Clinicopathological analysis of small intestinal metastasis from extra-abdominal/extra-pelvic malignancy

BACKGROUND The metastatic tumors in the small intestine secondary to extra-abdominal/extrapelvic malignancy are extremely rare.However,the small intestine metastases are extremely prone to misdiagnosis and missed diagnosis due to the lack of specific clinical manifestations and examination methods,thus delaying its treatment.Therefore,in order to improve clinical diagnosis and treatment capabilities,it is necessary to summarize its clinical pathological characteristics and prognosis.AIM To summarize the clinicopathological characteristics of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy,and to improve the clinical capability of diagnosis and treatment for rare metastatic tumors in the small intestine.METHODS The clinical data of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy were retrieved and summarized,who admitted to and treated in the Air Force Medical Center,Chinese People’s Liberation Army.Then descriptive statistics were performed on the general conditions,primary tumors,secondary tumors in the small intestine,diagnosis and treatment processes,and prognosis.RESULTS Totally 11 patients(9 males and 2 females)were enrolled in this study,including 8 cases(72.3%)of primary lung cancer,1 case(9.1%)of malignant lymphoma of the thyroid,1 case(9.1%)of cutaneous malignant melanoma,and 1 case(9.1%)of testicular cancer.The median age at the diagnosis of primary tumors was 57.9 years old,the median age at the diagnosis of metastatic tumors in the small intestine was 58.81 years old,and the average duration from initial diagnosis of primary tumors to definite diagnosis of small intestinal metastases was 9 months(0-36 months).Moreover,small intestinal metastases was identified at the diagnosis of primary tumors in 4 cases.The small intestinal metastases were distributed in the jejunum and ileum,with such clinical manifestations as hematochezia(5,45.4%)and abdominal pain,vomiting and other obstruction(4,36.4%).In addition,2 patients had no obvious symptoms at the diagnosis of small intestinal metastases,and 5 patients underwent radical resection of small intestinal malignancies and recovered well after surgery.A total of 3 patients did not receive subsequent treatment due to advanced conditions.CONCLUSION Small intestinal metastases of extra-abdominal/extra-pelvic malignancy is rare with high malignancy and great difficulty in diagnosis and treatment.Clinically,patients with extra-abdominal/extra-pelvic malignancy should be alert to the occurrence of this disease,and their prognosis may be improved through active surgery combined with standard targeted therapy.

Interlayer repair with porcine small intestinal submucosa versus internal repair with tragus cartilage in endoscopic tympanoplasty

Objective Endoscopic tympanoplasty includes various surgical methods,such as internal repair,interlayer repair,and external overlay.This technique requires autologous materials,allografts,and xenografts,which are used to repair tympanic membrane(TM)perforation.To obtain good results,appropriate surgical methods and repair materials should be selected.This study aims to assess the efficacy of repairing refractory TM perforations in the porcine small intestinal submucosa(SIS)during transcanal endoscopic type I tympanoplasty.Method A retrospective chart review was performed on patients who underwent TM perforation repair with porcine SIS and tragus cartilage between January 2022 and September 2022 at Sir Run Run Shaw Hospital,Zhejiang University School of Medicine.Perforation size,tympanic status,pre-and postoperative symptoms,follow-up data,wound healing rates,and hearing improvement were analysed.Results Of the 115 patients included in the study,56 underwent interlayer repair with porcine SIS of the TM,and 59 patients underwent internal repair with tragus cartilage.No significant difference was found between the two groups at baseline in terms of age,sex,disease course,perforation side,tympanic status,underlying disease,or preoperative infection.The total postoperative effective rate of interlayer implantation with porcine SIS was 91.07%(51 patients),and that of internal implantation with tragus cartilage was 88.14%(52 patients).No significant difference was found in terms of the graft success rate between the two surgical methods(p=0.887).Postoperative pure tone auditory(PTA)and air-bone gap(ABG)density significantly increased in both groups compared with before surgery(p<0.05).However,the postoperative PTA and ABG density were not significantly different 3 months post-surgery between the two groups(p>0.05).Compared to those in the internal implantation group,the patients in the interlayer group had a shorter operation duration(51.36±6.76 min vs.59.71±7.45 min,t=6.298,p<0.001)and less blood loss(11.91±2.61 mL vs.15.27±2.57 mL,t=7.019,p<0.001).Conclusions Our study suggests that the porcine SIS,as well as the tragus cartilage,has a high success rate in repairing irreversible TM perforation.Endoscopic tympanoplasty via interlayer implantation with porcine SIS offers distinct advantages,including the absence of donor-site incision and scar formation,and ease of graft modification and manipulation.

Intestinal tuberculosis with small bowel stricture and hemorrhage as the predominant manifestation: Three case reports

BACKGROUND Intestinal tuberculosis is a chronic disease caused by Mycobacterium tuberculosis that mainly affects the ileum and cecum.Small bowel tuberculosis,characterized by predominant involvement of the small intestine,is an extremely rare condition with highly atypical clinical presentations,making diagnosis even more challenging.CASE SUMMARY We report three cases of small intestinal tuberculosis,two of the patients pre-sented primarily with abdominal pain,and one presented with gastrointestinal bleeding.All patients underwent blood tests and imaging examinations.Small bowel endoscopy(SBE)revealed that the main lesions in these patients were in-testinal stenosis or gastrointestinal bleeding caused by small intestinal ulcers.One patient ultimately underwent surgical treatment.Following a complex diagnostic process and comprehensive analysis,all patients were confirmed to have small intestinal tuberculosis and received standard antituberculosis treatment,leading to an improvement in their condition.CONCLUSION Patients with SBTs present with nonspecific symptoms such as abdominal pain,weight loss,and occasional gastrointestinal bleeding.Accurate diagnosis requires a thorough evaluation of clinical symptoms and various tests to avoid misdiagno-sis and complications.

Massive bleeding in small intestinal mucosa-associated lymphoid tissue lymphoma associated with COVID-19 infection:a case report

The increased risk of mucosa-associated lymphoid tissue(MALT)lymphoma is closely associated with chronic antigenic stimulation,with infection being the most common cause of recurrence.Lesions are usually associated with the gastrointestinal tract,and the involvement of small intestinal is rare.Recent studies have established a close relationship between novel coronavirus 2019(COVID-19)and the occurrence and progression of various diseases.This article presents a rare case of a small intestinal MALT lymphoma.The patient was initially admitted with COVID-19 pneumonia and subsequently developed gastrointestinal bleeding during hospitalization.Medical and endoscopic treatments were ineffective,and an emergency exploratory laparotomy was performed.The affected segment of the small intestine was excised,and a pathological biopsy confirmed the diagnosis of MALT lymphoma.This case underscores the significance of raising clinical awareness of this condition among health care professionals.

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.

Evaluating the accuracy and reproducibility of ChatGPT-4 in answering patient questions related to small intestinal bacterial overgrowth

BACKGROUND Small intestinal bacterial overgrowth(SIBO)poses diagnostic and treatment challenges due to its complex management and evolving guidelines.Patients often seek online information related to their health,prompting interest in large language models,like GPT-4,as potential sources of patient education.AIM To investigate ChatGPT-4's accuracy and reproducibility in responding to patient questions related to SIBO.METHODS A total of 27 patient questions related to SIBO were curated from professional societies,Facebook groups,and Reddit threads.Each question was entered into GPT-4 twice on separate days to examine reproducibility of accuracy on separate occasions.GPT-4 generated responses were independently evaluated for accuracy and reproducibility by two motility fellowship-trained gastroenterologists.A third senior fellowship-trained gastroenterologist resolved disagreements.Accuracy of responses were graded using the scale:(1)Comprehensive;(2)Correct but inadequate;(3)Some correct and some incorrect;or(4)Completely incorrect.Two responses were generated for every question to evaluate reproducibility in accuracy.RESULTS In evaluating GPT-4's effectiveness at answering SIBO-related questions,it provided responses with correct information to 18/27(66.7%)of questions,with 16/27(59.3%)of responses graded as comprehensive and 2/27(7.4%)responses graded as correct but inadequate.The model provided responses with incorrect information to 9/27(33.3%)of questions,with 4/27(14.8%)of responses graded as completely incorrect and 5/27(18.5%)of responses graded as mixed correct and incorrect data.Accuracy varied by question category,with questions related to“basic knowledge”achieving the highest proportion of comprehensive responses(90%)and no incorrect responses.On the other hand,the“treatment”related questions yielded the lowest proportion of comprehensive responses(33.3%)and highest percent of completely incorrect responses(33.3%).A total of 77.8%of questions yielded reproducible responses.CONCLUSION Though GPT-4 shows promise as a supplementary tool for SIBO-related patient education,the model requires further refinement and validation in subsequent iterations prior to its integration into patient care.

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.

Current opinion on the regulation of small intestinal magnesium absorption

Magnesium(Mg^(2+))has an important role in numerous biological functions,and Mg^(2+)deficiency is associated with several diseases.Therefore,adequate intestinal absorption of Mg^(2+)is vital for health.The small intestine was previously thought to absorb digested Mg^(2+)exclusively through an unregulated paracellular mechanism,which is responsible for approximately 90%of total Mg^(2+)absorption.Recent studies,however,have revealed that the duodenum,jejunum,and ileum absorb Mg^(2+)through both transcellular and paracellular routes.Several regulatory factors of small intestinal Mg^(2+)uptake also have been explored,e.g.,parathyroid hormone,fibroblast growth factor-23,apical acidity,proton pump inhibitor,and pH-sensing channel and receptors.The mechanistic factors underlying proton pump inhibitor suppression of small intestinal Mg^(2+),such as magnesiotropic protein dysfunction,higher mucosal bicarbonate secretion,Paneth cell dysfunction,and intestinal inflammation,are currently being explored.The potential role of small intestinal microbiomes in Mg^(2+)absorption has also been proposed.In this article,we reviewed the current knowledge on the mechanisms and regulatory factors of small intestinal Mg^(2+)absorption.

Surgical aspects of small intestinal neuroendocrine tumors

Small intestinal neuroendocrine tumors(NETs)are a heterogeneous group of epithelial tumors with a predominant neuroendocrine differentiation.Although NETs are usually considered rare neoplasms,small intestinal NETs are the most common primary malignancy of the small bowel,with an increasing prevalence worldwide during the course of the past few decades.The indolent nature of these tumors often leads to a delayed diagnosis,resulting in over one-third of patients presenting with synchronous metastases.Primary tumor resection remains the only curative option for this type of tumor.In this review article,the various surgical aspects for the excision of small intestinal NETs are discussed.

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.

Multiple chronic non-specific ulcer of small intestine characterized by anemia and hypoalbuminemia

A female patient with anemia and hypoalbuminemia was admitted to our hospital due to an over 20-year history of recurrent dizziness,fatigue and ankle edema.She was diagnosed as multiple chronic nonspecific ulcer of the small intestine characterized by non-specific histology and persistent gastrointestinal bleeding.

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.

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.

Titanium dioxide induced inflammation in the small intestine

AIM:To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO 2 ) and microparticles (MPTiO 2 ) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO 2 (100 mg/kg body weight) as NPTiO 2 (66 nm), or MPTiO 2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4 + and CD8 + T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immuno-histochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4 + cells (cells/mm 2 ) in duodenum:NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum:NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum:NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO 2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE):IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99± 019 (P < 0.05); IFNγ: NP 15.85 ± 9.99, MP 34.08 ± 11.44 vs 2.81 ± 0.69 (P < 0.05); and TGF-β: NP 780.70 ± 318.50, MP 1409.00 ± 502.20 vs 205.50 ± 63.93 (P < 0.05). CONCLUSION:Our findings indicate that TiO2 particles induce a Th1-mediated inflammatory response in the small bowel in mice.

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.