Emotion regulation processes and middle-aged Japanese women's health.

OBJECTIVES: Emotion regulation processes, such as mindfulness, self-compassion, and acceptance, have been discussed as modifiable psychological factors related to middle-aged women's psychological distress and adjustment. Although these emotion regulation factors have been discussed separately, the question remains of which factors reflect the most variance in middle-aged women's health. Therefore, this study aimed to reveal the most relevant explanatory variable for middle-aged women's health: mindfulness, self-compassion, or acceptance. METHOD: A total of 200 middle-aged women completed self-reported measures of depressive symptoms, menopausal symptoms, physical quality of life, mental quality of life, and well-being. RESULTS: Correlation analysis showed that mindfulness, self-compassion, and acceptance were significantly associated with all variables of psychological distress and adjustment. Hierarchical multiple regression analysis revealed that acceptance significantly explained the most variance of depressive symptoms, menopausal symptoms, and mental quality of life. On the other hand, self-compassion significantly explained the greatest variance in well-being. CONCLUSIONS: These findings suggest that, for middle-aged women, 'acceptance' is an important explanatory variable of psychological distress and 'self-compassion' is an important variable of psychological adjustment.

Gene expression signature and response to the use of leucovorin, fluorouracil and oxaliplatin in colorectal cancer patients

PURPOSE: FOLFOX (a combination of leucovorin, fluorouracil and oxaliplatin) has achieved substantial success in the treatment of colorectal cancer (CRC) patients. However, about half of all patients show resistance to this regimen and some develop adverse symptoms such as neurotoxicity. In order to select patients who would benefit most from this therapy, we aimed to build a predictor for the response to FOLFOX using microarray gene expression profiles of primary CRC samples. PATIENTS AND METHODS: Forty patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received modified FOLFOX6. Responders and nonresponders were determined according to the best observed response at the end of the first-line treatment. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. We identified discriminating genes whose expression differed significantly between responders and nonresponders and then carried out supervised class prediction using the k-nearest-neighbour method. RESULTS: We identified 27 probes that were differentially expressed between responders and nonresponders at significant levels. Based on the expression of these genes, we constructed a FOLFOX response predictor with an overall accuracy of 92.5%. The sensitivity, specificity, positive and negative predictive values were 78.6%, 100%, 100% and 89.7%, respectively. CONCLUSION: The present model suggests the possibility of selecting patients who would benefit from FOLFOX therapy both in the metastatic and the adjuvant setting. To our knowledge, this is the first study to establish a prediction model for the response to FOLFOX chemotherapy based on gene expression by microarray analysis (AU)

Randomized, controlled trial of lateral node dissection vs. nerve-preserving resection in patients with rectal cancer after preoperative radiotherapy.

PURPOSE: The effectiveness of preoperative radiation therapy for advanced lower rectal carcinoma to preserve the function of pelvic organs and reduce local recurrences was examined in a prospective, randomized, controlled study. METHODS: Fifty-one patients with a diagnosis of localized and resectable adenocarcinoma of the lower rectum undergoing 50 Gy of preoperative radiotherapy were recruited into the trial between April 1993 and March 1995. The patients were randomly allocated to complete autonomic nerve-preserving surgery without lateral node dissection (D1), or surgery with dissection of the lateral lymph nodes including autonomic nerves (D2) followed by oral administration of carmofur for one year. RESULTS: No difference was observed in either survival or disease-free survival between D1 and D2 groups. There was no difference between the two groups in terms of recurrence rate. A significant difference was observed in urinary and sexual function (P = 0.02 and 0.02, respectively) one year after surgery between D1 and D2 groups. CONCLUSION: This study suggests that lateral node dissection is not necessary in terms of curability for patients with advanced carcinoma of the lower rectum who undergo preoperative radiotherapy.

Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO) is one of the paraneoplastic diseases characterized by hypophosphatemia caused by renal phosphate wasting. Because removal of responsible tumors normalizes phosphate metabolism, an unidentified humoral phosphaturic factor is believed to be responsible for this syndrome. To identify the causative factor of TIO, we obtained cDNA clones that were abundantly expressed only in a tumor causing TIO and constructed tumor-specific cDNA contigs. Based on the sequence of one major contig, we cloned 2,270-bp cDNA, which turned out to encode fibroblast growth factor 23 (FGF23). Administration of recombinant FGF23 decreased serum phosphate in mice within 12 h. When Chinese hamster ovary cells stably expressing FGF23 were s.c. implanted into nude mice, hypophosphatemia with increased renal phosphate clearance was observed. In addition, a high level of serum alkaline phosphatase, low 1,25-dihydroxyvitamin D, deformity of bone, and impairment of body weight gain became evident. Histological examination showed marked increase of osteoid and widening of growth plate. Thus, continuous production of FGF23 reproduced clinical, biochemical, and histological features of TIO in vivo. Analyses for recombinant FGF23 products produced by Chinese hamster ovary cells indicated proteolytic cleavage of FGF23 at the RXXR motif. Recent genetic study indicates that missense mutations in this RXXR motif of FGF23 are responsible for autosomal dominant hypophosphatemic rickets, another hypophosphatemic disease with similar features to TIO. We conclude that overproduction of FGF23 causes TIO, whereas mutations in the FGF23 gene result in autosomal dominant hypophosphatemic rickets possibly by preventing proteolytic cleavage and enhancing biological activity of FGF23.

Retrospective radiographic analysis of nonpedunculated colorectal carcinomas with special reference to tumor doubling time and morphological change.

OBJECTIVE: Our aim was to characterize the development of nonpedunculated colorectal carcinomas by retrospective radiographic analysis, with special reference to tumor doubling time and morphological change. METHODS: Eleven colorectal carcinomas, which were observed for >6 months by barium enema examinations, were collected and retrospectively reviewed. There were five early and six advanced carcinomas, including submucosally invasive, superficial depressed carcinomas. RESULTS: Mean diameter of lesions at initial barium enema examination was 13.5 mm (early, 10.4 mm; advanced, 16.0 mm) and that at final barium enema examination was 30.9 mm (early, 18.2 mm; advanced, 41.5 mm). Initial morphology of the lesions was superficial in three, sessile in seven, and semipedunculated in 1. There was no pedunculated lesion. Macroscopic morphology of the five early carcinomas was superficial depressed (IIc) in two cases, mostly depressed but partly elevated (IIc+IIa) in one case, and superficial elevated with a depressed component (IIa+IIc) in two cases; all of the advanced carcinomas were of the ulcerated type. Mean doubling time was 6.8 months (early, 9.4 months; advanced, 4.7 months). Early carcinomas had significantly longer doubling times than advanced carcinomas (p = 0.017, Wilcoxon's text). The lesions with the longest doubling times were superficial depressed lesions. CONCLUSIONS: Early carcinomas have longer doubling times than advanced carcinomas. Most nonpedunculated colorectal carcinomas grow without significant morphological changes. Superficial depressed type tumors grow slowly, maintaining their macroscopic morphology.

Relation between thymidylate synthase expression and survival in colon carcinoma, and determination of appropriate application of 5-fluorouracil by immunohistochemical method.

BACKGROUND: Thymidylate synthase (TS) is regarded as a parameter of 5-fluorouracil (5-FU) chemosensitivity for colorectal carcinoma. Recent researchers indicate that the chemosensitivity of 5-FU for colorectal carcinoma with low expression of TS is better than tumors with high expression of TS. But the relation between TS expression and overall survival of curatively resected colorectal cancer patients has been less studied. METHODS: Specimens of curatively resected colon carcinoma from 148 patients were included in this study. TS expression in the tumor was assessed by immunohistochemical staining technique, and the patients were categorized into TS-(+) and TS-(-) groups. First, the relation between TS expression and survival of patients was examined. Next, for each group, we compared survival between the chemotherapy-(+) and the chemotherapy-(-) subgroup. RESULTS: Overall survival was significantly better in the TS-(-) group (n = 107) than in the TS-(+) group (n = 41) (P = .0003). In the TS-(-) group, there was little difference between the chemotherapy-(+) and the chemotherapy-(-) subgroup. In the TS-(+) group, the survival of the chemotherapy-(+) subgroup was significantly better than the chemotherapy-(-) subgroup (P = .0439). CONCLUSIONS: TS, itself, may be a prognostic factor for colon carcinoma; and 5-FU adjuvant chemotherapy may be appropriate for colon carcinoma with high expression of TS.

Relative effects of glucose and glutamine on reactive oxygen intermediate production by neutrophils.

The energy source for neutrophils (PMNs) has long been believed to be glucose. However, it has been shown recently that PMNs use glutamine as well as glucose. Nevertheless, the comparative effects of glucose and glutamine on PMN function remain to be clarified. This study investigated the relative effects of glucose and glutamine on reactive oxygen intermediate (ROI) production by PMNs. In experiment 1, PMNs (1 x 10(6)/mL) isolated from healthy volunteers were incubated in RPMI 1640 medium containing neither glucose nor glutamine for 4, 12, 18, and 24 h at 37 degrees C. The medium was supplemented with 0 or 200 mg/dL (0 or 11 mM, respectively) glucose and glutamine (0, 0.5, 1, or 2 mM). PMN cell death was assessed on the basis of hypodiploid DNA by flow cytometry using propidium iodide DNA staining. ROI production by PMNs was determined by flow cytometry using dihydrorhodamine 123. In experiment 2, isolated PMNs were cultured in RPMI 1640 medium containing neither glucose nor glutamine. The medium was supplemented with glucose (0 or 11 mM) and a competitive inhibitor of glycolysis, 2-deoxy-D-glucose (2-DG; 0 or 20 mM). Each medium was supplemented with glutamine (0, 0.5, 1, or 2 mM) and incubated for 12 h at 37 degrees C. Then, ROI production by PMNs was measured. PMN cell death was not affected by glucose or glutamine in this experiment. In contrast, ROI production by PMNs was greater at 11 mM glucose than at 0 mM glucose at all incubation times studied. At 11 mM glucose, supplemental glutamine enhanced PMN ROI production after 18 and 24 h culture. In contrast, at 0 mM glucose, glutamine augmented ROI production by PMNs after 12 h as well as with 18 and 24 h incubations. PMN ROI production after 12 h culture was significantly greater at 11 mM glucose without 2-DG than at both 11 and 0 mM glucose with addition of 2-DG. In addition, supplemental glutamine enhanced ROI production by PMNs when 2-DG was added at 11 and 0 mM glucose. Glucose is essential for PMN ROI production. Under conditions of glucose depletion in vitro, glutamine is of importance in ROI production by PMNs, whereas the enhancing effect of glutamine on PMN ROI production is minor compared to that of glucose.

Intrahepatic interleukin-2 with chemotherapy for unresectable liver metastases: a randomized multicenter trial.

BACKGROUND/AIMS: A pilot study of Interleukin-2 (IL-2) with chemotherapy for unresectable colorectal liver metastases revealed a favorable response rate (76%). This prospective, randomized, multicenter study was conducted to evaluate the efficacy of this treatment protocol. METHODOLOGY: Over a period of 32 months, 46 patients with unresectable liver metastases were randomly assigned to 1 of 3 treatment groups: group A: chemotherapy alone, group B: chemotherapy plus high-dose, intermittent IL-2 (2.1 x 10(6) U twice weekly) or group C: chemotherapy plus low-dose, continuous IL-2 (7 x 10(5) U daily). Treatment continued for 4 weeks in the hospital and on an outpatient basis according to the clinical response. No crossover between treatment arms was permitted. RESULTS: IL-2 combined with chemotherapy produced a higher complete and partial response rate of 40% in group A, 60% in group B, and 78% in group C. Toxicity related to IL-2 included fever, chills, malaise, and eosinophilia. CONCLUSIONS: Hepatic arterial infusion of chemotherapy plus IL-2 resulted in an increased tumor response when compared with chemotherapy alone. To confirm the efficacy of this treatment protocol, we have started a large-scale, randomized, multi-institution trial.

External beam radiotherapy for pelvic node recurrence after curative resection of colon cancer: report of a case.

The role of radiotherapy in locally advanced or recurrent colon cancer has not yet been determined. A 59-year-old man undergoing curative resection for advanced descending colon cancer had pelvic lymph node metastasis detected by computed tomography 5 months postoperatively. Intravenous chemotherapy using 5-fluorouracil and CDDP was repeated bimonthly for 7 months; however, his condition deteriorated progressively. External beam radiotherapy (50 Gy) was started thereafter. His serum carcinoembryonic antigen level decreased promptly and abdominal computed tomography showed apparent shrinkage of the metastatic pelvic node with calcification. The patient maintained a partial response for at least 12 months. Radiotherapy has a more crucial role in the treatment of a subgroup of recurrent colorectal tumors.

Biological effects of preoperative radiotherapy on metastatic lymph nodes from rectal cancer.

The quantitative description of the proliferative activity of cancer cells correlates with the aggressiveness of malignant tumors. The aim of this retrospective study was to determine the biological effect of adjuvant therapy on metastatic lymph nodes from rectal cancer and to compare the results between patients treated with surgery alone and patients treated with preoperative radiotherapy. Expression of the proliferating cell nuclear antigen (PCNA) was examined in metastatic lymph node samples of 12 rectal cancer patients receiving and 14 patients not receiving preoperative radiotherapy. PCNA immunostaining was performed by an avidin-biotin complex immunoperoxidase technique. The results of the mean proliferation index (PI) between the two groups were compared. A semiquantitative PCNA grading system was also estimated. In patients receiving preoperative radiotherapy, the PI was 22.8 per cent, and only one patient had high proliferative grade. On the contrary, the PI in nonirradiated patients was 67.6 per cent, and nine patients showed high proliferative grade. Although not sufficient to reach significance in terms of prognosis, the present study confirms the clinical value of radiation therapy, and it supports the suggestion to treat Dukes' C patients with preoperative radiotherapy to decrease the risk of local recurrence.

Enteral administration of glutamine in purulent peritonitis.

The intestinal hypomotility associated with purulent peritonitis is generally regarded as a contraindication to enteral nutrition. However, enteral nutrition may be feasible in suppurative peritonitis if administered with great caution, i.e., assuring the appropriate amount, delivery speed, and osmolality of the enteral formulation. Glutamine (Gln) increases muscle protein synthesis and decreases muscle protein degradation in sepsis, regardless of the route of administration. Therefore, administering small amounts of supplemental Gln via the enteral route to peritonitis patients may be beneficial. Two purulent peritonitis patients received L-Gln through a jejunostomy tube. The average amount of supplemental Gln was 16 g/d. Systemic inflammatory responses, i.e., high temperature and a high serum C-reactive protein level, persisted throughout the treatment period. Femoral arterial and venous blood samples were drawn simultaneously for determination of amino acid levels before and after 7 d of Gln supplementation. Enterally administered Gln was well-tolerated by both patients. There was an increase in plasma Gln levels after Gln supplementation. Moreover, the release of Gln, alanine, and phenylalanine from the lower extremities was lower after as compared to before Gln supplementation. Enteral administration of Gln may be feasible even in purulent peritonitis.

Possible associations of rectal carcinoma with Schistosoma japonicum infection and membranous nephropathy: a case report with a review.

We report the first case of rectal carcinoma associated with S. japonicum and membranous nephropathy. A 57-year-old Japanese man noticed narrowing of his feces. He had lived in Yamanashi prefecture, an endemic area of S. japonicum. He had suffered from nephrotic syndrome for about 1 year. Barium enema study showed a severe stricture in the upper rectum and biopsy specimens from the tumor demonstrated well differentiated adenocarcinoma and many ova of S. japonicum. Sonography of the liver showed a network pattern and a linear high echoic area. Low anterior resection with incisional biopsy of the liver and the right kidney was performed. Histopathological findings showed well differentiated adenocarcinoma and schistosomal ova. The total number of ova in the resected colon amounted to 15,133, consisting of 2243 inside and 12,890 outside the carcinoma. The nearer to the carcinoma the area was, the higher was the density of ova. The findings of light microscopy and electron microscopy of the biopsy specimen from the kidney were compatible with membranous nephropathy (stage II). This case suggests that schistosomal ova have some effect on carcinogenesis and nephrotic syndrome. In patients with nephrotic syndrome of unknown cause, especially in inhabitants of endemic areas of S. japonicum, gastrointestinal malignancy should be ruled out as an etiological factor. Sigmoidoscopy would be useful for colorectal carcinoma surveillance in S. japonicum patients.

A schwannoma of the cecum: case report and review of Japanese schwannomas in the large intestine.

A 66-year-old Japanese man had a positive fecal occult blood test at a regular check-up, and a large polypoid mass was detected in the cecum by barium enema study. Colonoscopy showed a submucosal tumor with ulcer protruding into the cecal lumen. A large-forceps biopsy specimen was taken from the bottom of the ulcer. With the tentative diagnosis of neurogenic tumor, ileocecal resection was performed. The tumor showed spindle-cell proliferation in a concentric or fascicular pattern. Immunohistochemically, the tumor cells were diffusely positive for S-100 protein, and they had intracytoplasmic periodic acid Schiff (PAS)-positive crystalloids. The mitosis count was low (about 1 per 20 high-power fields). The pathological diagnosis of this tumor was benign gastrointestinal schwannoma. A large number of schwannoma cases have been reported since 1910 when Verocay reported it as a true tumor that stemmed from Schwann cells and did not contain neuroganglion cells. However, gastrointestinal schwannomas are rare, and schwannomas of the large intestine are extremely rare. We reviewed 40 cases already reported in Japan and this present case in order to clarify the clinicopathological features of this tumor.

[Clinical result of intraperitoneal hyperthermic chemoperfusion for gastric cancer with serosal invasion to prevent peritoneal recurrence].

In order to evaluate clinical effects of intraperitoneal hyperthermic chemoperfusion (IHCP) to prevent peritoneal recurrence in gastric cancer patients with serosal invasion, the clinical outcome was studied in 126 gastric cancer patients with macroscopic serosal invasion. Results of 59 patients who had surgery combined with IHCP (IHCP group) were compared with those of 67 patients who had surgery alone (control group). IHCP was performed for 120 minutes just after surgery under hypothermic general anesthesia with perfusate containing 10 micrograms/ml of mitomycin C. The inflow temperature and the outflow temperature of the perfusate were controlled to be 44.5 approximately 45 degrees C, and 43 approximately 44 degrees C, respectively. The 2-, 4- and 8-year survival rates for the IHCP group were 86%, 74% and 66%, respectively, against 78%, 59% and 50%, respectively, in the control group. The survival rates of the IHCP group were significantly better than those of the control group. Peritoneal recurrences after surgery were encountered in one of 59 patients in the IHCP group and 17 of 67 patients in the control group. The peritoneal recurrence rate of the IHCP group was significantly lower than that of the control group. These results suggest that IHCP treatment is effective in prevention of peritoneal recurrences after surgery for gastric cancer patients with serosal invasion.

Inhibitory effects of n-3 polyunsaturated fatty acids on sigmoid colon cancer transformants.

Various types of polyunsaturated fatty acids (PUFAs) have been suggested to exert different effects on the colon in terms of promotion or inhibition of tumor development. Results of in vitro and in vivo studies are, however, inconsistent and it remains unclear whether or not the cellular effects of PUFAs change along with the malignant transformation of colonic cells. In this study, we used the NIH3T3 cell line and its SIC (sigmoid colon cancer) oncogene transformants to compare the effects of PUFAs on the proliferation of non-malignant and malignant cells. We also determined the cellular utilization of fatty acids in media by a high-performance liquid chromatography method. The addition of exogenous arachidonic acid (ARA, an n-6 fatty acid), eicosapentaenoic acid (EPA, n-3), and docosahexaenoic acid (DHA, n-3) exerted different effects on NIH3T3 cells, and on SIC transformants, in which selective inhibitory effects were observed at media concentrations ranging from 10 to 20 microg/ml. In cells cultured in media supplemented with EPA or DHA at a concentration of 2 microg/ml, which had no effect on cell proliferation, the cellular utilization of linoleic acid (n-6), a precursor of n-3 fatty acids, was inhibited. This inhibition was stronger in SIC transformants than in NIH3T3 cells (P < 0.05). There was no difference in the utilization of fatty acids between the two cell lines cultured in media supplemented with ARA. We conclude that the cellular response to exogenous long-chain PUFAs is modified during the course of malignant transformation, and that EPA and DHA (n-3 PUFAs) appear to have specific inhibitory effects on cancer cells and may thus enhance the host defense against colon cancer.

Effects of growth hormone and insulin-like growth factor I on opsonin receptor expression on local and systemic phagocytes in a lethal peritonitis model.

OBJECTIVE: To investigate the effects of pretreatment with growth hormone (GH) and insulin-like growth factor I (IGF-I) on phagocyte exudation and bacterial clearance, focusing on CD11b and CD32/CD16 expression on local and systemic phagocytes, in a lethal peritonitis model. DESIGN: Prospective randomized experimental study. SETTING: Research laboratory in a university hospital. SUBJECTS: Balb/c mice (n = 21). INTERVENTIONS: Mice were challenged intraperitoneally with 1 x 10(8) Escherichia coli, after 6 days of pretreatment with saline (control), GH (4.8 mg/kg/day), or IGF-I (24 mg/kg/day). Samples were harvested at 4 hrs after the challenge. MEASUREMENTS AND MAIN RESULTS: Viable bacterial counts in peritoneal lavage fluid (PLF) and blood were determined. Peritoneal exudative cells and peripheral blood leukocytes were counted and analyzed for receptor expressions by flow cytometry. GH reduced viable bacterial counts in PLF, as compared with the saline control. GH (three-fold) and IGF-I (two-fold) increased the number of peritoneal exudative neutrophils (PENs), as compared with the saline control. The number of PENs showed an inverse correlation with PLF viable bacterial counts. By contrast, there were no differences in peripheral blood neutrophil (PN) counts among the three groups, nor was there a correlation between PN and PEN counts. CD11b expression was greater on PENs than on PNs in all three groups. CD11b expression on PNs did not differ among the three groups. However, GH increased CD11b expression on PENs, as compared with saline and IGF-I, and this expression showed a positive correlation with PEN numbers and an inverse correlation with PLF viable bacterial counts. CD11b expression on peritoneal macrophages and peripheral blood monocytes did not differ among the three groups. There were no differences in phagocyte CD32/CD16 expression among the three groups. CONCLUSIONS: GH pretreatment enhanced CD11b expression on PENs, but not PNs, possibly in association with enhanced neutrophil recruitment, phagocytosis, and bacterial elimination by PENs, without activation of PNs. GH prophylaxis may be useful for reducing the frequency rate and severity of septic complications, via modulation of CD11b expression on local and systemic neutrophils.

Dihydropyrimidine dehydrogenase but not thymidylate synthase expression is associated with resistance to 5-fluorouracil in colorectal cancer.

BACKGROUND/AIMS: In planning adjuvant treatment of colorectal cancer, it is of critical importance to optimize the treatment by identifying subsets of patients that will respond or not to chemotherapy. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are key enzymes involved in the biochemical functions of the antimetabolite 5-fluorouracil (5-FU). In searching for the factors determining the 5-FU sensitivity of colorectal cancer, TS and DPD were analyzed in relation to the inhibitory effect of 5-FU on cell proliferation in a series of human colorectal cancer cell lines. METHODOLOGY: TS and DPD protein expressions were quantified in 5 human colorectal cancer cell lines, using TS binding assay and Western blotting, respectively. Cellular growth inhibition was assessed by MTT assay after 48 hours of continuous exposure to 5-FU or cisplatin (CDDP). RESULTS: TS protein expression was detected in all but one of the cell lines studied and varied within a 17-fold range, while DPD protein expression was detectable in only one cell line (CaR1). CaR1, which expressed the highest level of DPD and no detectable TS, showed remarkable resistance to 5-FU. The other colorectal cancer cell lines with undetectable DPD expression were sensitive to 5-FU. There was no correlation between TS expression and 5-FU sensitivity. All of the cell lines studied showed similar sensitivity to CDDP. CONCLUSIONS: These data suggest that DPD, but not TS, expression predicts 5-FU sensitivity in colorectal cancer cell lines.

Glutamine-enhanced bacterial killing by neutrophils from postoperative patients.

Neutrophils play an important role in host defense by phagocytosing and destroying invading bacteria. A recent investigation revealed that glutamine (Gln) augmented the in vitro bactericidal activity of neutrophils from burn patients. However, it is unclear whether Gln enhances the function of neutrophils in postoperative patients. This study was designed to investigate the effect of Gln on the in vitro Escherichia coli-killing activity of neutrophils from postoperative patients. Nine randomly selected patients were included in this study. On the morning of the first postoperative day, blood was drawn and neutrophils were isolated. Eight healthy volunteers served as controls. E. coli was opsonized with pooled normal serum. Neutrophils (5 x 10(6)), together with opsonized E. coli (5 x 10(5)), were incubated for 2 h at 37 degrees C in Hanks' balanced salt solution supplemented with 0, 100, 500, or 1000 nmol/mL of Gln. The bactericidal function of neutrophils was determined by counting the number of viable bacteria. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-8, and granulocyte elastase levels in the cell culture supernatant were measured. Plasma C-reactive protein (CRP), cortisol, and amino acids were also analyzed. The plasma concentration of Gln was significantly lower in the postoperative patients than in the controls. Following culture with patient neutrophils, the number of viable E. coli decreased by 26% as the in vitro Gln concentration was increased from 500 to 1000 nmol/mL (P < 0.01). We defined the Gln 1000/Gln 500 ratio of the number of viable bacteria as the number of viable E. coli at an in vitro Gln concentration of 1000 nmol/mL divided by the number of viable E. coli at an in vitro Gln concentration of 500 nmol/mL. A positive correlation was thus demonstrated between the plasma Gln level and the Gln 1000/Gln 500 ratio of the number of viable bacteria in the patients (r = 0.69, P = 0.04). This finding indicated that as plasma Gln fell, there was an enhancement of neutrophil E. coli-killing activity by neutrophils in in vitro tests when the Gln concentration was increased from 500 to 1000 nmol/mL. Gln supplementation caused no appreciable changes in TNF-alpha, IL-1 beta, IL-8, or granulocyte elastase levels in cell culture supernatants. A negative correlation was recognized between the patient plasma Gln level and the Gln 1000/Gln 500 ratio of the cell culture supernatant IL-8 level (r = -0.73, P = 0.025). In conclusion, Gln supplementation enhanced the in vitro bactericidal function of neutrophils from postoperative patients.

Glutamine-enriched enteral diet enhances bacterial clearance in protected bacterial peritonitis, regardless of glutamine form.

BACKGROUND: The effects of glutamine (Gln)-enriched enteral diets on bacterial clearance were investigated in a rat protracted peritonitis model. The effects of the Gln form, peptide-based vs free amino acid-based, were also compared. METHODS: Twenty-three rats underwent gastrostomy. An osmotic pump was implanted in the peritoneal cavity. The rats received a continuous intragastric infusion of one of three diets: Gln-depleted (Gln 0), Gln-enriched with the Gln in free amino acid form (Gln F), or Gln-enriched with the Gln in oligopeptide form (Gln P). The three formulas were isocaloric and isonitrogenous. The pumps delivered a continuous infusion of Escherichia coli, starting at 48 hours after implantation, for 24 hours. Then, the animals were killed. RESULTS: Bacterial numbers in peritoneal lavaged fluid (PLF) and the liver were significantly lower in the Gln P and Gln F groups than in the Gln 0 group. The bacterial number in PLF correlated with that in the liver. Neither the number nor the population of peritoneal exudative cells differed among groups. Plasma levels of proline, alanine and citrulline were significantly higher in the Gln P and Gln F groups than in the Gln 0 group. Both Gln supplemented groups showed significantly greater villous height, crypt depth, and numbers of mitoses per crypt in the small intestine than the Gln 0 group. CONCLUSIONS: Supplemental Gln enhances peritoneal and hepatic bacterial clearance, regardless of Gln form. Gln-enriched may be more beneficial than Gln-depleted enteral diets in peritonitis.

Alanylglutamine-enriched total parenteral nutrition improves protein metabolism more than branched chain amino acid-enriched total parenteral nutrition in protracted peritonitis.

Branched chain amino acids (BCAAs) and glutamine are both recommended in catabolic states. The object of this study was to compare the efficacies of alanylglutamine (Ala-Gln)-enriched and BCAA-enriched total parenteral nutrition (TPN) on the protein kinetics in peritonitis. Rats were divided into Ala-Gln and BCAA groups after intraperitoneal implantation of an osmotic pump, delivering a continuous infusion of Escherichia coli. Glutamine composed 30.0% (w/v) of the total amino acids in the Ala-Gln group, and BCAA composed 30.5% (w/v) of the total amino acids in the BCAA group. The two solutions were isocaloric and isonitrogenous. Whole body protein turnover and organ fractional protein synthetic rates (FSR) were measured on days 3 and 5. Serum amino acid levels and mucosal morphology were determined. Ala-Gln group had higher rates of whole body protein turnover, and hepatic FSR on both days. Serum glutamine levels correlated with hepatic and muscle FSR. Ala-Gln TPN group had greater mucosal thickness, numbers of mitoses per crypt, and FSR in distal intestine. Ala-Gln-enriched TPN may be a useful nutritional treatment modality in sepsis.