Recovery of gut-associated lymphoid tissue and upper respiratory tract immunity after parenteral nutrition

OBJECTIVE: The authors characterize the recovery of parenteral nutrition-induced changes in gut-associated lymphoid tissue (GALT) and upper respiratory tract immunity with enteral nutrition and provide further information defining the effects of enteral feeding on mucosal immunity. SUMMARY BACKGROUND DATA: The small intestine plays a prominent role in development and maintenance of mucosal immunity, both intestinal and extraintestinal, primarily through immunoglobulin A (IgA)-mediated mechanisms. Prior research has shown that mice fed total parenteral nutrition (TPN) have reduced GALT T and B cells, the cells responsible for IgA production, as well as impaired upper respiratory tract immunity to viral challenge of previously immunized animals. The recovery of TPN-induced changes in GALT and upper respiratory tract immunity after enteral refeeding is studied. METHODS: Male institute of Cancer Research mice received 5 days of TPN followed by 0 to 4 days of chow. Small intestinal GALT was characterized by flow cytometry. In a second experiment, animals were immunized intranasally with moused-adapted influenza virus. Three weeks later, one group received a 5-day course of TPN followed by enteral refeeding for 5 days. A second group received TPN alone. Both groups were challenged with intranasal virus and killed 40 hours postchallenge to determine viral shedding from the upper respiratory tract. RESULTS: Animals fed TPN only had significantly fewer GALT lymphocytes compared with those chow-fed control subjects. Peyer's patch counts increased after a single day of refeeding, returning to normal levels by 48 hours. Lamina propria counts remained significantly depressed after 24 hours of refeeding, but also returned to normal after 48 hours of refeeding. The T-cell and B-cell populations mimicked total cell patterns. Lamina propria CD4+/CD8+ ratio returned to normal only after 72 hours of refeeding. None of the 9 animals refed enterally for 5 days were positive for viral shedding, compared with 8 of 12 matched TPN-fed animals. CONCLUSIONS: Enteral refeeding after TPN is associated with rapid repletion of GALT cellularity, initially within Peyer's patches and subsequently within the lamina propria. Refeeding corrects the impairment of IgA-mediated upper respiratory tract antiviral immunity occurring with TPN administration. This work further enhances the authors' knowledge of the underlying immunologic differences influenced by routes of nutrition.     

Tissue manganese concentrations and antioxidant enzyme activities in rats given total parenteral nutrition with and without supplemental manganese

BACKGROUND: Manganese is an essential but potentially toxic mineral. Parenteral administration of manganese via total parenteral nutrition (TPN) bypasses homeostatic mechanisms (intestinal absorption and presystemic hepatic elimination). Our objective in this study was to determine the effect of supplemental manganese in TPN solutions on manganese status in a rat model. METHODS: Male Sprague-Dawley rats underwent jugular catheterization and were given 61.0 +/- 0.4 g/d TPN solution providing 0.5 +/- 0.2 nmol manganese/g (Mn-; n = 6) or 16 +/- 3 nmol manganese/g (Mn+; n = 7) for 7 days. Reference rats (RF; n = 8) were fed a purified diet containing 1.3 mmol manganese/g. RESULTS: Liver manganese decreased in both TPN groups, but tibia, spleen, and pancreas manganese concentrations were greater in Mn+ rats than in Mn- or RF rats. Although no treatment differences were seen in heart or liver manganese superoxide dismutase activity, heart copper-zinc superoxide dismutase activity was lower in the Mn+ rats than in Mn- or RF rats (p < .05). Glutathione peroxidase activity was depressed in livers of both Mn- and Mn+ rats relative to RF rats (p < .0001), which was not due to selenium deficiency. CONCLUSIONS: Supplemental parenteral manganese is taken up to a greater extent by peripheral tissues than the liver. In this first report of antioxidant enzyme activities in animals maintained with TPN, we found that TPN as well as supplemental manganese can influence antioxidant enzyme activities. We conclude that it is generally unnecessary and potentially toxic to supplement TPN solutions with manganese during short-term usage.     

Reprioritization of liver protein synthesis resulting from recombinant human growth hormone supplementation in parenterally fed trauma patients: the effect of growth hormone on the acute-phase response

BACKGROUND: One of the major components of the metabolic response to severe trauma is the alteration in concentrations of a large number of plasma proteins referred to as acute-phase proteins (APP). The principle mediators of these liver-synthesized APP are mainly the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). METHODS: We have measured the plasma levels of IL-6, TNF alpha, and 20 APP in 24 adult, severely injured, hypermetabolic and highly catabolic patients with multiple injuries within 48-60 hours after injury, when they were receiving maintenance fluids without calories or nitrogen, and subsequently during 7 days of total parenteral nutrition with (n = 12) or without (n = 12) recombinant human growth hormone supplementation (rhGH, 0.15 mg/kg/d). RESULTS: Baseline positive APP due to severe trauma include C-reactive protein (CRP), alpha-1 antichymotrypsin, alpha-1 acid glycoprotein, alpha-1 antitrypsin, fibronectin, and factor B. Negative APP include IgG, IgM, complement-3, prealbumin, transferrin, ceruloplasmin, and albumin. Except for CRP, alpha-1 antichymotrypsin, and albumin, all the APP levels increase during 7 days of nutritional support. Plasma levels of cytokines IL-6 and TNF-alpha, although initially markedly increased after injury, decrease with parenteral refeeding. There is a linear correlation between CRP and IL-6 levels and also between the transport proteins prealbumin and transferrin. Trauma-induced increases in CRP and IL-6 levels decreased with nutrition alone, but did not change with rhGH supplementation. An immunosuppressed state of injury is evident from the decreased immunoglobulin levels (IgG, IgM, IgA) in the trauma patients. Total parenteral nutrition alone increases the immunoglobulin levels to normal. However, with adjuvant rhGH, only IgA levels are normalized. CONCLUSIONS: Adjuvant rhGH therapy does not attenuate the reprioritization of acute liver protein synthesis and results in only limited restoration of host defenses. The clinical implications of these findings await further study.     

Short-chain fatty acid-supplemented total parenteral nutrition improves nonspecific immunity after intestinal resection in rats

BACKGROUND: Total parenteral nutrition (TPN) alters both specific and nonspecific immune functions, resulting in immunosuppression. Short-chain fatty acids have been shown to improve the adaptive responses of the gut after surgery. The following study investigates the effects of adding short-chain fatty acids to TPN on the immune system after an 80% small bowel resection. METHODS: Rats (237 +/- 3 g) were infused with either TPN (n = 25) or TPN supplemented with short-chain fatty acids (n = 26) for 3 or 7 days. Hematologic analysis was performed on peripheral blood and splenocytes were isolated to characterize cell phenotypes, natural killer cell cytotoxicity and to estimate proliferative response. RESULTS: The relative percent of T (CD3+) cells increased (p < .05) and the relative percent of macrophages decreased (p < .001, n = 13) in the spleens of the 3-day TPN-fed rats. By day 7, these differences disappeared. The natural killer cells from rats that were supplemented with short-chain fatty acids had higher (p < .0001) cytotoxic activity than the TPN groups at day 3. Mitogenic response did not differ between groups but were depressed compared with sham-treated rats. By day 7, rats on standard TPN had larger (p < .0001) spleens than all other groups. This group also had a higher total white blood cell count because of increased numbers of macrophages and neutrophils (p < .02). CONCLUSION: Short-chain fatty acids improve components of nonspecific immune responses and may be beneficial in reducing certain aspects of TPN-associated immunosuppression after major surgery.     

Lamina propria T cell subsets in the small and large intestine of euthymic and athymic mice

We investigated lamina propria T cells from the small intestine (jejunum/ileum) and the large intestine (colon) of euthymic (BALB/c, C.B-17, C57BL/6) and athymic (C57BL/6 nu/nu; BNX bg/bg nu/nu xid/xid) mice. CD3+ T cells represented about 40% of the lamina propria lymphocytes (LPL) from the small or the large intestine of euthymic mice, and 20-30% of the LPL populations from the small or large intestine of athymic mice. In the lamina propria T cell population of the small intestine, 85% were of the alpha beta lineage in euthymic mice, but only 40% were of the alpha beta lineage in athymic mice. T cells of the gamma delta lineage were thus more frequent than T cells of the alpha beta lineage in the intestinal lamina propria T cells of extrathymic origin. CD4+ T cells represented 40% of the lamina propria T cells in the small as well as in the large intestine of euthymic mice, and 20-30% of the T cells in the lamina propria of the nude mouse gut. In euthymic mice, 40% of the T cells in the small intestine lamina propria, and 30% of the T cells in the colonic lamina propria were CD8+. In intestinal lamina propria T cell populations of athymic mice, the CD8+ T cell population was expanded. Most (60-70%) CD8+ T cells in the lamina propria of the small and the large intestine of euthymic and athymic mice expressed the homodimeric CD8 alpha + beta- form of the CD8 coreceptor. A fraction of 15-20% of all CD3+ T cells in the lamina propria of the small and the large intestine of euthymic and athymic mice were 'double negative' CD4- CD8-. A large fraction of the TCR alpha beta + T cells in the colonic lamina propria (but not in the small intestine lamina propria) of euthymic mice expressed the CD2 and the CD28 costimulator molecules, the adhesion molecule LECAM-1 (CD62 L), and could be activated in vitro by CD3 ligation. These data reveal a considerable heterogeneity in the surface phenotype and the functional phenotype of murine lamina propria T cells.     

Mucosal immunity in the female genital tract

Immunoglobulin (Ig)-producing cells in mucosal tissues represent quantitatively the most important humoral immune system of the body. All exocrine tissue sites contain immunocytes (B-cell blasts and plasma cells) that mainly synthesize dimers and larger polymers of IgA (collectively called pIgA) with incorporated J chain. Such pIgA is actively transported to external secretions as secretory IgA (SIgA) by the polymeric Ig receptor (pIgR), a transmembrane epithelial glycoprotein also called the secretory component (SC). The same transport mechanism includes pentameric IgM to generate SIgM. Although the most active SIgA system occurs in the gut, secretory immunity also operates in the female genital tract, with considerable pIgA production in the cervical mucosa and fallopian tubes. The origin of these local IgA immunocytes remains undefined. In mice, both lymphoid tissue in the large bowel (GALT) and nasopharynx (NALT) have been suggested as inductive sites for B cells homing to the urogenital tract. It is well established that integrin alpha 4 beta 7 is used by primed lymphoid cells to enter the intestinal lamina propria through interactions with mucosal addressin cell adhesion molecule (MAdCAM)-1 expressed on venule endothelium. However, alpha 4 beta 7 does not appear to be an important homing molecule in the airways, and the same might be true for the urogenital tract; this could explain that high levels of IgA antibodies occur in cervicovaginal secretions of mice after nasal immunization. The endometrium can likewise perform pIgR-mediated external translocation of pIgA that in this tissue appears to be mainly derived from serum, partly under hormonal regulation. In addition, paracellular diffusion of serum-derived and locally produced IgG through epithelia is an important part of humoral immunity in the female genital tract.     

Cell lines derived from ultraviolet radiation-induced benign melanocytic nevi in Monodelphis domestica exhibit cytogenetic aneuploidy

The GALT of carp was studied with monoclonal antibodies reacting with carp Ig or carp leukocytes, using (dual) immunofluorescence or immunogold staining on cryosections, cytocentrifuge slides, and cell suspensions of the intestine. The intestinal epithelium contained many Ig-negative lymphoid cells and, in the hindgut, also many large Ig-positive macrophages, which appeared to bind Ig. The lamina propria contained numerous Ig-positive lymphoid cells next to Ig-negative lymphoid cells and granulocytes. Leukocytes isolated from the intestine mainly consisted of Ig-negative lymphoid cells (> 90%). With the methods used, leukocytes were poorly released from the connective tissue. Nevertheless, two types of Ig-containing cells were found: a conventional plasma cell, frequently showing Ig at its surface, and a more common smaller lymphoid cell having a narrow rim of Ig-positive cytoplasm but hardly any Ig on its surface. Many of the Ig-positive lymphoid cells observed in the lamina propria may represent these small Ig-containing cells. Isolated Ig-positive macrophages were frequently associated with B- and T-like cells. Our data strongly suggests an immunological function for the gut of carp, especially for the antigen-transporting hindgut.     

Addition of glucagon to lipid-free total parenteral nutrition reduces production of prostaglandin E2 by stimulated splenic macrophages

Sepsis is a major complication of total parenteral nutrition (TPN). Impaired immunity has been suggested as being responsible for TPN-related sepsis, but it is unknown how the immune system is affected by TPN. We recently found that administration of lipid-free TPN resulted in an increase in prostaglandin E2 (PGE2) release by stimulated splenic macrophages. This observation suggested that TPN may impair immunity through the prominent immunosuppressive effects of PGE2. In the present study, we tested the hypothesis that addition of glucagon to TPN solution may protect against the immunosuppressive effect of TPN by modifying PGE2 secretion. Adult, male Sprague-Dawley rats (n = 18) underwent jugular vein cannulation: group 1 (n = 7) received intravenous saline and chow ad libitum; group 2 (n = 6) received TPN (80 mL/24 h); and group 3 (n = 5) received TPN (80 mL/24 h) plus glucagon (100 micrograms/24 h). After 10 days, spleens were removed and splenic macrophages were isolated and cultured for 24 h in plain M199 medium (nonstimulated) or in medium containing Escherichia coli lipopolysaccharide (5 micrograms/mL) (stimulated). PGE2 release was determined by enzyme-linked immunosorbent assay. There were no differences in PGE2 release between the groups of nonstimulated cells, but when stimulated with lipopolysaccharide, the macrophages from the TPN rats (group 2) released more PGE2 (81.68 +/- 25.99 ng/2.5 x 10(6) cells) than the control group (16.04 +/- 3.26 ng/2.5 x 10(6) cells). The release of PGE2 was normalized in the TPN animals treated with glucagon (15.71 +/- 3.33 ng/2.5 x 10(6) cells). This difference was significant, with p < .05 by Tukey's test after analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Local airways immune modifications induced by oral bacterial extracts in chronic bronchitis

Bacterial extracts can act as immune stimulants and in some instances have been used, rather empirically, to prevent recurrent infections in the nonimmunocompromised host. Some agents are administered via oral route with the goal to increase airways immune defenses. In animal models and in normal humans, gut-associated lymphoid tissue (GALT) stimulation is able to induce a generalized response by the whole mucosal-associated lymphoid tissue (MALT). The aim of this placebo-controlled, double-blind, parallel-group study was to evaluate whether the stimulation of the GALT through oral administration of a polyvalent bacterial extract (BE) could lead to significant immune modifications either systemically or locally in the respiratory tract in patients suffering from chronic bronchitis. We selected 20 subjects (5 nonsmokers, 6 smokers, and 9 ex-smokers) for at least 3 years. According to a balanced-block randomization method, ten patients received active treatment and ten received placebo. Either drug or placebo was to be taken as one capsule daily the first 10 days of 3 consecutive months. Each capsule of the active product contained 7 mg of a BE obtained from eight different bacterial strains. On entry (T0) and 90 days after beginning of treatment (T90), all patients underwent bronchoalveolar lavage (BAL) and peripheral blood withdrawal to assay BAL fluids and serum samples for immune parameters. The BAL recoveries, cellularity, cell differentials, and lymphocyte subsets (CD19, CD3, CD4, CD8) did not show significant differences. IgG/albumin and IgA/albumin values were not significantly different, but IgA/albumin was significantly increased in the treatment (T0 = 0.14, 0.01 to 0.27, median and range, T90 = 0.15, 0.08 to 0.45, p = 0.028) vs the placebo group when data from current smokers were excluded. Functional tests on alveolar macrophages (AM) (leading front stimulated motility and superoxide anion-O2(-)-release) showed a significant increase of random migration (T0 = 10.6, 7.0 to 23.6, T90 = 13.4, 8.1 to 28.8 microns, p = 0.02) and of stimulated motility after FMLP 10(-7) M (T0 = 13.2, 8.3 to 46.4, T90 = 18.3, 8.4 to 49.6 microns, p = 0.04), a significant increase of O2- release in basal conditions (T0 = 6.0, 1.7 to 30.5 nM/10(6) AM/10', T90 = 11.1, 5.5 to 24.5, p = 0.05) and after stimulation with opsonized zymosan (T0 = 17.7, 4.7 to 35.2, T90 = 22.1, 13.8 to 53.3, p = 0.009) in the treatment group only. Data were not significantly different in the placebo group between T0 and T90. No modifications in systemic immunity were ever observed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Carnitine supplementation accelerates normalization of food intake depressed during TPN

When total parenteral nutrition (TPN; containing glucose, fat, and amino acids; caloric ratio 50:30:20) providing 100% of the rat's daily caloric intake is given for 3-4 days, food intake rapidly decreases by approximately 85%. After stopping TPN, there is a lag period of 3-4 days before food intake returns to previous level, which appears to be related to fatty acid oxidation and fat deposition. Carnitine plays a key role in the oxidation of fatty acids, and was demonstrated to reduce fat deposition in rats receiving TPN, by increasing beta oxidation. We therefore investigated whether rats receiving TPN supplemented with carnitine may prevent either the decrease or speed up the resumption or normalization of food intake, after TPN is stopped. Fourteen adult Fischer-344 rats had a central venous catheter inserted. After 10 recovery days, controls (n = 7) were infused with TPN providing 100% of rat's daily caloric intake for 3 consecutive days, followed by 4 more days of normal saline. The carnitine group (n = 7) received the same solution, but which provided 100 mg/kg/day carnitine. Daily food intake was measured and data were analyzed using ANOVA and Student's t-test. Both parenteral solutions depressed food intake maximally by almost 90% by day 3. Carnitine accelerated the normalization of food intake by decreasing the lag period by 1 day. We conclude that the addition of carnitine enhanced the normalization of post-TPN food intake and argue that this may be on the basis of enhanced fatty acid oxidation, a substrate known to play a significant role in the anorexia induced by TPN.     

Autoimmune enteropathy with severe atrophic gastritis and colitis in an adult: proposal of a generalized autoimmune disorder of the alimentary tract

BACKGROUND: We describe the case of an adult with autoimmune enteropathy consistent with both severe atrophic gastritis accompanying antral stenosis and colitis. METHODS AND RESULTS: The patient, positive for anti-intrinsic factor antibody, had intractable diarrhea and protein-losing enteropathy. In the ileum inflammatory cells were observed infiltrating the lamina propria along with villus atrophy, and similar inflammation was also found in the lamina propria of the colon and stomach, with complete loss of specialized glands. The myenteric ganglion cells of the hypertrophied muscularis propria in the stenosed antrum showed degeneration with surrounding T-lymphocyte infiltration. There were more CD8+ than CD4 lymphocytes in the lamina propria of the stomach and colon. CONCLUSIONS: The CD8+ (suppressor-cytotoxic) T lymphocytes may have played an important role in the production of lesions in the stomach, small intestine, and colon, so we propose this case as an example of a generalized autoimmune disorder of the alimentary tract.     

Development of humoral immunity system of the small bowel

The study was performed in 24 children aged 2 months to 6 years, without intestinal or immunological diseases. Intestinal biopsies were obtained by a Crosby's capsule, pediatric size. The number of immunoglobulin forming cells of lamina propria was measured by planimetry. Under 12 months of age there are increased levels of IgM forming cells and a low IgA forming cells/IgM forming cells quotient, but over 1 year the difference disappears. This suggests that the maturity process is very rapid. There are no correlation between serum IgA, IgM, and IgG levels and its respective forming cells number of lamina propria. It seems to support that the participation of intestinal lymphoid tissue in serum pool of immunoglobulin is very poor and that systemic and intestinal immunity maturation are completely independent.     

Pediatric orthopedics at the Stuttgart Olga Hospital: the variety of disorders makes high demands on nursing]

Total parenteral nutrition (TPN) is associated with an increased incidence of bacterial translocation (BT) compared with enteral nutrition because of the disuse atrophy of the intestine. In this study, we assessed the effect of adding medium-chain triacylglycerols (MCT) to TPN for the prevention of mucosal atrophy in the intestine. Rats were subjected to either fat-free TPN, TPN with long-chain triacylglycerols (LCT), or TPN with MCT for 5 d and nutrition parameters were evaluated. In another set of rats receiving the same TPN regimen, 0.8 or 0.05 mg/kg endotoxin was administered on day 4. Survival was evaluated and BT to the mesenteric lymph nodes, liver, and systemic blood was measured 24 h later. The mucosal heights of the jejunum and ileum were evaluated concurrently. The survival rate was significantly improved in the MCT group (P < 0.05) at the endotoxin dose of 0.8 mg/kg. The nutrition condition presented by phospholipid, total cholesterol, and total ketone body levels was the best in the MCT group compared to the other groups. The intestinal villous height in the ileum was significantly greater in the MCT group. However, the improvement of BT in MCT group was not statistically significant. In this endotoxin-challenged rat model, survival rate was improved by the supplementation of MCT. This effect may be presented in some part by the improvement in nutrition condition and by the prevention of mucosal atrophy in the intestine.     

Experimental mucosal disease in cattle: changes in the number of lymphocytes and plasma cells in the mucosa of the small and large intestine

Changes in the number of lymphocyte and plasma cell subtypes were investigated in the lamina propria and in the epithelium of the small and large intestine of cattle with mucosal disease. Mucosal disease had been induced experimentally in seven out of 13 animals persistently viremic with non cytopathogenic BVD-virus by inoculation with a matching cytopathogenic BVD-virus. For comparison, six clinically healthy, persistently viremic cattle were used. IgA+, IgM+ and IgG1+ plasma cells, BoCD4+, BoCD8+ and gamma delta + T-lymphocytes, and the antigen of the cytopathogenic BVD-virus were demonstrated in tissue sections by immunohistochemistry. Distribution of cellular subtypes in the controls was consistent with data reported from non infected cattle. In cattle with mucosal disease, a decrease in the number of plasma cells which was significant for IgA+ and IgM+, but not for IgG1+ plasma cells was found in the lamina propria. The number of BoCD4+ T-lymphocytes was reduced in the small intestine, whereas their number per mm2 of mucosa was increased in the large intestine. Numbers of intraepithelial BoCD8+ and gamma delta + T-lymphocytes were severely decreased. Antigen of the cytopathogenic BVD-virus was detected predominantly in epithelial cells of the crypts. Overall there is a severe loss of effector cells which are essential components of the humoral and cell mediated immune protection of the mucosal barrier. The decrease of immunoregulatory cells in the lamina propria and epithelium may contribute to the transformation of mucosal architecture in mucosal disease.     

Microsphere uptake by the intestine of White Leghorn chickens

A study was conducted to determine the effective size for latex microsphere uptake in the intestine of white leghorn chickens. Three trials were conducted in which ligated intestinal segments of anesthetized 8-wk-old chickens were injected with 0.2-, 0.5-, 2-, 6-, 10-, or 20-mu diameter fluoresceinated latex microspheres. Microspheres were counted in brush border, epithelium, and lamina propria of each intestinal segment, liver, and spleen. After 1 hr, the 0.2-, 0.5-, and 2-mu microspheres were oriented along the brush border of epithelial cells and microsphere uptake into the epithelium and lamina propria was observed in the duodenum, ileum, cecum, cecal tonsil, and colon. Uptake of microspheres of 6, 10, and 20 mu diameter into epithelium and lamina propria was not observed in any intestinal segment. Also, no microspheres of any diameter were observed in sections of liver and spleen to suggest that there was no appreciable entry of microspheres into the bloodstream within 1 hr after administration. The results indicated that uptake of microspheres by the chicken intestine is a size-dependent process with microspheres < or = 2 mu being taken up to an equal extent by most segments of intestine.     

Effect of methionine-deprived total parenteral nutrition on tumor protein turnover in rats

BACKGROUND: Previous studies have shown that a methionine-lacking diet inhibited tumor growth in rats. The aim of this study was to determine how methionine free total parenteral nutrition (MTPN) can result in the inhibition of tumor growth on tumor protein metabolism in rats. METHODS: On day 0, AH109A rat ascites hepatoma cells were implanted subcutaneously into male Donryu rats (n = 68, body weight, 200-225 gm). On day 10, a catheter for total parenteral nutrition (TPN) was placed and either MTPN or standard TPN solution was given for 5 days. On day 15, 1-14C-leucine was infused continuously to measure tumor protein synthesis. Tumor proteolysis was calculated from tumor regional blood flow, using the 85Sr-microsphere injection method. RESULTS: 1) Tumor weight was reduced with MTPN. 2) MTPN did not affect tumor protein synthesis, probably because endogenous methionine production was increased with MTPN (87.3 +/- 13.5 mumole methionine/kg/hour vs. 218.6 +/- 29.5, P < 0.01); however, MTPN caused an increase of tumor proteolysis (2.68 +/- 0.53 mumole leucine/g/hour vs. 3.79 +/- 0.73, P < 0.05). CONCLUSION: The enhanced tumor protein breakdown contributed to the inhibition of tumor growth that was found with the rats given the methionine free diet.     

Effects of isoenergetic glucose-based or lipid-based parenteral nutrition on glucose metabolism, de novo lipogenesis, and respiratory gas exchanges in critically ill patients

OBJECTIVE: To compare the effects of isocaloric, isonitrogenous carbohydrate nutrition vs. lipid-based total parenteral nutrition on respiratory gas exchange and intermediary metabolism in critically ill patients. DESIGN: Prospective, clinical trial. SETTING: Surgical intensive care unit in a major university hospital in Switzerland. PATIENTS: Sixteen patients admitted to the surgical intensive care unit. INTERVENTIONS: Patients were randomized to receive isocaloric isonitrogenous total parenteral nutrition (TPN) containing 75% (TPN-glucose) or 15% (TPN-lipid) glucose over a 5-day period. MEASUREMENTS AND MAIN RESULTS: Indirect glucose metabolism was assessed from plasma carbon-13 (13C)-labeled glucose and 13C-labeled CO2 production during a tracer infusion of uniformly 13C-labeled glucose, and de novo lipogenesis was estimated from the incorporation of 13C into palmitate-very low density lipoproteins (VLDL) during a tracer infusion of 1-(13)C acetate. Compared with TPN-lipid, TPN-glucose increased plasma glucose more (by 26% vs. 7%, p < .05), increased insulin more (by 284% vs. 40%, p < .01), and increased total CO2 more (by 15% vs. 0%, p < .01). Both nutrient mixtures failed to inhibit endogenous glucose production and net protein oxidation, suggesting absence of suppression of gluconeogenesis. Fractional de novo lipogenesis was markedly increased by TPN-glucose to 17.4% vs. 3.3% with TPN lipids. CONCLUSIONS: The rate of glucose administration commonly used during TPN of critically ill patients does not suppress endogenous glucose production or net protein loss, but markedly stimulates de novo lipogenesis and CO2 production. Increasing the proportion of fat may be beneficial, provided that lipid emulsion has no adverse effects.     

B and T lymphocytes are enhanced in the gut of piglets fed heat-treated soyabean proteins

Gut immune responses have been suspected in food hypersensitivity reactions such as those to soyabean proteins in early-weaned piglets. The present study examines the lymphoid cell subset distribution in piglets fed heat-treated (HTSP) or ethanol-treated soyabean proteins (ETSP). Duodenal cryosections of 4-week-old HTSP piglets (n = 10) and ETSP piglets (n = 8) were analysed for IgA, IgM, IgG1 and IgG2 positive cells, CD2, CD4, CD8, WC1 T cell positive antigens using immunohistochemical peroxidase reactions. Densities of IgM+ and IgA+ cells were three times and, IgG1+ and IgG2+ six times higher in the lamina propria of HTSP piglets compared with ETSP (P < 0.05). Increased CD2+ T cells were accounted for by a rise in both CD4+ and CD8+ T cell subsets in the lamina propria (P < 0.01) as well as in the epithelium of the duodenal mucosa of piglets fed HTSP. The density of the WC1+ T cell subset in the epithelium was significantly higher in HTSP than in ETSP piglets (P < 0.01). Immune reactions in the duodenal mucosa, involving both B and T lymphocytes may be related to atrophy of the duodenal villi in HTSP piglets.     

Clinical trials in the elderly. Should we do more?

In this study, SPF rat models were used. The purpose of the study was to observe the impairment of gut barrier function subsequent to long-term TPN, and evaluate the effect of TPN enriched by alanyl-glutamine (Ala-Gln) on the gut. After 7 day standard TPN, there was a significant decrease of CD3+, CD4+, CD8+ and IgA-containing plasma cells in lamina propria. The percentage of intestinal bacteria coated by S-IgA declined, and bacterial adherence to intestinal epithelial cells increased with an increased incidence of bacterial translocation to mesenteric lymph nodes. All these adverse effects could be attenuated by addition of Ala-Gln to TPN solutions or oral glutamine (Gln) or Ala-Gln administration. The results of the study suggested that long-term standard TPN impaired the immune gut barrier function and therefor facilitated enterogenic infection, and addition of Gln or Ala-Gln significantly benifited gut barrier protection and infection prevention, which might be important to clinical practice.     

Rapid expression and specific localization of tenascin in gastric ulcer healing in rats

This study was done to investigate the gene expression and localization of tenascin in ulcerated gastric tissues during the healing process with Northern blot analysis and immunohistochemical technique. Gastric ulcers in rats were produced by acetic acid. Tenascin mRNA levels in the ulcerated tissue were significantly increased in a biphasic manner (12 h and day 5), preceding the increase in collagen type IV and laminin mRNA levels, and returned to control levels on day 11. In intact tissues, tenascin was mainly localized in the basement membrane above the proliferative zone, in contrast to the predominant localization of collagen type IV and laminin below the proliferative zone. On the ulcer margin from 12 h to day 5, tenascin was abundantly observed in the lamina propria around nonproliferating new epithelial cells, but collagen type IV and laminin were not seen in this lamina propria. On day 7, tenascin, expressed in the lamina propria, was replaced by collagen type IV and laminin. Thus, the rapid expression and unique localization of tenascin suggest the important role of tenascin in gastric ulcer healing.