Studies on the Mechanism of the Volatile Oils from Caoguo-4 Decoction in Regulating Spleen Deficiency Diarrhea by Adjusting Intestinal Microbiota.

BACKGROUND: The Caoguo-4 decoction, a classical Mongolian medicine formula, is widely used to treat spleen deficiency diarrhea (SDD) in Mongolian for decades. Previously, the Caoguo-4 decoction volatile oil has been confirmed to be effective in ameliorating symptoms of spleen deficiency diarrhea in an animal model. However, the underlying mechanism of the Caoguo-4 decoction volatile oil is yet to be established. The aim of the current study was to investigate the antidiarrheal effects and mechanism of the Caoguo-4 decoction volatile oil. METHOD: Wistar rats were randomly divided into 5 groups of 10 animals including control, model, positive, Caoguo-4 decoction, and Caoguo-4 decoction volatile oil groups (10 rats in each group). All the rats, besides those in the control group, were induced to develop SDD by a bitter-cold purgation method with Xiaochengqi decoction. The antidiarrheal effect of Caoguo-4 decoction volatile oil was evaluated by pathological section, serum D-xylose and AMS content, plasma MTL content, and gut microbiota analysis via 16S rRNA sequencing. RESULTS: The results showed that the developed SDD rat model (model group) had decreased food intake, increased weight loss, soft stool, and bad hair color. When compared with the control group, serum was significantly reduced serum D-xylose and AML but increased MTL levels in the model group (p < 0.05). However, after treatment with either the Caoguo-4 decoction (the decoction group) or Smecta (the positive group) or volatile oil from the Caoguo-4 decoction (the volatile oil group), a significant increase in the serum D-xylose levels was observed. Additionally, AML levels significantly increased in the positive and volatile oil groups, and MTL levels significantly decreased in the decoction and volatile oil groups, when compared with the model group (p < 0.05). The pathological changes of the intestinal mucosa showed that the structure of the epithelium in the villi of the small intestine was affected, deformed, and incomplete in the model group when compared with the control group. However, either the decoction group or the volatile oil group recovered the villous morphology. The results of OTU analysis and alpha diversity analysis of intestinal bacteria showed that the intestinal microbiota of the SDD model rats showed an obvious decrease in richness and diversity of intestinal microbiota. But the intervention treatment of decoction and volatile oil could significantly recover the richness and diversity of intestinal microbiota. CONCLUSION: The intestinal microbiota destroyed in SDD modelling could be significantly improved by the Caoguo-4 decoction volatile oils, which provides reference for clinical medication.

Poria ameliorates the side effects of rhubarb in pair treatment.

To investigate the effect of Poria and effective constituents on gastrointestinal injury animals in the area of the side effects which caused by Rhubarb. Mice were administered i.g. with Rhubarb until the induction of diarrhea followed by gastrointestinal injury. The gastrointestinal injured mice were treated with high, medium and low doses of poria water extract and it's subfractions for 5 days. All indexes were determined to evaluate the action of poria in the pair treatment. The results showed that the higher dose of poria water decoction was discovered to be the most effective dose to treat gastrointestinal injury induced by rhubarb. Body weight, thymus and spleen indexes, the small intestinal propulsion rate and D-xylose absorption in mice with diarrhea and intestinal injury were analyzed to reveal the significant difference with the model group (P<0.01). EAF (Ethyl Acetate Fraction), PEF (Petroleum Ether Fraction) and CPF (Crude Polysaccharide Fraction) not only increase the levels of AMS, GAS and VIP significantly but also ameliorate diarrhea and intestinal injury situation compared with the model group (P<0.01). EAF, PEF and CPF were the most effective components to alleviate diarrhea and gastrointestinal injury induced by rhubarb.

Gas chromatography-mass spectrometry based serum metabolic analysis for premature infants and the relationship with necrotizing enterocolitis: a cross-sectional study.

BACKGROUND: Preterm birth and feeding are the most important pathogenic factors of neonatal necrotizing enterocolitis (NEC). Metabonomic has been widely used in the diagnosis and treatment of other diseases, but there is no research on the related diseases of premature infants. Compared with full-term infants, the metabolism of preterm infants has its own specificity, so it can easily lead to NEC and other digestive tract inflammatory diseases. Metabonomic may be applied to the diagnosis of preterm related diseases, such as NEC. METHODS: The model was established with premature infant serum samples from 19 premature infants in our hospital, which was compared with the full-term infant control group. Serum was analyzed by gas chromatography-mass spectrometry (GC-MS), coupled with the analysis of serum metabolic characteristics. The variable important in projection, P value and Pearson correlation coefficient of samples were analyzed by using SIMCA, SPSS and other multivariate statistical analysis software. RESULTS: Compared to the term infants, premature infants had significantly higher levels of luteolin, and lower levels of xylose, O-succinyl-L-homoserine and lauric acid in the serum. There were some correlations among several different metabolites and clinically related indices (albumin, total bilirubin) for premature birth related diseases. CONCLUSIONS: There are metabolic alterations in the serum of premature infants, which make contribution to the diagnosis of NEC.

Shen-ling-bai-zhu-san, a spleen-tonifying Chinese herbal formula, alleviates lactose-induced chronic diarrhea in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-ling-bai-zhu-san (SLBZS) was firstly documented in ancient Chinese medical works "Tai Ping Hui Min He Ji Ju Fang" in Song-dynasty. It has been widely used for treating gastrointestinal disorders such as diarrhea with poor appetite for about 900 years. The present study is to observe the effects of SLBZS on high lactose diet-induced chronic diarrhea. MATERIALS AND METHODS: Rats were subjected to a high lactose diet to induce chronic diarrhea, which were then administrated with SLBZS or smecta. General symptom, body weight, food consumption, water intake and fecal fluid content were recorded every day. The intestinal absorption function was determined by d-xylose uptake assay. The ultrastructures of intestine segments including jejunum, ileum, proximal and distal colon were observed by transmission electron microscopy. Additionally, sodium transport proteins including γ-epithelial sodium channel (ENAC-γ) and sodium/potassium-transporting ATPase subunit alpha-1 (ATP1A1) in distal colon were detected by immunohistochemistry and western blotting. RESULTS: Diarrheal rats produced watery or loose, sticky feces, and presented inactiveness and grouping. A high lactose diet caused a significant decline in body weight, serum d-xylose level as well as food consumption rather than water intake. In contrast, general symptoms were improved to a certain extent and body weight loss was alleviated in the rats treated by SLBZS for one week. Fecal fluid content in diarrheal rats treated by SLBZS presented a gradual decrease trend with about 55% in the end, which was significantly less than the model group with about 81%. Meanwhile, SLBZS significantly improved the serum d-xylose level and reversed abnormal changes of tight junctions and microvilli in intestine. Additionally, SLBZS significantly modulated the abnormal expressions of ENAC-γ and ATP1A1 in distal colon of diarrheal rats. CONCLUSIONS: These findings suggested that SLBZS exhibited ameliorating effects against lactose-induced diarrhea, which might be attributed to its modulations on intestinal absorption function as well as mucosal ultrastructure.

Dietary l-arginine inhibits intestinal Clostridium perfringens colonisation and attenuates intestinal mucosal injury in broiler chickens.

We investigated the effects of dietary l-arginine level and feeding duration on the intestinal damage of broilers induced by Clostridium perfringens (CP) in vivo, and the antimicrobial effect of its metabolite nitric oxide (NO) in vitro. The in vivo experiment was designed as a factorial arrangement of three dietary treatments×two challenge statuses. Broilers were fed a basal diet (CON) or a high-arginine diet (ARG) containing 1·87 % l-arginine, or CON for the first 8 d and ARG from days 9 to 28 (CON/ARG). Birds were co-infected with or without Eimeria and CP (EM/CP). EM/CP challenge led to intestinal injury, as evidenced by lower plasma d-xylose concentration (P<0·01), higher paracellular permeability in the ileum (P<0·05) and higher numbers of Escherichia coli (P<0·05) and CP (P<0·001) in caecal digesta; however, this situation could be alleviated by l-arginine supplementation (P<0·05). The intestinal claudin-1 and occludin mRNA expression levels were decreased (P<0·05) following EM/CP challenge; this was reversed by l-arginine supplementation (P<0·05). Moreover, EM/CP challenge up-regulated (P<0·05) claudin-2, interferon-γ (IFN-γ), toll-like receptor 2 and nucleotide-binding oligomerisation domain 1 (NOD1) mRNA expression, and l-arginine supplementation elevated (P<0·05) IFN-γ, IL-10 and NOD1 mRNA expression. In vitro study showed that NO had bacteriostatic activity against CP (P<0·001). In conclusion, l-arginine supplementation could inhibit CP overgrowth and alleviate intestinal mucosal injury by modulating innate immune responses, enhancing barrier function and producing NO.

Effect of Ligation of the Thoracic Duct During Oesophagectomy on the Absorption of D-xylose.

OBJECTIVE: To assess if prophylactic thoracic duct ligation during oesophagectomy influences the absorptive function of oesophageal cancer patients. STUDY DESIGN: Randomized controlled trial. PLACE AND DURATION OF STUDY: Department of Thoracic Surgery, Tai'an City Central Hospital, Tai'an, from August 2014 to December 2015. METHODOLOGY: Based on the management of the thoracic duct during oesophagectomy, 60 patients were randomized into two groups. D-xylose absorption test was used to evaluate the absorptive function. The two-independent-samples t-test was employed for statistical analysis with statistical significance at p < 0.05. RESULTS: The serum D-xylose concentration of ligation-group was significantly lower than that of no-ligation group on the first day after operation, (t=2.82, p=0.0066). However, there was no significant differences between them even before operation (t=1.34, p=0.1849). CONCLUSION: Ligation of the thoracic duct during oesophagectomy immediately affected the absorption of D-xylose, which may lead to malabsorption in the long run.

Tolerance and Long-Term Efficacy of Polyethylene Glycol 4000 (Forlax®) Compared to Lactulose in Elderly Patients with Chronic Constipation.

OBJECTIVES: To assess the tolerance and potential nutritional consequences of long-term repeated doses of PEG 4000 (10 to 30 g/day) in elderly patients with chronic constipation as compared to lactulose (10-30 g/day). DESIGN: Single blind, randomised, multicentre, parallel group comparative study. SETTING: Community-dwelling patients and nursing homes residents aged 70 years and older with a history of chronic constipation. Treatment intervention: PEG 4000 (10-30 g/day) or lactulose (10-30 g/day) for six months. ASSESSMENTS: Clinical nutritional status (Mini Nutritional Assessment), blood and stool samples were taken at baseline and after three and six months for assay of nutritional and absorption parameters. A patient diary documented digestive symptoms and adverse events were recorded. Information on efficacy (stool frequency and consistency) was collected as a secondary outcome measure. RESULTS: Of the 316 patients screened, 245 eligible patients constituted the ITT population (PEG 4000: N = 118; lactulose group: N = 127). The proportion of patients receiving PEG 4000 with abnormal levels of electrolytes, nutritional markers or vitamins did not significantly change in the six months after initiating laxative treatment and do not differ between the two groups. After a D-xylose challenge test, the proportion of patients with abnormally low xylosaemia (suggesting malabsorption) varied from 24.6% at baseline to 35.8% after six months in the PEG 4000 group and from 29.1% to 42.4% in the lactulose group, with no significant between-group or within-group differences. The proportion of patients with poor nutritional status (MNA score <17) varied from 8.5% at baseline to 9.8% after 6 months in the PEG 4000 group and from 3.9% to 5.0% in the lactulose group. No changes in stool fat or total or soluble stool nitrogen were observed in the minority of patients for whom stool analysis was performed. A significantly higher stool frequency (p <0.05) and improved stool consistency (p <0.05) was observed in the PEG 4000 group compared to the lactulose group at each monthly evaluation period. CONCLUSIONS: After six months of treatment with PEG 4000, no clinically relevant changes in biochemical and nutritional parameters and no unanticipated treatment-related adverse events were detected, demonstrating the good clinical tolerance of PEG 4000 in this population of elderly constipated patients. This tolerance was associated with a better clinical efficacy of PEG 4000 compared to lactulose.

Metabolic Profiling Reveals Differences in Plasma Concentrations of Arabinose and Xylose after Consumption of Fiber-Rich Pasta and Wheat Bread with Differential Rates of Systemic Appearance of Exogenous Glucose in Healthy Men.

BACKGROUND: The consumption of products rich in cereal fiber and with a low glycemic index is implicated in a lower risk of metabolic diseases. Previously, we showed that the consumption of fiber-rich pasta compared with bread resulted in a lower rate of appearance of exogenous glucose and a lower glucose clearance rate quantified with a dual-isotope technique, which was in accordance with a lower insulin and glucose-dependent insulinotropic polypeptide response. OBJECTIVE: To gain more insight into the acute metabolic consequences of the consumption of products resulting in differential glucose kinetics, postprandial metabolic profiles were determined. METHODS: In a crossover study, 9 healthy men [mean ± SEM age: 21 ± 0.5 y; mean ± SEM body mass index (kg/m2): 22 ± 0.5] consumed wheat bread (132 g) and fresh pasta (119 g uncooked) enriched with wheat bran (10%) meals. A total of 134 different metabolites in postprandial plasma samples (at -5, 30, 60, 90, 120, and 180 min) were quantified by using a gas chromatography-mass spectrometry-based metabolomics approach (secondary outcomes). Two-factor ANOVA and advanced multivariate statistical analysis (partial least squares) were applied to detect differences between both food products. RESULTS: Forty-two different postprandial metabolite profiles were identified, primarily representing pathways related to protein and energy metabolism, which were on average 8% and 7% lower after the men consumed pasta rather than bread, whereas concentrations of arabinose and xylose were 58% and 53% higher, respectively. Arabinose and xylose are derived from arabinoxylans, which are important components of wheat bran. The higher bioavailability of arabinose and xylose after pasta intake coincided with a lower rate of appearance of glucose and amino acids. We speculate that this higher bioavailability is due to higher degradation of arabinoxylans by small intestinal microbiota, facilitated by the higher viscosity of arabinoxylans after pasta intake than after bread intake. CONCLUSION: This study suggests that wheat bran, depending on the method of processing, can increase the viscosity of the meal bolus in the small intestine and interfere with macronutrient absorption in healthy men, thereby influencing postprandial glucose and insulin responses. This trial was registered at www.controlled-trials.com as ISRCTN42106325.

The Effects of Oral Quercetin Supplementation on Splanchnic Glucose Metabolism in 1-Week-Old Calves Depend on Diet after Birth.

BACKGROUND: Inadequate colostrum supply results in insufficient intake of macronutrients and bioactive factors, thereby impairing gastrointestinal development and the maturation of glucose metabolism in neonatal calves. The flavonoid quercetin has been shown to have health-promoting properties, including effects in diabetic animals. However, quercetin interacts with intestinal glucose absorption and might therefore exert negative effects in neonates. OBJECTIVE: We evaluated the interaction between neonatal diet and quercetin feeding on splanchnic glucose metabolism in neonatal calves. METHODS: Calves (n = 28) were assigned to 4 groups and fed either colostrum or a milk-based formula on days 1 and 2 and supplemented daily with 148 µmol quercetin aglycone/kg body weight [colostrum with quercetin (CQ+)/formula with quercetin (FQ+)] or without this substance [colostrum without quercetin (CQ-)/formula with quercetin (FQ-)] from days 2-8. From day 3 onward, all calves received milk replacer. A xylose absorption test was performed on day 3, and on day 7, blood samples were collected to study glucose first-pass uptake after [(13)C6]-glucose feeding and intravenous [6,6-(2)H2]-glucose bolus injection. Plasma concentrations of metabolites and hormones were measured by taking additional blood samples. A biopsy specimen of the liver was harvested on day 8 to measure the mRNA expression of gluconeogenic enzymes. RESULTS: Higher postprandial plasma concentrations of glucose, lactate, urea, adrenaline, noradrenaline, insulin, and glucagon on day 7 in colostrum-fed calves indicate that metabolic processes were stimulated. Postabsorptive xylose and glucose plasma concentrations each increased by an additional 26%, and splanchnic glucose turnover decreased by 35% in colostrum-fed calves, suggesting improved glucose absorption and lower splanchnic glucose utilization in colostrum-fed calves. Quercetin supplementation resulted in higher noradrenaline concentrations and enhanced peak absorption and oxidation of [(13)C6]-glucose by 10%. Liver mitochondrial phosphoenolpyruvate carboxykinase mRNA abundance was reduced by 34% in colostrum-deprived calves. CONCLUSIONS: Feeding colostrum during the first 2 d of life is crucial for maturation of splanchnic glucose metabolism in calves. Supplementing quercetin improves gastrointestinal absorption capacity, particularly in colostrum-deprived calves.

Improvement and validation of d-xylose determination in urine and serum as a new tool for the noninvasive evaluation of lactase activity in humans.

BACKGROUND: The phloroglucinol assay is the current method for d-xylose determination in urine/plasma/serum. However, its sensitivity is limited when low amounts of d-xylose are to be measured, such as in the noninvasive evaluation of intestinal lactase with 4-galactosylxylose (gaxilose). An improved assay was therefore needed. METHODS: We developed and validated a modified version of the phloroglucinol-based assay for quantification of d-xylose in urine/serum samples. A method for gaxilose determination by gas chromatography (GC) was also optimized. RESULTS: Linearity ranged from 0.125 to 5.0 mg/l (5-200 mg/l in original sample). Accuracy at LOQ (0.125 mg/l) was 0.97/2.49% in spiked urine/serum; for other quality controls (QC), it was <1.27%. Intra- and interassay precision at LOQ were 6.02% and 6.45% for urine, and 8.86% and 10.00%, respectively, for serum; for other QC, precision was <2.15%. Linearity of gaxilose determination by GC was 3.90-195.17 for urine and 9.75-195.17 mg/l for serum with acceptable sensitivity and reproducibility. The method proved adequate for the d-xylose determination in healthy and hypolactasic subjects after oral administration of gaxilose. CONCLUSIONS: The modified method provides high sensitivity and robustness for d-xylose quantification in urine/serum for routine clinical use especially in the noninvasive diagnosis of intestinal lactase deficiency with the gaxilose test.

Gastric bypass increases postprandial insulin and GLP-1 in nonobese minipigs.

BACKGROUND: Gastric bypass in obese patients induces a dramatic increase of postprandial insulin and glucagon-like peptide-1 (GLP-1) secretion, independently of weight loss. We explored postprandial insulin and GLP-1 secretion in nonobese minipigs before and after RYGB. METHODS: Lean adult Göttingen minipigs (n = 7) were submitted to an open gastric bypass surgery mimicking the clinical procedure in humans (30-cm(3) gastric pouch/150-cm alimentary limb/70-cm biliary limb). All animals were evaluated at baseline and then 10 and 30 days after surgery. At each time point, serum glucose, insulin, GLP-1 and D-xylose levels were measured 3 h after a standardized mixed meal. RESULTS: Weight remained stable during follow-up. Insulin and GLP-1 responses to the test meal were dramatically and similarly increased at 10 days and 1 month after RYGB. Maximal postprandial insulin and GLP-1 levels were 16.3 ± 1.7 mIU/l and 71.7 ± 16.5 pmol/l at baseline, 111.5 ± 38.9 mIU/l and 320.8 ± 84.0 pmol/l at 10 days and 96.6 ± 10.4 mIU/l and 297.3 ± 79.1 pmol/l at 1 month, respectively. D-Xylose absorption remained unchanged before and after surgery. CONCLUSIONS: RYGB induced a dramatic increase of postprandial insulin and GLP-1 secretion in nonobese minipigs. This preclinical model could help to understand the underlying metabolic effects of RYGB, focusing on the role of postsurgical anatomical rearrangement, especially duodenojejunal exclusion and ileal brake. This study supports the use of RYGB in diabetic nonobese patients in absence of obesity.

Noninvasive diagnosis of hypolactasia with 4-Galactosylxylose (Gaxilose): a multicentre, open-label, phase IIB-III nonrandomized trial.

GOALS AND BACKGROUND: Hypolactasia affects over half of the world population. Diagnosis remains problematic as currently available tests, such as the hydrogen breath test, have low reliability and lactose intolerance symptoms are unspecific. We evaluated the diagnostic performance and safety of a new noninvasive diagnostic test based on urine or serum measurement of D-xylose after lactase cleavage of orally administered 4-galactosylxylose (gaxilose). STUDY: In a multicentre, open-label, nonrandomized, phase IIb-III study, consecutive patients with symptoms suggestive of lactose intolerance sequentially underwent intestinal biopsy for direct measurement of lactase activity (reference standard), hydrogen breath test, and blood glucose test after lactose challenge, 4- and 5-hour urine-based gaxilose test, and blood-based gaxilose test. For the gaxilose tests, 0 to 4 and 4 to 5 hours urine samples were taken after a 0.45 g gaxilose dose, whereas serum samples were taken 90 minutes after a 2.7 g dose for D-xylose determination. Genetic testing of hypolactasia was also assessed. RESULTS: Of the 222 patients enrolled, 203 completed all diagnostic tests; 108 were hypolactasic according to biopsy. The sensitivities and specificities and positive and negative predictive values of the gaxilose tests were all >90% versus 69% to 85% for the hydrogen breath test and the blood glucose test. The area under the ROC curve was significantly higher for the gaxilose tests (>0.9, P≤0.007). These tests also had higher sensitivity than genetic testing for hypolactasia and were well tolerated. CONCLUSIONS: The diagnostic performance of the gaxilose tests is excellent and can substantially improve the diagnosis of hypolactasia.

Clinical parameters, intestinal function, and IGF1 concentrations in colostrum-deprived and colostrum-fed newborn pony foals.

Colostrum (COL) contains cytokines and growth factors that may enhance intestinal development in neonates. The hypothesis of this study was that besides providing immunoglobulins, COL is important for intestinal function and meconium release in foals. Newborn foals were either fed COL (n = 5) or an equal amount of milk replacer (MR, n = 7) during the first 24 hours of life. To ensure passive immunity, all foals received 1 L plasma. Postnatal development, meconium release, intestinal motility, white blood cell count, insulin-like growth factor 1, and intestinal absorptive function (xylose absorption test) were evaluated. Clinical findings and meconium release were not affected by feeding of COL or MR. Ultrasonography revealed a slightly larger jejunum and stomach in group COL versus MR (P < 0.05). The percentage of polymorphonuclear leucocytes was higher in foals of group MR versus group COL (P < 0.05) and the percentage of lymphocytes was lower in MR compared with COL foals (P < 0.05). Plasma insulin-like growth factor 1 concentration increased during the first 14 days after birth in both groups. A xylose absorption test on Day 5 revealed similar increases in plasma xylose concentrations after oral intake. In conclusion, feeding of COL versus MR was without effect on meconium release and intestinal absorptive function. Differences between foals fed COL and MR with regard to intestinal function are apparently without clinical relevance. In foals that have not received maternal COL, there is no major risk of intestinal problems if they are fed MR and provided with immunoglobulins by transfusion of plasma.

Influence of laxatives on gastric emptying in healthy Warmblood horses evaluated with the D-xylose absorption test.

The use of laxatives is crucial in the treatment of horses with large colon impaction. To reach the impacted mass, the laxative must leave the stomach and pass through the small intestine. The aim of this study was to determine whether the most frequently used saline and lubricant laxatives influence gastric emptying. Six fasted normal adult Warmblood horses were used in a randomized study design with five laxative trials (1.8% sodium sulfate [1.8% Na2SO4], 4.2% magnesium sulfate [4.2% MgSO4], mineral oil [MOil], 25% sodium sulfate [25% Na2SO4], 25% magnesium sulfate [25% MgSO4]) and two trials with water (at either 20 ml/kg BW [Water 20] or 4 ml/kg BW [Water 4]), administered via nasogastric intubation. For indirect measurement of liquid-phase gastric emptying, a liquid passage marker (0.5 g D-xylose/kg BW as 10% solution) was added to each trial. Serum samples were collected at pre-determined time points for pharmacokinetic analysis. The time to reach maximum serum concentration (T(max)) was considered as gastric emptying rate. Significant differences were detected for T(max) of 4.2% MgSO4 compared to Water 20 and for T(max), the maximum serum concentration (C(max)) and the area under the curve determined up to 90 min (AUC90) of 25% Na2SO4 and 25% MgSO4 compared to Water 4. Neither 1.8% Na2SO4, nor MOil delayed gastric emptying rate compared to water (Water 20, Water 4, respectively). 4.2% MgSO4 as well as 25% Na2SO4 and 25% MgSO4 significantly delayed gastric emptying rate in comparison to water (Water 20, Water 4, respectively).

Five-year outcomes after serial transverse enteroplasty in children with short bowel syndrome.

AIM: The aim of this study is to report 5-year outcomes in patients who have received serial transverse enteroplasty (STEP) using clinical and biochemical assessments of intestinal function. METHODS: Thirty-one STEP procedures have been performed at our institution. Twelve patients who received STEP before January 2005 were analyzed. Clinical and biochemical outcomes were performed pre-STEP and post-STEP on an annual basis. Paired t tests were used to compare post-STEP outcomes to pre-STEP values (P < .05 was significant). MAIN RESULTS: There were 12 patients (3 females; median age, 5.5 months). Serial transverse enteroplasty resulted in mean increase in length of dilated bowel segment of 89% ± 26% and increase in total small bowel length of 46% ± 40%. Two patients received liver-intestinal transplants post-STEP (at 4 and 5 months), and 2 patients died of liver failure at 3 and 8 months. The remaining 8 of 12 patients all show stable intestinal absorptive capacity (data not shown). Of 8 patients, 7 were weaned off parenteral nutrition by 4 years. No patient has required repeat STEP or bowel tapering. Two patients developed staple line leak, and 1 patient developed gastrointestinal bleed from staple line ulcers. CONCLUSION: This report represents the largest series of STEP patients followed up beyond 5 years. Long-term clinical, biochemical, and radiologic outcomes appear to be robust.

Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide.

The neonatal small intestine is susceptible to damage by endotoxin, but effective methods for prevention and treatment are lacking. N-acetylcysteine (NAC) is a widely used precursor of L: -cysteine for animal cells and plays an important role in protecting cells against oxidative stress. This study was conducted with the lipopolysaccharide (LPS)-challenged piglet model to determine the effects of NAC on intestinal function. Eighteen piglets were randomly allocated into control, LPS and LPS + NAC groups. The control and LPS groups were fed a corn- and soybean meal-based diet, and the LPS + NAC group was fed the basal diet +500 mg/kg NAC. On days 10, 13 and 20 of the trial, the LPS and LPS + NAC groups received intraperitoneal administration of LPS (100 µg/kg BW), whereas the control piglets received saline. On day 20 of the trial, D-: xylose (0.1 g/kg BW) was orally administrated to all piglets 2 h after LPS or saline injection, and blood samples were collected 1 h thereafter. One hour blood xylose test was used to measure intestinal absorption capacity and mucosal integrity, and diamine oxidase (DAO) was used as a marker of intestinal injury. On day 21 of the trial, pigs were killed to obtain the intestinal mucosa. Compared to the control, LPS challenge reduced (P < 0.05) the concentrations of D-: xylose (a marker of intestinal absorption) in plasma, activities of DAO in the jejunal mucosa, the ratio of villus height to crypt depth in the jejunal mucosa, RNA/DNA and protein/DNA in the jejunal and ileal mucosae, while increasing (P < 0.05) DAO activity in plasma and caspase-3 expression in the intestinal mucosa. The adverse effects of LPS were partially ameliorated (P < 0.05) by NAC supplementation. Moreover, NAC prevented the LPS-induced decrease in claudin-1 and occludin expression in the jejunal and ileal mucosae. Collectively, these results indicate that dietary NAC supplementation alleviates the mucosal damage and improves the absorptive function of the small intestine in LPS-challenged piglets.

Effects of intestinal mucosal blood flow and motility on intestinal mucosa.

AIM: To investigate the role of intestinal mucosal blood flow (IMBF) and motility in the damage of intestinal mucosal barrier in rats with traumatic brain injury. METHODS: Sixty-four healthy male Wistar rats were divided randomly into two groups: traumatic brain injury (TBI) group (n=32), rats with traumatic brain injury; and control group (n=32), rats with sham-operation. Each group was divided into four subgroups (n=8) as 6, 12, 24 and 48 h after operation. Intestinal motility was measured by the propulsion ratio of a semi-solid colored marker (carbon-ink). IMBF was measured with the laser-Doppler technique. Endotoxin and D-xylose levels in plasma were measured to evaluate the change of intestinal mucosal barrier function following TBI. RESULTS: The level of endotoxin was significantly higher in TBI group than in the control group at each time point (0.382±0.014 EU/mL vs 0.102±0.007 EU/mL, 0.466±0.018 EU/mL vs 0.114±0.021 EU/mL, 0.478±0.029 EU/mL vs 0.112±0.018 EU/mL and 0.412±0.036 EU/mL vs 0.108±0.011 EU/mL, P<0.05). D-xylose concentrations in plasma in TBI group were significantly higher than in the control group (6.68±2.37 mmol/L vs 3.66±1.07 mmol/L, 8.51±2.69 mmol /L vs 3.15±0.95 mmol/L, 11.68±3.24 mmol/L vs 3.78±1.12 mmol/L and 10.23±2.83 mmol/L vs 3.34±1.23 mmol/ L, P<0.05). The IMBF in TBI group was significantly lower than that in the control group (38.5±2.8 PU vs 45.6±4.6 PU, 25.2±3.1 PU vs 48.2±5.3 PU, 21.5±2.7 PU vs 44.9±2.8 PU, 29. 4±3.8 PU vs 46.7±3.2 PU) (P<0.05). Significant decelerations of intestinal propulsion ratio in TBI groups were found compared with the control group (0.48%±0.06% vs 0.62%±0.03%, 0.37%±0.05% vs 0.64%±0.01%, 0.39%±0.07% vs 0.63%±0.05% and 0.46%±0.03% vs 0.65%±0.02%) (P<0.05). CONCLUSION: The intestinal mucosal permeability is increased obviously in TBI rats. Decrease of intestinal motility and IMBF occur early in TBI, both are important pathogenic factors for stress-related damage of the intestinal mucosal barrier in TBI.

Increased gut absorptive capacity in rats with severe head injury after feeding with probiotics.

OBJECTIVE: The absorptive capacity of the gut is decreased after severe head injury (SHI), and this may be related to poor recovery. Probiotics may be a promising approach to improving gut absorption. The aim of this study was to investigate the effect of probiotics on gut absorptive capacity (GAC) after SHI. METHODS: A rat model in which SHI was induced by air percussion was used. One hundred fourteen Sprague-Dawley rats were randomized into three groups: SHI followed by standard enteral nutrition (group A); SHI followed by standard enteral nutrition plus probiotics (group B); and standard chow diet ad libitum (group C, sham-operated). The enteral diets were infused for 14 d after SHI. RESULTS: SHI induced weight loss and decreased the serum concentration of D-xylose and the apparent protein digestibility. Probiotics significantly improved GAC after SHI. Apparent protein digestibility and the concentration of D-xylose were lower in group A than in B or C after 14 d. The rats receiving probiotics showed less weight loss than group A. SHI induced intestinal flora dysfunction and a decrease in villus height and surface area. Digestive enzyme activities and gut motion were also depressed significantly, and these changes were closely related to the decrease in GAC. Probiotics increased villus height and surface area; Escherichia coli counts decreased significantly, and anaerobic counts increased. CONCLUSION: Probiotics improve the GAC after SHI, perhaps because of enhanced villus surface area, and correction of intestinal flora dysfunction.

Spectrum of malabsorption in India--tropical sprue is still the leader.

INTRODUCTION: Two decades ago tropical sprue, Immunoproliferative Small Intestinal Disease (IPSID) and infections were common causes of malabsorption in India. It is possible that implementation of preventive health measures and improved sanitation may have changed the spectrum of disorders causing malabsorption. The aim of this study therefore was to assess the spectrum of malabsorption seen at our center during the past nine years. METHODOLOGY: Patients seen at our center with malabsorption from January 2000 to December 2008 were included in this study. The etiological, clinical and investigation details were recorded on uniform structured data forms. The data obtained was retrospectively analyzed. RESULTS: Malabsorption was detected in 124 patients during the study period. The mean age of patients was 31.9+16 years and 60.5% were males. Tropical sprue was the commonest etiology (29%) followed by celiac and Crohn's disease (15.3% each). Other important etiologies included parasitic infestations (9.7%) and immune deficiency disorders (5.6%). Intestinal tuberculosis was seen in only 2.4% patients. CONCLUSIONS: We are witnessing a change in etiological spectrum of malabsorption . Celiac disease and inflammatory bowel disorders are emerging as important causes and ImmunoProliferative Small Intestinal Disease (IPSID) and intestinal tuberculosis are on the decline. Tropical Sprue however continues to be the commonest cause as in the past.