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.

Comparison of the systemic phospholipid profile in dogs diagnosed with idiopathic inflammatory bowel disease or food-responsive diarrhea before and after treatment.

BACKGROUND: Inflammatory bowel disease (IBD) and food-responsive diarrhea (FRD) are common chronic enteropathies in dogs, of which the exact pathogenesis has not been fully understood. In people dyslipidemia has been reported in patients with IBD, and potential therapeutic benefits of polyunsaturated fatty acids (PUFA) in the treatment of IBD have been investigated. Studies on the phospholipid profile in dogs with IBD and FRD are still lacking. AIM: To investigate the systemic phospholipid profile of dogs with IBD or FRD and to evaluate possible differences in phospholipids before and after treatment. METHODS: The phospholipids in whole blood and EDTA plasma of 32 dogs diagnosed with either IBD (n = 16) or FRD (n = 16) were analyzed by hydrophilic interaction liquid chromatography (HILIC) prior to and after initiation of treatment, which included an elimination diet enriched with PUFAs. RESULTS: A clear separation of the phospholipids between whole blood and plasma was demonstrated on principal component analysis plots. In addition to the type of specimen, treatment and disease severity were the most significant factors determining the variance of the phospholipid profile. An increase in lysolipids was observed after treatment. The phosphatidylcholine (PC) species changed from PC 38:4 before treatment to mainly lysophosphatidylcholine 18:0 after treatment. Furthermore, several differences in the abundance of individual phospholipids were identified between dogs with IBD and dogs with FRD and between treatment statuses using random forest analysis. CONCLUSION: Significant variances were identified in the phospholipid profiles of dogs with IBD and FRD. These were particularly determined by type of specimen used, disease severity and treatment status. After treatment, a shift of phospholipid species towards lysophosphatidylcholine 18:0 was observed. Future studies should further investigate the role of lipids in the pathophysiology of IBD and FRD as well as their potential therapeutic benefits.

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.

Antidiarrheal and protein conservative activities of Psidium guajava in diarrheal rats.

OBJECTIVE: Psidium guajava occurs worldwide in tropical and subtropical areas. It has been used to treat inflammation, diabetes, fever, hypertension and ulcers. However, its antidiarrheal and protein conservative activities still need to be investigated. METHODS: Fifty-four male rats were divided into normal and diarrheal rats. The normal rats were divided into 4 groups: control, low-dose P. guajava leaf extract (50 mg/kg), high-dose P. guajava leaf extract (100 mg/kg) and gallic acid. Treatments were administrated orally in 1 mL saline for a 1-month period. The diarrheal rats were divided into 5 groups: desmopressin (0.2 mg/kg) drug, low-dose P. guajava leaf extract (50 mg/kg), high-dose P. guajava leaf extract (100 mg/kg), gallic acid and an untreated control. Doses were given daily for a 1-month period while the untreated control received no treatment. RESULTS: Diarrhea was responsible for an observed decline in kidney weight and serum sodium, potassium and chloride. Further, diarrhea was positively correlated with a significant increase in urine volume, and excretion of electrolytes, serum urea, creatinine and uric acid in the urine. In contrast, there was a proportional increase in the lipid peroxidation value in diarrhea and a significant decline was observed in serum superoxide dismutase, glutathione peroxidase and glutathione levels in diarrhea. Also, diarrhea inhibited blood proteins. The oral intake of P. guajava leaf extract by diarrheal rats restored all of these parameters to near normal levels. High-dose P. guajava leaf extract was more effective than the same compound at a low dose. CONCLUSION: P. guajava leaf extract elicited antidiarrheal and protein conservative effects.

Er Shen Wan extract reduces diarrhea and regulates AQP 4 and NHE 3 in a rat model of spleen-kidney Yang deficiency-induced diarrhea.

INTRODUCTION: Er Shen Wan (ESW), a traditional Chinese medicinal formula comprised of Psoraleae Fructus (Babchi seeds, from Psoralea corylifolia Linn.) and Myristicae Semen (Nutmeg, from Myristica fragrans Houtt.), is widely used to treat spleen-kidney Yang deficiency (SKYD)-induced diarrhea. Previous studies have demonstrated preliminarily that the petroleum ether extract of ESW (ESWP) exhibits significant anti-diarrheal activity. The present study aimed to evaluate the anti-diarrhea activity of ESWP and to explore the underlying mechanisms with respect to fluid metabolism in a rat model of SKYD-induced diarrhea. MATERIALS AND METHODS: A high-performance liquid chromatography-diode array detector (HPLC-DAD) approach was developed and validated for qualitative and quantitative analyses of the main constituents of ESWP. SKYD model rats were established and treated with an effective dose (3.5?g/kg) of the extract for two weeks. Anti-diarrheal activity and stool properties were observed. After the experiment, the appearance and histology of the intestines were evaluated. Serum levels of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were also determined. Furthermore, to characterize the regulation of aquaporin-4 (AQP 4) and Na+/H+ exchanger isoform 3 (NHE 3) in the colon, quantitative real-time RT-PCR (qRT-PCR), immunohistochemistry (IHC) and Western blotting (WB) were employed to detect mRNA and protein expression levels. RESULTS: In the rat models, oral ESWP administration significantly reduced the diarrhea score and the number and weight of wet stools. Jejunal and ileac histological damage was impeded, and the histology score decreased. Serum VIP levels were significantly decreased, in contrast to NPY levels. In addition, AQP 4 and NHE 3 expression levels increased significantly. CONCLUSIONS: These results showed that ESWP's anti-diarrheal effect might at least partially involve the regulation of hormones intimately involved in maintaining fluid and electrolyte levels, as well as by increasing AQP 4 and NHE 3 expression levels and enhancing the absorption of Na+ and water.

Pre-protective effects of dietary chitosan supplementation against oxidative stress induced by diquat in weaned piglets.

The protective effects of chitosan (CS) supplementations on oxidative stress induced by diquat in weaned piglets were investigated. A total of 36 crossbreed piglets with an average live body weight (BW) of 8.80 ± 0.53 kg were weaned at 28 ± 2 days and randomly divided into six dietary treatments (n = 6): control (basal diet), negative control (10 mg diquat/kg BW injected to piglets fed with basal diet), and basal diet treatments containing either 250, 500, 1000, or 2000 mg/kg of CS administered to piglets injected with 10 mg diquat/kg BW. The experiment conducted for 21 days which consisted of pre-starter period (14 days) and starter period (7 days). BW, feed intake, and fecal consistency were monitored. Blood samples were collected to determine antioxidative and immune parameters. CS supplementation improved the growth performance and decreased fecal score of piglets from days 1 to 14. Diquat also induced oxidative stress and inflammatory responses by decreasing the activities of antioxidant and regulating cytokines. But dietary CS alleviated these negative effects induced by diquat that showed decreasing serum concentrations of pro-inflammatory cytokines but increasing activities of antioxidant enzymes and anti-inflammatory cytokines. Results indicated that CS attenuated the oxidative stress of piglets caused by diquat injection.

The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review.

In infants and young children in Sub-Saharan Africa, iron-deficiency anemia (IDA) is common, and many complementary foods are low in bioavailable iron. In-home fortification of complementary foods using iron-containing micronutrient powders (MNPs) and oral iron supplementation are both effective strategies to increase iron intakes and reduce IDA at this age. However, these interventions produce large increases in colonic iron because the absorption of their high iron dose (≥12.5 mg) is typically <20%. We reviewed studies in infants and young children on the effects of iron supplements and iron fortification with MNPs on the gut microbiome and diarrhea. Iron-containing MNPs and iron supplements can modestly increase diarrhea risk, and in vitro and in vivo studies have suggested that this occurs because increases in colonic iron adversely affect the gut microbiome in that they decrease abundances of beneficial barrier commensal gut bacteria (e.g., bifidobacteria and lactobacilli) and increase the abundance of enterobacteria including entropathogenic Escherichia coli These changes are associated with increased gut inflammation. Therefore, safer formulations of iron-containing supplements and MNPs are needed. To improve MNP safety, the iron dose of these formulations should be reduced while maximizing absorption to retain efficacy. Also, the addition of prebiotics to MNPs is a promising approach to mitigate the adverse effects of iron on the infant gut.

Excess iron intake as a factor in growth, infections, and development of infants and young children.

The provision of iron via supplementation or the fortification of foods has been shown to be effective in preventing and treating iron deficiency and iron deficiency anemia in infants and young children. However, iron is a pro-oxidative element and can have negative effects on biological systems even at moderate amounts. An increasing number of studies have reported adverse effects of iron that was given to infants and young-children populations who initially were iron replete. These effects include decreased growth (both linear growth and weight), increased illness (usually diarrhea), interactions with other trace elements such as copper and zinc, altered gut microbiota to more pathogenic bacteria, increased inflammatory markers, and impaired cognitive and motor development. If these results can be confirmed by larger and well-controlled studies, it may have considerable programmatic implications (e.g., the necessity to screen for iron status before interventions to exclude iron-replete individuals). A lack of understanding of the mechanisms underlying these adverse outcomes limits our ability to modify present supplementation and fortification strategies. This review summarizes studies on the adverse effects of iron on various outcomes; suggests possible mechanisms that may explain these observations, which are usually made in clinical studies and intervention trials; and gives examples from animal models and in vitro studies. With a better understanding of these mechanisms, it may be possible to find novel ways of providing iron in a form that causes fewer or no adverse effects even when subjects are iron replete. However, it is apparent that our understanding is limited, and research in this area is urgently needed.

Small-quantity lipid-based nutrient supplements containing different amounts of zinc along with diarrhea and malaria treatment increase iron and vitamin A status and reduce anemia prevalence, but do not affect zinc status in young Burkinabe children: a cluster-randomized trial.

BACKGROUND: We assessed the effects of providing a package of interventions including small-quantity lipid-based nutrient supplements (SQ-LNS) containing 0, 5 or 10 mg zinc and illness treatment to Burkinabe children from 9 to 18 months of age, on biomarkers of zinc, iron and vitamin A status at 18 months and compared with a non-intervention cohort (NIC). METHODS: Using a two-stage cluster randomized trial design, communities were randomly assigned to the intervention cohort (IC) or NIC, and extended family compounds within the IC were randomly assigned to different treatment groups. IC children (n = 2435) were provided with 20 g SQ-LNS/d containing 0, 5 or 10 mg zinc, 6 mg of iron and 400 µg of vitamin A along with malaria and diarrhea treatment. NIC children (n = 785) did not receive the intervention package. At 9 and 18 months, hemoglobin (Hb), zinc, iron and vitamin A status were assessed in a sub-group (n = 404). Plasma concentrations of zinc (pZC), ferritin (pF), soluble transferrin receptor (sTfR) and retinol-binding protein (RBP) were adjusted for inflammation. RESULTS: At baseline, 35% of children had low adjusted pZC (<65 µg/dL), 93% were anemic (Hb <110 g/L), 25% had low adjusted pF (<12 µg/L), 90% had high adjusted sTfR (>8.3 mg/L) and 47% had low adjusted RBP (<0.94 µmol/L), with no group-wise differences. Compared with the NIC, at 18 months IC children had significantly lower anemia prevalence (74 vs. 92%, p = 0.001) and lower iron deficiency prevalence (13% vs. 32% low adjusted pF and 41% vs. 71% high adjusted sTfR, p < 0.001), but no difference in pZC. Mean adjusted RBP was greater at 18 months in IC vs. NIC (0.94 µmol/L vs. 0.86 µmol/L, p = 0.015), but the prevalence of low RBP remained high in both cohorts. Within the IC, different amounts of zinc had no effect on the prevalence of low pZC or indicators of vitamin A deficiency, whereas children who received SQ-LNS with 10 mg zinc had a significantly lower mean pF at 18 months compared to children who received SQ-LNS with 5 mg zinc (p = 0.034). CONCLUSIONS: SQ-LNS regardless of zinc amount and source provided along with illness treatment improved indicators of iron and vitamin A status, but not pZC. TRIAL REGISTRATION: NCT00944281 (July 21, 2009).

Cryptococcus laurentii diarrhea post hematopoietic stem cell transplant.

We report the recent isolation of Cryptococcus laurentii from the feces of a patient with Hodgkin's lymphoma who underwent autologous hematopoietic stem cell transplant (HSCT). The organism was identified using microscopic morphology, cultural characteristics, and biochemical tests including sugar assimilation. Minimum inhibitory concentration of various antifungals was determined by microbroth dilution method. The recovery of pure culture of C. laurentii from stool culture, and the patient's response to treatment with voriconazole support its potential etiological role. To the best of our knowledge, we report the first case of diarrhea caused by C. laurentii in an HSCT recipient.

Serum Cobalamin (Vitamin B12) Concentrations in Rhesus Macaques (Macaca mulatta) and Pigtailed Macaques (Macaca nemestrina) with Chronic Idiopathic Diarrhea.

Chronic diarrhea poses a significant threat to the health of NHP research colonies, and its primary etiology remains unclear. In macaques, the clinical presentation of intractable diarrhea and weight loss that are accompanied by inflammatory infiltrates within the gastrointestinal tract closely resembles inflammatory bowel disease of humans, dogs, and cats, in which low serum and tissue cobalamin (vitamin B12) levels are due to intestinal malabsorption. We therefore hypothesized that macaques with chronic idiopathic diarrhea (CID) have lower serum cobalamin concentrations than do healthy macaques. Here we measured serum cobalamin concentrations in both rhesus and pigtailed macaques with CID and compared them with those of healthy controls. Serum cobalamin levels were 2.5-fold lower in pigtailed macaques with CID than control animals but did not differ between rhesus macaques with CID and their controls. This finding supports the use of serum cobalamin concentration as an adjunct diagnostic tool in pigtailed macaques that present with clinical symptoms of chronic gastrointestinal disease. This use of serum vitamin B12 levels has implications for the future use of parenteral cobalamin supplementation to improve clinical outcomes in this species.

Is there a relationship between low vitamin D and rotaviral diarrhea?

BACKGROUND: For children under 5 years of age, 1700 000 000 episodes of diarrhea are seen worldwide, and death occurs in 700 000 of these cases due to diarrhea. Rotavirus is an important cause of diarrhea in this age group, and many studies have shown that vitamin D plays a pivotal role in the immune system, as well as in antimicrobial peptide gene expression. In addition, lower vitamin D has been correlated with higher rates of infectious diseases such as respiratory tract infection, tuberculosis, and viral infection. METHODS: Seventy patients with rotaviral diarrhea and 67 healthy patients were enrolled in this study. Serum 25-hydroxy vitamin D(3) (25(OH)D(3)), parathormone, calcium, phosphate, alkaline phosphatase, complete blood count parameters, and C-reactive protein were compared between pre-school children hospitalized due to rotaviral diarrhea and healthy children. Additionally, birthweight, feeding habits in the first 6 months of life, vitamin D and multivitamin supplements, and rotaviral vaccinations were also evaluated in each group. RESULTS: There were no differences between the groups with regard to gender and age, but 25(OH)D(3) was significantly different: 14.6 ± 8.7 ng/mL in the rotaviral diarrhea patients versus 29.06 ± 6.51 ng/mL in the health controls (P < 0.001), and serum 25(OH)D(3) <20 ng/mL (OR, 6.3; 95%CI: 3.638-10.909; P < 0.001) was associated with rotaviral diarrhea. CONCLUSIONS: Low vitamin D is associated with rotaviral diarrhea. This is the first study in the literature to show this, and this result needs to be repeated in larger controlled clinical studies.

Effect of short term zinc supplementation on iron status of children with acute diarrhea.

OBJECTIVE: To study the effect of short term (2 wk) zinc supplementation on hemoglobin and iron status of children with acute diarrhea. METHODS: This study was a prospective, open label, single arm interventional trial conducted from June 2008 through October 2009 in a teaching hospital of North India. Three to sixty months old children presenting with acute diarrhea participated in the study. Subjects were supplemented with recommended doses of oral zinc gluconate for 2 wk. Changes in levels of hemoglobin, serum iron, total iron binding capacity, and serum ferritin were the main outcome measures. RESULTS: Sixty-two patients completed the study successfully. The prevalence of anemia before and after 2 wk of zinc supplementation remained unchanged. However, a small decline (p > 0.05) was observed in mean hemoglobin (from 8.95 ± 1.4 to 8.73 ± 1.43 g/dL), serum iron (79.56 ± 45.81 to 78.61 ± 44.41 µg/dL) and ferritin (84.77 ± 45.35 to 83.55 ± 44.10 ng/mL) levels. Total iron binding capacity increased from 331.60 ± 109.72 to 341.30 ± 119.90 µg/dL post supplementation (p > 0.05). CONCLUSIONS: Even though statistically insignificant, the small change observed in the levels of hemoglobin, and indicators of iron status following short term zinc supplementation might assume significance in some settings in developing countries where children receive short courses of zinc repeatedly for frequent diarrheal episodes.

Methylglyoxal induces systemic symptoms of irritable bowel syndrome.

Patients with irritable bowel syndrome (IBS) show a wide range of symptoms including diarrhea, abdominal pain, changes in bowel habits, nausea, vomiting, headache, anxiety, depression and cognitive impairment. Methylglyoxal has been proved to be a potential toxic metabolite produced by intestinal bacteria. The present study was aimed at investigating the correlation between methylglyoxal and irritable bowel syndrome. Rats were treated with an enema infusion of methylglyoxal. Fecal water content, visceral sensitivity, behavioral tests and serum 5-hydroxytryptamine (5-HT) were assessed after methylglyoxal exposure. Our data showed that fecal water content was significantly higher than controls after methylglyoxal exposure except that of 30 mM group. Threshold volumes on balloon distension decreased in the treatment groups. All exposed rats showed obvious head scratching and grooming behavior and a decrease in sucrose preference. The serum 5-HT values were increased in 30, 60, 90 mM groups and decreased in 150 mM group. Our findings suggested that methylglyoxal could induce diarrhea, visceral hypersensitivity, headache as well as depression-like behaviors in rats, and might be the key role in triggering systemic symptoms of IBS.

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.

[Effects and efficacy observation of acupuncture on serum 5-HT in patients with diarrhea-predominant irritable bowel syndrome].

OBJECTIVE: To evaluate the clinical efficacy of acupuncture for treatment of diarrhea-predominant irritable bowel syndrome and discuss its action mechanism. METHODS: Fifty-seven cases were randomly divided into two groups. The acupuncture group (29 cases) was treated with acupuncture at Taichong (LR 3), Zusanli (ST 36) and Sanyinjiao (SP 6) etc., once a day and 5 times per week. The medication group (28 cases) was treated with oral administration of pinaverium (50 mg each time, 3 times a day) and live combined bifidobacterium and lactobacillus tablet (4 tablets each time, 3 times a day). Four weeks were taken as a treatment course in both groups. Before and after treatment ELISA method was applied to measure the level of serum 5-HT of the patients in two groups. The scores of clinical symptoms were observed before treatment, after one and four weeks of treatment and 3 months after treatment, respectively. RESULTS: The level of serum 5-HT was significantly reduced in the acupuncture group and medication group (P < 0.01, P < 0.05), which had no statistical difference between two groups (P > 0.05). Compared with the medication group, the scores of clinical symptoms were obviously improved in the acupuncture group after one and four weeks of treatment and 3 months after treatment (P < 0.01, P < 0.05). The total effective rate was 89.66% (26/29) in the acupuncture group, which was superior to 67.85% (19/28) in the medication group (P < 0.05). CONCLUSION: The efficacy of acupuncture is superior to that of medicine in the treatment of diarrhea-predominant irritable bowel syndrome. The acupuncture treatment could reduce the visceral sensitivity, improve the intestinal motility and regulate the imbalance of brain-intestine interactive function.

Preventive effects of skullcap (Scutellaria baicalensis) extract in a mouse model of food allergy.

ETHNOPHARMACOLOGICAL RELEVANCE: Food allergy, which accompanies acute symptoms such as pruritus, vomiting, diarrhea, and lethal anaphylactic shock is an increasing clinical problem. Skullcap (Scutellaria baicalensis Georgi) has been widely used as a traditional herbal medicine to treat inflammation, cancer, and allergy, but its effects in treating food allergy are not yet known. MATERIALS AND METHODS: To examine the effect of skullcap on food allergy, female BALB/c mice were sensitized with 20 µg OVA and 2mg alum by intraperitoneal injection on day 0. From day 17, mice were orally challenged with OVA (50 mg) in saline every 3 days, for a total of six times. To investigate the preventive effect, skullcap (25 mg/kg) was orally administered every day from day 17 to 34. RESULTS: Food allergy symptoms were evaluated by the criteria for diarrhea, anaphylactic response, and rectal temperature. Severe symptoms of food allergy were observed in the sham group (diarrhea, 3 points; anaphylactic response, 2.6 points; rectal temperature, -8.36 °C. In contrast, the skullcap treatment group had a significantly suppressed OVA-induced anaphylactic response (1.3 points) and rectal temperature (-4.76°C). Moreover, both OVA-specific IgE, Th17 cytokine (IL-17), and Th2-related cytokines (IL-4, IL-5, IL-10, and IL-13), which increased with food allergy, were significantly inhibited by skullcap treatment. CONCLUSION: We demonstrate that the administration of skullcap attenuates OVA-induced food allergy symptoms through regulating systemic immune responses of Th cells. These results indicate that skullcap may be a potential candidate as a preventive agent for food allergy.

Supplementation transgenic cow's milk containing recombinant human lactoferrin enhances systematic and intestinal immune responses in piglets.

Lactoferrin (LF) plays an important role in the body's immune system. However, the immunomodulatory effects of supplementation transgenic cow's milk containing recombinant human LF (rhLF) on the systemic and intestinal immune systems in infants remain unclear. Our laboratory has used genetic engineer to produce transgenic cow secreted rhLF. To assess the immune responses we took piglets as an animal model for infants. Eighteen piglets at 7 days of age were fed ordinary milk, 1:1 mix of ordinary and rhLF milk, or rhLF milk (LFM) for 30 days. The incidence of diarrhea in piglets in natural condition was observed. The protein abundances of immunoglobulin (Ig)G, IgA, IgM, IgE, histamine, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12 interferon, tumor necrosis factor in the plasma, spleen or intestine were measured by enzyme-linked immunosorbent assay. Intestinal structure was assessed by hematoxylin and eosin. The mRNA levels of immune and allergy-related genes were measured by quantitative reverse transcription-polymerase chain reaction. The results showed that LFM-fed significantly reduced incidence of diarrhea, enhanced humoral immunity, T helper (Th) 1, and Th2 cell responses, improved the structure of the intestinal mucosal and did not induce food allergy. LFM increased mRNA levels of toll-like receptor 2 and nuclear factor-κB p65 and decreased that of FCεRI ß. In conclusion, rhLF-enriched formula could improve systematic and intestinal immune responses and did not elicit food allergies in neonatal piglets.

[Effects of Xingpi Yang'er granule on serum gastrin, plasma motilin, and somatostatin contents in children patients with pneumonia induced diarrhea].

OBJECTIVE: To observe the effects of Xingpi Yang'er Granule (XYG) on serum gastrin (GAS), plasma motilin (MOT), and somatostatin (SS) in children patients with pneumonia induced diarrhea. METHODS: Recruited were 120 children inpatients with pneumonia induced diarrhea at the Department of Pediatrics, Liaocheng People's Hospital from June 2011 to June 2012. They were randomly assigned to two groups, the treatment group and the control group, 60 in each group. Those in the treatment group were treated with XYG, while those in the control group were treated with Live Combined Bifidobacterium and Lactobacillus Tablets. Besides, 30 healthy children who received physical examinations at our hospital were recruited as the healthy control group. The clinical efficacy, changes of GAS, MOT, and SS contents were observed. RESULTS: The total effective rate was 95.0% in the treatment group and 93.3% in the control group, showing no statistical difference (P > 0.05). Compared with healthy control group, the GAS and MOT contents increased, and SS decreased before treatment in the other two groups (P < 0.05). Compared with the same group before treatment, GAS and MOT contents obviously decreased, and SS increased in the other two groups after treatment (P<0.05). Compared with the control group at the same time point, GAS and MOT decreased, and SS increased in the treatment group after treatment, showing statistical differences (P < 0.05). CONCLUSIONS: The levels of GAS, MOT, and SS were obviously changed in children patients with pneumonia induced diarrhea. XYG had obvious regulation on their GAS, MOT and SS contents.

The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study.

BACKGROUND: Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating levels of zonulin, glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF) and ghrelin and their relationship with intestinal permeability and chemotherapy induced diarrhea (CTD). METHODS: Sixty breast cancer patients undergoing an FEC60 regimen were enrolled, 37 patients completed the study. CTD(+) patients were discriminated by appropriate questionnaire and criteria. During chemotherapy, intestinal permeability was assessed by lactulose/mannitol urinary test on day 0 and day 14. Zonulin, GLP-2, EGF and ghrelin circulating levels were evaluated by ELISA tests at five time-points (days 0, 3, 10, 14, and 21). RESULTS: During FEC60 administration, the lactulose/mannitol ratio was significantly higher on day 14 than at baseline. Zonulin levels were not affected by chemotherapy, whereas GLP-2 and EGF levels decreased significantly. GLP-2 levels on day 14 were significantly lower than those on day 0 and day 3, while EGF values were significantly lower on day 10 than at the baseline. In contrast, the total concentrations of ghrelin increased significantly at day 3 compared to days 0 and 21, respectively. Ten patients (27%) suffered from diarrhea. On day 14 of chemotherapy, a significant increase of the La/Ma ratio occurred in CTD(+) patients compared to CTD(-) patients. With regards to circulating gut peptides, the AUCg of GLP-2 and ghrelin were significantly lower and higher in CTD(+) patients than CTD(-) ones, respectively. Finally in CTD(+) patients a significant and inverse correlation between GLP-2 and La/Ma ratio was found on day 14. CONCLUSIONS: Breast cancer patients undergoing FEC60 showed alterations in the intestinal permeability, which was associated with modifications in the levels of GLP-2, ghrelin and EGF. In CTD(+) patients, a different GI peptide profile and increased intestinal permeability was found in comparison to CTD(-) patients. This evidence deserves further studies for investigating the potentially different intestinal luminal and microbiota conditions. TRIAL REGISTRATION: Clinical trial NCT01382667.