membranes and enzymes, a modifier of molecular activity via conjugation and glycine extension of hormone precursors, and an osmoprotectant. There is substantial experimental evidence that free glycine may have a role in protecting tissues against insults such as ischemia, hypoxia, and reperfusion. This impressive catalogue of functions makes an interesting contrast with glycine's perceived metabolic role as a nonessential amino acid. Glycine interconverts with serine to provide a mechanism for the transfer of activated one‐carbon groups. Glycine has just been viewed as a convenient source of nitrogen to add to solutions of nutrients. Although this may have unexpected benefits when such solutions are used in clinical practice, it does raise the specter of a possible confounding effect in experiments when glycine is added to control solutions to make them isonitrogenous. (Journal of Parenteral and Enteral Nutrition 22:393–398, 1998)
Alterations in Intestinal Barrier Function Do Not Predispose to Translocation of Enteric Bacteria in Gastroenterologic Patients CJ O'Boyle, J Macfie, K Dave, et al Nutrition 14:358–362, 1998
Authors: Buchman Alan L.
Published: May 2008

In this provocative study the authors investigated whether intestinal permeability in preoperative patients correlated with changes in small intestinal histology and permeability. Forty‐three patients (18 M, 25 F) aged 24 to 89 years (mean, 65 years) were studied. All patients were awaiting major abdominal surgery for the following diseases: colorectal cancer (n = 15), pancreatic cancer (n = 5), gastric cancer (n = 4), Crohn's disease (n = 4), ulcerative colitis (n = 3), diverticular disease (n = 3), and other (n = 9). No patient required total parenteral nutrition (TPN) or enteral nutrition support. “Subacute” obstruction was present in 18 patients (gastric outlet, intestinal, or colonic). Bacterial translocation was assessed by culture of a serosal biopsy taken from the antimesenteric border of the terminal ileum upon entering the abdomen and of a lymph node taken from the distal ileal mesentery. A simultaneous peripheral blood culture was taken. Histologic examination was performed on bowel removed from those patients who required small intestinal enterectomy. The villus height—total mucosal thickness ratio was measured using a measuring eyepiece on a light microscope. Intestinal permeability was measured 24 to 48 hours before surgery using the urinary lactulose (L)‐rhamnose (R) excretion ratio. Subjects ingested L‐rhamnose, 1 g, and lactulose, 5 g, and urine was collected for 5 hours.

Bacteria were cultured from the excised lymph node in 9 (20.9%) patients. Seven of nine of the organisms were Gram‐negative intestinal flora, and the other two Gram‐positive species were also intestinal flora. Three of these patients developed postoperative wound infections compared with one of the other 34 patients, although none became septic. Intestinal permeability was increased in 21 patients (L‐R ratio> 0.05, n = 21), primarily on the basis of a significant increase in lactulose absorption. Bacterial translocation occurred in 5 (22.7%) of 22 patients with normal permeability and in 4 (19.0%) of 21 patients with increased permeability (p =.77). Data on villus height were not reported, but the villus height‐total mucosal thickness ratio was similar in patients with and without bacterial translocation (0.55 ± 0.14 vs 0.62 ± 0.11).
Treatment With Glutathione Precursor Decreases Cytokine Activity
Authors: Pena Luis R. , Hill Daniell B. , McClain Craig J.
Published: May 2008

Background: Inflammatory cytokine activity is increased in many forms of experimental and clinical liver injury including alcoholic liver disease (ALD). Monocytes and Kupffer cells produce cytokines such as tumor necrosis factor (TNF), interleukin (IL)‐8, and IL‐6 in response to stimuli such as endotoxin (lipopolysaccharide [LPS]). This cytokine production is regulated by the oxidative stress‐sensitive transcription factor NFκB. Glutathione (GSH) prodrugs such as oxathizolidine‐4‐carboxylic acid (OTZ) can inhibit activation of NFκB and subsequent cytokine production in monocytes and Kupffer cellsin vitro.The objective of this study was to treat stable cirrhotic patients with OTZin vivoto evaluate its effects on monocyte cytokine production (TNF, IL‐8, and IL‐6) and whole blood GSH levels.Methods:Nine patients with stable cirrhosis received OTZ (70 mg/kg IV every 8 hours) for 9 days. Peripheral blood monocytes were obtained on study days 1 and 9, using density gradient centrifugation and adherence to plastic, and were stimulated with LPS (5 μg/mL). TNF, IL‐8, and IL‐6 were measured in culture supernatants by enzyme‐linked serum immunosorbent assay. Whole blood GSH levels were measured by high‐performance liquid chromatography.Results:There was a significant decrease in monocyte TNF, IL‐8, and IL‐6 production after OTZ therapy. Patients with cirrhosis had significantly lower admission whole blood GSH levels compared with controls and GSH normalized with OTZ administration.Conclusions:Treatment with the GSH prodrug OTZ inhibited monocyte cytokine production and increased whole blood GSH. This may have important therapeutic implications for multiple cytokine‐mediated disease processes.(Journal of Parenteral and Enteral Nutrition23:1–6, 1999)
Glutamine Attenuates Leukocyte‐Endothelial Cell Adhesion in Indomethacin‐Induced Intestinal Inflammation in the Rat
Authors: Arndt Holger , Kullmann Frank , Reuß Friedrich , Schölmerich Jürgen , Palitzsch Klaus‐Dieter
Published: May 2008

Background: Glutamine (Gln) is a major energy source for the intestinal mucosa. Its depletion results in epithelial atrophy and in bacterial translocation. Clinical substitution of this nonessential amino acid in critically ill persons results in a reduction of epithelial atrophy and in an accelerated recovery. The objective of this study was to assess the effect of Gln on leukocyte‐endothelial cell interaction in an indomethacin (Indo)‐induced long‐lasting ileitis in Sprague‐Dawley rats. Methods: Indo (7.5 mg/kg subcutaneously) was injected at time 0 and 24 hours later. Animals were fed with standard rat chow (ST) for 10 days until 12 hours before intravital microscopy analysis. Gln (3 g/kg body wt) was gavaged twice a day in the morning 4 hours apart (1) for 10 days between Indo administration and the experiment (ST/Gln, therapy), (2) for 14 days before Indo (Gln/ST, prophylaxis), or (3) from 14 days before Indo until the experiment (Gln/Gln, prophylaxis and therapy). Ten mesenteric venules (30 μm diameter) per animal (n = 5 per group) were observed using intravital microscopy, and the following parameters were monitored: number of adherent and emigrated leukocytes, leukocyte rolling velocity, erythrocyte velocity, venular blood flow, and shear rate. Macroscopically visible injury was scored 0 to 5. Results: Ten days after Indo treatment the macroscopic score was 3.5 ± 0.4 vs 0.6 ± 0.2 of controls, and leukocyte adherence and emigration were increased (2.2‐fold and 3.3‐fold vs control, respectively), whereas leukocyte rolling velocity and venular wall shear rate were reduced (both parameters to 81% of control). Glutamine prophylaxis, therapy, and the combination of both significantly attenuated macroscopic damage and prevented the microcirculatory disturbances to a similar extent. The beneficial effects of glutamine were accompanied by a normalization of fecal pH to control level, which had been lowered by Indo treatment. Conclusions: The long‐lasting Indo‐induced ileitis was accompanied by macroscopic ulceration and microcirculatory disturbances. Oral therapy and prophylaxis with glutamine reduced macroscopic and microcirculatory inflammatory activity, indicating a special demand for glutamine in this type of inflammation. (Journal of Parenteral and Enteral Nutrition 23:12–18, 1999)
Alanyl‐Glutamine‐Supplemented Parenteral Nutrition Increases Luminal Mucus Gel and Decreases Permeability in the Rat Small Intestine
Authors: Khan Jesmine , Iiboshi Yasuhiko , Cui Li , Wasa Masafumi , Sando Kinya , Takagi Yoji , Okada Akira
Published: May 2008

Background: Effect of supplemental alanyl‐glutamine in standard TPN (S‐TPN) on luminal mucus gel and small intestinal permeability was investigated. Methods: Thirty Sprague‐Dawley rats were divided into group I (n = 10), receiving standard rat diet; group II (n = 10), receiving S‐TPN; and group III (n = 10), receiving alanyl‐glutamine‐supplemented TPN for 1 week. After 1 week, fluorescein isothiocyanate (FITC)‐dextran was injected into the small intestine of the rats, and they were killed. A small intestinal sample and portal blood were obtained for morphologic and functional analysis of mucus gel and intestinal permeability. Results: In group II, thickness and optical density of mucus gel per millimeter serosal length of intestine were significantly lower than group I (p <.001) and were significantly higher in group III than in group II (p <.001). The number of goblet cells in the villi and in the crypt of the small intestine was significantly lower in group II than in group I (p <.001) and was significantly higher in group III than in group II (p <.001), with the exception of the villi of jejunum. Villous and crypt surface area per millimeter serosal length of intestine was significantly lower in group II than in group I (p <.001) and was significantly higher in group III than in group II (p <.001). Small intestinal permeability to FITC‐dextran was significantly higher in group II than in group I (p <.001) and was significantly lower in group III than in group II (p <.001). Glucosamine synthetase level was significantly higher in group III than in group I and ileum of group II (p <.001). Conclusions: Alanyl‐glutamine‐supplemented TPN prevents a decrease in mucus gel and an increase in small intestinal permeability associated with S‐TPN. (Journal of Parenteral and Enteral Nutrition 23:24–31, 1999)
Randomised Trial of Glutamine‐Enriched Enteral Nutrition on Infectious Morbidity in Patients With Multiple Trauma
Authors: Hammarqvist Folke
Published: May 2008

Patients with multiple trauma and an Injury Severity Score of more than 20 were randomized either to receive enteral nutrition enriched with glutamine (n = 29; 30.5 gram glutamine per 100 gram protein) or a control diet (n = 31; 3.5 gram glutamine per 100 gram protein). The two feedings were isocaloric and isonitrogenous. The nutritional treatment was started within 48 hours after trauma and was given continuously, aiming to cover 75% of the calculated energy expenditure measured by indirect calorimetry. The nutrition was given for at least 5 days through a nasoduodenal tube and was supplied until the patients tolerated oral feeding. No parenteral nutrition was given during the study period. Both groups were comparable both regarding clinical parameters as well as surgical interventions, caloric need, and numbers of days of enteral nutrition. The primary endpoint of the study was an infectious morbidity during the first 15 days following the trauma.
Protecting Solutions of Parenteral Nutrition From Peroxidation
Authors: Laborie Sophie , Lavoie Jean‐Claude , Pineault Marjolain , Chessex Philippe
Published: May 2008

Background : Light exposure induces the generation of peroxides in solutions of total parenteral nutrition (TPN). Peroxide toxicity has been documented in cell, in tissue, and in isolated organs. To decrease the infused peroxide load and to protect the quality of the parenteral nutrients, we tested the photoprotective properties of different infusion sets. Methods: Solutions of fat‐free TPN and all‐in‐one total nutrient admixture (TNA) were run through sets of bags (clear and covered) and tubings (clear and colored: black, orange, and yellow) offering different levels of protection against light. Peroxide levels were determined by ferrous oxidation of xylenol orange, thiol functions by the 5,5,dithiobis(2‐nitrobenzoic acid) technique, and absorbance of tubings by spectroscopy. Results: Protection of only the bag had little effect on peroxide generation. In fat‐free TPN solutions kept in covered bags, peroxide concentrations were 1.5 to 2 times higher when run through clear compared with colored tubings. When exposed to phototherapy or in the presence of lipids, peroxides were two to three times higher with the clear compared with the black tubing; meanwhile, orange and yellow tubings offered varying levels of protection related to their light‐absorbing properties. Colored tubings offered a greater protection against the disappearance of thiol functions. Conclusions: Covering bags and using orange and yellow tubings may be a practical solution to reduce infused peroxide loads from about 400 to 100 μM. This is especially relevant in patients with an immature or a compromised antioxidant capacity or when phototherapy or preparations of TNA are used. (Journal of Parenteral and Enteral Nutrition 23:104–108, 1999)
Compatibility of Medications With 3‐in‐1 Parenteral Nutrition Admixtures
Authors: Trissel Lawrence A. , Gilbert Doward L. , Martinez Juan F. , Baker Mary B. , Walter William V. , Mirtallo Jay M.
Published: May 2008

Background: The absence of drug compatibility information with 3‐in‐1 parenteral nutrition admixtures has been problematic. The purpose of this project was to evaluate the physical compatibility of 106 selected drugs during simulated Y‐site injection into nine different 3‐in‐1 parenteral nutrition admixture formulations. Methods: Four‐milliliter samples of each of the representative 3‐in‐1 parenteral nutrition admixture formulations were combined in a 1:1 ratio with 4‐mL samples of each of 106 drugs, including supportive care drugs, anti‐infectives, and antineoplastic drugs. Six replicate samples of each combination were prepared. Two samples were evaluated initially after mixing, two more after 1 hour, and the last two after 4 hours at 23°C. At each test interval, the samples were subjected to centrifugation, causing the fat to rise to the top. The top fat layer and most of the aqueous phase were removed, and the remaining liquid was diluted with about 7 mL of particle‐free, high‐performance liquid chromatography—grade water to facilitate observation of any particulates that might have formed. Visual examinations were performed in normal diffuse fluorescent laboratory light and under high‐intensity, monodirectional light. Results: Most of the drugs tested were physically compatible with the 3‐in‐1 parenteral nutrition admixtures for 4 hours at 23°C. However, 23 drugs exhibited various incompatibilities with one or more of the parenteral nutrition admixtures. Six drugs resulted in the formation of precipitate with some or all of the admixtures. Seventeen drugs caused disruption of the emulsion, usually with oiling out. Conclusions: Most of the test drugs were physically compatible with the nine representative 3‐in‐1 parenteral nutrition admixtures. However, the 23 drugs that resulted in incompatibilities should not be administered simultaneously with the incompatible parenteral nutrition admixtures via a Y injection site. (Journal of Parenteral and Enteral Nutrition 23:67–74, 1999)
Comparison Between Dodecanedioic Acid and Long‐Chain Triglycerides as an Energy Source in Liquid Formula Diets
Authors: Mingrone Geltrude , De Gaetano Andrea , Greco Aldo V. , Capristo Esmeralda , Benedetti Giuseppe , Castagneto Marco , Gasbarrini Giovanni
Published: May 2008

Background: Dicarboxylic acids (DA) are watersoluble substances with high‐energy density proposed as an alternative lipid substrate for nutrition purposes. The aim of the present study was to investigate the interaction between glucose and DA or long‐chain triglyceride (LCT) metabolism after oral administration. Methods: Two test meals containing either dodecanedioic acid (C12, the 12‐atom DA) or LCT, together with glucose and amino acids, were each administered to five healthy volunteers. Tracer amounts of 14C‐dodecanedioic acid were added to the C12 meal to recover expired traced CO2 and estimate the minimum rate of C12 oxidation. Glucose, insulin, and C12 plasma levels were measured for 360 minutes after the test meal. Indirect calorimetry was performed for the duration of the study. Results: LCTs proved ineffective in promoting their own oxidation after oral administration. On the contrary, C12 was promptly oxidized, a minimum of 21.9% ± 8.3% of the administered amount giving rise to the recovered expired CO2. This difference in metabolic fate was reflected in a sparing effect on glucose: suprabasal respiratory quotient and suprabasal carbohydrate oxidation were significantly (p <.05) lower under C12 administration than under LCT administration, with a difference of 0.024 ± 0.015 in respiratory quotient (RQ) and a difference of 0.791 ± 0.197 kJ/min in carbohydrate oxidation. In particular, carbohydrate oxidation increased by 54% over basal with LCT but only by 28% with C12 administration. RQ increased over basal by 5.8% with LCT but only by 3.0% with C12 administration. Conclusions: These results show a fundamental metabolic difference between conventional lipids and DAs, which is the basis for a possible role of DAs in clinical nutrition. The fate of spared glucose is likely to be storage in glycogen form when dodecanedioic acid is made available as an energy source. (Journal of Parenteral and Enteral Nutrition 23:80–84, 1999)
Bioimpedance Analysis: Potential for Measuring Lower Limb Skeletal Muscle Mass
Authors: Nuñez Christopher , Gallagher Dympna , Grammes Jill , Baumgartner Richard N. , Ross Robert , Wang ZiMian , Thornton John , Heymsfield Steven B.
Published: May 2008

Background: Ambulation, balance, and lower extremity bone mass and strength are all partially dependent on lower limb skeletal muscle mass. At present, both research and clinical methods of evaluating lower limb skeletal muscle mass as a component of nutrition assessment are limited. One potential simple and inexpensive method is lower extremity bioimpedance analysis (BIA). The present study had two objectives: to examine the determinants of lower limb resistance, with the underlying hypothesis that fluid‐containing muscle is the main electrical conductor of the lower limbs; and to establish if a correlation of equivalent magnitude and similar covariates is observed when height squared (H2) is used instead of lower limb length squared (L2) in multiple regression models relating resistance to independent variables. Methods: Lower limb resistance was measured using a contact‐electrode BIA system, and lower limb fat and skeletal muscle were estimated by dual‐energy x‐ray absorptiometry in healthy adults. A physical BIA model was developed in the form of a regression equation with pathlength (as L2 and H2)‐adjusted resistance as dependent variables and lower limb skeletal muscle, fat, age, and gender as potential independent variables. Results: There were 94 subjects, 34 men and 60 women, with a mean (±SD) age of 41.5 ± 17.8 years. Strong associations were observed between L2/resistance and lower limb skeletal muscle, although for both men and women, age entered into the model as a significant covariate (total R2, men =.79 and women =.72; both p <.001). Similar models were observed with H 2/resistance as dependent variable. Additional analyses showed a significantly lower resistance in lower limb skeletal muscle and height‐matched old us young subjects. Conclusions: Strong associations exist between measured lower limb resistance and lower limb muscle mass, adjusting for electrical path length either by L2 or H2. These observations suggest the potential of predicting skeletal muscle using BIA‐measured lower limb resistance adjusted for stature. Age is also an independent variable in lower limb resistance‐skeletal muscle associations, suggesting the need to establish underlying mechanisms of age‐related resistance effects and to consider subject age when developing BIA prediction models. (Journal of Parenteral and Enteral Nutrition 23:96–103, 1999)
Oral and Parenteral Glutamine in Bone Marrow Transplantation: A Randomized, Double‐Blind Study
Authors: Schloerb Paul R. , Skikne Barry S.
Published: May 2008

Background: Total parenteral nutrition (TPN) supplemented with glutamine (GLN) has been reported to be effective for patients with bone marrow transplantation (BMT). Our aim was to evaluate enteral and parenteral glutamine in patients undergoing BMT. Methods: For evaluation of GLN in BMT, 66 patients with 43 hematologic and 23 solid malignancies (21 breast carcinomas), were randomized, double‐blinded, to either oral GLN (n = 35) or glycine‐control (GLY) (n = 31), 10 g three times daily. When TPN became necessary, patients who received GLN orally were given TPN with GLN (0.57 g/kg). Those who received GLY received standard TPN, isocaloric and isonitrogenous. Patients with hematologic malignancies received high‐dose chemotherapy, total body irradiation, and either allogeneic (ALLO) BMT (n = 18) or autologous (AUTO) stem cell transplantation (n = 25). Patients with solid malignancies (n = 23) received AUTO. Results: There were 14 in‐hospital deaths without relationship to GLN administration. For respective comparisons of ALLO and AUTO transplants in the GLN and GLY hematologic groups and AUTO in the solid tumor groups, there were no significant differences in hospital stay, duration of stay after BMT, TPN days, neutrophil recovery >500/mm3, incidence of positive blood cultures, sepsis, mucositis, and diarrhea. Acute graft us host disease occurred in 1 of 10 hematologic patients receiving GLN and in 3 of 8 patients receiving GLY placebo (p >.05). Possible reduction in need for TPN and a suggestion of improved long‐term survival were associated with GLN. Conclusions: Oral and parenteral GLN seemed to be of limited benefit for patients having AUTO or ALLO BMT for hematologic or solid malignancies. Further study of long‐term effects of GLN in BMT seems warranted. (Journal of Parenteral and Enteral Nutrition 23:117–122, 1999)
Glutamine Reduces Phorbol‐12,13‐Dibutyrate‐Induced Macromolecular Hyperpermeability in HT‐29Cl.19A Intestinal Cells
Authors: Kouznetsova Luda , Bijlsma Pieter B. , van Leeuwen Paul A. M. , Groot Jack A. , Houdijk Alexander P. J.
Published: May 2008

Background: Loss of mucosal integrity is associated with intestinal hyperpermeability, which may be inhibited by glutamine. The nature of this effect is unknown. The effect of glutamine on protein kinase C (PKC)‐mediated hyperpermeability in HT‐29Cl.19A intestinal cells was studied. Methods: Confluent monolayers ofHT‐29Cl.19A cells were cultured on permeable filters and mounted in Ussing chambers for permeability studies. Apical to basolateral transepithelial permeability for intact horseradish peroxidase (HRP) was determined. Phorbol‐12,13‐dibutyrate (PDB) was used to activate PKC‐mediated hyperpermeability, and the effect of glutamine (0.6 mmol/L) was studied. Results: Two hours of PDB stimulation increased the HRP flux, reaching five times control values after 4 hours. Bilateral exposure to glutamine for 4 hours reduced PDB‐induced hyperpermeability (37%). Preincubation with glutamine 2 hours before PDB stimulation showed an earlier and greater effect (3 hours, 43%; 4 hours, 50%). This bilateral effect of glutamine was mimicked by separate apical exposure. Basolateral exposure alone had no effect. Conclusions: Glutamine rapidly reduced the PKC‐mediated hyperpermeability for HRP in HT‐29Cl.19A intestinal cells. The dependency on apical exposure suggests that glutamine may be more effective when delivered by the enteral route. (Journal of Parenteral and Enteral Nutrition 23:136–139, 1999)
Chronic Infusion of Interleukin 1 Induces Hyperlactatemia and Altered Regulation of Lactate Metabolism in Skeletal Muscle
Authors: Vary Thomas C. , O'Neill Patrick , Cooney Robert N. , Maish George , Shumate Margaret
Published: May 2008

Background: Hyperlactatemia is observed commonly in patients with severe inflammation syndrome or sepsis. Elevated plasma lactate concentrations may be caused by cytokine‐mediated alterations in specific organ systems responsible for lactate homeostasis. The role of interleukin 1 (IL‐1) in inducing hyperlactatemia and derangements in skeletal muscle and hepatic lactate metabolism was investigated by examining the consequences of infusing IL‐1 continuously into normal rats. Methods: Male Sprague‐Dawley rats were anesthetized, and catheters were placed in the jugular vein. Rats were allowed to recover for 48 hours and were infused subsequently with either saline (control) or human recombinant IL‐1α (20 μg/kg/d) for 6 days. On day 6, plasma, liver, and muscle samples were extracted and assayed for lactate and pyruvate dehydrogenase (PDH) activity. Results: Plasma glucose concentrations were not different in the two groups. IL‐1 infusion resulted in a twofold (p <.05) increase in the plasma lactate concentration compared with controls. IL‐1 infusion also resulted in an elevated lactate content in skeletal muscle (p <.05) but not in liver. The proportion of PDH in the active form (PDHa) was reduced significantly (p <.05) in the skeletal muscle of animals infused with IL‐1 compared with controls. In contrast to muscle, hepatic PDHa did not differ between the two groups. Total PDH complex activity was not affected in either liver or skeletal muscle. Conclusions: IL‐1 infusion results in hyperlactatemia, increased skeletal muscle lactate, and a reduced PDHa in skeletal muscle. We conclude that IL‐1 is a potential mediator of the derangements in lactate metabolism in skeletal muscle but not in liver. (Journal of Parenteral and Enteral Nutrition 23:213–217, 1999)
Trace Element Contamination of Total Parenteral Nutrition. 2. Effect of Storage Duration and Temperature
Authors: Pluhator‐Murton Michelle M. , Fedorak Richard N. , Audette Robert J. , Marriage Barbara J. , Yatscoff Randall W. , Gramlich Leah M.
Published: May 2008

Background: Patients who receive home total parenteral nutrition (TPN) frequently are supplied with solutions up to 30 days in advance of anticipated use. The purpose of this study was to determine the stability of trace elements relative to time and temperature conditions, in a typical adult TPN solution stored in a usual home environment by examining variations in delivery of intended trace elements and inadvertent trace element contamination. Methods: Trace element concentrations were determined using inductively coupled plasma‐mass spectrometry technology. The effect of the delivery apparatus, storage duration (36 hours or 30 days) after compounding, and storage temperature (4°C or 20°C) were examined. Results: The delivery apparatus contaminated the delivered TPN solution with cobalt but did not alter trace elements formulated into the TPN solution. Storage duration and temperature significantly decreased three (Zn, Cu, and Mn) of the six trace elements formulated into the TPN solution. Higher temperatures and longer duration of storage accelerated this decrease. Boron, Al, V, Ti, Ba, Sr, and CO were the trace elements that appeared as contaminants during storage. Boron, Al, V, and Ti contamination decreased with higher temperatures and longer duration of storage. Conclusions: Longer storage duration and higher storage temperature progressively reduced the deliverable concentrations of trace elements specifically formulated into the TPN solution and also of those trace elements that were not formulated into the TPN solution but that appeared as contaminants. (Journal of Parenteral and Enteral Nutrition 23:228–232, 1999)
Effects of Parenteral Nutrition Support and Chemotherapy on the Phasic Composition of Tumor Cells in Gastrointestinal Cancer
Authors: Jin Dayong , Phillips Michael , Byles Julie E.
Published: May 2008

Background: Some clinical studies report the effects of parenteral nutrition in malnourished cancer patients, but few discuss the tumor response to parenteral nutrition plus chemotherapy. If used in combination, the antitumor activity of chemotherapeutic agents may compensate for the tumor stimulation of parenteral nutrition. Methods: Ninety‐two patients with operable gastrointestinal cancer and malnutrition were randomly assigned to four interventions that were administered for 7 days preoperatively : parenteral nutrition alone, parenteral nutrition plus chemotherapy, chemotherapy alone, or no treatment (control). The preintervention and postintervention DNA content, DNA index, percentage of cells in S phase, and tumor cell sensitivity to chemotherapy were measured using image cytometry. Results: Parenteral nutrition resulted in a significant proliferation of tumor cells and a significant increase in the sensitivity of tumor cells to chemotherapy; these effects were not seen in tumors of patients receiving parenteral nutrition plus chemotherapy. There was, however, a nonsignificant increase in tumor cell proliferation and sensitivity to chemotherapy in the tumors of subjects receiving combined therapy compared with those of subjects who received chemotherapy alone. The postintervention nutritional status of both the parenteral nutrition group and the parenteral nutrition plus chemotherapy group were significantly better than that of the control group and the chemotherapy group. The short‐term, postoperative clinical outcomes in the chemotherapy group were significantly worse than those in the other three groups. Conclusions: These results indicate that combining chemotherapy and nutrition support preoperatively for malnourished patients with gastrointestinal cancer improves short‐term nutritional status without increasing the proliferation of tumor cells and prevents the postoperative complications that occur when such patients are given chemotherapy without nutrition support. The results also suggest—but do not prove—that parenteral nutrition may increase the effectiveness of chemotherapy in malnourished patients. (Journal of Parenteral and Enteral Nutrition 23:237–241, 1999)
Blood Clearance and Tissue Uptake of Intravenous Lipid Emulsions Containing Long‐Chain and Medium‐Chain Triglycerides and Fish Oil in a Mouse Model
Authors: Treskova Erena , Carpentier Yvon A. , Ramakrishnan Rajasekhar , Al‐Haideri Maysoon , Seo Toru , Deckelbaum Richard J.
Published: May 2008

Background: Increasing interest in using different triglycerides (TGs) for specific clinical applications raised the question as to how the emulsion TG composition would affect blood clearance and emulsion delivery to hepatic and extrahepatic tissues. Methods: Emulsions used were long‐chain soy oil TG (long‐chain triglyceride [LCT]), LCT/ medium‐chain triglyceride (MCT; 1:1, wt/wt), LCT/MCT/C/w‐3 (5:4:1, wt/wt) and pure fish oil (w‐3 TG) labeled with nondegradable 3H‐cholesteryl oleoyl ether (3H‐CE) as a particle marker. Mice (C57BL/6J) were injected with four different commercial emulsions at a nonsaturating dose of 0.4 mg TG/20 to 25 g per mouse to obtain 1st order kinetics. Blood was sampled at 0.5, 2, 5, 10, 15, and 25 minutes, and the fractional catabolic rate was determined by fitting a straight line to the logarithm of the blood 3H‐CE radioactivity. Retention of 3H‐CE for each tissue at 25 minutes reflected organ uptake of the emulsion. Results: Blood clearance of pure w‐3 TG (10.40% ± 0.54% pools/h; mean ± SE) was significantly slower than that of LCT, LCT/MCT, and LCT/MCT/w‐3 emulsion (18.9 ± 0.6 pools/h, 17.0 ± 0.96 pools/h, 16.5 ± 1.08 pools/h, respectively) (p <.01 Based on 3H‐CE uptake, LCT, LCT/MCT, and ω‐3 TG emulsions showed similar delivery to liver (39% ± 3.9%, 46% ± 3.6%, 34% ± 3.2%). Liver uptake of LCT/MCT/ω‐3, (23% ± 2.2%) was less than LCT/MCT (46% ± 3.6%, p <.0001) and LCT (39% ± 3.9%, p =.002). Conclusions: Results indicate slow blood clearance of pure ω‐3 TG emulsion from the blood compared with emulsion in which ω‐3 TG was mixed with LCT and MCT. Earlier data showed that ω‐3 TG are poorly hydrolyzed in extracellular media and therefore are delivered to tissues as part of the core of emulsion remnants. Thus, our data suggest that the incorporation of ω‐3 TG with LCT/MCT will result in greater delivery of ω‐3 fatty acids to extrahepatic tissue, which could be important in modulating immune and other responses. (Journal of Parenteral and Enteral Nutrition 23:253–259, 1999)
Plasma Choline Concentrations in Children Requiring Long‐Term Home Parenteral Nutrition: A Case Control Study
Authors: Misra Sudipta , Ahn Chul , Ament Marvin E. , Choi Ha‐Joo , Jenden Donald J. , Roch Margareth , Buchman Alan L.
Published: May 2008

Background: Low plasma free choline concentration has been associated with elevated serum hepatic aminotransferase concentrations and hepatic steatosis in adults who need home parenteral nutrition (HPN). We sought to determine if plasma free choline is similarly reduced in children who need home total parenteral nutrition (TPN). Methods: We compared the plasma free choline concentration in 21 children who required long‐term HPN with 31 normal controls. Patients had received HPN for 75 ± 13 (SD) months (range 3–206 months). All control children ingested a normal, mixed, nonvegetarian diet. Results: The mean plasma free choline concentration in the children receiving HPN was significantly lower than normal children (6.6 ± 4.3 us 8.0 ± 2.3 nmol/mL, p =.002). Plasma free choline concentration was correlated with age (r = ‐ 0.43, p =.049). Using multiple linear regression analysis for age, sex, and squared age (considered in order to account for possible nonlinearity between choline and age), HPN children showed a steady and significant decline in plasma free choline concentration with increased age at the rate of 0.03 nmol/mL per month. Plasma lipid bound choline concentration did not vary with age. No relationship was seen between either plasma free and lipid bound choline concentration and amount of daily IV lipid infusion. A significant negative correlation was observed between plasma free choline concentration and aspartate aminotransferase (AST) and alanine aminostransferase (ALT) (r = ‐0.72, p =.04 and r = ‐0.80, p =.02, respectively). Conclusion: Our data support the notion that patients who need long‐term HPN without significant enteral feeding have a significant risk for the development of choline deficiency with its associated hepatic dysfunction. (Journal of Parenteral and Enteral Nutrition 23:305–308, 1999)
A Prospective, Randomized Clinical Trial on Perioperative Feeding With an Arginine‐, Omega‐3 Fatty Acid‐, and RNA‐Enriched Enteral Diet: Effect on Host Response and Nutritional Status
Authors: Gianotti Luca , Braga Marco , Fortis Claudio , Soldini Laura , Vignali Andrea , Colombo Stefania , Radaelli Giovanni , Di Carlo Valerio
Published: May 2008

Background: The use of immune‐enhancing enteral diets in the postoperative period has given contrasting results. The purpose of this prospective, randomized, double‐blinded clinical study was to evaluate the effect of immunonutrition given perioperatively on cytokine release and nutritional parameters. Methods: Patients with cancer of the stomach or colo‐rectum were eligible. Subjects consumed 1 L/d of either a control enteral formula (n = 25; control group) or a formula supplemented with arginine, omega‐3 fatty acids, and RNA (n = 25; verum group) for 1 week before surgery. Both formulas were given by mouth. Six hours after the operation, jejunal infusion with the same diets was started and maintained for 7 days. Blood was drawn at different time points to assess albumin, prealbumin (PA), transferrin, cholinesterase activity, retinol binding protein (RBP), interleukin‐2 receptors alpha (IL‐2Rα), IL‐6, and IL‐1 soluble receptors (IL‐1RII). The composite score of delayed hypersensitivity response (DHR) to skin test also was determined (the higher the score, the lower the immune response). Results: During the 7 days of presurgical feeding, none of the above parameters changed in either group. Eight days after operation, in the control group, the concentration of PA and RBP was lower than in the verum group (0.18 us 0.26 g/L for PA and 30.5 us 38.7 mg/L for RBP; p <.05). IL‐2Rα concentration was 507 pg/mL in the verum group us 238 pg/mL in the control group (p <.001), whereas IL‐6 and IL‐1RII were higher in the control group than in the verum group (104 us 49 and 328 us 183 pg/mL, respectively; p <.01). The DHR score was 0.68 in the control group us 0.42 in the verum group (p <.05). Conclusions: Perioperative feeding with a supplemented enteral diet modulates cytokine production and enhances cell‐mediated immunity and the synthesis of short half‐life proteins. (Journal of Parenteral and Enteral Nutrition 23:314–320, 1999)
Sodium d‐Fructose‐1,6‐Diphosphate vs. Sodium Monohydrogen Phosphate in Total Parenteral Nutrition: A Comparative In Vitro Assessment of Calcium/Phosphate Compatibility
Authors: Prinzivalli Michela , Ceccarelli Stefano
Published: May 2008

Background: The supply of high amounts of calcium (Ca) and phosphorus (P) during total parenteral nutrition (TPN) is matter of concern because of the risk associated with calcium phosphate precipitation. The in vitro Ca‐P compatibility in ready‐for‐use TPN solutions after the addition of different concentrations of inorganic phosphate or d‐fructose‐1,6‐diphosphate (FDP) and calcium chloride was evaluated. Methods: Four series of experiments for each Ca + P couple were carried out by varying amino acid concentrations (2% or 4%), temperature (25°C or 37°C), and pH. The extent of precipitation was estimated by visual inspection and particle count. The areas of maximal compatibility (ie, areas showing the complete absence of precipitates) were drawn from the precipitation curves. Results: The precipitation extent was considerably higher in conditions mimicking body environment for both Ca + P couples. The compatibility area at 37°C and 2% amino acid for CaCl2 + Na2HPO4 admixtures was included within 2.50 mmol/L CaCl2 and 2.22 mmol/L Na2HPO4, whereas that for CaCl2 + FDP was within 33.3 mmol/L CaCl2 and 10.0 mmol/L FDP (20 mEq/L of P). Unlike inorganic calcium phosphate, FDP dicalcium salt precipitation was kinetically delayed and was only minimally enhanced by decreasing amino acid concentration. Conclusions: Our data indicated that the use of FDP as the P source in parenteral nutrition solutions was effective in avoiding the life‐threatening calcium phosphate precipitation. Thus, the addition of FDP to TPN admixtures represents a safe choice, allowing the simultaneous administration of high amounts of Ca and P in restricted fluid volumes, even at low amino acid concentrations. (journal of Parenteral and Enteral Nutrition 23:326–332, 1999)
Hypermanganesemia in Patients Receiving Total Parenteral Nutrition
Authors: Fitzgerald Kathleen , Mikalunas Vida , Rubin Halina , McCarthy Roberta , Vanagunas Arvydas , Craig Robert M.
Published: May 2008

Background: Manganese is one of the trace elements that is routinely administered to total parenteral nutrition (TPN) patients. The recommended daily IV dosage ranges from 100 to 800 μg. We have used 500 μg daily. Recent reports have suggested neurologic symptoms seen in some patients receiving home parenteral nutrition (HPN) may be due to hypermanganesemia. Therefore, HPN patients and some short‐term inpatients receiving TPN were studied to ascertain the relationship between dose and blood levels. Methods: Red blood cell manganese levels were obtained by atomic absorptiometry. Results: The levels in 36 hospitalized, short‐term patients obtained within 48 hours of initiating TPN were all normal. The 30 patients receiving TPN from 3 to 30 days had levels that ranged from 4.8 to 28 μg/L (normal, 11 to 23 μg/L). Two patients had abnormal levels, at days 14 and 18. Fifteen of the 21 patients receiving inpatient TPN or HPN for 36 to 5075 days had elevated Mn levels. Only one patient with hypermanganesemia, an inpatient, had abnormal biochemical liver tests (bilirubin and alkaline phosphatase). One of the patients with a high level had some vestibular symptoms attributed to aminoglycoside use and had increased signal density in the globus pallidus on T1‐weighted images on magnetic resonance imaging (MRI). A second patient with Mn levels twice normal had no neurologic symptoms, but had similar MRI findings. A third had some basal ganglia symptoms, confirmed by a neurologic evaluation, seizures, and very high Mn levels. The MRI showed no signal enhancement, but motion artifacts limited the study technically. Conclusions: Hypermanganesemia is seen in HPN patients receiving 500 μg manganese daily and may have resulted in some neurologic damage in three patients. Hypermanganesemia is sometimes seen after a short course of TPN in inpatients, as early as 14 days. Patients should be monitored for hypermanganesemia if they receive Mn in their TPN for >30 days. A 500 μg/d dose of Mn is probably excessive, and 100 μg/d should probably never be exceeded. Mn should be eliminated from the solution if the Mn level is elevated and should not be readministered unless the level returns to normal or subnormal. Mn should not be supplemented if the patient has liver disease with an elevated bilirubin. (Journal of Parenteral and Enteral Nutrition 23:333–336, 1999)
A Comparison of the Response Styles Theory and the Hopelessness Theory of Depression in Preadolescents
Authors: Weir Kirsty F. , Jose Paul E.
Published: May 2008

This study compares predictions from the Hopelessness Theory of depression (Abramson, Metalsky, & Alloy, 1989) with the Response Styles Theory of depression (RST; Nolen-Hoeksema, 1987) with data obtained from a preadolescent sample (ages 9 to 13 years). Three hundred ten preadolescents completed self-report measures of stress, sense of control, rumination, and depressive symptoms. Neither rumination nor perceived control moderated the relationship between stress and depressive symptoms. However, path models revealed that perceived control was a more powerful mediator of the relationship between stress and depressive symptoms than rumination. Rather than having a direct impact on depressive symptoms, rumination exerted an indirect effect by predicting lowered perceived control. Overall, these results provide support for the Hopelessness Theory of depression and partial support for the RST in this sample of preadolescents.
A Cost-Effectiveness Framework for Profiling the Value of Hospital Care
Authors: Timbie Justin W. , Newhouse Joseph P. , Rosenthal Meredith B. , Normand Sharon-Lise T.
Published: May 2008

Provider profiling and performance-based incentive programs have expanded in recent years but need a theoretical framework for measuring and comparing the ``value'' of clinical care across medical providers. Cost-effectiveness analysis provides such a framework but has rarely been used outside of the treatment choice context. The authors present a profiling framework based on cost-effectiveness methods and illustrate their approach using data on in-hospital survival and the cost of care for a heart attack from a sample of Massachusetts hospitals during fiscal year 2003. They model each outcome using hierarchical models that allow performance to vary across hospitals as a function of a latent quality effect and an effect of case mix. They also estimate incremental outcomes by conditioning on each hospital's pair of random effects, using indirect standardization to estimate ``expected'' outcomes, and then taking their difference. Incremental cost and effectiveness outcomes are combined using incremental net monetary benefits. Using cost-effectiveness methods to profile hospital ``value'' permits the comparison of the benefit of a service relative to the cost using existing societal weights.