Ability of lactulose breath test results to accurately identify colorectal polyps through the measurement of small intestine bacterial overgrowth

BACKGROUND While colorectal polyps are not cancerous,some types of polyps,known as adenomas,can develop into colorectal cancer over time.Polyps can often be found and removed by colonoscopy;however,this is an invasive and expensive test.Thus,there is a need for new methods of screening patients at high risk of developing polyps.AIM To identify a potential association between colorectal polyps and small intestine bacteria overgrowth(SIBO)or other relevant factors in a patient cohort with lactulose breath test(LBT)results.METHODS A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology.SIBO was diagnosed by measuring LBTderived hydrogen(H)and methane(M)levels according to 2017 North American Consensus recommendations.Logistic regression was used to assess the ability of LBT to predict colorectal polyps.Intestinal barrier function damage(IBFD)was determined by blood assays.RESULTS H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group(41%vs 23%,P<0.01;71%vs 59%,P<0.05,respectively).Within 90 min of lactulose ingestion,the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group(P<0.01,and P=0.03,respectively).In 227 patients with SIBO defined by combining H and M values,the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without(15%vs 5%,P<0.05).In regression analysis with age and gender adjustment,colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO.These models had a sensitivity of≥0.67,a specificity of≥0.64,and an accuracy of≥0.66.CONCLUSION The current study made key associations among colorectal polyps,SIBO,and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.

Simultaneously metastatic cholangiocarcinoma and small intestine cancer from breast cancer misdiagnosed as primary cholangiocarcinoma:A case report

BACKGROUND Cholangiocarcinoma and small intestine cancer are common clinical malignancies,but metastatic cholangiocarcinoma and small intestine cancer are rare,especially simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer.Since the clinical presentation of metastatic cholangiocarcinoma and small intestine cancer does not differ from primary tumor,it may lead to misdiagnosis preoperatively.CASE SUMMARY A 66-year-old woman was admitted to our hospital for further treatment due to abdominal pain and jaundice.Abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography showed an occupying lesion of the bile duct,considering a high possibility of primary bile duct tumor.Therefore,we performed a radical bile duct cancer surgery and cholecystectomy,and multiple tumors in the small intestine were found and removed during the surgery process.Postoperative pathology showed metastatic bile duct cancer and small intestine cancer from tumors in other parts.The patient underwent a right total mastectomy and axillary lymph node dissection because of right breast cancer 2 years ago.Combining with the immunohistochemical results,the patient was finally diagnosed as metastatic cholangiocarcinoma and metastatic small intestine cancer from breast cancer.Postoperatively,the patient received four cycles of chemotherapy and targeted therapy with docetaxel,capecitabine and trastuzumab.Unfortunately,the patient eventually died from tumor progression,thoracoabdominal infection,and sepsis 5 mo after surgery.CONCLUSION Simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer are rare and the prognosis is extremely poor.Improving preoperative diagnostic accuracy is beneficial to avoid excessive surgical treatment.Treatment should be aimed at relieving biliary obstruction and abdominal pain,and then supplemented with chemotherapy and targeted therapy to control tumor progression and prolong the patient’s life.

AN ANALYTICAL SOLUTION FOR THE MODEL OF DRUG DISTRIBUTION AND ABSORPTION IN SMALL INTESTINE

According to the physiological and anatomical characteristics of small intestine,neglecting the effect of its motility on the distribution and absorption of drug and nutrient,Y.Miyamoto et al.proposed a model of two-dimensional laminar flow in a circular porous tube with permeable wall and calculated the concentration profile of drugby numerical analysis.In this paper,we give a steady-state analytical solution of the above model including deactivationterm.The obtained results are in agreement with the results of their numerical analysis. Moreover the analytical solution presented in this paper reveals the relation among the physiological parameters of the model and describes the basic absorption rule of drug and nutrient through the intestinal wall and hence pro- vides a theoretical basis for determining the permeability and reflection coefficient through in situ experiments.

Effect of vitamin E on oxidative stress status in small intestine of diabetic rat

AIM:To investigate the effect of vitamin E on oxidative stress status in the small intestine of diabetic rats. METHODS:Twenty-four male Wistar rats were randomly divided into three groups:Control (C),non-treated diabetic (NTD) and vitamin E-treated diabetic (VETD) groups. The increases in lipid peroxidation,protein oxidation and superoxide dismutase (SOD) in these three groups was compared after 6 wk. RESULTS:There was no significant difference in catalase activity between NTD and control rats. Compared to NTD rats,the treatment with vitamin E significantly decreased lipid peroxidation and protein oxidation,and also increased catalase activity and SOD. CONCLUSION:The results revealed the occurrence of oxidative stress in the small intestine of diabetic rats. Vitamin E,as an antioxidant,attenuates lipid peroxidation and protein oxidation,and increases antioxidant defense mechanism.

Effect of bowel rehabilitative therapy on structural adaptation of remnant small intestine: animal experiment

AIM: To investigate the individual and the combined effects of glutamine, dietary fiber, and growth hormone on the structural adaptation of the remnant small bowel. METHODS: Forty-two adult male Sprague-Dawley rats underwent 85% mid-small bowel resection and received total parenteral nutrition (TPN) support during the first three postoperational days.From the 4th postoperational day, animals were randomly assigned to receive 7 different treatments for 8 days: TPNcon group, receiving TPN and enteral 20 g x L(-1) glycine perfusion; TPN+Gln group, receiving TPN and enteral 20 g x L(-1) glutamine perfusion; ENcon group, receiving enteral nutrition (EN) fortified with 20 g x L(-1) glycine; EN+Gln group, enteral nutrition fortified with 20 g x L(-1) glutamine; EN+Fib group, enteral nutrition and 2 g x d(-1) oral soybean fiber; EN+GH group, enteral nutrition and subcutaneous growth hormone (GH) (0.3 IU) injection twice daily; and ENint group, glutamine-enriched EN, oral soybean fiber, and subcutaneous GH injection. RESULTS: Enteral glutamine perfusion during TPN increased the small intestinal villus height (jejunal villus height 250 microm +/- 29 microm in TPNcon vs 330 microm +/- 54 microm in TPN+Gln, ileal villus height 260 microm +/- 28 microm in TPNcon vs 330 microm +/- 22 microm in TPN+Gln, P【0.05) and mucosa thickness (jejunal mucosa thickness 360 microm +/- 32 microm in TPNcon vs 460 microm +/- 65 microm in TPN+Gln, ileal mucosa thickness 400 microm +/- 25 microm in TPNcon vs 490 microm +/- 11 microm in TPN+Gln,P【 0.05) in comparison with the TPNcon group. Either fiber supplementation or GH administration improved body mass gain (end body weight 270 g +/- 3.6g in EN+Fib, 265.7 g +/- 3.3 g in EN+GH, vs 257 g +/- 3.3 g in ENcon, P【 0.05), elevated plasma insulin-like growth factor (IGF-I) level (880 microg x L(-1). 52 microg x L-(-1) in EN+Fib,1200 microg x L(-1). 96 microg x L-(-1) in EN +/- GH, vs 620 microg x L(-1).43 microg x L-(-1) in ENcon, P【 0.05), and increased the villus height (jejunum 560 microm +/- 44 microm in EN +/- Fib, 530 microm +/- 30 microm in EN +/- GH, vs 450 microm +/- 44 microm in ENcon, ileum 400 microm +/- 30 microm in EN+Fib, P【0.05) and the mucosa thickness (jejunum 740 microm +/- 66 microm in EN +/- Fib, 705 microm +/- 27 microm in EN +/- GH, vs 608 microm +/- 58 microm in ENcon, ileum 570 microm +/- 27 microm in EN +/- Fib, 560 microm +/- 56 microm in remnant jejunum and ileum. Glutamine-enriched EN produced little effect in body mass, plasma IGF-I level, and remnant small bowel mucosal structure. The ENint group had greater body mass (280 g +/- 2.2g), plasma IGF-I level (1450 microg x L(-1). 137 microg x L-(-1)), and villus height (jejunum 620 microm +/- 56 microm, ileum 450 microm +/- 31 microm) and mucosal thickness (jejunum 800 microm +/- 52 microm, ileum 633 microm +/- 33 microm) than those in ENcon, EN+Gln (jejunum villus height and mucosa thickness 450 microm +/- 47 microm and 610 +/- 63 microm, ileum villus height and mucosa thickness 330 microm +/- 39 microm and 500 microm +/- 52 microm), EN+GH groups (P【0.05), and than those in EN+Fib group although no statistical significance was attained. CONCLUSION: Both dietary fiber and GH when used separately can enhance the postresectional small bowel structural adaptation. Simultaneous use of these two gut-trophic factors can produce synergistic effects on small bowel structural adaptation. Enteral glutamine perfusion is beneficial in preserving small bowel mucosal structure during TPN, but has little beneficial effect during EN.

Plasmablastic lymphoma of the small intestine:Case report and literature review

Plasmablastic lymphoma(PBL) is a rare aggressive B-cell lymphoproliferative disorder,which has been characterized by the World Health Organization as a new entity.Although PBL is most commonly seen in the oral cavity of human immunodeficiency virus(HIV)-positive patients,it can also be seen in extraoral sites in immunocompromised patients who are HIV-negative.Here we present a rare case of PBL of the small intestine in a 55-year-old HIV-negative male.Histopathological examination of the excisional lesion showed a large cell lymphoma with plasmacytic differentiation diffusely infiltrating the small intestine and involving the surrounding organs.The neoplastic cells were diffusely positive for CD79a,CD138 and CD10 and partly positive for CD38 and epithelial membrane antigen.Approximately 80% of the tumor cells were positive for Ki-67.A monoclonal rearrangement of the kappa light chain gene was demonstrated.The patient died approximately 1.5 mo after diagnosis in spite of receiving two courses of the CHOP chemotherapy regimen.In a review of the literature,this is the first case report of PBL with initial presentation in the small intestine without HIV and Epstein-Barr virus infection,and a history of hepatitis B virus infection and radiotherapy probably led to the iatrogenic immunocompromised state.

Intestinal perforation with abdominal abscess caused by extramedullary plasmacytoma of small intestine: A case report and literature review

BACKGROUND Extramedullary plasmacytoma(EMP)of the gastrointestinal tract is an extremely rare disease.Clinical manifestations of EMPs are varied and depend on the location and progression of the tumor.CASE SUMMARY Here,we firstly report a case of intestinal perforation with abdominal abscess caused by EMP of the small intestine in a 55-year-old female patient.The patient received emergency surgery immediately after the necessary preoperative procedures.During the operation,EMP was found to have caused the perforation of the small intestine and the formation of multiple abscesses in the abdominal cavity.Partial resection of the small intestine with peritoneal irrigation and drainage was performed.EMP was finally confirmed by postoperative histopathology and laboratory tests.Additionally,we performed a literature review of gastrointestinal EMP to obtain a deeper understanding of this disease.CONCLUSION EMP of the small intestine may have spontaneous perforation,which requires emergency surgery.Surgical resection can obtain good therapeutic effects.

Rat small intestine absorption and membrane digestion in the process of aging

Recently, in our experiments, we used the short-circuit current technique to study the kinetic constants for nutrient transporters in rat gastric-intestinal tract and the thickness of the intestinal unstirred layer near the mucosa surface. It was shown that, during the process of aging, the number of nutrient monomer transporters in the small intestine increases twofold, whereas the affinity of transporters to the correspondent nutrients remains unchanged. The situation for peptides may be opposite. The layer thickness in the vicinity of the mucosa surface, measured through glucose, decreased during the process of aging. It was suggested that, in old rats, the role of the digestive volume is more important, which results in an increase of the number of nutrient monomer transporters.

Kinetics and mechanisms of glucose absorption in the rat small intestine under physiological conditions

Previous studies have shown two components of glucose absorption in the small intestine: a secondary active transport through SGLT1, and unsaturated component, recently attributed mainly to the facilitated diffusion through GLUT2, but the relationship between these two components under physiological conditions remains controversial. In chronic experiments on nonanesthetized rats we investigated for the first time the kinetics of maltose hydrolysis and glucose absorption in the isolated loop of the small intestine in a wide range of maltose and glucose concentrations (25 ÷ 200 mmol/l glucose). The processes were simulated on mathematical models which took into account the current views about mechanisms of hydrolysis and transport of nutrients and geometric characteristics of the intestinal surface. The results of chronic experiments and mathematical simulation have shown that under the close to physiological conditions the glucose transport mediated by SGLT1 is the main mechanism of its absorption in comparison with the unsaturated component. This was demonstrated not only at low, but also at high substrate concentrations. We conclude that correct evaluation of the relative contribution of different mechanisms in glucose transport through the intestinal epithelium requires taking into account the geometric specificities of its surface.

Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms:Experience with Rifaximin

AIM： TO estimate the prevalence of small intestinal bacterial overgrowth （SIBO） in our geographical area （Western Sicily, Italy） by means of an observational study, and to gather information on the use of locally active, non-absorbable antibiotics for treatment of SIBO.METHODS： Our survey included 115 patients fulfilling the Rome II criteria for diagnosis of irritable bowel syndrome （IBS）; a total of 97 patients accepted to perform a breath test with lactulose （BTLact）, and those who had a positive test, received Rifaximin （Normix , Alfa Wassermann） 1200 mg/d for 7 d; 3 wk after the end of treatment, the BTLact was repeated.RESULTS： Based on the BTLact results, SIBO was present in about 56% of IBS patients, and it was responsible for some IBS-related symptoms, such as abdominal bloating and discomfort, and diarrhoea. 1-wk treatment with Rifaximin turned the BTLact to negative in about 50% of patients and significantly reduced the symptoms, especially in those patients with an alternated constipation/diarrhoea-variant IBS. CONCLUSION： SIBO should be always suspected in patients with IBS, and a differential diagnosis is done by means of a ＂breath test＂. Rifaximin may represent a valid approach to the treatment of SIBO.

Heterogeneity across the murine small and large intestine

The small and large intestine of the gastrointestinal tract(GIT) have evolved to have discrete functions with distinct anatomies and immune cell composition.The importance of these differences is underlined when considering that different pathogens have uniquely adapted to live in each region of the gut.Furthermore,different regions of the GIT are also associated with differences in susceptibility to diseases such as cancer and chronic inflammation.The large and small intestine,given their anatomical and functional differences,should be seen as two separate immunological sites.However,this distinction is often ignored with findings from one area of the GIT being inappropriately extrapolated to the other.Focussing largely on the murine small and large intestine,this review addresses the literature relating to the immunology and biology of the two sites,drawing comparisons between them and clarifying similarities and differences.We also highlight the gaps in our understanding and where further research is needed.

Risk factors for small intestinal adenocarcinomas that are common in the proximal small intestine

The frequency of primary small intestinal adenocarcinoma is increasing but is still low.Its frequency is approximately 3%of that of colorectal adenocarcinoma.Considering that the small intestine occupies 90%of the surface area of the gastrointestinal tract,small intestinal adenocarcinoma is very rare.The main site of small intestinal adenocarcinoma is the proximal small intestine.Based on this characteristic,dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis.Since most nutrients are absorbed in the proximal small intestine,the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine.The proportion of aerobic bacteria is high in the proximal small intestine,but the absolute number of bacteria is low.In addition,the length and density of villi are greater in the proximal small intestine.However,the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas.On the other hand,the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there.Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma.In carcinogenesis experiments in which the positions of the small and large intestines were exchanged,tumors still occurred in the large intestinal mucosa more often.In other words,the influence of the intestinal contents is small,and there is a large difference in epithelial properties between the small intestine and the large intestine.In conclusion,small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium.It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.

What are the effects of proton pump inhibitors on the small intestine?

Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.

Morphological and molecular response of small intestine to lactulose and hydrogen-rich water in female piglets fed Fusarium mycotoxins contaminated diet

Background: Following the intake of Fusarium mycotoxin-contaminated feed,small intestines may be exposed to high levels of toxic substances that can potentially damage intestinal functions in livestock.It is well known that Fusarium mycotoxins will lead a breakdown of the normally impeccable epithelial barrier,resulting in the development of a "leaky" gut.H2 administration with different methods has been proved definitely potentials to prevent serious intestinal diseases.The goal of this study is to investigate the roles of lactulose(LAC) and hydrogenrich water(HRW) in preventing intestinal dysfunction in piglets fed Fusarium mycotoxin-contaminated feed.Methods: A total of 24 female piglets were evenly assigned to 4 groups: negative control(NC) group,mycotoxincontaminated(MC) feed group,MC feed with LAC treatment(MC + LAC),and MC feed with HRW treatment(MC +HRW),respectively.Piglets in the NC group were fed uncontaminated control diet,while remaining piglets were fed Fusarium mycotoxin-contaminated diet.For the NC and MC groups,10 mL/kg body weight(BW) of hydrogen-free water(HFW) was orally administrated to piglets twice daily;while in the MC + LAC and MC + HRW groups,piglets were treated with the same dose of LAC solution(500 mg/kg BW) and HRW twice daily,respectively.On d 25,serum was collected and used for biochemical analysis.Intestinal tissues were sampled for morphological examination as well as relative genes and protein expression analysis.Results: Our data showed that Fusarium mycotoxins induced higher serum diamine oxidase(DAO) activities(P < 0.05),D-lactic acid levels(P < 0.01),and endotoxin status(P < 0.01),lower villus height(P < 0.01) and ratio of villus height to crypt depth(P < 0.05) in small intestine,greater apoptosis index and higher mRNA expression related to tight junctions(P < 0.05).In addition,the distribution and down-regulation of claudin-3(CLDN3) protein in the small intestinal was also observed.As expected,oral administrations of HRW and LAC were found to remarkably provide beneficial effects against Fusarium mycotoxin-induced apoptosis and intestinal leaking.Moreover,either HRW or LAC treatments were also revealed to prevent abnormal intestinal morphological changes,disintegrate tight junctions,and restore the expression and distribution of CLDN3 protein in the small intestinal mucosal layer in female piglets that were fed Fusarium mycotoxins contaminated diet.Conclusions: Our data suggest that orally administrations of HRW and LAC result in less Fusarium mycotoxininduced apoptosis and leak in the small intestine.Either HRW or LAC treatments could prevent the abnormal changes of intestinal morphology and molecular response of tight junctions as well as restore the distribution and expression of CLDN3 protein of small intestinal mucosa layer in female piglets that were fed Fusarium mycotoxins contaminated diet.

Protective effects of Ligustrazine,Kakonein and Panax Notoginsenoside on the small intestine and immune organs of rats with severe acute pancreatitis

BACKGROUND:Severe acute pancreatitis (SAP) is characterized by fatal pathogenic conditions and a high mortality.It is important to study SAP complicated with multiple organ injury.In this study we compared the protective effects of three traditional Chinese medicines (Ligustrazine,Kakonein and Panax Notoginsenoside) on the small intestine and immune organs (thymus,spleen and lymph nodes) of rats with SAP and explored their mechanism of action.METHODS:One hundred forty-four rats with SAP were randomly divided into model control,Ligustrazine-treated,Kakonein-treated,and Panax Notoginsenoside-treated groups (n=36 per group).Another 36 normal rats comprised the sham-operated group.According to the different time points after operation,the experimental rats in each group were subdivided into 3-,6-and 12-hour subgroups (n=12).At various time points after operation,the mortality rate of rats and pathological changes in the small intestine and immune organs were recorded and the serum amylase levels were measured.RESULTS:Compared to the model control groups,the mortality rates in all treated groups declined and the pathological changes in the small intestine and immune tissues were relieved to different degrees.The serum amylase levels in the three treated groups were significantly lower than those in the model control group at 12 hours.The pathological severity scores for the small intestinal mucosa,thymus and spleen (at 3 and 12 hours) in the Ligustrazine-treated group,for the thymus (at 3 and 12 hours) and spleen (at 3 and 6 hours) in the Kakonein-treated group,and for the thymus (at 3 hours)and spleen (at 3 hours) in the Panax Notoginsenoside-treated group were significantly lower than those in the model control group.The pathological severity scores of the small intestinal mucosa (at 6 and 12 hours) and thymus (at 6 hours) in the Ligustrazine-treated group were significantly lower than those in the Kakonein-and Panax Notoginsenoside-treated groups.CONCLUSIONS:All the three traditional Chinese drugs significantly alleviated the pathological changes in the small intestine and immune organs of SAP rats.Ligustrazine was the most effective one among them.

Epidemiology of cancer of the small intestine

Cancer of the small intestine is very uncommon.There are 4 main histological subtypes:adenocarcinomas,carcinoid tumors,lymphoma and sarcoma.The incidence of small intestine cancer has increased over the past several decades with a four-fold increase for carcinoid tumors,less dramatic rises for adenocarcinoma and lymphoma and stable sarcoma rates.Very little is known about its etiology.An increased risk has been noted for individuals with Crohn's disease,celiac disease,adenoma,familial adenomatous polyposis and Peutz-Jeghers syndrome.Several behavioral risk factors including consumption of red or smoked meat,saturated fat,obesity and smoking have been suggested.The prognosis for carcinomas of the small intestine cancer is poor(5 years relative survival < 30%),better for lymphomas and sarcomas,and best for carcinoid tumors.There has been no signif icant change in longterm survival rates for any of the 4 histological subtypes.Currently,with the possible exceptions of obesity and cigarette smoking,there are no established modifiable risk factors which might provide the foundation for a prevention program aimed at reducing the incidence and mortality of cancers of the small intestine.More research with better quality and sufficient statistical power is needed to get better understanding of the etiology and biology of this cancer.In addition,more studies should be done to assess not only exposures of interest,but also host susceptibility.

Effects of psychological stress on small intestinal motility and expression of cholecystokinin and vasoactive intestinal polypeptide in plasma and small intestine in mice

AIM: To investigate the effects of psychological stress on small intestinal motility and expression of cholecystokinin (CCK) and vasoactive intestinal polypeptide (VIP) in plasma and small intestine, and to explore the relationship between small intestinal motor disorders and gastrointestinal hormones under psychological stress. METHODS: Thirty-six mice were randomly divided into psychological stress group and control group. A mouse model with psychological stress was established by housing the mice with a hungry cat in separate layers of a two-layer cage. A semi-solid colored marker (carbon-ink) was used for monitoring small intestinal transit. CCK and VIP levels in plasma and small intestine in mice were measured by radioimmunoassay (RIA). RESULTS: Small intestinal transit was inhibited (52.18±19.15% vs70.19±17.79%, P<0.01) in mice after psychological stress, compared to the controls. Small intestinal CCK levels in psychological stress mice were significantly lower than those in the control group (0.75±0.53 μg/g vs1.98±1.17 μg/g, P<0.01), whereas plasma CCK concentrations were not different between the groups. VIP levels in small intestine were significantly higher in psychological stress mice than those in the control group (8.45±1.09 μg/g vs7.03±2.36 μg/g, P<0.01), while there was no significant difference in plasma VIP levels between the two groups. CONCLUSION: Psychological stress inhibits the small intestinal transit, probably by down-regulating CCK and up-regulating VIP expression in small intestine.

Giant primary angiosarcoma of the small intestine showing severe sepsis

Primary malignant tumors of the small intestine are rare, comprising less than 2% of all gastrointestinal tumors. An 85-year-old woman was admitted with fever of 40&#x02005;&#x02005;&#x000b0;C and marked abdominal distension. Her medical history was unremarkable, but blood examination showed elevated inflammatory markers. Abdominal computed tomography showed a giant tumor with central necrosis, extending from the epigastrium to the pelvic cavity. Giant gastrointestinal stromal tumor of the small intestine communicating with the gastrointestinal tract or with superimposed infection was suspected. Because no improvement occurred in response to antibiotics, surgery was performed. Laparotomy revealed giant hemorrhagic tumor adherent to the small intestine and occupying the peritoneal cavity. The giant tumor was a solid tumor weighing 3490 g, measuring 24 cm &#x000d7; 17.5 cm &#x000d7; 18 cm and showing marked necrosis. Histologically, the tumor comprised spindle-shaped cells with anaplastic large nuclei. Immunohistochemical studies showed tumor cells positive for vimentin, CD31, and factor VIII-related antigen, but negative for c-kit and CD34. Angiosarcoma was diagnosed. Although no postoperative complications occurred, the patient experienced enlargement of multiple metastatic tumors in the abdominal cavity and died 42 d postoperatively. The prognosis of small intestinal angiosarcoma is very poor, even after volume-reducing palliative surgery.

Opiate-induced constipation related to activation of small intestine opioid μ2-receptors

AIM： To investigate the role of opioid p-receptor subtype in opiate-induced constipation （OIC）.METHODS： The effect of Ioperamide on intestinal transit was investigated in mice. Ileum strips were isolated from 12-wk-old male BALB/c mice for identification of isometric tension. The ileum strips were precontracted with 1 μmol/L acetylcholine （ACh）. Then, decrease in muscle tone （relaxation） was characterized after cumu- lative administration of 0.1-10μ~mol/L Ioperamide into the organ bath, for a concentration-dependent study. Specific blockers or antagonists were used for pretreat- ment to compare the changes in Ioperamide-induced relaxation.RESULTS： In addition to the delay in intestinal transit, Ioperamide produced a marked relaxation in isolated ileum precontracted with ACh, in a dose-dependent manner. This relaxation was abolished by cyprodime,a selective opioid p-receptor antagonist, but not modified by naloxonazine at a dose sufficient to block opioid μ-1 receptors. Also, treatment with opioid μ-1 receptor agonist failed to modify the muscle tone. Moreover, the relaxation by Ioperamide was attenuated by glibenclamide at a dose sufficient to block ATP-sensitive K^＋ （KATP） channels, and by protein kinase A （PKA） inhibitor, but was enhanced by an inhibitor of phosphodiesterase for cyclic adenosine monophosphate （cAMP）.CONCLUSION： Loperamide induces intestinal relaxa- tion by activation of opioid μ-2 receptors via the cAMP- PKA pathway to open KATp channels, relates to OIC.

Exogenous carbon monoxide attenuates inflammatory responses in the small intestine of septic mice

AIM： To determine whether the carbon monoxide （CO）-releasing molecules （CORM）-Iiberated CO sup- press inflammatory responses in the small intestine of septic mice. METHODS： The C57BL/6 mice （male, n = 36; weight 20±2 g） were assigned to four groups in three re- spective experiments. Sepsis in mice was induced by cecal ligation and puncture （CLP） （24 h）. Tricarbonyl- dichlororuthenium （Ⅱ） dimer （CORM-2） （8 mg/kg, i. v.） was administrated immediately after induction of CLP. The levels of inflammatory cytokines [interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）] in tis- sue homogenates were measured with enzyme-linked immunosorbent assay. The levels of malondialdehyde （MDA） in the tissues were determined. The levels of nitric oxide （NO） in tissue homogenate were measured and the expression levels of intercellular adhesion mol- ecule 1 （ICAM-1） and inducible nitric oxide synthase （iNOS） in the small intestine were also assessed. NO and IL-8 levels in the supernatants were determined after the human adenocarcinoma cell line Caco-2 was stimulated by lipopolysaccharide （LPS） （10 g/mL） for 4 h in vitro. RESULTS： At 24 h after CLP, histological analysis showed that the ileum and jejunum from CLP mice in- duced severe edema and sloughing of the villous tips, as well as infiltration of inflammatory cells into the mu- cosa. Semi-quantitative analysis of histological samples of ileum and jejunum showed that granulocyte infil- tration in the septic mice was significantly increased compared to that in the sham group. Administration of CORM-2 significantly decreased granulocyte infiltration. At 24 h after CLP, the tissue MDA levels in the mid- ileum and mid-jejunum significantly increased com- pared to the sham animals （103.68 ± 23.88 nmol/ml vs 39.66 ± 8.23 nmol/mL, 89.66±9.98 nmol/mL vs 32.32 ± 7.43 nmol/mL, P 〈 0.01）. In vitro administra- tion of CORM-2, tissue MDA levels were significantly decreased （50.65±11.46 nmol/mL, 59.32 ± 6.62 nmol/mL, P 〈 0.05）. Meanwhile, the tissue IL-1β and TNF-α levels in the mid-ileum significantly increased compared to the sham animals （6.66±1.09 pg/mL vs 1.67±0.45 pg/mL, 19.34±3.99 pg/mL vs 3.98 ± 0.87 pg/mL, P 〈 0.01）. In vitro administration of CORM-2, tissue IL-1β and TNF-α levels were significantly de- creased （3.87 ± 1.08 pg/mL, 10.45±2.48 pg/mL, P 〈 0.05）. The levels of NO in mid-ileum and mid-jejunum tissue homogenate were also decreased （14.69 ± 2.45 nmol/mL vs 24.36 ± 2.97 nmol/mL, 18.47 ± 2.47 nmol/mL vs 27.33 ± 3.87 nmol/mL, P 〈 0.05）. The ex- pression of iNOS and ICAM-1 in the mid-ileum of septic mice at 24 h after CLP induction significantly increased compared to the sham animals. In vitro administration of CORM-2, expression of iNOS and ICAM-1 were sig- nificantly decreased. In parallel, the levels of NO and IL-8 in the supernatants of Caco-2 stimulated by LPS was markedly decreased in CORM-2-treated Caco-2 cells （2.22 ± 0.12 nmol/mL vs 6.25±1.69 nmol/mL, 24.97 ± 3.01 pg/mL vs 49.45± 5.11 pg/mL, P 〈 0.05）. CONCLUSION： CORM-released CO attenuates the inflammatory cytokine production （IL-1β and TNF-α）, and suppress the oxidative stress in the small intestine during sepsis by interfering with protein expression of ICAM-1 and iNOS.