Mechanisms of Gegen Qinlian Pill to ameliorate irinotecan-induced diarrhea investigated by the combination of serum pharmacochemistry and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine suggests the use of natural extracts and compounds is a promising strategy to prevent irinotecan (CPT-11)-induced gut toxicity and resulting diarrhea. Previous work from our lab indicated the protective effect of Gegen Qinlian decoction; given this, we further speculated that Gegen Qinlian Pill (GQP) would exhibit similar therapeutic effects. The effective material basis as well as potential mechanisms underlying the effect of GQP for the treatment of CPT-11-induced diarrhea have not been fully elucidated. AIM OF THE STUDY: The application of natural extracts or compounds derived from Chinese medicine is deemed to a promising strategy to prevent irinotecan (CPT-11)-induced gut toxicity. The aim of this study was to investigated the beneficial effects of GQP on CPT-11-induced gut toxicity and further explored its anti-diarrheal mechanism. METHODS: First, the beneficial effect of GQP in alleviating diarrhea in mice following CPT-11 administration was investigated. We also obtained the effective ingredients in GQP from murine serum samples using HPLC-Q-TOF-MS analysis. Based on these active components, we next established an interaction network linking "compound-target-pathway". Finally, a predicted mechanism of action was obtained using in vivo GQP validation based on Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS: A total of 19, GQP-derived chemical compounds were identified in murine serum samples. An interaction network linking "compound-target-pathway" was then established to illuminate the interaction between the components present in serum and their targets that mitigated diarrhea. These results indicated GQP exerted a curative effect on diarrhea and diarrhea-related diseases through different targets, which cumulatively regulated inflammation, oxidative stress, and proliferation processes. CONCLUSION: Taken together, this study provides a feasible strategy to elucidate the effective constituents in traditional Chinese medicine formulations. More specifically, this work detailed the basic pharmacological effects and underlying mechanism behind GQP's effects in the treatment of CPT-11-induced gut toxicity.

Prevalence and clinical relevance of hypercobalaminaemia in dogs and cats.

Hypocobalaminaemia is common in dogs and cats with exocrine pancreatic insufficiency and/or chronic enteropathy. While hypocobalaminaemia has been extensively studied, naturally-occurring serum hypercobalaminaemia (i.e. without supplementation) might be an underestimated finding in small animal medicine. Studies in human medicine have associated hypercobalaminaemia with neoplastic, hepatic and renal disease. Medical records of all dogs and cats with serum cobalamin concentration measurements (2007-2019) were retrospectively analysed; any that had received supplemental cobalamin were excluded from the analysis. Of 654 dogs, 3% (n = 21) were hypercobalaminaemic (median serum cobalamin concentration, 1307 ng/L [965 pmol/L]; range, 914-3561 ng/L [675-2628 pmol/L]). Chronic gastrointestinal signs were common in hypercobalaminaemic dogs (48%). Two of the 21 hypercobalaminaemic dogs were diagnosed with hypoadrenocorticism. Of 323 cats, 11% (n = 34) were hypercobalaminaemic (median serum cobalamin concentration, 1713 ng/L [1264 pmol/L]; range, 1370-3107 ng/L [1011-2293 pmol/L]). The following comorbidities were diagnosed in hypercobalaminaemic cats: chronic enteropathy, 65% (n = 22); acute or chronic pancreatitis, 24% (n = 8); cholangiohepatopathy, 18% (n = 6); gastric lymphoma, 6% (n = 2); and 3% hyperthyroidism (n = 1). Naturally-occurring increased serum cobalamin concentrations occurred infrequently in cats and even less often in dogs. Since hypercobalaminaemia can occur in dogs and cats with severe inflammatory, immune-mediated, and neoplastic conditions, it should not be ignored.

Effect of acupuncture on hormone level in patients with gastrointestinal dysfunction after general anesthesia: A study protocol for a randomized controlled trial.

BACKGROUND: Postoperative gastrointestinal dysfunction (PGD) refers to one of the common postoperative complications. Acupuncture can facilitate the recovery of PGD, whereas no therapeutic schedule of acupuncture has been internationally recognized for treating PGD. In the present study, a scientific trial protocol has been proposed to verify the feasibility of acupuncture in treating gastrointestinal dysfunction after laparoscopic cholecystectomy under general anesthesia. We conduct this protocol to investigate whether acupuncture recovery gastrointestinal dysfunction by influencing the expression of gastrointestinal hormone. METHOD: The present study refers to a randomized, evaluator blinded, controlled, multi-center clinical trial; it was designed complying with the Consolidated Standards of Reporting Trials (CONSORT 2010) as well as the Standard for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA). The subjects will be taken from the inpatients having undergone laparoscopic surgery of Mianyang Affiliated Hospital of Chengdu University of traditional Chinese medicine, Mianyang Third Hospital and Mianyang Anzhou Hospital. Based on the random number yielded using SPSS 25.0 software, the qualified subjects will be randomly classified to the experimental group and the control group. Therapies will be performed 30 min once after operation, the experimental group will be treated with acupuncture, while the control group will receive intravenous injection of granisetron. The major outcome will be the time to first flatus, and the secondary outcomes will include the time to first defecation, abdominal pain, dosage of analgesia pump, abdominal distention, nausea, vomiting, gastrointestinal hormone, as well as mental state. The efficacy and safety of acupuncture will be also assessed following the principle of Good Clinical Practice (GCP). DISCUSS: A standardized and scientific clinical trial is conducted to assess the efficacy and safety of acupuncture for gastrointestinal dysfunction after laparoscopic cholecystectomy under general anesthesia. The aim is to objectively evidence and improves the clinical practice of acupoint prescription, as an attempt to promote the clinical application of this technology.

A Purported Detoxification Supplement Does Not Improve Body Composition, Waist Circumference, Blood Markers, or Gastrointestinal Symptoms in Healthy Adult Females.

Numerous popular "detoxification" supplements claim to promote the removal of harmful compounds from the body, thereby alleviating gastrointestinal symptoms, improving body composition, and enhancing overall health. The present double-blind, randomized, placebo-controlled trial was conducted to examine the effects of a purported detoxification supplement in healthy young adult females. Participants were randomly assigned to consume a multi-ingredient supplement or placebo daily for four weeks. The supplement contained 1,350 mg/serving of a proprietary blend of papaya leaf, cascara sagrada bark, slippery elm bark, peppermint leaf, red raspberry leaf, fenugreek seed, ginger root, and senna leaf. Body composition, waist circumferences, symptoms of gastrointestinal distress, and blood safety markers were evaluated before and after supplementation. Twenty-two participants completed the study, and data were analyzed via two-way mixed ANOVA and t tests. No beneficial or harmful effects of supplementation were found for body composition, waist circumference, gastrointestinal symptoms, or blood markers. These results indicate that consuming a commercially available dietary supplement that purportedly provides detoxification and body composition benefits is apparently safe in healthy young adult females but does not provide any beneficial effects for body composition or gastrointestinal symptoms.

Effects of 6 Weeks of Parenteral Cobalamin Supplementation on Clinical and Biochemical Variables in Cats with Gastrointestinal Disease.

BACKGROUND: Effects and duration of commonly used protocols for cobalamin (Cbl) supplementation on cellular Cbl deficiency have not been determined in hypocobalaminemic cats. HYPOTHESIS/OBJECTIVES: To evaluate effect of Cbl supplementation on clinical signs, serum and urine methylmalonic acid (MMA) concentrations over 16 weeks. ANIMALS: Twenty client-owned hypocobalaminemic cats with enteropathy. METHODS: Prospective study. Serum Cbl and serum and urine MMA concentrations were determined prospectively in cats at enrollment (t0), immediately before (t6), and 4 (t10) and 10 weeks (t16) after 6th Cbl injection (250 µg, IM q 7 days). Clinical signs severity (activity, appetite, vomiting, diarrhea, body weight) graded at each time point and expressed as clinical disease activity score. RESULTS: Clinical disease activity score decreased during supplementation and increased after treatment discontinuation. Median serum Cbl concentration increased significantly from t0 (111 pmol/L, range 111-212) to t6 (2,332.5 pmol/L, range 123-22,730) (P < 0.01). Values at t10 were 610.5 pmol/L (range, 111-2,527) and 180.5 pmol/L (range, 111-2,262) at t16 (P < 0.01). Median baseline serum MMA concentration (372 µmol/L, range 0.39-147,000) decreased significantly to 1.62 µmol/L (range, 0.18-806) at t6 (P < 0.01) and gradually increased to 5.34 µmol/L (range, 0.13-1,730) at t10 and 189 µmol/L (range, 0.4-983) at t16. Similar, nonsignificant, pattern observed for urine MMA concentration. Serum and urine MMA concentrations had not normalized in 12 and 6 cats, respectively, at t6. CONCLUSION AND CLINICAL IMPORTANCE: The Cbl supplementation protocol used here did not lead to complete normalization of cellular Cbl deficiency in all examined cats, and biochemical improvements were transient.

Vitamin D Status and Bone Mineral Density in Children with Inflammatory Bowel Disease Compared to Those with Functional Abdominal Pain.

Low vitamin D has been implicated in reduced bone mineral density (BMD) in children with inflammatory bowel disease (IBD). Our study aimed to evaluate differences in serum 25-hydroxyvitamin D (25[OH]D) and total body less head (TBLH) BMD z-scores in children with Crohn's disease (CD), ulcerative colitis (UC), and those with abdominal pain-related functional gastrointestinal disorder (AP-FGID) as the control group. We also examined the correlation between serum 25(OH)D and TBLH BMD z-score, and factors that affect each of these parameters. A total of 105 children were included and divided into 3 groups: AP-FGID (n = 45), CD (n = 43), and UC (n = 17). Among the 3 study groups, TBLH BMD z-scores were found to be significantly different (0.5 ± 0.8 in CD vs. 0.1 ± 0.8 in UC vs. -0.1 ± 1.1 in FGID; P = 0.037), despite similar levels of serum 25(OH)D. Within each study group, correlation between serum 25(OH)D and TBLH BMD z-score was not observed. Factors found to affect the TBLH BMD z-score were sex (P = 0.018), age (P = 0.005) and serum hemoglobin (P = 0.041), while factors influencing serum 25(OH)D were sex (P = 0.018), CD with reference to AP-FGID (P = 0.020), and serum phosphorus (P = 0.018). Based on our results, vitamin D is a relatively small contributor to bone loss in pediatric IBD and clinicians should consider female sex, older age, and low hemoglobin as risk factors for low BMD in children with IBD.

Lower levels of vitamin A are associated with increased gastrointestinal graft-versus-host disease in children.

Vitamin A promotes development of mucosal tolerance and enhances differentiation of regulatory T cells. Vitamin A deficiency impairs epithelial integrity, increasing intestinal permeability. We hypothesized that higher vitamin A levels would reduce the risk of graft-versus-host disease (GVHD) through reduced gastrointestinal (GI) permeability, reduced mucosal injury, and reduced lymphocyte homing to the gut. We tested this hypothesis in a cohort study of 114 consecutive patients undergoing allogeneic stem cell transplant. Free vitamin A levels were measured in plasma at day 30 posttransplant. GI GVHD was increased in patients with vitamin A levels below the median (38% vs 12.4% at 100 days, P = .0008), as was treatment-related mortality (17.7% vs 7.4% at 1 year, P = .03). Bloodstream infections were increased in patients with vitamin A levels below the median (24% vs 8% at 1 year, P = .03), supporting our hypothesis of increased intestinal permeability. The GI mucosal intestinal fatty acid-binding protein was decreased after transplant, confirming mucosal injury, but was not correlated with vitamin A levels, indicating that vitamin A did not protect against mucosal injury. Expression of the gut homing receptor CCR9 on T-effector memory cells 30 days after transplant was increased in children with vitamin A levels below the median (r = -0.34, P = .03). Taken together, these data support our hypothesis that low levels of vitamin A actively promote GI GVHD and are not simply a marker of poor nutritional status or a sicker patient. Vitamin A supplementation might improve transplant outcomes.

Multicomponent, multitarget integrated adjustment - Metabolomics study of Qizhiweitong particles curing gastrointestinal motility disorders in mice induced by atropine.

ETHNOPHARMACOLOGICAL RELEVANCE: Qizhiweitong particles (QZWT) which is derived from the Sinisan decoction in Shang Han Za Bing Lun, composed of Bupleurum chinenis, Paeonia obovata, Citrus aurantium L., Glycyrrhiza uralensis Fisch., Cyperus rotundus and Rhizoma Corydalis is a traditional Chinese medicine (TCM) treating gastrointestinal diseases. It have been used in clinical for years. It have been used in clinical for years. According to previous research, Bupleurum chinenis, Citrus aurantium, Cyperus rotundus in QZWT play the role of promoting gastric peristalsis, which consist of complex chemical constituents. The aim of this study is to probe the multiple effective components with gastrointestinal prokinetic efficacy in QZWT and investigate the multitarget integrated adjustment mechanism of QZWT curing atropine-induced gastrointestinal motility dysfunction mice. MATERIALS AND METHODS: One hundred and thirty two male mice were randomly divided into 11 groups, including control group, model group, Domperidone group, Mosapride group, QZWT group and six components groups. With gastric retention rate, rate of small intestine propulsion, serum content of GAS and MTL as indexes to evaluate the curing effect on gastrointestinal movement disorders caused by atropine in mice. A serum metabonomics method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) had been established to investigate the mechanism of QZWT and these components, and PCA and PLS-DA have been used to distinguish different groups and found potential biomarkers. RESULTS: Four components from six present good prokinetic effects, including Bupleurum Polysaccharide, Citrus aurantium flavonoid, Citrus aurantium essential oil and Cyperus rotundus flavonoids. These components and QZWT regulate 5 potential biomarkers in the body, and primarily involved in 5 metabolic pathways. These potential biomarkers possess direct or indirect connections, each biomarker regulated by multiple components, each component adjusting multiple targets, and QZWT is nearly the sum of its components. CONCLUSIONS: This experiment deepened our understanding of insufficient gastrointestinal dynamics, confirmed that QZWT treating gastrointestinal disorders was through multicomponent, multitarget ways. These results fully reflect the multiple targets synergy characteristics of TCM.

The role of vitamin D in reducing gastrointestinal disease risk and assessment of individual dietary intake needs: Focus on genetic and genomic technologies.

With the endogenous formation of vitamin D being significantly curtailed because of public awareness of skin cancer dangers, attention is turning to dietary sources. Cumulative evidence has implicated vitamin D deficiency in increasing susceptibility to various gastrointestinal disorders, including colorectal cancer, inflammatory bowel diseases, diverticulitis, and irritable bowel syndrome. There is also reason to suggest adjunct vitamin D therapy for such diseases. Although there is justification for increasing vitamin D intake overall, optimal intakes will vary among individuals. Genomic technologies have revealed several hundreds of genes associated with vitamin D actions. The nature of these genes emphasizes the potentially negative implications of modulating vitamin D intakes in the absence of complementary human genetic and genomic data, including information on the gut microbiome. However, we are not yet in a position to apply this information. Genomic data (transcriptomics, metabolomics, proteomics, and metagenomics) could provide evidence that vitamin D sufficiency has been achieved. We suggest that there is an increasingly strong case for considering the more widespread use of vitamin D fortified foods and/or dietary supplements to benefit gastrointestinal health. However, intake levels might beneficially be informed by personalized genetic and genomic information, for optimal disease prevention and maintenance of remission.

Electroacupuncture decreases the urinary bladder pressure in patients with acute gastrointestinal injury.

The present study investigates the effects of electroacupuncture (EA) on urinary bladder pressure (UBP) in patients with acute gastrointestinal injury (AGI). Twenty patients with AGI admitted to the First Hospital of Jiaxing intensive care unit from December 2011 to June 2013 were evaluated. Conventional group patients (n = 10) were administered moderate enteral nutritional support, and electroacupuncture group patients (n = 10) were administered enteral nutritional support followed by EA at bilateral Zusanli (ST-36), Shangjuxu (ST-37), Hegu (LI-4), and QuChi (LI-11) acupoints. UBP was then measured every 6 h and the serum creatinine once daily for 7 days. There were no statistically significant patient demographic differences in the study groups (P > 0.05). The initial UBP of both patient groups was ≥12 mmHg. On days 6 and 7, the UBP significantly decreased in the EA group compared to the conventional group (P < 0.05). The serum creatinine concentration on day 7 was significantly lower in the EA group than in the conventional group (P < 0.05). Based on these results, electroacupuncture contributed to gastrointestinal motility recovery in patients with AGI. This procedure may reduce UBP and provide organ-protective effects in AGI patients.

Clinical effects of the new phosphorus binder, bixalomer in hemodialysis patients switched from sevelamer hydrochloride.

It has been reported that sevelamer hydrochloride, which is often used as a polymer phosphorus (P) binder for managing serum P concentration in dialysis patients, causes gastrointestinal adverse effects such as constipation, etc. The reason for this is thought to be that sevelamer hydrochloride has high water absorption, causing it to absorb water and swell in the gastrointestinal tract. In June 2012, the new polymer P binder bixalomer was launched in Japan. Since bixalomer has low swelling due to water absorption, it can be expected to alleviate adverse effects in the gastrointestinal system. In our study, for 21 cases of maintenance hemodialysis patients undergoing treatment with sevelamer hydrochloride at our hospital, the P binder was switched from sevelamer hydrochloride to the same dosage of bixalomer, and the concentrations of serum P, corrected calcium (Ca) and whole parathyroid hormone (PTH) before and one month after the switch were compared. In addition, gastrointestinal symptoms (acid reflux, abdominal pain, indigestion, diarrhea and constipation) were evaluated before and after the switch using a questionnaire based on the Japanese version of the Gastrointestinal Symptom Rating Scale (GSRS). By switching to bixalomer, serum P concentration was significantly reduced (P=0.024), but there were no significant changes observed for serum corrected Ca and whole PTH. Furthermore, there were no significant changes observed for all five of the evaluation items of the GSRS, before and after the switch. These results suggest that although bixalomer can more potently reduce the serum P concentration than sevelamer hydrochloride, there were no significant differences in the effects of both P binders on the gastrointestinal symptoms.

Treatment of hyperphosphatemia with bixalomer in Japanese patients on long-term hemodialysis with gastrointestinal symptoms.

Bixalomer (Bix) is an amine-functional polymer, non-calcium-containing phosphate (P) binder, and has been clinically available in Japan recently. Bix is expected to cause fewer gastrointestinal (GI) side-effects as compared with sevelamer hydrochloride (SH), because of less expansion of Bix in the GI tract. In this prospective observational study, we evaluated changes in GI symptoms by the Gastrointestinal Symptom Rating Scale (GSRS) score in long-term hemodialysis (HD) outpatients with SH-associated GI symptoms who switched to Bix from SH. A total of 114 patients (age 63.7±10.8 year (mean±SD), female 65.5%, HD vintage 11.2±8.6 years, diabetes mellitus 27.4%) were enrolled. The GSRS score was checked at 0 and 12 weeks after the start of Bix. Bix was started at the initial dose of 750 mg/day, and then was titrated. Serum albumin, P and corrected calcium levels did not significantly change during Bix treatment. However, serum low-density lipoprotein-cholesterol and bicarbonate levels significantly increased during Bix treatment (P<0.001). In GSRS scores, total and domain-specific scores, including constipation, diarrhea, reflux and abdominal pain were significantly reduced at 0, 4, 12 and 24 weeks as compared with those at 0 weeks (P<0.05). This study shows that Bix was well tolerated and managed hyperphosphatemia effectively after switching from SH in Japanese patients on long-term HD. In addition, Bix might be less often associated with GI symptoms as compared with SH.

Administration of exogenous acylated ghrelin or rikkunshito, an endogenous ghrelin enhancer, improves the decrease in postprandial gastric motility in an acute restraint stress mouse model.

BACKGROUND: Physical or psychological stress causes functional disorders in the upper gastrointestinal tract. This study aims to elucidate the ameliorating effect of exogenous acylated ghrelin or rikkunshito, a Kampo medicine which acts as a ghrelin enhancer, on gastric dysfunction during acute restraint stress in mice. METHODS: Fasted and postprandial motor function of the gastric antrum was wirelessly measured using a strain gauge force transducer and solid gastric emptying was detected in mice exposed to restraint stress. Plasma corticosterone and ghrelin levels were also measured. To clarify the role of ghrelin on gastrointestinal dysfunction in mice exposed to stress, exogenous acylated ghrelin or rikkunshito was administered, then the mice were subjected to restraint stress. KEY RESULTS: Mice exposed to restraint stress for 60 min exhibited delayed gastric emptying and increased plasma corticosterone levels. Gastric motility was decreased in mice exposed to restraint stress in both fasting and postprandial states. Restraint stress did not cause any change in plasma acylated ghrelin levels, but it significantly increased the plasma des-acyl ghrelin levels. Administration of acylated ghrelin or rikkunshito improved the restraint stress-induced delayed gastric emptying and decreased antral motility. Ameliorating effects of rikkunshito on stress-induced gastric dysfunction were abolished by simultaneous administration of a ghrelin receptor antagonist. CONCLUSIONS & INFERENCES: Plasma acylated/des-acyl ghrelin imbalance was observed in acute restraint stress. Supplementation of exogenous acylated ghrelin or enhancement of endogenous ghrelin signaling may be useful in the treatment of decreased gastric function caused by stress.

Vitamin A deficiency is associated with gastrointestinal and respiratory morbidity in school-age children.

Infection is an important cause of morbidity throughout childhood. Poor micronutrient status is a risk factor for infection-related morbidity in young children, but it is not clear whether these associations persist during school-age years. We examined the relation between blood concentrations of micronutrient status biomarkers and risk of gastrointestinal and respiratory morbidity in a prospective study of 2774 children aged 5-12 y from public schools in Bogotá, Colombia. Retinol, zinc, ferritin, mean corpuscular volume, hemoglobin, erythrocyte folate, and vitamin B-12 concentrations were measured in blood at enrollment into the cohort. Children were followed for 1 academic year for incidence of morbidity, including diarrhea with vomiting, cough with fever, earache or ear discharge with fever, and doctor visits. Compared with adequate vitamin A status (≥30.0 µg/dL), vitamin A deficiency (<10.0 µg/dL) was associated with increased risk of diarrhea with vomiting [unadjusted incidence rate ratio (IRR): 2.17; 95% CI: 0.95, 4.96; P-trend = 0.03] and cough with fever (unadjusted IRR: 2.36; 95% CI: 1.30, 4.31; P-trend = 0.05). After adjustment for several sociodemographic characteristics and hemoglobin concentrations, every 10 µg/dL plasma retinol was associated with 18% fewer days of diarrhea with vomiting (P < 0.001), 10% fewer days of cough with fever (P < 0.001), and 6% fewer doctor visits (P = 0.01). Every 1 g/dL of hemoglobin was related to 17% fewer days with ear infection symptoms (P < 0.001) and 5% fewer doctor visits (P = 0.009) after controlling for sociodemographic factors and retinol concentrations. Zinc, ferritin, mean corpuscular volume, erythrocyte folate, and vitamin B-12 status were not associated with morbidity or doctor visits. Vitamin A and hemoglobin concentrations were inversely related to rates of morbidity in school-age children. Whether vitamin A supplementation reduces the risk or severity of infection in children over 5 y of age needs to be determined.

Vitamin D deficiency in children with a chronic illness-seasonal and age-related variations in serum 25-hydroxy Vitamin D concentrations.

INTRODUCTION: Children and adolescents with a chronic illness have potential risk factors for vitamin D deficiency. An optimal vitamin D status might have multiple health effects. This study evaluated vitamin D status and its association with age, gender, and season in a large cohort of chronically ill Finnish patients at a tertiary pediatric outpatient clinic. A cross-sectional register-based study was carried out, involving altogether 1351 children (51% boys, age range 0.2-18 years), who visited the outpatient clinic during 2007-2010 and had their vitamin D status (S-25-OHD) determined. A post-doc analysis was conducted to identify predisposing and preventing factors for vitamin D deficiency. RESULTS: Almost half (47%) of the S-25-OHD values were consistent with subnormal vitamin D status (S-25-OHD <50 nmol/L) while only 12% were >80 nmol/L. Age and season were the most important determinants for S-25-OHD concentration. Mean S-25-OHD concentration differed between age groups (Kruskal-Wallis; p<0.001), adolescents being at highest risk for vitamin D insufficiency. Young age and vitamin D supplementation were preventive factors for deficiency, while non-Finnish ethnic background was a predisposing factor. S-25-OHD showed significant seasonal variation in children older than 6 years. In the whole cohort, S-25-OHD was on average 13 nmol/L higher in summer than in winter, and the prevalence of vitamin D deficiency ( =  S-25-OHD <37.5 nmol/l) varied from 11% in summer to 29% in winter. CONCLUSIONS: The finding that almost half of the studied Finnish children with a chronic illness had suboptimal vitamin D status is alarming. Inferior vitamin D status was noted in adolescents compared with younger children, suggesting that imbalance between intake and requirement evolves with age. Although less common during summer, subnormal vitamin D status was still observed in 28% of those evaluated in summer. Clinicians should identify individuals at risk and actively recommend vitamin D supplementation.

Copper levels in cholestatic infants on parenteral nutrition.

BACKGROUND: Copper levels are primarily regulated by biliary excretion. In cholestatic patients, there is a concern that the standard dose of copper in parenteral nutrition (PN) will result in excessive copper levels. This study looked retrospectively at cholestatic infants receiving PN with measured copper levels to ascertain if this is an actual clinical concern. METHODS: All infants from the previous 10 years receiving PN who had a copper level checked and were cholestatic were reviewed. Children with metabolic or liver structural anomalies were excluded from the review. Of the 28 patients found, 26 had gastrointestinal disorders, and 82% of these infants were on the standard PN copper dose (20 µg/kg/d). RESULTS: Only one elevated copper level was found in a child with congenital heart disease, but 13 low levels were found. A smaller number of follow-up copper levels demonstrated that despite cholestasis, some patients require copper supplementation above standard recommendations. CONCLUSION: Cholestasis does not appear to impair copper excretion enough to result in elevated levels. In fact, infants with gastrointestinal disorders may require higher than standard dosing. Monitoring copper levels appears to be necessary to appropriately regulate copper dosing for cholestatic infants receiving PN.

Effect of tangweian jianji on upper gastrointestinal remodeling in streptozotocin-induced diabetic rats.

AIM: To investigate the effect of Tangweian Jianji (TWAJJ) on the biomechanical and morphometrical remodeling of the upper gastrointestinal tract in diabetic rats. METHODS: Diabetes was induced in 27 rats by injecting streptozotocin (40 mg/kg body weight), the animals were then divided into three groups (n = 9 in each group), i.e., diabetic control (DM); high dose (10 g/kg, T1) and low dose (5 g/kg, T2). Another 10 rats acted as normal controls (Control). TWAJJ was administered by gavage once daily. Blood glucose and serum insulin levels were measured. Circumferential length, wall thickness and opening angle were measured from esophageal, duodenal, jejunal and ileal ring segments. The residual strain was calculated from the morphometric data. Step-wise distension was carried out on esophageal and jejunal segments. The obtained data on the length, diameter and pressure changes were then used to calculate the circumferential and longitudinal stresses and strains. Real-time reverse transcription polymerase chain reaction was used to detect the receptor of advanced glycation end-products (RAGE) mRNA level in jejunal tissues. RESULTS: At the end of the experiment, the blood glucose level was significantly higher and the serum insulin level was significantly lower in DM, T1 and T2 groups than in the control group (Glucose: 30.23 ± 0.41 mmol/L, 27.48 ± 0.27 mmol/L and 27.84 ± 0.29 mmol/L vs 5.05 ± 0.04 mmol/L, P = 1.65 × 10(-16), P = 5.89 × 10(-19) and P = 1.63 × 10(-18), respectively; Insulin: 1.47 ± 0.32 µg/L, 2.66 ± 0.44 µg/L, 2.03 ± 0.29 µg/L and 4.17 ± 0.54 µg/L, P = 0.0001, P = 0.029 and P = 0.025, respectively). However, these levels did not differ among the DM, T1 and T2 groups. The wet weight per unit length, wall thickness and opening angle of esophageal and intestinal segments in the DM group were significantly higher than those in the control group (from P = 0.009 to P = 0.004). These parameters in the T1 group were significantly lower than those in the DM group (wet weight, duodenum: 0.147 ± 0.003 g/cm vs 0.158 ± 0.001 g/cm, P = 0.047; jejunum, 0.127 ± 0.003 g/cm vs 0.151 ± 0.002 g/cm, P = 0.017; ileum, 0.127 ± 0.004 g/cm vs 0.139 ± 0.003 g/cm, P = 0.046; wall thickness, esophagus: 0.84 ± 0.03 mm vs 0.94 ± 0.02 mm, P = 0.014; duodenum: 1.27 ± 0.06 mm vs 1.39 ± 0.05 mm, P = 0.031; jejunum: 1.19 ± 0.07 mm vs 1.34 ± 0.04 mm, P = 0.047; ileum: 1.09 ± 0.04 mm vs 1.15 ± 0.03 mm, P = 0.049; opening angle, esophagus: 112.2 ± 13.2˚ vs 134.7 ± 14.7˚, P = 0.027; duodenum: 105.9 ± 12.3˚ vs 123.1 ± 13.1˚, P = 0.046; jejunum: 90.1 ± 15.4˚ vs 115.5 ± 13.3˚, P = 0.044; ileum: 112.9 ± 13.4˚ vs 136.1 ± 17.1˚, P = 0.035). In the esophageal and jejunal segments, the inner residual stain was significantly smaller and the outer residual strain was larger in the DM group than in the control group (P = 0.022 and P = 0.035). T1 treatment significantly restored this biomechanical alteration (P = 0.011 and P = 0.019), but T2 treatment did not. Furthermore, the circumferential and longitudinal stiffness of the esophageal and jejunal wall increased in the DM group compared with those in the control group. T1, but not T2 treatment, significantly decreased the circumferential wall stiffness in the jejunal segment (P = 0.012) and longitudinal wall stiffness in the esophageal segment (P = 0.023). The mRNA level of RAGE was significantly decreased in the T1 group compared to that in the DM group (P = 0.0069). CONCLUSION: TWAJJ (high dose) treatment partly restored the morphometric and biomechanical remodeling of the upper gastrointestinal tract in diabetic rats.

[The alteration of concentration of essential microelements in blood plasma in children with chronic diseases of gastrointestinal tract and having different body mass].

The article deals with the characteristics of alterations of mineral metabolism indicators in children of various age with chronic diseases ofgastrointestinal tract and having body mass of normal and different surplus degrees. The sample consisted of 127 children aged from 6 to 15 years with chronic gastroduodenitis, pancreatitis and cholecystitis. The concentration of bioelements in plasma was determined using the technique of mass spectrometry with inductively coupled plasma. The study established the increase of concentration of molybdenum 4.3 times, chrome--8.4 times and selenium--1.36 times. The revealed bioelemental misbalance impacts the overall health of children and course of disease and hence has to be accounted in case of application of treatment targeted to the correction of mineral metabolism.

Folate in gastrointestinal health and disease.

OBJECTIVE: Folate has heterogeneous functions and is involved in several activities in both animal and human body. It is an important constituent of our organism, and its bioavailability is mainly dependent from the correct function of our gastrointestinal tract. Our aim is to describe what happens to folate homeostasis in gastrointestinal health and disease, analyzing the alterations of folate metabolism in some specific conditions of intestinal and liver impairment. DISCUSSION: Folate absorption and metabolization involve the small intestine and the liver; in conditions of gastrointestinal tract disease (i.e. celiac disease, liver disease) folate function may be compromised with important consequences on the whole organism. Moreover, folate deficiency may produce gastrointestinal alterations too. For this reason, the gastrointestinal tract could be the responsible but also the victim of folate deficiency. CONCLUSIONS: The presence of folate deficiency should always be assessed in patients with a gastrointestinal disease. Further studies are needed to assess the role of folates in gastrointestinal tract diseases and in other gynecologic, neurologic, psychiatric, cardiovascular, ophthalmic and neoplastic diseases. Folates supplementation could be considered, in the future, as an effective complimentary therapy in several pathologic conditions.

[Influence of enteral nutrition therapy on serum angiogenic growth factors concentrations in children]. / Wplyw zywienia enteralnego na stezenia czynników naczyniowzrostowych w surowicy u dzieci.

INTRODUCTION: Effectiveness of enteral nutrition therapy is not only connected with improvement of the nutritional status of the patient, but also with its strong anti-inflammatory activity. Angiogenic growth factors play an important role in the early stage of inflammation. Vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGF-beta 1) stimulate the angiogenesis and healing processes. The objective of our study was to assess the influence of the enteral nutrition therapy on the vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGF-beta 1) concentrations in serum in children with different diseases of gastro-intestinal tract, in which enteral nutrition therapy is effective method of treatment. MATERIAL AND METHODS: Sixty two children (29 boys, 33 girls, mean age: 12.5 yrs, range: 6-18 yrs) and 25 healthy controls were included into the study. The Crohn's disease group (CD) consisted of 25 patients, ulcerative colitis group (UC)-18 patients, acute pancreatitis (AP) group-12 patients and severe malnutrition (N) group-7 patients. Serum VEGF and TGF-beta 1 concentrations were assessed at baseline, before starting and after 2 and 4 weeks of enteral nutrition therapy using ELISA immunoassays (R and D Systems, USA). RESULTS: Before starting enteral nutrition, we found increased VEGF concentration in CD group (Me = 600 pg/ml) compared to UC group (266.9 pg/ml), AP group (552.6 pg/ml), N group (238.5 pg/ml) and controls (172 pg/ml) (p < 0.05). We found decrease of VEGF concentrations during enteral nutrition in CD, UC and N group and increase in AP at the beginning, followed by decrease to the initial values. Assessing TGF-beta 1, we found its concentration increased before starting enteral nutrition in UC group (37.5 ng/ml) compared to CD group (29.7 ng/ ml) and controls (24.8 ng/ml) (p < 0.05). During enteral nutrition we observed decrease of TGF-beta 1 concentration in UC group and increase in CD group (32,7 ng/ml) and AP group (26,6 ng/ml) (p < 0.05) The best improvement of nutritional status was observed in CD patients compared to N and AP patients. CONCLUSIONS: Differentiation of serum VEGF and TGF-beta 1 concentrations, what was observed in various gastro-intestinal diseases, reflects different mechanisms of enteral nutrition therapy acting on the inflammatory process. The most efficient therapeutic effect was seen in CD, where stimulation of TGF-beta 1 production was observed.