Dietary supplementation with tributyrin alleviates intestinal injury in piglets challenged with intrarectal administration of acetic acid.

Tributyrin (TBU) is a good dietary source of butyrate and has beneficial effects on the maintenance of normal intestinal morphology. The present study tested the hypothesis that dietary TBU supplementation could alleviate intestinal injury in the acetic acid (ACA)-induced porcine model of colitis. A total of eighteen piglets (25 d old) were randomly allocated to one of three treatment groups (control, ACA and TBU). The control and ACA groups were fed a basal diet and the TBU group was fed the basal diet supplemented with 0·1 % TBU. On day 15 of the trial, under anaesthesia, a soft catheter was inserted into the rectum of piglets (20-25 cm from the anus), followed by administration of either saline (control group) or ACA (10 ml of 10 % ACA solution for ACA and TBU groups). On day 22 of the trial, after venous blood samples were collected, piglets were killed to obtain mid-ileum and mid-colon mucosae. Compared with the control group, the ACA group exhibited an increase (P< 0·05) in lymphocyte counts, creatinine, PGE2, and malondialdehyde concentrations and diamine oxidase and inducible NO synthase activities in the plasma and lymphocyte density in the colon and a decrease in insulin concentrations and glutathione peroxidase activity, ileal villus height:crypt depth ratios and goblet cell numbers in the colon. These adverse effects of ACA were attenuated by TBU supplementation. Moreover, TBU prevented the ACA-induced increase in caspase-3 levels while enhancing claudin-1 protein and epidermal growth factor receptor (EGFR) mRNA expression in the colonic mucosa. Collectively, these results indicate that dietary supplementation with 0·1 % TBU alleviates ACA-induced intestinal injury possibly by inhibiting apoptosis, promoting tight-junction formation and activating EGFR signalling.

Intramammary infusion of Panax ginseng extract in the bovine mammary gland at cessation of milking modifies components of the insulin-like growth factor system during involution.

The objective of this study was to evaluate the effects of a single intramammary infusion of Panax ginseng extract (GS) on insulin-like growth factors (IGF) in bovine mammary gland during early involution. Eight mammary quarters from six nonpregnant cows in late lactation were infused with 10 mL of ginseng extract solution (3 mg/mL), six quarters were treated with 10 mL of placebo (vehicle alone) and six quarters were maintained as uninoculated controls. Milking was interrupted after infusion. Concentrations of IGF1 in mammary secretions were higher in GS-treated quarters than in placebo and uninoculated control quarters at 24, 48 and 72 h post-treatment (p<0.05). Treatment with GS did not affect mammary secretion of IGF2 (p=0.942). At 7 d of post-lactational involution, a decrease of immunostained area and mRNA expression for IGF1 was observed in mammary tissue of GS-treated quarters compared with placebo-treated quarters and uninoculated controls (p<0.05). The IGF2 immunostained area and mRNA expression for this growth factor were not affected by GS treatment (p=0.216 and p=0.785, respectively). An increase in protein levels and mRNA expression in mammary tissue of IGFBP3, IGFBP4 and IGFBP5 was observed in GS-treated quarters compared with placebo-treated quarters and uninoculated controls (p<0.05). These results provide evidence that intramammary inoculation of GS extract at cessation of milking may promote early mammary involution through the inhibition of IGF1 local production and bioavailability.

Green tea and breast cancer.

The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemopreventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remain not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of observational studies and areas of further investigations are discussed.

Performance, metabolic, and endocrine responses of periparturient Holstein cows fed 3 sources of fat.

The objective of this study was to examine the effect of feeding diets containing fat supplements enriched in either saturated fatty acids (n = 10), Ca salts of trans-octadecenoic fatty acids (tFA, n = 10) or Ca salts of safflower oil fatty acids (SFL, high in linoleic acid, n = 9) on performance, metabolic, and endocrine responses of periparturient Holstein cows. Dietary treatments were initiated at approximately 28 d before calculated calving dates and continued through 49 d postpartum. Blood samples for metabolite and hormone analyses were collected weekly beginning 1 wk before estimated calving date through 7 wk postpartum. Incorporation of tFA or SFL into the peripartum diet had no detectable effects on body weight or body condition score. Cows fed the SFL-enriched diet produced less milk fat and established a positive energy balance sooner after calving than those fed the tFA supplement. Analysis for individual fatty acids resulted in increased concentrations of trans 18:1 fatty acid and conjugated linoleic acid isomers in milk fat from cows supplemented with SFL. Across weeks, the average nonesterified fatty acids concentration in plasma was lower in cows fed the SFL-enriched diet than in those consuming the tFA-supplemented diet. Mean concentrations of plasma glucose, insulin-like growth factor-I, and progesterone were greater in cows fed the SFL-enriched diet compared with those fed the saturated fatty acid-supplemented diet. Feeding fat supplements that can suppress milk fat production during the early postpartum period may help minimize negative energy balance, reduce adipose tissue mobilization, and improve circulating concentrations of insulin-like growth factor-I and progesterone. Whether the SFL supplement would have similar effects without a decrease in milk fat production remains to be determined and warrants further investigation.

Effects of hyperbaric oxygen therapy on circulating interleukin-8, nitric oxide, and insulin-like growth factors in patients with type 2 diabetes mellitus.

BACKGROUND: The potential benefits of hyperbaric oxygen therapy (HBOT) have been reported in diabetic patients with foot ulcers. However, the roles of HBOT on wound healing-associated growth factors and inflammatory mediators are not completely understood in diabetes mellitus (DM). OBJECTIVES: The aim of this study was to investigate the effects of HBOT on circulating cytokines, NO, and insulin-like growth factors (IGF) in patients with type 2 DM. DESIGN AND METHODS: Serum samples were collected from patients with type 2 DM (n=31) and healthy subjects (n=29) before (baseline) and after the first and third exposure. RESULTS: Before HBOT, body mass index (BMI) and serum HbA1c were significantly greater, whereas serum IGF-I was significantly lower in diabetic patients compared to healthy subjects (one-way ANOVA, p<0.05). After adjusting for age, gender, and BMI, serum insulin, growth hormone (GH), IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-3, leptin, interleukin (IL)-8, and NO were not significantly altered by HBOT in diabetic patients and healthy subjects (repeated-measures ANOVA). Change in serum insulin (baseline to the third exposure) was a positive predictor of changes in leptin and NO in healthy subjects and diabetic patients, respectively. CONCLUSIONS: Our results suggest that short-term HBOT may not alter the circulating insulin, IGF, leptin, IL-8, and NO levels. In addition, healthy subjects and diabetic patients showed differential responses to HBOT in the relationships of leptin, insulin, and NO. Further studies are needed to clarify the mechanism of HBOT-improved wound healing in diabetic patients with foot ulcers.

A prospective study of the insulin-like growth factor axis in relation with prostate cancer in the SU.VI.MAX trial.

Several epidemiologic studies have examined with diverging results the relationships between circulating levels of insulin-like growth factors (IGF) and of IGF-binding proteins (IGFBP) and prostate cancer risk. We assessed the association of prediagnostic plasma levels of IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and subsequent occurrence of prostate cancer in a case-control study nested in the SU.VI.MAX trial. The SU.VI.MAX study was a primary prevention trial testing a daily supplementation with low-dose antioxidant vitamins and minerals in male and female middle-aged volunteers in France. One hundred prostate cancer cases were diagnosed among 4,855 SU.VI.MAX participants over a 9-year follow-up period. For each case, four age-matched controls were selected randomly. Frozen baseline plasma samples were used to measure IGF-I, IGF-II, IGFBP-2, and IGFBP-3. Conditional logistic regression was used to assess the association between these four biochemical markers and prostate cancer risk. After controlling for the intervention group in the trial and the other IGF axis variables, the odds ratios and 95% confidence interval (95% CI) comparing the upper quartile to the baseline quartile were 1.83 (95% CI, 0.85-3.95), 1.05 (95% CI, 0.35-3.18), 0.79 (95% CI, 0.39-1.58), and 0.42 (95% CI, 0.12-1.52) for IGF-I, IGF-II, IGFBP-2, and IGFBP-3, respectively. More suggestive associations for IGF-I and IGFBP-3 were observed with advanced and aggressive cancers. Our results are consistent with those of some previous prospective studies and suggest that IGF axis variables are not long-term predictors of the occurrence of prostate cancer.

Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial.

Randomized trials have shown, unexpectedly, that supplementation with selenium or vitamin E is associated with a reduction of prostate cancer risk. We assess whether a supplementation with low doses of antioxidant vitamins and minerals could reduce the occurrence of prostate cancer and influence biochemical markers. The SU.VI.MAX trial comprised 5,141 men randomized to take either a placebo or a supplementation with nutritional doses of vitamin C, vitamin E, beta-carotene, selenium and zinc daily for 8 years. Biochemical markers of prostate cancer risk such as prostate-specific antigen (PSA) and insulin-like growth factors (IGFs) were measured on plasma samples collected at enrollment and at the end of follow-up from 3,616 men. Cox regression models were used to estimate the hazard ratio and related 95% confidence interval of prostate cancer associated with the supplementation and to examine whether the effect differed among predetermined susceptible subgroups. During the follow-up, 103 cases of prostate cancer were diagnosed. Overall, there was a moderate nonsignificant reduction in prostate cancer rate associated with the supplementation (hazard ratio = 0.88; 95% CI = 0.60-1.29). However, the effect differed significantly between men with normal baseline PSA (< 3 microg/L) and those with elevated PSA (p = 0.009). Among men with normal PSA, there was a marked statistically significant reduction in the rate of prostate cancer for men receiving the supplements (hazard ratio = 0.52; 95% CI = 0.29-0.92). In men with elevated PSA at baseline, the supplementation was associated with an increased incidence of prostate cancer of borderline statistical significance (hazard ratio = 1.54; 95% CI = 0.87-2.72). The supplementation had no effect on PSA or IGF levels. Our findings support the hypothesis that chemoprevention of prostate cancer can be achieved with nutritional doses of antioxidant vitamins and minerals.

Effects of an enhanced vitamin A intake during the dry period on retinoids, lactoferrin, IGF system, mammary gland epithelial cell apoptosis, and subsequent lactation in dairy cows.

Studies in vitro show important interactions among vitamin A, lactoferrin, and insulin-like growth factor (IGF) binding proteins (IGFBP) and, thus, the IGF system. As a consequence, mammary gland epithelial cell proliferation and apoptosis during the bovine dry period and potential milk yield may be affected. We have studied effects of feeding vitamin A (550,000 IU/ d) that exceed daily requirements about 8-fold for up to 2 mo to dairy cows during the dry period on concentrations of retinol and its metabolites in plasma and milk, milk lactoferrin, plasma and milk IGF-I and IGFBP-3, lactoferrin and IGF-I mRNA levels in mammary gland tissue, mammary gland apoptosis, and 100-d milk yield in the ensuing lactation. In the group supplemented with vitamin A, the peripartal decrease of plasma retinol was delayed and attenuated, and colostral retinol plus retinylester concentration was enhanced, but colostral beta-carotene concentration decreased. The retinoic acid isomer 9,13-dicis retinoic acid that coeluted with 13-cis retinoic acid, was the predominant circulating retinoic acid and was higher in GrA than the control group. Plasma IGFBP-3 concentrations were positively correlated with plasma retinol concentrations (r = 0.51), but there were no group differences. Numbers of apoptotic epithelial cells in mammary epithelium were higher at drying off and parturition than in the middle of the dry period, coinciding with high concentrations of IGF-I and lactoferrin in mammary secretions. At parturition, numbers of apoptotic cells in mammary gland biopsies in cows supplemented with vitamin A were higher than in control cows. In conclusion, supplementation of dairy cows during the dry period with high amounts of vitamin A did not significantly modify concentrations of lactoferrin, IGFBP-3, and IGF-I in plasma and in mammary secretions, but slightly decreased energy-corrected 100-d milk yield and milk fat yield, possibly because of enhanced apoptic rates of mammary cells.

Effects of arginine-containing total parenteral nutrition on N balance and phagocytic activity in rats undergoing a partial gastrectomy.

The present study investigated the effect of arginine (Arg)-containing parenteral nutrition on phagocytic activity to elucidate the possible roles of Arg in the secretion of anabolic hormones and N balance in rats undergoing gastrectomy. Rats were divided into two experimental groups and received total parenteral nutrition (TPN). The TPN solutions were isonitrogenous and identical in nutrient compositions except for differences in amino acid content. One group received conventional TPN, the other group replaced 2 % of the total energy as Arg. After receiving TPN for 3 d, one-third of the rats in each experimental group were killed as the baseline group. The remaining rats underwent a partial gastrectomy and were killed 1 or 3 d after surgery. The results showed that there were no differences in N balance, plasma growth hormone and insulin-like growth factor-1 levels between the two groups before or after surgery. The phagocytic activity of peritoneal macrophages was higher in the Arg group than in the control group 1 d after surgery. There were no differences in the phagocytic activities of blood polymorphonuclear neutrophils between the two groups at various time points. TNF-alpha levels in peritoneal lavage fluid were lower in the Arg group than in the control group on post-operative day 3. These results suggest that parenterally infused Arg enhances phagocytic activity and reduces the production of inflammatory mediators at the site of injury. However, Arg supplementation did not influence the secretion of anabolic hormones nor N balance in rats with a partial gastrectomy.

Effects of reduced dialysate calcium on calcium-phosphorus product and bone metabolism in hemodialysis patients.

BACKGROUND: The safety of using reduced calcium dialysate (RDC) in hemodialysis (HD) patients is controversial due to related changes in bone metabolism. In the present study we investigated whether an 18-month treatment period with RDC may induce significant changes in calcium-phosphorus product (CaxP), bone metabolism, and components of the insulin-like growth factor (IGF) system in HD patients. STUDY DESIGN: In this prospective study, 13 HD patients with biochemical signs of diminished or low-normal bone turnover and high CaxP due to high serum calcium level were treated by lowering dialysate calcium from 3.5 to 2.5 mEq/l for 18 months. By specific immunometric assays, serum levels of intact parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), pyridinoline (PYR), desoxypyridinoline (D-PYR), 25-OH-vitamin D(3) (25-vit D(3)), 1,25-(OH)(2)-vitamin D(3) (1,25-vit D(3)), free IGF-I, IGF-II, and IGF-binding protein (IGFBP)-1 to -6 were measured. RESULTS: CaxP decreased significantly from 5.62 (baseline) to 3.95 mmol(2)/l(2) (at 18 months), whereas PTH increased from 81 +/- 57 pg/ml at baseline to 236 +/- 188 at 12 months (p < 0.01), remaining in this range thereafter. Parameters of bone resorption (PYR) as well as formation (B-ALP) significantly increased during RDC, with peak levels after 12 months. Despite increasing doses of oral alfacalcidol, levels of 25-vit D(3) and 1,25-vit D(3) subsequently declined during RDC. In parallel with the changes in bone markers, free IGF-I levels decreased (baseline: 1.9 +/- 0.9 ng/ml, after 18 months: 1.1 +/- 0.7; p < 0.01). The decline of free IGF-I correlated with decreasing levels of IGFBP-3 and increasing levels of IGFBP-1/-4. CONCLUSION: The treatment with RDC effectively lowered CaxP and stimulated bone formation and resorption. The different changes in bone markers and IGF system components mirror the complex effects on bone metabolism.

The insulin-like growth factor system in the GT1-7 GnRH neuronal cell line.

Evidence suggests that insulin-like growth factors (IGFs; IGF-I and IGF-II) are involved in the regulation of reproductive function including the development of the gonadotropin-releasing hormone (GnRH) neuronal system and the modulation of GnRH secretory activities. To further characterize the regulatory role of the IGF system on GnRH neuronal function, we have examined the gene expression of IGF-I, IGF-II, IGF-I receptor (IGF-IR), and IGF-binding proteins (IGFBPs) in a GnRH neuronal cell line (GT1-7 cells). The relative effects of IGFs and insulin on GnRH secretion by these cells was also investigated. RT-PCR analysis demonstrated IGF-I, IGF-II and IGF-IR mRNAs in GT1-7 cells. The mRNAs for IGFBP-2, -3, -4, -5 and -6 but not IGFBP-1 were also detected. Immunoreactive protein bands for IGFBP-2, -4 and -5 but not for other IGFBPs were demonstrated by Western blot with IGFBP-5 appearing to be the most abundant IGFBP secreted by GT1-7 cells. IGFBP-5 production by GT1-7 cells was stimulated by both IGF-I and IGF-II in a dose-dependent manner with approximately equal potency, whereas insulin caused no significant effect. GnRH secretion by GT1-7 cells treated with IGF-I or IGF-II but not insulin showed an increase (80-100%) at 2 h of treatment followed by a decrease (46%) at 6 h that continued up to 24 h. We conclude that the expression of IGFs, IGF-IR and IGFBPs and their interactions in the regulation of GnRH secretion by GT1-7 cells as demonstrated by our study provide a basis for an autocrine regulatory role for the IGF system in GnRH neuronal secretory activities.

The pattern of intracellular free amino acids in granulocytes from hemodialysis patients change to an oral protein supplement (granulocyte amino acids after protein in HD patients).

MATERIALS AND METHODS: The concentrations of free intracellular amino acids in granulocytes and plasma amino acids, normalized protein nitrogen appearance rate, serum insulin-like growth factors, plasma proteins, anthropometric and bioimpedance measurements were determined before and after an oral protein supplement in 19 stable patients on maintenance hemodialysis in a randomized, double-blind placebo-controlled study with crossover after 3 months. The hemodialysis patients were well-nourished with an ideal body weight of 91% after both protein supplementation and after placebo. RESULTS: After protein supplementation (7.8 g/d) the intracellular concentration of valine, isoleucine, threonine and tyrosine and the valine/glycine and tyrosine/phenylalanine ratios in the cells were significantly increased (p < 0.05). In contrast, the concentrations of plasma amino acids, serum insulin-like growth factors, and plasma proteins and body weight and anthropometric and bioimpedance measurements were unchanged. Dialysis efficiency was unchanged throughout the study. CONCLUSIONS: The present study supports the conclusion that protein supplementation to well-nourished hemodialysis patients does not improve the nutritional status measured by plasma proteins, body weight, anthropometric and bioimpedance measurements. The increase in intracellular amino acid concentrations indicates better cellular nutrition and metabolic control.

Insulin-like growth factor-I, GH, insulin and glucagon concentrations in bovine colostrum and in plasma of dairy cows and neonatal calves around parturition.

1. The IGF-I concentrations in colostrum on days 1 and 2 after parturition were higher than those in cow and neonate plasma. 2. The modest increase in GH concentrations in cow plasma around parturition would not be enough to stimulate IGF-I release by tissues. 3. The concentrations of insulin, GH and glucagon in colostrum were substantially lower than those in plasma.

Use of fibronectin and somatomedin-C as markers of enteral nutrition support in traumatized patients using a modified amino acid formula.

The purpose of this study was to evaluate the use of serum fibronectin and serum somatomedin-C as nutritional markers during enteral nutrition support (ENS) of critically ill, traumatized patients using an enteral product containing high concentrations of branched-chain amino acids. Twelve critically injured patients received a standard enteral formula with 30 g of a 44% branched-chain amino acid supplement added to each liter of formula. Fibronectin concentration, somatomedin-C concentration, and nitrogen balance were measured on study days 1, 4, 7, 14, 21, 28 or until adequate oral intake began. Both fibronectin and somatomedin-C concentrations increased significantly from baseline by day 7 of ENS. Nitrogen balance increased significantly from baseline by day 4. On days 14 and 21, only somatomedin-C and nitrogen balance increased significantly from baseline. Nitrogen balance was significantly correlated with somatomedin-C concentration (r = 0.53, p less than 0.01), cumulative caloric intake (r = 0.68, p less than 0.01), and cumulative nitrogen intake (r = 0.72, p less than 0.01). The results of this study suggest that serum somatomedin-C is useful and serum fibronectin has potential in monitoring nutrition support response in critically ill, traumatized patients.

Cerebral insulin-like immunoreactivity in rats and mice. Drastic decline during postnatal ontogenesis.

We studied the behavior of the insulin-like immunoreactivity in brains of rats and mice during the first 20 d post natum by immunohistochemistry and radioimmunoassay. It was found that a dramatic decline in the concentration of the peptide, accompanied by a strong reduction of immunoreactive cells, takes place during this period. A possible role of cerebral insulin as a promoter of nerve cell growth and development is briefly discussed.