Yoji Takagi

Alanyl-glutamine-enriched total parenteral nutrition restores intestinal adaptation after either proximal or distal massive resection in rats

This study was designed to determine whether alanyl glutamine-containing total parental nutrition (TPN) can restore the impaired adaptive process of the remaining intestine, observed with administration of conventional TPN, after massive small-bowel resection. Seventy-four male Sprague-Dawley rats weighing 250 g were randomly divided into seven groups. Group I rats (n = 10) were killed after overnight fasting. Group II animals (n = 32) underwent massive small bowel resection (85%) with preservation of the first 15 cm of jejunum. Group III animals (n = 32) were also submitted to massive small-bowel resection with preservation of 15 cm of terminal ileum. Three different TPN solutions were prepared. Solution A was a conventional formulation that did not contain glutamine. Solution B contained 1.88 times the amino acid concentration of solution A. Solution C was prepared by adding alanyl glutamine (2 g/100 mL) to solution A. Solutions B and C were isonitrogenous and isocaloric. Each solution was infused to groups II and III, which were subdivided into groups IIA (n = 10), IIB (n = 11), IIC (n = 11), IIIA (n = 10), IIIB (n = 11), and IIIC (n = 11). After 1 week of TPN (270 kcal/kg per day), the experimental animals were killed and the intestine was taken for examination. Final body weight did not differ significantly among the groups, and there was no difference in nitrogen balance among the animals that received solution B or C.(ABSTRACT TRUNCATED AT 250 WORDS)

The Dipeptide Alanyl-Glutamine Prevents Intestinal Mucosal Atrophy in Parenterally Fed Rats

This study was performed to determine whether the addition of alanyl-glutamine (Ala-Gln) can prevent intestinal mucosal atrophy induced by standard solution of total parenteral nutrition (S-TPN). Forty-one male Sprague-Dawley rats weighing 250 g were randomly divided into four groups: group I was killed after overnight fasting; group II received S-TPN. The other groups received S-TPN supplemented with amino acids other than glutamine (group III) or supplemented with Ala-Gln 2 g/100 mL (group IV); both solutions were isocaloric and isonitrogenous. After 1 week of TPN the rats were killed, and the duodenum, proximal jejunum, mid-small bowel, and distal ileum were obtained for morphologic and functional analysis. Weight gain did not differ significantly among these four groups, and there was no difference in nitrogen balance between groups III and IV. Serum glutamine in group IV (102.8 +/- 13.3 mumol/dL) was significantly increased (p less than .05) compared with groups I, II, and III (66.2 +/- 3.9, 55.7 +/- 7.8, and 61.3 +/- 10.8 mumol/dL, respectively). Mucosal wet weight, protein, RNA, sucrase, and maltase of group IV were significantly increased (p less than .05) compared with groups II and III. Villus height was significantly increased (p less than .05) in the jejunum of group IV rats compared with groups II and III, but not in any other segments of the intestine. No significant changes were observed in crypt depth among all groups. Diamine oxidase in groups II, III, and IV was significantly decreased (p less than .05) compared with group I in all segments except for the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)

Manganese Deposition in the Brain During Long-Term Total Parenteral Nutrition

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 micrograms/L (normal range 14.6 +/- 4.7 micrograms/L), whereas the level was 20 micrograms/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.

Alanyl-Glutamine-Supplemented Parenteral Nutrition Increases Luminal Mucus Gel and Decreases Permeability in the Rat Small Intestine

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.

Copper deficiency with pancytopenia during total parenteral nutrition.

Anemia and neutropenia are commonly observed hematologic changes in patients with copper (Cu) deficiency, but thrombocytopenia is rarely found. A-69-year-old patient with postoperative small-bowel obstruction underwent laparotomy three times. Because of persistent obstruction, nasoduodenal suction was continued and total parenteral nutrition was instituted. Fifteen months after the initiation of total parenteral nutrition, the patient gradually developed pancytopenia (red blood cell count 222 x 10(4)/mm3, neutrophil count 1254/mm3, and platelet count 9.2 x 10(4)/mm3). The serum Cu level was 10 micrograms/dL and the serum ceruloplasmin level was less than 5 mg/dL. After 2 weeks of Cu supplementation in a daily dose of 20 mumol, the serum Cu level increased to 81 micrograms/dL and the serum ceruloplasmin level to 20 mg/dL. Hematologic values showed a dramatic response: red blood cell count increased to 362 x 10(4)/mm3, neutrophil count to 4819/mm3, and platelet count to 22.1 x 10(4)/mm3. The improvement of pancytopenia could be attributed to Cu supplementation. This is the first case report of Cu deficiency with pancytopenia during total parenteral nutrition.

Total parenteral nutrition decreases luminal mucous gel and increases permeability of small intestine.

The distribution of fluorescein isothiocyanate dextran 70,000 (FITC-dextran) and mucous gel across the lumen of small intestine was observed as an investigation into the role of mucous gel on permeability in total parenteral nutrition (TPN). Thirty-two rats were randomly divided into two groups fed with either TPN or oral rat food. On day 4 or 7, FITC-dextran (750 mg/kg body weight) was given through the gastroduodenal tube. After 1 hour, blood samples were taken by aortic puncture to analyze plasma FITC-dextran by fluorescence spectrometry. Samples of small intestine with luminal contents were frozen and sectioned in a cryostat for fluorescence microscopy; the same sections were placed in a 0.2% celloidin solution for 3 minutes to preserve mucous gel and stained by periodic acid-Schiff reaction for light microscopy. The plasma level of FITC-dextran after 1 hour of this marker injection showed a significant increase (p < .01) in the TPN group compared with the rat food group on days 4 and 7. Morphologic findings on days 4 and 7 were similar in both the jejunum and ileum: The mucous gel filled the spaces between villi and FITC-dextran centered in the lumen in the rat food group, whereas the mucous gel decreased and FITC-dextran filled the spaces between villi in the TPN group. FITC-dextran and mucous gel showed complementary distributions in both groups. These data suggest that TPN decreases luminal mucous gel and increases permeability of small intestine in rats.

The effect of metronidazole on TPN-associated liver dysfunction in neonates

The effect of metronidazole (MNZ) on hepatic dysfunction associated with total parenteral nutrition (TPN) in neonates was investigated. Neonates receiving TPN for more than 2 weeks were divided into three groups. In group 1, TPN was given alone, in group 2, 25 mg/kg/d of MNZ was administered intravenously for the first 2 weeks of TPN, and in group 3, 50 mg/kg/d of MNZ was given for the first 3 weeks of TPN. Several parameters of liver function tests (LFTs) during the first 4 weeks of TPN were compared among these three groups. There was no significant difference of these parameters between group 1 and group 2. Although there was no significant difference of alkaline phosphatase, gamma-glutamyl transpeptidase, direct bilirubin, and total bile acid between groups 1 and 3, transaminase (glutamic oxaloacetic, glutamic pyruvic) of group 3 remained significantly lower than those of group 1. In conclusion, the administration of MNZ 50 mg/kg/d for 3 weeks, at least, prevented the elevation of transaminase during TPN in neonates, suggesting the possible involvement of intestinal anaerobic flora in the pathogenesis of TPN-associated liver dysfunction.

Prevention of Catheter-Related Sepsis During Parenteral Nutrition: Effect of a NeW Connection Device

A prospective study was carried out to determine the clinical effect of a newly devised catheter connection method (I system) and piggyback access system. Previous studies have demonstrated that the I system avoided bacterial contamination in vitro during tubing change that Luer-Lock connectors did not. The purpose of this study was to investigate the ability of this device coupled with a new closed-system piggyback technique for multipurpose access to reduce catheter-related sepsis in clinical practice. Two hundred and thirty patients receiving total parenteral nutrition were divided into two groups. Group I (n = 106) used the I system connector and group L (n = 124) used a Luer-Lock connector. Catheters in both groups were used for multipurpose access for infusion and blood sampling. In group L, a three-way stopcock and/or pig-gyback system was used for multiple access. In group I, a newly designed closed-system piggyback was used. The incidence of catheter-related sepsis was significantly lower in group I (1.89%/catheter) than in group L (12.10%/catheter) (p < .01, chi 2 analysis), and the average duration of use of each catheter was significantly longer in group I than in Group L (p < .01 by generalized Wilcoxon test). The results of this clinical study suggest that the newly designed connection method and piggyback access system are able to reduce catheter-related sepsis.

Copper Deficiency during Total Parenteral Nutrition: Clinical Analysis of Three Cases

Three adult cases in which copper deficiency developed during long-term total parenteral nutrition (TPN) without copper supplementation have been described, together with a brief review of the literature. All three patients were suffering from malabsorption when TPN was instituted, and overt symptoms of copper deficiency developed an average of 5.8 months after the start of TPN. Clinically, leukopenia with neutropenia and low plasma levels of copper and ceruloplasmin were seen in all cases. The dosage of copper administration in these cases was 0.3 to 7.2 mg of copper/day, or 5.3 to 133 micrograms of copper/kg/day, with total doses of 7 to 176 mg of copper.

Influence of glutamine-supplemented parenteral nutrition on intestinal amino acid metabolism in rats after small bowel resection.

Glutamine (Gln)-supplemented total parenteral nutrition (TPN) has been shown to improve mucosal adaptation after massive small bowel resection (SBR); however, its influences on intestinal amino acid metabolism remain unknown. In this study, intestinal amino acid flux, circulating plasma aminogram, mucosal glutaminase activity and protein, and DNA content were measured 7 days after massive SBR in rats receiving either standard (Std) or Gln-supplemented TPN. Sham-operated rats and rats fed chow after enterectomy served as controls. The uptake of Gln and the release of citrulline (Cit) by the remaining intestine was significantly decreased, with reduced mucosal glutaminase activity after SBR in the Chow and Std-TPN groups. Glutamine supplementation resulted in significantly increased gut Gln uptake compared with Std-TPN (P<0.01). Mucosal glutaminase activity, mucosal protein, and DNA content was also increased by Gln; however, the gut release of Cit remained unchanged (P>0.05). The subsequent decrease in circulating arginine (Arg) in the Gln-TPN group compared with the Std-TPN group (P<0.05) was attributed to an insufficient exogenous supply. These findings show that Gln-supplemented TPN improves mucosal growth and gut Gln uptake after SBR. However, the intestinal production of Cit, which remained low in both TPN groups, may lead to an insufficiency of endogenous Arg synthesis. Thus, both Gln and Arg may be essential amino acids after SBR.