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.

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.

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.

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.

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.

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.

Effect of endogenous GLP-1 on insulin secretion in type 2 diabetes.

OBJECTIVE: The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) account for up to 60% of postprandial insulin release in healthy people. Previous studies showed a reduced incretin effect in patients with type 2 diabetes but a robust response to exogenous GLP-1. The primary goal of this study was to determine whether endogenous GLP-1 regulates insulin secretion in type 2 diabetes. METHODS: Twelve patients with well-controlled type 2 diabetes and eight matched nondiabetic subjects consumed a breakfast meal containing D-xylose during fixed hyperglycemia at 5 mmol/l above fasting levels. Studies were repeated, once with infusion of the GLP-1 receptor antagonist, exendin-(9-39) (Ex-9), and once with saline. RESULTS: The relative increase in insulin secretion after meal ingestion was comparable in diabetic and nondiabetic groups (44 +/- 4% vs. 47 +/- 7%). Blocking the action of GLP-1 suppressed postprandial insulin secretion similarly in the diabetic and nondiabetic subjects (25 +/- 4% vs. 27 +/- 8%). However, Ex-9 also reduced the insulin response to intravenous glucose (25 +/- 5% vs. 26 +/- 7%; diabetic vs. nondiabetic subjects), when plasma GLP-1 levels were undetectable. The appearance of postprandial ingested d-xylose in the blood was not affected by Ex-9. CONCLUSIONS: These findings indicate that in patients with well-controlled diabetes, the relative effects of enteral stimuli and endogenous GLP-1 to enhance insulin release are retained and comparable with those in nondiabetic subjects. Surprisingly, GLP-1 receptor signaling promotes glucose-stimulated insulin secretion independent of the mode of glucose entry. Based on rates of D-xylose absorption, GLP-1 receptor blockade did not affect gastric emptying of a solid meal.

[Effect of acupuncture combined with American ginseng on cardiac function in rats with spleen-deficiency syndrome].

OBJECTIVE: To observe the changes of cardiac function of spleen-deficiency syndrome after joint administration of acupuncture and medication. METHODS: A total of 48 Wistar rats were randomized into normal control, model, medication (American ginseng, AG) and acupuncture + AG groups. Spleen-deficiency syndrome model was established by monophagia method. Rats of medication group were fed with AG decoction (1 ml/100 g), once daily for 10 days. Acupuncture stimulation (uniform reinforcing and reducing method) was applied to bilateral "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) for 1 min (with the needles retained for 20 min), once daily for 10 days. Then, all the rats anesthetized underwent right common carotid artery-left-cardiac catheter and right femoral arterial catheter surgery to accept detection of the left ventricular end diastolic pressure (LVEDP), left ventricular pressure (LVP), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and cardiac output (CO). RESULTS: Compared with normal control group, the levels of SBP, DBP, HR and CO of model group were significantly lower (P < 0.05). In comparison with model group, SBP, DBP, HR and CO of medication and acupuncture + AG groups were markedly higher (P < 0.05). No significant differences were found between medication and acupuncture + AG groups in SBP, DBP, HR, LVEDP, LVP and CO levels (P > 0.05). CONCLUSION: Administration of both acupuncture + AG and AG can effectively improve spleen-deficiency syndrome rats' cardiac function.

Intestinal mucosal dysfunction and infection during remission-induction therapy for acute myeloid leukaemia.

Intestinal barrier function was prospectively examined in the course of a clinical trial evaluating the efficacy and safety of lisofylline for reducing cytotoxic therapy-induced intestinal epithelial damage-related infectious morbidity in patients receiving standard remission-induction therapy for acute myeloid leukaemia. The absorption and permeation of oral D-Xylose, lactulose and mannitol were measured weekly from baseline until marrow recovery in adult recipients of idarubicin plus cytarabine for untreated acute myeloid leukaemia. These studies were correlated with non-haematologic chemotherapy-related toxicities reflecting mucosal damage, including nausea, vomiting, stomatitis, diarrhoea, abdominal pain and systemic infection. D-xylose absorption decreased and lactulose:mannitol ratio reflecting intestinal permeability increased from baseline until the second and third week after the beginning of the treatment followed by recovery. These measures correlated with infection rates, nausea, vomiting, diarrhoea and increased blood product utilization. Lisofylline was associated with increased intestinal permeability, nausea, vomiting and infection-related morbidity despite a reduction in the duration of neutropaenia. These surrogates of intestinal barrier function correlated well with clinically important outcomes despite the failure to demonstrate reduced morbidity with lisofylline and represent useful objective outcome measurements for future clinical trials of products for the amelioration of the effects of cytotoxic therapy on the intestinal mucosa.

Use of the D-xylose absorption test to measure abomasal emptying rate in healthy lactating Holstein-Friesian cows and in cows with left displaced abomasum or abomasal volvulus.

We determined the abomasal emptying rates of Holstein-Friesian cows at different stages of lactation, with left displaced abomasum (LDA), or immediately after surgical correction of LDA or abomasal volvulus (AV). D-xylose (0.5 g/kg body weight [BW], 50% solution) was injected into the abomasum in healthy cows (group 1, 4-7 days in milk [DIM], n = 7; group 2, 90-120 DIM, n = 7; group 3, > 300 DIM, n = 7) and in cows with LDA (n = 10; group 4). D-xylose was injected into the abomasum during right flank laparotomy in cows with LDA (n = 22; group 5) and cows with AV (n = 15; group 6). The time to maximal serum D-xylose concentration was used as an index of emptying rate. The abomasal emptying rates for cows in groups 1, 2, and 3 were similar, whereas emptying was slower in cows with LDA and in cows after surgical correction of LDA or AV. The abomasal emptying rate of cows with LDA was slowed to a greater extent immediately after surgery, when compared to the rate obtained before surgery. There was no difference in abomasal emptying rate immediately after surgical correction between cows with LDA or AV. The results indicate that the increased incidence of LDA in the first month of lactation is not associated with an intrinsic decrease in abomasal emptying rate in healthy cows. Our findings also demonstrate that surgical correction further slows the emptying rate in cows with LDA.

Serial transverse enteroplasty is associated with successful short-term outcomes in infants with short bowel syndrome.

BACKGROUND: The serial transverse enteroplasty (STEP) has been shown to improve nutritional indices in an animal model of short bowel syndrome. The aim of this study was to review short-term surgical and nutritional outcomes in the first cohort of infants to undergo the STEP procedure at our institution. METHODS: All patients who underwent the STEP procedure during a 26-month period from February 2002 to March 2004 were reviewed. Paired t tests were used for comparisons between values pre-STEP and post-STEP (P < .05 deemed significant). Data are expressed as mean and range. RESULTS: The STEP was performed on 5 patients, including 1 newborn. The STEP was used as a primary lengthening operation in 4 patients. Intestinal length was significantly increased in all patients with 18 (10-26) stapler applications. There were no perioperative complications and no evidence of intestinal leak or obstruction on routine postoperative contrast study. Nutritional follow-up was available on 3 subjects at 17 (11-26) months post-STEP. Percentage of enteral nutrition was significantly increased in these subjects (P < .05). One subject was fully weaned from total parenteral nutrition 6 weeks after the STEP, and bilirubin in another patient with profound cholestasis who had been listed for liver-small bowel transplant normalized after the STEP. An additional patient, with established cirrhosis before operation, underwent successful liver-small bowel transplantation 8 months after intestinal lengthening. CONCLUSION: The STEP procedure is a simple bowel-lengthening procedure with promising early surgical and nutritional outcomes. Further data from a multicenter registry are needed to demonstrate its long-term efficacy.

Absorption of D(+)-xylose, cobalamin, and folic acid after autologic-allotopic ileum mucosa transplantation in beagles.

BACKGROUND/PURPOSE: Ileum mucosa transplantation in a demucosed colon coat was developed as a new method for small bowel elongation. In an animal model, the authors investigated the absorptive capacity of the transplanted mucosa for D(+)-xylose, cobalamin (vitamin B12), and folic acid. METHODS: Ileum mucosa was transplanted in a vascularized demucosed segment of transverse colon in 18 beagle dogs. The colon coat-ileum mucosa complex then was integrated in the ileal continuity. Absorptive capacity for D(+)-xylose, cobalamin, and folic acid was measured before and 4 weeks after transplantation. The results were compared and analyzed with the Students' t test for matched pairs. All determined blood values with P values less than.05 were considered to show a significant reduction in the absorptive capacity of the transplanted ileum mucosa. RESULTS: Fifteen minutes after application there was no significant difference in the absorption of D(+)-Xylose and cobalamin between normal and transplanted ileum mucosa (P >.1). Absorption of folic acid in the transplanted segment was lower but not significant (P <.1). After 30 minutes D(+)-xylose and cobalamin again showed no difference between the absorptive capacity of normal and transplanted ileum mucosa (P >.1), whereas folic acid continued with the tendency toward an impaired absorption (P <.1). However, after 60 minutes, the difference of the absorptive capacity of the transplanted ileum mucosa was significant (P <.05) for folic acid. D(+)-xylose showed a tendency for an impaired uptake (P <.1), whereas absorption of cobalamin did not differ significantly after transplantation (P >.1). CONCLUSIONS: Experimental autologic-allotopic ileum mucosa transplantation is a feasible new method for small bowel elongation in an animal model. Examination of the absorptive capacity of the transplanted ileum mucosa showed a normal uptake for cobalamin, while there was an impaired absorption of D(+)-xylose and folic acid.

Intestinal morphology, epithelial cell proliferation, and absorptive capacity in neonatal calves fed milk-born insulin-like growth factor-I or a colostrum extract.

Concentrations of nonnutritional factors, such as insulin-like growth factor-I (IGF-I), in bovine colostrum are high and can modulate neonatal gastrointestinal tract development and function. In neonatal calves, we have investigated effects on intestinal epithelial cell morphology, proliferation, and absorption of feeding milk-born human IGF-I (hIGF-I) or a bovine colostrum extract. Calves were fed a milk-based formula containing amounts of nutrients comparable to colostrum for the first 3 d and a milk replacer from d 4 on. Formula and milk replacer contained only traces of nonnutritional factors. In experiment 1, supraphysiological amounts of hIGF-I (3.8 mg/L formula; secreted by transgenic rabbits with their milk) were added to the formula. Xylose appearance in blood (after feeding xylose on d 5) and intestinal traits (after euthanasia on d 8) did not differ between groups. In experiment 2, an extract of first-milked bovine colostrum that provided physiological amounts of IGF-I (0.50, 0.15, and 0.09 mg of IGF-I/L formula on d 1, 2, and 3, respectively, and 0.09 mg of IGF-I/L milk replacer on d 4) was added to formula or milk replacer. Plasma xylose concentration in the control group was transiently higher than in calves fed the colostrum extract. On d 5 (after euthanasia), villus circumferences and heights in small intestine, and epithelial cell proliferation rate in intestine were higher in calves fed the colostrum extract than in controls. In conclusion, orally administered hIGF-I from transgenic rabbits had no effect on the intestinal tract. However, feeding a bovine colostrum extract enhanced intestinal villus size, although it appeared to transiently decrease the absorptive capacity.

Physiologic response to a protein, carbohydrate, fat meal in patients with human immunodeficiency virus who underwent small intestinal enteropathy as characterized by a kinetic model of D-xylose absorption.

PURPOSE: Small intestinal human immunodeficiency virus enteropathy is characterized by profound absorptive dysfunction unrelated to histology or pathogens. Frequently an attempt is made to compensate for this intestinal failure by supplementing nutrient intake with nourishing liquid meals. It is not known how the diminished absorptive function in these patients will respond to this intake. With the use of a D-xylose kinetic model of absorption, we determined the absorptive response of patients with small intestinal enteropathy to an isotonic liquid feeding. METHODS: Seven male patients with acquired immunodeficiency syndrome (AIDS), diarrhea, weight loss, and no detectable pathogens (stool studies and duodenal biopsy) were enrolled. After an overnight fast, the patients were studied on three separate days. On day 1, the patients received 15 g oral D-xylose. On day 2, 10 g i.v. D-xylose was given. On day 3, 15 g oral D-xylose was again given along with 250 mL of a liquid polymeric isotonic diet. Serum and urine collections were obtained to calculate the kinetic rate constants and extent of D-xylose absorption. RESULTS: Mean values for the rate constant for absorption of D-xylose, Ka, (0.26/h; N > 0.65) and the rate constant for nonabsorptive loss, K0' (2.47/h; N < 0.353) were very abnormal before the meal. Mean K0 improved (decreased to 0.66), but Ka and bioavailability, F, did not have a statistically significant change after the meal. The improvement in mean K0 with the meal was much more pronounced in the five subjects with high K0 values before the meal (without meal 3.22: with meal 0.67; p < .05). CONCLUSIONS: (1) An isotonic liquid polymeric diet leads to less nonabsorptive loss of D-xylose, but does not affect the extent of D-xylose absorption in this group as a whole. This is probably due to the meal slowing gastric emptying. (2) Improvement in nonabsorptive loss with a meal is most pronounced when there is excessive nonabsorptive loss, K0, without a meal. (3) Improvement in nonabsorptive losses with a meal might predict which patients will benefit from antimotility agents and continued feedings vs those requiring i.v. hyperalimentation.

Cytotoxic therapy-induced D-xylose malabsorption and invasive infection during remission-induction therapy for acute myeloid leukemia in adults.

PURPOSE: To study the sequential changes in the intestinal absorption of an oral pentose probe, D-xylose, in patients receiving therapy for untreated acute myeloid leukemia (AML), and to correlate these changes to infectious morbidity. PATIENTS AND METHODS: Serial D-xylose absorption studies were conducted in 110 consecutive adult patients admitted to a university-affiliated tertiary care hospital for remission-induction therapy for untreated newly diagnosed AML. Serial serum D-xylose levels were obtained 1 hour after a 5-g oral dose of D-xylose at baseline and weekly for 4 weeks until marrow recovery. These results were correlated with invasive infection using multivariate techniques. RESULTS: The mean (+/- SEM) serum D-xylose levels were 0.88 +/- 0.03, 0.69 +/- 0.03, 0.58 +/- 0.02, 0.53 +/- 0.02, and 0.73 +/- 0.02 mmol/L at baseline and weeks 1 to 4, respectively (P < .0001, analysis of variance [AN-OVA]). Time to malabsorption varied with induction regimen (P = .007, log-rank test). Bloodstream infections during week 2 correlated with malabsorption (P = .007). Neutropenic enterocolitis correlated independently with induction regimen (P = .009), malabsorption at week 2 (P = .02), and the development of candidemia (P = .005). Hepatosplenic fungal infection correlated with induction regimen (P = .03), malabsorption at week 2 (P = .02), and fever at diagnosis (P = .003). Malabsorption was unrelated to the duration of severe neutropenia and the administration of parenteral nutrition. CONCLUSION: Serial D-xylose absorption studies in subjects with AML produced a characteristic profile of cytotoxic therapy-related damage to the functional integrity of the intestinal epithelium that was regimen dependent, myelosuppression independent, and predictive for invasive infectious complications. Further study to validate these observations appears warranted.