Diverticular Disease

MedlinePlus

... recommend: a high-fiber diet fiber supplements medicines probiotics. For mild cases of diverticulitis, your doctor may ... bacteria and yeasts) found in your intestines. Similar probiotics are available in some foods and…Colorectal CancerRead ...

Measurement of intestinal edema using an impedance analyzer circuit.

PubMed

Radhakrishnan, Ravi S; Shah, Kunal; Xue, Hasen; Moore-Olufemi, Stacey D; Moore, Frederick A; Weisbrodt, Norman W; Allen, Steven J; Gill, Brijesh; Cox, Charles S

2007-03-01

Acute intestinal edema adversely affects intestinal transit, permeability, and contractility. Current resuscitation modalities, while effective, are associated with development of acute intestinal edema. Knowledge of levels of tissue edema would allow clinicians to monitor intestinal tissue water and may help prevent the detrimental effects of edema. However, there is no simple method to measure intestinal tissue water without biopsy. We sought to develop a tissue impedance analyzer to measure tissue edema, without the need for invasive biopsy. Oscillating voltage input was applied to the analyzer circuit and an oscilloscope measured the voltage output across any load. Rats were randomized to three groups: sham, mild edema (80 mL/kg of NS resuscitation), and severe edema (80 mL/kg of NS resuscitation with intestinal venous hypertension). Intestinal edema was measured by wet-to-dry tissue weight ratio. Bowel impedance was measured and converted to capacitance using a standard curve. Acute intestinal edema causes a significant increase in bowel capacitance. This capacitance can be used to predict tissue water concentration. Using an impedance analyzer circuit, it is possible to measure intestinal edema reliably and quickly. This may prove to be a useful tool in the resuscitation of critically ill patients.

2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor

PubMed Central

Hanuš, Lumír; Abu-Lafi, Saleh; Fride, Ester; Breuer, Aviva; Vogel, Zvi; Shalev, Deborah E.; Kustanovich, Irina; Mechoulam, Raphael

2001-01-01

Two types of endogenous cannabinoid-receptor agonists have been identified thus far. They are the ethanolamides of polyunsaturated fatty acids—arachidonoyl ethanolamide (anandamide) is the best known compound in the amide series—and 2-arachidonoyl glycerol, the only known endocannabinoid in the ester series. We report now an example of a third, ether-type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether), isolated from porcine brain. The structure of noladin ether was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by comparison with a synthetic sample. It binds to the CB1 cannabinoid receptor (Ki = 21.2 ± 0.5 nM) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. It binds weakly to the CB2 receptor (Ki > 3 μM). PMID:11259648

[Gut barrier in the critically ill patient: facts and trends].

PubMed

Velasco, Nicolás

2006-08-01

The disturbances of gut barrier in critically ill patients may influence their outcome and prognosis. Experiments in animals show that fasting and stress collaborate to produce intestinal atrophy and translocation of microorganisms and toxins. This fact is one of the main arguments to promote the use of early enteral feeding in critically ill patients. However, the intestinal barrier behaves differently in humans than in animals. The human enteral cells have a good tolerance to fasting and stress, mucosal atrophy is mild and it is not always associated with changes in intestinal permeability. Moreover, the relationship between intestinal permeability with sepsis and bacterial translocation is controversial. This last phenomenon also happens in normal subjects and may be a mechanism to build immunological memory. One of the most important factors that influence bacterial translocation is the microorganism, that under stress conditions can adhere to the intestinal cell and penetrate the intestinal barrier. Splanchnic ischemia and reperfusion is one of the main pathogenic factors in the failure of intestinal barrier. Finally, the fact that the small bowel is an inflammatory target of extra intestinal injuries, explains several clinical situations. The pathophysiology of the intestinal barrier definitely requires more research.

Rangelia vitalii in a free-ranging maned wolf (Chrysocyon brachyurus) and co-infections.

PubMed

Silveira, Julia Angélica Gonçalves; D'Elia, Mirella Lauria; de Oliveira Avelar, Isabela; de Almeida, Lara Ribeiro; Dos Santos, Hudson Andrade; de Magalhães Soares, Danielle Ferreira; Ribeiro, Múcio Flávio Barbosa; Dos Santos Lima, Walter; Ecco, Roselene

2016-12-01

An adult free-ranged female maned wolf was rescued from a periurban area subject to anthropogenic disturbances in the Minas Gerais, Brazil. The animal presented poor body condition and anemia. The clinical condition rapidly deteriorated culminating in dead and a necropsy was performed. The main gross lesions were marked anemia and blood content in the intestines accompanied by many types of parasites. The protozoa Rangelia vitalii was identified by histopathological analysis predominantly within the cytoplasm of endothelial cells of capillaries of the small intestine. The lymph nodes, spleen, bone marrow, dermis, lungs and kidney had similar protozoal forms but with mild or moderate intensity. Rangelia vitalii was confirmed by molecular assays. Hepatozoon sp., Leishmania sp., and Entamoeba spp., apparently not related to the clinical signs were also detected. The myriad parasites found in the intestines included nematodes ( Ancylostoma caninum , A . braziliensis ,, Molineus sp., Pterygodermatites sp., and Trichuris sp.), cestodes ( Spirometra sp.) and (acanthocephalans. To our knowledge, R . vitalii was identified in C . brachyurus for the first time. These findings emphasize the fragility of Brazilian ecosystems, especially in disturbed areas, reinforcing the necessity of efforts to preserve these areas and wild carnivores, some of which are threatened with extinction, such as the maned wolf.

Lipid rafts are disrupted in mildly inflamed intestinal microenvironments without overt disruption of the epithelial barrier.

PubMed

Bowie, Rachel V; Donatello, Simona; Lyes, Clíona; Owens, Mark B; Babina, Irina S; Hudson, Lance; Walsh, Shaun V; O'Donoghue, Diarmuid P; Amu, Sylvie; Barry, Sean P; Fallon, Padraic G; Hopkins, Ann M

2012-04-15

Intestinal epithelial barrier disruption is a feature of inflammatory bowel disease (IBD), but whether barrier disruption precedes or merely accompanies inflammation remains controversial. Tight junction (TJ) adhesion complexes control epithelial barrier integrity. Since some TJ proteins reside in cholesterol-enriched regions of the cell membrane termed lipid rafts, we sought to elucidate the relationship between rafts and intestinal epithelial barrier function. Lipid rafts were isolated from Caco-2 intestinal epithelial cells primed with the proinflammatory cytokine interferon-γ (IFN-γ) or treated with methyl-β-cyclodextrin as a positive control for raft disruption. Rafts were also isolated from the ilea of mice in which colitis had been induced in conjunction with in vivo intestinal permeability measurements, and lastly from intestinal biopsies of ulcerative colitis (UC) patients with predominantly mild or quiescent disease. Raft distribution was analyzed by measuring activity of the raft-associated enzyme alkaline phosphatase and by performing Western blot analysis for flotillin-1. Epithelial barrier integrity was estimated by measuring transepithelial resistance in cytokine-treated cells or in vivo permeability to fluorescent dextran in colitic mice. Raft and nonraft fractions were analyzed by Western blotting for the TJ proteins occludin and zonula occludens-1 (ZO-1). Our results revealed that lipid rafts were disrupted in IFN-γ-treated cells, in the ilea of mice with subclinical colitis, and in UC patients with quiescent inflammation. This was not associated with a clear pattern of occludin or ZO-1 relocalization from raft to nonraft fractions. Significantly, a time-course study in colitic mice revealed that disruption of lipid rafts preceded the onset of increased intestinal permeability. Our data suggest for the first time that lipid raft disruption occurs early in the inflammatory cascade in murine and human colitis and, we speculate, may contribute to subsequent disruption of epithelial barrier function.

Presumptive fenbendazole toxicosis in North American porcupines.

PubMed

Weber, Martha A; Miller, Michele A; Neiffer, Donald L; Terrell, Scott P

2006-04-15

4 North American porcupines were evaluated because of diarrhea or neutropenia (or both) that developed after treatment with fenbendazole for intestinal parasites. Complete blood cell count abnormalities included severe neutropenia in all affected porcupines and mild anemia in some of them. In 2 porcupines, postmortem findings included bone marrow hypoplasia and intestinal crypt cell necrosis. Affected porcupines received supportive care including fluid supplementation and broad-spectrum antimicrobials. The 2 surviving animals recovered after 9 to 33 days of treatment. Fenbendazole is an anthelminthic that may be used in an extralabel manner for the treatment of intestinal parasitism in wildlife species. The drug inhibits mitosis and can affect rapidly dividing cell lines, such as those in the bone marrow and intestinal crypt mucosa. Fenbendazole may not be an appropriate anthelminthic choice in North American porcupines.

Cholera in Children

MedlinePlus

... Issues Listen Español Text Size Email Print Share Cholera Page Content Article Body Cholera is an infection of the intestines caused by ... that can range from mild to extremely severe. Cholera is rare in the United States but if ...

The Schistosoma Granuloma: Friend or Foe?

PubMed Central

Hams, Emily; Aviello, Gabriella; Fallon, Padraic G.

2013-01-01

Infection of man with Schistosoma species of trematode parasite causes marked chronic morbidity. Individuals that become infected with Schistosomes may develop a spectrum of pathology ranging from mild cercarial dermatitis to severe tissue inflammation, in particular within the liver and intestines, which can lead to life threatening hepatosplenomegaly. It is well established that the etiopathology during schistosomiasis is primarily due to an excessive or unregulated inflammatory response to the parasite, in particular to eggs that become trapped in various tissue. The eggs forms the foci of a classical type 2 granulomatous inflammation, characterized by an eosinophil-rich, CD4+ T helper (Th) 2 cell dominated infiltrate with additional infiltration of alternatively activated macrophages (M2). Indeed the sequela of the type 2 perioval granuloma is marked fibroblast infiltration and development of fibrosis. Paradoxically, while the granuloma is the cause of pathology it also can afford some protection, whereby the granuloma minimizes collateral tissue damage in the liver and intestines. Furthermore, the parasite is exquisitely reliant on the host to mount a granulomatous reaction to the eggs as this inflammatory response facilitates the successful excretion of the eggs from the host. In this focused review we will address the conundrum of the S. mansoni granuloma acting as both friend and foe in inflammation during infection. PMID:23596444

Nodular Gastritis and Pathologic Findings in Children and Young Adults with Helicobacter pylori Infection

PubMed Central

Koh, Hong; Noh, Tae-Woong; Baek, Seoung-Yon

2007-01-01

Purpose The aim of this study was to investigate the pathologic characteristics of nodular gastritis in children and young adults infected with Helicobacter pylori (H. pylori). Materials and Methods A total of 328 patients were enrolled in this study, and the diagnosis of H. pylori infection was done with gastroduodenal endoscopy concomitant with a CLO™ test and pathologic analysis of the biopsy specimens. Diagnoses of normal, superficial gastritis, nodular gastritis, and peptic ulcer disease were made from the gastroduodenal endoscopic findings. The density of H. pylori organisms in the gastric mucosa was rated as normal, mild, moderate, or marked. The pathologic findings of nodular gastritis were based on the histopathologic findings of inflammation, immune activity, glandular atrophy and intestinal metaplasia. Each of these findings was scored as either normal (0), mild (1), moderate (2), or marked (3) according to the updated Sydney system and using visual analog scales. The gastritis score was the sum of the four histopathologic scores. Results In this study, nodular gastritis (50.6%) was most common, and mild density (51.5%) H. pylori infection was also common upon microscopic examination. Intestinal metaplasia occurred in 9 patients (2.7%). Conclusion Logistic regression revealed a significant increase in the incidence of nodular gastritis with gastritis score (p = 0.008), but not an association with sex, age, or H. pylori density. Gastritis score was the only significant factor influencing the occurrence of nodular gastritis. Intestinal metaplasia, which was originally thought to be a pre-malignant lesion, occurred in 2.7% of the patients with H. pylori infection. PMID:17461522

Incidence and Antimicrobial Susceptibility to Clostridium perfringens in Premarket Broilers in Taiwan.

PubMed

Fan, Yang-Chi; Wang, Chia-Lan; Wang, Chinling; Chen, Tsung-Cheng; Chou, Chung-Hsi; Tsai, Hsiang-Jung

2016-06-01

Clostridium perfringens infection causes subclinical and clinical necrotic enteritis in poultry flocks, and it is estimated to result in US$2 billion of losses worldwide every year. The aims of this study were to determine the incidence, toxin types, and antimicrobial resistance levels to C. perfringens isolated from premarket, 5-wk-old, clinically healthy broiler chickens in Taiwan, and to examine the relationships between intestinal lesions and the numbers of C. perfringens in intestinal contents. In total, 435 samples of chicken ileum contents were collected from 98 broiler farms during June 2012 to February 2013. The C. perfringens isolation rate was 9.9% (43/435). The positive rate of tested farms was 29.6% (29/98). All the isolates were C. perfringens type A, only possessing the cpa gene encoding for toxin α. No netB gene encoding NetB toxin associated with necrotic enteritis, and no cpe gene encoding for the C. perfringens enterotoxin causing human intestinal disorder were detected. A quantitative PCR analysis revealed that the mean C. perfringens number in the intestinal contents was 3.9 × 10(6) colony-forming units (CFU)/g, ranging from 6.85 × 10(2) to 1.61 × 10(7) CFU/g. The gross and histopathologic lesions revealed a positive correlation (p < 0.05) between lesion score and C. perfringens number in the ilea of C. perfringens -positive chickens. Antimicrobial susceptibility tests of all C. perfringens isolates indicated that the minimum inhibitory concentration inhibiting 50% of isolates (MIC50) for amoxicillin, bacitracin, chlortetracycline, enrofloxacin, erythromycin, florfenicol, and lincomycin was ≤0.125, 0.5, 128, 0.25, ≥256, 2, and ≥256 μg/ml, respectively. Most of the C. perfringens isolates were susceptible to amoxicillin, bacitracin, and enrofloxacin but resistant to chlortetracycline, erythromycin, and lincomycin. Interestingly, C. perfringens isolated from chickens with severe lesions had higher MIC50 for erythromycin and lincomycin than those isolates from chickens with mild lesions. Conclusively, reductions in both the incidence of C. perfringens infection on farms and the concentrations of C. perfringens in intestines to improve broiler health are still needed in Taiwan.

Proliferative enteritis in leopard geckos (Eublepharis macularius) associated with Cryptosporidium sp. infection.

PubMed

Terrell, Scott P; Uhl, Elizabeth W; Funk, Richard S

2003-03-01

Twenty-three leopard geckos (Eublepharis macularius) with various clinical histories of weight loss, anorexia, lethargy, and diarrhea were submitted either intact or as biopsy specimens to the University of Florida Anatomic Pathology Service. Gross necropsy findings in the intact geckos included marked reduction of subcutaneous adipose tissue stores at the tail base and mild thickening and reddening of the small intestine. Histologic examination revealed Cryptosporidium sp. infection associated with hyperplasia and mononuclear inflammation of the small intestine in all geckos. Parasites and lesions were only rarely observed in the stomach and large intestine of geckos. The histologic and ultrastructural lesions in the small intestine of leopard geckos infected with Cryptosporidium sp. have not been well characterized previously. This report implicates Cryptosporidium sp. as the cause of disease in the geckos and describes the range of histologic lesions observed.

Chronic constipation recognized as a sign of a SOX10 mutation in a patient with Waardenburg syndrome.

PubMed

Arimoto, Yukiko; Namba, Kazunori; Nakano, Atsuko; Matsunaga, Tatsuo

2014-05-01

Waardenburg syndrome is characterized by hearing loss, pigmentation abnormalities, dysmorphologic features, and neurological phenotypes. Waardenburg syndrome consists of four distinct subtypes, and SOX10 mutations have been identified in type II and type IV. Type IV differs from type II owing to the presence of Hirschsprung disease. We identified a de novo nonsense mutation in SOX10 (p.G39X) in a female pediatric patient with Waardenburg syndrome with heterochromia iridis, profound bilateral sensorineural hearing loss, inner ear malformations, and overall hypopigmentation of the hair without dystopia canthorum. This patient has experienced chronic constipation since she was a neonate, but anorectal manometry showed a normal anorectal reflex. Chronic constipation in this patient was likely to be a consequence of a mild intestinal disorder owing to the SOX10 mutation, and this patient was considered to have a clinical phenotype intermediate between type II and type IV of the syndrome. Chronic constipation may be recognized as indicative of a SOX10 mutation in patients with Waardenburg syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

To observe the intensity of the inflammatory reaction caused by neonatal urine and meconium on the intestinal wall of rats in order to understand etiology of intestinal damage in gastroschisis

PubMed Central

Samala, Devdas S.; Parelkar, Sandesh V.; Sanghvi, Beejal V.; Vageriya, Natasha L.; Paradkar, Bhupesh A.; Kandalkar, Bhuvaneshwari M.; Sathe, Pragati A.

2014-01-01

Objectives: The aim of this experimental study was to observe the intensity of the inflammatory reaction caused by neonatal urine and meconium on the intestinal wall of rats to better understand etiology of intestinal damage in gastroschisis. Materials and Methods: A total of 24 adult Wistar rats were used as experimental models to simulate the effect of exposed bowel in cases of gastroschisis. The peritoneal cavity of the rats was injected with substances which constitute human amniotic fluid to study the effect on the bowel. Sterile urine and meconium were obtained from newborn humans. The rats were divided into four groups according to the material to be injected. In Group I (Control group) 3 mL of distilled water was injected, in Group II (Urine group) 3 mL of neonatal urine was injected, in Group III (Meconium group) 5% meconium suspension was injected, while in Group IV, a combination of 5% meconium suspension and urine was injected. A total of 3mL solution was injected into the right inferior quadrant twice a day for 5 days. The animals were sacrificed on the 6th day by a high dose of thiopentone sodium. A segment of small bowel specimen was excised, fixed in paraffin, and stained with hematoxylin-eosin for microscopic analysis for determination of the degree of inflammatory reaction in the intestinal wall. All pathology specimens were studied by the same pathologist. Results: The maximum bowel damage was seen in Group II (Urine group) in the form of serositis, severe enteritis, parietal necrosis, and peeling. A lesser degree of damage was observed in Group III (Meconium group) as mild enteritis (mild lymphoid hyperplasia). The least damage was seen in Group IV (Combination of meconium and urine) and Group I (Control group). Conclusion: The intraabdominal injection of neonatal human urine produces significant inflammatory reactions in the intestinal wall of rats. PMID:24604977

Clostridium perfringens type-D enterotoxaemia in cattle: the diagnostic significance of intestinal epsilon toxin.

PubMed

Jones, A L; Dagleish, M P; Caldow, G L

2015-10-17

The aims of this study were to describe 42 cases of Clostridium perfringens type-D enterotoxaemia in cattle seen between 2003 and 2014 and to determine the diagnostic value of detecting epsilon toxin in bovine intestinal content. All cases in the series had histological brain changes considered pathognomonic for C. perfringens type-D enterotoxaemia in sheep and goats and the epsilon toxin of C. perfringens was concurrently detected in the intestinal contents of 15 (36 per cent) cases. The data from the case series indicate that intestinal epsilon toxin has a sensitivity of 56 per cent compared with histology of the brain for diagnosis of bovine C. perfringens type-D enterotoxaemia. The diagnostic specificity of detecting epsilon toxin in bovine intestinal content was investigated by screening intestinal contents of 60 bovine carcases submitted for postmortem examination. Epsilon toxin was detected in 11 (18 per cent) carcases but no pathognomonic histological brain change was found in any. The specificity of intestinal epsilon toxin was estimated to be 80.4 per cent. These studies demonstrate that for a definitive diagnosis of C. perfringens type-D enterotoxaemia in cattle histological examination of the brain is essential as the presence of epsilon toxin in the intestinal contents alone is neither sensitive nor specific enough. British Veterinary Association.

Small Intestine Cancer—Health Professional Version

Cancer.gov

Adenocarcinoma is the most common type of small intestine cancer. Other types of small intestine cancer are sarcomas, carcinoid tumors, gastrointestinal stromal tumors, and lymphomas. Find evidence-based information on small intestine cancer treatment, research, and statistics.

Cross-reactive protection against enterohemorrhagic Escherichia coli infection by enteropathogenic E. coli in a mouse model.

PubMed

Calderon Toledo, Carla; Arvidsson, Ida; Karpman, Diana

2011-06-01

Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are related attaching and effacing (A/E) pathogens. The genes responsible for the A/E pathology are carried on a chromosomal pathogenicity island termed the locus of enterocyte effacement (LEE). Both pathogens share a high degree of homology in the LEE and additional O islands. EHEC prevalence is much lower in areas where EPEC is endemic. This may be due to the development of antibodies against common EPEC and EHEC antigens. This study investigated the hypothesis that EPEC infections may protect against EHEC infections. We used a mouse model to inoculate BALB/c mice intragastrically, first with EPEC and then with EHEC (E. coli O157:H7). Four control groups received either a nonpathogenic E. coli (NPEC) strain followed by EHEC (NPEC/EHEC), phosphate-buffered saline (PBS) followed by EHEC (PBS/EHEC), EPEC/PBS, or PBS/PBS. Mice were monitored for weight loss and symptoms. EPEC colonized the intestine after challenge, and mice developed serum antibodies to intimin and E. coli secreted protein B (encoded in the LEE). Prechallenge with an EPEC strain had a protective effect after EHEC infection, as only a few mice developed mild symptoms, from which they recovered. These mice had an increase in body weight similar to that in control animals, and tissue morphology exhibited mild intestinal changes and normal renal histology. All mice that were not prechallenged with the EPEC strain developed mild to severe symptoms after EHEC infection, with weight loss as well as intestinal and renal histopathological changes. These data suggest that EPEC may protect against EHEC infection in this mouse model.

Submission of nucleotide sequence eimeria acervulina profilin to genbank database

USDA-ARS?s Scientific Manuscript database

Poultry coccidiosis, caused by intestinal protozoa Eimeria, is a severe problem for the poultry industry, leading to a substantial economic burden of over three billion dollars worldwide. Conventional vaccines including live vaccines and attenuated vaccines could cause mild to severe reactions Numer...

Enterobius vermicularis in the male urinary tract: a case report

PubMed Central

Zahariou, Athanasios; Karamouti, Maria; Papaioannou, Polyanthi

2007-01-01

Enterobius vermicularis is an intestinal nematode of humans. Adults usually have low worm burdens and are asymptomatic. Ectopic infections in the pelvic area or urinary tract rarely occur in women. We report a case of the patient with mild voiding difficulties such as urgency, frequency, nocturia, dysuria, mild low back pain or perineal discomfort. The patient's prostatic secretions showed a large number of inflammatory cells and several eggs. The size and the shape of the eggs identified them as a group of E. vermicularis. On examination we found a soft palpable material which was 5 mm diameter in size and spherical shape. Palpation gave the impression of a tissue than a stone. An incision was performed and a 4 mm long living worm was found. The microscopic examination identified the worm as E- vermicularis. It is an extremely rare manifestation of enterobius vermicularis infection since an intestinal-breeding worm is rarely found in the male genital tract. PMID:18001478

The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, Eiichi; Hosokawa, Masaya; Faculty of Human Sciences, Tezukayama Gakuin University, Osaka

2011-01-07

Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucosemore » absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather than through a GLP-1-mediated pathway.« less

[Dolichomegacolon of the Andes and intestinal volvulus due to altitude].

PubMed

Frisancho, Oscar

2008-01-01

Sigmoid volvulus is a frequent cause of emergencies in hospitals in the Andean area, representing more than 50% of all intestinal obstructions. Andean dolichomegacolon (DCMA) and retractile mesocolonitis are the main contributing factors for volvulus. The mesocolonitis nears the proximal and distal segment of the sigmoid handle, favoring its torsion. Copious intake of fermentable food is the precipitating factor for volvulus. The majority of patients are seen during sowing and harvest periods, in which the consumption of this type of food increases. Andean people who live at an altitude of 3,000 m have a larger and thicker colon than coastal residents. We call this acquired characteristic the Andean dolichomegacolon (DCMA). A fiber-rich diet may inhibit the histological phenomenon known as elastogenesis, developing--over the years--the megacolon. Another important factor may be the lower atmospheric pressure in the altitude, and according to Boyle and Mariotte's physical law, the expansion of intraluminal gas may have an influence on intestinal enlargement. DCMA has many special anatomic, clinical, radiological, histological and serological features which make it different from the . chagasic megacolon. Mild emergency procedures may be performed to treat the sigmoid volvulus, such as endoscopic disvolvulation. Changing the colon rotation is helpful in diminishing abdominal pressure and restore complete blood circulation. An emergency surgery treatment must take the patient's general condition and the colon handle condition during surgery as a guiding point. High rates of mortality are found in relation to elderly patients, disease evolution time and stage of intestinal ischemia. Other new therapeutic procedures such as percutaneous sigmoidpexy, laparoscopic sigmoidectomy and mesosigmoplasty are under review, and have precise indications. Wider series are needed to evaluate them better.

Protective Effects of Female Reproductive Factors on Lauren Intestinal-Type Gastric Adenocarcinoma.

PubMed

Kim, Su Mi; Min, Byung Hoon; Lee, Jeeyun; An, Ji Yeong; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Jae J; Kang, Won Ki; Kim, Sung; Choi, Min Gew

2018-01-01

Gastric cancer shows a male predominance that might be explained by protective effects from estrogens in females. Two Lauren classification histological subtypes, intestinal and diffuse, have distinct carcinogeneses. The purpose of this study was to estimate the effects of sex hormone on female gastric cancer according to Lauren classification. We reviewed medical records for and administered questionnaires, surveying reproductive and hormonal factors, to 758 patients who underwent gastrectomy for gastric cancer at Samsung Medical Center from May 2012 to November 2014. Clinicopathological characteristics were compared between females and males. The incidence of intestinal-type gastric cancer was compared between females subgroups, consist of premenopausal women and three groups of postmenopausal women (five-year intervals after menopause), and males. The association between reproductive factors and intestinal-type gastric cancer was analyzed by multivariate models for the female group. In total, 227 females (29.9%) and 531 males (70.9%) were included in the analysis. Undifferentiated adenocarcinoma and diffuse-type histology were more frequent in female patients than male patients. While 221 (41.6%) male patients had intestinal-type gastric cancer, no premenopausal female patient had this type of gastric cancer. The incidence of intestinal-type gastric cancer increased with time after menopause, and was similar to males after 10 years from menopause. Parity was associated with an increased risk of intestinal-type gastric cancer in menopausal women. These findings support that female sex hormones might be protective against intestinal-type gastric cancer. © Copyright: Yonsei University College of Medicine 2018

Intestinal granulomatous disease: what is the first call.

PubMed

Guri, Alex; Kori, Michal; Herskovitz, Pearl; Zimhony, Oren

2018-04-19

A 15-year-old girl presented with erythema nodosum and mild abdominal complaints. Her intestinal granulomatous disease was erroneously diagnosed as Crohn's disease despite the fact that the possibility of tuberculosis was considered. The final diagnosis of tuberculosis was made only when an anti-tumour necrosis factor therapy resulted in further deterioration. The patient was treated with isoniazid, rifampin, pyrazinamide and ethambutol, with slow and steady clinical improvement until complete recovery was achieved. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Intestinal lymphangiectasia in a patient with autoimmune polyglandular syndrome type III.

PubMed

Choudhury, Bipul Kumar; Saiki, Uma Kaimal; Sarm, Dipti; Choudhury, Bikash Narayan; Choudhury, Sarojini Dutta; Saharia, Dhiren; Saikia, Mihir

2011-11-01

Autoimmune polyglandular syndromes (APS) comprise a wide clinical spectrum of autoimmune disorders. APS is divided into Type I, Type II, Type I and Type IV depending upon the pattern of disease combination. Ghronic diarrhoea is one of the many manifestations of APS and many aetiological factors have been suggested for it. Apart from the established aetiological factors, intestinal lymphangiectasia may be responsible for chronic diarrhea in some cases.Intestinal lymphangiectasia has been reported in Type I APS. We report a case of Type III APS with hypocalcaemia and hypothyroidism who had chronic diarrhea of long duration and was finally diagnosed to have intestinal lymphangiectasia.

Prediction of Gut Wall Integrity Loss in Viral Gastroenteritis by Non-Invasive Marker

PubMed Central

Elnady, Hala G.; Sherif, Lobna S.; Saleh, Maysa T.; El-Alameey, Inas R.; Youssef, Mai M.; El Shafie, Amal I.; Helwa, Iman; Raouf, Haiam Abdel; EL-Taweel, Ahmed N.

2015-01-01

BACKGROUND: Intestinal fatty acid binding proteins (I-FABPs) are mainly expressed in the intestinal villi, which are the initial site of destruction in viral gastroenteritis. AIM: This study was designed to assess serum I-FABPs as a predictor of gut wall integrity loss in viral gastroenteritis. PATIENTS AND METHODS: This case-control cross-sectional study was conducted on 93 cases of acute viral gastroenteritis. Twenty-eight healthy children matching in age were recruited as control group. Serum I-FABPs were measured using ELISA technique. Viral detection and typing were done by PCR for adenovirus, and by Reverse transcriptase PCR for rotavirus, astrovirus and norovirus. RESULTS: Serum I-FABPs level was significantly higher in the cases compared to the controls and was also higher in the 46 rotavirus gastroenteritis cases compared to other viral gastroenteritis cases. Serum I- FABPs level was significantly higher in severely dehydrated cases as compared to mildly dehydrated ones (P=0.037). CONCLUSION: Serum I-FABPs could be used as an early and sensitive predictor marker of gut wall integrity loss in children with viral gastroenteritis and its level can indicate case severity. PMID:27275194

1-alpha,25-Dihydroxyvitamin D3 up-regulates the expression of 2 types of human intestinal alkaline phosphatase alternative splicing variants in Caco-2 cells and may be an important regulator of their expression in gut homeostasis.

PubMed

Noda, Seiko; Yamada, Asako; Nakaoka, Kanae; Goseki-Sone, Masae

2017-10-01

Vitamin D insufficiency is associated with a greater risk of osteoporosis and also influences skeletal muscle functions, differentiation, and development. The principal function of vitamin D in calcium homeostasis is to increase the absorption of calcium from the intestine, and the level of alkaline phosphatase (ALP) activity, a differentiation marker for intestinal epithelial cells, is regulated by vitamin D. Intestinal-type ALP is expressed at a high concentration in the brush border membrane of intestinal epithelial cells, and is known to be affected by several kinds of nutrients. Recent reviews have highlighted the importance of intestinal-type ALP in gut homeostasis. Intestinal-type ALP controls bacterial endotoxin-induced inflammation by dephosphorylating lipopolysaccharide and is a gut mucosal defense factor. In this study, we investigated the influence of vitamin D on the expression of 2 types of alternative mRNA variants encoding the human alkaline phosphatase, intestinal (ALPI) gene in human Caco-2 cells as an in vitro model of the small intestinal epithelium. After treatment with 1-alpha,25-dihydroxyvitamin D 3 , the biologically active form of vitamin D 3 , there were significant increases in the ALP activities of Caco-2 cells. Inhibitor and thermal inactivation experiments showed that the increased ALP had properties of intestinal-type ALP. Reverse transcription-polymerase chain reaction analysis revealed that expression of the 2 types of alternative mRNA variants from the ALPI gene was markedly enhanced by vitamin D in Caco-2 cells. In conclusion, these findings agree with the hypothesis: vitamin D up-regulated the expression of 2 types of human intestinal alkaline phosphatase alternative splicing variants in Caco-2 cells; vitamin D may be an important regulator of ALPI gene expression in gut homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Contributions of HLA haplotypes, IL8 level and Toxoplasma gondii infection in defining celiac disease's phenotypes.

PubMed

Rostami-Nejad, Mohammad; Hejazi, Seyed Hossein; Peña, Amado Salvador; Asadzadeh-Aghdaei, Hamid; Rostami, Kamran; Volta, Umberto; Zali, Mohammad Reza

2018-05-18

It is not clear why some patients with coeliac disease (CD) present with severe symptoms and small intestinal mucosal damages while others present with milder symptoms and no frank enteropathy. There is no study to assess the associated factors with mild/severe symptoms and enteropathy. The terminologies like latent, silent and potential are difficult to use and are unrepresentative. In the present study we describe coeliac disease's phenotypes based on HLA haplotypes, IL8 production and past infection with Toxoplasma gondii (T. gondii) infection. In this case-control study, sera originating from 150 healthy subjects and 150 patients diagnosed with CD during the years 2013-14 were analyzed for the presence of antibodies specific T. gondii of the IgG and IgM subclasses. The level of IL8 were measured and HLA-DQ2 and HLA-DQ8 alleles were genotyped. The correlation between these parameters and the damages in intestinal mucosal were assessed using an accepted histopathological classification. High levels of IgG antibodies against T. gondii were found in the sera of control group compared to the CD group (52.6% vs. 39.4%, P = 0.02). Mean serum levels of IL8 was significantly higher in CD patients compared with control (P ≤ 0.05). By comparing the level of anti- T. gondii IgG and mucosal damage in celiac disease, we found a significant relationship between the severity of mucosal damages and anti- T. gondii IgG level (P = 0.02). No correlation was detected between Toxoplasma gondii infection and types of HLA (P > 0.05). However, patients with severely abnormal histology carried HLA-DQ2 risk alleles (92 patients (61%)) more often than the controls and those with mild histological abnormalities. CD patients with severe histological changes had more often Toxoplasma gondii infection than those affected with mild histological features. This suggests that CD's phenotypes are correlated to additional factors like infections and to particular HLA DQ2 alleles that may need additional investigations and potentially will require additional treatment.

The Impact of Mild Heat Stress During Prolonged Running On Gastrointestinal Integrity, Gastrointestinal Symptoms, Systemic Endotoxin and Cytokine Profiles.

PubMed

Snipe, Rhiannon M J; Khoo, Anthony; Kitic, Cecilia M; Gibson, Peter R; Costa, Ricardo J S

2018-02-07

The study aimed to determine the effects of mild exertional heat stress on intestinal injury, permeability, gastrointestinal symptoms, and systemic endotoxin and cytokine responses. Ten endurance runners completed 2 h of running at 60% V̇O 2max in warm (WARM: 30°C) and temperate (TEMP: 22°C) ambient conditions. Rectal temperature (T re ) and gastrointestinal symptoms were recorded every 10 min during exercise. Blood samples were collected pre- and post-exercise, and during recovery to determine plasma intestinal fatty acid-binding protein (I-FABP) and cortisol concentrations, and systemic endotoxin and inflammatory cytokine profiles. Urinary lactulose:L-rhamnose ratio (L/R) was used to measure small intestine permeability. Compared with TEMP, WARM significantly increased T re from 50 min onwards (38.1±0.3°C vs. 38.4±0.5°C, respectively; p<0.01), gastrointestinal symptoms (p=0.017), post-exercise plasma cortisol (26% vs. 59%, respectively; p<0.001) and I-FABP (127% vs. 184%, respectively; p<0.001) concentrations. Circulatory anti-endotoxin antibodies increased post-exercise (p<0.001) on WARM (20%) and TEMP (28%). No differences were observed for plasma endotoxin concentration (6% vs. 5% increase, respectively) or small intestine permeability (L/R 0.026±0.010 and 0.025±0.015, respectively). Both pro- and anti-inflammatory cytokines increased post-exercise, with inflammatory response cytokines TNF-α (p=0.015) and IL-8 (p=0.044), and compensatory anti-inflammatory cytokines IL-10 (p=0.065), and IL-1ra higher on WARM than TEMP. Findings suggest that exposure to warm ambient conditions during prolonged submaximal running induces transient intestinal epithelial injury, increases gastrointestinal symptoms, and promotes greater perturbations to the systemic cytokine profile compared to running in temperate conditions. © Georg Thieme Verlag KG Stuttgart · New York.

Paneth and intestinal stem cells preserve their functional integrity during worsening of acute cellular rejection in small bowel transplantation.

PubMed

Pucci Molineris, M; Gonzalez Polo, V; Perez, F; Ramisch, D; Rumbo, M; Gondolesi, G E; Meier, D

2018-04-01

Graft survival after small bowel transplantation remains impaired due to acute cellular rejection (ACR), the leading cause of graft loss. Although it was shown that the number of enteroendocrine progenitor cells in intestinal crypts was reduced during mild ACR, no results of Paneth and intestinal stem cells localized at the crypt bottom have been shown so far. Therefore, we wanted to elucidate integrity and functionality of the Paneth and stem cells during different degrees of ACR, and to assess whether these cells are the primary targets of the rejection process. We compared biopsies from ITx patients with no, mild, or moderate ACR by immunohistochemistry and quantitative PCR. Our results show that numbers of Paneth and stem cells remain constant in all study groups, whereas the transit-amplifying zone is the most impaired zone during ACR. We detected an unchanged level of antimicrobial peptides in Paneth cells and similar numbers of Ki-67 + IL-22R + stem cells revealing cell functionality in moderate ACR samples. We conclude that Paneth and stem cells are not primary target cells during ACR. IL-22R + Ki-67 + stem cells might be an interesting target cell population for protection and regeneration of the epithelial monolayer during/after a severe ACR in ITx patients. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring

PubMed Central

Sabet, Julia A.; Park, Lara K.; Iyer, Lakshmanan K.; Tai, Albert K.; Koh, Gar Yee; Pfalzer, Anna C.; Parnell, Laurence D.; Mason, Joel B.; Liu, Zhenhua; Byun, Alexander J.; Crott, Jimmy W.

2016-01-01

Background The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well. Objective In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content. Methods Male Apc1638N mice (prone to intestinal tumor formation) were fed diets containing replete (control, CTRL), mildly deficient (DEF), or supplemental (SUPP) quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden. Results No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring. Conclusions In this animal model, modulation of paternal B vitamin intake prior to mating alters offspring weight gain, lipid metabolism and tumor growth in a sex-specific fashion. These results highlight the need to better define how paternal nutrition affects the health of offspring. PMID:26968002

Combined inadequacies of multiple B vitamins amplify colonic Wnt signaling and promote intestinal tumorigenesis in BAT-LacZ×Apc1638N mice

PubMed Central

Liu, Zhenhua; Ciappio, Eric D.; Crott, Jimmy W.; Brooks, Ryan S.; Nesvet, Jared; Smith, Donald E.; Choi, Sang-Woon; Mason, Joel B.

2011-01-01

The Wnt pathway is a pivotal signaling cascade in colorectal carcinogenesis. The purpose of this work is to determine whether depletion of folate and other metabolically related B vitamins induces in vivo activation of intestinal Wnt signaling and whether this occurs in parallel with increased tumorigenesis. A hybrid mouse was created by crossing a Wnt-reporter animal (BAT-LacZ) with a model of colorectal cancer (Apc1638N). A mild depletion of folate and vitamins B2, B6, and B12 was induced over 16 wk, and the control animals in each instance were pair fed a diet containing the basal requirement of these nutrients. The multiplicity of macroscopic tumors and aberrant crypt foci both increased by ∼50% in the hybrid mice fed the depletion diet (P<0.05). A 4-fold elevation in Wnt signaling was produced by the depletion diet (P<0.05) and was accompanied by significant changes in the expression of a number of Wnt-related genes in a pattern consistent with its activation. Proliferation and apoptosis of the colonic mucosa both changed in a protransformational direction (P<0.05). In summary, mild depletion of multiple B vitamins produces in vivo activation of colonic Wnt signaling, implicating it as a key pathway by which B-vitamin inadequacies enhance intestinal tumorigenesis.—Liu, Z., Ciappio, E. D., Crott, J. W., Brooks, R. S., Nesvet, J., Smith, D. E., Choi, S.-W., Mason, J. B. Combined inadequacies of multiple B vitamins amplify colonic Wnt signaling and promote intestinal tumorigenesis in BAT-LacZ×Apc1638N mice. PMID:21646397

Expression of an Intestine-Specific Transcription Factor (CDX1) in Intestinal Metaplasia and in Subsequently Developed Intestinal Type of Cholangiocarcinoma in Rat Liver

PubMed Central

Ren, Ping; Silberg, Debra G.; Sirica, Alphonse E.

2000-01-01

CDX1 is a caudal-type homeobox intestine-specific transcription factor that has been shown to be selectively expressed in epithelial cells in intestinal metaplasia of the human stomach and esophagus and variably expressed in human gastric and esophageal adenocarcinomas (Silberg DG, Furth EE, Taylor JK, Schuck T, Chiou T, Traber PG: Gastroenterology 1997, 113: 478–486). Through the use of immunohistochemistry and Western blotting, we investigated whether CDX1 is also uniquely associated with the intestinal metaplasia associated with putative precancerous cholangiofibrosis induced in rat liver during furan cholangiocarcinogenesis, as well as expressed in neoplastic glands in a subsequently developed intestinal type of cholangiocarcinoma. In normal, control adult rat small intestine, specific nuclear immunoreactivity for CDX1 was most prominent in enterocytes lining the crypts. In comparison, epithelium from intestinal metaplastic glands within furan-induced hepatic cholangiofibrosis and neoplastic epithelium from later developed primary intestinal-type cholangiocarcinoma each demonstrated strong nuclear immunoreactivity for CDX1. CDX1-positive cells were detected in hepatic cholangiofibrotic tissue as early as 3 weeks after the start of chronic furan treatment. We further determined that the percentages of CDX1-positive neoplastic glands and glandular nuclei are significantly higher in primary tumors than in a derived, transplantable cholangiocarcinoma serially-propagated in vivo. Western blotting confirmed our immunohistochemical results, and no CDX1 immunoreactivity was detected in normal adult rat liver or in hyperplastic biliary epithelial cells. These findings indicate that CDX1 is specifically associated with early intestinal metaplasia and a later developed intestinal-type of cholangiocarcinoma induced in the liver of furan-treated rats. PMID:10666391

Expression of an intestine-specific transcription factor (CDX1) in intestinal metaplasia and in subsequently developed intestinal type of cholangiocarcinoma in rat liver.

PubMed

Ren, P; Silberg, D G; Sirica, A E

2000-02-01

CDX1 is a caudal-type homeobox intestine-specific transcription factor that has been shown to be selectively expressed in epithelial cells in intestinal metaplasia of the human stomach and esophagus and variably expressed in human gastric and esophageal adenocarcinomas (Silberg DG, Furth EE, Taylor JK, Schuck T, Chiou T, Traber PG: Gastroenterology 1997, 113: 478-486). Through the use of immunohistochemistry and Western blotting, we investigated whether CDX1 is also uniquely associated with the intestinal metaplasia associated with putative precancerous cholangiofibrosis induced in rat liver during furan cholangiocarcinogenesis, as well as expressed in neoplastic glands in a subsequently developed intestinal type of cholangiocarcinoma. In normal, control adult rat small intestine, specific nuclear immunoreactivity for CDX1 was most prominent in enterocytes lining the crypts. In comparison, epithelium from intestinal metaplastic glands within furan-induced hepatic cholangiofibrosis and neoplastic epithelium from later developed primary intestinal-type cholangiocarcinoma each demonstrated strong nuclear immunoreactivity for CDX1. CDX1-positive cells were detected in hepatic cholangiofibrotic tissue as early as 3 weeks after the start of chronic furan treatment. We further determined that the percentages of CDX1-positive neoplastic glands and glandular nuclei are significantly higher in primary tumors than in a derived, transplantable cholangiocarcinoma serially-propagated in vivo. Western blotting confirmed our immunohistochemical results, and no CDX1 immunoreactivity was detected in normal adult rat liver or in hyperplastic biliary epithelial cells. These findings indicate that CDX1 is specifically associated with early intestinal metaplasia and a later developed intestinal-type of cholangiocarcinoma induced in the liver of furan-treated rats.

Intestinal alkaline phosphatase at the crossroad of intestinal health and disease - a putative role in type 1 diabetes.

PubMed

Lassenius, M I; Fogarty, C L; Blaut, M; Haimila, K; Riittinen, L; Paju, A; Kirveskari, J; Järvelä, J; Ahola, A J; Gordin, D; Härma, M-A; Kumar, A; Hamarneh, S R; Hodin, R A; Sorsa, T; Tervahartiala, T; Hörkkö, S; Pussinen, P J; Forsblom, C; Jauhiainen, M; Taskinen, M-R; Groop, P-H; Lehto, M

2017-06-01

Patients with type 1 diabetes have shown an increase in circulating cytokines, altered lipoprotein metabolism and signs of vascular dysfunction in response to high-fat meals. Intestinal alkaline phosphatase (IAP) regulates lipid transport and inflammatory responses in the gastrointestinal tract. We therefore hypothesized that changes in IAP activity could have profound effects on gut metabolic homeostasis in patients with type 1 diabetes. Faecal samples of 41 nondiabetic controls and 46 patients with type 1 diabetes were analysed for IAP activity, calprotectin, immunoglobulins and short-chain fatty acids (SCFAs). The impact of oral IAP supplementation on intestinal immunoglobulin levels was evaluated in C57BL/6 mice exposed to high-fat diet for 11 weeks. Patients with type 1 diabetes exhibited signs of intestinal inflammation. Compared to controls, patients with diabetes had higher faecal calprotectin levels, lower faecal IAP activities accompanied by lower propionate and butyrate concentrations. Moreover, the amount of faecal IgA and the level of antibodies binding to oxidized LDL were decreased in patients with type 1 diabetes. In mice, oral IAP supplementation increased intestinal IgA levels markedly. Deprivation of protective intestinal factors may increase the risk of inflammation in the gut - a phenomenon that seems to be present already in patients with uncomplicated type 1 diabetes. Low levels of intestinal IgA and antibodies to oxidized lipid epitopes may predispose such patients to inflammation-driven complications such as cardiovascular disease and diabetic nephropathy. Importantly, oral IAP supplementation could have beneficial therapeutic effects on gut metabolic homeostasis, possibly through stimulation of intestinal IgA secretion. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Primary intestinal lymphangiectasia as a component of autoimmune polyglandular syndrome type I: a report of 2 cases.

PubMed

Makharia, Govind K; Tandon, Nikhil; Stephen, Neil de Jesus Rangel; Gupta, Siddhartha Datta; Tandon, Rakesh K

2007-01-01

Chronic diarrhea and steatorrhea occur frequently in patients with autoimmune polyglandular syndrome (APS) type I. Intestinal lymphangiectasia has been reported earlier as a cause of steatorrhea in a young girl with APS Type I. We describe 2 patients with APS Type I who were found to have intestinal lymphangiectasia, one of whom had symptomatic protein-losing enteropathy.

Apple-peel intestinal atresia: enteroplasty for intestinal lengthening and primary anastomosis.

PubMed

Onofre, Luciano Silveira; Maranhão, Renato Frota de Albuquerque; Martins, Elaine Cristina Soares; Fachin, Camila Girardi; Martins, Jose Luiz

2013-06-01

Apple-peel atresia (or Type-IIIb intestinal atresia) is an unusual type of jejunoileal atresia. They present with jejunal atresia near the ligament of Treitz and a foreshortened small bowel. Many surgical options have been used, but the optimal method of repair remains unclear. We present a case of a newborn with apple-peel intestinal atresia managed by enteroplasty for intestinal lengthening and primary anastomosis. Copyright © 2013 Elsevier Inc. All rights reserved.

Resveratrol and inflammatory bowel disease: the evidence so far.

PubMed

Nunes, Sandra; Danesi, Francesca; Del Rio, Daniele; Silva, Paula

2018-06-01

Despite the fact that inflammatory bowel disease (IBD) has still no recognised therapy, treatments which have proven at least mildly successful in improving IBD symptoms include anti-inflammatory drugs and monoclonal antibodies targeting pro-inflammatory cytokines. Resveratrol, a natural (poly)phenol found in grapes, red wine, grape juice and several species of berries, has been shown to prevent and ameliorate intestinal inflammation. Here, we discuss the role of resveratrol in the improvement of inflammatory disorders involving the intestinal mucosa. The present review covers three specific aspects of resveratrol in the framework of inflammation: (i) its content in food; (ii) its intestinal absorption and metabolism; and (iii) its anti-inflammatory effects in the intestinal mucosa in vitro and in the very few in vivo studies present to date. Actually, if several studies have shown that resveratrol may down-regulate mediators of intestinal immunity in rodent models, only two groups have performed intervention studies in human subjects using resveratrol as an agent to improve IBD conditions. The effects of resveratrol should be further investigated by conducting well-designed clinical trials, also taking into account different formulations for the delivery of the bioactive compound.

A common molecular signature of intestinal-type gastric carcinoma indicates processes related to gastric carcinogenesis.

PubMed

Binato, Renata; Santos, Everton Cruz; Boroni, Mariana; Demachki, Samia; Assumpção, Paulo; Abdelhay, Eliana

2018-01-26

Gastric carcinoma (GC) is one of the most aggressive cancers and the second leading cause of cancer death in the world. According to the Lauren classification, this adenocarcinoma is divided into two subtypes, intestinal and diffuse, which differ in their clinical, epidemiological and molecular features. Several studies have attempted to delineate the molecular signature of gastric cancer to develop new and non-invasive screening tests that improve diagnosis and lead to new treatment strategies. However, a consensus signature has not yet been identified for each condition. Thus, this work aimed to analyze the gene expression profile of Brazilian intestinal-type GC tissues using microarrays and compare the results to those of non-tumor tissue samples. Moreover, we compared our intestinal-type gastric carcinoma profile with those obtained from populations worldwide to assess their similarity. The results identified a molecular signature for intestinal-type GC and revealed that 38 genes differentially expressed in Brazilian intestinal-type gastric carcinoma samples can successfully distinguish gastric tumors from non-tumor tissue in the global population. These differentially expressed genes participate in biological processes important to cell homeostasis. Furthermore, Kaplan-Meier analysis suggested that 7 of these genes could individually be able to predict overall survival in intestinal-type gastric cancer patients.

Immunologic and metabolic effects of high-refined carbohydrate-containing diet in food allergic mice.

PubMed

Yamada, Letícia Tamie Paiva; de Oliveira, Marina Chaves; Batista, Nathália Vieira; Fonseca, Roberta Cristelli; Pereira, Rafaela Vaz Sousa; Perez, Denise Alves; Teixeira, Mauro Martins; Cara, Denise Carmona; Ferreira, Adaliene Versiani Matos

2016-02-01

Allergic mice show a reduction in body weight and adiposity with a higher inflammatory response in the adipose tissue similar to obese fat tissue. This study aimed to evaluate whether the low-grade inflammatory milieu of mice with diet-induced mild obesity interferes with the allergic response induced by ovalbumin (OVA). BALB/c mice were divided into four groups: 1) non-allergic (OVA-) mice fed chow diet, 2) allergic (OVA+) mice fed chow diet, 3) OVA- mice fed high-refined carbohydrate-containing (HC) diet, and 4) OVA+ mice fed HC diet. After 5 wk, allergic groups were sensitized with OVA and received a booster 14 d later. All groups received an oral OVA challenge 7 d after the booster. Allergic groups showed increased serum levels of total IgE, anti-OVA IgE, and IgG1; a high disease activity index score; aversion to OVA; and increased intestinal eosinophil infiltration. Non-allergic mild-obese mice also showed aversion to OVA and an increased number of eosinophils in the proximal jejunum. After the allergic challenge, OVA+ mice fed chow diet showed weight loss and lower adiposity in several adipose tissue depots. OVA+ mice fed HC diet showed a loss of fat mass only in the mesenteric adipose tissue. Furthermore, increased levels of TNF, IL-6, and IL-10 were observed in this tissue. Our data show that mild-obese allergic mice do not present severe pathologic features of food allergy similar to those exhibited by lean allergic mice. Mild obesity promoted by HC diet ingestion causes important intestinal disorders that appear to modulate the inflammatory response during the antigen challenge. Copyright © 2016 Elsevier Inc. All rights reserved.

Lactobacillus reuteri 6475 Increases Bone Density in Intact Females Only under an Inflammatory Setting

PubMed Central

Collins, Fraser L.; Irwin, Regina; Bierhalter, Hayley; Schepper, Jonathan; Britton, Robert A.

2016-01-01

Background & Aims We previously demonstrated that short-term oral administration of the probiotic Lactobacillus reuteri 6475 enhanced bone density in male but not female mice. We also established that L. reuteri 6475 enhanced bone health and prevented bone loss in estrogen-deficient female mice. In this study, we tested whether a mild inflammatory state and/or a long-term treatment with the probiotic was required to promote a positive bone effect in estrogen-sufficient female mice. Methods A mild inflammatory state was induced in female mice by dorsal surgical incision (DSI). Following DSI animals were orally supplemented with L. reuteri or vehicle control for a period of 8 weeks. Gene expression was measured in the intestine and bone marrow by qPCR. Distal femoral bone density and architecture was analyzed by micro-CT. Results We report that 8 weeks after DSI there is a significant increase in the weight of spleen, thymus and visceral (retroperitoneal) fat pads. Expression of intestinal cytokines and tight junction proteins are also altered 8 weeks post-DSI. Interestingly, L. reuteri treatment was found to display both intestinal region- and inflammation-dependent effects. Unexpectedly we identified that 1) L. reuteri treatment increased bone density in females but only in those that underwent DSI and 2) DSI benefited cortical bone parameters. In the bone marrow, dorsal surgery induced CD4+ T cell numbers, a response that was unaffected by L. reuteri treatment, whereas expression of RANKL, OPG and IL-10 were significantly affected by L. reuteri treatment. Conclusion Our data reveals a previously unappreciated effect of a mild surgical procedure causing a long-lasting effect on inflammatory gene expression in the gut and the bone. Additionally, we demonstrate that in intact female mice, the beneficial effect of L. reuteri on bone requires an elevated inflammatory status. PMID:27058036

Enteroendocrine K and L cells in healthy and type 2 diabetic individuals.

PubMed

Jorsal, Tina; Rhee, Nicolai A; Pedersen, Jens; Wahlgren, Camilla D; Mortensen, Brynjulf; Jepsen, Sara L; Jelsing, Jacob; Dalbøge, Louise S; Vilmann, Peter; Hassan, Hazem; Hendel, Jakob W; Poulsen, Steen S; Holst, Jens J; Vilsbøll, Tina; Knop, Filip K

2018-02-01

Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis. Knowledge of their distribution in humans is sparse and it is unknown whether alterations occur in type 2 diabetes. We aimed to evaluate the distribution of enteroendocrine K and L cells and relevant prohormone-processing enzymes (using immunohistochemical staining), and to evaluate the mRNA expression of the corresponding genes along the entire intestinal tract in individuals with type 2 diabetes and healthy participants. In this cross-sectional study, 12 individuals with type 2 diabetes and 12 age- and BMI-matched healthy individuals underwent upper and lower double-balloon enteroscopy with mucosal biopsy retrieval from approximately every 30 cm of the small intestine and from seven specific anatomical locations in the large intestine. Significantly different densities for cells positive for chromogranin A (CgA), glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, peptide YY, prohormone convertase (PC) 1/3 and PC2 were observed along the intestinal tract. The expression of CHGA did not vary along the intestinal tract, but the mRNA expression of GCG, GIP, PYY, PCSK1 and PCSK2 differed along the intestinal tract. Lower counts of CgA-positive and PC1/3-positive cells, respectively, were observed in the small intestine of individuals with type 2 diabetes compared with healthy participants. In individuals with type 2 diabetes compared with healthy participants, the expression of GCG and PYY was greater in the colon, while the expression of GIP and PCSK1 was greater in the small intestine and colon, and the expression of PCSK2 was greater in the small intestine. Our findings provide a detailed description of the distribution of enteroendocrine K and L cells and the expression of their products in the human intestinal tract and demonstrate significant differences between individuals with type 2 diabetes and healthy participants. NCT03044860.

Canine distemper virus infection in fennec fox (Vulpes zerda).

PubMed

Woo, Gye-Hyeong; Jho, Yeon-Sook; Bak, Eun-Jung

2010-08-01

Fifteen 8-month-old fennec foxes imported from Sudan showed fever, mucopurulent ocular discharge, diarrhea, severe emaciation, seizures, and generalized ataxia, and died. Three of the 15 animals were presented for diagnostic investigation. Severe dehydration, brain congestion, and gastric ulcers were observed in all animals. In one animal, the lungs had failed to collapse and were multifocally dark red in appearance. Histopathologically, there were lymphohistiocytic meningoencephalitis with malacia, mild interstitial pneumonia, lymphoid depletion of lymphoid tissues and organs, and intestinal villous atrophy with intralesional coccidia. There were many intracytoplasmic and/or intranuclear inclusion bodies in the epithelial cells of the medullary velum, lungs, liver, kidneys, trachea, pancreas, stomach, gall bladder, urinary bladder, and ureters, and in macrophages of malacia foci and lymphocytes and macrophages of lymphoid organs. Additionally, intestinal coccidia were confirmed to be Isospora species by a fecal test. To our knowledge, this is the first report of canine distemper with intestinal coccidiosis in fennec fox.

Examining urea flux across the intestine of the spiny dogfish, Squalus acanthias.

PubMed

Gary Anderson, W; McCabe, Chris; Brandt, Catherine; Wood, Chris M

2015-03-01

Recent examination of urea flux in the intestine of the spiny dogfish shark, Squalus acanthias, has shown that feeding significantly enhances urea uptake across the intestine, and this was significantly inhibited following mucosal addition of phloretin. The present study examined potential mechanisms of urea uptake across the dogfish intestine in starved and fed dogfish. Unidirectional flux chambers were used to examine the kinetics of urea uptake, and to determine the influence of sodium, ouabain, competitive urea analogues, and phloretin on urea uptake across the gut of fed dogfish. Intestinal epithelial preparations from starved and fed dogfish were mounted in Ussing chambers to examine the effect of phloretin on bidirectional solute transport across the intestine. In the unidirectional studies, the maximum uptake rate of urea was found to be 35.3±6.9 μmol.cm(-2).h(-1) and Km was found to be 291.8±9.6 mM in fed fish, and there was a mild inhibition of urea uptake following mucosal addition of competitive agonists. Addition of phloretin, Na-free Ringers and ouabain to the mucosal side of intestinal epithelia also led to a significant reduction in urea uptake in fed fish. In the Ussing chamber studies there was a net influx of urea in fed fish and a small insignificant efflux in starved fish. Addition of phloretin blocked urea uptake in fed fish when added to the mucosal side. Furthermore, phloretin had no effect on ion transport across the intestinal epithelia with the exception of the divalent cations, magnesium and calcium. Copyright © 2015 Elsevier Inc. All rights reserved.

Transitional metaplasia in intestinal epithelium of rats submitted to intestinal cystoplasty and treatment with L -lysine.

PubMed

Santos, Alessandra Marques Dos; Coelho, Joao Paulo Ferreira; Juanes, Camila de Carvalho; Azevedo, Rafael Barbosa de; Diniz, Clara Araujo; Jamacaru, Francisco Vagnaldo Fechine; Dornelas, Conceição Aparecida

2017-04-01

To evaluated the effects of L-lysine on the intestinal and urothelial epithelia in cystoplasty in rats. Twenty-eight 9-week-old rats were assigned to 4 groups: Group A (n=8) cystoplasty followed by administration of L-lysine (150 mg/kg body weight by gavage) for 30 weeks; Group B (n=8) cystoplasty + water for 30 weeks; Group C (n=6) L-lysine for 30 weeks; Group D (n=6) water for 30 weeks. On histopathology with hematoxylin and eosin, mild to moderate hyperplasia transitional was observed in at the site of anastomosis in all animals submitted to cystoplasty (Groups A and B), but "transitional metaplasia" of the intestinal glandular epithelium was more accentuated in Group A (p=0.045). No inflammatory cells, dysplasia or abnormalities were observed. Staining with Alcian blue revealed a substantial reduction of goblet cells and mucins in the colon segment (Groups A and B). The administration of L-lysine to rats accelerated the development of transitional metaplasia in the epithelium of the colon segment in cystoplasty.

Discovery of three novel coccidian parasites infecting California sea lions (Zalophus californianus), with evidence of sexual replication and interspecies pathogenicity.

PubMed

Colegrove, Kathleen M; Grigg, Michael E; Carlson-Bremer, Daphne; Miller, Robin H; Gulland, Frances M D; Ferguson, David J P; Rejmanek, Daniel; Barr, Bradd C; Nordhausen, Robert; Melli, Ann C; Conrad, Patricia A

2011-10-01

Enteric protozoal infection was identified in 5 stranded California sea lions (Zalophus californianus). Microscopically, the apical cytoplasm of distal jejunal enterocytes contained multiple stages of coccidian parasites, including schizonts with merozoites and spherical gametocytes, which were morphologically similar to coccidians. By histopathology, organisms appeared to be confined to the intestine and accompanied by only mild enteritis. Using electron microscopy, both sexual (microgametocytes, macrogamonts) and asexual (schizonts, merozoites) coccidian stages were identified in enterocytes within parasitophorous vacuoles, consistent with apicomplexan development in a definitive host. Serology was negative for tissue cyst-forming coccidians, and immunohistochemistry for Toxoplasma gondii was inconclusive and negative for Neospora caninum and Sarcocystis neurona. Analysis of ITS-1 gene sequences amplified from frozen or formalin-fixed paraffin-embedded intestinal sections identified DNA sequences with closest homology to Neospora sp. (80%); these novel sequences were referred to as belonging to coccidian parasites "A," "B," and "C." Subsequent molecular analyses completed on a neonatal harbor seal (Phoca vitulina) with protozoal lymphadenitis, hepatitis, myocarditis, and encephalitis showed that it was infected with a coccidian parasite bearing the "C" sequence type. Our results indicate that sea lions likely serve as definitive hosts for 3 newly described coccidian parasites, at least 1 of which is pathogenic in a marine mammal intermediate host species.

A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection.

PubMed

Saxena, Kapil; Simon, Lukas M; Zeng, Xi-Lei; Blutt, Sarah E; Crawford, Sue E; Sastri, Narayan P; Karandikar, Umesh C; Ajami, Nadim J; Zachos, Nicholas C; Kovbasnjuk, Olga; Donowitz, Mark; Conner, Margaret E; Shaw, Chad A; Estes, Mary K

2017-01-24

The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III IFN (IFN-λ) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue. We infected nontransformed human intestinal enteroid cultures from multiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNA-sequencing and functional assays. The dominant transcriptional pathway induced by HRV infection is a type III IFN-regulated response. Early after HRV infection, low levels of type III IFN protein activate IFN-stimulated genes. However, this endogenous response does not restrict HRV replication because replication-competent HRV antagonizes the type III IFN response at pre- and posttranscriptional levels. In contrast, exogenous IFN treatment restricts HRV replication, with type I IFN being more potent than type III IFN, suggesting that extraepithelial sources of type I IFN may be the critical IFN for limiting enteric virus replication in the human intestine.

A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

PubMed Central

Saxena, Kapil; Simon, Lukas M.; Zeng, Xi-Lei; Blutt, Sarah E.; Crawford, Sue E.; Sastri, Narayan P.; Karandikar, Umesh C.; Ajami, Nadim J.; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark; Conner, Margaret E.; Shaw, Chad A.; Estes, Mary K.

2017-01-01

The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III IFN (IFN-λ) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue. We infected nontransformed human intestinal enteroid cultures from multiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNA-sequencing and functional assays. The dominant transcriptional pathway induced by HRV infection is a type III IFN-regulated response. Early after HRV infection, low levels of type III IFN protein activate IFN-stimulated genes. However, this endogenous response does not restrict HRV replication because replication-competent HRV antagonizes the type III IFN response at pre- and posttranscriptional levels. In contrast, exogenous IFN treatment restricts HRV replication, with type I IFN being more potent than type III IFN, suggesting that extraepithelial sources of type I IFN may be the critical IFN for limiting enteric virus replication in the human intestine. PMID:28069942

Fecal markers of inflammation, protein loss, and microbial changes in dogs with the acute hemorrhagic diarrhea syndrome (AHDS).

PubMed

Heilmann, Romy M; Guard, Melissa M; Steiner, Jörg M; Suchodolski, Jan S; Unterer, Stefan

2017-09-01

Idiopathic acute hemorrhagic diarrhea syndrome (AHDS) is characterized by acute onset of bloody diarrhea, severe dehydration, and increased vascular and intestinal mucosal permeability. Markers of gastrointestinal inflammation, protein loss, and changes in the intestinal microbiota have not been studied extensively in dogs with AHDS. For 3 consecutive days, feces were collected from dogs with AHDS, and assayed for calprotectin and S100A12 (both markers of inflammation), α 1 -proteinase inhibitor (a marker of gastrointestinal protein loss), and the presence of selected species of bacteria. Concentrations of all assayed markers were significantly greater than the institutional reference intervals at the time of presentation, and all decreased significantly by Day 3 of treatment. Abundances of selected bacterial groups (Ruminococcaceae, Faecalibacterium spp., Bifidobacterium spp., and Proteobacteria) at the time of diagnosis were consistent with an intestinal bacterial dysbiosis. No differences in the abundance of bacterial groups over time was seen, except for a mild but significant decrease in Ruminococcaceae at Day 3. These results suggest that canine AHDS is associated with a significant but transient gastrointestinal loss of protein and intestinal inflammation. The intestinal bacterial dysbiosis appears to outlast the protein loss and inflammation. © Veterinary Emergency and Critical Care Society 2017.

Distinguishing Intestinal Lymphoma From Inflammatory Bowel Disease in Canine Duodenal Endoscopic Biopsy Samples.

PubMed

Carrasco, V; Rodríguez-Bertos, A; Rodríguez-Franco, F; Wise, A G; Maes, R; Mullaney, T; Kiupel, M

2015-07-01

Inflammatory bowel disease (IBD) and intestinal lymphoma are intestinal disorders in dogs, both causing similar chronic digestive signs, although with a different prognosis and different treatment requirements. Differentiation between these 2 conditions is based on histopathologic evaluation of intestinal biopsies. However, an accurate diagnosis is often difficult based on histology alone, especially when only endoscopic biopsies are available to differentiate IBD from enteropathy-associated T-cell lymphoma (EATL) type 2, a small cell lymphoma. The purpose of this study was to evaluate the utility of histopathology; immunohistochemistry (IHC) for CD3, CD20, and Ki-67; and polymerase chain reaction (PCR) for antigen receptor rearrangement (T-cell clonality) in the differential diagnosis of severe IBD vs intestinal lymphoma. Endoscopic biopsies from 32 dogs with severe IBD or intestinal lymphoma were evaluated. The original diagnosis was based on microscopic examination of hematoxylin and eosin (HE)-stained sections alone followed by a second evaluation using morphology in association with IHC for CD3 and CD20 and a third evaluation using PCR for clonality. Our results show that, in contrast to feline intestinal lymphomas, 6 of 8 canine small intestinal lymphomas were EATL type 1 (large cell) lymphomas. EATL type 2 was uncommon. Regardless, in dogs, intraepithelial lymphocytes were not an important diagnostic feature to differentiate IBD from EATL as confirmed by PCR. EATL type 1 had a significantly higher Ki-67 index than did EATL type 2 or IBD cases. Based on the results of this study, a stepwise diagnostic approach using histology as the first step, followed by immunophenotyping and determining the Ki67 index and finally PCR for clonality, improves the accuracy of distinguishing intestinal lymphoma from IBD in dogs. © The Author(s) 2014.

Experimental investigation into biomechanical and biotribological properties of a real intestine and their significance for design of a spiral-type robotic capsule.

PubMed

Zhou, Hao; Alici, Gursel; Than, Trung D; Li, Weihua

2014-03-01

This article reports on the results and implications of our experimental investigation into the biomechanical and biotribological properties of a real intestine for the optimal design of a spiral-type robotic capsule. Dynamic shear experiments were conducted to evaluate how the storage and loss moduli and damping factor of the small intestine change with the speed or the angular frequency. The sliding friction between differently shaped test pieces, with a topology similar to that of the spirals, and the intestine sample was experimentally determined. Our findings demonstrate that the intestine's biomechanical and biotribological properties are coupled, suggesting that the sliding friction is strongly related to the internal friction of the intestinal tissue. The significant implication of this finding is that one can predict the reaction force between the capsule with a spiral-type traction topology and the intestine directly from the intestine's biomechanical measurements rather than employing complicated three-dimensional finite element analysis or an inaccurate analytical model. Sliding friction experiments were also conducted with bar-shaped solid samples to determine the sliding friction between the samples and the small intestine. This sliding friction data will be useful in determining spiral material for an optimally designed robotic capsule.

Effects of Clostridium perfringens iota toxin in the small intestine of mice.

PubMed

Redondo, Leandro M; Redondo, Enzo A; Dailoff, Gabriela C; Leiva, Carlos L; Díaz-Carrasco, Juan M; Bruzzone, Octavio A; Cangelosi, Adriana; Geoghegan, Patricia; Fernandez-Miyakawa, Mariano E

2017-12-01

Iota toxin is a binary toxin solely produced by Clostridium perfringens type E strains, and is structurally related to CDT from C. difficile and CST from C. spiroforme. As type E causes hemorrhagic enteritis in cattle, it is usually assumed that associated diseases are mediated by iota toxin, although evidence in this regard has not been provided. In the present report, iota toxin intestinal effects were evaluated in vivo using a mouse model. Histological damage was observed in ileal loops treated with purified iota toxin after 4 h of incubation. Luminal iota toxin induced fluid accumulation in the small intestine in a dose dependent manner, as determined by the enteropooling and the intestinal loop assays. None of these changes were observed in the large intestine. These results suggest that C. perfringens iota toxin alters intestinal permeability, predominantly by inducing necrosis and degenerative changes in the mucosal epithelium of the small intestine, as well as changes in intestinal motility. The obtained results suggest a central role for iota toxin in the pathogenesis of C. perfringens type E hemorrhagic enteritis, and contribute to remark the importance of clostridial binary toxins in digestive diseases. Published by Elsevier Ltd.

The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes.

PubMed

Rubino, Francesco; Forgione, Antonello; Cummings, David E; Vix, Michel; Gnuli, Donatella; Mingrone, Geltrude; Castagneto, Marco; Marescaux, Jacques

2006-11-01

Most patients who undergo Roux-en-Y gastric bypass (RYGB) experience rapid resolution of type 2 diabetes. Prior studies indicate that this results from more than gastric restriction and weight loss, implicating the rearranged intestine as a primary mediator. It is unclear, however, if diabetes improves because of enhanced delivery of nutrients to the distal intestine and increased secretion of hindgut signals that improve glucose homeostasis, or because of altered signals from the excluded segment of proximal intestine. We sought to distinguish between these two mechanisms. Goto-Kakizaki (GK) type 2 diabetic rats underwent duodenal-jejunal bypass (DJB), a stomach-preserving RYGB that excludes the proximal intestine, or a gastrojejunostomy (GJ), which creates a shortcut for ingested nutrients without bypassing any intestine. Controls were pair-fed (PF) sham-operated and untreated GK rats. Rats that had undergone GJ were then reoperated to exclude the proximal intestine; and conversely, duodenal passage was restored in rats that had undergone DJB. Oral glucose tolerance (OGTT), food intake, body weight, and intestinal nutrient absorption were measured. There were no differences in food intake, body weight, or nutrient absorption among surgical groups. DJB-treated rats had markedly better oral glucose tolerance compared with all control groups as shown by lower peak and area-under-the-curve glucose values (P < 0.001 for both). GJ did not affect glucose homeostasis, but exclusion of duodenal nutrient passage in reoperated GJ rats significantly improved glucose tolerance. Conversely, restoration of duodenal passage in DJB rats reestablished impaired glucose tolerance. This study shows that bypassing a short segment of proximal intestine directly ameliorates type 2 diabetes, independently of effects on food intake, body weight, malabsorption, or nutrient delivery to the hindgut. These findings suggest that a proximal intestinal bypass could be considered for diabetes treatment and that potentially undiscovered factors from the proximal bowel might contribute to the pathophysiology of type 2 diabetes.

Influence of proton pump inhibitors on gastritis diagnosis and pathologic gastric changes

PubMed Central

Nasser, Soumana C; Slim, Mahmoud; Nassif, Jeanette G; Nasser, Selim M

2015-01-01

AIM: To investigate the influence of proton pump inhibitors (PPIs) exposure on the diagnosis of Helicobacter pylori (H. pylori) gastritis and intestinal metaplasia. METHODS: Chronic PPI use is associated with masking of H. pylori infection. Patients with H. pylori infection are predisposed to gastric and duodenal ulcers, and long-term infection with this organism has been associated with gastric mucosal atrophy and serious long-term complications, such as gastric lymphoma and adenocarcinoma. Three hundred patients diagnosed with gastritis between January 2008 and April 2010 were included in our study. The computerized medical database of these patients was reviewed retrospectively in order to assess whether the type of gastritis diagnosed (H. pylori vs non-H. pylori gastritis) is influenced by PPI exposure. H. pylori density was graded as low, if corresponding to mild density following the Updated Sydney System, or high, if corresponding to moderate or severe densities in the Updated Sydney System. RESULTS: Patients were equally distributed between males and females with a median age at the time of diagnosis of 50 years old (range: 20-87). The histological types of gastritis were classified as H. pylori gastritis (n = 156, 52%) and non-H. pylori gastritis (n = 144, 48%). All patients with non-H. pylori gastritis had inactive chronic gastritis. Patients with no previous PPI exposure were more likely to be diagnosed with H. pylori gastritis than those with previous PPI exposure (71% vs 34.2%, P < 0.001). Intestinal metaplasia was more likely to be detected in the latter patients (1.4% vs 6.5%, P = 0.023). Multivariate analysis has also demonstrated that in the presence of previous PPI exposure (OR = 0.217, 95%CI: 0.123-0.385), GERD (OR = 0.317, 95%CI: 0.132-0.763, P = 0.01), alcohol intake (OR = 0.396, 95%CI: 0.195-0.804, P = 0.01), the detection of H. pylori was less likely. Chronic use of PPIs may mask H. pylori infections promoting the diagnosis of non-H. pylori gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia. CONCLUSION: The use of PPIs masks H. pylori infection, promotes the diagnosis of non-H. pylori inactive chronic gastritis diagnosis, and increases the incidence of intestinal metaplasia. PMID:25914469

Influence of proton pump inhibitors on gastritis diagnosis and pathologic gastric changes.

PubMed

Nasser, Soumana C; Slim, Mahmoud; Nassif, Jeanette G; Nasser, Selim M

2015-04-21

To investigate the influence of proton pump inhibitors (PPIs) exposure on the diagnosis of Helicobacter pylori (H. pylori) gastritis and intestinal metaplasia. Chronic PPI use is associated with masking of H. pylori infection. Patients with H. pylori infection are predisposed to gastric and duodenal ulcers, and long-term infection with this organism has been associated with gastric mucosal atrophy and serious long-term complications, such as gastric lymphoma and adenocarcinoma. Three hundred patients diagnosed with gastritis between January 2008 and April 2010 were included in our study. The computerized medical database of these patients was reviewed retrospectively in order to assess whether the type of gastritis diagnosed (H. pylori vs non-H. pylori gastritis) is influenced by PPI exposure. H. pylori density was graded as low, if corresponding to mild density following the Updated Sydney System, or high, if corresponding to moderate or severe densities in the Updated Sydney System. Patients were equally distributed between males and females with a median age at the time of diagnosis of 50 years old (range: 20-87). The histological types of gastritis were classified as H. pylori gastritis (n = 156, 52%) and non-H. pylori gastritis (n = 144, 48%). All patients with non-H. pylori gastritis had inactive chronic gastritis. Patients with no previous PPI exposure were more likely to be diagnosed with H. pylori gastritis than those with previous PPI exposure (71% vs 34.2%, P < 0.001). Intestinal metaplasia was more likely to be detected in the latter patients (1.4% vs 6.5%, P = 0.023). Multivariate analysis has also demonstrated that in the presence of previous PPI exposure (OR = 0.217, 95%CI: 0.123-0.385), GERD (OR = 0.317, 95%CI: 0.132-0.763, P = 0.01), alcohol intake (OR = 0.396, 95%CI: 0.195-0.804, P = 0.01), the detection of H. pylori was less likely. Chronic use of PPIs may mask H. pylori infections promoting the diagnosis of non-H. pylori gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia. The use of PPIs masks H. pylori infection, promotes the diagnosis of non-H. pylori inactive chronic gastritis diagnosis, and increases the incidence of intestinal metaplasia.

Subchronic mild noise stress increases HRP permeability in rat small intestine in vitro.

PubMed

Bijlsma, P B; van Raaij, M T; Dobbe, C J; Timmerman, A; Kiliaan, A J; Taminiau, J A; Groot, J A

2001-05-01

Recently we reported an increased trans- and paracellular protein permeability in rat small intestine after acute cold restraint stress. In the present study, we applied randomized 95- or 105-dB white noise pulses during 45 min/h, 12 h/day, duration 8 days, as a milder, but more chronic stressor to male rats. At 8 days before the noise experiments, 50% of the animals were cannulated in the vena cava for blood sampling during the experimental period. The other 50% of the animals were sacrificed at Day 9, segments of ileum were mounted in Ussing chambers and perfused at 37 degrees C. Horseradish peroxidase (HRP) was added mucosally, serosal appearance was detected enzymatically and tissues were fixed for electron microscopy. In the animals exposed to 95-dB noise, plasma corticosterone levels were enhanced twofold compared to controls, and ileal HRP flux was enhanced twofold. Electron micrographs of tissue from stressed or control animals showed no detectable paracellular staining of HRP. Quantification of HRP-containing endosomes in enterocytes revealed a twofold increase in endosome number in the animals exposed to 95-db noise indicating that the increased HRP permeability was primarily due to increased endocytosis. In contrast to the animals exposed to 95-dB noise, rats exposed to 105-dB noise showed no increase in corticosterone levels and ileal HRP fluxes were not significantly different from controls. We conclude that mild subchronic noise stress may cause a decrease in intestinal barrier function by increased transcytosis of luminal antigens.

Benign intestinal glandular lesions in the vagina: a possible correlation with implantation.

PubMed

Lu, Weiwei; Zhang, Xiaofei; Lu, Bingjian

2016-06-17

Enteric-type glandular lesions are extremely rare in the vagina. Their histological origin remains a matter of speculation at present. We review two rectal mucosal prolapse-like polyps and one intestinal-type adenosis in the vagina. Case 1, a 64-year-old woman, presented with a vaginal polypoid lesion with a size of 4 × 3 × 3 cm. Case 2, an 8-year-old girl, had a 1.5 × 1.5 × 0.8-cm pedunculated polyp in the vaginal navicular fossa and a clinically suspected rectovaginal fistula. Case 1 and 3 had an obsolete severe perineal laceration. On histopathological examination, cases 1 and 2 resembled rectal mucosal prolapse or inflammatory cloacogenic polyp (rectal mucosal prolapse-like polyp). Case 3 had an incidental intestinal-type adenosis in the removed vaginal wall. Immunohistochemistry confirmed the intestinal differentiation in all 3 lesions by showing diffuse CDX2-positive, CK20-positive, and scattered chromogranin A-positive neuroendocrinal cells in the lower compartment of the crypt. In summary, we report herein three unusual cases of benign intestinal-type glandular lesions in the vagina including two rectal mucosal prolapse-like polyps and one case of intestinal-type adenosis, and discuss possibilities for their histogenetic basis.

Systematic review of loperamide: No proof of antibiotics being superior to loperamide in treatment of mild/moderate travellers' diarrhoea.

PubMed

Lääveri, Tinja; Sterne, Jesper; Rombo, Lars; Kantele, Anu

2016-01-01

Looking at the worldwide emergency of antimicrobial resistance, international travellers appear to have a central role in spreading the bacteria across the globe. Travellers' diarrhoea (TD) is the most common disease encountered by visitors to the (sub)tropics. Both TD and its treatment with antibiotics have proved significant independent risk factors of colonization by resistant intestinal bacteria while travelling. Travellers should therefore be given preventive advice regarding TD and cautioned about taking antibiotics: mild or moderate TD does not require antibiotics. Logical alternatives are medications with effects on gastrointestinal function, such as loperamide. The present review explores literature on loperamide in treating TD. Adhering to manufacturer's dosage recommendations, loperamide offers a safe and effective alternative for relieving mild and moderate symptoms. Moreover, loperamide taken singly does no predispose to contracting MDR bacteria. Most importantly, we found no proof that would show antibiotics to be significantly more effective than loperamide in treating mild/moderate TD. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Intestinal metaplasia in Barrett's oesophagus may be an epiphenomenon rather than a preneoplastic condition, and CDX2-positive cardiac-type epithelium is associated with minute Barrett's tumour.

PubMed

Watanabe, Gen; Ajioka, Yoichi; Takeuchi, Manabu; Annenkov, Alexey; Kato, Takashi; Watanabe, Kaori; Tani, Yusuke; Ikegami, Kikuo; Yokota, Yoko; Fukuda, Mutsumi

2015-01-01

Although intestinal-type epithelium in Barrett's oesophagus has been traditionally recognized as having a distinct malignant potential, whether this also holds true for cardiac-type epithelium remains controversial. The aim of this study was to identify a type of epithelium that is highly associated with Barrett's tumour. We analysed tumours and the corresponding background mucosa with special regard to tumour size in 40 cases of superficial Barrett's tumour by using immunohistochemical staining for CDX2, CD10, MUC2, MUC5AC, and MUC6. Intestinal metaplasia in tumour-adjacent mucosa was not associated with tumour size, but was significantly correlated with the extent of Barrett's oesophagus (P < 0.001). The majority (69.2%, 9/13) of small tumours (≤10 mm) had no intestinal metaplasia in adjacent non-neoplastic mucosae. Minute (≤5 mm) tumours were significantly associated with a gastric immunophenotype (P < 0.001). Purely gastric-immunophenotype tumour cells expressed CDX2, and cardiac-type epithelium adjacent to small tumours also showed low-level CDX2 expression. Our data suggest that intestinal metaplasia in Barrett's oesophagus is an epiphenomenon rather than a preneoplastic condition, and that CDX2-positive cardiac-type epithelium is highly associated with minute Barrett's tumour. Further prospective studies are needed to evaluate the risk of malignancy of cardiac-type epithelium with regard to sub-morphological intestinalization. © 2014 The Authors. Histopathology published by John Wiley & Sons Ltd.

HLA-G is expressed in intestinal samples of ulcerative colitis and Crohn's disease patients and HLA-G5 expression is differentially correlated with TNF and IL-10 cytokine expression.

PubMed

Gomes, Renan Garcia; Brito, Carlos Alexandre Antunes de; Martinelli, Valéria Ferreira; Santos, Rossana Nascimento Dos; Gomes, Fabiana Oliveira Dos Santos; Peixoto, Christina Alves; Crispim, Janaína Oliveira; Diniz, George Tadeu Nunes; Donadi, Eduardo Antônio; Lucena-Silva, Norma

2018-06-01

HLA-G is an immunomodulatory molecule that can be produced by epithelial cells. Considering that TNF and IL-10 participate in bowel inflammatory disorders and that both cytokines modulate HLA-G, we evaluated HLA-G, TNF and IL-10 mRNA expression by qPCR and HLA-G protein levels by immunohistochemistry in two intestinal samples exhibiting different degree of inflammation within a patient suffering from Crohn's disease (CD) or ulcerative colitis (UC). Tissue HLA-G5 (P < 0.0001), TNF (P = 0.0004) and IL-10 (P = 0.0169) mRNA expression levels were higher in intestinal areas exhibiting intense inflammation compared to areas of low inflammation, and HLA-G protein levels were not associated with degree of mucosal inflammation. In CD, the expression of TNF was correlated with IL-10 in low inflamed areas, exhibiting a TNF:IL-10 ratio = 3, but in inflamed areas the ratio increased to 9-folds. In UC, the expression of TNF was correlated to IL-10, irrespective of the inflammation grade, with little variation of the TNF:IL-10 ratio in the various inflamed areas. TNF and IL-10 expression was correlated with HLA-G5 expression in mild inflamed areas. Both CD and UC samples exhibited gene and protein expression of HLA-G; and the HLA-G5 expression is differentially correlated with TNF and IL-10 levels depending on the type of the underlying inflammatory bowel disorder. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Granulomatous encephalomyelitis and intestinal ganglionitis in a spectacled Amazon parrot (Amazona albifrons) infected with Mycobacterium genavense.

PubMed

Gomez, G; Saggese, M D; Weeks, B R; Hoppes, S M; Porter, B F

2011-01-01

An approximately 30-year-old male spectacled Amazon parrot (Amazona albifrons) was presented with a 2-week history of ataxia, head shaking, weight loss and seizures. Gross findings on necropsy examination included atrophy of the musculature, ruffled feathers and minimal epicardial and abdominal fat. Microscopically, there were perivascular cuffs of macrophages with fewer lymphocytes in the grey and white matter of the brain and spinal cord. These lesions were accompanied by gliosis and mild vacuolation of the white matter. In the small intestine, up to 70% of the intestinal ganglia were effaced by infiltrates of macrophages and fewer lymphocytes. The intestinal lamina propria contained multiple inflammatory aggregates of a similar nature. Ziehl-Neelsen staining revealed the presence of numerous bacilli within the cytoplasm of macrophages in the central nervous system (CNS) and enteric ganglia. Amplification of the DNAJ gene confirmed a mycobacterial infection and subsequent polymerase chain reaction (PCR) using a species-specific primer confirmed the aetiology as Mycobacterium genavense. Infection of the CNS with Mycobacterium spp. is uncommon and has not been previously reported in a parrot. This case is unusual in that the organism exhibited tropism for neural tissue. Copyright © 2010 Elsevier Ltd. All rights reserved.

Evaluation of isolation methods for pathogenic Yersinia enterocolitica from pig intestinal content.

PubMed

Laukkanen, R; Hakkinen, M; Lundén, J; Fredriksson-Ahomaa, M; Johansson, T; Korkeala, H

2010-03-01

The aim of this study was to evaluate the efficiency of four isolation methods for the detection of pathogenic Yersinia enterocolitica from pig intestinal content. The four methods comprised of 15 isolation steps using selective enrichments (irgasan-ticarcillin-potassium chlorate and modified Rappaport broth) and mildly selective enrichments at 4 or 25 degrees C. Salmonella-Shigella-desoxycholate-calcium chloride agar, cefsulodin-irgasan-novobiocin agar were used as plating media. The most sensitive method detected 78% (53/68) of the positive samples. Individual isolation steps using cold enrichment as the only enrichment or as a pre-enrichment step with further selective enrichment showed the highest sensitivities (55-66%). All isolation methods resulted in high numbers of suspected colonies not confirmed as pathogenic Y. enterocolitica. Cold enrichment should be used in the detection of pathogenic Y. enterocolitica from pig intestinal contents. In addition, more than one parallel isolation step is needed. The study shows that depending on the isolation method used for Y. enterocolitica, the detected prevalence of Y. enterocolitica in pig intestinal contents varies greatly. More selective and sensitive isolation methods need to be developed for pathogenic Y. enterocolitica.

A Case of Intestinal Obstruction Caused by Prominent Kyphosis Resulting in Compression of the Intestine by the Costal Arch

PubMed Central

Yoneyama, Satoshi; Kato, Takehito; Yumoto, Tetsuya; Ohwada, Masami; Terashima, Toru; Koizumi, Masanori; Ueki, Hamaichi

2013-01-01

An 85-year-old woman with no history of abdominal surgery complained of abdominal pain and vomiting and was referred to us with a diagnosis of intestinal obstruction a few days later. Upon admission to our facility, she presented with marked abdominal swelling and prominent kyphosis. Because of the kyphosis, most of the dilated bowel was compressing her thoracic cavity. No obvious strangulation or free air was observed via abdominal computed tomography imaging. We attempted decompression using a nasogastric tube, but the symptoms persisted. Surgery was performed 2 days after admission. The origin of the obstruction was a compression of the ileocecal region by the costal arch. The bowel was discolored, and thus surgically excised. There were no major postsurgical complications other than a mild wound infection. Until now, there have been no reports of advanced kyphosis inducing ileus, but there are concerns of an increase in similar cases as society continues to age. PMID:23971780

Clinical, ultrasonographic, and pathologic findings in 70 camels (Camelus dromedarius) with Johne’s disease

PubMed Central

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Hashad, Mahmoud; Buczinski, Sébastien

2012-01-01

This study evaluated the use of ultrasonography for the diagnosis of Johne’s disease in camels (Camelus dromedarius). Seventy camels with confirmed Johne’s disease were examined by ultrasonography and subsequent necropsy; 15 healthy camels were included as controls. The most outstanding findings were visible enlargement of the mesenteric lymph nodes in 52 (74%) camels. Lesions had either echogenic (26%; n = 18) or anechoic (69%; n = 48) capsule and the contents were either anechoic (21%; n = 15), echogenic (27%; n = 19), or heterogeneous (46%; n = 32). Clumps of echogenic tissue interspersed with fluid pockets were imaged between the intestinal loops in 9 (13%) camels. There was mild, moderate, or severe thickening and corrugation of the intestinal wall, excessive anechoic fluid in the abdominal cavity in 18 (26%) camels, increased hepatic brightness in 30 (43%) camels, and pericardial and pleural effusions in 22 (31%) camels. Sensitivity values for detecting intestinal lesions and enlarged mesenteric lymph nodes were 95% and 84%, respectively. PMID:23115369

Clinical, ultrasonographic, and pathologic findings in 70 camels (Camelus dromedarius) with Johne's disease.

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Hashad, Mahmoud; Buczinski, Sébastien

2012-05-01

This study evaluated the use of ultrasonography for the diagnosis of Johne's disease in camels (Camelus dromedarius). Seventy camels with confirmed Johne's disease were examined by ultrasonography and subsequent necropsy; 15 healthy camels were included as controls. The most outstanding findings were visible enlargement of the mesenteric lymph nodes in 52 (74%) camels. Lesions had either echogenic (26%; n = 18) or anechoic (69%; n = 48) capsule and the contents were either anechoic (21%; n = 15), echogenic (27%; n = 19), or heterogeneous (46%; n = 32). Clumps of echogenic tissue interspersed with fluid pockets were imaged between the intestinal loops in 9 (13%) camels. There was mild, moderate, or severe thickening and corrugation of the intestinal wall, excessive anechoic fluid in the abdominal cavity in 18 (26%) camels, increased hepatic brightness in 30 (43%) camels, and pericardial and pleural effusions in 22 (31%) camels. Sensitivity values for detecting intestinal lesions and enlarged mesenteric lymph nodes were 95% and 84%, respectively.

DENTAL ABNORMALITIES OF EIGHT WILD QINLING GIANT PANDAS (AILUROPODA MELANOLEUCA QINLINGENSIS), SHAANXI PROVINCE, CHINA.

PubMed

Jin, Yipeng; Chen, Si; Chao, Yanqiao; Pu, Tianchun; Xu, Hongqian; Liu, Xiaobin; Zhao, Kaihui; Nie, Yonggang; Wei, Wei; Lin, Degui

2015-10-01

Eight adult (six male and two female) wild Qinling giant pandas (Ailuropoda melanoleuca qinlingensis) from China National Foping Nature Reserve were tracked, and their dental data collected and recorded from October 2010 to April 2014. Each panda had dental abnormalities of varying severity. Dental wear and fracture were the most common conditions. Absent teeth were common, with premolars missing most often. Mild caries were present in five molar teeth between two animals. Different degrees of dental plaque and calculus occurred in all animals but without severe periodontal disease. Two animals with severe dental abnormalities died due to intestinal problems. Large segments of bamboo were found in their intestinal tracts, and intestinal perforation and ulcers were evident, indicating dental abnormalities can be an important factor in the health of wild giant pandas and may lead to death. Further research with larger sample sizes of wild and captive giant pandas will be required to substantiate the relationship between dental abnormalities and mortality in giant pandas.

Campylobacter spp. as a Foodborne Pathogen: A Review

PubMed Central

Silva, Joana; Leite, Daniela; Fernandes, Mariana; Mena, Cristina; Gibbs, Paul Anthony; Teixeira, Paula

2011-01-01

Campylobacter is well recognized as the leading cause of bacterial foodborne diarrheal disease worldwide. Symptoms can range from mild to serious infections of the children and the elderly and permanent neurological symptoms. The organism is a cytochrome oxidase positive, microaerophilic, curved Gram-negative rod exhibiting corkscrew motility and is carried in the intestine of many wild and domestic animals, particularly avian species including poultry. Intestinal colonization results in healthy animals as carriers. In contrast with the most recent published reviews that cover specific aspects of Campylobacter/campylobacteriosis, this broad review aims at elucidating and discussing the (i) genus Campylobacter, growth and survival characteristics; (ii) detection, isolation and confirmation of Campylobacter; (iii) campylobacteriosis and presence of virulence factors; and (iv) colonization of poultry and control strategies. PMID:21991264

Hyperinfection with Strongyloides in a HIV-negative elderly male

PubMed Central

Girija, S; Kannan, Suresh; Jeyakumari, D; Gopal, R

2012-01-01

Strongyloides stercoralis is an intestinal nematode producing mild infection in the immunocompetent and fatal hyperinfection syndrome in the immunocompromised. An elderly HIV-negative male presented with symptoms of chronic respiratory disease and vague abdominal symptoms. Examination of sputum and stools showed larvae of S. stercoralis. Bacterial and fungal causes of respiratory infections were ruled out. The patient responded to oral ivermectin. PMID:23508878

Leaky gut and diabetes mellitus: what is the link?

PubMed

de Kort, S; Keszthelyi, D; Masclee, A A M

2011-06-01

Diabetes mellitus is a chronic disease requiring lifelong medical attention. With hundreds of millions suffering worldwide, and a rapidly rising incidence, diabetes mellitus poses a great burden on healthcare systems. Recent studies investigating the underlying mechanisms involved in disease development in diabetes point to the role of the dys-regulation of the intestinal barrier. Via alterations in the intestinal permeability, intestinal barrier function becomes compromised whereby access of infectious agents and dietary antigens to mucosal immune elements is facilitated, which may eventually lead to immune reactions with damage to pancreatic beta cells and can lead to increased cytokine production with consequent insulin resistance. Understanding the factors regulating the intestinal barrier function will provide important insight into the interactions between luminal antigens and immune response elements. This review analyses recent advances in the mechanistic understanding of the role of the intestinal epithelial barrier function in the development of type 1 and type 2 diabetes. Given our current knowledge, we may assume that reinforcing the intestinal barrier can offer and open new therapeutic horizons in the treatment of type 1 and type 2 diabetes. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.

Endothelial binding of beta toxin to small intestinal mucosal endothelial cells in early stages of experimentally induced Clostridium perfringens type C enteritis in pigs.

PubMed

Schumacher, V L; Martel, A; Pasmans, F; Van Immerseel, F; Posthaus, H

2013-07-01

Beta toxin (CPB) is known to be an essential virulence factor in the development of lesions of Clostridium perfringens type C enteritis in different animal species. Its target cells and exact mechanism of toxicity have not yet been clearly defined. Here, we evaluate the suitability of a neonatal piglet jejunal loop model to investigate early lesions of C. perfringens type C enteritis. Immunohistochemically, CPB was detected at microvascular endothelial cells in intestinal villi during early and advanced stages of lesions induced by C. perfringens type C. This was first associated with capillary dilatation and subsequently with widespread hemorrhage in affected intestinal segments. CPB was, however, not demonstrated on intestinal epithelial cells. This indicates a tropism of CPB toward endothelial cells and suggests that CPB-induced endothelial damage plays an important role in the early stages of C. perfringens type C enteritis in pigs.

Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice

PubMed Central

Hartmann, Phillipp; Chen, Peng; Wang, Hui J.; Wang, Lirui; McCole, Declan F.; Brandl, Katharina; Stärkel, Peter; Belzer, Clara; Hellerbrand, Claus; Tsukamoto, Hidekazu; Ho, Samuel B.; Schnabl, Bernd

2013-01-01

The intestinal mucus layer protects the epithelium from noxious agents, viruses, and pathogenic bacteria present in the gastrointestinal tract. It is composed of mucins, predominantly mucin-2 (Muc2), secreted by goblet cells of the intestine. Experimental alcoholic liver disease requires translocation of bacterial products across the intestinal barrier into the systemic circulation, which induces an inflammatory response in the liver and contributes to steatohepatitis. We investigated the roles of the intestinal mucus layer, and in particular Muc2, in development of experimental alcohol-associated liver disease in mice. We studied experimental alcohol-induced liver disease, induced by the Tsukamoto-French method (which involves continuous intragastric feeding of an isocaloric diet or alcohol) in wild-type and Muc2−/− mice. Muc2−/− mice showed less alcohol-induced liver injury and steatosis that developed in wild-type mice. Most notably, Muc2−/− mice had significantly lower plasma levels of lipopolysaccharide than wild-type mice after alcohol feeding. In contrast to wild-type mice, Muc2−/− mice were protected from alcohol-associated microbiome changes that are dependent on intestinal mucins. The anti-microbial proteins Reg3b and Reg3g were expressed at significantly higher levels in the jejunum of Muc2−/− mice fed the isocaloric diet or alcohol, compared with wild-type mice. Consequently, Muc2−/− mice showed increased killing of commensal bacteria and prevented intestinal bacterial overgrowth. Conclusion: Muc2−/− mice are protected from intestinal bacterial overgrowth and dysbiosis in response to alcohol feeding. Subsequently, lower amounts of bacterial products such as endotoxin translocate into the systemic circulation, decreasing liver disease. PMID:23408358

Comparison of gene-expression profiles between diffuse- and intestinal-type gastric cancers using a genome-wide cDNA microarray.

PubMed

Jinawath, Natini; Furukawa, Yoichi; Hasegawa, Suguru; Li, Meihua; Tsunoda, Tatsuhiko; Satoh, Seiji; Yamaguchi, Toshiharu; Imamura, Hiroshi; Inoue, Masatomo; Shiozaki, Hitoshi; Nakamura, Yusuke

2004-09-02

Gastric cancer is the fourth leading cause of cancer-related death in the world. Two histologically distinct types of gastric carcinoma, 'intestinal' and 'diffuse', have different epidemiological and pathophysiological features that suggest different mechanisms of carcinogenesis. A number of studies have investigated intestinal-type gastric cancers at the molecular level, but little is known about mechanisms involved in the diffuse type, which has a more invasive phenotype and poorer prognosis. To clarify the mechanisms that underlie its development and/or progression, we compared the expression profiles of 20 laser-microbeam-microdissected diffuse-type gastric-cancer tissues with corresponding noncancerous mucosae by means of a cDNA microarray containing 23,040 genes. We identified 153 genes that were commonly upregulated and more than 1500 that were commonly downregulated in the tumors. We also identified a number of genes related to tumor progression. Furthermore, comparison of the expression profiles of diffuse-type with those of intestinal-type gastric cancers identified 46 genes that may represent distinct molecular signatures of each histological type. The putative signature of diffuse-type cancer exhibited altered expression of genes related to cell-matrix interaction and extracellular-matrix (ECM) components, whereas that of intestinal-type cancer represented enhancement of cell growth. These data provide insight into different mechanisms underlying gastric carcinogenesis and may also serve as a starting point for identifying novel diagnostic markers and/or therapeutic targets for diffuse-type gastric cancers.

Ongoing ingestive behavior is rapidly suppressed by a preabsorptive, intestinal “bitter taste” cue

PubMed Central

Davidson, Terry L.; Powley, Terry L.

2011-01-01

The discovery that cells in the gastrointestinal (GI) tract express the same molecular receptors and intracellular signaling components known to be involved in taste has generated great interest in potential functions of such post-oral “taste” receptors in the control of food intake. To determine whether taste cues in the GI tract are detected and can directly influence behavior, the present study used a microbehavioral analysis of intake, in which rats drank from lickometers that were programmed to simultaneously deliver a brief yoked infusion of a taste stimulus to the intestines. Specifically, in daily 30-min sessions, thirsty rats with indwelling intraduodenal catheters were trained to drink hypotonic (0.12 M) sodium chloride (NaCl) and simultaneously self-infuse a 0.12 M NaCl solution. Once trained, in a subsequent series of intestinal taste probe trials, rats reduced licking during a 6-min infusion period, when a bitter stimulus denatonium benzoate (DB; 10 mM) was added to the NaCl vehicle for infusion, apparently conditioning a mild taste aversion. Presentation of the DB in isomolar lithium chloride (LiCl) for intestinal infusions accelerated the development of the response across trials and strengthened the temporal resolution of the early licking suppression in response to the arrival of the DB in the intestine. In an experiment to evaluate whether CCK is involved as a paracrine signal in transducing the intestinal taste of DB, the CCK-1R antagonist devazepide partially blocked the response to intestinal DB. In contrast to their ability to detect and avoid the bitter taste in the intestine, rats did not modify their licking to saccharin intraduodenal probe infusions. The intestinal taste aversion paradigm developed here provides a sensitive and effective protocol for evaluating which tastants—and concentrations of tastants—in the lumen of the gut can control ingestion. PMID:21865540

The effect of chronic feeding of diacetoxyscirpenol and T-2 toxin on performance, health, small intestinal physiology and antibody production in turkey poults.

PubMed

Sklan, D; Shelly, M; Makovsky, B; Geyra, A; Klipper, E; Friedman, A

2003-03-01

1. The effects of feeding T-2 toxin or diacetoxyscirpenol (DAS) at levels up to 1 ppm for 32 d on performance, health, small intestinal physiology and immune response to enteral and parenteral immunisation were examined in young poults. 2. Slight improvement in growth was observed in some groups of poults fed T-2 or DAS mycotoxins for 32 d, with no change in feed efficiency. Feeding both T-2 and DAS resulted in oral lesions which had maximal severity after 7-15 d. 3. Mild intestinal changes were observed at 32 d but no pathological or histopathological lesions were found. Both mycotoxins altered small intestinal morphology, especially in the jejunum where villi were shorter and thinner. In addition, both DAS and T-2 mycotoxins enhanced the proportion of proliferating cells both in the crypts and along the villi. Migration rates were reduced in the jejunum of poults fed T-2 toxin but did not change in the duodenum or in poults fed DAS. 4. No significant effects of T-2 or DAS were observed on antibody production to antigens administered by enteral or parenteral routes. 5. This study indicates that tricothecene toxins at concentrations of up to 1 ppm for more than 30 d influenced small intestinal morphology but did not affect growth or antibody production.

Epidermal growth factor receptor signaling pathway is frequently altered in ampullary carcinoma at protein and genetic levels.

PubMed

Mikhitarian, Kaidi; Pollen, Maressa; Zhao, Zhiguo; Shyr, Yu; Merchant, Nipun B; Parikh, Alexander; Revetta, Frank; Washington, M Kay; Vnencak-Jones, Cindy; Shi, Chanjuan

2014-05-01

Our objective was to explore alteration of the epidermal growth factor receptor (EGFR) signaling pathway in ampullary carcinoma. Immunohistochemical studies were employed to evaluate expression of amphiregulin as well as expression and activation of EGFR. A lab-developed assay was used to identify mutations in the EGFR pathway genes, including KRAS, BRAF, PIK3CA, PTEN, and AKT1. A total of 52 ampullary carcinomas were identified, including 25 intestinal-type and 24 pancreatobiliary-type tumors, with the intestinal type being associated with a younger age at diagnosis (P=0.03) and a better prognosis (P<0.01). Expression of amphiregulin correlated with better differentiation (P<0.01), but no difference was observed between two major histologic types. Expression and activation of EGFR was more commonly seen in the pancreatobiliary type (P<0.01). Mutations were detected in 50% of the pancreatobiliary type and 60% of the intestinal type. KRAS was the most common gene mutated in the pancreatobiliary type (42%) as well as the intestinal type (52%). Other mutations detected included PIK3CA, SMAD4 and BRAF. KRAS mutations at codons 12 and 13 did not adversely affect overall survival. In conclusion, EGFR expression and activation were different between intestinal- and pancreatobiliary-type ampullary carcinoma. KRAS mutation was common in both histologic types; however, the incidence appeared to be lower in the pancreatobiliary type compared with its pancreatic counterpart, pancreatic ductal adenocarcinoma. Mutational analysis of the EGFR pathway genes may provide important insights into personalized treatment for patients with ampullary carcinoma.

Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs.

PubMed

Kono, Yoshiyasu; Kawano, Seiji; Takaki, Akinobu; Shimomura, Yasuyuki; Onji, Masahiro; Ishikawa, Hisashi; Takahashi, Sakuma; Horii, Joichiro; Kobayashi, Sayo; Kawai, Daisuke; Yamamoto, Kazuhide; Okada, Hiroyuki

2017-01-01

Video-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model. A total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group). Serum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P < 0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P < 0.01). Serum d-ROM levels were lower in NC and NE than N (P < 0.01), and OXY levels were higher in NC than N and NE (P < 0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N. Non-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Propionyl-L-Carnitine is Efficacious in Ulcerative Colitis Through its Action on the Immune Function and Microvasculature.

PubMed

Scioli, Maria Giovanna; Stasi, Maria Antonietta; Passeri, Daniela; Doldo, Elena; Costanza, Gaetana; Camerini, Roberto; Fociani, Paolo; Arcuri, Gaetano; Lombardo, Katia; Pace, Silvia; Borsini, Franco; Orlandi, Augusto

2014-03-20

Microvascular endothelial dysfunction characterizes ulcerative colitis (UC), the most widespread form of inflammatory bowel disease. Intestinal mucosal microvessels in UC display aberrant expression of cell adhesion molecules (CAMs) and increased inflammatory cell recruitment. Propionyl-L-carnitine (PLC), an ester of L-carnitine required for the mitochondrial transport of fatty acids, ameliorates propionyl-CoA bioavailability and reduces oxidative stress in ischemic tissues. The present study aimed to document the efficacy of anti-oxidative stress properties of PLC in counteracting intestinal microvascular endothelial dysfunction and inflammation. To evaluate the efficacy in vivo, we analyzed the effects in intestinal biopsies of patients with mild-to-moderate UC receiving oral PLC co-treatment and in rat TNBS-induced colitis; in addition, we investigated antioxidant PLC action in TNF-α-stimulated human intestinal microvascular endothelial cells (HIMECs) in vitro. Four-week PLC co-treatment reduced intestinal mucosal polymorph infiltration and CD4(+) lymphocytes, ICAM-1(+) and iNOS(+) microvessels compared with placebo-treated patients with UC. Oral and intrarectal administration of PLC but not L-carnitine or propionate reduced intestinal damage and microvascular dysfunction in rat TNBS-induced acute and reactivated colitis. In cultured TNF-α-stimulated HIMECs, PLC restored β-oxidation and counteracted NADPH oxidase 4-generated oxidative stress-induced CAM expression and leukocyte adhesion. Inhibition of β-oxidation by L-aminocarnitine increased reactive oxygen species production and PLC beneficial effects on endothelial dysfunction and leukocyte adhesion. Finally, PLC reduced iNOS activity and nitric oxide accumulation in rat TNBS-induced colitis and in HIMEC cultures. Our results show that the beneficial antioxidant effect of PLC targeting intestinal microvasculature restores endothelial β-oxidation and function, and reduces mucosal inflammation in UC patients.

Propionyl-L-Carnitine is Efficacious in Ulcerative Colitis Through its Action on the Immune Function and Microvasculature

PubMed Central

Scioli, Maria Giovanna; Stasi, Maria Antonietta; Passeri, Daniela; Doldo, Elena; Costanza, Gaetana; Camerini, Roberto; Fociani, Paolo; Arcuri, Gaetano; Lombardo, Katia; Pace, Silvia; Borsini, Franco; Orlandi, Augusto

2014-01-01

Objectives: Microvascular endothelial dysfunction characterizes ulcerative colitis (UC), the most widespread form of inflammatory bowel disease. Intestinal mucosal microvessels in UC display aberrant expression of cell adhesion molecules (CAMs) and increased inflammatory cell recruitment. Propionyl-L-carnitine (PLC), an ester of L-carnitine required for the mitochondrial transport of fatty acids, ameliorates propionyl-CoA bioavailability and reduces oxidative stress in ischemic tissues. The present study aimed to document the efficacy of anti-oxidative stress properties of PLC in counteracting intestinal microvascular endothelial dysfunction and inflammation. Methods: To evaluate the efficacy in vivo, we analyzed the effects in intestinal biopsies of patients with mild-to-moderate UC receiving oral PLC co-treatment and in rat TNBS-induced colitis; in addition, we investigated antioxidant PLC action in TNF-α-stimulated human intestinal microvascular endothelial cells (HIMECs) in vitro. Results: Four-week PLC co-treatment reduced intestinal mucosal polymorph infiltration and CD4+ lymphocytes, ICAM-1+ and iNOS+ microvessels compared with placebo-treated patients with UC. Oral and intrarectal administration of PLC but not L-carnitine or propionate reduced intestinal damage and microvascular dysfunction in rat TNBS-induced acute and reactivated colitis. In cultured TNF-α-stimulated HIMECs, PLC restored β-oxidation and counteracted NADPH oxidase 4-generated oxidative stress-induced CAM expression and leukocyte adhesion. Inhibition of β-oxidation by L-aminocarnitine increased reactive oxygen species production and PLC beneficial effects on endothelial dysfunction and leukocyte adhesion. Finally, PLC reduced iNOS activity and nitric oxide accumulation in rat TNBS-induced colitis and in HIMEC cultures. Conclusions: Our results show that the beneficial antioxidant effect of PLC targeting intestinal microvasculature restores endothelial β-oxidation and function, and reduces mucosal inflammation in UC patients. PMID:24646507

Intestinal inflammation induces genotoxicity to extraintestinal tissues and cell types in mice

PubMed Central

Westbrook, Aya M.; Wei, Bo; Braun, Jonathan; Schiestl, Robert H.

2011-01-01

Chronic intestinal inflammation leads to increased risk of colorectal and small intestinal cancers, and is also associated with extraintestinal manifestations such as lymphomas, other solid cancers, and autoimmune disorders. We have previously found that acute and chronic intestinal inflammation causes DNA damage to circulating peripheral leukocytes, manifesting a systemic effect in genetic and chemically-induced models of intestinal inflammation. This study addresses the scope of tissue targets and genotoxic damage induced by inflammation-associated genotoxicity. Using several experimental models of intestinal inflammation, we analyzed various types of DNA damage in leukocyte subpopulations of the blood, spleen, mesenteric and peripheral lymph nodes; and, in intestinal epithelial cells, hepatocytes, and the brain. Genotoxicity in the form of DNA single and double stranded breaks accompanied by oxidative base damage was found in leukocyte subpopulations of the blood, diverse lymphoid organs, intestinal epithelial cells, and hepatocytes. The brain did not demonstrate significant levels of DNA double strand breaks as measured by γ-H2AX immunostaining. CD4+ and CD8+ T-cells were most sensitive to DNA damage versus other cell types in the peripheral blood. In vivo measurements and in vitro modeling suggested that genotoxicity was induced by increased levels of systemically circulating proinflammatory cytokines. Moreover, genotoxicity involved increased damage rather than reduced repair, since it not associated with decreased expression of the DNA double-strand break recognition and repair protein, ataxia telangiectasia mutated (ATM). These findings suggest that levels of intestinal inflammation contribute to the remote tissue burden of genotoxicity, with potential effects on non-intestinal diseases and cancer. PMID:21520038

Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion.

PubMed

Knauf, Felix; Thomson, Robert B; Heneghan, John F; Jiang, Zhirong; Adebamiro, Adedotun; Thomson, Claire L; Barone, Christina; Asplin, John R; Egan, Marie E; Alper, Seth L; Aronson, Peter S

2017-01-01

Patients with cystic fibrosis have an increased incidence of hyperoxaluria and calcium oxalate nephrolithiasis. Net intestinal absorption of dietary oxalate results from passive paracellular oxalate absorption as modified by oxalate back secretion mediated by the SLC26A6 oxalate transporter. We used mice deficient in the cystic fibrosis transmembrane conductance regulator gene (Cftr) to test the hypothesis that SLC26A6-mediated oxalate secretion is defective in cystic fibrosis. We mounted isolated intestinal tissue from C57BL/6 (wild-type) and Cftr -/- mice in Ussing chambers and measured transcellular secretion of [ 14 C]oxalate. Intestinal tissue isolated from Cftr -/- mice exhibited significantly less transcellular oxalate secretion than intestinal tissue of wild-type mice. However, glucose absorption, another representative intestinal transport process, did not differ in Cftr -/- tissue. Compared with wild-type mice, Cftr -/- mice showed reduced expression of SLC26A6 in duodenum by immunofluorescence and Western blot analysis. Furthermore, coexpression of CFTR stimulated SLC26A6-mediated Cl - -oxalate exchange in Xenopus oocytes. In association with the profound defect in intestinal oxalate secretion, Cftr -/- mice had serum and urine oxalate levels 2.5-fold greater than those of wild-type mice. We conclude that defective intestinal oxalate secretion mediated by SLC26A6 may contribute to the hyperoxaluria observed in this mouse model of cystic fibrosis. Future studies are needed to address whether similar mechanisms contribute to the increased risk for calcium oxalate stone formation observed in patients with cystic fibrosis. Copyright © 2016 by the American Society of Nephrology.

Staging of intestinal- and diffuse-type gastric cancers with the OLGA and OLGIM staging systems.

PubMed

Cho, S-J; Choi, I J; Kook, M-C; Nam, B-H; Kim, C G; Lee, J Y; Ryu, K W; Kim, Y-W

2013-11-01

Operative link on gastritis assessment (OLGA) and Operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems have been proposed for gastric cancer (GC) risk estimation. To validate the OLGA and OLGIM staging systems in a region with high risk of GC. This retrospective study included 474 GC patients and age- and sex-matched health screening control persons in a cancer centre hospital. We classified gastritis patterns according to the OLGA and OLGIM systems using the histological database that a pathologist prospectively evaluated using the updated Sydney system. GC risk according to the OLGA and OLGIM stages was evaluated using logistic regression analysis. More GC patients had OLGA stages III-IV (46.2%) than controls (26.6%, P < 0.001), particularly among patients with intestinal-type GCs (62.2%) compared with diffuse-type GCs (30.9%). OLGA stages III and IV were significantly associated with increased risk of GC [odds ratios (ORs), 2.09; P = 0.008 and 2.04; P = 0.014 respectively] in multivariate analysis. The association was more significant for intestinal-type (ORs, 4.76; P = 0.001 and 4.19; P = 0.002 respectively), but not diffuse-type GC. OLGIM stages from I to IV were significantly associated with increased risk of both intestinal-type (ORs, 3.64, 5.15, 7.89 and 13.20 respectively) and diffuse-type GC (ORs, 1.84, 2.59, 5.08 and 6.32 respectively) with a significantly increasing trend. As high OLGA and OLGIM stages are independent risk factors for gastric cancer, the staging systems may be useful for risk assessment in high-risk regions, especially for intestinal-type gastric cancer. © 2013 John Wiley & Sons Ltd.

Expression of MUC4 mucin is observed mainly in the intestinal type of intraductal papillary mucinous neoplasm of the pancreas.

PubMed

Kitazono, Iwao; Higashi, Michiyo; Kitamoto, Sho; Yokoyama, Seiya; Horinouchi, Michiko; Osako, Masahiko; Shimizu, Takeshi; Tabata, Mineo; Batra, Surinder K; Goto, Masamichi; Yonezawa, Suguru

2013-10-01

This study aimed to examine expression profile of MUC4 in intraductal papillary mucinous neoplasm of the pancreas (IPMN). We performed immunohistochemistry (IHC) of MUC4 in 142 IPMNs, with evaluation of the specificity of 2 anti-MUC4 monoclonal antibodies, 8G7 and 1G8, in cancer cell lines. Monoclonal antibody 8G7 showed a clear immunoreactivity, whereas MAb 1G8 did not show any immunoreactivity, in the Western blotting and IHC for human pancreatic carcinoma cell lines expressing MUC4 messenger RNA. However, IHC signals detected by both monoclonal antibodies were observed in the tissue specimens. The expression rates of MUC4/8G7 detected by MAb 8G7 and MUC4/1G8 detected by MAb 1G8 in the intestinal-type IPMNs were significantly higher than those in the gastric-type IPMNs. In the intestinal-type IPMNs, MUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells, whereas MUC4/1G8 was expressed mainly at the cell apexes. Even in the gastric-type IPMNs with rare MUC4 expression in the low-grade dysplasia, both MUC4 expression rates increased when dysplasia advanced. A significantly higher expression of MUC4 in intestinal-type IPMNs than in gastric-type IPMNs will be one of the biomarkers to discriminate between the intestinal-type IPMNs with high malignancy potential from gastric-type IPMNs with low malignancy potential.

Acute radiation enteritis caused by dose-dependent radiation exposure in dogs: experimental research.

PubMed

Xu, Wenda; Chen, Jiang; Xu, Liu; Li, Hongyu; Guo, Xiaozhong

2014-12-01

Accidental or intended radiation exposure in mass casualty settings presents a serious and on-going threat. The development of mitigating and treating agents requires appropriate animal models. Unfortunately, the majority of research on radiation enteritis in animals has lacked specific assessments and targeted therapy. Our study showed beagle dogs, treated by intensity-modulated radiation therapy (IMRT) for abdominal irradiation, were administered single X-ray doses of 8-30 Gy. The degree of intestinal tract injury for all of the animals after radiation exposure was evaluated with regard to clinical syndrome, endoscopic findings, histological features, and intestinal function. The range of single doses (8 Gy, 10-14 Gy, and 16-30 Gy) represented the degree of injury (mild, moderate, and severe, respectively). Acute radiation enteritis included clinical syndrome with fever, vomiting, diarrhea, hemafecia, and weight loss; typical endoscopic findings included edema, bleeding, mucosal abrasions, and ulcers; and intestinal biopsy results revealed mucosal necrosis, erosion, and loss, inflammatory cell infiltration, hemorrhage, and congestion. Changes in serum diamine oxides (DAOs) and d-xylose represented intestinal barrier function and absorption function, respectively, and correlated with the extent of damage (P < 0.05 and P < 0.05, respectively). We successfully developed a dog model of acute radiation enteritis, thus obtaining a relatively objective evaluation of intestinal tract injury based on clinical performance and laboratory examination. The method of assessment of the degree of intestinal tract injury after abdominal irradiation could be beneficial in the development of novel and effective therapeutic strategies for acute radiation enteritis. © 2014 by the Society for Experimental Biology and Medicine.

Diagnosis and surgical management of abdominal cocoon: results from 12 cases.

PubMed

Liu, Hai-yan; Wang, Yong-sheng; Yang, Wan-guang; Yin, Sheng-lu; Pei, Hui; Sun, Tong-wen; Wang, Lexin

2009-01-01

This study was designed to describe the characteristics, diagnostic and therapeutic methods of abdominal cocoon. Twelve patients with abdominal cocoon were surgically treated. The clinical findings from these patients were analyzed. All patients presented with acute complete intestinal obstruction, and 10 had a previous history of abdominal mass. In nine patients, the whole or part of the small intestines were covered by an ash gray, dense and tough fibrous membrane. The capsule was surgically excised, and the adhesion was released. Partial resection of the small intestines was performed. In the other three patients, the small intestines were only partially covered by a membrane, and there was an extensive adhesion of intestinal tract, forming a large mass which could not be relieved by surgical lysis. Intestinal tube was put in, and fistulation procedures were performed. All patients recovered fully after the surgery. There are four types of surgical findings in abdominal cocoon. The most common type is that the small intestines are fully covered by a thick white membrane, causing intestinal obstruction. Surgical excision of the membrane and the release of adhesion is the treatment of choice.

TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota.

PubMed

Ihara, Sozaburo; Hirata, Yoshihiro; Koike, Kazuhiko

2017-07-01

Inflammatory bowel disease (IBD) is defined as chronic intestinal inflammation, and includes ulcerative colitis and Crohn's disease. Multiple factors are involved in the pathogenesis of IBD, and the condition is characterized by aberrant mucosal immune reactions to intestinal microbes in genetically susceptible hosts. Transforming growth factor-β (TGF-β) is an immune-suppressive cytokine produced by many cell types and activated by integrins. Active TGF-β binds to its receptor and regulates mucosal immune reactions through the TGF-β signaling pathway. Dysregulated TGF-β signaling is observed in the intestines of IBD patients. TGF-β signal impairment in specific cell types, such as T-cells and dendritic cells, results in spontaneous colitis in mouse models. In addition, specific intestinal microbes contribute to immune homeostasis by modulating TGF-β production. In this review, we describe the role of TGF-β in intestinal immunity, focusing on immune cells, epithelium, and intestinal microbes. In addition, we present potential therapeutic strategies for IBD that target TGF-β.

Prevalence of celiac disease in patients with severe food allergy.

PubMed

Pillon, R; Ziberna, F; Badina, L; Ventura, A; Longo, G; Quaglia, S; De Leo, L; Vatta, S; Martelossi, S; Patano, G; Not, T; Berti, I

2015-10-01

The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nutrient-induced intestinal adaption and its effect in obesity.

PubMed

Dailey, Megan J

2014-09-01

Obese and lean individuals respond differently to nutrients with changes in digestion, absorption and hormone release. This may be a result of differences in intestinal epithelial morphology and function driven by the hyperphagia or the type of diet associated with obesity. It is well known that the maintenance and growth of the intestine is driven by the amount of luminal nutrients, with high nutrient content resulting in increases in cell number, villi length and crypt depth. In addition, the type of nutrient appears to contribute to alterations in the morphology and function of the epithelial cells. This intestinal adaptation may be what is driving the differences in nutrient processing in lean versus obese individuals. This review describes how nutrients may be able to induce changes in intestinal epithelial cell proliferation, differentiation and function and the link between intestinal adaptation and obesity. Copyright © 2014 Elsevier Inc. All rights reserved.

Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator.

PubMed

Bijvelds, Marcel J C; Bot, Alice G M; Escher, Johanna C; De Jonge, Hugo R

2009-09-01

Lubiprostone alleviates constipation by stimulating intestinal fluid secretion, purportedly through activation of ClC-2-type Cl(-) channels. Intestinal obstruction is also a recurrent cause of distress in cystic fibrosis (CF) patients, caused by loss of CF transmembrane conductance regulator (CFTR) Cl(-) channel activity. Because ClC-2 recruitment might be beneficial to CF patients, we investigated lubiprostone's mode of action. Cl(-) transport was measured in an Ussing chamber, in 3 model systems: (1) T84 colonocytes, (2) intestinal epithelium of wild-type and CF mice, and (3) intestinal epithelium of CF patients and controls. In T84 monolayers, lubiprostone induced a robust secretory response. Selective permeabilization of the basolateral plasma membrane revealed that lubiprostone activated an apical Cl(-) conductance. The lubiprostone response was attenuated by H89, an inhibitor of the cAMP-dependent protein kinase, and lubiprostone precluded responsiveness to the cAMP agonist forskolin. CFTR blockage by CFTRinh172, but not ClC-2 blockage by CdCl(2), inhibited the lubiprostone response. Lubiprostone induced a CdCl(2)-insensitive secretory response in mouse intestine, but failed to induce intestinal Cl(-) secretion in Cftr-null mice. Correspondingly, lubiprostone induced a secretory response in human intestinal epithelium, but not in tissue of CF patients. The EP(4)-type prostanoid receptor antagonist L-161,982 blocked the lubiprostone response in all 3 models studied. In T84 cells, lubiprostone induced a rise in cAMP levels that was sensitive to EP(4)-receptor blockage. Lubiprostone enhances intestinal Cl(-) and fluid secretion via prostanoid receptor signaling, triggering activation of CFTR. Therefore, it is of limited use for treatment of CF-related intestinal disease.

[Clinical research progress of mesenteric internal hernia after Roux-en-Y reconstruction].

PubMed

Xu, Zhengrong; Guo, Wenjun

2017-03-25

Postoperative internal hernia is a rare clinical complication which often occurs after digestive tract reconstruction. Roux-en-Y anastomosis is a common type of digestive tract reconstruction. Internal hernia after Roux-en-Y reconstruction, which occurs mainly in the mesenteric defect caused by incomplete closure of mesenteric gaps in the process of digestive tract reconstruction, is systematically called, in our research, as mesenteric internal hernia after Roux-en-Y reconstruction. Such internal hernia can be divided, according to the different structures of mesentric defect, into 3 types: the type of mesenteric defect at the jejunojejunostomy (J type), the type of Petersen's defect (P type), and the type of mesenteric defect in the transverse mesocolon (M type). Because of huge differences in the number of cases and follow-up time among existing research reports, the morbidity of internal hernia after LRYGB fluctuates wildly between 0.2% and 9.0%. Delayed diagnosis and treatment of mesenteric internal hernia after Roux- en-Y reconstruction may result in disastrous consequences such as intestinal necrosis. Clinical manifestations of internal hernia vary from person to person: some, in mild cases, may have no symptoms at all while others in severe cases may experience acute intestinal obstruction. Despite the difference, one common manifestation of internal hernia is abdominal pain. Surgical treatment should be recommended for those diagnosed as internal hernia. A safer and more feasible way to conduct the manual reduction of the incarcerated hernia is to start from the distal normal empty bowel and trace back to the hernia ring mouth, enabling a faster identification of hernia ring and its track. The prevention of mesenteric internal hernia after Roux-en-Y reconstruction is related to the initial surgical approach and the technique of mesenteric closure. Significant controversy remains on whether or not the mesenteric defect should be closed in laparoscopic Roux-en-Y anastomosis. This article is to review the reports and researches on internal hernia resulting from the mesenteric defect after Roux-en-Y digestive tract reconstruction in recent years, so as to promote understanding and attention on this disease. And more active preventive measures are strongly suggested to be taken in operations where digestive tract reconstruction is involved.

Liver Ischemic Preconditioning (IPC) Improves Intestinal Microbiota Following Liver Transplantation in Rats through 16s rDNA-Based Analysis of Microbial Structure Shift

PubMed Central

Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Background Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”. PMID:24098410

Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats through 16s rDNA-based analysis of microbial structure shift.

PubMed

Ren, Zhigang; Cui, Guangying; Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The "gut-liver axis" closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the "gut-liver axis".

Synergism between Trichuris suis and the microbial flora of the large intestine causing dysentery in pigs.

PubMed

Rutter, J M; Beer, R J

1975-02-01

The role of the microbial flora of the large intestine in experimental Trichuris suis infection was studied by comparing the clinical syndrome in conventionally reared (CR) pigs, specific pathogen-free pigs, and gnotobiotic pigs. Thedisease in CR pigs was characterized by a severe mucohemorrhagic enteritis; in contrast, a mild catarrhal enteritis was observed in specific pathogen-free and gnotobiotic pigs. Spirochaetes and vibrio-like organisms were observed only in CR pigs and increased during the clinical phase of the disease. The clinical syndrome was not transmitted by oral administration of intestinal or fecal material from infected CR pigs to CR pigs free of T. suis. Smaller numbers of T. suis produced diarrhea in CR pigs and significantly reduced the growth rates of infected animals; clinical signs and the reduction in growth rate was prevented by incorporating an antibacterial substance (dimetridazole) in the food. Although clinical trichuriasis closely resembles swin dysentery, the two syndromes seem to be distinct. The present results suggest that a microbial component acts synergistically with T. suis to produce the severe clinical syndrome in CR pigs, but identification of the microbial component and the mechanism by which clinical signs are produced await further studies of the bacterial flora of the large intestine of pigs.

Expression of MUC4 mucin is observed mainly in the intestinal-type of intraductal papillary mucinous neoplasm of the pancreas

PubMed Central

Kitazono, Iwao; Higashi, Michiyo; Kitamoto, Sho; Yokoyama, Seiya; Horinouchi, Michiko; Osako, Masahiko; Shimizu, Takeshi; Tabata, Mineo; Batra, Surinder K.; Goto, Masamichi; Yonezawa, Suguru

2013-01-01

Objectives This study aimed to examine expression profile of MUC4 in intraductal papillary mucinous neoplasm of the pancreas (IPMN). Methods We performed immonohistochemistry (IHC) of MUC4 in 142 IPMNs, with evaluation of the specificity of two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, in cancer cell lines. Results MAb 8G7 showed a clear immunoreactivity, whereas MAb 1G8 did not show any immunoreactivity, in the Western blotting and IHC for human pancreatic carcinoma cell lines expressing MUC4 mRNA. However, IHC signals detected by both MAbs were observed in the tissue specimens. The expression rates of MUC4/8G7 detected by MAb 8G7 and MUC4/1G8 detected by MAb 1G8 in the intestinal-type IPMNs were significantly higher than those in the gastric-type IPMNs. In the intestinal-type IPMNs, MUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells, whereas MUC4/1G8 was expressed mainly at the cell apexes. Even in the gastric-type IPMNs with rare MUC4 expression in the low-grade dysplasia, both MUC4 expression rates increased when dysplasia advanced. Conclusions A significantly higher expression of MUC4 in intestinal-type IPMNs than in gastric-type IPMNs will be one of the biomarkers to discriminate between the intestinal-type IPMNs with high malignancy potential from gastric-type IPMNs with low malignancy potential. PMID:23921963

Intestinal development and differentiation

PubMed Central

Noah, Taeko K.; Donahue, Bridgitte; Shroyer, Noah F.

2011-01-01

In this review, we present an overview of intestinal development and cellular differentiation of the intestinal epithelium. The review is separated into two sections: Section one summarizes organogenesis of the small and large intestines, including endoderm and gut tube formation in early embryogenesis, villus morphogenesis, and crypt formation. Section two reviews cell fate specification and differentiation of each cell type within the intestinal epithelium. Growth factor and transcriptional networks that regulate these developmental processes are summarized. PMID:21978911

Inhibition of IKKβ in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality.

PubMed

Dominguez, Jessica A; Samocha, Alexandr J; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Coopersmith, Craig M

2013-10-01

Nuclear factor-κB is a critical regulator of cell-survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase. Prospective, randomized controlled study. Animal laboratories in university medical centers. Mice lacking functional NF-kB in their intestinal epithelium (Vil-Cre/Ikkβ) and wild-type mice were subjected to sham laparotomy or cecal ligation and puncture. Animals were killed at 24 hours or followed 7 days for survival. Septic wild-type mice had decreased villus length compared with sham mice, whereas villus atrophy was further exacerbated in septic Vil-Cre/Ikkβ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared with sham mice, which was further exacerbated in Vil-Cre/Ikkβ mice. Sepsis induced intestinal hyperpermeability in wild-type mice compared with sham mice, which was further exacerbated in septic Vil-Cre/Ikkβ mice. This was associated with increased intestinal expression of claudin-2 in septic wild-type mice, which was further increased in septic Vil-Cre/Ikkβ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following cecal ligation and puncture, and interleukin 10 and monocyte chemoattractant protein-1 levels were higher in septic Vil-Cre/Ikkβ mice than in septic wild-type mice. All septic mice were bacteremic, but no differences in bacterial load were identified between wild-type and Vil-Cre/Ikkβ mice. To determine the functional significance of these results, animals were followed for survival. Septic wild-type mice had lower mortality than septic Vil-Cre/Ikkβ mice (47% vs 80%, p<0.05). Antitumor necrosis factor administration decreased intestinal apoptosis, permeability, and mortality in wild-type septic mice, and a similar improvement in intestinal integrity and survival were seen when antitumor necrosis factor was given to Vil-Cre/Ikkβ mice. Enterocyte-specific NF-kB has a beneficial role in sepsis by partially preventing sepsis-induced increases in apoptosis and permeability, which are associated with worsening mortality.

Lactobacillus johnsonii N6.2 Mitigates the Development of Type 1 Diabetes in BB-DP Rats

PubMed Central

Li, Nan; Williams, Emily; Lai, Kin-Kwan; Abdelgeliel, Asmaa Sayed; Gonzalez, Claudio F.; Wasserfall, Clive H.; Larkin, Joseph; Schatz, Desmond; Atkinson, Mark A.; Triplett, Eric W.; Neu, Josef; Lorca, Graciela L.

2010-01-01

Background The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development. Methodology/Principal Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNγ were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin. Conclusions It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data suggest that the gut and the gut microbiota are potential agents of influence in type 1 diabetes development. These data also support therapeutic efforts that seek to modify gut microbiota as a means to modulate development of this disorder. PMID:20463897

Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats.

PubMed

Valladares, Ricardo; Sankar, Dhyana; Li, Nan; Williams, Emily; Lai, Kin-Kwan; Abdelgeliel, Asmaa Sayed; Gonzalez, Claudio F; Wasserfall, Clive H; Larkin, Joseph; Schatz, Desmond; Atkinson, Mark A; Triplett, Eric W; Neu, Josef; Lorca, Graciela L

2010-05-06

The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development. Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin. It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data suggest that the gut and the gut microbiota are potential agents of influence in type 1 diabetes development. These data also support therapeutic efforts that seek to modify gut microbiota as a means to modulate development of this disorder.

Keratins Are Altered in Intestinal Disease-Related Stress Responses.

PubMed

Helenius, Terhi O; Antman, Cecilia A; Asghar, Muhammad Nadeem; Nyström, Joel H; Toivola, Diana M

2016-09-10

Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery.

Comparative analysis of the intestinal flora in type 2 diabetes and nondiabetic mice

PubMed Central

Horie, Masanori; Miura, Takamasa; Hirakata, Satomi; Hosoyama, Akira; Sugino, Sakiko; Umeno, Aya; Murotomi, Kazutoshi; Yoshida, Yasukazu; Koike, Taisuke

2017-01-01

A relationship between type 2 diabetes mellitus (T2DM) and intestinal flora has been suggested since development of analysis technology for intestinal flora. An animal model of T2DM is important for investigation of T2DM. Although there are some animal models of T2DM, a comparison of the intestinal flora of healthy animals with that of T2DM animals has not yet been reported. The intestinal flora of Tsumura Suzuki Obese Diabetes (TSOD) mice was compared with that of Tsumura, Suzuki, Non Obesity (TSNO) mice in the present study. The TSOD mice showed typical type 2 diabetes symptoms, which were high-fat diet-independent. The TSOD and the TSNO mouse models were derived from the same strain, ddY. In this study, we compared the intestinal flora of TSOD mice with that if TSNO mice at 5 and 12 weeks of age. We determined that that the number of operational taxonomic units (OTUs) was significantly higher in the cecum of TSOD mice than in that of TSNO mice. The intestinal flora of the cecum and that of the feces were similar between the TSNO and the TSOD strains. The dominant bacteria in the cecum and feces were of the phyla Firmicutes and Bacteroidetes. However, the content of some bacterial species varied between the two strains. The percentage of Lactobacillus spp. within the general intestinal flora was higher in TSOD mice than in TSNO mice. In contrast, the percentages of order Bacteroidales and family Lachnospiraceae were higher in TSNO mice than in TSOD mice. Some species were observed only in TSOD mice, such as genera Turicibacter and SMB53 (family Clostridiaceae), the percentage of which were 3.8% and 2.0%, respectively. Although further analysis of the metabolism of the individual bacteria in the intestinal flora is essential, genera Turicibacter and SMB53 may be important for the abnormal metabolism of type 2 diabetes. PMID:28701620

Comparative analysis of the intestinal flora in type 2 diabetes and nondiabetic mice.

PubMed

Horie, Masanori; Miura, Takamasa; Hirakata, Satomi; Hosoyama, Akira; Sugino, Sakiko; Umeno, Aya; Murotomi, Kazutoshi; Yoshida, Yasukazu; Koike, Taisuke

2017-10-30

A relationship between type 2 diabetes mellitus (T2DM) and intestinal flora has been suggested since development of analysis technology for intestinal flora. An animal model of T2DM is important for investigation of T2DM. Although there are some animal models of T2DM, a comparison of the intestinal flora of healthy animals with that of T2DM animals has not yet been reported. The intestinal flora of Tsumura Suzuki Obese Diabetes (TSOD) mice was compared with that of Tsumura, Suzuki, Non Obesity (TSNO) mice in the present study. The TSOD mice showed typical type 2 diabetes symptoms, which were high-fat diet-independent. The TSOD and the TSNO mouse models were derived from the same strain, ddY. In this study, we compared the intestinal flora of TSOD mice with that if TSNO mice at 5 and 12 weeks of age. We determined that that the number of operational taxonomic units (OTUs) was significantly higher in the cecum of TSOD mice than in that of TSNO mice. The intestinal flora of the cecum and that of the feces were similar between the TSNO and the TSOD strains. The dominant bacteria in the cecum and feces were of the phyla Firmicutes and Bacteroidetes. However, the content of some bacterial species varied between the two strains. The percentage of Lactobacillus spp. within the general intestinal flora was higher in TSOD mice than in TSNO mice. In contrast, the percentages of order Bacteroidales and family Lachnospiraceae were higher in TSNO mice than in TSOD mice. Some species were observed only in TSOD mice, such as genera Turicibacter and SMB53 (family Clostridiaceae), the percentage of which were 3.8% and 2.0%, respectively. Although further analysis of the metabolism of the individual bacteria in the intestinal flora is essential, genera Turicibacter and SMB53 may be important for the abnormal metabolism of type 2 diabetes.

Th2 and Th1 Responses: Clear and Hidden Sides of Immunity Against Intestinal Helminths.

PubMed

Cortés, Alba; Muñoz-Antoli, Carla; Esteban, J Guillermo; Toledo, Rafael

2017-09-01

Intestinal helminthiases affect millions of people worldwide, mainly in developing regions, where they cause a significant negative impact on human health and socioeconomic growth of affected populations. However, intestinal helminthiases are still among the most neglected tropical diseases. Protective immunity against intestinal helminths is associated with development of type 2 responses. Nevertheless, in some host-intestinal helminth combinations, local Th1 responses are initiated, inducing chronicity. The usage of helminth-mouse models is useful for elucidating the mechanisms behind the initiation of each type of response. Herein, the current knowledge on these topics is reviewed, paying particular attention to the earliest events of the immune cascade which eventually lead to either susceptibility or resistance to infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of sea buckthorn protein on the intestinal microbial community in streptozotocin-induced diabetic mice.

PubMed

Yuan, Huaibo; Shi, Fangfang; Meng, Lina; Wang, Wenjuan

2018-02-01

This study investigated the intestinal microbial community distribution of Type 2 diabetic mice and discussed the effects of the sea buckthorn protein on the regulation of gut microbes. Date was collected for 12 cases of normal mice (NC group), 12 cases of Type 2 diabetic mice (DC group), and 12 cases of highly concentrated sea buckthorn seed protein dosed mice (SSPH group). This study analysed fecal samples, measured faecal pH value, and cultivated and determined intestinal bacteria count. This investigation also included the extraction of faecal samples for genomic DNA, PCR amplification of bacterial V3 16S rDNA products by denaturing gradient gel electrophoresis, DGGE map analysis of intestinal flora, determination of intestinal bacteria richness, Shannon-Wiener index and evenness index, and image similarity cluster analysis with UPGMA clustering. This study analysed and elucidated differences between the normal mice group, diabetic mice group, and sea buckthorn protein supplemented group, and the structures of respective intestinal flora. The mice supplemented with sea buckthorn protein exhibited an obvious drop in body weight and blood glucose levels. The Bifidobacterium, Lactobacillus, Bacteroides, and Clostridium coccoides populations recovered. The amplification of the 16S rDNA gene V3 region revealed that the species of intestinal microbes in the treatment group were adjusted to a certain extent. Analysis by ARDRA confirmed that sea buckthorn protein could increase type 2 diabetes in mice intestinal microorganism diversity (H) and simpson (E). Copyright © 2017 Elsevier B.V. All rights reserved.

A novel transanal tube designed to prevent anastomotic leakage after rectal cancer surgery: the WING DRAIN.

PubMed

Nishigori, Hideaki; Ito, Masaaki; Nishizawa, Yuji

2017-04-01

We introduce a novel transanal tube (TAT), named the "WING DRAIN", designed to prevent anastomotic leakage after rectal cancer surgery, and report the fundamental experiments that led to its development. We performed the basic experiments to evaluate the effect of TATs on intestinal decompression, the changes they make in patterns of watery fluid drainage, the changes in their decompression effect when the extension tube connecting the TAT to the collection bag fills with watery drainage fluid, and the variations in intestinal contact and crushing pressure made by some types of TAT. Any type of TAT contributed to decompression in the intestinal tract. Watery drainage commenced from when the water level first rose to the hole in the tip of drain. The intestinal pressure increased with the length of the vertical twist in an extension tube. The crushing pressures of most types of TAT were high enough to cause injury to the intestine. We resolved the problems using an existing TAT for the purpose of intestinal decompression and by creating the first specialized TAT designed to prevent anastomotic leakage after rectal cancer surgery in Japan.

Clinical radiology of the small intestine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herlinger, H.; Maglinte, D.

1989-01-01

This book discussed embryology, anatomy, physiology, and immunology of the small intestine. Radiographic procedures in the small intestine especially enterolysis are presented. Focus is on the role of other types of imaging techniques including sonography, computed tomography, radionuclide imaging, angiography, biopsy, and enteroscopy.

A case of retrograde intussusception at Roux-en-Y anastomosis 10 years after total gastrectomy: review of the literature.

PubMed

Kitasato, Yuhei; Midorikawa, Ryuta; Uchino, Yoshihiro; Saku, Shuko; Minami, Taizan; Shirahama, Takahisa; Kiyomatsu, Kazumitsu; Okuda, Koji; Akagi, Yoshito; Tanaka, Hiroyuki

2016-12-01

A 63-year-old man, who had undergone total gastrectomy and Roux-en-Y reconstruction for gastric cancer 10 years previously, was admitted to our hospital with complaints of abdominal pain, palpable abdominal tumor, and hematemesis. On admission, the abdominal tenderness was improving and no abdominal tumor was palpable. Mild inflammatory changes and anemia were noted on blood examination. Abdominal computed tomography revealed a tumor with a layered structure in the left abdomen. The patient was diagnosed with intestinal obstruction secondary to intussusception, and surgery was performed. Retrograde intussusception was found at the site of the Y anastomosis. We conducted manual reduction using the Hutchinson procedure. The intestinal color after the reduction was good, and no intestinal resection was required. Postoperative recovery was uneventful, and the patient was discharged 12 days after surgery. Reports of jejunal intussusception after total gastrectomy with Roux-en-Y reconstruction are relatively rare. Here, we report a case of jejunal intussusception after total gastrectomy with Roux-en-Y reconstruction.

Histopathologic characteristics of gastric adenocarcinoma in Mexican patients: a 10-year experience at the Hospital Juárez of Mexico.

PubMed

Martínez-Galindo, M G; Zamarripa-Dorsey, F; Carmona-Castañeda, A; Angeles-Labra, A; Peñavera-Hernández, R; Ugarte-Briones, C; Blanco-Vela, C I

2015-01-01

Gastric cancer is the second cause of death by cancer worldwide. Histologic classification may predict tumor biology, clinical behavior, and outcome. According to the Lauren classification, the disease is divided into 2 types, diffuse and intestinal, and the latter has a better prognosis. To determine the frequency of gastric adenocarcinoma and compare the histopathologic characteristics of intestinal and diffuse-type gastric adenocarcinoma in Mexican patients treated at a tertiary referral hospital. A retrospective study evaluated the pathology reports of patients with gastric adenocarcinoma corresponding to the time frame of January 2003 to December 2012. Adenocarcinomas of the gastric cardia were excluded. Frequencies were expressed as percentages and the categorical variables were compared with the chi-square test. Statistical significance was set at a P<.05. A total of 417 cases of gastric adenocarcinoma were found, 230 (55.2%) of which were diffuse-type and 118 (28.2%) were intestinal-type. The mean age of the patients with diffuse type gastric cancer was 54.02±14.93 and 119 (51.3%) of those patients were men. The mean age of the patients with intestinal-type gastric cancer was 63.43±13.78, and 69 (62.2%) were men. Ninety-two of the diffuse-type patients were under the age of 50 years, compared with 22 of the patients with intestinal-type carcinoma. This is the first study on the Mexican population to analyze the differences in the histologic types of adenocarcinoma. Diffuse-type gastric carcinoma was the most frequent subtype in our study population and it is associated with worse outcome. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Intestinal Decontamination of Multidrug-resistant Klebsiella pneumoniae After Recurrent Infections in an Immunocompromised Host

PubMed Central

Kronman, Matthew P.; Zerr, Danielle M.; Qin, Xuan; Englund, Janet; Cornell, Cathy; Sanders, Jean E.; Myers, Jeffrey; Rayar, Jaipreet; Berry, Jessica E.; Adler, Amanda L.; Weissman, Scott J.

2014-01-01

Multidrug-resistant (MDR) Enterobacteriaceae infections are associated with increased morbidity. We describe a 20-year-old hematopoietic cell transplantation recipient with recurrent MDR Klebsiella pneumoniae infection, prolonged intestinal colonization, and subsequent intestinal decontamination. Further study should evaluate stool surveillance, molecular typing, and fecal microbiota transplantation for patients with intestinal MDR Enterobacteriaceae carriage. PMID:25041704

Exclusion of linkage between RET and Neuronal Intestinal Dysplasia type B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barone, V.; Yin Luo; Brancolini, V.

1996-03-15

Neuronal Intestinal Dysplasia type B (NID B) is a complex alteration of the enteric nervous system belonging to the group of intestinal dysganglionoses which may involve rectum, colon, and small intestine. Second only to Hirschsprung diseases (HSCR), NID B is one of the most frequent causes of chronic constipation and pseudo-obstructive intestinal dysmotility. Since NID B is often associated with HSCR and point mutations in the RET proto-oncogene have been identified in HSCR patients, we analyzed two NID B pedigrees to investigate if RET mutations might cause also the NID B phenotype. Linkage analysis demonstrated that the NID B locusmore » is not linked to RET in the pedigrees analysed. Further genetic analyses will possibility improve the understanding of the cause and facilitate diagnostic procedures in NID B. 20 refs., 1 fig., 2 tabs.« less

Short-type single balloon enteroscope for endoscopic retrograde cholangiopancreatography with altered gastrointestinal anatomy

PubMed Central

Yamauchi, Hiroshi; Kida, Mitsuhiro; Okuwaki, Kosuke; Miyazawa, Shiro; Iwai, Tomohisa; Takezawa, Miyoko; Kikuchi, Hidehiko; Watanabe, Maya; Imaizumi, Hiroshi; Koizumi, Wasaburo

2013-01-01

AIM: To evaluate the effectiveness of a short-type single-balloon-enteroscope (SBE) for endoscopic retrograde cholangiopancreatography (ERCP) in patients with a reconstructed intestine. METHODS: Short-type SBE was developed to perform ERCP in postoperative patients with a reconstructed intestine. Short-type SBE is a direct-viewing endoscope with the following specifications: working length, 1520 mm; total length, 1840 mm; channel diameter, 3.2 mm. In addition, short-type SBE has a water-jet channel. The study group comprised 22 patients who underwent 31 sessions of short-type SBE-assisted ERCP from June 2011 through May 2012. Reconstruction was performed by Billroth-II (B-II) gastrectomy in 6 patients (8 sessions), Roux-en-Y (R-Y) gastrectomy in 14 patients (21 sessions), and R-Y hepaticojejunostomy in 2 patients (2 sessions). We retrospectively studied the rate of reaching the blind end (papilla of Vater or choledochojejunal anastomosis), mean time required to reach the blind end, diagnostic success rate (defined as the rate of successfully imaging the bile and pancreatic ducts), therapeutic success rate (defined as the rate of successfully completing endoscopic treatment), mean procedure time, and complications. RESULTS: Among the 31 sessions of ERCP, the rate of reaching the blind end was 88% in B-II gastrectomy, 91% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. The mean time required to reach the papilla was 18.3 min in B-II gastrectomy, 21.1 min in R-Y gastrectomy, and 32.5 min in R-Y hepaticojejunostomy. The diagnostic success rates in all patients and those with an intact papilla were respectively 86% and 86% in B-II gastrectomy, 90% and 87% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. The therapeutic success rates in all patients and those with an intact papilla were respectively 100% and 100% in B-II gastrectomy, 94% and 92% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. Because the channel diameter was 3.2 mm, stone extraction could be performed with a wire-guided basket in 12 sessions, and wire-guided intraductal ultrasonography could be performed in 8 sessions. As for complications, hyperamylasemia (defined as a rise in serum amylase levels to more than 3 times the upper limit of normal) occurred in 1 patient (7 sessions) with a B-II gastrectomy and 4 patients (19 sessions) with an R-Y gastrectomy. After ERCP in patients with an R-Y gastrectomy, 2 patients (19 sessions) had pancreatitis, 1 patient (21 sessions) had gastrointestinal perforation, and 1 patient (19 sessions) had papillary bleeding. Pancreatitis and bleeding were both mild. Gastrointestinal perforation improved after conservative treatment. CONCLUSION: Short-type SBE is effective for ERCP in patients with a reconstructed intestine and allows most conventional ERCP devices to be used. PMID:23555161

Advanced three-dimensional culture of equine intestinal epithelial stem cells.

PubMed

Stewart, A Stieler; Freund, J M; Gonzalez, L M

2018-03-01

Intestinal epithelial stem cells are critical to epithelial repair following gastrointestinal injury. The culture of intestinal stem cells has quickly become a cornerstone of a vast number of new research endeavours that range from determining tissue viability to testing drug efficacy for humans. This study aims to describe the methods of equine stem cell culture and highlights the future benefits of these techniques for the advancement of equine medicine. To describe the isolation and culture of small intestinal stem cells into three-dimensional (3D) enteroids in horses without clinical gastrointestinal abnormalities. Descriptive study. Intestinal samples were collected by sharp dissection immediately after euthanasia. Intestinal crypts containing intestinal stem cells were dissociated from the underlying tissue layers, plated in a 3D matrix and supplemented with growth factors. After several days, resultant 3D enteroids were prepared for immunofluorescent imaging and polymerase chain reaction (PCR) analysis to detect and characterise specific cell types present. Intestinal crypts were cryopreserved immediately following collection and viability assessed. Intestinal crypts were successfully cultured and matured into 3D enteroids containing a lumen and budding structures. Immunofluorescence and PCR were used to confirm the existence of stem cells and all post mitotic, mature cell types, described to exist in the horse intestinal epithelium. Previously frozen crypts were successfully cultured following a freeze-thaw cycle. Tissues were all derived from normal horses. Application of this technique for the study of specific disease was not performed at this time. The successful culture of equine intestinal crypts into 3D "mini-guts" allows for in vitro studies of the equine intestine. Additionally, these results have relevance to future development of novel therapies that harness the regenerative potential of equine intestine in horses with gastrointestinal disease (colic). © 2017 EVJ Ltd.

Development and application of bio-sample quantification to evaluate stability and pharmacokinetics of inulin-type fructo-oligosaccharides from Morinda Officinalis.

PubMed

Chi, Liandi; Chen, Lingxiao; Zhang, Jiwen; Zhao, Jing; Li, Shaoping; Zheng, Ying

2018-07-15

Inulin-type fructooligosaccharides (FOS) purified from Morinda Officinalis, with degrees of polymerization (DP) from 3 to 9, have been approved in China as an oral prescribed drug for mild and moderate depression episode, while the stability and oral absorption of this FOS mixtures are largely unknown. As the main active component and quality control marker for above FOS, DP5 was selected as the representative FOS in this study. Desalting method by ion exchange resin was developed to treat bio-sample, followed by separation and quantification by high performance liquid chromatography-charged aerosol detector. Results showed that the DP5 was stepwisely hydrolyzed in simulated gastric fluid and gut microbiota, while maintained stable in intestinal fluid. DP5 has poor permeability across Caco-2 monolayer with P app of 5.22 × 10 -7  cm/s, and very poor oral absorption with bioavailability of (0.50 ± 0.12)% in rat. In conclusion, FOS in Morinda Officinalis demonstrated poor chemical stability in simulated gastric fluid and human gut microbiota, and low oral absorption in rats. Copyright © 2018 Elsevier B.V. All rights reserved.

Prenatal Diagnosis of a Segmental Small Bowel Volvulus with Threatened Premature Labor

PubMed Central

Mottet, Nicolas; Ramanah, Rajeev; Riethmuller, Didier

2017-01-01

Fetal primary small bowel volvulus is extremely rare but represents a serious life-threatening condition needing emergency neonatal surgical management to avoid severe digestive consequences. We report a case of primary small bowel volvulus with meconium peritonitis prenatally diagnosed at 27 weeks and 4 days of gestation during threatened premature labor with reduced fetal movements. Ultrasound showed a small bowel mildly dilated with thickened and hyperechogenic intestinal wall, with a typical whirlpool configuration. Normal fetal development allowed continuation of pregnancy with ultrasound follow-up. Induction of labor was decided at 37 weeks and 2 days of gestation because of a significant aggravation of intestinal dilatation appearing more extensive with peritoneal calcifications leading to the suspicion of meconium peritonitis, associated with reduced fetal movements and reduced fetal heart rate variability, for neonatal surgical management with a good outcome. PMID:29230337

Protection against an infectious disease by enterohaemorrhagic E. coli 0-157.

PubMed

Ota, A

1999-07-01

Preventive measures against infection by enterohaemorrhagic E. coli 0-157 are described. Eating yoghurt and Kefir supposedly induces more bifid bacteria and lactic acid bacteria to colonize in the intestines, thereby protecting humans from infection by E. coli 0-157. Some foods, such as plum extract, act as a mild antibiotic and produce an acidic environment within the intestine, thus interfering with growth of the E. coli 0-157. The natural colonization of harmless E. coli or other bacteria that are more powerful than E. coli 0-157 can possibly protect against infection. A vaccination against E. coli 0-157 H7 may also be effective. In addition, it has been suggested that the correct levels of nitric oxide and calcium in the blood may activate immunity and protect against infection by E. coli 0-157.

Intestinal decontamination of multidrug-resistant Klebsiella pneumoniae after recurrent infections in an immunocompromised host.

PubMed

Kronman, Matthew P; Zerr, Danielle M; Qin, Xuan; Englund, Janet; Cornell, Cathy; Sanders, Jean E; Myers, Jeffrey; Rayar, Jaipreet; Berry, Jessica E; Adler, Amanda L; Weissman, Scott J

2014-09-01

Multidrug-resistant (MDR) Enterobacteriaceae infections are associated with increased morbidity. We describe a 20-year-old hematopoietic cell transplantation recipient with recurrent MDR Klebsiella pneumoniae infection, prolonged intestinal colonization, and subsequent intestinal decontamination. Further study should evaluate stool surveillance, molecular typing, and fecal microbiota transplantation for patients with intestinal MDR Enterobacteriaceae carriage. Copyright © 2014 Elsevier Inc. All rights reserved.

Symbiotic Bacteria Direct Expression of an Intestinal Bactericidal Lectin

PubMed Central

Cash, Heather L.; Whitham, Cecilia V.; Behrendt, Cassie L.; Hooper, Lora V.

2009-01-01

The mammalian intestine harbors complex societies of beneficial bacteria that are maintained in the lumen with minimal penetration of mucosal surfaces. Microbial colonization of germ-free mice triggers epithelial expression of RegIIIγ, a secreted C-type lectin. RegIIIγ binds intestinal bacteria but lacks the complement recruitment domains present in other microbe-binding mammalian C-type lectins. We show that RegIIIγ and its human counterpart, HIP/PAP, are directly antimicrobial proteins that bind their bacterial targets via interactions with peptidoglycan carbohydrate. We propose that these proteins represent an evolutionarily primitive form of lectin-mediated innate immunity, and that they reveal intestinal strategies for maintaining symbiotic host-microbial relationships. PMID:16931762

Botulism outbreak associated with poultry litter consumption in three Brazilian cattle herds.

PubMed

Ortolani, E L; Brito, L A; Mori, C S; Schalch, U; Pacheco, J; Baldacci, L

1997-04-01

One hundred fifty-five of 201 cattle from 3 different farms showed clinical signs and died of botulism after eating the same batch of poultry litter contaminated with poultry and rodent carcasses. The cattle had access to poultry litter for only 1 d; afterwards it was removed from the diet. Death occurred over a period of 17 d after the poultry litter intake. The peak mortality was on day 4; 20 animals died within 10 d of the ingestion. The greater the intake of poultry litter, the higher the cattle mortality. Three steers which died on the first day had peracute effects while the remaining cattle showed classical signs. Twenty-five of the 46 surviving cattle had mild clinical signs, but recovered in a few days. Type C Clostridium botulinum toxin was found in extracts of the poultry litter, carcasses and cattle intestinal contents. Nutrient composition of the poultry litter was normal but pH was lower (6.9) than usual (7.5 to 9.3).

Keratins Are Altered in Intestinal Disease-Related Stress Responses

PubMed Central

Helenius, Terhi O.; Antman, Cecilia A.; Asghar, Muhammad Nadeem; Nyström, Joel H.; Toivola, Diana M.

2016-01-01

Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery. PMID:27626448

[Endoscopic and pathological characteristics of gastric cancer in a Peruvian public hospital].

PubMed

Parillo Durand, Lilian Brenda

2017-01-01

The endoscopic and pathological characteristics of gastric cancer in Luis N. Sáenz National Hospital between 2008 and 2013. retrospective cross-sectional observational study. We reviewed the endoscopic reports of patients older than 30 years, we studied the histological diagnosis of gastric adenocarcinoma, pathological variables such as histological type, presence of H. pylori and complete and incomplete intestinal metaplasia. 92 cases of gastric adenocarcinoma were identified. Average prevalence 0.6%, 0.34% in 2009 and 0.82% in 2013; 62% male, 38% female, age less than 55 years 16%, greater than 76 years 42%; endoscopic presentation Borrmann III 57%, II 16.3%, IV 15%, V 7.6%, I 3.3%; 8 times most frequent presentations distal the proximal v, 75% histologic intestinal type, H. pylori in 50% cases, intestinal metaplasia in 40% of cases of gastric cancer. We found high prevalence of gastric cancer. Common in males, and in people over 76, more frequent endoscopic presentation was Borrmann III, the presence of H. pylori and incomplete intestinal metaplasia associated with intestinal cancer type.

Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake

PubMed Central

Li, Xiuying; Chen, Dan; Le, Chaoyi; Zhu, Chunliu; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

2011-01-01

Background The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127). Methods The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry. Results The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells. Conclusion PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery. PMID:22163166

DISCOVERY OF THREE NOVEL COCCIDIAN PARASITES INFECTING CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS), WITH EVIDENCE OF SEXUAL REPLICATION AND INTERSPECIES PATHOGENICITY

PubMed Central

Colegrove, Kathleen M.; Grigg, Michael E.; Carlson-Bremer, Daphne; Miller, Robin H.; Gulland, Frances M. D.; Ferguson, David J. P.; Rejmanek, Daniel; Barr, Bradd C.; Nordhausen, Robert; Melli, Ann C.; Conrad, Patricia A.

2016-01-01

Enteric protozoal infection was identified in 5 stranded California sea lions (Zalophus californianus). Microscopically, the apical cytoplasm of distal jejunal enterocytes contained multiple stages of coccidian parasites, including schizonts with merozoites and spherical gametocytes, which were morphologically similar to coccidians. By histopathology, organisms appeared to be confined to the intestine and accompanied by only mild enteritis. Using electron microscopy, both sexual (microgametocytes, macrogamonts) and asexual (schizonts, merozoites) coccidian stages were identified in enterocytes within parasitophorous vacuoles, consistent with apicomplexan development in a definitive host. Serology was negative for tissue cyst-forming coccidians, and immunohistochemistry for Toxoplasma gondii was inconclusive and negative for Neospora caninum and Sarcocystis neurona. Analysis of ITS-1 gene sequences amplified from frozen or formalin-fixed paraffin-embedded intestinal sections identified DNA sequences with closest homology to Neospora sp. (80%); these novel sequences were referred to as belonging to coccidian parasites ‘‘A,’’ ‘‘B,’’ and ‘‘C.’’ Subsequent molecular analyses completed on a neonatal harbor seal (Phoca vitulina) with protozoal lymphadenitis, hepatitis, myocarditis, and encephalitis showed that it was infected with a coccidian parasite bearing the ‘‘C’’ sequence type. Our results indicate that sea lions likely serve as definitive hosts for 3 newly described coccidian parasites, at least 1 of which is pathogenic in a marine mammal intermediate host species. PMID:21495828

An oil containing EPA and DHA from transgenic Camelina sativa to replace marine fish oil in feeds for Atlantic salmon (Salmo salar L.): Effects on intestinal transcriptome, histology, tissue fatty acid profiles and plasma biochemistry

PubMed Central

Betancor, Mónica B.; Li, Keshuai; Sprague, Matthew; Bardal, Tora; Sayanova, Olga; Usher, Sarah; Han, Lihua; Måsøval, Kjell; Torrissen, Ole; Napier, Johnathan A.; Tocher, Douglas R.; Olsen, Rolf Erik

2017-01-01

New de novo sources of omega 3 (n-3) long chain polyunsaturated fatty acids (LC-PUFA) are required as alternatives to fish oil in aquafeeds in order to maintain adequate levels of the beneficial fatty acids, eicosapentaenoic and docosahexaenoic (EPA and DHA, respectively). The present study investigated the use of an EPA+DHA oil derived from transgenic Camelina sativa in Atlantic salmon (Salmo salar) feeds containing low levels of fishmeal (35%) and fish oil (10%), reflecting current commercial formulations, to determine the impacts on tissue fatty acid profile, intestinal transcriptome, and health of farmed salmon. Post-smolt Atlantic salmon were fed for 12-weeks with one of three experimental diets containing either a blend of fish oil/rapeseed oil (FO), wild-type camelina oil (WCO) or transgenic camelina oil (DCO) as added lipid source. The DCO diet did not affect any of the fish performance or health parameters studied. Analyses of the mid and hindgut transcriptomes showed only mild effects on metabolism. Flesh of fish fed the DCO diet accumulated almost double the amount of n-3 LC-PUFA than fish fed the FO or WCO diets, indicating that these oils from transgenic oilseeds offer the opportunity to increase the n-3 LC-PUFA in farmed fish to levels comparable to those found a decade ago. PMID:28403232

An oil containing EPA and DHA from transgenic Camelina sativa to replace marine fish oil in feeds for Atlantic salmon (Salmo salar L.): Effects on intestinal transcriptome, histology, tissue fatty acid profiles and plasma biochemistry.

PubMed

Betancor, Mónica B; Li, Keshuai; Sprague, Matthew; Bardal, Tora; Sayanova, Olga; Usher, Sarah; Han, Lihua; Måsøval, Kjell; Torrissen, Ole; Napier, Johnathan A; Tocher, Douglas R; Olsen, Rolf Erik

2017-01-01

New de novo sources of omega 3 (n-3) long chain polyunsaturated fatty acids (LC-PUFA) are required as alternatives to fish oil in aquafeeds in order to maintain adequate levels of the beneficial fatty acids, eicosapentaenoic and docosahexaenoic (EPA and DHA, respectively). The present study investigated the use of an EPA+DHA oil derived from transgenic Camelina sativa in Atlantic salmon (Salmo salar) feeds containing low levels of fishmeal (35%) and fish oil (10%), reflecting current commercial formulations, to determine the impacts on tissue fatty acid profile, intestinal transcriptome, and health of farmed salmon. Post-smolt Atlantic salmon were fed for 12-weeks with one of three experimental diets containing either a blend of fish oil/rapeseed oil (FO), wild-type camelina oil (WCO) or transgenic camelina oil (DCO) as added lipid source. The DCO diet did not affect any of the fish performance or health parameters studied. Analyses of the mid and hindgut transcriptomes showed only mild effects on metabolism. Flesh of fish fed the DCO diet accumulated almost double the amount of n-3 LC-PUFA than fish fed the FO or WCO diets, indicating that these oils from transgenic oilseeds offer the opportunity to increase the n-3 LC-PUFA in farmed fish to levels comparable to those found a decade ago.

Intestinal toxemia botulism in 3 adults, Ontario, Canada, 2006-2008.

PubMed

Sheppard, Yolanda D; Middleton, Dean; Whitfield, Yvonne; Tyndel, Felix; Haider, Shariq; Spiegelman, Jamie; Swartz, Richard H; Nelder, Mark P; Baker, Stacey L; Landry, Lisa; Maceachern, Ross; Deamond, Sherri; Ross, Lorrie; Peters, Garth; Baird, Michelle; Rose, David; Sanders, Greg; Austin, John W

2012-01-01

Five cases of intestinal toxemia botulism in adults were identified within an 18-month period in or near Toronto, Ontario, Canada. We describe findings for 3 of the 5 case-patients. Clinical samples contained Clostridium botulinum spores and botulinum neurotoxins (types A and B) for extended periods (range 41-61 days), indicative of intestinal toxemia botulism. Patients' clinical signs improved with supportive care and administration of botulinum antitoxin. Peanut butter from the residence of 1 case-patient yielded C. botulinum type A, which corresponded with type A spores found in the patient's feces. The food and clinical isolates from this case-patient could not be distinguished by pulsed-field gel electrophoresis. Two of the case-patients had Crohn disease and had undergone previous bowel surgery, which may have contributed to infection with C. botulinum. These cases reinforce the view that an underlying gastrointestinal condition is a risk factor for adult intestinal toxemia botulism.

Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

NASA Astrophysics Data System (ADS)

Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

2015-11-01

Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

Significance and Regional Dependency of Peptide Transporter (PEPT) 1 in the Intestinal Permeability of Glycylsarcosine: In Situ Single-Pass Perfusion Studies in Wild-Type and Pept1 Knockout Mice

PubMed Central

Jappar, Dilara; Wu, Shu-Pei; Hu, Yongjun

2010-01-01

The purpose of this study was to evaluate the role, relevance, and regional dependence of peptide transporter (PEPT) 1 expression and function in mouse intestines using the model dipeptide glycylsarcosine (GlySar). After isolating specific intestinal segments, in situ single-pass perfusions were performed in wild-type and Pept1 knockout mice. The permeability of [3H]GlySar was measured as a function of perfusate pH, dipeptide concentration, potential inhibitors, and intestinal segment, along with PEPT1 mRNA and protein. We found the permeability of GlySar to be saturable (Km = 5.7 mM), pH-dependent (maximal value at pH 5.5), and specific for PEPT1; other peptide transporters, such as PHT1 and PHT2, were not involved, as judged by the lack of GlySar inhibition by excess concentrations of histidine. GlySar permeabilities were comparable in the duodenum and jejunum of wild-type mice but were much larger than that in ileum (approximately 2-fold). A PEPT1-mediated permeability was not observed for GlySar in the colon of wild-type mice (<10% residual uptake compared to proximal small intestine). Moreover, GlySar permeabilities were very low and not different in the duodenum, jejunum, ileum, and colon of Pept1 knockout mice. Functional activity of intestinal PEPT1 was confirmed by real-time polymerase chain reaction and immunoblot analyses. Our findings suggest that a loss of PEPT1 activity (e.g., due to polymorphisms, disease, or drug interactions) should have a major effect in reducing the intestinal absorption of di-/tripeptides, peptidomimetics, and peptide-like drugs. PMID:20660104

Lactobacillus salivarius reverse diabetes-induced intestinal defense impairment in mice through non-defensin protein.

PubMed

Chung, Pei-Hsuan; Wu, Ying-Ying; Chen, Pei-Hsuan; Fung, Chang-Phone; Hsu, Ching-Mei; Chen, Lee-Wei

2016-09-01

Altered intestinal microbiota and subsequent endotoxemia play pathogenic roles in diabetes. We aimed to study the mechanisms of intestinal defense impairment in type 1 diabetes and the effects of Lactobacillus salivarius as well as fructooligosaccharides (FOS) supplementation on diabetes-induced bacterial translocation. Alterations in the enteric microbiome, expression of mucosal antibacterial proteins and bacteria-killing activity of the intestinal mucosa in streptozotocin (STZ)-induced diabetic mice and Ins2(Akita) mice were investigated. The effects of dead L. salivarius (2×10(8)CFU/ml) and FOS (250 mg per day) supplementation for 1 week on endotoxin levels and Klebsiella pneumoniae translocation were also examined. Finally, germ-free mice were cohoused with wild-type or Ins2(Akita) mice for 2 weeks to examine the contribution of microbiota on the antibacterial protein expression. STZ-induced diabetic mice developed intestinal defense impairment as demonstrated by decreased mucosal bacteria-killing activity; reduction of non-defensin family proteins, such as Reg3β, Reg3γ, CRP-ductin and RELMβ, but not the defensin family proteins; and increased bacterial translocation. Intestinal bacteria overgrowth, enteric dysbiosis and increased intestinal bacterial translocation, particularly pathogenic K. pneumoniae in STZ-induced diabetic mice and Ins2(Akita) mice, were noted. Treating diabetic mice with dead L. salivarius or FOS reversed enteric dysbiosis, restored mucosal antibacterial protein and lessened endotoxin levels as well as K. pneumoniae translocation. Moreover, germ-free mice cohoused with wild-type mice demonstrated more intestinal Reg3β and RELMβ expression than those cohoused with Ins2(Akita) mice. These results indicate that hyperglycemia induces enteric dysbiosis, reduction of non-defensin proteins as well as bacteria-killing activity of the intestinal mucosa and intestinal defense impairment. Reversal of enteric dysbiosis with dead L. salivarius or FOS supplementation decreases diabetes-induced K. pneumoniae translocation and endotoxin levels through the induction of non-defensin proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Wild-Type Shigella Species and Attenuated Shigella Vaccine Candidates on Small Intestinal Barrier Function, Antigen Trafficking, and Cytokine Release

PubMed Central

Fiorentino, Maria; Levine, Myron M.

2014-01-01

Bacterial dysentery due to Shigella species is a major cause of morbidity and mortality worldwide. The pathogenesis of Shigella is based on the bacteria's ability to invade and replicate within the colonic epithelium, resulting in severe intestinal inflammatory response and epithelial destruction. Although the mechanisms of pathogenesis of Shigella in the colon have been extensively studied, little is known on the effect of wild-type Shigella on the small intestine and the role of the host response in the development of the disease. Moreover, to the best of our knowledge no studies have described the effects of apically administered Shigella flexneri 2a and S. dysenteriae 1 vaccine strains on human small intestinal enterocytes. The aim of this study was to assess the coordinated functional and immunological human epithelial responses evoked by strains of Shigella and candidate vaccines on small intestinal enterocytes. To model the interactions of Shigella with the intestinal mucosa, we apically exposed monolayers of human intestinal Caco2 cells to increasing bacterial inocula. We monitored changes in paracellular permeability, examined the organization of tight-junctions and the pro-inflammatory response of epithelial cells. Shigella infection of Caco2 monolayers caused severe mucosal damage, apparent as a drastic increase in paracellular permeability and disruption of tight junctions at the cell-cell boundary. Secretion of pro-inflammatory IL-8 was independent of epithelial barrier dysfunction. Shigella vaccine strains elicited a pro-inflammatory response without affecting the intestinal barrier integrity. Our data show that wild-type Shigella infection causes a severe alteration of the barrier function of a small intestinal cell monolayer (a proxy for mucosa) and might contribute (along with enterotoxins) to the induction of watery diarrhea. Diarrhea may be a mechanism by which the host attempts to eliminate harmful bacteria and transport them from the small to the large intestine where they invade colonocytes inducing a strong inflammatory response. PMID:24416363

The Effect of Intestinal Parasitic Infection on the Clinical Outcome of Malaria in Coinfected Children in Cameroon

PubMed Central

Kwenti, Tebit E.; Nkume, Franklin A.; Tanjeko, Ajime T.; Kwenti, Tayong D. B.

2016-01-01

Background The interaction between intestinal parasites and malaria is still not clear. Data in published literature are conflicting. We studied the effect of intestinal parasitic infection (IPI) on the clinical outcome of malaria in coinfected children. Methods In a cross sectional study performed between October 2014 and September 2015, children infected with malaria, as demonstrated by the presence of asexual parasites in Giemsa stained blood films, were enrolled. Stool samples were obtained from participants and subjected to the formol-ether concentration technique for the detection of intestinal parasites. The Complete blood count was performed using an automated haematology analyser (Mindray, BC-2800). The risk ratio, Pearson’s chi-square and the student T test were all performed as part of the statistical analyses. Statistical significance was set at p < 0.05. Results In all, 405 children successfully took part in the study. The children were between 1 week and 120 months of age (mean ± SD = 41.5 ± 33.5). Coinfection with intestinal parasites was observed in 11.6%. The rate of severe malaria (SM) attack in this study was 10.9%. SM was not observed to be associated with age (p = 0.377) or gender (p = 0.387), meanwhile coinfection with intestinal parasites was associated with age (p = 0.003). Among SM cases, IPI prevalence was higher in children with mild (WHO group 3) severe malaria (p = 0.027). Overall, IPI was not observed to be associated with SM (p = 0.656) or malaria parasite density (p = 0.185) or haemoglobin concentration (p = 0.205). The main clinical features of SM observed were hyperpyrexia (68.2%), severe malarial anaemia (61.4%), and multiple convulsion (52.3%). Conclusion IPI was not observed to be associated with the severity of malaria, the malaria parasite density, and the haemoglobin concentration in coinfected children in Cameroon. The clinical outcome of malaria in children coinfected with intestinal parasites may depend on the geographical setting after all. PMID:27128975

The Effect of Intestinal Parasitic Infection on the Clinical Outcome of Malaria in Coinfected Children in Cameroon.

PubMed

Kwenti, Tebit E; Nkume, Franklin A; Tanjeko, Ajime T; Kwenti, Tayong D B

2016-04-01

The interaction between intestinal parasites and malaria is still not clear. Data in published literature are conflicting. We studied the effect of intestinal parasitic infection (IPI) on the clinical outcome of malaria in coinfected children. In a cross sectional study performed between October 2014 and September 2015, children infected with malaria, as demonstrated by the presence of asexual parasites in Giemsa stained blood films, were enrolled. Stool samples were obtained from participants and subjected to the formol-ether concentration technique for the detection of intestinal parasites. The Complete blood count was performed using an automated haematology analyser (Mindray, BC-2800). The risk ratio, Pearson's chi-square and the student T test were all performed as part of the statistical analyses. Statistical significance was set at p < 0.05. In all, 405 children successfully took part in the study. The children were between 1 week and 120 months of age (mean ± SD = 41.5 ± 33.5). Coinfection with intestinal parasites was observed in 11.6%. The rate of severe malaria (SM) attack in this study was 10.9%. SM was not observed to be associated with age (p = 0.377) or gender (p = 0.387), meanwhile coinfection with intestinal parasites was associated with age (p = 0.003). Among SM cases, IPI prevalence was higher in children with mild (WHO group 3) severe malaria (p = 0.027). Overall, IPI was not observed to be associated with SM (p = 0.656) or malaria parasite density (p = 0.185) or haemoglobin concentration (p = 0.205). The main clinical features of SM observed were hyperpyrexia (68.2%), severe malarial anaemia (61.4%), and multiple convulsion (52.3%). IPI was not observed to be associated with the severity of malaria, the malaria parasite density, and the haemoglobin concentration in coinfected children in Cameroon. The clinical outcome of malaria in children coinfected with intestinal parasites may depend on the geographical setting after all.

Domestication and cereal feeding developed domestic pig-type intestinal microbiota in animals of suidae.

PubMed

Ushida, Kazunari; Tsuchida, Sayaka; Ogura, Yoshitoshi; Toyoda, Atsushi; Maruyama, Fumito

2016-06-01

Intestinal microbiota are characterized by host-specific microorganisms, which have been selected through host-microbe interactions under phylogenetic evolution and transition of feeding behavior by the host. Although many studies have focused on disease-related intestinal microbiota, the origin and evolution of host-specific intestinal microbiota have not been well elucidated. Pig is the ideal mammal model to reveal the origin and evolution of host-specific intestinal microbiota because their direct wild ancestor and close phylogenetic neighbors are available for comparison. The pig has been recognized as a Lactobacillus-type animal. We analyzed the intestinal microbiota of various animals in Suidae: domestic pigs, wild boars and Red river hogs to survey the origin and evolution of Lactobacillus-dominated intestinal microbiota by metagenomic approach and following quantitative PCR confirmation. The metagenomic datasets were separated in two clusters; the wild animal cluster being characterized by a high abundance of Bifidobacterium, whereas the domesticated (or captured) animal cluster by Lactobacillus. In addition, Enterobacteriaceae were harbored as the major family only in domestic Sus scrofa. We conclude that domestication may have induced a larger Enterobacteriaceae population in pigs, and the introduction of modern feeding system further caused the development of Lactobacillus-dominated intestinal microbiota, with genetic and geographical factors possibly having a minor impact. © 2015 Japanese Society of Animal Science.

Protein tyrosine phosphatase non-receptor type 2 and inflammatory bowel disease.

PubMed

Spalinger, Marianne R; McCole, Declan F; Rogler, Gerhard; Scharl, Michael

2016-01-21

Genome wide association studies have associated single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) with the onset of inflammatory bowel disease (IBD) and other inflammatory disorders. Expression of PTPN2 is enhanced in actively inflamed intestinal tissue featuring a marked up-regulation in intestinal epithelial cells. PTPN2 deficient mice suffer from severe intestinal and systemic inflammation and display aberrant innate and adaptive immune responses. In particular, PTPN2 is involved in the regulation of inflammatory signalling cascades, and critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses, and finally for maintaining intestinal homeostasis. On one hand, dysfunction of PTPN2 has drastic effects on innate host defence mechanisms, including increased secretion of pro-inflammatory cytokines, limited autophagosome formation in response to invading pathogens, and disruption of the intestinal epithelial barrier. On the other hand, PTPN2 function is crucial for controlling adaptive immune functions, by regulating T cell proliferation and differentiation as well as maintaining T cell tolerance. In this way, dysfunction of PTPN2 contributes to the manifestation of IBD. The aim of this review is to present an overview of recent findings on the role of PTPN2 in intestinal homeostasis and the impact of dysfunctional PTPN2 on intestinal inflammation.

Editorial: Emerging approaches for typing, detection, characterization, and traceback of Escherichia coli

USDA-ARS?s Scientific Manuscript database

Commensal E. coli inhabit the large intestines of humans and animals and are important in maintaining normal intestinal homeostasis. There are also many groups of disease-causing E. coli, including diarrheagenic and extra-intestinal pathogenic E. coli (ExPEC). There are approximately O188 somatic O...

Mapping the intestinal alpha-glucogenic enzyme specificities of starch digesting maltase-glucoamylase and sucrase-isomaltase

USDA-ARS?s Scientific Manuscript database

Inhibition of intestinal alpha-glucosidases and pancreatic alpha-amylases is an approach to controlling blood glucose and serum insulin levels in individuals with Type II diabetes. The two human intestinal glucosidases are maltase-glucoamylase and sucrase-isomaltase. Each incorporates two family 31 ...

The Agaricus blazei-Based Mushroom Extract, Andosan™, Protects against Intestinal Tumorigenesis in the A/J Min/+ Mouse.

PubMed

Hetland, Geir; Eide, Dag M; Tangen, Jon M; Haugen, Mads H; Mirlashari, Mohammad R; Paulsen, Jan E

2016-01-01

The novel A/J Min/+ mouse, which is a model for human Familial Adenomatous Polyposis (FAP), develops spontaneously multiple adenocarcinomas in the colon as well as in the small intestine. Agaricus blazei Murill (AbM) is an edible Basidiomycetes mushroom that has been used in traditional medicine against cancer and other diseases. The mushroom contains immunomodulating β-glucans and is shown to have antitumor effects in murine cancer models. Andosan™ is a water extract based on AbM (82%), but it also contains the medicinal Basidiomycetes mushrooms Hericeum erinaceus and Grifola frondosa. Tap water with 10% Andosan™ was provided as the only drinking water for 15 or 22 weeks to A/J Min/+ mice and A/J wild-type mice (one single-nucleotide polymorphism (SNP) difference), which then were exsanguinated and their intestines preserved in formaldehyde and the serum frozen. The intestines were examined blindly by microscopy and also stained for the tumor-associated protease, legumain. Serum cytokines (pro- and anti-inflammatory, Th1-, Th2 -and Th17 type) were measured by Luminex multiplex analysis. Andosan™ treated A/J Min/+ mice had a significantly lower number of adenocarcinomas in the intestines, as well as a 60% significantly reduced intestinal tumor load (number of tumors x size) compared to control. There was also reduced legumain expression in intestines from Andosan™ treated animals. Moreover, Andosan™ had a significant cytotoxic effect correlating with apoptosis on the human cancer colon cell line, Caco-2, in vitro. When examining serum from both A/J Min/+ and wild type mice, there was a significant increase in anti-tumor Th1 type and pro-inflammatory cytokines in the Andosan™ treated mice. The results from this mouse model for colorectal cancer shows significant protection of orally administered Andosan™ against development of intestinal cancer. This is supported by the finding of less legumain in intestines of Andosan™ treated mice and increased systemic Th1 cytokine response. The mechanism is probably both immuno-modulatory and growth inhibition of tumor cells by induction of apoptosis.

The Agaricus blazei-Based Mushroom Extract, Andosan™, Protects against Intestinal Tumorigenesis in the A/J Min/+ Mouse

PubMed Central

Eide, Dag M.; Tangen, Jon M.; Haugen, Mads H.; Mirlashari, Mohammad R.; Paulsen, Jan E.

2016-01-01

Background The novel A/J Min/+ mouse, which is a model for human Familial Adenomatous Polyposis (FAP), develops spontaneously multiple adenocarcinomas in the colon as well as in the small intestine. Agaricus blazei Murill (AbM) is an edible Basidiomycetes mushroom that has been used in traditional medicine against cancer and other diseases. The mushroom contains immunomodulating β-glucans and is shown to have antitumor effects in murine cancer models. Andosan™ is a water extract based on AbM (82%), but it also contains the medicinal Basidiomycetes mushrooms Hericeum erinaceus and Grifola frondosa. Methods and findings Tap water with 10% Andosan™ was provided as the only drinking water for 15 or 22 weeks to A/J Min/+ mice and A/J wild-type mice (one single-nucleotide polymorphism (SNP) difference), which then were exsanguinated and their intestines preserved in formaldehyde and the serum frozen. The intestines were examined blindly by microscopy and also stained for the tumor-associated protease, legumain. Serum cytokines (pro- and anti-inflammatory, Th1-, Th2 -and Th17 type) were measured by Luminex multiplex analysis. Andosan™ treated A/J Min/+ mice had a significantly lower number of adenocarcinomas in the intestines, as well as a 60% significantly reduced intestinal tumor load (number of tumors x size) compared to control. There was also reduced legumain expression in intestines from Andosan™ treated animals. Moreover, Andosan™ had a significant cytotoxic effect correlating with apoptosis on the human cancer colon cell line, Caco-2, in vitro. When examining serum from both A/J Min/+ and wild type mice, there was a significant increase in anti-tumor Th1 type and pro-inflammatory cytokines in the Andosan™ treated mice. Conclusions The results from this mouse model for colorectal cancer shows significant protection of orally administered Andosan™ against development of intestinal cancer. This is supported by the finding of less legumain in intestines of Andosan™ treated mice and increased systemic Th1 cytokine response. The mechanism is probably both immuno-modulatory and growth inhibition of tumor cells by induction of apoptosis. PMID:28002446

Therapeutic perspectives for melatonin agonists and antagonists.

PubMed

Delagrange, P; Atkinson, J; Boutin, J A; Casteilla, L; Lesieur, D; Misslin, R; Pellissier, S; Pénicaud, L; Renard, P

2003-04-01

Melatonin is a neurohormone synthesized in the pineal gland during the dark period in all species, including humans. The diversity and differences in melatonin receptor distribution in the brain and extracerebral organs suggest multiple functional roles for melatonin. Administration of melatonin agonists reduces neophobia and treatment with a melatonin antagonist during the dark period reverses the anxiolytic-like effect of endogenous melatonin. Chronic treatment with agonists prevents various perturbations induced by chronic mild stress. Melatonin in vivo directly constricts cerebral arterioles in rats and decreases the lower limit of cerebral blood flow autoregulation, suggesting that melatonin may diminish the risk of hypoperfusion-induced cerebral ischemia. At the extracerebral level, melatonin regulates intestinal motility in rats. The intestinal postprandial motor response is shorter in the dark phase than in the light phase and this reduction is reversed in animals pretreated with a melatonin antagonist. Moreover, melatonin reduces the duration of cholecystokinin excitomotor effect. Endogenous melatonin may modulate intestinal motility to coordinate intestinal functions such as digestion and transit and control the metabolism of the animal. An adipocyte melatonin binding site may also participate in this control. Melatonin is involved in a wide range of physiological functions. The question remains as to whether evolution, adaptation and diurnal life have modified the physiological role of melatonin in humans. Moreover, the functional role of each of the receptor subtypes has to be characterized to design selective ligands to treat specific diseases.

Prevalence of malnutrition and associated risk factors among adult visceral leishmaniasis patients in Northwest Ethiopia: a cross sectional study.

PubMed

Mengesha, Bewketu; Endris, Mengistu; Takele, Yegnasew; Mekonnen, Kalehiwot; Tadesse, Takele; Feleke, Amsalu; Diro, Ermias

2014-02-04

Visceral leishmaniasis (VL) causes considerable morbidity and mortality in Ethiopia. Data on the prevalence and associated risk factors on malnutrition among VL patients in Ethiopia are scarce. This study aimed to assess the prevalence of malnutrition and its associated risk factor among VL patients in Northwest Ethiopia. An institution-based cross-sectional study was conducted from June to September 2012 at four leishmaniasis treatment sites in Northwest Ethiopia. Four hundred and three adult VL patients were enrolled in the study. Malnutrition was defined as a body mass index (BMI) ≤ 18.5 kg/m2. The data collected from the VL patients included sex, age, residence, occupation, weight, height, laboratory results (HIV, hemoglobin, intestinal parasites). Multivariate logistic regression model was used to determine the strength of association between malnutrition and associated risk factors. Among 403 adult VL patients 385 (95.5%) were malnourished. Twenty eight percent (n = 113), 30.3% (n = 122), and 37.2% (n = 150) were mildly, moderately and severely malnourished, respectively. The prevalence of intestinal parasitic infection was 47.6% (n = 192) and it was associated with malnutrition (P = 0.01). The prevalence of VL-HIV co-infection was 10.4% (n = 42). Hook worm, Giardia intestinalis and Ascaris lumbircoides were the leading prevalent intestinal parasites. Factors such as age, sex, residence, occupation, HIV status and anemia were not associated with severe malnutrition. The prevalence of malnutrition in VL patients was very high and it was associated with intestinal parasitic infections. Therefore, screening of severely malnourished VL patients for intestinal parasitic infections during admission is recommended.

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

PubMed Central

Coats, Stephen R.; Hashim, Ahmed; Paramonov, Nikolay A.; Curtis, Michael A.

2016-01-01

ABSTRACT Intestinal homeostasis mechanisms must protect the host intestinal tissue from endogenous lipopolysaccharides (LPSs) produced by the intestinal microbiota. In this report, we demonstrate that murine intestinal fecal lipids effectively block Toll-like receptor 4 (TLR4) responses to naturally occurring Bacteroidetes sp. LPS. Cardiolipin (CL) represents a significant proportion of the total intestinal and fecal lipids and, furthermore, potently antagonizes TLR4 activation by reducing LPS binding at the lipopolysaccharide binding protein (LBP), CD14, and MD-2 steps of the TLR4 signaling pathway. It is further demonstrated that intestinal lipids and CL are less effective at neutralizing more potent Enterobacteriaceae-type LPS, which is enriched in feces obtained from mice with dextran sodium sulfate (DSS)-treated inflammatory bowel disease. The selective inhibition of naturally occurring LPS structures by intestinal lipids may represent a novel homeostasis mechanism that blocks LPS activation in response to symbiotic but not dysbiotic microbial communities. IMPORTANCE The guts of animals harbor a variety of Gram-negative bacteria associated with both states of intestinal health and states of disease. Environmental factors, such as dietary habits, can drive the microbial composition of the host animal's intestinal bacterial community toward a more pathogenic state. Both beneficial and harmful Gram-negative bacteria are capable of eliciting potentially damaging inflammatory responses from the host intestinal tissues via a lipopolysaccharide (LPS)-dependent pathway. Physical mucosal barriers and antibodies produced by the intestinal immune system protect against the undesired inflammatory effects of LPS, although it is unknown why some bacteria are more effective at overcoming the protective barriers than others. This report describes the discovery of a lipid-type protective barrier in the intestine that reduces the deleterious effects of LPSs from beneficial bacteria but is less effective in dampening the inflammatory effects of LPSs from harmful bacteria, providing a novel mechanistic insight into inflammatory intestinal disorders. PMID:27208127

Absence of post-translational aspartyl beta-hydroxylation of epidermal growth factor domains in mice leads to developmental defects and an increased incidence of intestinal neoplasia.

PubMed

Dinchuk, Joseph E; Focht, Richard J; Kelley, Jennifer A; Henderson, Nancy L; Zolotarjova, Nina I; Wynn, Richard; Neff, Nicola T; Link, John; Huber, Reid M; Burn, Timothy C; Rupar, Mark J; Cunningham, Mark R; Selling, Bernard H; Ma, Jianhong; Stern, Andrew A; Hollis, Gregory F; Stein, Robert B; Friedman, Paul A

2002-04-12

The BAH genomic locus encodes three distinct proteins: junctin, humbug, and BAH. All three proteins share common exons, but differ significantly based upon the use of alternative terminal exons. The biological roles of BAH and humbug and their functional relationship to junctin remain unclear. To evaluate the role of BAH in vivo, the catalytic domain of BAH was specifically targeted such that the coding regions of junctin and humbug remained undisturbed. BAH null mice lack measurable BAH protein in several tissues, lack aspartyl beta-hydroxylase activity in liver preparations, and exhibit no hydroxylation of the epidermal growth factor (EGF) domain of clotting Factor X. In addition to reduced fertility in females, BAH null mice display several developmental defects including syndactyly, facial dysmorphology, and a mild defect in hard palate formation. The developmental defects present in BAH null mice are similar to defects observed in knock-outs and hypomorphs of the Notch ligand Serrate-2. In this work, beta-hydroxylation of Asp residues in EGF domains is demonstrated for a soluble form of a Notch ligand, human Jagged-1. These results along with recent reports that another post-translational modification of EGF domains in Notch gene family members (glycosylation by Fringe) alters Notch pathway signaling, lends credence to the suggestion that aspartyl beta-hydroxylation may represent another post-translational modification of EGF domains that can modulate Notch pathway signaling. Previous work has demonstrated increased levels of BAH in certain tumor tissues and a role for BAH in tumorigenesis has been proposed. The role of hydroxylase in tumor formation was tested directly by crossing BAH KO mice with an intestinal tumor model, APCmin mice. Surprisingly, BAH null/APCmin mice show a statistically significant increase in both intestinal polyp size and number when compared with BAH wild-type/APCmin controls. These results suggest that, in contrast to expectations, loss of BAH catalytic activity may promote tumor formation.

[The detection of strains of Esherichia coll producing Shiga toxin in populations of normal intestinal microbiota in children with functional disorders of gastrointestinal tract].

PubMed

Ivanova, E I; Popkova, S M; Dzhioev, Iu P; Rakova, E B; Nemchenko, U M; Rychkova, L V

2014-11-01

In intestinal ecosystem, interchange of genetic material between different types of bacteria and other representatives of family Enterobacteriaceae results in development of types of normal colibacillus with genetic characteristics of pathogenicity. This occurrence can be considered as a theoretical substantiation for labeling such strains as pathobionts. The polymerase chain reaction was implemented to analyze 96 strains of different types of Escherichia coli (with normal and weak zymogenic activity and hemolytic activity) isolated from children with functional disorders of gastrointestinal tract. The purpose was to detect presence of gens coding capacity of toxin production (six1, stx2). In intestinal biotope of children, circulation of strains of Escherichia coli producing shiga toxin having no relation to pathogenic group being representatives of normal indigenous microbiota. The presence of gens stx1 and stx2 in various biochemical types of Escherichia coli permits establishing fact of forming of reservoir of potential pathogenicity in non-pathogenic forms of Escherichia coli. The presence of gen (verotoxin 1) in genome of various types of Escherichia coli isolated from one single biotope testifies possible horizontal transmission of factors of pathogenicity in intestinal biotope.

Toxicity of food-relevant nanoparticles in intestinal epithelial models

NASA Astrophysics Data System (ADS)

McCracken, Christie

Nanoparticles are increasingly being incorporated into common consumer products, including in foods and food packaging, for their unique properties at the nanoscale. Food-grade silica and titania are used as anti-caking and whitening agents, respectively, and these particle size distributions are composed of approximately one-third nanoparticles. Zinc oxide and silver nanoparticles can be used for their antimicrobial properties. However, little is known about the interactions of nanoparticles in the body upon ingestion. This study was performed to investigate the role of nanoparticle characteristics including surface chemistry, dissolution, and material type on toxicity to the intestinal epithelium. Only mild acute toxicity of zinc oxide nanoparticles was observed after 24-hour treatment of intestinal epithelial C2BBe1 cells based on the results of toxicity assays measuring necrosis, apoptosis, membrane damage, and mitochondrial activity. Silica and titanium dioxide nanoparticles were not observed to be toxic although all nanoparticles were internalized by cells. In vitro digestion of nanoparticles in solutions representing the stomach and intestines prior to treatment of cells did not alter nanoparticle toxicity. Long-term repeated treatment of cells weekly for 24 hours with nanoparticles did not change nanoparticle cytotoxicity or the growth rate of the treated cell populations. Thus, silica, titanium dioxide, and zinc oxide nanoparticles were found to induce little toxicity in intestinal epithelial cells. Fluorescent silica nanoparticles were synthesized as a model for silica used in foods that could be tracked in vitro and in vivo. To maintain an exterior of pure silica, a silica shell was hydrolyzed around a core particle of quantum dots or a fluorescent dye electrostatically associated with a commercial silica particle. The quantum dots used were optimized from a previously reported microwave quantum dot synthesis to a quantum yield of 40%. Characterization of the silica particles showed that the surface properties resembled pure silica. These particles were able to be detected in vitro as well as in vivo after oral administration of nanoparticles to mice by gavage. After four daily administrations, nanoparticles were detected by fluorescence confocal microscopy in intestines as well as liver, kidney, spleen, lung, and brain. Thus, silica nanoparticles were able to traverse the intestinal epithelium. Further investigation is needed to determine nanoparticle accumulation and potential functional consequences throughout the body. Silver nanoparticles were particularly toxic to proliferating (subconfluent) C2BBe1 cells plated at low density, inducing 15% necrosis and a 76% decrease in mitochondrial activity. Silver nanoparticle treatment induced oxidative stress in cells based on increased GSH/GSSG ratios. In addition, silver nanoparticles induced G2/M phase cell cycle arrest and inhibited cell proliferation at doses forty times lower than those at which silica, titanium dioxide, and zinc oxide nanoparticles had inhibitory effects. Silver nanoparticles subjected to in vitro digestion before cell exposure required higher doses to induce toxicity, likely due to slower dissolution because of greater surface species adsorption. Silver nanoparticles did not cause toxicity or oxidative stress in confluent (stationary) cells. Thus, upon ingestion, silver nanoparticles may be especially toxic to proliferating stem cells in intestinal crypts, particularly in disease states with a compromised epithelium.

[The detection of occurrence rate of genes coding capability to form pili binding in auto-strains of Escherichia coli].

PubMed

Ivanova, E I; Popkova, S M; Dzhioev, Iu P; Rakova, E B; Dolgikh, V V; Savel'kaeva, M V; Nemchenko, U M; Bukharova, E V; Serdiuk, L V

2015-01-01

E. coli is a commensal of intestine of the vertebrata. The exchange of genetic material of different types of bacteria between themselves and with other representatives of family of Enterobacteriaceae in intestinal ecosystem results in development of types of normal colibacillus with genetic characteristics of pathogenicity that can serve as a theoretical substantiation to attribute such strains to pathobionts. The entero-pathogenic colibacillus continues be an important cause of diarrhea in children in developing countries. The gene responsible for formation of pili binding is a necessary condition for virulence of entero-pathogenic colibacillus. The polymerase chain reaction was applied to examine 316 strains of different types of E. coli (normal, with weak enzyme activity and hemolytic activity) isolated from healthy children and children with functional disorders of gastro-intestinal tract for presence of genes coding capability to form pill binding. The presence of this gene in different biochemical types of E. coli permits to establish the fact of formation of reservoir of pathogenicity in indigent microbiota of intestinal biocenosis.

Intestinal Immune Responses to Type 2 Oral Polio Vaccine (OPV) Challenge in Infants Previously Immunized With Bivalent OPV and Either High-Dose or Standard Inactivated Polio Vaccine.

PubMed

Brickley, Elizabeth B; Strauch, Carolyn B; Wieland-Alter, Wendy F; Connor, Ruth I; Lin, Shu; Weiner, Joshua A; Ackerman, Margaret E; Arita, Minetaro; Oberste, M Steven; Weldon, William C; Sáez-Llorens, Xavier; Bandyopadhyay, Ananda S; Wright, Peter F

2018-01-17

The impact of inactivated polio vaccines (IPVs) on intestinal mucosal immune responses to live poliovirus is poorly understood. In a 2014 phase 2 clinical trial, Panamanian infants were immunized at 6, 10, and 14 weeks of age with bivalent oral polio vaccine (bOPV) and randomized to receive either a novel monovalent high-dose type 2-specific IPV (mIPV2HD) or a standard trivalent IPV at 14 weeks. Infants were challenged at 18 weeks with a monovalent type 2 oral polio vaccine (mOPV2). Infants' intestinal immune responses during the 3 weeks following challenge were investigated by measuring poliovirus type-specific neutralization and immunoglobulin (Ig) A, IgA1, IgA2, IgD, IgG, and IgM antibodies in stool samples. Despite mIPV2HD's 4-fold higher type 2 polio D-antigen content and heightened serum neutralization profile, mIPV2HD-immunized infants' intestinal immune responses to mOPV2 challenge were largely indistinguishable from those receiving standard IPV. Mucosal responses were tightly linked to evidence of active infection and, in the 79% of participants who shed virus, robust type 2-specific IgA responses and stool neutralization were observed by 2 weeks after challenge. Enhancing IPV-induced serum neutralization does not substantively improve intestinal mucosal immune responses or limit viral shedding on mOPV2 challenge. NCT02111135. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

Intestinal Immune Responses to Type 2 Oral Polio Vaccine (OPV) Challenge in Infants Previously Immunized With Bivalent OPV and Either High-Dose or Standard Inactivated Polio Vaccine

PubMed Central

Brickley, Elizabeth B; Strauch, Carolyn B; Wieland-Alter, Wendy F; Connor, Ruth I; Lin, Shu; Weiner, Joshua A; Ackerman, Margaret E; Arita, Minetaro; Oberste, M Steven; Weldon, William C; Sáez-Llorens, Xavier; Bandyopadhyay, Ananda S; Wright, Peter F

2018-01-01

Abstract Background The impact of inactivated polio vaccines (IPVs) on intestinal mucosal immune responses to live poliovirus is poorly understood. Methods In a 2014 phase 2 clinical trial, Panamanian infants were immunized at 6, 10, and 14 weeks of age with bivalent oral polio vaccine (bOPV) and randomized to receive either a novel monovalent high-dose type 2–specific IPV (mIPV2HD) or a standard trivalent IPV at 14 weeks. Infants were challenged at 18 weeks with a monovalent type 2 oral polio vaccine (mOPV2). Infants’ intestinal immune responses during the 3 weeks following challenge were investigated by measuring poliovirus type-specific neutralization and immunoglobulin (Ig) A, IgA1, IgA2, IgD, IgG, and IgM antibodies in stool samples. Results Despite mIPV2HD’s 4-fold higher type 2 polio D–antigen content and heightened serum neutralization profile, mIPV2HD-immunized infants’ intestinal immune responses to mOPV2 challenge were largely indistinguishable from those receiving standard IPV. Mucosal responses were tightly linked to evidence of active infection and, in the 79% of participants who shed virus, robust type 2–specific IgA responses and stool neutralization were observed by 2 weeks after challenge. Conclusions Enhancing IPV-induced serum neutralization does not substantively improve intestinal mucosal immune responses or limit viral shedding on mOPV2 challenge. Clinical Trials Registration NCT02111135. PMID:29304199

Signet-ring cell carcinoma in gastric biopsies: expecting the unexpected.

PubMed

Golembeski, Christopher P; Genta, Robert Maximilian

2013-02-01

This study was designed to establish the relative prevalence of intestinal-type and signet-ring carcinoma in gastric biopsy specimens from ambulatory patients, to determine the percentage of signet-ring carcinomas that could be expected based on the available clinical and endoscopic information, and to estimate the likelihood of missing a tumour. We extracted data of all patients with a diagnosis of primary gastric carcinoma from a national pathology database. We then reviewed clinical information and original slides, classified tumours as intestinal or signet-ring-type, and categorised the latter as 'unexpected' (no alarming symptoms, no mention of suspicious lesions) or 'expected' (clinical or endoscopic information suggestive of tumour). Unexpected signet-ring carcinomas were categorised as 'obvious' or 'challenging' (rare signet-ring cells; immunohistochemical stains used to confirm the nature of the infiltrates). There were 310 109 patients with gastric biopsies; 615 patients had primary gastric carcinoma (359 intestinal and 256 signet-ring-type). Gastric cancer was more common in men (OR 2.54; 95% CI 2.05 to 3.14; p<.0001) for intestinal-type and (OR 1.90; 95% CI 1.48 to 2.42; p<0.0001) for signet-ring cell type). Intestinal-type carcinoma occurred in older patients than signet-ring-type (median age 74 vs 65 years, p<0.001). There were 196 expected and 60 unexpected signet-ring carcinomas; 47 of the 60 unexpected cases were histopathologically obvious. Thus, only 13 signet-ring carcinomas (1 in 25 000 gastric biopsy sets) were truly unexpected. Signet-ring carcinoma is a rare finding in gastric biopsy specimens from ambulatory patients; routine due diligence and the clinical/endoscopic information provided are usually adequate to raise pathologists' index of suspicion.

Expression responses of five cold tolerant related genes to two temperature dropping treatments in sea cucumber Apostichopus japonicus

NASA Astrophysics Data System (ADS)

Li, Chengze; Chang, Yaqing; Pang, Zhenguo; Ding, Jun; Ji, Nanjing

2015-03-01

Environmental conditions, including ambient temperature, play important roles in survival, growth development, and reproduction of the Japanese sea cucumber, Apostichopus japonicus. Low temperatures result in slowed growth and skin ulceration disease. In a previous study, we investigated the effect of low temperature on gene expression profiles in A. japonicus by suppression subtractive hybridization (SSH). Genes encoding Ferritin, Lysozyme, Hsp70, gp96, and AjToll were selected from a subtracted cDNA library of A. japonicus under acute cold stress. The transcriptional expression profiles of these genes were investigated in different tissues (coelomocyte, respiratory tree, intestine, longitudinal muscle) after exposure to acute and mild temperature dropping treatments. The results show that (1) the five cold-tolerance-related genes were found in all four tissues and the highest mRNA levels were observed in coelomocyte and respiratory tree; (2) under the temperature dropping treatments, three types of transcriptional regulation patterns were observed: primary suppression followed by up-regulation at -2°C, suppressed expression throughout the two treatments, and more rarely an initial stimulation followed by suppression; and (3) gene expression suppression was more severe under acute temperature dropping than under mild temperature dropping treatment. The five cold-tolerance-related genes that were distributed mainly in coelomocyte and respiratory tissues were generally down-regulated by low temperature stress but an inverse up-regulation event was found at the extreme temperature (-2°C).

Type 1 fimbriae are important factors limiting the dissemination and colonization of mice by Salmonella Enteritidis and contribute to the induction of intestinal inflammation during Salmonella invasion

PubMed Central

Kuźmińska-Bajor, Marta; Grzymajło, Krzysztof; Ugorski, Maciej

2015-01-01

We have recently shown that Salmonella Gallinarum type 1 fimbriae with endogenous mannose-resistant (MR) variant of the FimH protein increase systemic dissemination of S. Gallinarum and colonization of internal organs in comparison to the S. Gallinarum fimH knockout strain or the mutant expressing mannose-sensitive (MS) FimH variant from S. Enteritidis. Elaborating from these studies, we proposed that MS variants of FimH are advantageous in gastrointestinal infections, in contrast to MR FimH variants which decrease intestinal colonization and promote their systemic spreading. To support our hypothesis, we carried out in vivo studies using mice infected with wild-type S. Enteritidis and its fimH knockout strain (S. Enteritidis), which was characterized by significantly lower adhesion and invasiveness of murine ICE-1 intestinal cells. Using bioluminescence imaging, we observed that the loss of MS FimH adhesin correlates well with the highly increased colonization of mice by these bacteria. The appearance of the mutant strain was observed much earlier than wild-type Salmonella, and mice infected with 104–107 S. Enteritidis fimH::kan CFUs had significantly (P < 0.05) shorter infection-free time than animals inoculated with wild-type S. Enteritidis. Infections caused by non-typhoid Salmonella, such as S. Enteritidis, are associated with massive inflammation of the lamina propria and lymph nodes in the intestinal tract. Therefore, we evaluated the role of MS type 1 fimbriae in the induction of cytokine expression and secretion, using murine ICE-1 intestinal cells. We showed that the expression, as well as secretion, of Il-1b, Il-6, Il-10, and Il-12b was significantly higher in cells infected with wild-type S. Enteritidis compared to cells infected with the mutant strain. Based on our results, we propose that type 1 fimbriae may play an important role in the pathogenicity of S. Enteritidis and may contribute to an intestinal inflammatory response. PMID:25914682

CLINICOPATHOLOGIC CORRELATES OF FASCIOLIASIS IN TWO EASTERN GREY KANGAROOS (MACROPUS GIGANTEUS).

PubMed

Portas, Timothy J; Taylor, David

2015-12-01

Infection with the introduced trematode Fasciola hepatica was associated with anemia, mild to moderate azotemia, hypoalbuminemia, and elevated liver enzymes and creatine kinase values in two free-ranging eastern grey kangaroos (Macropus giganteus). Both kangaroos were euthanized because of the severity of clinical signs associated with infection. Histopathologic changes included severe cholangiohepatitis, biliary hyperplasia, and fibrosis. Hepatic, splenic, and intestinal amyloidosis was present in one kangaroo and hepatic abscessation in the other; neither histologic change has been reported in macropodids with fascioliasis previously.

[The structure of the glycerophosphate-containing O-specific polysaccharide from Escherichia coli 0130].

PubMed

Perepelov, A V; Lu, B; Sebchenkova, S N; Shevelev, S D; Wang, V; Shashkov, A S; Feng, L; Wang, L; Knirel', Iu A

2007-01-01

A phosphorylated O-specific polysaccharide was obtained by mild acidic degradation of the lipopolysaccharide from the intestinal bacterium Escherichia coli 0130 and characterized by the methods of chemical analysis, including dephosphorylation, and 1H and 13C NMR spectroscopy. The polysaccharide was shown to be composed of branched tetrasaccharide repeating units containing two N-acetyl-D-galactosamine residues, D-galactose, D-glucose, and glycerophosphate residues (one of each). The polysaccharide has the following structure, which is unique among the known bacterial polysaccharides.

The effect of mild traumatic brain injury on peripheral nervous system pathology in wild-type mice and the G93A mutant mouse model of motor neuron disease.

PubMed

Evans, T M; Jaramillo, C A; Sataranatarajan, K; Watts, L; Sabia, M; Qi, W; Van Remmen, H

2015-07-09

Traumatic brain injury (TBI) is associated with a risk of neurodegenerative disease. Some suggest a link between TBI and motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS). To investigate the potential mechanisms linking TBI to MND, we measured motor function and neuropathology following mild-TBI in wild-type and a transgenic model of ALS, G93A mutant mice. Mild-TBI did not alter the lifespan of G93A mice or age of onset; however, rotarod performance was impaired in G93A verses wild-type mice. Grip strength was reduced only in G93A mice after mild-TBI. Increased electromyography (EMG) abnormalities and markers of denervation (AchR, Runx1) indicate that mild-TBI may result in peripheral effects that are exaggerated in G93A mice. Markers of inflammation (cell edema, astrogliosis and microgliosis) were detected at 24 and 72h in the brain and spinal cord in wild-type and G93A mice. Levels of F2-isoprostanes, a marker of oxidative stress, were increased in the spinal cord 24h post mild-TBI in wild-type mice but were not affected by TBI in G93A mice. In summary, our data demonstrate that mild-TBI induces inflammation and oxidative stress and negatively impacts muscle denervation and motor performance, suggesting mild-TBI can potentiate motor neuron pathology and influence the development of MND in mice. Published by Elsevier Ltd.

Effects of turpentine-induced inflammation on the hypoxic stimulation of intestinal Fe3+ absorption in mice.

PubMed Central

Raja, K. B.; Duane, P.; Peters, T. J.

1990-01-01

Chronic subcutaneous turpentine administration (weekly for 6 weeks) induced a mild normocytic anaemia in mice. In-vitro and in-vivo intestinal Fe3+ absorption parameters were, however, not significantly altered from values in saline-treated or untreated mice. Normal mice, when exposed to 3 days hypoxia demonstrated a 2-3-fold increase in iron absorption in vivo, mainly due to changes in the amount of iron transferred from the mucosa to the plasma and thence to the carcass. A 2-3-fold increase in Vmax was also observed in in-vitro uptake experiments using isolated duodenal fragments. In contrast, turpentine-treated animals, though demonstrating an enhanced in-vitro maximal uptake capacity, failed to elicit an adaptive response in vivo following hypoxic exposure. These findings suggest that a circulating (humoral) factor may be responsible for the inhibition in absorption in vivo in this turpentine-induced inflammatory model. PMID:2278822

The Drosophila Nora virus is an enteric virus, transmitted via feces.

PubMed

Habayeb, Mazen S; Cantera, Rafael; Casanova, Gabriela; Ekström, Jens-Ola; Albright, Shannon; Hultmark, Dan

2009-04-01

The biology of the Drosophila viruses has not been intensely investigated. Here we have investigated the biology of the Nora virus, a persistent Drosophila virus. We find that injected Nora virus is able to replicate in the files, reaching a high titer that is maintained in the next generation. There is a remarkable variation in the viral loads of individual flies in persistently infected stocks; the titers can differ by three orders of magnitude. The Nora virus is mainly found in the intestine of infected flies, and the histology of these infected intestines show increased vacuolization. The virus is excreted in the feces and is horizontally transmitted. The Nora virus infection has a very mild effect on the longevity of the flies, and no significant effect on the number of eggs laid and the percent of eggs that develop to adults.

Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats.

PubMed

Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

2017-04-01

Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC 50 = 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU 50 = 3.5% ± 1.6%) or without insulin (GU 50 = 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.

The Functions of Type I and Type II Natural Killer T (NKT) Cells in Inflammatory Bowel Diseases

PubMed Central

Liao, Chia-Min; Zimmer, Michael I.; Wang, Chyung-Ru

2013-01-01

CD1d-restricted natural killer T (NKT) cells are a distinct subset of T cells that rapidly produce an array of cytokines upon activation and play a critical role in regulating various immune responses. NKT cells are classified into two groups based on differences in T cell receptor (TCR) usage. Type I NKT cells have an invariant TCRα-chain and are readily detectable by α-galactosylceramide (α-GalCer)-loaded CD1d tetramers. Type II NKT cells have a more diverse TCR repertoire and cannot be directly identified. Both types of NKT cells as well as multiple CD1d-expressing cell types are present in the intestine and their interactions are likely to be modulated by pathogenic and commensal microbes, which in turn contribute to the intestinal immune responses in health and disease. Indeed, in several animal models of inflammatory bowel disease (IBD), Type I NKT cells have been shown to make both protective and pathogenic contributions to disease. In contrast, in human patients suffering from ulcerative colitis (UC), and a mouse model in which both CD1d expression and the frequency of Type II NKT cells are increased, Type II NKT cells appear to promote intestinal inflammation. In this review, we summarize present knowledge on the antigen recognition, activation and function of NKT cells with a particular focus on their role in IBD, and discuss factors that may influence the functional outcome of NKT cell responses in intestinal inflammation. PMID:23518808

Injection of celiac disease patient sera or immunoglobulins to mice reproduces a condition mimicking early developing celiac disease.

PubMed

Kalliokoski, Suvi; Caja, Sergio; Frias, Rafael; Laurila, Kaija; Koskinen, Outi; Niemelä, Onni; Mäki, Markku; Kaukinen, Katri; Korponay-Szabó, Ilma R; Lindfors, Katri

2015-01-01

Typical features of celiac disease are small-bowel villus atrophy, crypt hyperplasia, and inflammation which develop gradually concomitant with ingestion of gluten. In addition, patients have anti-transglutaminase 2 (TG2) autoantibodies in their serum and tissues. The aim of this study was to establish whether celiac disease can be passively transferred to mice by serum or immunoglobulins. Serum aliquots or purified immunoglobulins (Ig) were intraperitoneally injected into Hsd:Athymic Nude-Foxn1nu mice for 8 or 27 days. As mice do not have proper IgA transport from peritoneum to blood, sera with a high content of IgG class anti-TG2 antibodies from untreated IgA-deficient celiac patients were used. Mouse sera were tested for celiac disease-specific autoantibodies, and several tissues were analyzed for autoantibody deposits targeted to TG2. Morphological assessment was made of the murine small intestinal mucosa. Injection of celiac disease patient sera or total IgG led to a significant delay in weight gain and mild diarrhea in a subset of mice. The mice injected with celiac patient sera or IgG had significantly decreased villus height crypt depth (Vh/CrD) ratios and celiac disease-specific autoantibody deposits targeted to TG2 in several tissues, including the small intestine. None of these features were observed in control mice. We conclude that administration of IgA-deficient celiac disease patient serum or total IgG induces both deterioration of the intestinal mucosa and clinical features of celiac disease in mice. The experimentally induced condition in the mice injected with patient serum or IgG resembles early developing celiac disease in humans. Celiac disease patient sera or total IgG was injected into athymic mice. A significant delay in weight gain and mild diarrhea was observed. Mice evinced significantly decreased villus height crypt depth ratios. Celiac disease-specific autoantibody deposits were present in several tissues. The condition in mice resembles early stage celiac disease in humans.

The association between multiple intestinal helminth infections and blood group, anaemia and nutritional status in human populations from Dore Bafeno, southern Ethiopia.

PubMed

Degarege, A; Animut, A; Medhin, G; Legesse, M; Erko, B

2014-06-01

In this cross-sectional study, the associations between helminth infections and ABO blood group, anaemia and undernutrition were investigated in 480 febrile outpatients who visited Dore Bafeno Health Centre, southern Ethiopia, in December 2010. Stool specimens were processed using the Kato-Katz method and examined for intestinal helminth infections. Haemoglobin level was measured using a HemoCue machine and blood group was determined using an antisera haemagglutination test. Nutritional status of the study participants was assessed using height and weight measurements. Among the study participants, 50.2% were infected with intestinal helminths. Ascaris lumbricoides (32.7%), Trichuris trichiura (12.7%), Schistosoma mansoni (11.9%) and hookworm (11.0%) were the most frequently diagnosed helminths. The odds of infection and mean eggs per gram of different intestinal helminth species were comparable between the various blood groups. Among individuals who were infected with intestinal helminth(s), the mean haemoglobin level was significantly lower in individuals harbouring three or more helminth species and blood type AB compared to cases with double or single helminth infection and blood type O, respectively. The odds of being underweight was significantly higher in A. lumbricoides and T. trichiura infected individuals of age ≤ 5 and ≥ 20 years, respectively, when compared to individuals of the matching age group without intestinal helminths. In conclusion, infection with multiple intestinal helminths was associated with lower haemoglobin level, which was more severe in individuals with blood type AB. Future studies should focus on mechanisms by which blood group AB exacerbates the helminth-related reduction in mean haemoglobin level.

Claudin-18 overexpression in intestinal-type mucinous borderline tumour of the ovary.

PubMed

Halimi, Sultan Ahmad; Maeda, Daichi; Shinozaki-Ushiku, Aya; Koso, Takahiro; Matsusaka, Keisuke; Tanaka, Mariko; Arimoto, Takahide; Oda, Katsutoshi; Kawana, Kei; Yano, Tetsu; Fujii, Tomoyuki; Fukayama, Masashi

2013-10-01

Mucinous borderline tumours of the ovary are subclassified as intestinal-type (IMBT) and endocervical-like (EMBT), which differ in their clinicopathological features. In this study, we attempted to elucidate characteristics of the mucinous epithelium in each subtype. The expression of claudin-18, a marker of gastric differentiation, MUCs, CDX2, CK7, CK20, oestrogen receptor (ER), progesterone receptor (PgR), CA-125 and vimentin in IMBTs (n = 54), EMBTs (n = 25) and serous borderline tumours (SBTs) (n = 22) were compared by immunohistochemistry. Claudin-18 positivity was identified in 98% of the IMBTs, whereas only 4% of the EMBTs were claudin-18-positive. Expression of intestinal markers such as CDX2 and MUC2 was relatively infrequent in IMBTs (48% and 33%, respectively). Müllerian-lineage markers such as ER, PgR and vimentin were expressed rarely in IMBTs, while most EMBTs and SBTs were positive for these markers. Hierarchial clustering revealed a close association between EMBTs and SBTs, while IMBTs were clearly separate. Claudin-18 positivity is a specific phenotype that is characteristic of IMBTs. Frequent and diffuse expression of gastric markers, along with less frequent and usually focal expression of intestinal markers, suggests that IMBTs are essentially composed of gastrointestinal-type mucinous epithelium (gastric-type epithelium with a variable degree of intestinal differentiation). © 2013 John Wiley & Sons Ltd.

Maltitol inhibits small intestinal glucose absorption and increases insulin mediated muscle glucose uptake ex vivo but not in normal and type 2 diabetic rats.

PubMed

Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

2017-02-01

This study investigated the effects of maltitol on intestinal glucose absorption and muscle glucose uptake using ex vivo and in vivo experimental models. The ex vivo experiment was conducted in isolated jejunum and psoas muscle from normal rats. The in vivo study investigated the effects of a single bolus dose of maltitol on gastric emptying, intestinal glucose absorption and digesta transit in normal and type 2 diabetic rats. Maltitol inhibited glucose absorption in isolated rat jejunum and increased glucose uptake in isolated rat psoas muscle in the presence of insulin but not in the absence of insulin. In contrast, maltitol did not significantly (p > 0.05) alter small intestinal glucose absorption or blood glucose levels as well as gastric emptying and digesta transit in normal or type 2 diabetic rats. The results suggest that maltitol may not be a suitable dietary supplement for anti-diabetic food and food products to improve glycemic control.

In Vivo Myeloperoxidase Imaging and Flow Cytometry Analysis of Intestinal Myeloid Cells.

PubMed

Hülsdünker, Jan; Zeiser, Robert

2016-01-01

Myeloperoxidase (MPO) imaging is a non-invasive method to detect cells that produce the enzyme MPO that is most abundant in neutrophils, macrophages, and inflammatory monocytes. While lacking specificity for any of these three cell types, MPO imaging can provide guidance for further flow cytometry-based analysis of tissues where these cell types reside. Isolation of leukocytes from the intestinal tract is an error-prone procedure. Here, we describe a protocol for intestinal leukocyte isolation that works reliable in our hands and allows for flow cytometry-based analysis, in particular of neutrophils.

Transporters for the Intestinal Absorption of Cholesterol, Vitamin E, and Vitamin K

PubMed Central

Yamanashi, Yoshihide; Kurauchi, Ryoya; Tanaka, Yusuke; Komine, Toko; Suzuki, Hiroshi

2017-01-01

Humans cannot synthesize fat-soluble vitamins such as vitamin E and vitamin K. For this reason, they must be obtained from the diet via intestinal absorption. As the deficiency or excess of these vitamins has been reported to cause several types of diseases and disorders in humans, the intestinal absorption of these nutrients must be properly regulated to ensure good health. However, the mechanism of their intestinal absorption remains poorly understood. Recent studies on cholesterol using genome-edited mice, genome-wide association approaches, gene mutation analyses, and the development of cholesterol absorption inhibitors have revealed that several membrane proteins play crucial roles in the intestinal absorption of cholesterol. Surprisingly, detailed analyses of these cholesterol transporters have revealed that they can also transport vitamin E and vitamin K, providing clues to uncover the molecular mechanisms underlying the intestinal absorption of these fat-soluble vitamins. In this review, we focus on the membrane proteins (Niemann-Pick C1 like 1, scavenger receptor class B type I, cluster of differentiation 36, and ATP-binding cassette transporter A1) that are (potentially) involved in the intestinal absorption of cholesterol, vitamin E, and vitamin K and discuss their physiological and pharmacological importance. We also discuss the related uncertainties that need to be explored in future studies. PMID:28100881

Transporters for the Intestinal Absorption of Cholesterol, Vitamin E, and Vitamin K.

PubMed

Yamanashi, Yoshihide; Takada, Tappei; Kurauchi, Ryoya; Tanaka, Yusuke; Komine, Toko; Suzuki, Hiroshi

2017-04-03

Humans cannot synthesize fat-soluble vitamins such as vitamin E and vitamin K. For this reason, they must be obtained from the diet via intestinal absorption. As the deficiency or excess of these vitamins has been reported to cause several types of diseases and disorders in humans, the intestinal absorption of these nutrients must be properly regulated to ensure good health. However, the mechanism of their intestinal absorption remains poorly understood. Recent studies on cholesterol using genome-edited mice, genome-wide association approaches, gene mutation analyses, and the development of cholesterol absorption inhibitors have revealed that several membrane proteins play crucial roles in the intestinal absorption of cholesterol. Surprisingly, detailed analyses of these cholesterol transporters have revealed that they can also transport vitamin E and vitamin K, providing clues to uncover the molecular mechanisms underlying the intestinal absorption of these fat-soluble vitamins. In this review, we focus on the membrane proteins (Niemann-Pick C1 like 1, scavenger receptor class B type I, cluster of differentiation 36, and ATP-binding cassette transporter A1) that are (potentially) involved in the intestinal absorption of cholesterol, vitamin E, and vitamin K and discuss their physiological and pharmacological importance. We also discuss the related uncertainties that need to be explored in future studies.

Haemocytes control stem cell activity in the Drosophila intestine.

PubMed

Ayyaz, Arshad; Li, Hongjie; Jasper, Heinrich

2015-06-01

Coordination of stem cell activity with inflammatory responses is critical for regeneration and homeostasis of barrier epithelia. The temporal sequence of cell interactions during injury-induced regeneration is only beginning to be understood. Here we show that intestinal stem cells (ISCs) are regulated by macrophage-like haemocytes during the early phase of regenerative responses of the Drosophila intestinal epithelium. On tissue damage, haemocytes are recruited to the intestine and secrete the BMP homologue DPP, inducing ISC proliferation by activating the type I receptor Saxophone and the Smad homologue SMOX. Activated ISCs then switch their response to DPP by inducing expression of Thickveins, a second type I receptor that has previously been shown to re-establish ISC quiescence by activating MAD. The interaction between haemocytes and ISCs promotes infection resistance, but also contributes to the development of intestinal dysplasia in ageing flies. We propose that similar interactions influence pathologies such as inflammatory bowel disease and colorectal cancer in humans.

Hemocytes control stem cell activity in the Drosophila intestine

PubMed Central

Ayyaz, Arshad; Li, Hongjie; Jasper, Heinrich

2015-01-01

SUMMARY Coordination of stem cell activity with inflammatory responses is critical for regeneration and homeostasis of barrier epithelia. The temporal sequence of cell interactions during injury-induced regeneration is only beginning to be understood. Here we show that intestinal stem cells (ISCs) are regulated by macrophage-like hemocytes during the early phase of regenerative responses of the Drosophila intestinal epithelium. Upon tissue damage, hemocytes are recruited to the intestine and secrete the TGFβ/BMP homologue Dpp, inducing ISC proliferation by activating the Type I receptor Saxophone and the Smad homologue Smox. Activated ISCs then switch their response to Dpp by inducing expression of Thickveins, a second Type I receptor that has previously been shown to re-establish ISC quiescence by activating Mad. The interaction between hemocytes and ISCs promotes infection resistance, but also contributes to the development of intestinal dysplasia in aging flies. We propose that similar interactions influence pathologies like inflammatory bowel disease and colorectal cancer in humans. PMID:26005834

Intestinal microbiota and type 2 diabetes: from mechanism insights to therapeutic perspective.

PubMed

Han, Jun-Ling; Lin, Hui-Ling

2014-12-21

The incidence of type 2 diabetes (T2DM) is rapidly increasing worldwide. However, the pathogenesis of T2DM has not yet been well explained. Recent evidence suggests that the intestinal microbiota composition is associated with obesity and T2DM. In this review, we provide an overview about the mechanisms underlying the role of intestinal microbiota in the pathogenesis of T2DM. There is clear evidence that the intestinal microbiota influences the host through its effect on body weight, bile acid metabolism, proinflammatory activity and insulin resistance, and modulation of gut hormones. Modulating gut microbiota with the use of probiotics, prebiotics, antibiotics, and fecal microbiota transplantation may have benefits for improvement in glucose metabolism and insulin resistance in the host. Further studies are required to increase our understanding of the complex interplay between intestinal microbiota and the host with T2DM. Further studies may be able to boost the development of new effective therapeutic approaches for T2DM.

Regulatory immune cells in regulation of intestinal inflammatory response to microbiota

PubMed Central

Cong, Y; Liu, Z

2015-01-01

The intestinal lumen harbors nearly 100 trillion commensal bacteria that exert crucial function for health. An elaborate balance between immune responses and tolerance to intestinal microbiota is required to maintain intestinal homeostasis. This process depends on diverse regulatory mechanisms, including both innate and adaptive immunity. Dysregulation of the homeostasis between intestinal immune systems and microbiota has been shown to be associated with the development of inflammatory bowel diseases (IBD) in genetically susceptible populations. In this review, we discuss the recent progress reported in studies of distinct types of regulatory immune cells in the gut, including intestinal intraepithelial lymphocytes, Foxp3+ regulatory T cells, regulatory B cells, alternatively activated macrophages, dendritic cells, and innate lymphoid cells, and how dysfunction of this immune regulatory system contributes to intestinal diseases such as IBD. Moreover, we discuss the manipulation of these regulatory immune cells as a potential therapeutic method for management of intestinal inflammatory disorders. PMID:26080708

Regulatory immune cells in regulation of intestinal inflammatory response to microbiota.

PubMed

Sun, M; He, C; Cong, Y; Liu, Z

2015-09-01

The intestinal lumen harbors nearly 100 trillion commensal bacteria that exert crucial function for health. An elaborate balance between immune responses and tolerance to intestinal microbiota is required to maintain intestinal homeostasis. This process depends on diverse regulatory mechanisms, including both innate and adaptive immunity. Dysregulation of the homeostasis between intestinal immune systems and microbiota has been shown to be associated with the development of inflammatory bowel diseases (IBD) in genetically susceptible populations. In this review, we discuss the recent progress reported in studies of distinct types of regulatory immune cells in the gut, including intestinal intraepithelial lymphocytes, Foxp3(+) regulatory T cells, regulatory B cells, alternatively activated macrophages, dendritic cells, and innate lymphoid cells, and how dysfunction of this immune regulatory system contributes to intestinal diseases such as IBD. Moreover, we discuss the manipulation of these regulatory immune cells as a potential therapeutic method for management of intestinal inflammatory disorders.

Mannose-specific interaction of Lactobacillus plantarum with porcine jejunal epithelium.

PubMed

Gross, Gabriele; van der Meulen, Jan; Snel, Johannes; van der Meer, Roelof; Kleerebezem, Michiel; Niewold, Theo A; Hulst, Marcel M; Smits, Mari A

2008-11-01

Host-microorganism interactions in the intestinal tract are complex, and little is known about specific nonpathogenic microbial factors triggering host responses in the gut. In this study, mannose-specific interactions of Lactobacillus plantarum 299v with jejunal epithelium were investigated using an in situ pig Small Intestinal Segment Perfusion model. The effects of L. plantarum 299v wild-type strain were compared with those of two corresponding mutant strains either lacking the gene encoding for the mannose-specific adhesin (msa) or sortase (srtA; responsible for anchoring of cell surface proteins like Msa to the cell wall). A slight enrichment of the wild-type strain associated with the intestinal surface could be observed after 8 h of perfusion when a mixture of wild-type and msa-mutant strain had been applied. In contrast to the mutant strains, the L. plantarum wild-type strain tended to induce a decrease in jejunal net fluid absorption compared with control conditions. Furthermore, after 8 h of perfusion expression of the host gene encoding pancreatitis-associated protein, a protein with proposed bactericidal properties, was found to be upregulated by the wild-type strain only. These observations suggest a role of Msa in the induction of host responses in the pig intestine.

Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

PubMed

Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

2015-03-01

The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats.

[Epidemiological situation of human parasitic diseases through three investigations in Jinhu County, Jiangsu Province].

PubMed

Shu-Mei, Li; Dao-Kuan, Sun; Cui-Ping, Zhang; De-Zhen, Chen; Qian, Li

2016-03-08

To understand the epidemiological situation of human parasitic diseases in Jinhu County, so as to provide the evidence for formulating further control strategy. The investigated local residents were sampled by the random cluster sampling method in 1989, 1999 and 2015. The infections of intestinal helminthes were detected by Kato-Katz technique, the eggs of Enterubius vermicularis were examined by cellophane anal swab for children, the intestinal protozoa were examined by the saline smear and iodine staining methods. The total rates of parasitic infections were 62.57%, 9.32% and 0.49% in 1989, 1999 and 2015, respectively. Compared to those in 1989 and in 1999, the infection rate in 2015 was decreased by 99.22% and 94.74%, respectively. The numbers of detected parasite species were 14, 10 and 4 in 1989, 1999 and 2015, respectively. The intensities of infections were mainly mild in three investigations, and the intensities of all the infections in 2015 were mild. The species of infected parasites were mainly single, however, multiple infections were observed in 1989, including 4 parasite species (0.72%) and 3 parasite species (7.02%). Only in 1989, the difference between sexes was significant and the infection rate of the female was higher than that of the male ( χ 2 ＝18.01, P ＜0.01). The infection rates of human parasites are decreased gradually and stabilized at the low level in Jinhu County. However, the surveillance work still should be strengthened to consolidate the achievement.

Immunosuppressive therapies after intestinal transplant modulate the expression of Th1 signature genes during acute cellular rejection. Implications in the search for rejection biomarkers.

PubMed

Zambernardi, Agustina; Chiodetti, Ana; Meier, Dominik; Cabanne, Ana; Nachman, Fabio; Solar, Héctor; Rumbo, Carolina; Gondolesi, Gabriel E; Rumbo, Martin

2014-12-01

Acute cellular rejection (ACR) and infections are leading causes of graft loss and death in intestinal transplant patients. Our aim was to evaluate the impact of maintenance immunosuppressive therapies on the expression of pro-inflammatory mediators in small bowel at ACR diagnosis. We analyzed expression levels of Th1-associated genes, IFNG, CXCL10, and CXCL11 by qPCR in 46 selected graft biopsies unequivocally assigned to mild ACR (n = 14) or normal histopathology and clinical condition (n = 32) from 15 patients receiving two different immunosuppressive (IS) schemes. Double treatment: corticosteroids and tacrolimus (n = 17) and triple treatment: sirolimus or mycophenolate mofetil in addition to the basal therapy (n = 29). IFNG, CXCL10, and CXCL11 were induced during rejection (p < 0.05; p < 0.005, and p < 0.05, respectively). However, when rejection and control groups were classified according to immunosuppressive treatment, in the rejection group, significant differences of IFNG, CXCL10, and CXCL11 expression (p < 0.001; p < 0.005, and 0.01, respectively) were detected, whereas no differences were observed in the control group. Gene expression of Th1 response mediators is higher during ACR. Triple IS group showed significantly lower expression of pro-inflammatory Th1 mediators during mild ACR indicating that use of these markers to monitor rejection can be affected by the IS treatment used. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Expression pattern of peptide and amino acid genes in digestive tract of transporter juvenile turbot ( Scophthalmus maximus L.)

NASA Astrophysics Data System (ADS)

Xu, Dandan; He, Gen; Mai, Kangsen; Zhou, Huihui; Xu, Wei; Song, Fei

2016-04-01

Turbot ( Scophthalmus maximus L.), a carnivorous fish species with high dietary protein requirement, was chosen to examine the expression pattern of peptide and amino acid transporter genes along its digestive tract which was divided into six segments including stomach, pyloric caeca, rectum, and three equal parts of the remainder of the intestine. The results showed that the expression of two peptide and eleven amino acid transporters genes exhibited distinct patterns. Peptide transporter 1 (PepT1) was rich in proximal intestine while peptide transporter 2 (PepT2) was abundant in distal intestine. A number of neutral and cationic amino acid transporters expressed richly in whole intestine including B0-type amino acid transporter 1 (B0AT1), L-type amino acid transporter 2 (LAT2), T-type amino acid transporter 1 (TAT1), proton-coupled amino acid transporter 1 (PAT1), y+L-type amino acid transporter 1 (y+LAT1), and cationic amino acid transporter 2 (CAT2) while ASC amino acid transporter 2 (ASCT2), sodium-coupled neutral amino acid transporter 2 (SNAT2), and y+L-type amino acid transporter 2 (y+LAT2) abundantly expressed in stomach. In addition, system b0,+ transporters (rBAT and b0,+AT) existed richly in distal intestine. These findings comprehensively characterized the distribution of solute carrier family proteins, which revealed the relative importance of peptide and amino acid absorption through luminal membrane. Our findings are helpful to understand the mechanism of the utilization of dietary protein in fish with a short digestive tract.

Evaluation of intestinal absorption of amtolmetin guacyl in rats: breast cancer resistant protein as a primary barrier of oral bioavailability.

PubMed

Rong, Zhihui; Xu, Yanjiao; Zhang, Chengliang; Xiang, Daochun; Li, Xiping; Liu, Dong

2013-02-27

The purpose of the present study was to investigate the role of efflux transporters on the intestinal absorption of amtolmetin guacyl (MED-15). The effects of P-glycoprotein (P-gp), multiple resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on intestinal absorption amount of MED-5 (tolmetin-glycine amide derivative), the metabolite formed from MED-15 in the intestinal epithelial cells were studied in the in vitro everted gut sac experiments. Moreover, the in situ single-pass intestine perfusion was adopted to clarify the role of efflux transporters in excreting MED-5 in knockout mice. The plasma concentration of MED-5 and tolmetin, the metabolite formed from MED-5 was determined in Bcrp1 knockout mice and wild-type mice. BCRP inhibitor Ko143 (50 μM and 100 μM) significantly increased the intestinal absorption amount in jejunum, ileum and colon (p<0.05). However, no effect was observed in the presence of P-gp inhibitor verapamil and MRP2 inhibitor MK571 in each intestinal segment. Furthermore, the plasma concentration MED-5 and tolmetin, metabolites of MED-15, increased 2-fold and 4-fold, respectively, in Bcrp1 knockout mice compared with wild-type mice after the single-pass perfusion of small intestine with MED-15. It may be concluded that BCRP plays an important role in the intestinal efflux of MED-5 and limits the bioavailability after oral administration of MED-15. Copyright © 2013. Published by Elsevier Inc.

[Stratified sampling survey of major human parasitic diseases in Henan province].

PubMed

Xu, B L; Zhang, H W; Deng, Y; Chen, Z L; Chen, W Q; Lu, D L; Zhang, Y L; Zhao, Y L; Lin, X M; Huang, Q; Yang, C Y; Liu, Y; Zhou, R M; Li, P; Chen, J S; He, L J; Qian, D

2018-03-10

Objective: To understand the prevalence of major human parasitic diseases and related factors in Henan province. Methods: This stratified sampling survey was carried out according to the requirement of national survey protocol of major human parasitic diseases, 2014-2015. The prevalence of soil-transmitted helminths infection, taeniasis and intestinal protozoiasis were surveyed in 104 sites selected from 35 counties (districts) and the prevalence of clonorchiasis was surveyed in 62 sites selected from 37 townships. In each survey spot, 250 persons were surveyed. A total of 26 866 persons and 15 893 persons were surveyed. Modified Kato-Katz thick smear was used to detect the eggs of intestinal helminthes. Tube fecal culture was used to identify the species of hookworm. The Enterobius eggs were detected in children aged 3 to 6 years by using adhesive tape. The cyst and trophozoite of intestinal protozoa were examined with physiological saline direct smear method and iodine stain method. Results: The overall infestation rate of intestinal parasites was2.02% in Henan, and the worm infection rate was higher than protozoa infection rate. Fourteen kinds of intestinal parasites were found, including nematode (5 species), trematode (2 species), and protozoan (7 species). The infection rate of Enterobius vermicularis was highest, and Qinba Mountain ecological area had the highest infestation rate of intestinal parasites in 4 ecological areas of Henan. There was no significant difference in intestinal parasite infection rate between males and females ( χ (2)=3.630, P =0.057), and the differences in intestinal parasite infection rate among different age groups had significance ( χ (2)=124.783, P =0.000 1). The infection rate reached the peak in age group ≤9 years and the major parasite was Enterobius vermicularis . Furthermore the overall human infection rate of parasite showed a downward trend with the increase of educational level of the people ( χ (2)=70.969, P =0.000 1), the differences had significance ( χ (2)=120.118, P =0.000 1). For different populations, the infection rate of intestinal parasites was highest among preschool children. The infection of intestinal helminth was mainly mild, only 2 severe cases were detected. The infection rate of Clonorchis sinensis in urban residents was only 0.006%. Logistic regression analysis showed that being preschool children ( χ (2)=15.765, P =0.000 1) and drinking well water ( χ (2)=45.589, P =0.000 1) were the risk factors for intestinal parasite infection, and annual income per capita of farmers was the protective factor against intestinal parasite infection. The infection rates of protozoa and intestinal parasites decreased sharply compared with the results of previous two surveys, and the rate of intestinal helminth infection also dropped sharply compared with the second survey. The numbers of protozoa, helminth and intestinal parasites detected in this survey were all less than the numbers found in the previous two surveys. Conclusions: Compared the results of three surveys in Henan, the infection rate of protozoa and intestinal parasites showed a downward trend. The prevention and treatment of Enterobius vermicularis infection in children should be the key point of parasitic disease control in the future.

Breast Milk Enhances Growth of Enteroids: An Ex Vivo Model of Cell Proliferation.

PubMed

Lanik, Wyatt E; Xu, Lily; Luke, Cliff J; Hu, Elise Z; Agrawal, Pranjal; Liu, Victoria S; Kumar, Rajesh; Bolock, Alexa M; Ma, Congrong; Good, Misty

2018-02-15

Human small intestinal enteroids are derived from the crypts and when grown in a stem cell niche contain all of the epithelial cell types. The ability to establish human enteroid ex vivo culture systems are important to model intestinal pathophysiology and to study the particular cellular responses involved. In recent years, enteroids from mice and humans are being cultured, passaged, and banked away for future use in several laboratories across the world. This enteroid platform can be used to test the effects of various treatments and drugs and what effects are exerted on different cell types in the intestine. Here, a protocol for establishing primary stem cell-derived small intestinal enteroids derived from neonatal mice and premature human intestine is provided. Moreover, this enteroid culture system was utilized to test the effects of species-specific breast milk. Mouse breast milk can be obtained efficiently using a modified human breast pump and expressed mouse milk can then be used for further research experiments. We now demonstrate the effects of expressed mouse, human, and donor breast milk on the growth and proliferation of enteroids derived from neonatal mice or premature human small intestine.

Clinicopathological characteristics and prognostic factors of primary gastrointestinal lymphoma: a 22-year experience from South China.

PubMed

Li, Minrui; Zhang, Shenghong; Gu, Fang; Xiao, Weiwei; Yao, Jiayan; Chao, Kang; Chen, Minhu; Li, Juan; Zhong, Bihui

2014-01-01

Primary gastrointestinal lymphoma (PGIL) is a kind of relatively rare cancer and easily misdiagnosed due to its unspecific signs in digestive tract. Data including 216 patients histologically diagnosed as PGIL between January 1991 and October 2012 from The First Affiliated Hospital of Sun Yat-sen University were reviewed. This study was to investigate the clinicopathological features and prognosis, and make the comparison between the different sites of PGIL. Abdominal pain (75.9%) was the most frequent symptom and intermediate-grade lymphoma (53.7%) presented as the most common histological type. Intestine (55.1%) was the most common site involved, followed by stomach (38.5%), both intestine and stomach (6.4%). PGIL of different original site showed distinguished clinicopathological characteristics that patients in Stomach and GI group were older than Intestine group (Mean age: 54 and 53 vs. 43 years, p<0.001); diarrhea, B symptom, abdominal mass and complication occurred more in intestine group. Histologically, high-grade lymphoma (especially T-cell type) almost located in Intestine group (82.5%). Five-year overall survival (OS) and event-free survival (EFS) for all PGIL patients were 56.4% and 49.3%, respectively. Stomach group had better OS (72.3%) and EFS (48.4%) than Intestine group (43.1% and 23.6% respectively), but it lost the significance in the multivariate analysis. Univariate and multivariate analysis revealed that performance status, lactate dehydrogenase (LDH) level and histological type were independent prognostic factors for PGIL.

The immunopathogenesis of celiac disease reveals possible therapies beyond the gluten-free diet.

PubMed

McAllister, Christopher S; Kagnoff, Martin F

2012-07-01

Celiac disease is a T cell-mediated autoimmune inflammatory disease of the small intestine that is activated by gluten. The diagnosis of celiac disease is challenging as patients display a wide range of symptoms and some are asymptomatic. A lifelong gluten-free diet is the only currently approved treatment of celiac disease. Although the diet is safe and effective, the compliance rates and patient acceptance vary. Furthermore, many patients treated with a gluten-free diet continue to be mildly to severely symptomatic with persistent histological abnormalities, and a small number of patients develop refractory celiac disease. New therapeutic adjuncts and potential alternatives to the gluten-free diet could improve the treatment options for these patients. Advances in understanding the immunopathogenesis of celiac disease have suggested several types of therapeutic strategies that may augment or supplant the gluten-free diet. Some of these strategies attempt to decrease the immunogenicity of gluten-containing grains by manipulating the grain itself or by using oral enzymes to break down immunogenic peptides that normally remain intact during digestion. Other strategies focus on preventing the absorption of these peptides, preventing tissue transglutaminase from rendering gluten peptides more immunogenic, or inhibiting their binding to celiac disease-specific antigen-presenting molecules. Strategies that limit T cell migration to the small intestine or that reestablish mucosal homeostasis and tolerance to gluten antigens are also being explored. Additionally, it is vital to develop new therapeutic options for refractory celiac disease patients. This review highlights therapeutic strategies that may ultimately improve the health and well-being of individuals with celiac disease.

Role of interleukin 10 in norfloxacin prevention of luminal free endotoxin translocation in mice with cirrhosis.

PubMed

Gómez-Hurtado, Isabel; Moratalla, Alba; Moya-Pérez, Ángela; Peiró, Gloria; Zapater, Pedro; González-Navajas, José M; Giménez, Paula; Such, José; Sanz, Yolanda; Francés, Rubén

2014-10-01

Bacterial endotoxin is present in patients with advanced cirrhosis and can induce an immunogenic response without an overt infection. Norfloxacin is a gram-negative bactericidal drug able to maintain low endotoxin levels and stimulate IL-10 production. We aimed at investigating the role of IL-10 in decreasing endotoxin absorption in cirrhotic mice treated with norfloxacin. Cirrhosis was induced by carbon tetrachloride or bile duct ligation in wild type and IL10-deficient mice with or without norfloxacin prior to an intragastrical administration of E. coli, K. pneumonia or E. faecalis. Spontaneous and induced bacterial translocation, free endotoxin and cytokine levels were evaluated in mesenteric lymph nodes. Intestinal permeability was followed by fluorimetry and barrier integrity markers were measured in disrupted intestinal samples. The inflammatory-modulating mechanism was characterized in purified intestinal mononuclear cells. Norfloxacin reduced spontaneous and induced MLN positive-cultures in wild type and IL-10-deficient animals. However, reduction of free endotoxin levels was associated with norfloxacin in wild type but not in IL-10-deficient mice. Wild type but not IL-10-deficient mice treated with norfloxacin significantly normalized intestinal permeability and improved gut barrier integrity markers. The toll-like receptor 4-mediated pro-inflammatory milieu was modulated by norfloxacin in a concentration-dependent manner in cultured intestinal mononuclear cells of wild type mice but not of IL-10-deficient mice. The restoration of IL-10 levels in IL-10-deficient animals reactivated the norfloxacin effect on inflammatory-modulation, gut barrier permeability, and luminal endotoxin absorption. Norfloxacin not only reduces gram-negative intestinal flora but also participates in an IL-10-driven modulation of gut barrier permeability, thus reducing luminal free endotoxin absorption in experimental cirrhosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Lactobacillus rhamnosus GG Intake Modifies Preschool Children's Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use.

PubMed

Korpela, Katri; Salonen, Anne; Virta, Lauri J; Kumpu, Minna; Kekkonen, Riina A; de Vos, Willem M

2016-01-01

Antibiotic use is considered among the most severe causes of disturbance to children's developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children's microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children's antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2-7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use. ClinicalTrials.gov NCT01014676.

Relationship Between Nutritional Status and Intensity of Common Intestinal Helminths Among Children in Enugu, South-East Nigeria

PubMed Central

Ilechukwu, GC; Ilechukwu, CGA; Ubesie, AC; Onyire, NB; Emechebe, G; Eze, JC

2014-01-01

Background: Intestinal helminthiasis is associated with malnutrition in children. Aim: The objective of this study was to determine the intensity and effect of the common intestinal helminths on the nutritional status of children in Enugu, Nigeria. Subjects and Methods: A cross-sectional study of 460 children conducted in Enugu metropolis, south-east Nigeria between August and September 2003. Their stools were analyzed at the research laboratory of the Federal Ministry of Health, National Arbovirus and Vector Research Center, Enugu. The intensity of the common intestinal helminths was determined using the standard Kato-Katz method of fresh stool samples. The classification intensity of helminthic infestation was according to the World Health Organization classification. Data were analyzed using Statistical Software for Social Sciences version 11.0 (Chicago IL, USA). P < 0.05 was regarded as statistically significant. Results: 452 of 460 children (98.3%) had normal height for age, weight for age and weight for height Z-scores. Six of the 460 children (1.3% were wasted), 1/460 stunted (0.2%) and 1/460 wasted and stunted (0.2%). 150 out of 460 (32.6%) studied were infected with helminths. There was no significant relationship between the intensity of helminth infection and the nutritional status of the children. Conclusion: Although the prevalence of helminthiasis in children in Enugu was high, intensity of helminthiasis in these children was mainly mild. Hence, majority of them had normal weight and height measurements for age and sex. PMID:25184077

Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water.

PubMed

Cullen, John M; Ward, Jerrold M; Thompson, Chad M

2016-02-01

Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response. © The Author(s) 2015.

Intestinal Fatty Acid Binding Protein and Citrulline as Markers of Gut Injury and Prognosis in Patients With Acute Pancreatitis.

PubMed

Goswami, Pooja; Sonika, Ujjwal; Moka, Praneeth; Sreenivas, Vishnubhatla; Saraya, Anoop

Severe acute pancreatitis (AP) is associated with high mortality due to systemic inflammatory response syndrome in the early phase and secondary infection in the later phase. Concomitant intestinal ischemia often results in gut injury. We studied intestinal fatty acid binding protein (IFABP) and citrulline levels as markers of gut injury to predict prognosis in AP. Acute pancreatitis patients at admission and controls were studied. Serum IFABP was measured by enzyme-linked immunosorbent assay and plasma citrulline by high-performance liquid chromatography technique. Ultrastructural changes in duodenal biopsy were also compared between the 2 groups. The IFABP concentration was significantly higher in AP cases (n = 94) compared with controls (n = 100) (mean [standard deviation], 592.5 [753.6] vs 87.8 [67.6] pg/mL; P < 0.001) and in patients with severe AP versus mild AP (738.3 [955.3] vs 404.0 [263.3] pg/ mL, P = 0.03). Citrulline concentration was lower in AP versus controls (29.9 [33.8] vs 83.9 [60.1] μg/L, P < 0.001). We propose a model by which these biomarkers (IFABP >350 pg/mL and citrulline <18 μg/L) are able to predict poor prognosis in 33.9% of patients with AP. The gut injury was also validated via ultrastructural changes. Intestinal fatty acid binding protein is a promising prognostic marker in acute pancreatitis.

Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water

PubMed Central

Cullen, John M.; Ward, Jerrold M.

2015-01-01

Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response. PMID:26538584

Lactobacillus rhamnosus GG Intake Modifies Preschool Children’s Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use

PubMed Central

Korpela, Katri; Salonen, Anne; Virta, Lauri J.; Kumpu, Minna; Kekkonen, Riina A.; de Vos, Willem M.

2016-01-01

Antibiotic use is considered among the most severe causes of disturbance to children’s developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children’s microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children’s antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2–7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use. Trial Registration: ClinicalTrials.gov NCT01014676 PMID:27111772

Interleukin-1 gene polymorphisms in chronic gastritis patients infected with Helicobacter pylori as risk factors of gastric cancer development.

PubMed

Hnatyszyn, Andrzej; Wielgus, Karolina; Kaczmarek-Rys, Marta; Skrzypczak-Zielinska, Marzena; Szalata, Marlena; Mikolajczyk-Stecyna, Joanna; Stanczyk, Jerzy; Dziuba, Ireneusz; Mikstacki, Adam; Slomski, Ryszard

2013-12-01

Epidemiological investigations indicated association of the Helicobacter pylori infections with the occurrence of inflammatory conditions of the gastric mucosa and development of chronic gastritis and intestinal type of gastric cancer. IL1A and IL1B genes have been proposed as key factors in determining risk of gastritis and malignant transformation. The aim of this paper was to evaluate association of interleukin-1 gene polymorphisms with chronic gastritis, atrophy, intestinal metaplasia, dysplasia and intestinal type of gastric cancer in H. pylori-infected patients. Patients subjected to analysis represent group of 144 consecutive cases that suffered from dyspepsia with coexisting infection of H. pylori and chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer. Molecular studies involved analysis of -889C>T polymorphism of IL1A gene and +3954C>T polymorphism of IL1B gene. Statistical analysis of association of polymorphism -889C>T of gene IL1A with changes in gastric mucosa showed lack of significance, whereas +3954C>T polymorphism of IL1B gene showed significant association. Frequency of allele T of +3954C>T polymorphism of IL1B gene was higher in group of patients with chronic gastritis, atrophy, intestinal metaplasia, dysplasia or intestinal type of gastric cancer (32.1 %) as compared with population group (23 %), χ(2) = 4.61 and p = 0.03. This corresponds to odds ratio: 1.58, 95 % CI: 1.04-2.4. Our results indicate that +3954C>T polymorphism of IL1B gene increase susceptibility to inflammatory response of gastric mucosa H. pylori-infected patients and plays a significant role in the development of chronic gastritis, atrophy, intestinal metaplasia, dysplasia and the initiation of carcinogenesis.

Association of Beta2-Positive Clostridium perfringens Type A With Focal Duodenal Necrosis in Egg-Laying Chickens in the United States.

PubMed

França, M; Barrios, M A; Stabler, L; Zavala, Guillermo; Shivaprasad, H L; Lee, M D; Villegas, A M; Uzal, Francisco A

2016-03-01

Focal duodenal necrosis (FDN) is a poorly understood intestinal disease of egg layers, and has been associated with drops in egg production and decreased egg weights. The etiology of this disease is still unknown, but the condition has been associated with Clostridium colinum and Clostridium perfringens. In order to investigate the etiology, duodenal samples were taken from hens with FDN. The hens originated from table egg layer farms in three states. The samples were examined by histopathology, bacteriology, and immunohistochemistry. Macroscopically, all samples contained focal to multifocal, variably sized, reddened or brownish gray areas of mucosal erosion. Histopathology revealed mild to severe heterophilic and lymphoplasmacytic enteritis with loss of enterocytes at the villous tips, luminal fibrinonecrotic exudate, and variable numbers of Gram-positive and Gram-negative rod-shaped bacteria within the lesions in 16/30 samples. Clostridium perfringens was isolated by anaerobic bacteriology from 4/13 samples that had characteristic microscopic lesions of FDN. Polymerase chain reaction (PCR) revealed that all four isolates were Type A C. perfringens, positive for beta2 gene and negative for necrotic enteritis toxin B and enterotoxin genes. PCR for Clostridium colinum applied to DNA extracted from frozen intestinal samples yielded negative results in 14/14 duodenal samples. Immunohistochemistry (IHC) for 7C. perfringens, alpha and beta2 toxins stained a few to numerous long rod-shaped bacteria present in the lesions. IHC for alpha and beta2 toxins also stained enterocytes at the villous tips, inflammatory cells in the lamina propria, as well as degenerated and sloughed enterocytes present within the luminal exudate. These findings suggest that C. perfringens may play a role in the development of FDN. Experimental challenge studies with these isolates still need to be performed in order to reproduce the disease and fulfill Koch's postulates.

Dysplastic intestinal-type metaplasia of appendiceal endometriosis: a mimic of low grade appendiceal mucinous neoplasm

PubMed Central

2014-01-01

We report an example of dysplastic intestinal-type metaplasia involving endometriosis of the appendix in a 45 year old woman. One other example of this phenomenon has been reported. As it occurs within the muscular wall of the appendix, confusion with low grade appendiceal mucinous neoplasm (LAMN) may occur. Evidence supporting the metaplastic nature of the intestinal epithelium is offered. As the initial pathological diagnosis was of invasive cancer with perforation of the appendix treatment consisted of peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC). Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1068246472111756. PMID:24559059

New technique for correcting mild types of cryptotia: elevate cavum conchae cartilage and suture to cranial periosteum.

PubMed

Shen, Weimin; Cui, Jie; Chen, Jianbin; Chen, Haini; Zou, Jijun; Ji, Yi

2012-11-01

We have developed a new technique for the treatment of mild types of cryptotia in which the cavum conchae cartilage was pulled superiorly and sutured it to the temporal bone to the temporal parietal junction periosteum securely. Then, the stitches for bolster fixation were inserted parallel to the auricular temporal sulcus and temporarily left untied. Our technique is easy to use and secures a firm bolster fixation, and the scar is hidden. We recommend it for the treatment of mild types of cryptotia.

Eosinophils may play regionally disparate roles in influencing IgA(+) plasma cell numbers during large and small intestinal inflammation.

PubMed

Forman, Ruth; Bramhall, Michael; Logunova, Larisa; Svensson-Frej, Marcus; Cruickshank, Sheena M; Else, Kathryn J

2016-05-31

Eosinophils are innate immune cells present in the intestine during steady state conditions. An intestinal eosinophilia is a hallmark of many infections and an accumulation of eosinophils is also observed in the intestine during inflammatory disorders. Classically the function of eosinophils has been associated with tissue destruction, due to the release of cytotoxic granule contents. However, recent evidence has demonstrated that the eosinophil plays a more diverse role in the immune system than previously acknowledged, including shaping adaptive immune responses and providing plasma cell survival factors during the steady state. Importantly, it is known that there are regional differences in the underlying immunology of the small and large intestine, but whether there are differences in context of the intestinal eosinophil in the steady state or inflammation is not known. Our data demonstrates that there are fewer IgA(+) plasma cells in the small intestine of eosinophil-deficient ΔdblGATA-1 mice compared to eosinophil-sufficient wild-type mice, with the difference becoming significant post-infection with Toxoplasma gondii. Remarkably, and in complete contrast, the absence of eosinophils in the inflamed large intestine does not impact on IgA(+) cell numbers during steady state, and is associated with a significant increase in IgA(+) cells post-infection with Trichuris muris compared to wild-type mice. Thus, the intestinal eosinophil appears to be less important in sustaining the IgA(+) cell pool in the large intestine compared to the small intestine, and in fact, our data suggests eosinophils play an inhibitory role. The dichotomy in the influence of the eosinophil over small and large intestinal IgA(+) cells did not depend on differences in plasma cell growth factors, recruitment potential or proliferation within the different regions of the gastrointestinal tract (GIT). We demonstrate for the first time that there are regional differences in the requirement of eosinophils for maintaining IgA+ cells between the large and small intestine, which are more pronounced during inflammation. This is an important step towards further delineation of the enigmatic functions of gut-resident eosinophils.

Goblet Cells and Mucus Types in the Digestive Intestine and Respiratory Intestine in Bronze Corydoras (Callichthyidae: Teleostei).

PubMed

Leknes, I L

2015-10-01

The structure and histochemical properties of the intestine in bronze corydoras (Corydoras aeneus), a stomach-containing teleost, are described, with emphasis on goblet cells and mucin types. The proximal intestine displayed a normal structure for teleosts, whereas the distal intestine was wide, translucent, thin-walled, richly vascularized and constantly filled with air, suggesting an important respiratory role. Goblet cells were common throughout the entire intestine and displayed a variable, but mainly faint metachromatic colour after toluidine blue. They were moderately coloured by alcian blue at both pH 2.5 and 0.2 and displayed no colour after periodic acid followed by Schiff's solution (PAS), but a distinct purple-brown colour after high iron diamine followed by alcian blue (pH 2.5). Together, these results suggest that the mucin in the intestine goblet cells consists mainly of sulphated proteoglycans. Further, the results from the present lectin and neuraminidase tests suggest that these mucins contain much N-acetylglucoseamines and some N-acetylgalactosamines and sialic acid, but seem to lack glucose and mannose. They also contain some galactose-N-acetylgalactosamines sequences, normally hidden by sialic acid. The distinct brush border and mucus layer on the epithelial cells in the respiratory intestine may indicate some digestive roles, such as absorption of water, ions and simple carbohydrates. As sulphated proteoglycans are tough and attract much water, this mucus may play important roles in the protection against mechanical and chemical damages and in the defence against micro-organisms throughout the entire intestine, but in the respiratory intestine it may impede significantly the oxygen uptake. However, as this part of the intestine usually contains no digesta, but is completely filled with air, frequently renewed by dry air from the atmosphere, and the main function of the mucus may be to protect the respiratory epithelium against a destroying and dangerous desiccation. © 2014 Blackwell Verlag GmbH.

Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats.

PubMed

Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

2016-01-01

Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and L-NAME. BPC 157 completely ameliorated symptoms in massive intestinal resection-, massive intestinal resection plus diclofenac-, and massive intestinal resection plus diclofenac plus L-NAME-treated short bowel rats that presented with cyclooxygenase (COX)-NO-system inhibition. L-arginine ameliorated only L-NAME-induced aggravation of symptoms in rats subjected to massive intestinal resection and administered diclofenac plus L-NAME.

Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats

PubMed Central

Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

2016-01-01

Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and L-NAME. BPC 157 completely ameliorated symptoms in massive intestinal resection-, massive intestinal resection plus diclofenac-, and massive intestinal resection plus diclofenac plus L-NAME-treated short bowel rats that presented with cyclooxygenase (COX)-NO-system inhibition. L-arginine ameliorated only L-NAME-induced aggravation of symptoms in rats subjected to massive intestinal resection and administered diclofenac plus L-NAME. PMID:27627764

Possible involvement of the transient receptor potential vanilloid type 1 channel in postoperative adhesive obstruction and its prevention by a kampo (traditional Japanese) medicine, daikenchuto.

PubMed

Tokita, Yohei; Yamamoto, Masahiro; Satoh, Kazuko; Nishiyama, Mitsue; Iizuka, Seiichi; Imamura, Sachiko; Kase, Yoshio

2011-01-01

This study focused on the localization of transient receptor potential vanilloid type 1 (TRPV1) in the intestines in postoperative adhesion model rats and investigated the underlying mechanism for the anti-adhesion action of daikenchuto (DKT), especially in relation to TRPV1. Postoperative intestinal adhesion was induced by sprinkling talc in the small intestine. The expression of TRPV1 mRNA was examined by in situ hybridization and real-time RT-PCR. The effects of DKT and its major ingredient, hydroxy sanshool, with or without ruthenium red, a TRP-channel antagonist, on talc-induced intestinal adhesions were evaluated. The level of TRPV1 mRNA was higher in the adhesion regions of talc-treated rats than in normal small intestine of sham-operated rats. Localization of TRPV1 mRNA expression was identified in the submucosal plexus of both sham-operated and talc-treated rats; and in talc-treated rats, it was observed also in the myenteric plexus and regions of adhesion. Capsaicin, DKT, and hydroxy sanshool significantly prevented formation of intestinal adhesions. The effects of DKT and hydroxy sanshool were abrogated by subcutaneous injection of ruthenium red. These results suggest that pharmacological modulation of TRPV1 might be a possible therapeutic option in postoperative intestinal adhesion, which might be relevant to the prevention of postoperative adhesive obstruction by DKT.

Molecular Diagnostics in the Neoplasms of Small Intestine and Appendix: 2018 Update.

PubMed

Zhang, Yingtao; Zulfiqar, Muhammad; Bluth, Martin H; Bhalla, Amarpreet; Beydoun, Rafic

2018-06-01

Neoplasms of the small intestine are rare in comparison with colorectal tumors. The most common tumor types arising in the small intestine are adenocarcinomas, well-differentiated neuroendocrine tumors, gastrointestinal stromal tumors, and lymphoma. Primary appendiceal neoplasms are rare and found in less than 2% of appendectomy specimens with an incidence of approximately 1.2 cases per 100,000 people per year in the United States. This article explores molecular diagnostics in the neoplasms of small intestine and appendix. Copyright © 2018 Elsevier Inc. All rights reserved.

[ON THE ORIGIN OF HYPERVIRULENCE OF THE CAUSATIVE AGENT OF PLAGUE].

PubMed

Anisimov, N V; Kislichkina, A A; Platonov, M E; Evseeva, V V; Kadnikova, L A; Lipatnikova, N A; Bogun, A G; Dentovskaya, S V; Anisimov, A P

2016-01-01

The attempt to combine Yersinia pseudotuberculosis and Yersinia pestis into one species has been unsupported by microbiologists due to the specific features of the epidemiology and clinical presentations of their induced diseases and to basic differences in their virulence. Pseudotuberculosis is predominantly a relatively mild human intestinal infection transmitted through contaminated food and plague is an acute generalized disease with high mortality, which is most frequently transmitted by the bites of infected fleas. Y. pestis hypervirulence, the ability of single bacteria to ensure the development of predagonal bacteriemia in rodents, which is sufficient to contaminate the fleas, is one of the main events during pathogen adaptation to a new ecological niche. By analyzing the data of molecular typing of the representative kits of naturally occurring Y. pestis isolates, the authois consider the issues of formation of intraspecies groups with universal hypervirulence, as well as biovars that are highly virulent only to their major host. A strategy for searching for selective virulence factors, the potential molecular targets for vaccination and etiotropic treatment of plague, is discussed.

Low Rectal Cancer Study (MERCURY II)

ClinicalTrials.gov

2016-03-11

Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

The role of intestinal microbiota in the pathogenesis of metabolic diseases.

PubMed

Węgielska, Iwona; Suliburska, Joanna

2016-01-01

The incidence of metabolic diseases is increasing rapidly all over the world. This situation has led researchers to attempt to explain the pathomechanisms of these disorders and to develop specific recommendations for the prevention and treatment of diseases such as obesity, type-2 diabetes, and atherosclerosis. Recent studies show clear evidence of the role of human intestinal microbiota in health and in predispositions to diseases. Gut microbiota affect a number of complex metabolic reactions, significantly altering the functioning of the human body. Numerous experiments have shown the key role played by the formation process of the intestinal ecosystem in the early stages of human life for programming its metabolic health. The following article is a compilation of the literature available on the formation of the complex intestinal ecosystem and its impact on the incidence of diseases such as obesity, type-2 diabetes, and atherosclerosis.

Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

PubMed

Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

2016-02-01

Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk. Copyright © 2016 Chenery et al.

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells.

PubMed

Sessa, F; Bonato, M; Frigerio, B; Capella, C; Solcia, E; Prat, M; Bara, J; Samloff, I M

1990-06-01

It has been found by immunohistochemical staining that antigens normally found in gastric and/or intestinal epithelial cells are expressed in most differentiated duct cell carcinomas of the pancreas. Among 88 such tumors, 93% and 92%, respectively, expressed M1 and cathepsin E, markers of gastric surface-foveolar epithelial cells, 51% expressed pepsinogen II, a marker of gastroduodenal mucopeptic cells, 48% expressed CAR-5, a marker of colorectal epithelial cells, and 35% expressed M3SI, a marker of small intestinal goblet cells. Most of the tumors also expressed normal pancreatic duct antigens; 97% expressed DU-PAN-2, and 59% expressed N-terminus gastrin-releasing peptide. In agreement with these findings, electron microscopy revealed malignant cells with fine structural features of gastric foveolar cells, gastric mucopeptic cells, intestinal goblet cells, intestinal columnar cells, pancreatic duct epithelial cells, and cells with features of more than one cell type. Normal pancreatic duct epithelium did not express any marker of gastrointestinal epithelial cells, whereas such benign lesions as mucinous cell hypertrophy and papillary hyperplasia commonly expressed gut-type antigens but rarely expressed pancreatic duct cell markers. By contrast, lesions characterized by atypical papillary hyperplasia commonly expressed both gastric and pancreatic duct cell markers. Metaplastic pyloric-type glands expressed pepsinogen II and, except for their expression of cathepsin E, were indistinguishable from normal pyloric glands. In marked contrast, the immunohistochemical and ultrastructural features of 14 ductuloacinar cell tumors were those of cells lining terminal ductules, centroacinar cells, and/or acinar cells; none expressed any gut-type antigen. The results indicate that gastrointestinal differentiation is common in both benign and malignant lesions of pancreatic duct epithelium and suggest that duct cell carcinomas are histogenetically related to gastric- and intestinal-type metaplastic changes of epithelial cells lining the main and interlobular ducts of the pancreas.

Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia.

PubMed

Dominguez, Jessica A; Vithayathil, Paul J; Khailova, Ludmila; Lawrance, Christopher P; Samocha, Alexandr J; Jung, Enjae; Leathersich, Ann M; Dunne, W Michael; Coopersmith, Craig M

2011-10-01

Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P < 0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.

The frequency of Th17 cells in the small intestine exhibits a day-night variation dependent on circadian clock activity.

PubMed

Thu Le, Ha Pham; Nakamura, Yuki; Oh-Oka, Kyoko; Ishimaru, Kayoko; Nakajima, Shotaro; Nakao, Atsuhito

2017-08-19

Interleukin-17-producing CD4 + T helper (Th17) cells are a key immune lineage that protects against bacterial and fungal infections at mucosal surfaces. At steady state, Th17 cells are abundant in the small intestinal mucosa of mice. There are several mechanisms for regulating the population of Th17 cells in the small intestine, reflecting the importance of maintaining their numbers in the correct balance. Here we demonstrate the existence of a time-of-day-dependent variation in the frequency of Th17 cells in the lamina propria of the small intestine in wild-type mice, which was not observed in mice with a loss-of-function mutation of the core circadian gene Clock or in mice housed under aberrant light/dark conditions. Consistent with this, expression of CCL20, a chemokine that regulates homeostatic trafficking of Th17 cells to the small intestine, exhibited circadian rhythms in the small intestine of wild-type, but not Clock-mutated, mice. In support of these observations, the magnitude of ovalbumin (OVA)-specific antibody and T-cell responses in mice sensitized with OVA plus cholera toxin, a mucosal Th17 cell-dependent adjuvant, was correlated with daily variations in the proportion of Th17 cells in the small intestine. These results suggest that the proportion of Th17 cells in the small intestine exhibits a day-night variation in association with CCL20 expression, which depends on circadian clock activity. The findings provide novel insight into the regulation of the Th17 cell population in the small intestine at steady state, which may have translational potential for mucosal vaccination strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

Regional expression and dietary regulation of rat small intestinal peptide and amino acid transporter mRNAs.

PubMed

Erickson, R H; Gum, J R; Lindstrom, M M; McKean, D; Kim, Y S

1995-11-02

RT-PCR was used to obtain rat small intestinal cDNAs for two peptide transporters, showing conclusively for the first time that both are present in normal intestinal mucosa. Sequencing of these cDNAs showed them to be highly homologous and similar to two different types of peptide transport proteins from either colorectal carcinoma cells (Caco-2) or human and rabbit intestine. An even distribution profile of steady state levels of mRNA for both peptide transporters was observed along the longitudinal axis of small intestine. Both were upregulated in the distal regions of intestine by a high protein diet. Also, high levels of the rat high affinity glutamate transporter EAAC1 were observed in the distal intestine. These results suggest that the distal regions of small intestine play an important role in the absorption of some amino acids and peptides. Furthermore this area appears to be a primary site where dietary-induced changes in peptide and amino acid transport occurs.

Normative Values for the German Version of the Montreal Cognitive Assessment (MoCA)

ClinicalTrials.gov

2018-05-30

Cognitive Impairment; Cognitive Decline; Cognition Disorders; Cognitive Symptom; Cognitive Change; Cognitive Deterioration; Cognitive Abnormality; Cognitive Impairment, Mild; Cognition Disorders in Old Age; Dementia; Dementia Alzheimers; Dementia, Alzheimer Type; Dementia, Mild; Dementia of Alzheimer Type

Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist.

PubMed

Sugawara, Reiko; Lee, Eun-Jung; Jang, Min Seong; Jeun, Eun-Ji; Hong, Chun-Pyo; Kim, Jung-Hwan; Park, Areum; Yun, Chang Ho; Hong, Sung-Wook; Kim, You-Me; Seoh, Ju-Young; Jung, YunJae; Surh, Charles D; Miyasaka, Masayuki; Yang, Bo-Gie; Jang, Myoung Ho

2016-04-04

Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the ΔdblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+)T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra. © 2016 Sugawara et al.

Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist

PubMed Central

Sugawara, Reiko; Lee, Eun-Jung; Jang, Min Seong; Jeun, Eun-Ji; Hong, Chun-Pyo; Kim, Jung-Hwan; Park, Areum; Yun, Chang Ho; Hong, Sung-Wook; Kim, You-Me; Seoh, Ju-Young; Jung, YunJae; Surh, Charles D.; Miyasaka, Masayuki

2016-01-01

Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the ΔdblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4+ T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β. Moreover, small intestinal eosinophils isolated from IL-1Ra−deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra. PMID:26951334

Immunoproteomics Approach for Screening of Vaccine Candidates against Intestinal Botulism.

PubMed

Sharma, Arti; Rani, Sarita; Alam, Syed Imteyaz; Ponmariappan, Sarkaraisamy

2017-01-01

Intestinal botulism is an infectious form of botulism in which disease results from ingesting spores, which is followed by spore germination and intraluminal production of botulinum neurotoxins over an extended period. Botulinum neurotoxin is produced by endospore forming bacteria called C. botulinum. Immunoproteomic study was used to screen the cross reactive immunogenic proteins of Clostridium botulinum type B using C. botulinum type B live spore antiserum. The whole cell proteins were separated by two dimensional gel electrophoresis and transferred to polyvinylidene difluoride membranes. Further, the Western blotting was performed with mouse pups immune serum against C. botulinum type B live spores. Eight predominant cross immunoreactive proteins were identified by mass spectrometry. These immunogenic proteins might be used to develop novel subunit vaccine candidates against the intestinal botulism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Primary mucinous adenocarcinoma of the vulva, intestinal type

PubMed Central

Lee, In Ho; Kim, Mi Kyung; Lee, Yoo Kyung; Hong, Sung Ran

2017-01-01

Primary vulva malignancy is a rare gynecologic malignancy. Most of them are squamous cell carcinomas and adenocarcinomas are much less common. Intestinal type is a rare variant of primary adenocarcinoma of the vulva. It histologically resembles mucinous colonic carcinomas. Origin from cloacal remnants has been suggested but remains speculative. A 64-year-old woman was referred to our clinic with a 1-month history of an itching vulva mass. An incisional biopsy was performed at other hospital and disclosed adenocarcinoma of intestinal type. Extensive workups were performed to detect other underlying carcinomas but revealed nothing abnormal. She underwent wide local excision without lymph node dissection for a primary vulva carcinoma. She received no adjuvant therapy and has been free from recurrent disease for 12 months after surgery. The authors report a rare case and review the relevant literature. PMID:28791269

Clinical application of entire gastrointestinal barium meal combined with multi-temporal abdominal films in patients with intestinal neuronal dysplasia type B.

PubMed

Li, Xiao-Yun; Li, Xiao-Gang; Du, Ming-Guo; Chen, Zhi-Dan; Tao, Zheng-Gui; Liao, Xiao-Feng

2013-01-01

To report and evaluate the application of entire gastrointestinal barium meal combined with multi-temporal abdominal films in the diagnosis of patients with intestinal neuronal dysplasia type B (IND type B). Thirty-six patients with symptoms of long-standing constipation were enrolled in this study. The study took place at the Department of General Surgery, Xiangyang Central Hospital, Hubei Province, China from July 2007 to October 2012. All of them had already been subjected to the tests of barium enema and anorectal manometry and were suspected to be IND type B, but were not confirmed by mucous membrane acetylcholinesterase determination. All underwent the entire gastrointestinal barium meal combined with multi-temporal abdominal films. The data was collected and then analyzed retrospectively. After entire gastrointestinal barium meal combined with multi-temporal abdominal films, 30 out of 36 cases in this group were diagnosed with intestinal neuronal diseases, and then were treated with appropriate surgical treatment. The postoperative pathological diagnosis was IND type B. The other 6 patients in this group still could not be diagnosed explicitly after the test; thus, we treated them with conservative treatment. Entire gastrointestinal barium meal combined with multi-temporal abdominal films has the advantage of being able to test the gastrointestinal transfer capabilities and to find physiological and pathological changes simultaneously. It could provide important proof for the diagnosis of patients with intestinal neuronal dysplasia type B.

Photodermatitis and photokeratoconjunctivitis in a ball python (Python regius) and a blue-tongue skink (Tiliqua spp.).

PubMed

Gardiner, David W; Baines, Frances M; Pandher, Karamjeet

2009-12-01

A male ball python (Python regius) and a female blue tongue skink (Tiliqua spp.) of unknown age were evaluated for anorexia, lethargy, excessive shedding, corneal opacity (python), and weight loss (skink) of approximately three weeks' duration. These animals represented the worst affected animals from a private herpetarium where many animals exhibited similar signs. At necropsy, the python had bilateral corneal opacity and scattered moderate dysecdysis. The skink had mild dysecdysis, poor body condition, moderate intestinal nematodiasis, and mild liver atrophy. Microscopic evaluation revealed epidermal erosion and ulceration, with severe epidermal basal cell degeneration and necrosis, and superficial dermatitis (python and skink). Severe bilateral ulcerative keratoconjunctivitis with bacterial colonization was noted in the ball python. Microscopic findings within the skin and eyes were suggestive of ultraviolet (UV) radiation damage or of photodermatitis and photokeratoconjunctivitis. Removal of the recently installed new lamps from the terrariums of the surviving reptiles resulted in resolution of clinical signs. Evaluation of a sample lamp of the type associated with these cases revealed an extremely high UV output, including very-short-wavelength UVB, neither found in natural sunlight nor emitted by several other UVB lamps unassociated with photokeratoconjunctivitis. Exposure to high-intensity and/or inappropriate wavelengths of UV radiation may be associated with significant morbidity, and even mortality, in reptiles. Veterinarians who are presented with reptiles with ocular and/or cutaneous disease of unapparent cause should fully evaluate the specifics of the vivarium light sources. Further research is needed to determine the characteristics of appropriate and of toxic UV light for reptiles kept in captivity.

Lymphotoxin Alpha-Deficient Mice Clear Persistent Rotavirus Infection after Local Generation of Mucosal IgA

PubMed Central

Lopatin, Uri; Blutt, Sarah E.; Conner, Margaret E.

2013-01-01

Rotavirus is a major cause of pediatric diarrheal illness worldwide. To explore the role of organized intestinal lymphoid tissues in infection by and immunity to rotavirus, lymphotoxin alpha-deficient (LTα−/−) mice that lack Peyer's patches and mesenteric lymph nodes were orally infected with murine rotavirus. Systemic rotavirus was cleared within 10 days in both LTα−/− and wild-type mice, and both strains developed early and sustained serum antirotavirus antibody responses. However, unlike wild-type mice, which resolved the intestinal infection within 10 days, LTα−/− mice shed fecal virus for approximately 50 days after inoculation. The resolution of fecal virus shedding occurred concurrently with induction of intestinal rotavirus-specific IgA in both mouse strains. Induction of intestinal rotavirus-specific IgA in LTα−/− mice correlated with the (late) appearance of IgA-producing plasma cells in the small intestine. This, together with the absence of rotavirus-specific serum IgA, implies that secretory rotavirus-specific IgA was produced locally. These findings indicate that serum IgG responses are insufficient and imply that local intestinal IgA responses are important for the clearance of rotavirus from intestinal tissues. Furthermore, they show that while LTα-dependent lymphoid tissues are important for the generation of IgA-producing B cells in the intestine, they are not absolutely required in the setting of rotavirus infection. Moreover, the induction of local IgA-producing B cell responses can occur late after infection and in an LTα-independent manner. PMID:23097456

Primary peri-anal adenocarcinoma of intestinal type - a new proposed entity.

PubMed

Gill, Pelvender S; Wong, Newton A C S

2018-02-21

The currently recognised subtypes of anal canal/peri-anal adenocarcinoma are those arising from low rectal mucosa or columnar cuff, fistula-related tumours and anal gland carcinoma. This report presents two examples of a hitherto undescribed subtype of peri-anal adenocarcinoma with an intestinal phenotype. A 74-year-old man had a peri-anal tumour locally excised, whereas a 73-year-old female underwent an abdominoperineal resection for peri-anal Paget's disease with an underlying carcinoma. Neither patient had a history of perineal fistulae, Crohn's disease or previous gastrointestinal neoplasia, and neither showed clinical, radiological or endoscopic evidence of another abdominal or pelvic tumour. Both resection specimens contained adenocarcinoma, which were similar in demonstrating an intestinal morphology and CDX2 immunopositivity. The man has shown a disease-free outcome thus far, but the woman has suffered with nodal and pelvic recurrence within a few months of surgery. The name 'primary peri-anal adenocarcinoma of intestinal type' is proposed for this previously unrecognised subtype of perineal neoplasia. Awareness of its distinct existence - by recognising its intestinal morphology and immunophenotype while excluding metastasis from the intestinal tract - should help to collate data to determine its specific prognosis and to formulate its best management. © 2018 John Wiley & Sons Ltd.

Adaptation of Haplobothrium globuliforme (Cestoda: Pseudophyllidea) to the intestinal architecture of the bowfin (Amia calva L).

PubMed

Joy, James E; Triest, William E; Walker, Ernest M

2009-02-01

Haplobothrium globuliforme maintains its position in the proximal mid-gut epithelium of Amia calva with the aid of tentacles, i.e., proboscides, everted from scolices of a primary strobila and craspedote proglottids of a secondary strobila. Weakly developed scolices of the secondary strobila appear to have little holdfast action, but the distinctly craspedote proglottids of these individuals project into the intestinal mucosa, altering the configuration of gut epithelial cells and pushing the tapeworm deeper into mucosal crypts. The basement membrane underlying the epithelium appears to act as a barrier that prevents tapeworms from penetrating into the deeper tissue layers of the lamina propria, muscularis mucosa, or submucosa. Scolex tegument modification occurs at the point of contact with host basement membrane. A mild background infiltrate of lymphocytes and granulocytes was evident adjacent to the scolex and proglottid tegument. There was no evidence of blood vessel proliferation, edema, mast cell degranulation, eosinophilia, or subsequent collagen formation associated with tapeworm activity.

Phylogenetic and pathogenic characterization of novel adenoviruses from long-tailed ducks (Clangula hyemalis)

USGS Publications Warehouse

Counihan, Katrina; Skerratt, Lee; Franson, J. Christian; Hollmen, Tuula E.

2015-01-01

Novel adenoviruses were isolated from a long-tailed duck (Clangula hyemalis) mortality event near Prudhoe Bay, Alaska in 2000. The long-tailed duck adenovirus genome was approximately 27 kb. A 907 bp hexon gene segment was used to design primers specific for the long-tailed duck adenovirus. Nineteen isolates were phylogenetically characterized based on portions of their hexon gene and 12 were most closely related to Goose adenovirus A. The remaining 7 shared no hexon sequences with any known adenoviruses. Experimental infections of mallards with a long-tailed duck reference adenovirus caused mild lymphoid infiltration of the intestine and paint brush hemorrhages of the mucosa and dilation of the intestine. This study shows novel adenoviruses from long-tailed ducks are diverse and provides further evidence that they should be considered in cases of morbidity and mortality in sea ducks. Conserved and specific primers have been developed that will help screen sea ducks for adenoviral infections.

A PQM-1-Mediated Response Triggers Transcellular Chaperone Signaling and Regulates Organismal Proteostasis.

PubMed

O'Brien, Daniel; Jones, Laura M; Good, Sarah; Miles, Jo; Vijayabaskar, M S; Aston, Rebecca; Smith, Catrin E; Westhead, David R; van Oosten-Hawle, Patricija

2018-06-26

In metazoans, tissues experiencing proteotoxic stress induce "transcellular chaperone signaling" (TCS) that activates molecular chaperones, such as hsp-90, in distal tissues. How this form of inter-tissue communication is mediated to upregulate systemic chaperone expression and whether it can be utilized to protect against protein misfolding diseases remain open questions. Using C. elegans, we identified key components of a systemic stress signaling pathway that links the innate immune response with proteostasis maintenance. We show that mild perturbation of proteostasis in the neurons or the intestine activates TCS via the GATA zinc-finger transcription factor PQM-1. PQM-1 coordinates neuron-activated TCS via the innate immunity-associated transmembrane protein CLEC-41, whereas intestine-activated TCS depends on the aspartic protease ASP-12. Both TCS pathways can induce hsp-90 in muscle cells and facilitate amelioration of Aβ 3-42 -associated toxicity. This may have powerful implications for the treatment of diseases related to proteostasis dysfunction. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

[The microbial flora in the digestive tract and diabetes].

PubMed

Svačina, Štěpán

2015-04-01

The microbial flora in the digestive tract has been recently studied in relation to metabolic diseases. There are relations to both type 1 diabetes and type 2 diabetes. The intestinal flora is affected by diet, physical exercise and it significantly changes after bariatric surgeries. Giving birth by caesarean section affects the gut flora development and increases the risk of type 1 diabetes in further life of the child. Obese patients with type 2 diabetes may lack protective microbes which improve glucoregulation in the experiment or on the contrary their patogenous microbes may grow which have been proven to even be able to penetrate into abdominal adipose tissue and play a role, inter alia, in the hepatic impairment and systemic inflammation. Also vaccination against these microbes is under consideration. Microbiome can be also positively affected by metformin treatment. The transfer of intestinal flora by means of fecal transplantation can improve glucoregulation. The influencing of intestinal flora is likely to become a new mechanism of diabetes treatment.

Three-Dimensional Organotypic Co-Culture Model of Intestinal Epithelial Cells and Macrophages to Study "Salmonella Enterica" Colonization Patterns

NASA Technical Reports Server (NTRS)

Ott, Mark; Yang, J; Barilla, J.; Crabbe, A.; Sarker, S. F.; Liu, Y.

2017-01-01

Three-dimensional/3-D organotypic models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by 2-D monolayers and respond to Salmonella in ways that reflect in vivo infections. To further enhance the physiological relevance of 3-D models to more closely approximate in vivo intestinal microenvironments during infection, we developed and validated a novel 3-D intestinal co-culture model containing multiple epithelial cell types and phagocytic macrophages, and applied to study enteric infection by different Salmonella pathovars.

Mechanisms and function of autophagy in intestinal disease.

PubMed

Lassen, Kara G; Xavier, Ramnik J

2018-01-01

The discovery of numerous genetic variants in the human genome that are associated with inflammatory bowel disease (IBD) has revealed critical pathways that play important roles in intestinal homeostasis. These genetic studies have identified a critical role for macroautophagy/autophagy and more recently, lysosomal function, in maintaining the intestinal barrier and mucosal homeostasis. This review highlights recent work on the functional characterization of IBD-associated human genetic variants in cell type-specific functions for autophagy.

Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut.

PubMed

Howitt, Michael R; Lavoie, Sydney; Michaud, Monia; Blum, Arthur M; Tran, Sara V; Weinstock, Joel V; Gallini, Carey Ann; Redding, Kevin; Margolskee, Robert F; Osborne, Lisa C; Artis, David; Garrett, Wendy S

2016-03-18

The intestinal epithelium forms an essential barrier between a host and its microbiota. Protozoa and helminths are members of the gut microbiota of mammals, including humans, yet the many ways that gut epithelial cells orchestrate responses to these eukaryotes remain unclear. Here we show that tuft cells, which are taste-chemosensory epithelial cells, accumulate during parasite colonization and infection. Disruption of chemosensory signaling through the loss of TRMP5 abrogates the expansion of tuft cells, goblet cells, eosinophils, and type 2 innate lymphoid cells during parasite colonization. Tuft cells are the primary source of the parasite-induced cytokine interleukin-25, which indirectly induces tuft cell expansion by promoting interleukin-13 production by innate lymphoid cells. Our results identify intestinal tuft cells as critical sentinels in the gut epithelium that promote type 2 immunity in response to intestinal parasites. Copyright © 2016, American Association for the Advancement of Science.

Palynological Investigation of Mummified Human Remains.

PubMed

Reinhard, Karl J; Amaral, Marina Milanello do; Wall, Nicole

2018-01-01

Pollen analysis was applied to a mummified homicide victim in Nebraska, U.S.A., to determine the location of death. A control sample showed the normal ambient pollen in the garage crime scene. Ambient windborne types, common in the air of the region, dominated the control. Internal samples were analyzed from the sacrum, intestine, and diaphragm. Microfossils were recovered from the rehydrated intestine lumen. The intestinal sample was dominated by Brassica (broccoli). The sacrum sample was high in dietary types but with a showing of ambient types. The pollen from the diaphragm was dominated by ambient pollen similar to the control samples. The discovery of diverse pollen spectra from within a single mummy was unexpected. They show that ingested and inhaled pollen mixed in the corpse. The data linked the decedent to a specific crime scene in her Nebraska home in the southern tier of eastern counties on the border with Kansas. © 2017 American Academy of Forensic Sciences.

The Overlap between Irritable Bowel Syndrome and Non-Celiac Gluten Sensitivity: A Clinical Dilemma.

PubMed

Makharia, Archita; Catassi, Carlo; Makharia, Govind K

2015-12-10

The spectrum of gluten-related disorders has widened in recent times and includes celiac disease, non-celiac gluten sensitivity, and wheat allergy. The complex of symptoms associated with these diseases, such as diarrhea, constipation or abdominal pain may overlap for the gluten related diseases, and furthermore they can be similar to those caused by various other intestinal diseases, such as irritable bowel syndrome (IBS). The mechanisms underlying symptom generation are diverse for all these diseases. Some patients with celiac disease may remain asymptomatic or have only mild gastrointestinal symptoms and thus may qualify for the diagnosis of IBS in the general clinical practice. Similarly, the overlap of symptoms between IBS and non-celiac gluten sensitivity (NCGS) often creates a dilemma for clinicians. While the treatment of NCGS is exclusion of gluten from the diet, some, but not all, of the patients with IBS also improve on a gluten-free diet. Both IBS and NCGS are common in the general population and both can coexist with each other independently without necessarily sharing a common pathophysiological basis. Although the pathogenesis of NCGS is not well understood, it is likely to be heterogeneous with possible contributing factors such as low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Innate immunity may also play a pivotal role. One possible inducer of innate immune response has recently been reported to be amylase-trypsin inhibitor, a protein present in wheat endosperm and the source of flour, along with the gluten proteins.

The Overlap between Irritable Bowel Syndrome and Non-Celiac Gluten Sensitivity: A Clinical Dilemma

PubMed Central

Makharia, Archita; Catassi, Carlo; Makharia, Govind K.

2015-01-01

The spectrum of gluten-related disorders has widened in recent times and includes celiac disease, non-celiac gluten sensitivity, and wheat allergy. The complex of symptoms associated with these diseases, such as diarrhea, constipation or abdominal pain may overlap for the gluten related diseases, and furthermore they can be similar to those caused by various other intestinal diseases, such as irritable bowel syndrome (IBS). The mechanisms underlying symptom generation are diverse for all these diseases. Some patients with celiac disease may remain asymptomatic or have only mild gastrointestinal symptoms and thus may qualify for the diagnosis of IBS in the general clinical practice. Similarly, the overlap of symptoms between IBS and non-celiac gluten sensitivity (NCGS) often creates a dilemma for clinicians. While the treatment of NCGS is exclusion of gluten from the diet, some, but not all, of the patients with IBS also improve on a gluten-free diet. Both IBS and NCGS are common in the general population and both can coexist with each other independently without necessarily sharing a common pathophysiological basis. Although the pathogenesis of NCGS is not well understood, it is likely to be heterogeneous with possible contributing factors such as low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Innate immunity may also play a pivotal role. One possible inducer of innate immune response has recently been reported to be amylase-trypsin inhibitor, a protein present in wheat endosperm and the source of flour, along with the gluten proteins. PMID:26690475

Effects of zeolite supplementation on parameters of intestinal barrier integrity, inflammation, redoxbiology and performance in aerobically trained subjects.

PubMed

Lamprecht, Manfred; Bogner, Simon; Steinbauer, Kurt; Schuetz, Burkhard; Greilberger, Joachim F; Leber, Bettina; Wagner, Bernhard; Zinser, Erwin; Petek, Thomas; Wallner-Liebmann, Sandra; Oberwinkler, Tanja; Bachl, Norbert; Schippinger, Gert

2015-01-01

Zeolites are crystalline compounds with microporous structures of Si-tetrahedrons. In the gut, these silicates could act as adsorbents, ion-exchangers, catalysts, detergents or anti-diarrheic agents. This study evaluated whether zeolite supplementation affects biomarkers of intestinal wall permeability and parameters of oxidation and inflammation in aerobically trained individuals, and whether it could improve their performance. In a randomized, double-blinded, placebo controlled trial, 52 endurance trained men and women, similar in body fat, non-smokers, 20-50 years, received 1.85 g of zeolite per day for 12 weeks. Stool samples for determination of intestinal wall integrity biomarkers were collected. From blood, markers of redox biology, inflammation, and DNA damage were determined at the beginning and the end of the study. In addition, VO2max and maximum performance were evaluated at baseline and after 12 weeks of treatment. For statistical analyses a 2-factor ANOVA was used. At baseline both groups showed slightly increased stool zonulin concentrations above normal. After 12 weeks with zeolite zonulin was significantly (p < 0.05) decreased in the supplemented group. IL-10 increased tendentially (p < 0.1) in the zeolite group. There were no significant changes observed in the other measured parameters. Twelve weeks of zeolite supplementation exerted beneficial effects on intestinal wall integrity as indicated via decreased concentrations of the tight junction modulator zonulin. This was accompanied by mild anti-inflammatory effects in this cohort of aerobically trained subjects. Further research is needed to explore mechanistic explanations for the observations in this study.

(abstract) Effects of Radiation and Oxidative Stress on Development and Morphology of Intestinal Cells

NASA Technical Reports Server (NTRS)

Honda, Shuji; Nelson, Gregory; Schubert, Wayne

1993-01-01

Intestinal cells when subjected to oxidative stress or radiation exhibit abnormal nuclear divisions observed as: 1) supernumerary cell divisions in anterior intestinal cells or 2) incomplete nuclear division and the persistence of anaphase bridges between daughter nuclei. Two oxygen sensitive mutants, mev-1 and rad-8 were observed to exhibit spontaneous supernumerary nuclear divisions at low frequency. N2 can be induced to undergo these divisions by treatment with the superoxide dismutase (SOD) inhibitor diethyl dithicarbamate or with the free radical generator methyl viologen. By contrast, the free radical generator bleomycin produces anaphase bridges in N2 intestinal nuclei at high frequency. Intestinal anaphase bridges can be induced by ionizing radiation and their formation is dependent on dose and radiation type.

[THE MODES OF EVALUATION OF TYPE OF DEHYDRATION IN CHILDREN HOSPITALIZED BECAUSE OF ACUTE INTESTINAL INFECTION].

PubMed

Krieger, E A; Samodova, O V; Gulakova, N N; Aruiev, A B; Krylova, L A; Titova, L V

2015-11-01

Every year about 800,000 cases of intestinal infections end in lethal outcome due to dehydration. The different types of dehydration acquire differential approach to correction. Everywhere there is no application of routine detection of osmolarity of blood plasma under exicosis in children in view of absence of possibility of instrumental measurement. The search of techniques is needed to make it possible to indirectly detect types of dehydration in children hospitalized because of acute intestinal infection with purpose to apply rationale therapy of water-electrolyte disorders. The sampling of 32 patients with intestinal infections accompanied with signs of exicosis degree I-III was examined. The detection of osmolarity of blood was implemented by instrumental technique using gas analyzer ABL 800 Flex (Radiometer; Denmark) and five estimate techniques according to results of biochemical analysis of blood. The differences in precision of measurement of osmolarity of blood plasma by instrumental and estimate techniques were compared using Bland-Altman graphic technique. It is established that formula: 2x[Na+kp] + [glucosekp] (mmol/l) is the most recise. Its application provided results comparable with values detected by instrumental mode.

Hypervitaminosis D mediates compensatory Ca2+ hyperabsorption in TRPV5 knockout mice.

PubMed

Renkema, Kirsten Y; Nijenhuis, Tom; van der Eerden, Bram C J; van der Kemp, Annemiete W C M; Weinans, Harrie; van Leeuwen, Johannes P T M; Bindels, René J M; Hoenderop, Joost G J

2005-11-01

Vitamin D plays an important role in Ca(2+) homeostasis by controlling Ca(2+) (re)absorption in intestine, kidney, and bone. The epithelial Ca(2+) channel TRPV5 mediates the Ca(2+) entry step in active Ca(2+) reabsorption. TRPV5 knockout (TRPV5(-/-)) mice show impaired Ca(2+) reabsorption, hypercalciuria, hypervitaminosis D, and intestinal hyperabsorption of Ca(2+). Moreover, these mice demonstrate upregulation of intestinal TRPV6 and calbindin-D(9K) expression compared with wild-type mice. For addressing the role of the observed hypervitaminosis D in the maintenance of Ca(2+) homeostasis and the regulation of expression levels of the Ca(2+) transport proteins in kidney and intestine, TRPV5/25-hydroxyvitamin-D(3)-1alpha-hydroxylase double knockout (TRPV5(-/-)/1alpha-OHase(-/-)) mice, which show undetectable serum 1,25(OH)(2)D(3) levels, were generated. TRPV5(-/-)/1alpha-OHase(-/-) mice displayed a significant hypocalcemia compared with wild-type mice (1.10 +/- 0.02 and 2.54 +/- 0.01 mM, respectively; P < 0.05). mRNA levels of renal calbindin-D(28K) (7 +/- 2%), calbindin-D(9K) (32 +/- 4%), Na(+)/Ca(2+) exchanger (12 +/- 2%), and intestinal TRPV6 (40 +/- 8%) and calbindin-D(9K) (26 +/- 4%) expression levels were decreased compared with wild-type mice. Hyperparathyroidism and rickets were present in TRPV5(-/-)/1alpha-OHase(-/-) mice, more pronounced than observed in single TRPV5 or 1alpha-OHase knockout mice. It is interesting that a renal Ca(2+) leak, as demonstrated in TRPV5(-/-) mice, persisted in TRPV5(-/-)/1alpha-OHase(-/-) mice, but a compensatory upregulation of intestinal Ca(2+) transporters was abolished. In conclusion, the elevation of serum 1,25(OH)(2)D(3) levels in TRPV5(-/-) mice is responsible for the upregulation of intestinal Ca(2+) transporters and Ca(2+) hyperabsorption. Hypervitaminosis D, therefore, is of crucial importance to maintain normocalcemia in impaired Ca(2+) reabsorption in TRPV5(-/-) mice.

Passive immunity in transmissible gastroenteritis of swine: immunoglobulin characteristics of antibodies in milk after inoculating virus by different routes.

PubMed Central

Bohl, E H; Saif, L J

1975-01-01

Pregnant swine were exposed to transmissible gastroenteritis (TGE) virus by different routes, and their serum, colostrum, and mild were examined for titer and immunoglobulin (Ig) class of antibodies. When 2 to 4 days old, the litters of most of these animals were challenged with virulent TGE virus to determine the effectiveness of passive immunity. After two oral/intranasal exposures to attenuated virus, none of the six pregnant animals became sick. TGE antibodies in milk were primarily or solely of the IgG class, although low levels of IgA antibodies were detected in three animals. Pigs in the five challenged litters received some passive immunity, the mortality being 25%. After intramuscular injection of six pregnant swine with virulent virus, two types of clinical and immunological responses were observed, presumably dependent on whether the gut was infected by an hematogenous spread of the virus. Three became sick, showing typical clinical signs of TGE, and their immunological response was characterized by the occurrence in milk of antibodies of the IgA class. A good degree (0% mortality) of passive immunity occurred upon challenge of the suckling pigs. In contrast, in three pregnant animals that did not sicken, antibody in milk was primarily of the IgG calss, and poor (69% mortality) passive immunity occurred. After intramammary injections of three pregnant swine with virulent virus, no sickness was observed and the immunological response was characterized by the occurrence in colostrum of high titers of TGE antibodies that were primarily or solely of the IgG class; good (0% mortality) passive immunity occured. The occurrence in milk of TGE antibodies of the IgA class was associated with an intestinal infection, whereas antibodies of the IgG class resulted from a parenteral antigenic stimulation. The role of antigenic stimulation of the intestinal tract for providing antibodies in milk of the IgA class is discussed. Passive immunity against intestinal infection with TGE virus was generally more complete in pigs ingesting antibodies of the IgA than of the IgG class. PMID:803922

Toxicity and hazard of vanadium to mallard ducks (Anas platyrhynchos) and Canada geese (Branta canadensis).

PubMed

Rattner, Barnett A; McKernan, Moira A; Eisenreich, Karen M; Link, William A; Olsen, Glenn H; Hoffman, David J; Knowles, Kathy A; McGowan, Peter C

2006-02-01

A recent Canada goose (Branta canadensis) die-off at a petroleum refinery fly ash pond in Delaware was attributed to vanadium (V) toxicity. Because of the paucity of V toxicity data for wild birds, a series of studies was undertaken using the forms of V believed to have resulted in this incident. In 7-d single oral dose trials with mallard drakes (Anas platyrhynchos), the estimated median lethal dose (LD50) for vanadium pentoxide was 113 mg/kg body weight, while the LD50 for sodium metavanadate was 75.5 mg/kg. Sodium metavanadate was found to be even more potent (LD50 = 37.2 mg/kg) in male Canada geese. The most distinctive histopathological lesion of both forms of V was lympho-granulocytic enteritis with hemorrhage into the intestinal lumen. Vanadium accumulation in liver and kidney was proportional to the administered dose, and predictive analyses based on these data suggest that V concentrations of 10 microg/g dry weight (dw) in liver and 25 microg/g dw in kidney are associated with mortality (>90% confidence that exposure is >LD50) in mallards acutely exposed to sodium metavanadate. Chronic exposure to increasing dietary concentrations of sodium metavanadate (38.5 to 2651 ppm) over 67 d resulted in V accumulation in liver and kidney (25.2 and 13.6 microg/g dw, respectively), mild intestinal hemorrhage, blood chemistry changes, and evidence of hepatic oxidative stress in mallards, although some of these responses may have been confounded by food avoidance and weight loss. Dietary exposure of mallards to 250 ppm sodium metavanadate for 4 wk resulted in modest accumulation of V in liver and kidney (<5 microg/g dw) and mild intestinal hemorrhage. Based on these data and other observations, it is unlikely that chronic low-level dietary exposure to V poses a direct lethal hazard to wildlife. However, point sources, such as the V-laden fly ash pond encountered by geese at the petroleum refinery in Delaware, may pose a significant hazard to water birds.

Toxicity and hazard of vanadium to mallard ducks (Anas platyrhynchos) and Canada geese (Branta canadensis)

USGS Publications Warehouse

Rattner, Barnett A.; McKernan, Moira A.; Eisenreich, Karen M.; Link, William A.; Olsen, Glenn H.; Hoffman, David J.; Knowles, K.A.; McGowan, Peter C.

2006-01-01

A recent Canada goose (Branta canadensis) die-off at a petroleum refinery fly ash pond in Delaware was attributed to vanadium (V) toxicity. Because of the paucity of V toxicity data for wild birds, a series of studies was undertaken using the forms of V believed to have resulted in this incident. In 7-d single oral dose trials with mallard drakes (Anas platyrhynchos), the estimated median lethal dose (LD50) for vanadium pentoxide was 113 mg/kg body weight, while the LD50 for sodium metavanadate was 75.5 mg/kg. Sodium metavanadate was found to be even more potent (LD50 = 37.2 mg/kg) in male Canada geese. The most distinctive histopathological lesion of both forms of V was lympho-granulocytic enteritis with hemorrhage into the intestinal lumen. Vanadium accumulation in liver and kidney was proportional to the administered dose, and predictive analyses based on these data suggest that V concentrations of 10 μg/g dry weight (dw) in liver and 25 μg/g dw in kidney are associated with mortality (>90% confidence that exposure is >LD50) in mallards acutely exposed to sodium metavanadate. Chronic exposure to increasing dietary concentrations of sodium metavanadate (38.5 to 2651 ppm) over 67 d resulted in V accumulation in liver and kidney (25.2 and 13.6 μg/g dw, respectively), mild intestinal hemorrhage, blood chemistry changes, and evidence of hepatic oxidative stress in mallards, although some of these responses may have been confounded by food avoidance and weight loss. Dietary exposure of mallards to 250 ppm sodium metavanadate for 4 wk resulted in modest accumulation of V in liver and kidney (<5 μg/g dw) and mild intestinal hemorrhage. Based on these data and other observations, it is unlikely that chronic low-level dietary exposure to V poses a direct lethal hazard to wildlife. However, point sources, such as the V-laden fly ash pond encountered by geese at the petroleum refinery in Delaware, may pose a significant hazard to water birds.

Intestinal complications following irradiation for gynecologic cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashbaugh, D G; Owens, J C

1963-07-01

Intestinal injury following irradiation for gynecologic cancer is discussed with reference to 49 cases. These cases could be divided into three groups on the basis of the severity of the damage: group 1, (8 cases), those with mild injury and littie or no residual damage and symptoms; group II (9 cases), those with moderate injury and some permanent changes with or without symptoms; and group III (32 cases), those with severe injury who were incapacitated or required surgery. Group III includes seven patients who were cured of their malignancies but who died of the complications of radiation injury and themore » subsequent attempts to correct this damage. In group I the symptoms consisted mainly of rectal pain, diarrhea, tenesmus, and constipation, and in two instances, mild rectal stricture. All patients became asymptomatic with nonoperative management. In group II the initial symptoms were also pain, diarrhea, constipation, tenesmus, and rectal bleeding, persistent in varying degrees. Five patients developed stricture or narrowing of the rectum and sigmoid, but none required operation. In group III there were 19 bowel strictures and 32 fistulss, and 84 operations were performed in attempts to correct these problems. In the seven patients who died from complications of radiation therapy no tumor was found at postmortem examination. A review of other reports shows an incidence of intestinal complications following pelvic irradiation ranging from 2.4% to 17%, with one estimate as high as 50 to 75%. The problem here was not and overdosage of radiation, but the necessity in treating carcinoma, the primary aim of which is eradication of the malignancy, in using adequate dosage. It is suggested that with prompt recognition and early, vigorous treatment, many of the more severe cases could probably have been greatly modified. Treatment is generally nonoperative in the acute stsge, which is best mansged by supportive measures and the cessation of radiation therapy. The chronic stage frequently requires operative intervention for the relief of stricture or fistula, and and initial diverting colostomy is the operation of choice. Subsequently, additional procedures may be performed, but these sometimes lead to increased morbidity and even mortality.« less

The probability and severity of decompression sickness

PubMed Central

Hada, Ethan A.; Vann, Richard D.; Denoble, Petar J.

2017-01-01

Decompression sickness (DCS), which is caused by inert gas bubbles in tissues, is an injury of concern for scuba divers, compressed air workers, astronauts, and aviators. Case reports for 3322 air and N2-O2 dives, resulting in 190 DCS events, were retrospectively analyzed and the outcomes were scored as (1) serious neurological, (2) cardiopulmonary, (3) mild neurological, (4) pain, (5) lymphatic or skin, and (6) constitutional or nonspecific manifestations. Following standard U.S. Navy medical definitions, the data were grouped into mild—Type I (manifestations 4–6)–and serious–Type II (manifestations 1–3). Additionally, we considered an alternative grouping of mild–Type A (manifestations 3–6)–and serious–Type B (manifestations 1 and 2). The current U.S. Navy guidance allows for a 2% probability of mild DCS and a 0.1% probability of serious DCS. We developed a hierarchical trinomial (3-state) probabilistic DCS model that simultaneously predicts the probability of mild and serious DCS given a dive exposure. Both the Type I/II and Type A/B discriminations of mild and serious DCS resulted in a highly significant (p << 0.01) improvement in trinomial model fit over the binomial (2-state) model. With the Type I/II definition, we found that the predicted probability of ‘mild’ DCS resulted in a longer allowable bottom time for the same 2% limit. However, for the 0.1% serious DCS limit, we found a vastly decreased allowable bottom dive time for all dive depths. If the Type A/B scoring was assigned to outcome severity, the no decompression limits (NDL) for air dives were still controlled by the acceptable serious DCS risk limit rather than the acceptable mild DCS risk limit. However, in this case, longer NDL limits were allowed than with the Type I/II scoring. The trinomial model mild and serious probabilities agree reasonably well with the current air NDL only with the Type A/B scoring and when 0.2% risk of serious DCS is allowed. PMID:28296928

In utero exposure to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) did not increase body weight or intestinal tumorigenesis in multiple intestinal neoplasia (Min/+) mice.

PubMed

Ngo, Ha Thi; Hetland, Ragna Bogen; Sabaredzovic, Azemira; Haug, Line Småstuen; Steffensen, Inger-Lise

2014-07-01

We examined whether perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) had obesogenic effects and if they increased spontaneous intestinal tumorigenesis in the mouse model C57BL/6J-Min/+ (multiple intestinal neoplasia) after in utero exposure. The dams were exposed to PFOA or PFOS (0.01, 0.1 or 3.0mg/kg bw/day) by po gavage on GD1-17. The Min/+ and wild-type offspring were terminated at week 11 for examination of intestinal tumorigenesis or at week 20 for obesogenic effect, respectively. Body weights of the dams and pups were recorded throughout life. Food intake was determined at week 6 and 10. Blood glucose (non-fasted) was measured at week 6 and 11. No obesogenic effect of PFOA or PFOS was observed up to 20 weeks of age. PFOA or PFOS did not increase the incidence or number of tumors in the small intestine or colon of the Min/+ mice or affect their location along the intestines. Feed intake was not affected. There were some indications of toxicity of PFOA, but not of PFOS. There was lower survival of pups after 3.0mg/kg PFOA, lower body weight in pups after 3.0 and possibly 0.1mg/kg PFOA, and increased relative liver weight after 0.01 and possibly 0.1mg/kg PFOA. Plasma glucose was lower after 0.01 and 0.1mg/kg PFOA. In conclusion, exposure to PFOA and PFOS in utero with the doses used did not have obesogenic effect on either Min/+ or wild-type mice, at least not up to 11 or 20 weeks of age, nor increased intestinal tumorigenesis in Min/+ mice. Copyright © 2014 Elsevier Inc. All rights reserved.

Curcumin improves intestinal barrier function: modulation of intracellular signaling, and organization of tight junctions.

PubMed

Wang, Jing; Ghosh, Siddhartha S; Ghosh, Shobha

2017-04-01

Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as type 2 diabetes and atherosclerosis) has shifted the focus from high-fat high-cholesterol containing Western-type diet (WD)-induced changes in gut microbiota per se to release of gut bacteria-derived products (e.g., LPS) into circulation due to intestinal barrier dysfunction as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. We demonstrated earlier that oral supplementation with curcumin attenuates WD-induced development of type 2 diabetes and atherosclerosis. Poor bioavailability of curcumin has precluded the establishment of a causal relationship between oral supplementation and it is in vivo effects. We hypothesized that curcumin attenuates WD-induced chronic inflammation and associated metabolic diseases by modulating the function of intestinal epithelial cells (IECs) and the intestinal barrier function. The objective of the present study was to delineate the underlying mechanisms. The human IEC lines Caco-2 and HT-29 were used for these studies and modulation of direct as well as indirect effects of LPS on intracellular signaling as well as tight junctions were examined. Pretreatment with curcumin significantly attenuated LPS-induced secretion of master cytokine IL-1β from IECs and macrophages. Furthermore, curcumin also reduced IL-1β-induced activation of p38 MAPK in IECs and subsequent increase in expression of myosin light chain kinase involved in the phosphorylation of tight junction proteins and ensuing disruption of their normal arrangement. The major site of action of curcumin is, therefore, likely the IECs and the intestinal barrier, and by reducing intestinal barrier dysfunction, curcumin modulates chronic inflammatory diseases despite poor bioavailability. Copyright © 2017 the American Physiological Society.

Contribution of Secretory Antibodies to Intestinal Mucosal Immunity against Helicobacter pylori

PubMed Central

Wijburg, Odilia L. C.; Pedersen, John S.; Walduck, Anna K.; Kwok, Terry; Strugnell, Richard A.; Robins-Browne, Roy M.

2013-01-01

The natural immune response to Helicobacter pylori neither clears infection nor prevents reinfection. However, the ability of secretory antibodies to influence the course of H. pylori infection has not been determined. We compared the natural progression of H. pylori infection in wild-type C57BL/6 mice with that in mice lacking the polymeric immunoglobulin receptor (pIgR) that is essential for the secretion of polymeric antibody across mucosal surfaces. H. pylori SS1-infected wild-type and pIgR knockout (KO) mice were sampled longitudinally for gastrointestinal bacterial load, antibody response, and histological changes. The gastric bacterial loads of wild-type and pIgR KO mice remained constant and comparable at up to 3 months postinfection (mpi) despite SS1-reactive secretory IgA in the intestinal contents of wild-type mice at that time. Conversely, abundant duodenal colonization of pIgR KO animals contrasted with the near-total eradication of H. pylori from the intestine of wild-type animals by 3 mpi. H. pylori was cultured only from the duodenum of those animals in which colonization in the distal gastric antrum was of sufficient density for immunohistological detection. By 6 mpi, the gastric load of H. pylori in wild-type mice was significantly lower than in pIgR KO animals. While there was no corresponding difference between the two mouse strains in gastric pathology results at 6 mpi, reductions in gastric bacterial load correlated with increased gastric inflammation together with an intestinal secretory antibody response in wild-type mice. Together, these results suggest that naturally produced secretory antibodies can modulate the progress of H. pylori infection, particularly in the duodenum. PMID:23918779

Cdx genes, inflammation, and the pathogenesis of intestinal metaplasia

PubMed Central

Stairs, Doug B.; Kong, Jianping; Lynch, John P.

2018-01-01

Intestinal metaplasia is a biologically interesting and clinically relevant condition in which one differentiated type of epithelium is replaced by another that is morphologically similar to normal intestinal epithelium. Two classic examples of this are gastric intestinal metaplasia and Barrett’s esophagus. In both, a chronic inflammatory microenvironment, provoked either by Helicobacter pylori infection of the stomach or acid and bile reflux into the esophagus, precedes the metaplasia. The Caudal-related homeodomain transcription factors Cdx1 and Cdx2 are critical regulators of the normal intetinal epithelial cell phenotype. Ectopic expression of Cdx1 and Cdx2 occurs in both gastric intestinal metaplasia as well as in Barrett’s esophagus. This expression precedes the onset of the metaplasia and implies a causal role for these factors in this process. We will review the observations regarding the role of chronic inflammation and the Cdx transcription factors in the pathogenesis of gastric intestinal metaplasia and Barrett’s esophagus. PMID:21075347

Tissue damage-induced intestinal stem cell division in Drosophila

PubMed Central

Amcheslavsky, Alla; Jiang, Jin; Ip, Y. Tony

2009-01-01

SUMMARY Stem cell division is essential for tissue integrity during growth, aging, and pathogenic assaults. Adult gastrointestinal tract encounters numerous stimulations and impaired tissue regeneration may lead to inflammatory diseases and cancer. Intestinal stem cells in adult Drosophila have recently been identified and shown to replenish the various cell types within the midgut. However, it is not known whether these intestinal stem cells can respond to environmental challenges. By feeding dextran sulfate sodium and bleomycin to flies and by expressing apoptotic proteins, we show that Drosophila intestinal stem cells can increase the rate of division in response to tissue damage. Moreover, if tissue damage results in epithelial cell loss, the newly formed enteroblasts can differentiate into mature epithelial cells. By using this newly established system of intestinal stem cell proliferation and tissue regeneration, we find that the insulin receptor signaling pathway is required for intestinal stem cell division. PMID:19128792

Morphogenesis and maturation of the embryonic and postnatal intestine.

PubMed

Chin, Alana M; Hill, David R; Aurora, Megan; Spence, Jason R

2017-06-01

The intestine is a vital organ responsible for nutrient absorption, bile and waste excretion, and a major site of host immunity. In order to keep up with daily demands, the intestine has evolved a mechanism to expand the absorptive surface area by undergoing a morphogenetic process to generate finger-like units called villi. These villi house specialized cell types critical for both absorbing nutrients from food, and for protecting the host from commensal and pathogenic microbes present in the adult gut. In this review, we will discuss mechanisms that coordinate intestinal development, growth, and maturation of the small intestine, starting from the formation of the early gut tube, through villus morphogenesis and into early postnatal life when the intestine must adapt to the acquisition of nutrients through food intake, and to interactions with microbes. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Gasdermin D (Gsdmd) is dispensable for mouse intestinal epithelium development.

PubMed

Fujii, Tomoaki; Tamura, Masaru; Tanaka, Shigekazu; Kato, Yoriko; Yamamoto, Hiromi; Mizushina, Youichi; Shiroishi, Toshihiko

2008-08-01

Members of the novel gene family Gasdermin (Gsdm) are exclusively expressed in a highly tissue-specific manner in the epithelium of skin and the gastrointestinal tract. Based on their expression patterns and the phenotype of the Gsdma3 spontaneous mutations, it is inferred that the Gsdm family genes are involved in epithelial cell growth and/or differentiations in different tissues. To investigate possible roles of the Gsdm gene family in the development of intestinal tracts, we generated a Gsdmd mutant mouse, which is a solitary member of the Gsdmd subfamily and which is predominantly expressed in the intestinal tract by means of targeted disruption. In the mutant homozygotes, we found no abnormality of intestinal tract morphology. Moreover, in mutant mice, there was normal differentiation of all constituent cell types of the intestinal epithelium. Thus, this study clearly shows that Gsdmd is not essential for development of mouse intestinal tract or epithelial cell differentiation.

Coincident filarial, intestinal helminth, and mycobacterial infection: helminths fail to influence tuberculin reactivity, but BCG influences hookworm prevalence.

PubMed

Lipner, Ettie M; Gopi, P G; Subramani, R; Kolappan, C; Sadacharam, K; Kumaran, Paul; Prevots, D Rebecca; Narayanan, P R; Nutman, Thomas B; Kumaraswami, V

2006-05-01

The prevalence of helminth and tuberculosis infections is high in South India, whereas Bacille-Calmette-Guerin (BCG) vaccine efficacy is low. Our aim was to determine whether concurrent helminth infection alters the ability to mount a delayed-type hypersensitivity response to tuberculin. In a cross-sectional study in southern India, individuals 6-65 years of age were screened for intestinal helminths, circulating filarial antigenemia, tuberculin reactivity, active tuberculosis, and history of BCG vaccination; 54% were purified protein derivative (PPD) positive, 32% had intestinal helminth infection, 9% were circulating filarial antigen positive, and 0.5% had culture-confirmed active tuberculosis. Only age and BCG vaccination were significantly associated with PPD reactivity; however, BCG vaccination was associated with a lower prevalence of hookworm infection relative to those without prior BCG vaccination. Neither intestinal helminth infection nor filarial infection was associated with diminished frequencies of PPD positivity. Our findings suggest that preceding helminth infection does not influence significantly the delayed-type hypersensitivity response to tuberculin.

The homeodomain transcription factor Cdx1 does not behave as an oncogene in normal mouse intestine.

PubMed

Crissey, Mary Ann S; Guo, Rong-Jun; Fogt, Franz; Li, Hong; Katz, Jonathan P; Silberg, Debra G; Suh, Eun Ran; Lynch, John P

2008-01-01

The Caudal-related homeobox genes Cdx1 and Cdx2 are intestine-specific transcription factors that regulate differentiation of intestinal cell types. Previously, we have shown Cdx1 to be antiproliferative and to promote cell differentiation. However, other studies have suggested that Cdx1 may be an oncogene. To test for oncogenic behavior, we used the murine villin promoter to ectopically express Cdx1 in the small intestinal villi and colonic surface epithelium. No changes in intestinal architecture, cell differentiation, or lineage selection were observed with expression of the transgene. Classic oncogenes enhance proliferation and induce tumors when ectopically expressed. However, the Cdx1 transgene neither altered intestinal proliferation nor induced spontaneous intestinal tumors. In a murine model for colitis-associated cancer, the Cdx1 transgene decreased, rather than increased, the number of adenomas that developed. In the polyps, the expression of the endogenous and the transgenic Cdx1 proteins was largely absent, whereas endogenous Villin expression was retained. This suggests that transgene silencing was specific and not due to a general Villin inactivation. In conclusion, neither the ectopic expression of Cdx1 was associated with changes in intestinal cell proliferation or differentiation nor was there increased intestinal cancer susceptibility. Our results therefore suggest that Cdx1 is not an oncogene in normal intestinal epithelium.

Intestinal parasites of the Pacific.

PubMed

Small, Ethan A; Tice, Alan D; Zheng, Xiaotian

2003-10-01

Information about intestinal parasites in Hawaii and the Pacific is not current. We reviewed reports on fecal samples obtained from two laboratories and found recovery rates of 9.3% in Hawaii, 14.2% in Saipan, 18% in Rota and 9.5% in Guam. The most frequently identified parasites were Blastocystis hominis (7.6%), Giardia lamblia (1.2%), and Entamoeba coli (0.7%). Although the incidence and types of organisms have changed with time, physicians in Hawaii should continue looking for intestinal parasites.

Altered intestinal epithelium-associated lymphocyte repertoires and function in ApcMin/+ mice.

PubMed

Marsh, Lorraine; Coletta, P Louise; Hull, Mark A; Selby, Peter J; Carding, Simon R

2012-01-01

ApcMin/+ mice spontaneously develop multiple intestinal adenomas along the length of the small intestine and colon. Currently little is known about the role of the immune system in regulating intestinal tumorigenesis in these animals. This study characterised small intestinal intraepithelial lympho-- cyte (IEL) populations in C56BL/6J ApcMin/+ mice and wild-type (Apc+/+) mice. We also determined the effect that T cells expressing either γδ or αβ encoded T cell receptors (TcR) exert on intestinal tumorigenesis. ApcMin/+ mice had significantly lower numbers of CD3+ IELs compared with Apc+/+ littermates and displayed reduced cytotoxicity against tumour target cells. Further analysis of IEL cytotoxicity revealed differences in the cytotoxic pathways utilised by IELs in ApcMin/+ and Apc+/+ mice with ApcMin/+ IELs displaying an absence of perforin/granzyme-mediated killing and increased levels of Fas-FasL-mediated cytotoxicity compared with wild-type IELs. Analysis of ApcMin/+ mice crossed with αβ T-cell deficient (TcRβ-/-) or γδ T-cell deficient (TcRδ-/-) mice on the same genetic background revealed decreased tumour multiplicity in the absence of both αβ and γδ T-cells. This study demonstrates that altered T-cell subsets play important roles in promoting tumorigenesis in ApcMin/+ mice and forms the basis for future mechanistic studies.

In Silico Analysis of Usher Encoding Genes in Klebsiella pneumoniae and Characterization of Their Role in Adhesion and Colonization

PubMed Central

Khater, Fida; Balestrino, Damien; Charbonnel, Nicolas; Dufayard, Jean François; Brisse, Sylvain; Forestier, Christiane

2015-01-01

Chaperone/usher (CU) assembly pathway is used by a wide range of Enterobacteriaceae to assemble adhesive surface structures called pili or fimbriae that play a role in bacteria-host cell interactions. In silico analysis revealed that the genome of Klebsiella pneumoniae LM21 harbors eight chromosomal CU loci belonging to γκп and ϭ clusters. Of these, only two correspond to previously described operons, namely type 1 and type 3-encoding operons. Isogenic usher deletion mutants of K. pneumoniae LM21 were constructed for each locus and their role in adhesion to animal (Intestine 407) and plant (Arabidopsis thaliana) cells, biofilm formation and murine intestinal colonization was investigated. Type 3 pili usher deleted mutant was impaired in all assays, whereas type 1 pili usher deleted mutant only showed attenuation in adhesion to plant cells and in intestinal colonization. The LM21ΔkpjC mutant was impaired in its capacity to adhere to Arabidopsis cells and to colonize the murine intestine, either alone or in co-inoculation experiments. Deletion of LM21kpgC induced a significant decrease in biofilm formation, in adhesion to animal cells and in colonization of the mice intestine. The LM21∆kpaC and LM21∆kpeC mutants were only attenuated in biofilm formation and the adhesion abilities to Arabidopsis cells, respectively. No clear in vitro or in vivo effect was observed for LM21∆kpbC and LM21∆kpdC mutants. The multiplicity of CU loci in K. pneumoniae genome and their specific adhesion pattern probably reflect the ability of the bacteria to adhere to different substrates in its diverse ecological niches. PMID:25751658

Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions

PubMed Central

Rashu, Rasheduzzaman; Begum, Yasmin Ara; Ciorba, Matthew A.; Hultgren, Scott J.; Qadri, Firdausi

2017-01-01

Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host. Among genes significantly upregulated on cell contact are those encoding type 1 pili. We therefore investigated the role played by these pili in facilitating ETEC adhesion, and toxin delivery to model intestinal epithelia. We demonstrate that type 1 pili, encoded in the E. coli core genome, play an essential role in ETEC virulence, acting in concert with plasmid-encoded pathovar specific colonization factor (CF) fimbriae to promote optimal bacterial adhesion to cultured intestinal epithelium (CIE) and to epithelial monolayers differentiated from human small intestinal stem cells. Type 1 pili are tipped with the FimH adhesin which recognizes mannose with stereochemical specificity. Thus, enhanced production of highly mannosylated proteins on intestinal epithelia promoted FimH-mediated ETEC adhesion, while conversely, interruption of FimH lectin-epithelial interactions with soluble mannose, anti-FimH antibodies or mutagenesis of fimH effectively blocked ETEC adhesion. Moreover, fimH mutants were significantly impaired in delivery of both heat-stable and heat-labile toxins to the target epithelial cells in vitro, and these mutants were substantially less virulent in rabbit ileal loop assays, a classical model of ETEC pathogenesis. Collectively, our data suggest that these highly conserved pili play an essential role in virulence of these diverse pathogens. PMID:28531220

Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist

PubMed Central

Spaulding, Caitlin N.; Klein, Roger D.; Ruer, Ségolène; Kau, Andrew L.; Schreiber, Henry L.; Cusumano, Zachary T.; Dodson, Karen W.; Pinkner, Jerome S.; Fremont, Daved H.; Janetka, James W.; Remaut, Han; Gordon, Jeffrey I.; Hultgren, Scott J.

2017-01-01

Summary Urinary tract infections (UTI) caused by uropathogenic E. coli (UPEC) affect 150 million people annually1,2. Despite effective antibiotic therapy, 30–50% of patients experience recurrent UTI (rUTI)1. Additionally, the growing prevelance of UPEC resistant to last-line antibiotic treatments, and more recently carbapenems and colistin, make UTIs a prime example of the antibiotic-resistance crisis and emphasize the need for new approaches to treat and prevent bacterial infections3–5. UPEC strains establish reservoirs in the gut from which they are shed in the feces, can colonize the peri-urethral area or vagina and subsequently ascend through the urethra to the urinary tract, where they cause UTI6. UPEC isolates encode up to 16 distinct chaperone-usher pathway (CUP) pili and each pilus type likely enables colonization of a habitat in the host or environment7. For example, the type 1 pilus adhesin, FimH, binds mannose on the bladder surface, mediating bladder colonization. However, little is known regarding the mechanisms underlying UPEC persistence in the gut5. Using a mouse model, we found that F17-like and type 1 pili promote intestinal colonization and show distinct binding to epithelial cells distributed along colonic crypts. Phylogenomic and structural analyses reveal that F17-like pili are closely related to pilus types carried by intestinal pathogens, but are restricted to extra-intestinal pathogenic E. coli. Moreover, we show that targeting FimH with a high-affinity inhibitor, mannoside M4284, reduces intestinal colonization of genetically diverse UPEC isolates, while simultaneously treating UTI, without significantly disrupting the the structural configuration of the gut microbiota. By selectively depleting the intestinal UPEC reservoir, mannosides could significantly reduce the rate of UTI and rUTI. PMID:28614296

IKKε and TBK1 expression in gastric cancer.

PubMed

Lee, Seung Eun; Hong, Mineui; Cho, Junhun; Lee, Jeeyun; Kim, Kyoung-Mee

2017-03-07

Inhibitor of kappa B kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IKKs. IKKε and TBK1 share the kinase domain and are similar in their ability to activate the nuclear factor-kappa B signaling pathway. IKKε and TBK1 are overexpressed through multiple mechanisms in various human cancers. However, the expression of IKKε and TBK1 in gastric cancer and their role in prognosis have not been studied.To investigate overexpression of the IKKε and TBK1 proteins in gastric cancer and their relationship with clinicopathologic factors, we performed immunohistochemical staining using a tissue microarray. Tissue microarray samples were obtained from 1,107 gastric cancer patients who underwent R0 gastrectomy with extensive lymph node dissection and adjuvant chemotherapy.We identified expression of IKKε in 150 (13.6%) and TBK1 in 38 (3.4%) gastric cancers. Furthermore, co-expression of IKKε and TBK1 was identified in 1.5% of cases. Co-expression of IKKε and TBK1 was associated with differentiated intestinal histology and earlier T stage. In a multivariate binary logistic regression model, intestinal histologic type by Lauren classification and early AJCC stage were significant predictors for expression of IKKε and TBK1 proteins in gastric cancer. Changes in IKKε and TBK1 expression may be involved in the development of intestinal-type gastric cancer. The overexpression of IKKε and TBK1 should be considered in selected patients with intestinal-type gastric cancer.In conclusion, this is the first large-scale study investigating the relationships between expression of IKKε and TBK1 and clinicopathologic features of gastric cancer. The role of IKKε and TBK1 in intestinal-type gastric cancer pathogenesis should be elucidated by further investigation.

Comparative Metagenomics Revealed Commonly Enriched Gene Sets in Human Gut Microbiomes

PubMed Central

Kurokawa, Ken; Itoh, Takehiko; Kuwahara, Tomomi; Oshima, Kenshiro; Toh, Hidehiro; Toyoda, Atsushi; Takami, Hideto; Morita, Hidetoshi; Sharma, Vineet K.; Srivastava, Tulika P.; Taylor, Todd D.; Noguchi, Hideki; Mori, Hiroshi; Ogura, Yoshitoshi; Ehrlich, Dusko S.; Itoh, Kikuji; Takagi, Toshihisa; Sakaki, Yoshiyuki; Hayashi, Tetsuya; Hattori, Masahira

2007-01-01

Numerous microbes inhabit the human intestine, many of which are uncharacterized or uncultivable. They form a complex microbial community that deeply affects human physiology. To identify the genomic features common to all human gut microbiomes as well as those variable among them, we performed a large-scale comparative metagenomic analysis of fecal samples from 13 healthy individuals of various ages, including unweaned infants. We found that, while the gut microbiota from unweaned infants were simple and showed a high inter-individual variation in taxonomic and gene composition, those from adults and weaned children were more complex but showed a high functional uniformity regardless of age or sex. In searching for the genes over-represented in gut microbiomes, we identified 237 gene families commonly enriched in adult-type and 136 families in infant-type microbiomes, with a small overlap. An analysis of their predicted functions revealed various strategies employed by each type of microbiota to adapt to its intestinal environment, suggesting that these gene sets encode the core functions of adult and infant-type gut microbiota. By analysing the orphan genes, 647 new gene families were identified to be exclusively present in human intestinal microbiomes. In addition, we discovered a conjugative transposon family explosively amplified in human gut microbiomes, which strongly suggests that the intestine is a ‘hot spot’ for horizontal gene transfer between microbes. PMID:17916580

Interrelationship between TP53 gene deletion, protein expression and chromosome 17 aneusomy in gastric adenocarcinoma

PubMed Central

2009-01-01

Background This study evaluates the existence of numerical alterations of chromosome 17 and TP53 gene deletion in gastric adenocarcinoma. The p53 protein expression was also evaluated, as well as, possible associations with clinicopathological characteristics. Methods Dual-color fluorescence in situ hybridization and immunostaining were performed in twenty gastric cancer samples of individuals from Northern Brazil. Results Deletion of TP53 was found in all samples. TP53 was inactivated mainly by single allelic deletion, varying to 7–39% of cells/case. Aneusomy of chromosome 17 was observed in 85% of cases. Chromosome 17 monosomy and gain were both observed in about half of cases. Cells with gain of chromosome 17 frequently presented TP53 deletion. The frequency of cells with two chr17 and one TP53 signals observed was higher in diffuse than in intestinal-type GC. Immunoreactivity of p53 was found only in intestinal-type samples. The frequency of cells with two chr17 and two TP53 signals found was higher in samples with positive p53 expression than in negative cases in intestinal-type GC. Conclusion We suggest that TP53 deletion and chromosome 17 aneusomy is a common event in GC and other TP53 alterations, as mutation, may be implicated in the distinct carcinogenesis process of diffuse and intestinal types. PMID:19619279

Modeling and Experimental Studies of Obeticholic Acid Exposure and the Impact of Cirrhosis Stage

PubMed Central

LaCerte, C; Peyret, T; Gosselin, NH; Marier, JF; Hofmann, AF; Shapiro, D

2016-01-01

Obeticholic acid (OCA), a semisynthetic bile acid, is a selective and potent farnesoid X receptor (FXR) agonist in development for the treatment of chronic nonviral liver diseases. Physiologic pharmacokinetic models have been previously used to describe the absorption, distribution, metabolism, and excretion (ADME) of bile acids. OCA plasma levels were measured in healthy volunteers and cirrhotic subjects. A physiologic pharmacokinetic model was developed to quantitatively describe the ADME of OCA in patients with and without hepatic impairment. There was good agreement between predicted and observed increases in systemic OCA exposure in subjects with mild, moderate, and severe hepatic impairment, which were 1.4‐, 8‐, and 13‐fold relative to healthy volunteers. Predicted liver exposure for subjects with mild, moderate, and severe hepatic impairment were increased only 1.1‐, 1.5‐, and 1.7‐fold. In subjects with cirrhosis, OCA exposure in the liver, the primary site of pharmacological activity along with the intestine, is increased marginally (∼2‐fold). PMID:27743502

Hypothyroxinemia induced by mild iodine deficiency deregulats thyroid proteins during gestation and lactation in dams.

PubMed

Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

2013-08-02

The main object of the present study was to explore the effect on thyroidal proteins following mild iodine deficiency (ID)-induced maternal hypothyroxinemia during pregnancy and lactation. In the present study, we established a maternal hypothyroxinemia model in female Wistar rats by using a mild ID diet. Maternal thyroid iodine content and thyroid weight were measured. Expressions of thyroid-associated proteins were analyzed. The results showed that the mild ID diet increased thyroid weight, decreased thyroid iodine content and increased expressions of thyroid transcription factor 1, paired box gene 8 and Na+/I- symporter on gestational day (GD) 19 and postpartum days (PN) 21 in the maternal thyroid. Moreover, the up-regulated expressions of type 1 iodothyronine deiodinase (DIO1) and type 2 iodothyronine deiodinase (DIO2) were detected in the mild ID group on GD19 and PN21. Taken together, our data indicates that during pregnancy and lactation, a maternal mild ID could induce hypothyroxinemia and increase the thyroidal DIO1 and DIO2 levels.

Cytomegalovirus-induced colonic stricture presenting as acute intestinal obstruction in an immunocompetent adult.

PubMed

Dinesh, B V; Selvaraju, Karthikeyan; Kumar, Sampath; Thota, Sumath

2013-09-10

Cytomegalovirus (CMV) infection causes significant morbidty and mortality in immunopromised patients. Though it is usually silent in immunocompetent adults, rarely it can cause serious life-threatening complications. Gastrointestinal tract is one of the commonly involved organs, where it produces a spectrum of clinical manifestation ranging from mild non-specific abdominal pain and diarrhoea to severe infection with toxic megacolon and death. We present a 65-year-old immunocompetent male patient admitted with acute colonic obstruction secondary to CMV-induced colonic stricture, highlighting the importance of considering it as a differential diagnosis for colonic obstruction and reviewing its management.

[Clinical-pathogenetic features of meningococcal infection in children].

PubMed

Buriak, V N; Serhyenko, A S

2011-01-01

Analysis features of clinical manifestation and pathogenetic mechanisms of development of meningococcal infection is introduced. It is emphasized that in most cases mentioned infection is characterized by mild course as nasopharyngitidis. However relatively seldom developing generalize form put this phatology on third place after intestinal infections and septicemia in structure of child mortality from infection deseases. Occurence of generalize forms of meningococcal infection depend on peculiarity of immune response is followed by release of endotoxin and exotoxin in blood stream. This toxins start up pathogenetic mechanisms, which lead to toxic shock, adrenal glands hemorrhage, brain edema, brain stem wedge in big occipital foramen.

Autoimmunity and Gastric Cancer

PubMed Central

Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo

2018-01-01

Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

Fibrinogen deficiency suppresses the development of early and delayed radiation enteropathy

PubMed Central

Wang, Junru; Pathak, Rupak; Garg, Sarita; Hauer-Jensen, Martin

2017-01-01

AIM To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy. METHODS Fibrinogen wild-type (Fib+/+), fibrinogen heterozygous (Fib+/-), and fibrinogen knockout (Fib-/-) mice were exposed to localized intestinal irradiation and assessed for early and delayed structural changes in the intestinal tissue. A 5-cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x-irradiation. Intestinal tissue injury was assessed by quantitative histology, morphometry, and immunohistochemistry at 2 wk and 26 wk after radiation. Plasma fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTS There was no difference between sham-irradiated Fib+/+ and Fib+/- mice in terms of fibrinogen concentration in plasma and intestinal tissue, intestinal histology, morphometry, intestinal smooth muscle cell proliferation, and neutrophil infiltration. Therefore, Fib+/- mice were used as littermate controls. Unlike sham-irradiated Fib+/+ and Fib+/- mice, no fibrinogen was detected in the plasma and intestinal tissue of sham-irradiated Fib-/- mice. Moreover, fibrinogen level was not elevated after irradiation in the intestinal tissue of Fib-/- mice, while significant increase in intestinal fibrinogen level was noticed in irradiated Fib+/+ and Fib+/- mice. Importantly, irradiated Fib-/- mice exhibited substantially less overall intestinal structural injury (RIS, P = 0.000002), intestinal wall thickness (P = 0.003), intestinal serosal thickness (P = 0.009), collagen deposition (P = 0.01), TGF-β immunoreactivity (P = 0.03), intestinal smooth muscle proliferation (P = 0.046), neutrophil infiltration (P = 0.01), and intestinal mucosal injury (P = 0.0003), compared to irradiated Fib+/+ and Fib+/- mice at both 2 wk and 26 wk. CONCLUSION These data demonstrate that fibrinogen deficiency directly attenuates development of early and delayed radiation enteropathy. Fibrinogen could be a novel target in treating intestinal damage. PMID:28765691

High rates of intestinal bicarbonate secretion in seawater tilapia (Oreochromis mossambicus).

PubMed

Ruiz-Jarabo, I; Gregório, S F; Gaetano, P; Trischitta, F; Fuentes, J

2017-05-01

Osmoregulation in fish is a complex process that requires the orchestrated cooperation of many tissues. In fish facing hyperosmotic environments, the intestinal absorption of some monovalent ions and the secretion of bicarbonate are key processes to favor water absorption. In the present study, we showed that bicarbonate levels in the intestinal fluid are several fold higher in seawater than in freshwater acclimated tilapia (Oreochromis mossambicus). In addition, we analyzed gene expression of the main molecular mechanisms involved in HCO 3 - movements i.e. slc26a6, slc26a3, slc4a4 and v-type H-ATPase sub C in the intestine of tilapia acclimated to both seawater and freshwater. Our results show an anterior/posterior functional regionalization of the intestine in tilapia in terms of expression patterns, which is affected by environmental salinity mostly in the anterior and mid intestine. Analysis of bicarbonate secretion using pH-Stat in tissues mounted in Ussing chambers reveals high rates of bicarbonate secretion in tilapia acclimated to seawater from anterior intestine to rectum ranging between ~900 and ~1700nmolHCO 3 - cm -2 h -1 . However, a relationship between the expression of slc26a6, slc26a3, slc4a4 and the rate of bicarbonate secretion seems to be compromised in the rectum. In this region, the low expression of the bicarbonate transporters could not explain the high bicarbonate secretion rates here described. However, we postulate that the elevated v-type H-ATPase mRNA expression in the rectum could be involved in this process. Copyright © 2017 Elsevier Inc. All rights reserved.

[Advance in studies on food allergy mechanism based on gut barrier].

PubMed

Wang, Juan-hong; Li, Huan-zhou; Li, Meng; Pan, Su-hua

2015-04-01

Food allergies, as a type of adverse immune-mediated reactions to ingested food proteins, have become a serious public health issue that harms children and adults health, with increasing incidence year by year. However, without effective therapy for food allergies, doctors-have mostly advised to avoid allergens and provided symptomatic treatment. According to the findings of many studies, allergic diseases are correlated with intestinal barrier function injury, as evidenced by the significant increase in the intestinal permeability among patients with food allergies. In this paper, recent studies on correlations between food allergies and intestinal barrier functions, intestinal barrier function injury mechanisms of allergic foods and food allergy intervention strategies based on intestinal barrier functions were summarized to provide reference for laboratory researches and clinical treatment of food allergic diseases.

Impaired small-bowel barrier integrity in the presence of lumenal pancreatic digestive enzymes leads to circulatory shock.

PubMed

Kistler, Erik B; Alsaigh, Tom; Chang, Marisol; Schmid-Schönbein, Geert W

2012-08-01

In bowel ischemia, impaired mucosal integrity may allow intestinal pancreatic enzyme products to become systemic and precipitate irreversible shock and death. This can be attenuated by pancreatic enzyme inhibition in the small-bowel lumen. It is unresolved, however, whether ischemically mediated mucosal disruption is the key event allowing pancreatic enzyme products systemic access and whether intestinal digestive enzyme activity in concert with increased mucosal permeability leads to shock in the absence of ischemia. To test this possibility, the small intestinal lumen of nonischemic rats was perfused for 2 h with either digestive enzymes, a mucin disruption strategy (i.e., mucolytics) designed to increase mucosal permeability, or both, and animals were observed for shock. Digestive enzymes perfused included trypsin, chymotrypsin, elastase, amylase, and lipase. Control (n = 6) and experimental animals perfused with pancreatic enzymes only (n = 6) or single enzymes (n = 3 for each of the five enzyme groups) maintained stable hemodynamics. After mucin disruption using a combination of enteral N-acetylcysteine, atropine, and increased flow rates, rats (n = 6) developed mild hypotension (P < 0.001 compared with groups perfused with pancreatic enzymes only after 90 min) and increased intestinal permeability to intralumenally perfused fluorescein isothiocyanate-dextran 20 kd (P < 0.05) compared with control and enzyme-only groups, but there were no deaths. All animals perfused with both digestive enzymes and subjected to mucin disruption (n = 6) developed hypotension and increased intestinal permeability (P < 0.001 after 90 min). Pancreatic enzymes were measured in the intestinal wall of both groups subjected to mucin disruption, but not in the enzyme-only or control groups. Depletion of plasma protease inhibitors was found only in animals perfused with pancreatic enzymes plus mucin disruption, implicating increased permeability and intralumenal pancreatic enzyme egress in this group. These experiments demonstrate that increased bowel permeability via mucin disruption in the presence of pancreatic enzymes can induce shock and increase systemic protease activation in the absence of ischemia, implicating bowel mucin disruption as a key event in early ischemia. Digestive enzymes and their products, if allowed to penetrate the gut wall, may trigger multiorgan failure and death.

IMPAIRED SMALL BOWEL BARRIER INTEGRITY IN THE PRESENCE OF LUMENAL PANCREATIC DIGESTIVE ENZYMES LEADS TO CIRCULATORY SHOCK

PubMed Central

Kistler, Erik B.; Alsaigh, Tom; Chang, Marisol; Schmid-Schönbein, Geert W.

2012-01-01

In bowel ischemia, impaired mucosal integrity may allow intestinal pancreatic enzyme products to become systemic and precipitate irreversible shock and death. This can be attenuated by pancreatic enzyme inhibition in the small bowel lumen. It is unresolved, however, whether ischemically-mediated mucosal disruption is the key event allowing pancreatic enzyme products systemic access, and whether intestinal digestive enzyme activity in concert with increased mucosal permeability leads to shock in the absence of ischemia. To test this possibility, the small intestinal lumen of non-ischemic rats was perfused for two hours with either digestive enzymes, a mucin disruption strategy (i.e., mucolytics) designed to increase mucosal permeability, or both, and animals were observed for shock. Digestive enzymes perfused included trypsin, chymotrypsin, elastase, amylase and lipase. Control (n=6) and experimental animals perfused with pancreatic enzymes only (n=6) or single enzymes (n=3 for each of the five enzyme groups) maintained stable hemodynamics. After mucin disruption using a combination of enteral N-acetylcysteine, atropine, and increased flow rates, rats (n=6) developed mild hypotension (p<0.001 compared to groups perfused with pancreatic enzymes only after 90 minutes) and increased intestinal permeability to intralumenally perfused FITC-dextrans-20kD (p<0.05) compared to control and enzyme-only groups, but there were no deaths. All animals perfused with both digestive enzymes and subjected to mucin disruption (n=6) developed hypotension and increased intestinal permeability (p<0.001 after 90 minutes). Pancreatic enzymes were measured in the intestinal wall of both groups subjected to mucin disruption, but not in the enzyme-only or control groups. Depletion of plasma protease inhibitors was found only in animals perfused with pancreatic enzymes plus mucin disruption, implicating increased permeability and intralumenal pancreatic enzyme egress in this group. These experiments demonstrate that increased bowel permeability via mucin disruption in the presence of pancreatic enzymes can induce shock and increase systemic protease activation in the absence of ischemia, implicating bowel mucin disruption as a key event in early ischemia. Digestive enzymes and their products, if allowed to penetrate the gut wall may trigger multiorgan failure and death. PMID:22576000

Optimum Timing for Surgery After Pre-operative Radiotherapy 6 vs 12 Weeks

ClinicalTrials.gov

2015-06-22

Adenocarcinoma of the Rectum; Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Contribution of H. pylori and smoking trends to US incidence of intestinal-type noncardia gastric adenocarcinoma: a microsimulation model.

PubMed

Yeh, Jennifer M; Hur, Chin; Schrag, Deb; Kuntz, Karen M; Ezzati, Majid; Stout, Natasha; Ward, Zachary; Goldie, Sue J

2013-01-01

Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence. We developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS). Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%-58%) of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%-21%). With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%-100%). Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men. Trends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be realized, and further discouragement of smoking and reduction of H. pylori should be priorities for gastric cancer control efforts.

Intestinal metaplasia with a high salt diet induces epithelial proliferation and alters cell composition in the gastric mucosa of mice.

PubMed

Xiao, Fang; Crissey, Mary Ann S; Lynch, John P; Kaestner, Klaus H; Silberg, Debra G; Suh, Eunran

2005-06-01

Intestinal metaplasia of the gastric mucosa is an important component in the pathway to adenocarcinoma. The mechanisms that induce the progression from intestinal metaplasia to cancer have not been elucidated. High dietary salt has been known as one of the risk factors for gastric cancer development in humans. Therefore, we investigated the role of high salt diet on gastric epithelial cell proliferation and differentiation, using our mouse model that ectopically expressed Cdx2 homeodomain transcription factor and induced an intestinal metaplastic phenotype in the gastric epithelia. Sixty Cdx2 transgenic and sixty age-matched wild-type littermates were studied. Fifty-percent Cdx2 transgenic and wild type mice were administered a high-salt diet and the other fifty-percent was fed a standard diet starting at 12 weeks after birth. At 10, 20 and 40 weeks after initiation of the diets, histopathological changes were determined by Hemotoxylin and Eosin, alcian blue, and periodic acid-Schiff (PAS) staining. Cell types and cell kinetics were assessed by immunohistochemistry. At 52 weeks, significant alterations in pathology were observed in the Cdx2 transgenic mice fed a high-salt diet, including elongation of gastric pits, reduction of the glandular zone in the gastric corpus, and deepening of glands in the antrum. In the Cdx2 transgenic mice fed a high salt diet, the parietal and chief cells were significantly decreased in the gastric corpus. A significant increase in cell proliferation and apoptosis in the corpus and antrum were observed in Cdx2 transgenic mice fed a high-salt diet as compared to wild-type littermates. Taken together, these data implicate that intestinal metaplasia in concert with a high-salt diet induces epithelial proliferation, apoptosis, and alters cellular types in the gastric mucosa of mice. Alteration in the composition of the gastric epithelium may play a role in influencing the microenvironment to engender susceptibility to carcinogens.

Investigation of auranofin-induced diarrhoea.

PubMed Central

Behrens, R; Devereaux, M; Hazleman, B; Szaz, K; Calvin, J; Neale, G

1986-01-01

Gastrointestinal function was assessed in six patients with rheumatoid arthritis who had developed diarrhoea on treatment with Auranofin. With the administration of Auranofin whole gut transit time decreased markedly (to 50% or less of control values) in five of six patients. The speed of passage of intestinal contents through the colon was certainly increased but attempts to assess transit through the upper gastrointestinal tract failed because the breath hydrogen method gave inconclusive results. There was no evidence of colitis and in all cases biopsy of the rectal mucosa appeared normal by light microscopy. In the five patients with rapid intestinal transit faecal weight increased more than two-fold (range +44 to +335%) although in only three cases were the changes sufficient to cause an increased frequency of bowel action. Overall the concentration of sodium in faecal water increased three-fold (mean values rose from 10.6 to 38.3 mmol/l). There were no significant changes in the concentrations of either potassium or chloride but bicarbonate was reduced. Faecal pH fell from a mean value of 7.5 (range 6.8-7.9) to a mean value of 6.4 (range 6.0-7.4). In the three patients who developed overt diarrhoea and in two others taking Auranofin the intestinal uptake of 51Cr-EDTA was increased on average three-fold and there was a similar change in the ratio of the absorption of lactulose/mannitol. The mean clearance of alpha-1-antitrypsin from the circulation into the gastrointestinal tract was doubled. These data indicate an increase in intestinal permeability. In contrast the absorption of vitamin B12 was unaffected and there was no significant change in the excretion of faecal fat although one patient developed mild steatorrhoea. Thus in a selected group of subjects with rheumatoid arthritis the administration of Auranofin caused diarrhoea in association with a reversible defect in intestinal permeability but without significant change in the absorption of nutrients. PMID:3081411

Alpha-galactosidase versus active charcoal for improving sonographic visualization of abdominal organs in patients with excessive intestinal gas

PubMed Central

Maconi, G.; Bolzacchini, E.; Radice, E.; Marzocchi, M.; Badini, M.

2012-01-01

Background and aims Intestinal gas is a frequent cause of poor visualization during gastrointestinal ultrasound (US). The enzyme alpha-galactosidase may reduce intestinal gas production, thereby improving abdominal US visualization. We compared the efficacies of alpha-galactosidase and active charcoal in improving US visualization in patients with previous unsatisfactory abdominal US scans caused by excessive intestinal gas. Materials and methods: 45 patients with poor visualization of at least one target organ: pancreas, hepatic lobes (score 0–2) or common bile duct (CBD) (score 0–1) were enrolled in a prospective randomized, crossover, observer-blinded study. The patients received alpha-galactosidase (Sinaire Forte, Promefarm, Milan, Italy) 600 GalU t.i.d. for 2 days before abdominal US plus 900 GalU the morning of exam or active charcoal 448 mg t.i.d., for 2 days before the exam plus 672 mg the morning of the exam. Visualization was graded as follows: 0 = none (complete gas interference); 1 = severe interference, 2 = moderate interference, 3 = mild interference; 4 = complete (no gas interference). Results: 42 patients completed the study. Both alpha-galactosidase and active charcoal improved the visualization of target organs. Visualization of the right hepatic lobe, CBD and pancreatic tail was significantly improved (vs. baseline) only by alpha-galactosidase (p < 0.01). Scores ≥3 for all parts of the pancreas and both hepatic lobes were achieved in only 12.5% of the patients after both treatments. Both products were well tolerated. Conclusion: Alpha-galactosidase and active charcoal can improve US visualization of abdominal organs in patients whose scans are frequently unsatisfactory due to excessive intestinal gas. Visualization of the pancreatic tail and right hepatic lobe was significantly improved only by alpha-galactosidase. However, both treatments allowed adequate visualization of all target organs during the same examination only in a few patients. PMID:23730387

New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering

PubMed Central

Shirafkan, Ali; Montalbano, Mauro; McGuire, Joshua; Rastellini, Cristiana; Cicalese, Luca

2016-01-01

Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic scaffold to generate a neo-formed intestinal tissue that showed, for the first time, evidence of absorption in vivo. In the large intestine, studies are more focused on regeneration and engineering of sphincters and will be briefly reviewed. From the review of the existing literature, it can be concluded that significant progress has been achieved in these experimental methods but that these now need to be fully translated into a pre-clinical and clinical experimentation to become a future viable therapeutic option. PMID:27011901

Meeting the support needs of persons with mild intellectual disability or borderline intellectual functioning: still a long way to go.

PubMed

Nouwens, P J G; Smulders, N B M; Embregts, P J C M; van Nieuwenhuizen, C

2017-12-01

Among persons with a mild intellectual disability or borderline intellectual functioning, differences in their characteristics imply that a differentiated approach is required to meet their needs. This retrospective study examined whether the history of support/treatment programs and the type of healthcare providers involved matched the specific support needs of persons with a mild intellectual disability or borderline intellectual functioning. Five (previously identified) profiles of persons with a mild intellectual disability or borderline intellectual functioning were used to investigate to what extent the support needs of this group had been met. For the 250 persons with mild intellectual disability or borderline intellectual functioning who matched these five profiles, data were collected retrospectively from their case files. Persons with mild intellectual disability or borderline intellectual functioning received a very similar amount and type of support/treatment programs. Differences between the profiles were found for non-verbal therapy, residential treatment and contacts with social work. Regarding the type of healthcare providers involved, differences between the profiles emerged for specialised intellectual disability services, youth services and specialised addiction services. The support programs for a heterogeneous population of persons with mild intellectual disability or borderline intellectual functioning seem to be suboptimal, indicating that more differentiation is required in the services offered to these individuals. © 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

A case of mild phenotype Alport syndrome caused by COL4A3 mutations.

PubMed

Kamijo, Masafumi; Kitamura, Mineaki; Muta, Kumiko; Uramatsu, Tadashi; Obata, Yoko; Nozu, Kandai; Kaito, Hiroshi; Iijima, Kazumoto; Mukae, Hiroshi; Nishino, Tomoya

2017-11-01

In a case of 41-year-old man with mild nephropathy, Alport syndrome (AS) was diagnosed from the renal biopsy. However, the α5 chain of type IV collagen expressed in the glomerular basement membrane, which was the atypical staining pattern of AS. Genetic testing suggested autosomal recessive AS from heterozygous mutations at two positions in the type IV collagen α3 chain. These two gene mutations represented a new pattern of mutation and was suggested the association with an atypical α5 chain expression and mild phenotype.

Severe changes in colon epithelium in the Mecp2-null mouse model of Rett syndrome.

PubMed

Millar-Büchner, Pamela; Philp, Amber R; Gutierrez, Noemí; Villanueva, Sandra; Kerr, Bredford; Flores, Carlos A

2016-12-01

Rett syndrome is best known due to its severe and devastating symptoms in the central nervous system. It is produced by mutations affecting the Mecp2 gene that codes for a transcription factor. Nevertheless, evidence for MECP2 activity has been reported for tissues other than those of the central nervous system. Patients affected by Rett presented with intestinal affections whose origin is still not known. We have observed that the Mecp2-null mice presented with episodes of diarrhea, and decided to study the intestinal phenotype in these mice. Mecp2-null mice or bearing the conditional intestinal deletion of MECP2 were used. Morphometirc and histologic analysis of intestine, and RT-PCR, western blot and immunodetection were perfomed on intestinal samples of the animals. Electrical parameters of the intestine were determined by Ussing chamber experiments in freshly isolated colon samples. First we determined that MECP2 protein is mainly expressed in cells of the lower part of the colonic crypts and not in the small intestine. The colon of the Mecp2-null mice was shorter than that of the wild-type. Histological analysis showed that epithelial cells of the surface have abnormal localization of key membrane proteins like ClC-2 and NHE-3 that participate in the electroneutral NaCl absorption; nevertheless, electrogenic secretion and absorption remain unaltered. We also detected an increase in a proliferation marker in the crypts of the colon samples of the Mecp2-null mice, but the specific silencing of Mecp2 from intestinal epithelium was not able to recapitulate the intestinal phenotype of the Mecp2-null mice. In summary, we showed that the colon is severely affected by Mecp2 silencing in mice. Changes in colon length and epithelial histology are similar to those observed in colitis. Changes in the localization of proteins that participate in fluid absorption can explain watery stools, but the exclusive deletion of Mecp2 from the intestine did not reproduce colon changes observed in the Mecp2-null mice, indicating the participation of other cells in this phenotype and the complex interaction between different cell types in this disease.

Chemical Composition and Immuno-Modulatory Effects of Urtica dioica L. (Stinging Nettle) Extracts.

PubMed

Francišković, Marina; Gonzalez-Pérez, Raquel; Orčić, Dejan; Sánchez de Medina, Fermín; Martínez-Augustin, Olga; Svirčev, Emilija; Simin, Nataša; Mimica-Dukić, Neda

2017-08-01

The purpose of this work was to determine the chemical profile of stinging nettle and to provide an insight into the mechanisms by which it ameliorates the immune response. Qualitative and quantitative liquid chromatography tandem mass spectrometry analyses indicated that phenolic acids (5-O-caffeoylquinic acid as dominant) and flavonol glycosides (rutin, isoquercitrin, and kaempferol 3-O-glucoside) are present in the aerial parts, while lignans (secoisolariciresinol, 9,9'-bisacetyl-neo-olivil and their glucosides) were detected in the root. Herb and root extracts expressed selective inhibition toward cyclooxygenase and lipoxygenase branches in human platelets: root extracts were better at inhibiting thromboxane production, while herb extracts were more specific toward inhibition of 12-lipoxygenase pathway. Stinging nettle extracts mildly increased monocyte chemoattractant protein-1 and growth-related oncogene release from nonstimulated intestinal epithelial cells, stimulating MyD88/NF-κB/p38 signaling, hence preserving the epithelial integrity and enhancing intestinal steady-state defense. Additionally, root extract reduced lipopolysaccharide-induced monocyte chemoattractant protein-1/growth-related oncogene secretion and cyclooxygenase-2 expression in intestinal epithelial cells, thus showing the potential protective effect against tissue damage caused by inflammation processes. These observations suggest that stinging nettle is an interesting candidate for the development of phytopharmaceuticals or dietary supplements for cotreatment of various inflammatory diseases, particularly inflammatory bowel diseases. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial

ClinicalTrials.gov

2017-03-08

Adenocarcinoma; Rectal Diseases; Colorectal Neoplasms; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases

Obturator Hernia: A Rare Case of Acute Mechanical Intestinal Obstruction

PubMed Central

Yucel, Ahmet Fikret; Pergel, Ahmet; Sahin, Dursun Ali

2013-01-01

Obturator hernia is a rare type of pelvic hernia which generally occurs in elderly patients with accompanying diseases. Because it is difficult to diagnose before surgery, the morbidity and mortality rates for obturator hernia are high. The most common symptom is strangulation combined with mechanical intestinal obstruction. PMID:23738179

Obturator hernia: a rare case of acute mechanical intestinal obstruction.

PubMed

Aydin, Ibrahim; Yucel, Ahmet Fikret; Pergel, Ahmet; Sahin, Dursun Ali

2013-01-01

Obturator hernia is a rare type of pelvic hernia which generally occurs in elderly patients with accompanying diseases. Because it is difficult to diagnose before surgery, the morbidity and mortality rates for obturator hernia are high. The most common symptom is strangulation combined with mechanical intestinal obstruction.

Complete Genome Sequences of Lactobacillus johnsonii Strain N6.2 and Lactobacillus reuteri Strain TD1.

PubMed

Leonard, Michael T; Valladares, Ricardo B; Ardissone, Alexandria; Gonzalez, Claudio F; Lorca, Graciela L; Triplett, Eric W

2014-05-08

We report here the complete genome sequences of Lactobacillus johnsonii strain N6.2, a homofermentative lactic acid intestinal bacterium, and Lactobacillus reuteri strain TD1, a heterofermentative lactic acid intestinal bacterium, both isolated from a type 1 diabetes-resistant rat model.

Synthesis of fluorophore encapsulated silica nanoparticles for the evaluation of the biological fate and toxicity of food relevant nanoparticles

NASA Astrophysics Data System (ADS)

Zane, Andrew Paul

We show that commercially available TiO2, SiO2, and ZnO nanoparticles are all internalized by C2BBe1 intestinal epithelial cells, but do not appear to be toxic, even after long term repeat-exposures. When particles were exposed to a simulated digestion protocol mimicking the stomach and intestinal environment, TiO2 particles did show mild toxicity by MTT assay, indicating a decrease in metabolic activity. IR spectra of these particles indicate presence of material from the digestion media, and these absorbed species may be responsible for the effects noted. Though the three particles were not significantly toxic, we note internalization by the intestinal epithelial cells, opening a possibility for absorption into circulation where they may localize in organs throughout the body. This will be observed by functionalizing the particles with fluorophores, after which they can be measured via fluorescence. To optimize the quantum yield efficiency, and thus the brightness, of one such fluorophore, we seek to improve a microwave synthesis of CdSe/CdS/ZnS quantum dots our lab has previously reported. By coupling the microwave reactor to a fluorescence spectrometer via fiber optic cables, we were able to monitor the development of the particles throughout the microwave heating. Time-dependent fluorescence shows the development of an early fluorescence peak at 502 nm attributed to CdSe cores. We then note two isosbestic points which we attribute to the development of CdS layer around CdSe cores, and eventually the formation of outer ZnS shell. We utilize this in situ monitoring along with a study of various nucleation temperatures ranging from 0 to 100°C, and pre-and-post microwave heating UV exposure treatments to obtain optimized CdSe/CdS/ZnS particles with a QY of 40%. This is an improvement over our previous particles' 13% QY, and the highest yet reported for an aqueous synthesis of CdSe/ZnS type particles. Finally, we incorporate these QDs as well as two organic fluorophores, rhodamine 6G and rhodamine 800, into silica shells for direct monitoring in intestinal epithelial cells and tissues of exposed mice. We show that, for small nanoparticles, a typical Stober-type ammonia driven synthesis does not yield stable fluorescence. This has been observed in literature and is attributed to incompletely hydrolyzed silica precursor causing partial dissolution of the silica shell. We remedy this by applying an arginine driven silica shell synthesis, which is known to produce a denser and more stable product at smaller particle sizes. We show that all three fluorophores can be coated in a simple generalized procedure, and the resulting particles all show stable fluorescence with no evidence of dye leakage. Using these particles, we demonstrate that silica nanoparticles can be observed internalizing into C2BBe1 intestinal epithelial cells, and in the tissues of mice that were fed the particles by gavage. We find direct evidence that the particles are absorbed into circulation and subsequently localize in organs throughout the body. Future efforts will attempt to better quantify this accumulation, as well as generalize the procedure to other food relevant nanoparticles such as TiO2.

A ganglioneuroma of the sigmoid colon presenting as leading point of intussusception in a child: a case report.

PubMed

Soccorso, Giampiero; Puls, Florian; Richards, Cathy; Pringle, Howard; Nour, Shawqui

2009-01-01

We present a case of intestinal ganglioneuroma (GN) of the sigmoid colon in a 5-year-old girl, which caused intermittent colocolic intussusception. Ganglioneuromas are rare benign tumors of the autonomic nervous system composed of mature ganglion cells and satellite cells. Colonic GNs are uncommon. The unusual intramural proliferation of neural elements in this case resembled the diffuse intestinal ganglioneuromatosis, which is known to be associated with multiple endocrine neoplasia type 2B. However, the specific mutations of multiple endocrine neoplasia type 2B were not found by genetic sequencing. This is the first pediatric case described in the literature of a solitary polypoid GN presenting as a colocolic intussusception. We present a brief overview of intestinal ganglioneuromatous lesions and associated conditions.

Digit Symbol Performance in Mild Dementia and Depression.

ERIC Educational Resources Information Center

Hart, Robert P.; And Others

1987-01-01

Patients with mild dementia of the Alzheimer's type (DAT), patients with major depression, and normal control subjects completed the Wechsler Adult Intelligence Scale (WAIS) Digit Symbol test of incidental memory. Though mild DAT and depressed patients had equivalent deficits in psychomotor speed, DAT patients recalled fewer digit-symbol items.…

75 FR 60431 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

..., Department of Defense. DPR 41 DoD System Name: Combined Mild Traumatic Brain Injury Registry. System Location... concussive or mild traumatic brain injury and/or related incidents in deployed settings, to include blast... Type Memoranda 09-033, Policy Guidance for Management of Concussion/Mild Traumatic Brain Injury in the...

Self-Reported versus Informant-Reported Depressive Symptoms in Adults with Mild Intellectual Disability

ERIC Educational Resources Information Center

Mileviciute, I.; Hartley, S. L.

2015-01-01

Background: Virtually nothing is known about potential differences in the types of depression symptoms reported by adults with mild intellectual disability (ID) on self-reported questionnaires as compared with the types of symptoms reported by caregivers on informant questionnaires. Moreover, little is known about how the presentation of…

Peptide Transporter 1 is Responsible for Intestinal Uptake of the Dipeptide Glycylsarcosine: Studies in Everted Jejunal Rings from Wild-type and Pept1 Null Mice

PubMed Central

Ma, Katherine; Hu, Yongjun; Smith, David E.

2010-01-01

The purpose of this study was to determine the relative importance of PEPT1 in the uptake of peptides/mimetics from mouse small intestine using glycylsarcosine (GlySar). After isolating jejunal tissue from wild-type and Pept1 null mice, 2-cm intestinal segments were everted and mounted on glass rods for tissue uptake studies. [14C]GlySar (4 μM) was studied as a function of time, temperature, sodium and pH, concentration, and potential inhibitors. Compared to wild-type animals, Pept1 null mice exhibited a 78% reduction of GlySar uptake at pH 6.0, 37°C. GlySar uptake showed pH dependence with peak values between pH 6.0-6.5 in wild-type animals, while no such tendency was observed in Pept1 null mice. GlySar exhibited Michaelis-Menten uptake kinetics and a minor nonsaturable component in wild-type animals. In contrast, GlySar uptake occurred by only a nonsaturable process in Pept1 null mice. GlySar uptake was significantly inhibited by dipeptides, aminocephalosporins, angiotensin-converting enzyme inhibitors, and the antiviral prodrug valacyclovir; these inhibitors had little, if any, effect on the uptake of GlySar in Pept1 null mice. The findings demonstrate that PEPT1 plays a critical role in the uptake of GlySar in jejunum, and suggest that PEPT1 is the major transporter responsible for the intestinal absorption of small peptides. PMID:20862774

Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats.

PubMed

Alama, Tammam; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

2016-02-29

In general, the intestinal absorption of small hydrophilic molecules and macromolecules like peptides, after oral administration is very poor. Absorption enhancers are considered to be one of the most promising agents to enhance the intestinal absorption of drugs. In this research, we focused on a gemini surfactant, a new type of absorption enhancer. The intestinal absorption of drugs, with or without sodium dilauramidoglutamide lysine (SLG-30), a gemini surfactant, was examined by an in situ closed-loop method in rats. The intestinal absorption of 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) was significantly enhanced in the presence of SLG-30, such effect being reversible. Furthermore, the calcium levels in the plasma significantly decreased when calcitonin was co-administered with SLG-30, suggestive of the increased intestinal absorption of calcitonin. In addition, no significant increase in the of lactate dehydrogenase (LDH) activity or in protein release from the intestinal epithelium was observed in the presence of SLG-30, suggestive of the safety of this compound. These findings indicate that SLG-30 is an effective absorption-enhancer for improving the intestinal absorption of poorly absorbed drugs, without causing serious damage to the intestinal epithelium. Copyright © 2015 Elsevier B.V. All rights reserved.

Intestine-specific Disruption of Hypoxia-inducible Factor (HIF)-2α Improves Anemia in Sickle Cell Disease.

PubMed

Das, Nupur; Xie, Liwei; Ramakrishnan, Sadeesh K; Campbell, Andrew; Rivella, Stefano; Shah, Yatrik M

2015-09-25

Sickle cell disease (SCD) is caused by genetic defects in the β-globin chain. SCD is a frequently inherited blood disorder, and sickle cell anemia is a common type of hemoglobinopathy. During anemia, the hypoxic response via the transcription factor hypoxia-inducible factor (HIF)-2α is highly activated in the intestine and is essential in iron absorption. Intestinal disruption of HIF-2α protects against tissue iron accumulation in iron overload anemias. However, the role of intestinal HIF-2α in regulating anemia in SCD is currently not known. Here we show that in mouse models of SCD, disruption of intestinal HIF-2α significantly decreased tissue iron accumulation. This was attributed to a decrease in intestinal iron absorptive genes, which were highly induced in a mouse model of SCD. Interestingly, disruption of intestinal HIF-2α led to a robust improvement in anemia with an increase in RBC, hemoglobin, and hematocrit. This was attributed to improvement in RBC survival, hemolysis, and insufficient erythropoiesis, which is evident from a significant decrease in serum bilirubin, reticulocyte counts, and serum erythropoietin following intestinal HIF-2α disruption. These data suggest that targeting intestinal HIF-2α has a significant therapeutic potential in SCD pathophysiology. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Cdx function is required for maintenance of intestinal identity in the adult.

PubMed

Hryniuk, Alexa; Grainger, Stephanie; Savory, Joanne G A; Lohnes, David

2012-03-15

The homeodomain transcription factors Cdx1 and Cdx2 are expressed in the intestinal epithelium from early development, with expression persisting throughout the life of the animal. While our understanding of the function of Cdx members in intestinal development has advanced significantly, their roles in the adult intestine is relatively poorly understood. In the present study, we found that ablation of Cdx2 in the adult small intestine severely impacted villus morphology, proliferation and intestinal gene expression patterns, resulting in the demise of the animal. Long-term loss of Cdx2 in a chimeric model resulted in loss of all differentiated intestinal cell types and partial conversion of the mucosa to a gastric-like epithelium. Concomitant loss of Cdx1 did not exacerbate any of these phenotypes. Loss of Cdx2 in the colon was associated with a shift to a cecum-like epithelial morphology and gain of cecum-associated genes which was more pronounced with subsequent loss of Cdx1. These findings suggest that Cdx2 is essential for differentiation of the small intestinal epithelium, and that both Cdx1 and Cdx2 contribute to homeostasis of the colon. Copyright © 2012 Elsevier Inc. All rights reserved.

Regulatory Efficacy of Brown Seaweed Lessonia nigrescens Extract on the Gene Expression Profile and Intestinal Microflora in Type 2 Diabetic Mice.

PubMed

Zhao, Chao; Yang, Chengfeng; Chen, Mingjun; Lv, Xucong; Liu, Bin; Yi, Lunzhao; Cornara, Laura; Wei, Ming-Chi; Yang, Yu-Chiao; Tundis, Rosa; Xiao, Jianbo

2018-02-01

In this study, the antidiabetic activity of Lessonia nigrescens ethanolic extract (LNE) is investigated in streptozotocin (SZT)-induced type 2 diabetic mice fed with a high-sucrose/high-fat diet. Ultra high performance liquid chromatography coupled with photo-DAD and electospray ionization-mass spectrometry (ESI-MS) is employed to analyze the major compounds in LNE. The components of the intestinal microflora in type 2 diabetic mice are analyzed by high-throughput next-generation 16S rRNA gene sequencing. Fasting blood glucose levels in diabetic mice are significantly decreased after LNE administration. The histology reveals that LNE could protect the cellular architecture of liver and kidney. LNE treatment significantly increases Bacteroidetes and decreases Firmicutes populations in intestinal microflora. Specifically, It could selectively enrich the amounts of beneficial bacteria, Barnesiella, as well as reduce the abundances of Clostridium and Alistipes. The increased gene and protein expression levels of phosphatidylinositol 3-kinase (PI3K) in the liver are observed in LNE treatment groups, while the expressions of c-Jun N-terminal kinase (JNK) are significantly downregulated. The above findings suggest that LNE could be considered as a functional food for reducing blood glucose and regulating intestinal microflora. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thyroid Hormone Induces Apoptosis in Primary Cell Cultures of Tadpole Intestine: Cell Type Specificity and Effects of Extracellular Matrix

PubMed Central

Su, Yuan; Shi, Yufang; Stolow, Melissa A.; Shi, Yun-Bo

1997-01-01

Thyroid hormone (T3 or 3,5,3′-triiodothyronine) plays a causative role during amphibian metamorphosis. To investigate how T3 induces some cells to die and others to proliferate and differentiate during this process, we have chosen the model system of intestinal remodeling, which involves apoptotic degeneration of larval epithelial cells and proliferation and differentiation of other cells, such as the fibroblasts and adult epithelial cells, to form the adult intestine. We have established in vitro culture conditions for intestinal epithelial cells and fibroblasts. With this system, we show that T3 can enhance the proliferation of both cell types. However, T3 also concurrently induces larval epithelial apoptosis, which can be inhibited by the extracellular matrix (ECM). Our studies with known inhibitors of mammalian cell death reveal both similarities and differences between amphibian and mammalian cell death. These, together with gene expression analysis, reveal that T3 appears to simultaneously induce different pathways that lead to specific gene regulation, proliferation, and apoptotic degeneration of the epithelial cells. Thus, our data provide an important molecular and cellular basis for the differential responses of different cell types to the endogenous T3 during metamorphosis and support a role of ECM during frog metamorphosis. PMID:9396758

The Homeodomain Transcription Factor Cdx1 Does Not Behave as an Oncogene in Normal Mouse Intestine1

PubMed Central

Crissey, Mary Ann S; Guo, Rong-Jun; Fogt, Franz; Li, Hong; Katz, Jonathan P; Silberg, Debra G; Suh, Eun Ran; Lynch, John P

2008-01-01

The Caudal-related homeobox genes Cdx1 and Cdx2 are intestine-specific transcription factors that regulate differentiation of intestinal cell types. Previously, we have shown Cdx1 to be antiproliferative and to promote cell differentiation. However, other studies have suggested that Cdx1 may be an oncogene. To test for oncogenic behavior, we used the murine villin promoter to ectopically express Cdx1 in the small intestinal villi and colonic surface epithelium. No changes in intestinal architecture, cell differentiation, or lineage selection were observed with expression of the transgene. Classic oncogenes enhance proliferation and induce tumors when ectopically expressed. However, the Cdx1 transgene neither altered intestinal proliferation nor induced spontaneous intestinal tumors. In a murine model for colitis-associated cancer, the Cdx1 transgene decreased, rather than increased, the number of adenomas that developed. In the polyps, the expression of the endogenous and the transgenic Cdx1 proteins was largely absent, whereas endogenous Villin expression was retained. This suggests that transgene silencing was specific and not due to a general Villin inactivation. In conclusion, neither the ectopic expression of Cdx1 was associated with changes in intestinal cell proliferation or differentiation nor was there increased intestinal cancer susceptibility. Our results therefore suggest that Cdx1 is not an oncogene in normal intestinal epithelium. PMID:18231635

Intestinal helminthic infection and anemia among pregnant women attending ante-natal care (ANC) in East Wollega, Oromia, Ethiopia.

PubMed

Mengist, Hylemariam Mihiretie; Zewdie, Olifan; Belew, Adugna

2017-09-05

Ethiopia is a developing country where intestinal helminthic infections are major public health problems. The burden of intestinal parasites, particularly the soil-transmitted helminths (STHs), is often very high in school children and pregnant women. Anemia, associated with STH, is a major factor in women's health, especially during pregnancy; it is an important contributor to maternal mortality. The aim of this study was to determine the prevalence of intestinal helminthic infection and anemia among pregnant women attending ANC in East Wollega Zone, Ethiopia. A cross-sectional study was conducted in five health centers of East Wollega Zone of Oromia Region, Ethiopia between November 2015 and January 2016. The health centers were selected randomly and study participants were enrolled consecutively with proportions from all the health centers. Stool and blood specimens were processed using standard operating procedures in accordance with structured questionnaires. Logistic regression models were applied to assess the association between predictors and outcome variables. P values less than 0.05 were taken as significant levels. Results were presented in tables and figures. A total of 372 pregnant women were enrolled in this study with a median age of 25 years (range 17-40 years). The total prevalence of intestinal helminths was 24.7% (92/372) with the predominance of Hookworm (15.1%) followed by Ascaris lumbricoides (6.5%). Illiteracy [AOR, 95% CI 2.21 (1.3, 4.8), P = 0.042], absence of latrine [AOR, 95% CI 4.62 (1.7, 8.3), P = 0.013] and regular consumption of raw and/or unwashed fruit [AOR, 95% CI 3.30 (1.2, 6.3), P = 0.011] were significant predictors of intestinal helminthic infection. The overall prevalence of anemia was 17.5% (65/372) where mild anemia accounts for 80% of the total anemia. Anemia was significantly associated with the first trimester of gestation [AOR, 95% CI 2.82 (1.3, 6.2), P = 0.009], previous malaria infection [AOR, 95% CI 2.32 (1.3, 5.3), P = 0.003], failing to take iron supplements regularly [AOR, 95% CI 1.82 (1.1, 4.8), P = 0.022] and infection with intestinal helminths specifically with Hookworm (P = 0.001) and Ascaris lumbricoides (P = 0.022). The prevalence of intestinal helminths and anemia was significantly high in this study. Different socio-demographic, lifestyle and obstetric factors were identified as significant contributors of intestinal helminthic infection and anemia among pregnant women. Therefore, public health measures and intensive antenatal care services are vital to promoting safe pregnancy.

IL-2 receptor γ-chain molecule is critical for intestinal T-cell reconstitution in humanized mice.

PubMed

Denton, P W; Nochi, T; Lim, A; Krisko, J F; Martinez-Torres, F; Choudhary, S K; Wahl, A; Olesen, R; Zou, W; Di Santo, J P; Margolis, D M; Garcia, J V

2012-09-01

Intestinal immune cells are important in host defense, yet the determinants for human lymphoid homeostasis in the intestines are poorly understood. In contrast, lymphoid homeostasis has been studied extensively in mice, where the requirement for a functional common γ-chain molecule has been established. We hypothesized that humanized mice could offer insights into human intestinal lymphoid homeostasis if generated in a strain with an intact mouse common γ-chain molecule. To address this hypothesis, we used three mouse strains (non-obese diabetic (NOD)/severe-combined immunodeficient (SCID) (N/S); NOD/SCID γ-chain(-/-) (NSG); and Rag2(-/-) γ-chain(-/-) (DKO)) and two humanization techniques (bone marrow liver thymus (BLT) and human CD34(+) cell bone marrow transplant of newborn mice (hu)) to generate four common types of humanized mice: N/S-BLT, NSG-BLT, NSG-hu, and DKO-hu mice. The highest levels of intestinal human T cells throughout the small and large intestines were observed in N/S-BLT mice, which have an intact common γ-chain molecule. Furthermore, the small intestine lamina propria T-cell populations of N/S-BLT mice exhibit a human intestine-specific surface phenotype. Thus, the extensive intestinal immune reconstitution of N/S-BLT mice was both quantitatively and qualitatively better when compared with the other models tested such that N/S-BLT mice are well suited for the analysis of human intestinal lymphocyte trafficking and human-specific diseases affecting the intestines.

Comprehensive intestinal T helper cell profiling reveals specific accumulation of IFN-γ+IL-17+coproducing CD4+ T cells in active inflammatory bowel disease.

PubMed

Globig, Anna-Maria; Hennecke, Nadine; Martin, Bianca; Seidl, Maximilian; Ruf, Günther; Hasselblatt, Peter; Thimme, Robert; Bengsch, Bertram

2014-12-01

Skewed T helper (TH) cell responses and specific functions of TH1, TH2, TH17, and Treg cells have been implicated in the pathogenesis of inflammatory bowel disease (IBD) that led to the establishment of the pathogenic TH1/TH2 and TH17/Treg cell imbalance paradigms. However, the relevant TH cell population driving mucosal inflammation is still unknown. We performed a comprehensive TH cell profiling of circulating and intestinal lymphocytes isolated from patients with Crohn's disease (CD; n = 69) and ulcerative colitis (UC; n = 41) undergoing endoscopy or surgical resection and compared them with healthy controls (n = 45). Mucosal inflammation was assessed endoscopically and histologically. TH cells were analyzed by flow cytometric evaluation of cytokine production and differentiation marker expression. Specialized TH cell populations were enriched in the intestinal mucosa compared with peripheral blood. Specifically, we observed a concomitant upregulation of TH17 cells and Tregs in active inflammatory lesions in patients with both CD and UC compared with quiescent/mildly inflamed lesions and healthy tissue. Of note, interferon γ+ interleukin (IL)-17+coproducing CD4+ T cells with high expression of T-bet, CD26, and IL-22 resembling recently described pathogenic TH17 cells were specifically enriched in the inflamed mucosal tissue. Our results argue against the controversial TH1/TH2 or TH17/Treg paradigms. In contrast, they suggest that a subpopulation of TH17 cells sharing a TH1 signature may be specifically involved in intestinal inflammation in CD and UC. These findings provide a better understanding of IBD pathogenesis and may help explain the efficacy of anti-IL-12p40/IL-23 and failure of anti-IL-17A therapies despite the enrichment of TH17 cells.

Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs.

PubMed

Shen, René L; Thymann, Thomas; Østergaard, Mette V; Støy, Ann Cathrine F; Krych, Łukasz; Nielsen, Dennis S; Lauridsen, Charlotte; Hartmann, Bolette; Holst, Jens J; Burrin, Douglas G; Sangild, Per T

2015-09-01

It is unclear when and how to start enteral feeding for preterm infants when mother's milk is not available. We hypothesized that early and slow advancement with either formula or bovine colostrum stimulates gut maturation and prevents necrotizing enterocolitis (NEC) in preterm pigs, used as models for preterm infants. Pigs were given either total parenteral nutrition (TPN, n = 14) or slowly advancing volumes (16-64 ml·kg(-1)·day(-1)) of preterm infant formula (IF, n = 15) or bovine colostrum (BC, n = 13), both given as adjunct to parenteral nutrition. On day 5, both enteral diets increased intestinal mass (27 ± 1 vs. 22 ± 1 g/kg) and glucagon-like peptide 2 release, relative to TPN (P < 0.05). The incidence of mild NEC lesions was higher in IF than BC and TPN pigs (60 vs. 0 and 15%, respectively, P < 0.05). Only the IF pigs showed reduced gastric emptying and gastric inhibitory polypeptide release, and increased tissue proinflammatory cytokine levels (IL-1β and IL-8, P < 0.05) and expression of immune-related genes (AOAH, LBP, CXCL10, TLR2), relative to TPN. The IF pigs also showed reduced intestinal villus-to-crypt ratio, lactose digestion, and some plasma amino acids (Arg, Cit, Gln, Tyr, Val), and higher intestinal permeability, compared with BC pigs (all P < 0.05). Colonic microbiota analyses showed limited differences among groups. Early feeding with formula induces intestinal dysfunction whereas bovine colostrum supports gut maturation when mother's milk is absent during the first week after preterm birth. A diet-dependent feeding guideline may be required for newborn preterm infants. Copyright © 2015 the American Physiological Society.

E. Coli Infections

MedlinePlus

E. coli is the name of a type of bacteria that lives in your intestines. Most types of E. coli are harmless. However, some types can make you ... type causes travelers' diarrhea. The worst type of E. coli causes bloody diarrhea, and can sometimes cause kidney ...

Immunological characteristics of patients infected with common intestinal helminths: results of a study based on reverse-transcriptase PCR.

PubMed

Lertanekawattana, S; Wichatrong, T; Chaisari, K; Uchikawa, R; Arizono, N

2005-01-01

To determine whether common helminth infections could modify the intestinal immunopathological status of the host, the expression in the human duodenal mucosa of cytokines, eosinophil- and mast-cell-specific molecules and monosaccharide transporters of the glucose-transporter (GLUT) family was explored. The 31 subjects were all patients at the gastro-intestinal disease unit of Nongkhai Hospital, Thailand. Four of the 10 patients who presented with eosinophilia (> or = 6.0% of their leucocytes were eosinophils), and five of the other 21 patients, had intestinal infections with helminths when they presented or within the previous 3 months. Studies based on semi-quantitative, reverse-transcriptase PCR revealed that the interleukin-5/interferon-gamma ratio was significantly higher in the noneosinophilic, helminth-infected patients than in the non-eosinophilic, uninfected patients, whereas the IgE receptor type I (Fc epsilon RI)/mast-cell tryptase ratio was significantly higher in the eosinophilic, helminth-infected patients than in the eosinophilic, uninfected patients. Expression of Charcot-Leyden-crystal protein, GLUT-1 and GLUT-5, however, showed no significant inter-group differences. Principal-components analysis of the data on eosinophils, interleukin-5, interferon-gamma, Fc epsilon RI and mast-cell tryptase revealed that one principal component could discriminate the patients who had helminth infection from the non-eosinophilic, uninfected patients, but not from the eosinophilic, uninfected patients. These results indicate that, whatever the intestinal pathology, patients infected with common intestinal helminths tend to develop a mucosal immunological response of the Th2 type.

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

PubMed Central

Vatanen, Tommi; Droit, Lindsay; Kostic, Aleksandar D.; Poon, Tiffany W.; Vlamakis, Hera; Siljander, Heli; Härkönen, Taina; Hämäläinen, Anu-Maaria; Peet, Aleksandr; Tillmann, Vallo; Ilonen, Jorma; Wang, David; Knip, Mikael; Xavier, Ramnik J.

2017-01-01

Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment of Circoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease. PMID:28696303

Capsular locomotive microrobot for gastrointestinal tract.

PubMed

Park, Sukho; Park, Hyunjun; Park, Sungjin; Jee, Changyeol; Kim, Jinseok; Kim, Byungkyu

2006-01-01

Diagnosis using a flexible endoscope in gastro-intestinal tract becomes very important. In addition, the endoscope is a basic tool of diagnosis and treatment for digestive organ. However, the operation of endoscope is very labor intensive work and gives patients some pains. Therefore, the capsule-type endoscope is developed for the diagnosis of digestive organs. For its conveniences for diagnosis, the capsule endoscope comes into the spotlight. However, it is passively moved by the peristaltic waves of gastro-intestinal tract and thus has some limitations for doctor to get the image of the organ and to diagnose more thoroughly. In order to solve these problems, therefore, a locomotive mechanism of capsule endoscopes has being developed. For the locomotion in the gastro-intestinal tract, our proposed capsule-type microrobot has synchronized multiple legs that are actuated by a linear actuator and two mobile cylinders inside of the capsule. For the feasibility test of the proposed locomotive mechanism, a series of in-vitro experiments using small intestine without incision were carried out. In addition, in-vivo animal tests under a general anesthesia are also executed. From the experimental results, we conclude that the proposed locomotive mechanism is not only applicable to micro capsule endoscopes but also effective to advance inside of intestinal tract.

A comparison between lactose breath test and quick test on duodenal biopsies for diagnosing lactase deficiency in patients with self-reported lactose intolerance.

PubMed

Furnari, Manuele; Bonfanti, Daria; Parodi, Andrea; Franzè, Jolanda; Savarino, Edoardo; Bruzzone, Luca; Moscatelli, Alessandro; Di Mario, Francesco; Dulbecco, Pietro; Savarino, Vincenzo

2013-02-01

A lactose breath test (LBT) is usually used to diagnose lactase deficiency, and a lactose quick test (LQT) has been proposed as a new test on duodenal biopsies to detect this disorder. We aimed to assess the diagnostic accuracy of LBT and LQT and their ability to predict the clinical response to a lactose-free diet in patients with self-reported lactose intolerance. Fifty-five patients (age 47 ± 14 y; M/F 15/36) underwent upper gastrointestinal endoscopy and 25g-LBT. Two duodenal biopsies were taken to determine lactase deficiency (normal, mild, or severe) by LQT and to rule out other causes of secondary lactose malabsorption. Patients with a positive LBT and normal LQT also underwent a glucose breath test to exclude small intestinal bacterial overgrowth as a cause of the former result. The severity of gastrointestinal symptoms was measured with a GSS questionnaire, under basal condition and 1 month after a lactose-free diet. Lactose malabsorption was detected in 31/51 patients with LBT and in 37/51 patients with LQT (P = NS). Celiac disease was found in 2 patients. Two LBT+ patients showed a positive glucose breath test for small intestinal bacterial overgrowth. Eight patients had a mild hypolactasia by LQT and a negative LBT, but they had a significant improvement of symptoms after diet. LQT and LBT were concordant in 83% of cases and predicted the response to a lactose-free diet in 98% and 81% of the cases, respectively (P = 0.03). LQT is as sensitive as LBT in detecting lactase deficiency; however, it seems to be more accurate than LBT in predicting the clinical response to a lactose-free diet.

Primary Intestinal Lymphangiectasia Manifested as Unusual Edemas and Effusions: A Case Report.

PubMed

Wang, Xuefeng; Jin, Hong; Wu, Weilu

2016-03-01

Primary intestinal lymphangiectasia (PIL) is a rare disorder of unknown etiology characterized by diffuse or localized dilation and eventual rupture of the enteric lymphatic vessels in mucosa, submucosa, and/or subserosa. Lymph, rich in all kinds of proteins and lymphocytes, leaks into the gastrointestinal tract via the affected lymphatic vessels causing hypoproteinemia and lymphopenia. The main symptom is variable degrees of pitting edemas of bilateral lower limbs. But edemas of any other parts of body, and mild serous effusions may also occur sometimes. PIL occurs in conjunction with a right hemifacial edema, a right upper limb lymphedema, asymmetric bilateral calves edemas, and a unilateral massive pleural effusion seems never to be reported before. In addition, increased enteric protein loss that may cause severe hypoproteinemia usually get overlooked, and the lymphatic system disorders always put the diagnoses in a dilemma.We described a case of a 17-year-old Chinese girl with a history of gradually progressive swellings of right-sided face, right upper limb, and bilateral calves since 3 to 4 months of age. A right-sided massive pleural effusion, a moderate pericardial effusion, and a mild ascites have been proved unchanged by a series of computerized tomography (CT) scans since 5 years ago. The diagnosis of PIL was finally confirmed by severe hypoproteinemia, endoscopic changes, and histology of jejunum biopsy. Further lymphoscintigraphy and lymphangiography also identified lymph leakage in her bowel and several abnormal lymphatic vessels. A high-protein, low-fat diet supplemented with medium-chain triglycerides (MCT) showed some benefit.This case suggested that PIL was a rare but important etiology of hypoproteinemia, effusions, and edemas. PIL, effusions, and lymphedema can be the features of multisegmental generalized lymphatic dysplasia. In addition, both lymphoscintigraphy and intranodal lymphangiography could be considered when lymphatic system disorders are suspected.

Primary Intestinal Lymphangiectasia Manifested as Unusual Edemas and Effusions

PubMed Central

Wang, Xuefeng; Jin, Hong; Wu, Weilu

2016-01-01

Abstract Primary intestinal lymphangiectasia (PIL) is a rare disorder of unknown etiology characterized by diffuse or localized dilation and eventual rupture of the enteric lymphatic vessels in mucosa, submucosa, and/or subserosa. Lymph, rich in all kinds of proteins and lymphocytes, leaks into the gastrointestinal tract via the affected lymphatic vessels causing hypoproteinemia and lymphopenia. The main symptom is variable degrees of pitting edemas of bilateral lower limbs. But edemas of any other parts of body, and mild serous effusions may also occur sometimes. PIL occurs in conjunction with a right hemifacial edema, a right upper limb lymphedema, asymmetric bilateral calves edemas, and a unilateral massive pleural effusion seems never to be reported before. In addition, increased enteric protein loss that may cause severe hypoproteinemia usually get overlooked, and the lymphatic system disorders always put the diagnoses in a dilemma. We described a case of a 17-year-old Chinese girl with a history of gradually progressive swellings of right-sided face, right upper limb, and bilateral calves since 3 to 4 months of age. A right-sided massive pleural effusion, a moderate pericardial effusion, and a mild ascites have been proved unchanged by a series of computerized tomography (CT) scans since 5 years ago. The diagnosis of PIL was finally confirmed by severe hypoproteinemia, endoscopic changes, and histology of jejunum biopsy. Further lymphoscintigraphy and lymphangiography also identified lymph leakage in her bowel and several abnormal lymphatic vessels. A high-protein, low-fat diet supplemented with medium-chain triglycerides (MCT) showed some benefit. This case suggested that PIL was a rare but important etiology of hypoproteinemia, effusions, and edemas. PIL, effusions, and lymphedema can be the features of multisegmental generalized lymphatic dysplasia. In addition, both lymphoscintigraphy and intranodal lymphangiography could be considered when lymphatic system disorders are suspected. PMID:26962779

Therapeutic mild hypothermia improves early outcomes in rats subjected to severe sepsis.

PubMed

Ding, Wu; Shen, Yuehong; Li, Qiang; Jiang, Shouyin; Shen, Huahao

2018-04-15

Therapeutic hypothermia has shown beneficial effects in sepsis. This study focused on its mechanism. Sixteen male Sprague-Dawley rats underwent cecal ligation and perforation and subsequently were treated with either hypothermia (HT; body temperature cooled and maintained at 34 °C by ice pad for 10 h; n = 8) or normothermia (NT; n = 8). Three additional rats underwent sham surgery. The body temperatures of the sham-operated and NT groups were maintained at 38 °C with a thermal pad. After the hypothermia treatment, the HT rats were rewarmed for 2 h. The groups were compared for circulating cytokines (IL-6, IL-10), lactate, high mobility group box-1 protein (HMGB1), and lung and intestinal lesions. Animals were observed for 24 h. Compared with the sham-operated group, the 2 sepsis group rats had significantly higher circulating IL-6, HMGB1, and lactate levels, and tissue injury. In the HT rats, the levels of IL-6, HMGB1, and lactate, the lung wet-to-dry ratio, and lung and intestinal damage were significantly lower than that of the NT group. Circulating IL-10 levels increased significantly after 12 h in the sepsis groups compared with sham animals, while that of the NT and HT groups were comparable. The survival rates of the NT and HT rats were also comparable. Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema. These results suggest that mild hypothermia has potential as a therapy in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.

Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota

PubMed Central

von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A.; Bereswill, Stefan

2017-01-01

Background Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Methodology/Principal findings Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. Conclusion/Significance With respect to the intestinal microbiota composition “humanized” mice display acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation. PMID:28414794

Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota.

PubMed

von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A; Bereswill, Stefan; Heimesaat, Markus M

2017-01-01

Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. With respect to the intestinal microbiota composition "humanized" mice display acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation.

Water and solute absorption from carbohydrate-electrolyte solutions in the human proximal small intestine: a review and statistical analysis.

PubMed

Shi, Xiaocai; Passe, Dennis H

2010-10-01

The purpose of this study is to summarize water, carbohydrate (CHO), and electrolyte absorption from carbohydrate-electrolyte (CHO-E) solutions based on all of the triple-lumen-perfusion studies in humans since the early 1960s. The current statistical analysis included 30 reports from which were obtained information on water absorption, CHO absorption, total solute absorption, CHO concentration, CHO type, osmolality, sodium concentration, and sodium absorption in the different gut segments during exercise and at rest. Mean differences were assessed using independent-samples t tests. Exploratory multiple-regression analyses were conducted to create prediction models for intestinal water absorption. The factors influencing water and solute absorption are carefully evaluated and extensively discussed. The authors suggest that in the human proximal small intestine, water absorption is related to both total solute and CHO absorption; osmolality exerts various impacts on water absorption in the different segments; the multiple types of CHO in the ingested CHO-E solutions play a critical role in stimulating CHO, sodium, total solute, and water absorption; CHO concentration is negatively related to water absorption; and exercise may result in greater water absorption than rest. A potential regression model for predicting water absorption is also proposed for future research and practical application. In conclusion, water absorption in the human small intestine is influenced by osmolality, solute absorption, and the anatomical structures of gut segments. Multiple types of CHO in a CHO-E solution facilitate water absorption by stimulating CHO and solute absorption and lowering osmolality in the intestinal lumen.

A randomized cross over study comparing the efficacy of two mandibular advancement appliances in the treatment of mild-moderate obstructive sleep apnea.

PubMed

Al-Dharrab, Ayman

2017-11-01

To compare efficacy, side effects, patient compliance, and preference between two types of custom-made mandibular advancement appliances (MAAs) in the treatment of patients with mild to moderate obstructive sleep apnea (OSA). This prospective, randomized, crossover study of 12 patients with mild to moderate OSA compared a titratable and a non-titratable MAA. Each patient was fitted with both appliances in a random order with a washout period of two weeks. Efficacy, side effects, compliance, and preference were evaluated by a questionnaire. All patients underwent overnight home sleep recordings prior to and after the use of each appliance in order to objectively assess sleep quality in terms of the apnea and hypopnea index (AHI), snoring frequency and oxygen desaturation index. Treatment successes (relief of symptoms and/or reduction of AHI to <10/h) were reported with both types of appliances. No compliance failure was reported, and in most patients, the side effects were mild, and improved with time. Both types of oral appliances were effective treatments for patients with mild to moderate OSA, with fewer side effects and higher patient satisfaction.

Intestinal Intraepithelial Lymphocyte-Enterocyte Crosstalk Regulates Production of Bactericidal Angiogenin 4 by Paneth Cells upon Microbial Challenge

PubMed Central

Dalton, Jane E.; Overweg, Karin; Egan, Charlotte E.; Bongaerts, Roy J.; Newton, Darren J.; Cruickshank, Sheena M.; Andrew, Elizabeth M.; Carding, Simon R.

2013-01-01

Antimicrobial proteins influence intestinal microbial ecology and limit proliferation of pathogens, yet the regulation of their expression has only been partially elucidated. Here, we have identified a putative pathway involving epithelial cells and intestinal intraepithelial lymphocytes (iIELs) that leads to antimicrobial protein (AMP) production by Paneth cells. Mice lacking γδ iIELs (TCRδ-/-) express significantly reduced levels of the AMP angiogenin 4 (Ang4). These mice were also unable to up-regulate Ang4 production following oral challenge by Salmonella, leading to higher levels of mucosal invasion compared to their wild type counterparts during the first 2 hours post-challenge. The transfer of γδ iIELs from wild type (WT) mice to TCRδ-/- mice restored Ang4 production and Salmonella invasion levels were reduced to those obtained in WT mice. The ability to restore Ang4 production in TCRδ-/- mice was shown to be restricted to γδ iIELs expressing Vγ7-encoded TCRs. Using a novel intestinal crypt co-culture system we identified a putative pathway of Ang4 production initiated by exposure to Salmonella, intestinal commensals or microbial antigens that induced intestinal epithelial cells to produce cytokines including IL‑23 in a TLR-mediated manner. Exposure of TCR-Vγ7+ γδ iIELs to IL-23 promoted IL‑22 production, which triggered Paneth cells to secrete Ang4. These findings identify a novel role for γδ iIELs in mucosal defence through sensing immediate epithelial cell cytokine responses and influencing AMP production. This in turn can contribute to the maintenance of intestinal microbial homeostasis and epithelial barrier function, and limit pathogen invasion. PMID:24358364

Intestinal intraepithelial lymphocyte-enterocyte crosstalk regulates production of bactericidal angiogenin 4 by Paneth cells upon microbial challenge.

PubMed

Walker, Catherine R; Hautefort, Isabelle; Dalton, Jane E; Overweg, Karin; Egan, Charlotte E; Bongaerts, Roy J; Newton, Darren J; Cruickshank, Sheena M; Andrew, Elizabeth M; Carding, Simon R

2013-01-01

Antimicrobial proteins influence intestinal microbial ecology and limit proliferation of pathogens, yet the regulation of their expression has only been partially elucidated. Here, we have identified a putative pathway involving epithelial cells and intestinal intraepithelial lymphocytes (iIELs) that leads to antimicrobial protein (AMP) production by Paneth cells. Mice lacking γδ iIELs (TCRδ(-/-)) express significantly reduced levels of the AMP angiogenin 4 (Ang4). These mice were also unable to up-regulate Ang4 production following oral challenge by Salmonella, leading to higher levels of mucosal invasion compared to their wild type counterparts during the first 2 hours post-challenge. The transfer of γδ iIELs from wild type (WT) mice to TCRδ(-/-) mice restored Ang4 production and Salmonella invasion levels were reduced to those obtained in WT mice. The ability to restore Ang4 production in TCRδ(-/-) mice was shown to be restricted to γδ iIELs expressing Vγ7-encoded TCRs. Using a novel intestinal crypt co-culture system we identified a putative pathway of Ang4 production initiated by exposure to Salmonella, intestinal commensals or microbial antigens that induced intestinal epithelial cells to produce cytokines including IL‑23 in a TLR-mediated manner. Exposure of TCR-Vγ7(+) γδ iIELs to IL-23 promoted IL‑22 production, which triggered Paneth cells to secrete Ang4. These findings identify a novel role for γδ iIELs in mucosal defence through sensing immediate epithelial cell cytokine responses and influencing AMP production. This in turn can contribute to the maintenance of intestinal microbial homeostasis and epithelial barrier function, and limit pathogen invasion.

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

PubMed Central

Fujimori, Shunji

2015-01-01

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, non-alcoholic 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. PMID:26078557

Starring role of toll-like receptor-4 activation in the gut-liver axis

PubMed Central

Carotti, Simone; Guarino, Michele Pier Luca; Vespasiani-Gentilucci, Umberto; Morini, Sergio

2015-01-01

Since the introduction of the term “gut-liver axis”, many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extra-intestinal diseases alter microbiota composition and lead to dysbiosis, which aggravates impaired intestinal barrier function via increased lipopolysaccharide translocation. The subsequent increased passage of gut-derived product from the intestinal lumen to the organ wall and bloodstream affects gut motility and liver biology. The activation of the toll-like receptor 4 (TLR-4) likely plays a key role in both cases. This review analyzed the most recent literature on the gut-liver axis, with a particular focus on the role of TLR-4 activation. Findings that linked liver disease with dysbiosis are evaluated, and links between dysbiosis and alterations of intestinal permeability and motility are discussed. We also examine the mechanisms of translocated gut bacteria and/or the bacterial product activation of liver inflammation and fibrogenesis via activity on different hepatic cell types. PMID:26600967

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

PubMed

Fujimori, Shunji

2015-06-14

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, non-alcoholic 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.

An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells

NASA Astrophysics Data System (ADS)

Powell, Jonathan J.; Thomas-McKay, Emma; Thoree, Vinay; Robertson, Jack; Hewitt, Rachel E.; Skepper, Jeremy N.; Brown, Andy; Hernandez-Garrido, Juan Carlos; Midgley, Paul A.; Gomez-Morilla, Inmaculada; Grime, Geoffrey W.; Kirkby, Karen J.; Mabbott, Neil A.; Donaldson, David S.; Williams, Ifor R.; Rios, Daniel; Girardin, Stephen E.; Haas, Carolin T.; Bruggraber, Sylvaine F. A.; Laman, Jon D.; Tanriver, Yakup; Lombardi, Giovanna; Lechler, Robert; Thompson, Richard P. H.; Pele, Laetitia C.

2015-05-01

In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule ‘programmed death-ligand 1’, whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis.

Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota.

PubMed

Bates, Jennifer M; Akerlund, Janie; Mittge, Erika; Guillemin, Karen

2007-12-13

Vertebrates harbor abundant lipopolysaccharide (LPS) in their gut microbiota. Alkaline phosphatases can dephosphorylate and detoxify the endotoxin component of LPS. Here, we show that expression of the zebrafish intestinal alkaline phosphatase (Iap), localized to the intestinal lumen brush border, is induced during establishment of the gut microbiota. Iap-deficient zebrafish are hypersensitive to LPS toxicity and exhibit the excessive intestinal neutrophil influx characteristic of wild-type zebrafish exposed to LPS. Both of these Iap mutant phenotypes are dependent on Myd88 and Tumor Necrosis Factor Receptor (Tnfr), proteins also involved in LPS sensitivity in mammals. When reared germ-free, the intestines of Iap-deficient zebrafish are devoid of neutrophils. Together, these findings demonstrate that the endogenous microbiota establish the normal homeostatic level of neutrophils in the zebrafish intestine through a process involving Iap, Myd88, and Tnfr. Thus, by preventing inflammatory responses, Iap plays a crucial role in promoting mucosal tolerance to resident gut bacteria.

An Endogenous Nanomineral Chaperones Luminal Antigen and Peptidoglycan to Intestinal Immune Cells

PubMed Central

Powell, Jonathan J; Thomas-McKay, Emma; Thoree, Vinay; Robertson, Jack; Hewitt, Rachel E; Skepper, Jeremy N; Brown, Andy; Hernandez-Garrido, Juan Carlos; Midgley, Paul A; Gomez-Morilla, Inmaculada; Grime, Geoffrey W; Kirkby, Karen J; Mabbott, Neil A; Donaldson, David S; Williams, Ifor R; Rios, Daniel; Girardin, Stephen E; Haas, Carolin T; Bruggraber, Sylvaine FA; Laman, Jon D; Tanriver, Yakup; Lombardi, Giovanna; Lechler, Robert; Thompson, Richard P H; Pele, Laetitia C

2015-01-01

In humans and other mammals, it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally-fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer’s patches - small areas of the intestine concentrated with particle-scavenging immune cells. In wild type mice, intestinal immune cells containing these naturally-formed nanoparticles expressed the immune tolerance-associated molecule ‘programmed death-ligand 1 (PD-L1)’, whereas in NOD1/2 double knock-out mice, which cannot recognize peptidoglycan, PD-L1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and how this helps to shape intestinal immune homeostasis. PMID:25751305

Non-Hematopoietic MLKL Protects Against Salmonella Mucosal Infection by Enhancing Inflammasome Activation.

PubMed

Yu, Shui-Xing; Chen, Wei; Liu, Zhen-Zhen; Zhou, Feng-Hua; Yan, Shi-Qing; Hu, Gui-Qiu; Qin, Xiao-Xia; Zhang, Jie; Ma, Ke; Du, Chong-Tao; Gu, Jing-Min; Deng, Xu-Ming; Han, Wen-Yu; Yang, Yong-Jun

2018-01-01

The intestinal mucosal barrier is critical for host defense against pathogens infection. Here, we demonstrate that the mixed lineage kinase-like protein (MLKL), a necroptosis effector, promotes intestinal epithelial barrier function by enhancing inflammasome activation. MLKL -/- mice were more susceptible to Salmonella infection compared with wild-type counterparts, with higher mortality rates, increased body weight loss, exacerbated intestinal inflammation, more bacterial colonization, and severe epithelial barrier disruption. MLKL deficiency promoted early epithelial colonization of Salmonella prior to developing apparent intestinal pathology. Active MLKL was predominantly expressed in crypt epithelial cells, and experiments using bone marrow chimeras found that the protective effects of MLKL were dependent on its expression in non-hematopoietic cells. Intestinal mucosa of MLKL -/- mice had impaired caspase-1 and gasdermin D cleavages and decreased interleukin (IL)-18 release. Moreover, administration of exogenous recombinant IL-18 rescued the phenotype of increased bacterial colonization in MLKL -/- mice. Thus, our results uncover the role of MLKL in enhancing inflammasome activation in intestinal epithelial cells to inhibit early bacterial colonization.

Get Well Care: Guidelines for Programs Serving Mildly Ill Children.

ERIC Educational Resources Information Center

Montanari, Ellen Orton, Ed.

Although child care programs for mildly ill children are proliferating around the country, very few states have developed regulations for these types of programs, and no states have developed standards or guidelines. Based upon this concern, a group of medical and early childhood professionals, parents, and directors of programs for mildly ill…

Hypothyroxinemia Induced by Mild Iodine Deficiency Deregulats Thyroid Proteins during Gestation and Lactation in Dams

PubMed Central

Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

2013-01-01

The main object of the present study was to explore the effect on thyroidal proteins following mild iodine deficiency (ID)-induced maternal hypothyroxinemia during pregnancy and lactation. In the present study, we established a maternal hypothyroxinemia model in female Wistar rats by using a mild ID diet. Maternal thyroid iodine content and thyroid weight were measured. Expressions of thyroid-associated proteins were analyzed. The results showed that the mild ID diet increased thyroid weight, decreased thyroid iodine content and increased expressions of thyroid transcription factor 1, paired box gene 8 and Na+/I− symporter on gestational day (GD) 19 and postpartum days (PN) 21 in the maternal thyroid. Moreover, the up-regulated expressions of type 1 iodothyronine deiodinase (DIO1) and type 2 iodothyronine deiodinase (DIO2) were detected in the mild ID group on GD19 and PN21. Taken together, our data indicates that during pregnancy and lactation, a maternal mild ID could induce hypothyroxinemia and increase the thyroidal DIO1 and DIO2 levels. PMID:23917811

Detection of Clostridium botulinum type C cells in the gastrointestinal tracts of Mozambique tilapia (Oreochromis mossambicus) by polymerase chain reaction

USGS Publications Warehouse

Nol, P.; Williamson, J.L.; Rocke, T.E.; Yuill, Thomas M.

2004-01-01

We established a method of directly detecting Clostridium botulinum type C cells, while minimizing spore detection, in the intestinal contents of Mozambique tilapia (Oreochromis mossambicus). This technique involved extraction of predominantly cellular DNA from tilapia intestinal tracts and used a polymerase chain reaction assay to detect presence of type C1 toxin gene. We consistently detected C. botulinum type C cells in tilapia gastrointestinal contents at a level of 7.5×104 cells per 0.25 g material or 1.9×103 cells. This technique is useful for determining prevalence of the potentially active organisms within a given population of fish and may be adapted to other types of C. botulinum and vertebrate populations as well.

Formation of intestinal atresias in the Fgfr2IIIb-/- mice is not associated with defects in notochord development or alterations in Shh expression.

PubMed

Reeder, Amy L; Botham, Robert A; Franco, Marta; Zaremba, Krzysztof M; Nichol, Peter F

2012-09-01

The etiology of intestinal atresia remains elusive but has been ascribed to a number of possible events including in utero vascular accidents, failure of recanalization of the intestinal lumen, and mechanical compression. Another such event that has been postulated to be a cause in atresia formation is disruption in notochord development. This hypothesis arose from clinical observations of notochord abnormalities in patients with intestinal atresias as well as abnormal notochord development observed in a pharmacologic animal model of intestinal atresia. Atresias in this model result from in utero exposure to Adriamycin, wherein notochord defects were noted in up to 80% of embryos that manifested intestinal atresias. Embryos with notochord abnormalities were observed to have ectopic expression of Sonic Hedgehog (Shh), which in turn was postulated to be causative in atresia formation. We were interested in determining whether disruptions in notochord development or Shh expression occurred in an established genetic model of intestinal atresia and used the fibroblast growth factor receptor 2IIIb homozygous mutant (Fgfr2IIIb-/-) mouse model. These embryos develop colonic atresias (100% penetrance) and duodenal atresias (42% penetrance). Wild-type and Fgfr2IIIb-/- mouse embryos were harvested at embryonic day (E) 10.5, E11.5, E12.5, and E13.5. Whole-mount in situ hybridization was performed on E10.5 embryos for Shh. Embryos at each time point were harvested and sectioned for hematoxylin-eosin staining. Sections were photographed specifically for the notochord and resulting images reconstructed in 3-D using Amira software. Colons were isolated from wild-type and Fgfr2IIIb-/- embryos at E10.5, then cultured for 48 hours in Matrigel with FGF10 in the presence or absence of exogenous Shh protein. Explants were harvested, fixed in formalin, and photographed. Fgfr2IIIb-/- mouse embryos exhibit no disruptions in Shh expression at E10.5, when the first events in atresia formation are known to occur. Three-dimensional reconstructions failed to demonstrate any anatomical disruptions in the notochord by discontinuity or excessive branching. Culture of wild-type intestines in the presence of Shh failed to induce atresia formation in either the duodenum or colon. Cultured Fgfr2IIIb-/- intestines developed atresias of the colon in either the presence or absence of Shh protein. Although disruptions in notochord development can be associated with intestinal atresia formation, in the Fgfr2IIIb-/- genetic animal model neither disruptions in notochord development nor the presence of exogenous Shh protein are causative in the formation of these defects. Copyright © 2012 Elsevier Inc. All rights reserved.

Formation of Intestinal Atresias in the Fgfr2IIIb−/− Mice is not Associated with Defects in Notochord Development or Alterations in Shh Expression

PubMed Central

Reader, Amy L.; Botham, Robert A.; Franco, Marta; Zaremba, Krzysztof M.; Nichol, Peter F.

2012-01-01

Purpose The etiology of intestinal atresia remains elusive but has been ascribed to a number of possible events including in utero vascular accidents, failure of recanalization of the intestinal lumen and mechanical compression. Another such event that has been postulated to be a cause in atresia formation is disruption in notochord development. This hypothesis arose from clinical observations of notochord abnormalities in patients with intestinal atresias as well as abnormal notochord development observed in a pharmacological animal model of intestinal atresia. Atresias in this model result from in utero exposure to Adriamycin, wherein notochord defects were noted in up to 80% of embryos that manifested intestinal atresias. Embryos with notochord abnormalities were observed to have ectopic expression of Sonic Hedgehog (Shh) which in turn was postulated to be causative in atresia formation. We were interested in determining whether disruptions in notochord development or Shh expression occurred in an established genetic model of intestinal atresia and utilized the Fibroblast Growth Factor Receptor 2IIIb homozygous mutant (Fgfr2IIIb−/−) mouse model. These embryos develop colonic atresias (100% penetrance) and duodenal atresias (42% penetrance). Methods Wild-type and Fgfr2IIIb−/− mouse embryos were harvested at E10.5, E11.5, E12.5 and E13.5. Whole mount in situ hybridization was performed on E10.5 embryos for Shh. Embryos at each time point were harvested and sectioned for H&E staining. Sections were photographed specifically for the notochord and resulting images reconstructed in 3-D using Amira software. Colons were isolated from wild-type and Fgfr2IIIb−/− embryos at E10.5, then cultured for 48 hours in matrigel with FGF10 in the presence or absence of exogenous SHH protein. Explants were harvested, fixed in formalin and photographed. Results Fgfr2IIIb−/− mouse embryos exhibit no disruptions in Shh expression at E10.5, when the first events in atresia formation are known to occur. Three-dimensional reconstructions failed to demonstrate any anatomical disruptions in the notochord by discontinuity or excessive branching. Culture of wild-type intestines in the presence of Shh failed to induce atresia formation in either the duodenum or colon. Cultured Fgfr2IIIb−/− intestines developed atresias of the colon in either the presence, or absence, of Shh protein. Conclusions Although disruptions in notochord development can be associated with intestinal atresia formation, in the Fgfr2IIIb−/− genetic animal model neither disruptions in notochord development nor the presence of exogenous Shh protein are causative in the formation of these defects. PMID:22572615

49 CFR 537.7 - Pre-model year and mid-model year reports.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... List the model types in order of increasing average inertia weight from top to bottom down the left... form. List the model types in order of increasing average inertia weight from top to bottom down the... trucks in your fleet that meet the mild and strong hybrid vehicle definitions. For each mild and strong...

49 CFR 537.7 - Pre-model year and mid-model year reports.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... List the model types in order of increasing average inertia weight from top to bottom down the left... form. List the model types in order of increasing average inertia weight from top to bottom down the... trucks in your fleet that meet the mild and strong hybrid vehicle definitions. For each mild and strong...

RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium.

PubMed

Knoop, Kathryn A; Kumar, Nachiket; Butler, Betsy R; Sakthivel, Senthilkumar K; Taylor, Rebekah T; Nochi, Tomonori; Akiba, Hisaya; Yagita, Hideo; Kiyono, Hiroshi; Williams, Ifor R

2009-11-01

Microfold cells (M cells) are specialized epithelial cells situated over Peyer's patches (PP) and other organized mucosal lymphoid tissues that transport commensal bacteria and other particulate Ags into intraepithelial pockets accessed by APCs. The TNF superfamily member receptor activator of NF-kappaB ligand (RANKL) is selectively expressed by subepithelial stromal cells in PP domes. We found that RANKL null mice have <2% of wild-type levels of PP M cells and markedly diminished uptake of 200 nm diameter fluorescent beads. Ab-mediated neutralization of RANKL in adult wild-type mice also eliminated most PP M cells. The M cell deficit in RANKL null mice was corrected by systemic administration of exogenous RANKL. Treatment with RANKL also induced the differentiation of villous M cells on all small intestinal villi with the capacity for avid uptake of Salmonella and Yersinia organisms and fluorescent beads. The RANK receptor for RANKL is expressed by epithelial cells throughout the small intestine. We conclude that availability of RANKL is the critical factor controlling the differentiation of M cells from RANK-expressing intestinal epithelial precursor cells.

Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease

PubMed Central

Emmi, Giacomo; Silvestri, Elena; Bella, Chiara Della; Grassi, Alessia; Benagiano, Marisa; Cianchi, Fabio; Squatrito, Danilo; Cantarini, Luca; Emmi, Lorenzo; Selmi, Carlo; Prisco, Domenico; D’Elios, Mario Milco

2016-01-01

Abstract Background: Gastrointestinal involvement is one of the most serious in Behçet disease, potentially leading to severe complications. Aim of this study was to investigate at mucosal level the T-cell responses in Behçet patients with early intestinal involvement. Methods: We isolated T cells from intestinal mucosa of 8 patients with intestinal symptoms started within 6 months. T lymphocytes were cloned and analyzed for surface phenotype and cytokines production. Results: We obtained 382 T-cell clones: 324 were CD4+ and 58 were CD8+. Within the 324 CD4+ clones, 195 were able to secrete IFN-γ and TNF-α, but not IL-4, nor IL-17 thus showing a polarized Th1 profile, whereas CD4 clones producing both IFN-γ and IL-17 (Th1/Th17 profile) were 79. Likewise, the number of CD8 clones producing type 1 cytokines was higher than those of CD8 clones producing both type 1 and 2 cytokines. Almost all intestinal-derived T-cell clones expressed perforin-mediated cytotoxicity and Fas–Fas Ligand-mediated pro-apoptotic activity. Conclusions: Our results indicate that in the early stages of the disease, both Th1 and Th17 cells drive inflammation leading to mucosal damage via abnormal and long-lasting cytokines production as well as via both perforin- and Fas–Fas ligand-mediated cytotoxicity. Finally, all the T cells at mucosal level were able to produce large amount of TNF-α, suggesting that its production is a property of intestinal T cells of patients with early active intestinal disease. These results support the therapy with anti-TNF-α agents and suggest the use of anti-IL-17 monoclonal antibodies in Behçet patients with early intestinal involvement. PMID:27930541

Regression of gastric intestinal metaplasia after the eradication of Helicobacter pylori infection in a hospital in Mexico.

PubMed

Sánchez Cuén, Jaime Alberto; Irineo Cabrales, Ana Bertha; Bernal Magaña, Gregorio; Peraza Garay, Felipe

2016-12-01

Intestinal metaplasia is a precursor lesion of gastric cancer. Infection by Helicobacter pylori is the principal cause of metaplasia. While evidence of the regression of metaplasia after treatment to eradicate this infection has been demonstrated, controversy remains with regard to this subject. The objective of this study was to determine the frequency of the regression of gastric intestinal metaplasia one year after the eradication of Helicobacter pylori. A prospective longitudinal designed study was carried out. The population studied in this research consisted of patients attending the Endoscopy Unit to undergo an upper endoscopy, in whom various symptoms indicated intestinal metaplasia associated with Helicobacter pylori, and who received standard empiric triple therapy to eradicate the bacteria. An upper endoscopy was performed in which four gastric biopsy samples were taken (two from the antrum and two from the body) before and after the eradicating treatment, with the endoscopic and histological findings studied after one year of monitoring. The statistical analysis was conducted using the Fisher's exact test and the McNemar's test. Forty-six patients were studied, of whom 20 (43.5%) were men and 26 (56.5%) were women, with an average age of 58.9 (DE 11.2). Intestinal metaplasia was found in 46 (100%) patients before treatment and in 21 (45.7%) patients post-eradication. Complete intestinal metaplasia (type I) was found in 35 patients (76.1%) before treatment and in 11 (23.9%) patients post-eradication (p = 0.000), while incomplete intestinal metaplasia (type II) was found in 10 (21.7%) patients before treatment and in 10 (21.7%) patients post-eradication. Non-atrophic chronic gastritis was found in 35 (76.1%) patients before treatment and in 32 (69.6%) patients post-eradication. In this study, gastric intestinal metaplasia associated with Helicobacter pylori infection showed a regression of 54.3% one year after the eradication of this microorganism. This treatment could modify the natural history of the development of gastric cancer.

Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells

PubMed Central

2011-01-01

Background Vaccination with live attenuated SIV can protect against detectable infection with wild-type virus. We have investigated whether target cell depletion contributes to the protection observed. Following vaccination with live attenuated SIV the frequency of intestinal CD4+CCR5+ T cells, an early target of wild-type SIV infection and destruction, was determined at days 3, 7, 10, 21 and 125 post inoculation. Results In naive controls, modest frequencies of intestinal CD4+CCR5+ T cells were predominantly found within the LPL TTrM-1 and IEL TTrM-2 subsets. At day 3, LPL and IEL CD4+CCR5+ TEM cells were dramatically increased whilst less differentiated subsets were greatly reduced, consistent with activation-induced maturation. CCR5 expression remained high at day 7, although there was a shift in subset balance from CD4+CCR5+ TEM to less differentiated TTrM-2 cells. This increase in intestinal CD4+CCR5+ T cells preceded the peak of SIV RNA plasma loads measured at day 10. Greater than 65.9% depletion of intestinal CD4+CCR5+ T cells followed at day 10, but overall CD4+ T cell homeostasis was maintained by increased CD4+CCR5- T cells. At days 21 and 125, high numbers of intestinal CD4+CCR5- naive TN cells were detected concurrent with greatly increased CD4+CCR5+ LPL TTrM-2 and IEL TEM cells at day 125, yet SIV RNA plasma loads remained low. Conclusions This increase in intestinal CD4+CCR5+ T cells, following vaccination with live attenuated SIV, does not correlate with target cell depletion as a mechanism of protection. Instead, increased intestinal CD4+CCR5+ T cells may correlate with or contribute to the protection conferred by vaccination with live attenuated SIV. PMID:21291552

Experimental miniature piglet model for the infection of human norovirus GII.

PubMed

Seo, Dong Joo; Jung, Day; Jung, Soontag; Ha, Seung-Kwon; Ha, Sang-Do; Choi, In-Soo; Myoung, Jinjong; Choi, Changsun

2018-04-01

Ten Yucatan miniature piglets were challenged with the human norovirus (NoV) GII.12/GII.3 CAU140599 strain and five piglets were used as negative controls. Stool, serum, and organs were collected and processed from two NoV-infected piglets and one negative piglet at 1, 2, 3, 5, and 7 days post-inoculation (dpi). NoV was detected in stool and serum samples by real-time RT-PCR. Mild diarrhea was observed at 1-3 dpi. Fecal shedding and viremia were detected intermittently at 1, 3, and 7 dpi. While interferon-α was significantly elevated at 2-3 dpi, interferon-γ was not changed. Immunohistochemistry demonstrated that the NoV capsid antigen was present in macrophages, lymphocytes, and dendritic cells of the stomach, intestines, lymph nodes, spleen, and tonsils. Intestinal epithelium did not exhibit a positive signal for NoV. In addition, negative-sense viral RNA was confirmed in immune cells by fluorescence in situ hybridization. Therefore, NoV might be associated with macrophages and lymphocytes in gastrointestinal tract and immune organs of experimentally infected miniature piglets. © 2017 Wiley Periodicals, Inc.

[Discovery of a focus of intestinal bilharziasis in te Republic of Djibouti].

PubMed

Koeck, J L; Modica, C; Tual, F; Czarnecki, E; Fabre, R; Merle, C; Montfort, F; Jouvenin, N; Cavallo, J D

1999-01-01

An unprecedented pocket of intestinal schistosomiasis was discovered in the Republic of Djibouti in 1997. The first cases were diagnosed in French and Djiboutian tourists who presented initial symptoms of bilharzian infection after bathing in the fresh-water basin under Hassan Gari Bira Falls, near Randa. Seventeen cases were subsequently confirmed by detection of anti-schistosome antibodies using indirect hemagglutination (IH) and indirect immunofluorescence (IIF) and/or detection of Schistosoma mansoni eggs in the stool. Further testing was performed in 35 village inhabitants, mostly children, who had been exposed by bathing in the basin. The IH reaction was positive in 28 patients (80 p. 100) including 17 (49 p. 100) with levels greater than 1/64. In 92 p. 100 of cases, IH findings were confirmed by IIF which indicated that association with hypereosinophilia was common. Schistosoma mansoni eggs were found in stools from 7 patients (19 p. 100) who generally displayed mild hypereosinophilia. Information concerning the zone of risk was distributed and control measures were undertaken as widely as possible in Djibouti and abroad.

Microbial ecology perturbation in human IgA deficiency.

PubMed

Fadlallah, Jehane; El Kafsi, Hela; Sterlin, Delphine; Juste, Catherine; Parizot, Christophe; Dorgham, Karim; Autaa, Gaëlle; Gouas, Doriane; Almeida, Mathieu; Lepage, Patricia; Pons, Nicolas; Le Chatelier, Emmanuelle; Levenez, Florence; Kennedy, Sean; Galleron, Nathalie; de Barros, Jean-Paul Pais; Malphettes, Marion; Galicier, Lionel; Boutboul, David; Mathian, Alexis; Miyara, Makoto; Oksenhendler, Eric; Amoura, Zahir; Doré, Joel; Fieschi, Claire; Ehrlich, S Dusko; Larsen, Martin; Gorochov, Guy

2018-05-02

Paradoxically, loss of immunoglobulin A (IgA), one of the most abundant antibodies, does not irrevocably lead to severe infections in humans but rather is associated with relatively mild respiratory infections, atopy, and autoimmunity. IgA might therefore also play covert roles, not uniquely associated with control of pathogens. We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. Metagenomic analysis highlights an expected pathobiont expansion but a less expected depletion in some typically beneficial symbionts. Gut colonization by species usually present in the oropharynx is also reminiscent of spatial microbiota disorganization. IgM only partially rescues IgA deficiency because not all typical IgA targets are efficiently bound by IgM in the intestinal lumen. Together, IgA appears to play a nonredundant role at the forefront of the immune/microbial interface, away from the intestinal barrier, ranging from pathobiont control and regulation of systemic inflammation to preservation of commensal diversity and community networks. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Immunogenicity and protective efficacy of heparan sulphate binding proteins of Entamoeba histolytica in a guinea pig model of intestinal amoebiasis.

PubMed

Kaur, Upninder; Khurana, Sumeeta; Saikia, Uma Nahar; Dubey, M L

2013-11-01

Entamoeba histolytica infection is associated with considerable morbidity and mortality in the form of intestinal and extraintestinal amoebiasis. No vaccine is yet available for amoebiasis. Heparan Sulphate Binding Proteins (HSBPs) from E. histolytica were evaluated for immunogenicity and protective efficacy in a Guinea pig model. Animals were immunized subcutaneously with 30μg of HSBP by three weekly inoculations. The immunogenicity of HSBP was determined by antibody response (IgG, IgM and IgA), splenocyte proliferation assay and in vitro direct amoebicidal assay with splenic lymphocytes and monocytes from vaccinated and control animals. The efficacy of the vaccine was evaluated by challenge infection to vaccinated and control animals by intra-caecal inoculation of E. histolytica trophozoites and comparing gross and histopathological findings in caeca of these animals. HSBP was found to induce specific anti-amoebic response as seen by specific antibody production and direct amoebicidal activity of splenocytes. The vaccine also showed partial protection against challenge infection in vaccinated animals as shown by mild/absent lesions and histopathological findings. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinicopathological characteristics of duodenal epithelial neoplasms: Focus on tumors with a gastric mucin phenotype (pyloric gland-type tumors).

PubMed

Mitsuishi, Takehiro; Hamatani, Shigeharu; Hirooka, Shinichi; Fukasawa, Nei; Aizawa, Daisuke; Hara, Yuko; Dobashi, Akira; Goda, Kenichi; Fukuda, Takahiro; Saruta, Masayuki; Urashima, Mitsuyoshi; Ikegami, Masahiro

2017-01-01

Epithelial tumors less commonly occur in the duodenum than in the stomach or large intestine. The clinicopathological characteristics of duodenal epithelial tumors remain a matter of debate. We therefore studied resected specimens to investigate the clinicopathological characteristics of duodenal epithelial tumors. Among duodenal epithelial tumors resected endoscopically or surgically in our hospital, we studied the clinicopathological characteristics of 110 adenomas or intramucosal carcinomas. The grade of atypia of all tumors was classified into 3 groups according to the World Health Organization (WHO) 2010 classification. The tumors were immunohistochemically evaluated to determine the frequency of differentiation toward fundic glands. As for patient characteristics, there were 76 men (75.2%) and 25 women (24.8%), with a median age of 65 years (range, 34 to 84). The tumors most commonly arose in the first to second part of the duodenum. Many lesions were flat, and the median tumor diameter was 8.0 mm. The lesions were classified into 2 types according to mucin phenotype: intestinal-type tumors (98 lesions, 89.1%) and gastric-type tumors (12 lesions, 10.9%). Intestinal-type tumors were subdivided into 2 groups: tubular-type tumors (91 lesions, 82.7%) and tubulovillous-type tumors (7 lesions, 6.4%). Gastric-type tumors were classified into 2 types: foveolar type (3 lesions, 2.7%) and pyloric gland-type (PG) tumors (9 lesions, 8.2%). The grade of atypia was significantly higher in gastric-type tumors (p<0.01). PG tumors were gastric-type tumors characterized by pyloric glands and findings suggesting differentiation toward fundic glands. About 10% of the duodenal tumors had a gastric-type mucin phenotype. Gastric-type tumors showed high-grade atypia. In particular, PG tumors showed similarities to PG tumors of the stomach, such as differentiation toward fundic glands.

Diversity of halophilic archaea in fermented foods and human intestines and their application.

PubMed

Lee, Han-Seung

2013-12-01

Archaea are prokaryotic organisms distinct from bacteria in the structural and molecular biological sense, and these microorganisms are known to thrive mostly at extreme environments. In particular, most studies on halophilic archaea have been focused on environmental and ecological researches. However, new species of halophilic archaea are being isolated and identified from high salt-fermented foods consumed by humans, and it has been found that various types of halophilic archaea exist in food products by culture-independent molecular biological methods. In addition, even if the numbers are not quite high, DNAs of various halophilic archaea are being detected in human intestines and much interest is given to their possible roles. This review aims to summarize the types and characteristics of halophilic archaea reported to be present in foods and human intestines and to discuss their application as well.

Investigation of mucosal pattern of gastric antrum using magnifying narrow-band imaging in patients with chronic atrophic fundic gastritis.

PubMed

Yamasaki, Yasushi; Uedo, Noriya; Kanzaki, Hiromitsu; Kato, Minoru; Hamada, Kenta; Aoi, Kenji; Tonai, Yusuke; Matsuura, Noriko; Kanesaka, Takashi; Yamashina, Takeshi; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Ishihara, Ryu; Tomita, Yasuhiko; Iishi, Hiroyasu

2017-01-01

Magnifying narrow-band imaging (M-NBI) can reportedly help predict the presence and distribution of atrophy and intestinal metaplasia in the gastric corpus. However, the micro-mucosal pattern of the antrum shown by M-NBI differs from that of the corpus. We studied the distribution and histology of the micro-mucosal pattern in the antrum based on magnifying endoscopy. Endoscopic images of the greater curvature of the antrum were evaluated in 50 patients with chronic atrophic fundic gastritis (CAFG). The extent of CAFG was evaluated by autofluorescence imaging. The micro-mucosal pattern was evaluated by M-NBI and classified into groove and white villiform types. The localization of white villiform type mucosa was classified into three types in relation to the areae gastricae : null, central, and segmental types. Biopsies were taken from regions showing different micro-mucosal patterns. Associations among the extent of CAFG, micro-mucosal pattern, and histology were examined. As the extent of CAFG increased, the proportion of white villiform type mucosa increased, whereas that of groove type mucosa decreased (P=0.022). In patients with extensive CAFG, most of the areae gastricae was composed of the segmental or central type of white villiform type mucosa (P=0.044). The white villiform type mucosa had significantly higher grades of atrophy (P=0.002) and intestinal metaplasia (P<0.001) than did the groove type mucosa. White villiform type mucosa is indicative of atrophy and intestinal metaplasia in the gastric antrum. It extends to the whole or central part of the areae gastricae as CAFG becomes more extensive.

Less common etiologies of exocrine pancreatic insufficiency

PubMed Central

Singh, Vikesh K; Haupt, Mark E; Geller, David E; Hall, Jerry A; Quintana Diez, Pedro M

2017-01-01

Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases (diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin (CCK); celiac or inflammatory bowel disease (IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery (asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy (PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI (66%-92%). EPI occurs in patients with type 1 (26%-57%) or type 2 diabetes (20%-36%) and is typically mild to moderate; by definition, all patients with type 3c (pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease (4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD (14%-74%) and up to 100% of gastrointestinal surgery patients (47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT. PMID:29093615

Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice.

PubMed

Rogala, Allison R; Schoenborn, Alexi A; Fee, Brian E; Cantillana, Viviana A; Joyce, Maria J; Gharaibeh, Raad Z; Roy, Sayanty; Fodor, Anthony A; Sartor, R Balfour; Taylor, Gregory A; Gulati, Ajay S

2018-02-07

Crohn's disease (CD) represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-related GTPase M ( IRGM ) is an established risk allele in CD. We have shown previously that conventionally raised (CV) mice lacking the IRGM ortholog, Irgm1 exhibit abnormal Paneth cells (PCs) and increased susceptibility to intestinal injury. In the present study, we sought to utilize this model system to determine if environmental conditions impact these phenotypes, as is thought to be the case in human CD. To accomplish this, wild-type and Irgm1 -/- mice were rederived into specific pathogen-free (SPF) and germ-free (GF) conditions. We next assessed how these differential housing environments influenced intestinal injury patterns, and epithelial cell morphology and function in wild-type and Irgm1 -/- mice. Remarkably, in contrast to CV mice, SPF Irgm1 -/- mice showed only a slight increase in susceptibility to dextran sodium sulfate-induced inflammation. SPF Irgm1 -/- mice also displayed minimal abnormalities in PC number and morphology, and in antimicrobial peptide expression. Goblet cell numbers and epithelial proliferation were also unaffected by Irgm1 in SPF conditions. No microbial differences were observed between wild-type and Irgm1 -/- mice, but gut bacterial communities differed profoundly between CV and SPF mice. Specifically, Helicobacter sequences were significantly increased in CV mice; however, inoculating SPF Irgm1 -/- mice with Helicobacter hepaticus was not sufficient to transmit a pro-inflammatory phenotype. In summary, our findings suggest the impact of Irgm1-deficiency on susceptibility to intestinal inflammation and epithelial function is critically dependent on environmental influences. This work establishes the importance of Irgm1 -/- mice as a model to elucidate host-environment interactions that regulate mucosal homeostasis and intestinal inflammatory responses. Defining such interactions will be essential for developing novel preventative and therapeutic strategies for human CD. © 2018. Published by The Company of Biologists Ltd.

[Effect of dexamethasone contamination in drinking water on intestinal flora in mice].

PubMed

Yang, Xi; Li, Xiao-Yu; Si, Dan; Yang, Zhi-Bang; He, Zhong-Yuan; Zhang, Nan-Chen; Zhang, Shan-Shan; Shi, Zhong-Quan

2016-02-01

To evaluate the effect of water pollution with dexamethasone on intestinal flora in mice. Twenty Balb/c mice were randomly divided into control group and low-, moderate- and high-dose dexamethasone groups. The mice in dexamethasone groups were exposed to dexamethasone sodium phosphate in drinking water at doses of 0.035, 0.225, and 2.25 ng for 36 days. The changes in behaviors, fur condition, and feces of the mice were observed daily. All the mice were sacrificed at 36 days and the tissues in the ileocecal region was collected for denaturant gradient gel electrophoresis (DGGE) of 16S rDNA V6 variable regions of microbes and sequence analysis with BLAST. The mice in the 3 dexamethasone groups all showed aggressive behaviors. Cluster analysis of DGGE graph showed relatively stable floras in the ileocecal region in all the mice, but principal component analysis identified differences in the dominating flora among the groups. Diversity analysis of the flora revealed significantly increased amount and types of bacteria in the intestinal flora in all the 3 dexamethasone groups (P<0.05 or 0.01) compared with the control group. Sequence analysis of 16S rDNA V6 regions showed 15 common bacterial species and 2 differential species between the dexamethasone groups and the control group with changes in the type and proportion of the dominating bacterium in the dexamethasone groups. Lactobacillus colonization was detected in the control group but not in moderate- and high-dose dexamethasone groups, and Shigella species were found in the latter two groups. Water contamination with dexamethasone can affect the nervous system of mice, cause changes in the types and amounts of intestinal bacteria and the dominating bacteria, and inhibit the colonization of probiotics in the intestinal floras to increase the risk of invasion by intestinal pathogenic bacteria.

Nocturia and Prevalence of Depressive Symptoms in Japanese Adult Patients With Type 2 Diabetes Mellitus: The Dogo Study.

PubMed

Furukawa, Shinya; Sakai, Takenori; Niiya, Tetsuji; Miyaoka, Hiroaki; Miyake, Teruki; Yamamoto, Shin; Kanzaki, Sayaka; Maruyama, Koutatsu; Tanaka, Keiko; Ueda, Teruhisa; Senba, Hidenori; Torisu, Masamoto; Minami, Hisaka; Tanigawa, Takeshi; Matsuura, Bunzo; Hiasa, Yoichi; Miyake, Yoshihiro

2018-02-01

No studies have investigated the association between nocturia and depressive symptoms in patients with type 2 diabetes mellitus. Because nocturia and depressive symptoms are common in patients with type 2 diabetes, we examined this association in Japanese patients with type 2 diabetes. We studied 762 Japanese patients with type 2 diabetes. A self-administered questionnaire was used to collect information about the variables under study. The subjects were divided into 3 groups according to their nocturnal micturition: 1) no nocturia; 2) mild nocturia (1 void per night) and 3) moderate to severe nocturia (2 or more voids per night). Depressive symptoms were defined as being present when a subject had a Self-Rating Depression Scale score higher than 49. The prevalence values of mild nocturia, moderate to severe nocturia and depressive symptoms were 39.5%, 41.9% and 16.8%, respectively. Both mild nocturia and moderate to severe nocturia were independently positively associated with depressive symptoms in all patients; the adjusted ORs were 1.96 (95% CI 1.06 to 3.77) and 2.58 (95% CI 1.38 to 5.04). In female patients, both mild nocturia and moderate to severe nocturia were independently associated with depressive symptoms; the adjusted ORs were 5.26 (95% CI 1.73 to 20.61) and 6.91 (95% CI 2.15 to 28.54), respectively. In male patients, neither mild nocturia nor moderate to severe nocturia was significantly related to depressive symptoms. In Japanese female patients with type 2 diabetes, nocturia may be positively associated with depressive symptoms. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing.

PubMed

Gao, Shuai; Yan, Liying; Wang, Rui; Li, Jingyun; Yong, Jun; Zhou, Xin; Wei, Yuan; Wu, Xinglong; Wang, Xiaoye; Fan, Xiaoying; Yan, Jie; Zhi, Xu; Gao, Yun; Guo, Hongshan; Jin, Xiao; Wang, Wendong; Mao, Yunuo; Wang, Fengchao; Wen, Lu; Fu, Wei; Ge, Hao; Qiao, Jie; Tang, Fuchou

2018-06-01

The development of the digestive tract is critical for proper food digestion and nutrient absorption. Here, we analyse the main organs of the digestive tract, including the oesophagus, stomach, small intestine and large intestine, from human embryos between 6 and 25 weeks of gestation as well as the large intestine from adults using single-cell RNA-seq analyses. In total, 5,227 individual cells are analysed and 40 cell types clearly identified. Their crucial biological features, including developmental processes, signalling pathways, cell cycle, nutrient digestion and absorption metabolism, and transcription factor networks, are systematically revealed. Moreover, the differentiation and maturation processes of the large intestine are thoroughly investigated by comparing the corresponding transcriptome profiles between embryonic and adult stages. Our work offers a rich resource for investigating the gene regulation networks of the human fetal digestive tract and adult large intestine at single-cell resolution.

Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Response to the Gut Microbiota

PubMed Central

Bates, Jennifer M.; Akerlund, Janie; Mittge, Erika; Guillemin, Karen

2009-01-01

SUMMARY Vertebrates harbor abundant lipopolysaccharide (LPS) or endotoxin in their gut microbiota. Here we demonstrate that the brush border enzyme intestinal alkaline phosphatase (Iap), which dephosphorylates LPS, is induced during establishment of the microbiota and plays a crucial role in promoting mucosal tolerance to gut bacteria in zebrafish. We demonstrate that Iap deficient animals are hypersensitive to LPS toxicity through a mechanism mediated by Myd88 and Tumor Necrosis Factor Receptor (Tnfr). We further show that the endogenous microbiota establish the normal homeostatic level of neutrophils in the intestine through a process involving Myd88 and Tnfr. Iap deficient animals exhibit excessive intestinal neutrophil influx, similar to wild type animals exposed to LPS. When reared germ-free, however, the intestines of Iap deficient animals are devoid of neutrophils, demonstrating that Iap functions to prevent inflammatory responses to resident gut bacteria. PMID:18078689

Commensal Fungi Recapitulate the Protective Benefits of Intestinal Bacteria.

PubMed

Jiang, Tony T; Shao, Tzu-Yu; Ang, W X Gladys; Kinder, Jeremy M; Turner, Lucien H; Pham, Giang; Whitt, Jordan; Alenghat, Theresa; Way, Sing Sing

2017-12-13

Commensal intestinal microbes are collectively beneficial in preventing local tissue injury and augmenting systemic antimicrobial immunity. However, given the near-exclusive focus on bacterial species in establishing these protective benefits, the contributions of other types of commensal microbes remain poorly defined. Here, we show that commensal fungi can functionally replace intestinal bacteria by conferring protection against injury to mucosal tissues and positively calibrating the responsiveness of circulating immune cells. Susceptibility to colitis and influenza A virus infection occurring upon commensal bacteria eradication is efficiently overturned by mono-colonization with either Candida albicans or Saccharomyces cerevisiae. The protective benefits of commensal fungi are mediated by mannans, a highly conserved component of fungal cell walls, since intestinal stimulation with this moiety alone overrides disease susceptibility in mice depleted of commensal bacteria. Thus, commensal enteric fungi safeguard local and systemic immunity by providing tonic microbial stimulation that can functionally replace intestinal bacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon.

PubMed

Jeon, Seong Gyu; Kayama, Hisako; Ueda, Yoshiyasu; Takahashi, Takuya; Asahara, Takashi; Tsuji, Hirokazu; Tsuji, Noriko M; Kiyono, Hiroshi; Ma, Ji Su; Kusu, Takashi; Okumura, Ryu; Hara, Hiromitsu; Yoshida, Hiroki; Yamamoto, Masahiro; Nomoto, Koji; Takeda, Kiyoshi

2012-01-01

Specific intestinal microbiota has been shown to induce Foxp3(+) regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103(+) dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103(+) DCs from Il10(-/-), Tlr2(-/-), and Myd88(-/-) mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103(+) DCs failed to induce IL-10 production from co-cultured Il27ra(-/-) T cells. B. breve treatment of Tlr2(-/-) mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103(+) DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4(+) T cells from wild-type mice, but not Il10(-/-) mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells.

Changes of intestinal mucosal and plasma PYY in a diarrhea model rat and influence of loperamide as the treatment agent for diarrhea.

PubMed

Hirotani, Yoshihiko; Mikajiri, Kyoko; Ikeda, Kenji; Myotoku, Michiaki; Kurokawa, Nobuo

2008-09-01

Peptide YY (PYY) is produced by endocrine cells in the lower gastrointestinal tract. The main functions of PYY are antisecretory effects in the colon and inhibition of gastrointestinal motility. We chose PYY as an index of the intrinsic factor in diarrhea and examined the influence of changes induced in a diarrhea rat model by administration of 4 types of laxative and loperamide hydrochloride (loperamide) as an agent for the treatment of diarrhea. A specific radioimmunoassay was performed to determine plasma and intestinal mucosal PYY concentrations. PYY in the rat intestinal tissue extract was distributed at a high density in the lower intestinal mucosa. In the diarrhea rat model, multiple changes in PYY concentrations in the intestinal mucosa and plasma were observed. In rats administered castor oil and sodium picosulfate, the intestinal mucosal PYY levels significantly decreased in a dose-dependent manner. Plasma PYY levels significantly decreased only in rats administered magnesium citrate. Next, we examined the influence of loperamide administration on the intestinal mucosa and plasma PYY concentrations in these rats. Loperamide administration resulted in multiple changes in plasma and intestinal mucosa PYY concentrations, along with an improvement in the diarrhea. Our research showed that the endocrine hormone PYY is involved in the onset of diarrhea, the course of the condition, and the manifestation of medicinal effects in the lower intestine.

Establishing Caenorhabditis elegans as a model for Mycobacterium avium subspecies hominissuis infection and intestinal colonization

PubMed Central

Everman, Jamie L.; Ziaie, Navid R.; Bechler, Jessica; Bermudez, Luiz E.

2015-01-01

ABSTRACT The nematode Caenorhabditis elegans has become a model system for studying the disease interaction between pathogens and the host. To determine whether the transparent nematode could serve as a useful model for Mycobacterium avium subspecies hominissuis (MAH) infection of the intestinal tract, worms were fed MAH and assayed for the effects of the bacterial infection on the worm. It was observed during feeding that viable MAH increases in the intestinal lumen in a time dependent manner. Ingestion of MAH was deemed non-toxic to worms as MAH-fed populations have similar survival curves to those fed E. coli strain OP50. Pulse-chase analysis using E. coli strain OP50 revealed that MAH colonize the intestinal tract, as viable MAH remain within the intestine after the assay. Visualization of intestinal MAH using histology and transmission electron microscopy demonstrates that MAH localizes to the intestinal lumen, as well as establishes direct contact with intestinal epithelium. Bacterial colonization appears to have a detrimental effect on the microvilli of the intestinal epithelial cells. The MAH ΔGPL/4B2 strain with a mutation in glycopeptidolipid production is deficient in binding to human epithelial cells (HEp-2), as well as deficient in its ability to bind to and colonize the intestinal tract of C. elegans as efficiently as wild-type MAH. These data indicate the C. elegans may serve as a useful model system for MAH pathogenesis and in determining the mechanisms used by MAH during infection and colonization of the intestinal epithelium. PMID:26405050

Dendritic cell-associated immune inflammation of cardiac mucosa: a possible factor in the formation of Barrett's esophagus.

PubMed

Bobryshev, Yuri V; Tran, Dinh; Killingsworth, Murray C; Buckland, Michael; Lord, Reginald V N

2009-03-01

The development of Barrett's esophagus is poorly understood, but it has been suggested that cardiac mucosa is a precursor of intestinal type metaplasia and that inflammation of cardiac mucosa may play a role in the formation of Barrett's esophagus. The present study was undertaken to examine the presence and distribution of immune-inflammatory cells in cardiac mucosa, specifically focusing on dendritic cells because of their importance as regulators of immune reactions. Endoscopic biopsy specimens were obtained from 12 patients with cardiac mucosa without Barrett's esophagus or adenocarcinoma and from 21 patients with Barrett's esophagus without dysplasia (intestinal metaplasia). According to histology, in nine of the 21 specimens with Barrett's esophagus, areas of mucosa composed of cardiac type epithelium-lined glands were present as well. Immunohistochemical staining and electron microscopy were used to examine immune-inflammatory cells in paraffin-embedded sections. Immune-inflammatory cells, including T cells, B cells, dendritic cells, macrophages, and mast cells, were present in the connective tissue matrix that surrounded cardiac type epithelium-lined glands in all patients with cardiac mucosa. Clustering of dendritic cells with each other and with lymphocytes and the intrusion of dendritic cells between glandular mucus cells were observed. In the Barrett's esophagus specimens that contained cardiac type glands, computerized CD83 expression quantitation revealed that there were more dendritic cells in cardiac mucosa than in intestinal metaplasia. Immune-inflammatory infiltrates containing dendritic cells are consistently present in cardiac mucosa. The finding of a larger number of dendritic cells in areas of cardiac mucosa in Barrett's esophagus biopsies suggests that the immune inflammation of cardiac mucosa might play a role in modifying the local tissue environment to promote the development of specialized intestinal type metaplasia.

Epidemiology of Mild Traumatic Brain Injury with Intracranial Hemorrhage: Focusing Predictive Models for Neurosurgical Intervention.

PubMed

Orlando, Alessandro; Levy, A Stewart; Carrick, Matthew M; Tanner, Allen; Mains, Charles W; Bar-Or, David

2017-11-01

To outline differences in neurosurgical intervention (NI) rates between intracranial hemorrhage (ICH) types in mild traumatic brain injuries and help identify which ICH types are most likely to benefit from creation of predictive models for NI. A multicenter retrospective study of adult patients spanning 3 years at 4 U.S. trauma centers was performed. Patients were included if they presented with mild traumatic brain injury (Glasgow Coma Scale score 13-15) with head CT scan positive for ICH. Patients were excluded for skull fractures, "unspecified hemorrhage," or coagulopathy. Primary outcome was NI. Stepwise multivariable logistic regression models were built to analyze the independent association between ICH variables and outcome measures. The study comprised 1876 patients. NI rate was 6.7%. There was a significant difference in rate of NI by ICH type. Subdural hematomas had the highest rate of NI (15.5%) and accounted for 78% of all NIs. Isolated subarachnoid hemorrhages had the lowest, nonzero, NI rate (0.19%). Logistic regression models identified ICH type as the most influential independent variable when examining NI. A model predicting NI for isolated subarachnoid hemorrhages would require 26,928 patients, but a model predicting NI for isolated subdural hematomas would require only 328 patients. This study highlighted disparate NI rates among ICH types in patients with mild traumatic brain injury and identified mild, isolated subdural hematomas as most appropriate for construction of predictive NI models. Increased health care efficiency will be driven by accurate understanding of risk, which can come only from accurate predictive models. Copyright © 2017 Elsevier Inc. All rights reserved.

Key differences between apoC-III regulation and expression in intestine and liver.

PubMed

West, Gabrielle; Rodia, Cayla; Li, Diana; Johnson, Zania; Dong, Hongli; Kohan, Alison B

2017-09-23

ApoC-III is a critical cardiovascular risk factor, and humans expressing null mutations in apoC-III are robustly protected from cardiovascular disease. Because of its critical role in elevating plasma lipids and CVD risk, hepatic apoC-III regulation has been studied at length. Considerably less is known about the factors that regulate intestinal apoC-III. In this work, we use primary murine enteroids, Caco-2 cells, and dietary studies in wild-type mice to show that intestinal apoC-III expression does not change in response to fatty acids, glucose, or insulin administration, in contrast to hepatic apoC-III. Intestinal apoC-III is not sensitive to changes in FoxO1 expression (which is itself very low in the intestine, as is FoxO1 target IGFBP-1), nor is intestinal apoC-III responsive to western diet, a significant contrast to hepatic apoC-III stimulation during western diet. These data strongly suggest that intestinal apoC-III is not a FoxO1 target and support the idea that apoC-III is not regulated coordinately with hepatic apoC-III, and establishes another key aspect of apoC-III that is unique in the intestine from the liver. Copyright © 2017 Elsevier Inc. All rights reserved.

Two-dimensional grayscale ultrasound and spectral Doppler waveform evaluation of dogs with chronic enteropathies.

PubMed

Gaschen, Lorrie; Kircher, Patrick

2007-08-01

Sonography is an important diagnostic tool to examine the gastrointestinal tract of dogs with chronic diarrhea. Two-dimensional grayscale ultrasound parameters to assess for various enteropathies primarily focus on wall thickness and layering. Mild, generalized thickening of the intestinal wall with maintenance of the wall layering is common in inflammatory bowel disease. Quantitative and semi-quantitative spectral Doppler arterial waveform analysis can be utilized for various enteropathies, including inflammatory bowel disease and food allergies. Dogs with inflammatory bowel disease have inadequate hemodynamic responses during digestion of food. Dogs with food allergies have prolonged vasodilation and lower resistive and pulsatility indices after eating allergen-inducing foods.

Two outbreaks of type C and type D botulism in sheep and goats in south Africa.

PubMed

Van der Lugt, J J; De Wet, S C; Bastianello, S S; Kellerman, T S; Van Jaarsveld, L P

1995-06-01

Two outbreaks of botulism in sheep and goats are described; in one, 329 out of 900 sheep in a feedlot died within 9 d of the onset of the disease and in the other, 100 sheep and goats out of 330 succumbed over a period of about 3 weeks. Animals were found dead or died suddenly, without exhibiting clinical signs. Others stood with lowered heads and showed drooling of saliva or a stiff gait. Paresis and/or paralysis were frequent signs in the terminal stages of the disease. Gross lesions such as the accumulation of fluids in body cavities, pulmonary oedema, foam in the trachea, epicardial haemorrhages and congestion of the mucosa of the small intestine, suggestive of heart failure, were present in animals from both outbreaks. Botulism was confirmed via the mouse toxicity test, by the demonstration of Type C and Type D toxins in the feed and intestinal contents of sheep from the first outbreak and Type D toxin in intestinal contents of sheep from the second. The clinical signs and macropathology in the outbreaks of botulism in sheep and goats in South Africa may resemble "krimpsiekte" and cardiac glycoside and ionophore poisoning, as well as other conditions causing heart failure.

Distinct Effects of Type I and III Interferons on Enteric Viruses

PubMed Central

Peterson, Stefan T.

2018-01-01

Interferons (IFNs) are key host cytokines in the innate immune response to viral infection, and recent work has identified unique roles for IFN subtypes in regulating different aspects of infection. Currently emerging is a common theme that type III IFNs are critical in localized control of infection at mucosal barrier sites, while type I IFNs are important for broad systemic control of infections. The intestine is a particular site of interest for exploring these effects, as in addition to being the port of entry for a multitude of pathogens, it is a complex tissue with a variety of cell types as well as the presence of the intestinal microbiota. Here we focus on the roles of type I and III IFNs in control of enteric viruses, discussing what is known about signaling downstream from these cytokines, including induction of specific IFN-stimulated genes. We review viral strategies to evade IFN responses, effects of IFNs on the intestine, interactions between IFNs and the microbiota, and briefly discuss the role of IFNs in controlling viral infections at other barrier sites. Enhanced understanding of the coordinate roles of IFNs in control of viral infections may facilitate development of antiviral therapeutic strategies; here we highlight potential avenues for future exploration. PMID:29361691

[Celiac disease in a group of children and adolescents with type 1 diabetes mellitus].

PubMed

Brandt, Katia G; Silva, Giselia A P; Antunes, Margarida M C

2004-12-01

To know the prevalence of celiac disease (CD) in a group of children and adolescents with type I diabetes mellitus. A cross sectional study was conducted at the Instituto Materno Infantil de Pernambuco (IMIP) in March 2000. The sample consisted of 19 children and adolescents with type I diabetes mellitus that had the human anti-tissue transglutaminase antibodies assessed using kits from the Eurospital Laboratory. In case of positive results it was realized small intestine biopsy to confirm the diagnosis. For the calculation of the prevalence of CD it was considered the number of patients with serum positive histological alterations of the mucous membrane of the small intestine compatible with CD. Four patients presented serum positivity for human anti-tissue transglutaminase antibodies with a serum prevalence of 21% (4/19). Out of these four subjects, three who accomplished small intestine biopsy presented histological alterations compatible with CD. The prevalence of CD in this group was 15.8% (3/19). The prevalence of CD in this study group was high, suggesting that those with type I diabetes mellitus should be led as a group of high risk to develop this disease.

Traditional Chinese medicine typing of affective disorders and treatment.

PubMed

Zhang, L D; Zhang, Y L; Xu, S H; Zhou, G; Jin, S B

1994-01-01

According to the theory of Traditional Chinese Medicine (TCM), 50 patients with affective disorders were typed into the categories of depressed liver resulting in fire, mild Yang deficiency and mild Yin deficiency and were treated with Xiao Yao San Jia Wei. The results are 26 patients with marked improvement, 17 patients with improvement and 7 patients with no improvement.

Significance of Peptide Transporter 1 in the Intestinal Permeability of Valacyclovir in Wild-Type and PepT1 Knockout Mice

PubMed Central

Yang, Bei

2013-01-01

The purpose of this study was to quantitatively determine the contribution of PepT1 [peptide transporter 1 (SLC15A1)] to the intestinal permeability of valacyclovir, an ester prodrug of the antiviral drug acyclovir. In situ single-pass intestinal perfusions were employed (pH 6.5 × 90 minutes) to assess the effective permeability (Peff) of 100 μM [3H]valacyclovir in wild-type and PepT1 knockout mice. Acyclovir pharmacokinetics was also evaluated after oral administration of 25 nmol/g valacyclovir. In wild-type mice, jejunal uptake of valacyclovir was best described by both saturable (Km = 10.2 mM) and nonsaturable components where the saturable pathway accounted for 82% of total transport. Valacyclovir Peff was 2.4 × 10−4 cm/s in duodenum, 1.7 × 10−4 cm/s in jejunum, 2.1 × 10−4 cm/s in ileum, and 0.27 × 10−4 cm/s in colon. In Pept1 knockout mice, Peff values were about 10% of that in wild-type animals for these small intestinal segments. Valacyclovir Peff was similar in the colon of both genotypes. There were no differences in valacyclovir Peff between any of the intestinal segments of PepT1 knockout mice. Valacyclovir Peff was significantly reduced by the dipeptide glycylsarcosine and the aminocephalosporin cefadroxil, but not by the amino acids l-valine or l-histidine, the organic acid p-aminohippurate, or the organic base tetraethylammonium (all at 25 mM). PepT1 ablation resulted in 3- to 5-fold reductions in the in vivo rate and extent of valacyclovir absorption. Our findings conclusively demonstrate, using in situ and in vivo validations in genetically modified mice, that PepT1 has a major influence in improving the oral absorption of valacyclovir. PMID:23264448

Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease.

PubMed

Hayashi, Atsuko; Nomura, Hiroshi; Mochizuki, Ruriko; Ohnuma, Ayumu; Kimpara, Teiko; Suzuki, Kyoko; Mori, Etsuro

2015-01-01

We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients.

Intra amniotic administration of raffinose and stachyose affects the intestinal brush border functionality and alters gut microflora populations

USDA-ARS?s Scientific Manuscript database

This study investigates the effectiveness of two types of prebiotics, stachyose and raffinose, which are present in staple food crops that are widely consumed in regions where dietary Fe deficiency is a health concern. The hypothesis is that these prebiotics will improve Fe status, intestinal functi...

Without Adaptive Immunity, There's a Cost to Responding STAT.

PubMed

Brown, Eric M; Xavier, Ramnik J

2018-04-03

The relative contributions of innate and adaptive immune mechanisms in responding to the intestinal microbiota during ontogeny are largely unknown. A recent study in Nature by Mao et al. (2018) elegantly dissects the role of each cell type in the intestine and further describes the metabolic cost to innate immunity. Copyright © 2018. Published by Elsevier Inc.

Interactions between bacteria and the gut mucosa: Do enteric neurotransmitters acting on the mucosal epithelium influence intestinal colonization or infection?

USDA-ARS?s Scientific Manuscript database

The intestinal epithelium is a critical barrier between the internal and external milieux of the mammalian host. Epithelial interactions between these two host environments have been shown to be modulated by several different, cross-communicating cell types residing in the gut mucosa. These includ...

Interactions between bacteria and the gut mucosa: Do enteric neurotransmitters acting on the mucosal epithelium influence intestinal colonization or infection?

USDA-ARS?s Scientific Manuscript database

The intestinal epithelium is a critical barrier between the internal and external milieux of the mammalian host. Epithelial interactions between these two host environments have been shown to be modulated by several different, cross-communicating cell types residing in the gut mucosa. These include ...

Role of macrophages in the altered epithelial function during a type 2 immune response induced by enteric nematode infection

USDA-ARS?s Scientific Manuscript database

Two major functions of the intestinal epithelium are to act as a physical barrier and to regulate the movement of nutrients, ions and fluid. Nematode infection induces alterations in smooth and epithelial cell function, including increased fluid in the intestinal lumen, which are attributed to a ST...

Microvillus-Specific Protein Tyrosine Phosphatase SAP-1 Plays a Role in Regulating the Intestinal Paracellular Transport of Macromolecules.

PubMed

Mori, Shingo; Kamei, Noriyasu; Murata, Yoji; Takayama, Kozo; Matozaki, Takashi; Takeda-Morishita, Mariko

2017-09-01

The stomach cancer-associated protein tyrosine phosphatase 1 (SAP-1) is a receptor-type protein tyrosine phosphatase that is specifically expressed on the apical membrane of the intestinal epithelium. SAP-1 is known to maintain the balance of phosphorylation of proteins together with protein kinases; however, its biological function and impact on pharmacokinetics in the intestine remain unclear. The present study, therefore, aimed at clarifying the relationship between SAP-1 and the intestinal absorption behaviors of typical transporter substrates and macromolecules. The endogenous levels of glucose and total cholesterol in the blood were similar between wild-type and SAP-1-deficient mice (Sap1 -/- ), suggesting no contribution of SAP-1 to biogenic influx. Moreover, in vitro transport study with everted ileal sacs demonstrated that there was no difference in the absorption of breast cancer resistance protein, P-glycoprotein, and peptide transporter substrates between both mice. However, absorptive clearance of macromolecular model dextrans (FD-4 and FD-10) in Sap1 -/- mice was significantly higher than that in wild-type mice, and this was confirmed by the trend of increased FD-4 absorption from colonic loops of Sap1 -/- mice. Therefore, the results of this study suggest the partial contribution of SAP-1 to the regulated transport of hydrophilic macromolecules through paracellular tight junctions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

SipA Activation of Caspase-3 Is a Decisive Mediator of Host Cell Survival at Early Stages of Salmonella enterica Serovar Typhimurium Infection

PubMed Central

McIntosh, Anne; Meikle, Lynsey M.; Ormsby, Michael J.; McCormick, Beth A.; Christie, John M.; Brewer, James M.; Roberts, Mark

2017-01-01

ABSTRACT Salmonella invasion protein A (SipA) is a dual-function effector protein that plays roles in both actin polymerization and caspase-3 activation in intestinal epithelial cells. To date its function in other cell types has remained largely unknown despite its expression in multiple cell types and its extracellular secretion during infection. Here we show that in macrophages SipA induces increased caspase-3 activation early in infection. This activation required a threshold level of SipA linked to multiplicity of infection and may be a limiting factor controlling bacterial numbers in infected macrophages. In polymorphonuclear leukocytes, SipA or other Salmonella pathogenicity island 1 effectors had no effect on induction of caspase-3 activation either alone or in the presence of whole bacteria. Tagging of SipA with the small fluorescent phiLOV tag, which can pass through the type three secretion system, allowed visualization and quantification of caspase-3 activation by SipA-phiLOV in macrophages. Additionally, SipA-phiLOV activation of caspase-3 could be tracked in the intestine through multiphoton laser scanning microscopy in an ex vivo intestinal model. This allowed visualization of areas where the intestinal epithelium had been compromised and demonstrated the potential use of this fluorescent tag for in vivo tracking of individual effectors. PMID:28630067

Non-HLA Antibodies May Accelerate Immune Responses After Intestinal and Multivisceral Transplantation.

PubMed

Gerlach, Undine Ariane; Lachmann, Nils; Ranucci, Giuseppina; Sawitzki, Birgit; Schoenemann, Constanze; Pratschke, Johann; Dragun, Duska; Pascher, Andreas

2017-01-01

Non-HLA alloantibodies and autoantibodies are involved in allograft rejection in kidney and heart transplantation. Their role in intestinal transplantation has not yet been described. We examined the development of antiangiotensin II type I receptor antibodies (anti-AT1R) and antiendothelin type A receptor antibodies associated with the clinical course and histopathological findings of intestinal transplantation recipients. Thirty-seven patients underwent intestinal or multivisceral transplantation. Non-HLA antibodies (non-HLAabs) were screened in 29 transplant recipients. Antibody-levels greater than 12 U/L were considered positive and were evaluated retrospectively regarding rejection episodes. Twenty patients developed anti-AT1R and/or antiendothelin type A receptor antibodies (non-HLAabs group), 9 did not (control group). The non-HLAabs group had a higher rate of allograft rejection than controls (80% vs 55%), especially a higher rate of antibody-mediated rejections (55% vs 11%, P < 0.01) with detection of donor-specific anti-HLAabs. All rejection episodes in the non-HLAabs group appeared around the time of positive non-HLAabs detection. Five patients had acute cellular rejections at the time of non-HLAabs development, 4 had viral infections. Our data suggest that antibody-mediated mechanisms targeting antigens beyond HLA may trigger and accelerate immune responses. Given the possibility of pharmacologic targeting of non-HLA receptors, future studies will focus on the explanation of mechanisms how non-HLAabs may enhance rejection and affect long-term allograft survival.

Bioengineered intestinal muscularis complexes with long-term spontaneous and periodic contractions

PubMed Central

Wang, Qianqian; Wang, Ke; Solorzano-Vargas, R. Sergio; Lin, Po-Yu; Walthers, Christopher M.; Thomas, Anne-Laure; Martín, Martín G.

2018-01-01

Although critical for studies of gut motility and intestinal regeneration, the in vitro culture of intestinal muscularis with peristaltic function remains a significant challenge. Periodic contractions of intestinal muscularis result from the coordinated activity of smooth muscle cells (SMC), the enteric nervous system (ENS), and interstitial cells of Cajal (ICC). Reproducing this activity requires the preservation of all these cells in one system. Here we report the first serum-free culture methodology that consistently maintains spontaneous and periodic contractions of murine and human intestinal muscularis cells for months. In this system, SMC expressed the mature marker myosin heavy chain, and multipolar/dipolar ICC, uniaxonal/multipolar neurons and glial cells were present. Furthermore, drugs affecting neural signals, ICC or SMC altered the contractions. Combining this method with scaffolds, contracting cell sheets were formed with organized architecture. With the addition of intestinal epithelial cells, this platform enabled up to 11 types of cells from mucosa, muscularis and serosa to coexist and epithelial cells were stretched by the contracting muscularis cells. The method constitutes a powerful tool for mechanistic studies of gut motility disorders and the functional regeneration of the engineered intestine. PMID:29718926

Intestinal Rehabilitation Programs in the Management of Pediatric Intestinal Failure and Short Bowel Syndrome.

PubMed

Merritt, Russell J; Cohran, Valeria; Raphael, Bram P; Sentongo, Timothy; Volpert, Diana; Warner, Brad W; Goday, Praveen S

2017-11-01

Intestinal failure is a rare, debilitating condition that presents both acute and chronic medical management challenges. The condition is incompatible with life in the absence of the safe application of specialized and individualized medical therapy that includes surgery, medical equipment, nutritional products, and standard nursing care. Intestinal rehabilitation programs are best suited to provide such complex care with the goal of achieving enteral autonomy and oral feeding with or without intestinal transplantation. These programs almost all include pediatric surgeons, pediatric gastroenterologists, specialized nurses, and dietitians; many also include a variety of other medical and allied medical specialists. Intestinal rehabilitation programs provide integrated interdisciplinary care, more discussion of patient management by involved specialists, continuity of care through various treatment interventions, close follow-up of outpatients, improved patient and family education, earlier treatment of complications, and learning from the accumulated patient databases. Quality assurance and research collaboration among centers are also goals of many of these programs. The combined and coordinated talents and skills of multiple types of health care practitioners have the potential to ameliorate the impact of intestinal failure and improve health outcomes and quality of life.

Parenteral Nutrition and Intestinal Failure

PubMed Central

Bielawska, Barbara; Allard, Johane P.

2017-01-01

Severe short bowel syndrome (SBS) is a major cause of chronic (Type 3) intestinal failure (IF) where structural and functional changes contribute to malabsorption and risk of micronutrient deficiencies. Chronic IF may be reversible, depending on anatomy and intestinal adaptation, but most patients require long-term nutritional support, generally in the form of parenteral nutrition (PN). SBS management begins with dietary changes and pharmacologic therapies taking into account individual anatomy and physiology, but these are rarely sufficient to avoid PN. New hormonal therapies targeting intestinal adaptation hold promise. Surgical options for SBS including intestinal transplant are available, but have significant limitations. Home PN (HPN) is therefore the mainstay of treatment for severe SBS. HPN involves chronic administration of macronutrients, micronutrients, fluid, and electrolytes via central venous access in the patient’s home. HPN requires careful clinical and biochemical monitoring. Main complications of HPN are related to venous access (infection, thrombosis) and metabolic complications including intestinal failure associated liver disease (IFALD). Although HPN significantly impacts quality of life, outcomes are generally good and survival is mostly determined by the underlying disease. As chronic intestinal failure is a rare disease, registries are a promising strategy for studying HPN patients to improve outcomes. PMID:28481229

Parenteral Nutrition and Intestinal Failure.

PubMed

Bielawska, Barbara; Allard, Johane P

2017-05-06

Severe short bowel syndrome (SBS) is a major cause of chronic (Type 3) intestinal failure (IF) where structural and functional changes contribute to malabsorption and risk of micronutrient deficiencies. Chronic IF may be reversible, depending on anatomy and intestinal adaptation, but most patients require long-term nutritional support, generally in the form of parenteral nutrition (PN). SBS management begins with dietary changes and pharmacologic therapies taking into account individual anatomy and physiology, but these are rarely sufficient to avoid PN. New hormonal therapies targeting intestinal adaptation hold promise. Surgical options for SBS including intestinal transplant are available, but have significant limitations. Home PN (HPN) is therefore the mainstay of treatment for severe SBS. HPN involves chronic administration of macronutrients, micronutrients, fluid, and electrolytes via central venous access in the patient's home. HPN requires careful clinical and biochemical monitoring. Main complications of HPN are related to venous access (infection, thrombosis) and metabolic complications including intestinal failure associated liver disease (IFALD). Although HPN significantly impacts quality of life, outcomes are generally good and survival is mostly determined by the underlying disease. As chronic intestinal failure is a rare disease, registries are a promising strategy for studying HPN patients to improve outcomes.

Differential expression of pancreatic protein and chemosensing receptor mRNAs in NKCC1-null intestine.

PubMed

Bradford, Emily M; Vairamani, Kanimozhi; Shull, Gary E

2016-02-15

To investigate the intestinal functions of the NKCC1 Na(+)-K(+)-2Cl cotransporter (SLC12a2 gene), differential mRNA expression changes in NKCC1-null intestine were analyzed. Microarray analysis of mRNA from intestines of adult wild-type mice and gene-targeted NKCC1-null mice (n = 6 of each genotype) was performed to identify patterns of differential gene expression changes. Differential expression patterns were further examined by Gene Ontology analysis using the online Gorilla program, and expression changes of selected genes were verified using northern blot analysis and quantitative real time-polymerase chain reaction. Histological staining and immunofluorescence were performed to identify cell types in which upregulated pancreatic digestive enzymes were expressed. Genes typically associated with pancreatic function were upregulated. These included lipase, amylase, elastase, and serine proteases indicative of pancreatic exocrine function, as well as insulin and regenerating islet genes, representative of endocrine function. Northern blot analysis and immunohistochemistry showed that differential expression of exocrine pancreas mRNAs was specific to the duodenum and localized to a subset of goblet cells. In addition, a major pattern of changes involving differential expression of olfactory receptors that function in chemical sensing, as well as other chemosensing G-protein coupled receptors, was observed. These changes in chemosensory receptor expression may be related to the failure of intestinal function and dependency on parenteral nutrition observed in humans with SLC12a2 mutations. The results suggest that loss of NKCC1 affects not only secretion, but also goblet cell function and chemosensing of intestinal contents via G-protein coupled chemosensory receptors.

Risk factors associated with intestinal necrosis in children with failed non-surgical reduction for intussusception.

PubMed

Huang, Hui-Ya; Huang, Xiao-Zhong; Han, Yi-Jiang; Zhu, Li-Bin; Huang, Kai-Yu; Lin, Jing; Li, Zhong-Rong

2017-05-01

Intestinal necrosis is the most serious complication of intussusception. The risk factors associated with intestinal necrosis in pediatric patients with intussusception have not been well characterized. This study aimed to investigate the risk factors associated with intestinal necrosis in pediatric patients with failed non-surgical reduction for intussusception. Hospitalized patients who failed the air-enema reduction for intussusception in the outpatient department and subsequently underwent surgery were retrospectively reviewed. All cases were categorized into two groups: intestinal necrosis group and non-intestinal necrosis group based on the surgical findings. Demographic and clinical features including the findings from the surgery were recorded and analyzed. Factors associated with intestinal necrosis were analyzed using univariate and multivariate unconditional logistic regression analyses. A total of 728 cases were included. Among them, 171 had intestinal necrosis at the time of surgery. The group with intestinal necrosis had a longer duration of symptom or length of illness (P = 0.000), and younger (P = 0.000) than the non-intestinal necrosis group. Complex/compound type of intussusceptions is more likely to have intestinal necrosis. Multivariate analysis showed that the presence of grossly bloody stool (OR = 2.12; 95% CI 1.19-3.76, P = 0.010) and duration of symptom (OR = 1.07; 95% CI 1.06-1.08, P = 0.000) were independent risk factors for intestinal necrosis in patients hospitalized for surgical reduction for intussusceptions. At time of admission, the presence of bloody stools and duration of symptom are the important risk factors for developing intestinal necrosis for those patients who failed non-surgical reduction. The length of illness has the highest sensitivity and specificity to correlate with intestinal necrosis. This finding may suggest that we should take the intussusception cases that have the longer duration of symptom directly to operation room for reduction.

An immunohistochemical study of endocrine cells in the alimentary tract of the grass lizard, Takydromus wolteri Fischer (Laceridae).

PubMed

Lee, Hyeung Sik; Ku, Sae Kwang

2004-01-01

Distribution patterns and the relative frequency of different types of endocrine cells were demonstrated in the alimentary tract of the grass lizard, Takydromus wolteri, using nine specific antibodies raised against mammalian regulatory peptides. The alimentary tract of the lizard was divided into six portions from the esophagus to the rectum. Most endocrine cells were found in the epithelial lining and were generally spindle shaped with long cytoplasmic processes ending in the lumen (open cell type), whereas cells that were spherical in shape (closed cell type) were occasionally found in gastric, esophageal and intestinal glands. Endocrine cells were stained for the following regulatory peptides: bovine Sp-1/chromogranin (BCG), serotonin, somatostatin, gastrin, cholecystokinin (CCK)-8, glucagon, insulin, human pancreatic polypeptide (HPP) and secretin. Cells stained for BCG and serotonin were present throughout the entire gastrointestinal tract and they occurred with the highest frequency in stomach and pylorus, respectively. Somatostatin-positive cells were detected throughout the entire gastrointestinal tract except for the esophagus and large intestine, and were most predominant in pylorus and duodenum. Cells stained for gastrin were restricted to the pylorus and duodenum and occurred with a relatively low frequency. CCK-8-positive cells were observed from pylorus to small intestine and showed the highest frequency in the pylorus. Glucagon- and insulin-containing cells were located in duodenum and small intestine but were found only rarely. HPP-stained cells were detected in duodenum and small intestine with the highest frequency in duodenum. Cells stained for secretin were restricted to duodenum and were found only rarely. In conclusion, distribution patterns and the relative frequency of these endocrine cells correspond well with previous reports on distribution patterns of endocrine cells in reptile species but some deviating patterns were also observed.

TGR5 signalling inhibits the production of pro-inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease

PubMed Central

Yoneno, Kazuaki; Hisamatsu, Tadakazu; Shimamura, Katsuyoshi; Kamada, Nobuhiko; Ichikawa, Riko; Kitazume, Mina T; Mori, Maiko; Uo, Michihide; Namikawa, Yuka; Matsuoka, Katsuyoshi; Sato, Toshiro; Koganei, Kazutaka; Sugita, Akira; Kanai, Takanori; Hibi, Toshifumi

2013-01-01

Bile acids (BAs) play important roles not only in lipid metabolism, but also in signal transduction. TGR5, a transmembrane receptor of BAs, is an immunomodulative factor, but its detailed mechanism remains unclear. Here, we aimed to delineate how BAs operate in immunological responses via the TGR5 pathway in human mononuclear cell lineages. We examined TGR5 expression in human peripheral blood monocytes, several types of in vitro differentiated macrophages (Mϕs) and dendritic cells. Mϕs differentiated with macrophage colony-stimulating factor and interferon-γ (Mγ-Mϕs), which are similar to the human intestinal lamina propria CD14+ Mϕs that contribute to Crohn's disease (CD) pathogenesis by production of pro-inflammatory cytokines, highly expressed TGR5 compared with any other type of differentiated Mϕ and dendritic cells. We also showed that a TGR5 agonist and two types of BAs, deoxycholic acid and lithocholic acid, could inhibit tumour necrosis factor-α production in Mγ-Mϕs stimulated by commensal bacterial antigen or lipopolysaccharide. This inhibitory effect was mediated by the TGR5–cAMP pathway to induce phosphorylation of c-Fos that regulated nuclear factor-κB p65 activation. Next, we analysed TGR5 levels in lamina propria mononuclear cells (LPMCs) obtained from the intestinal mucosa of patients with CD. Compared with non-inflammatory bowel disease, inflamed CD LPMCs contained more TGR5 transcripts. Among LPMCs, isolated CD14+ intestinal Mϕs from patients with CD expressed TGR5. In isolated intestinal CD14+ Mϕs, a TGR5 agonist could inhibit tumour necrosis factor-α production. These results indicate that TGR5 signalling may have the potential to modulate immune responses in inflammatory bowel disease. PMID:23566200

Prevalence of Helicobacter pylori infection and intestinal metaplasia in subjects who had undergone surgery for gastric adenocarcinoma in Northwest Italy

PubMed Central

Palestro, Giorgio; Pellicano, Rinaldo; Fronda, Gian Ruggero; Valente, Guido; Giuli, Marco De; Soldati, Tito; Pugliese, Agostino; Taraglio, Stefano; Garino, Mauro; Campra, Donata; Cutufia, Miguel Angel; Margaria, Elena; Spinzi, Giancarlo; Ferrara, Aldo; Marenco, Giorgio; Rizzetto, Mario; Ponzetto, Antonio

2005-01-01

AIM: To investigate the seroprevalence of Helicobacter pylori (H pylori) infection and its more virulent strains as well as the correlation with the histologic features among patients who had undergone surgery for gastric cancer (GC). METHODS: Samples from 317 (184 males, 133 females, mean age 69±3.4 years) consecutive patients who had undergone surgery for gastric non-cardia adenocarcinoma were included in the study. Five hundred and fifty-five (294 males, 261 females, mean age 57.3±4.1 years) patients consecutively admitted to the Emergency Care Unit served as control. Histological examination of tumor, lymph nodes and other tissues obtained at the time of surgery represented the diagnostic “gold standard”. An enzyme immunosorbent assay was used to detect serum anti-H pylori (IgG) antibodies and Western blotting technique was utilized to search for anti-CagA protein (IgG). RESULTS: Two hundred and sixty-one of three hundred and seventeen (82.3%) GC patients and 314/555 (56.5%) controls were seropositive for anti-H pylori (P<0.0001; OR, 3.58; 95%CI, 2.53-5.07). Out of the 317 cases, 267 (84.2%) were seropositive for anti-CagA antibody vs 100 out of 555 (18%) controls (P<0.0001; OR, 24.30; 95%CI, 16.5-35.9). There was no difference between the frequency of H pylori in intestinal type carcinoma (76.2%) and diffuse type cancer (78.8%). Intestinal metaplasia (IM) was more frequent but not significant in the intestinal type cancer (83.4% vs 75.2% in diffuse type and 72.5% in mixed type). Among the patients examined for IM, 39.8% had IM type I, 8.3% type II and 51.9% type III (type III vs others, P = 0.4). CONCLUSION: This study confirms a high seroprevalence of H pylori infection in patients suffering from gastric adenocarcinoma and provides further evidence that searching for CagA status over H pylori infection might confer additional benefit in identifying populations at greater risk for this tumor. PMID:16437659

Role of T Cell TGF-β Signaling in Intestinal Cytokine Responses and Helminthic Immune Modulation

PubMed Central

Ince, M. Nedim; Elliott, David E.; Setiawan, Tommy; Metwali, Ahmed; Blum, Arthur; Chen, Hung-lin; Urban, Joseph F.; Flavell, Richard A.; Weinstock, Joel V.

2010-01-01

Colonization with helminthic parasites induces mucosal regulatory cytokines, like IL-10 or TGF-β that are important in suppressing colitis. Helminths induce mucosal T cell IL-10 secretion and regulate lamina propria mononuclear cell Th1 cytokine generation in an IL-10 dependent manner in wild-type mice. Helminths also stimulate mucosal TGF-β release. As TGF-β exerts major regulatory effects on T lymphocytes, we investigated the role of T lymphocyte TGF-β signaling in helminthic modulation of intestinal immunity. T cell TGF-β signaling is interrupted in TGF-βRII DN mice by T cell-specific over-expression of a dominant negative TGF-β receptor II. We studied lamina propria mononuclear cell responses in wild-type and TGF-βRII DN mice that were uninfected or colonized with the nematode, Heligmosomoides polygyrus. Our results indicate an essential role of T cell TGF-β signaling in limiting mucosal Th1 and Th2 responses. Furthermore, we demonstrate that helminthic induction of intestinal T cell IL-10 secretion requires intact T cell TGF-β signaling pathway. Helminths fail to curtail robust, dysregulated intestinal Th1 cytokine production and chronic colitis in TGF-βRII DN mice. Thus, T cell TGF-β signaling is essential for helminthic stimulation of mucosal IL-10 production, helminthic modulation of intestinal interferon-γ generation and H. polygyrus-mediated suppression of chronic colitis. PMID:19544487

Expression of recombinant human lysozyme in bacterial artificial chromosome transgenic mice promotes the growth of Bifidobacterium and inhibits the growth of Salmonella in the intestine.

PubMed

Dan, Lu; Liu, Shen; Shang, Shengzhe; Zhang, Huihua; Zhang, Ran; Li, Ning

2018-04-20

Targeted gene modification is a novel intervention strategy to increase disease resistance more quickly than traditional animal breeding. Human lysozyme, a natural, non-specific immune factor, participates in innate immunity, exerts a wide range of antimicrobial activities against pathogens, and has immuneregulatory effects. Therefore, it is a candidate gene for improved disease resistance in animals. In this study, we successfully generated a transgenic mouse model by microinjecting a modified bacterial artificial chromosome containing a recombinant human lysozyme (rhLZ) gene into the pronuclei of fertilized mouse embryos. rhLZ was expressed in serum, liver, spleen, lung, kidney, stomach, small intestine, and large intestine but not in milk. rhLZ protein concentrations in the serum of transgenic mice ranged from 2.09 to 2.60 mg/l. To examine the effect of rhLZ on intestinal microbiota, total aerobes, total anaerobes, Clostridium, Enterococcus, Streptococcus, Salmonella, Escherichia coli, Staphylococcus, Bifidobacterium, and Lactobacillus were measured in the intestines of transgenic and wild type mice. Results showed that Bifidobacteria were significantly increased (p < 0.001), whereas Salmonella were significantly decreased (p < 0.001) in transgenic mice compared to wild type mice. Our study suggests that rhLZ expression is a potential strategy to increase animal disease resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

Pathogenic Natural Antibodies Recognizing Annexin IV Are Required to Develop Intestinal Ischemia-Reperfusion Injury1

PubMed Central

Kulik, Liudmila; Fleming, Sherry D.; Moratz, Chantal; Reuter, Jason W.; Novikov, Aleksey; Chen, Kuan; Andrews, Kathy A.; Markaryan, Adam; Quigg, Richard J.; Silverman, Gregg J.; Tsokos, George C.; Holers, V. Michael

2010-01-01

Intestinal ischemia-reperfusion (IR)3 injury is initiated when natural IgM antibodies recognize neo-epitopes that are revealed on ischemic cells. The target molecules and mechanisms whereby these neo-epitopes become accessible to recognition are not well understood. Proposing that isolated intestinal epithelial cells (IEC) may carry IR-related neo-epitopes, we used in vitro IEC binding assays to screen hybridomas created from B cells of unmanipulated wild type C57BL/6 mice. We identified a novel IgM monoclonal antibody (mAb B4) that reacted with the surface of IEC by flow cytometric analysis and was alone capable of causing complement activation, neutrophil recruitment and intestinal injury in otherwise IR-resistant Rag1−/− mice. Monoclonal Ab B4 was found to specifically recognize mouse annexin IV. Pre-injection of recombinant annexin IV blocked IR injury in wild type C57BL/6 mice, demonstrating the requirement for recognition of this protein in order to develop IR injury in the context of a complex natural antibody repertoire. Humans were also found to exhibit IgM natural antibodies that recognize annexin IV. These data in toto identify annexin IV as a key ischemia-related target antigen that is recognized by natural Abs in a pathologic process required in vivo to develop intestinal IR injury. PMID:19380783

The synergistic necrohemorrhagic action of Clostridium perfringens perfringolysin and alpha toxin in the bovine intestine and against bovine endothelial cells

PubMed Central

2013-01-01

Bovine necrohemorrhagic enteritis is a major cause of mortality in veal calves. Clostridium perfringens is considered as the causative agent, but there has been controversy on the toxins responsible for the disease. Recently, it has been demonstrated that a variety of C. perfringens type A strains can induce necrohemorrhagic lesions in a calf intestinal loop assay. These results put forward alpha toxin and perfringolysin as potential causative toxins, since both are produced by all C. perfringens type A strains. The importance of perfringolysin in the pathogenesis of bovine necrohemorrhagic enteritis has not been studied before. Therefore, the objective of the current study was to evaluate the role of perfringolysin in the development of necrohemorrhagic enteritis lesions in calves and its synergism with alpha toxin. A perfringolysin-deficient mutant, an alpha toxin-deficient mutant and a perfringolysin alpha toxin double mutant were less able to induce necrosis in a calf intestinal loop assay as compared to the wild-type strain. Only complementation with both toxins could restore the activity to that of the wild-type. In addition, perfringolysin and alpha toxin had a synergistic cytotoxic effect on bovine endothelial cells. This endothelial cell damage potentially explains why capillary hemorrhages are an initial step in the development of bovine necrohemorrhagic enteritis. Taken together, our results show that perfringolysin acts synergistically with alpha toxin in the development of necrohemorrhagic enteritis in a calf intestinal loop model and we hypothesize that both toxins act by targeting the endothelial cells. PMID:23782465

Accelerated Senescence and Enhanced Disease Resistance in Hybrid Chlorosis Lines Derived from Interspecific Crosses between Tetraploid Wheat and Aegilops tauschii

PubMed Central

Tosa, Yukio; Yoshida, Kentaro; Park, Pyoyun; Takumi, Shigeo

2015-01-01

Hybrid chlorosis, a type of hybrid incompatibility, has frequently been reported in inter- and intraspecific crosses of allopolyploid wheat. In a previous study, we reported some types of growth abnormalities such as hybrid necrosis and observed hybrid chlorosis with mild or severe abnormalities in wheat triploids obtained in crosses between tetraploid wheat cultivar Langdon and four Ae. tauschii accessions and in their derived synthetic hexaploids. However, the molecular mechanisms underlying hybrid chlorosis are not well understood. Here, we compared cytology and gene expression in leaves to characterize the abnormal growth in wheat synthetics showing mild and severe chlorosis. In addition, we compared disease resistance to wheat blast fungus. In total 55 and 105 genes related to carbohydrate metabolism and 53 and 89 genes for defense responses were markedly up-regulated in the mild and severe chlorosis lines, respectively. Abnormal chloroplasts formed in the mesophyll cells before the leaves yellowed in the hybrid chlorosis lines. The plants with mild chlorosis showed increased resistance to wheat blast and powdery mildew fungi, although significant differences only in two, third internode length and maturation time, out of the examined agricultural traits were found between the wild type and plants showing mild chlorosis. These observations suggest that senescence might be accelerated in hybrid chlorosis lines of wheat synthetics. Moreover, in wheat synthetics showing mild chlorosis, the negative effects on biomass can be minimized, and they may show substantial fitness under pathogen-polluted conditions. PMID:25806790

Simultaneous quadruple modal nonlinear optical imaging for gastric diseases diagnosis and characterization

NASA Astrophysics Data System (ADS)

Wang, Zi; Zheng, Wei; Lin, Jian; Huang, Zhiwei

2015-03-01

We report the development of a unique simultaneous quadruple-modal nonlinear optical microscopy (i.e., stimulated Raman scattering (SRS), second-harmonic generation (SHG), two-photon excitation fluorescence (TPEF), and third-harmonic generation (THG)) platform for characterization of the gastric diseases (i.e., gastritis, intestinal metaplasia (IM), intestinal type adenocarcinoma). SRS highlights the goblet cells found in IM. SHG images the distribution of collagen in lamina propria. Collagen is found to aggregate for intestinal type adenocarcinoma. TPEF reveals the cell morphology and can reflect the damage inside glands caused by the diseases. THG visualizes the nuclei with high spatial resolution, which facilitates the identification of neutrophils that are usually used as a feature of inflammation. This work shows that the co-registration of quadruple-modal images can be an effective means for diagnosis and characterization of gastric diseases at the cellular and molecular levels.

Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness

PubMed Central

Pickard, Joseph M.; Maurice, Corinne F.; Kinnebrew, Melissa A.; Abt, Michael C.; Schenten, Dominik; Golovkina, Tatyana; Bogatyrev, Said R.; Ismagilov, Rustem F.; Pamer, Eric G.; Turnbaugh, Peter J.; Chervonsky, Alexander V.

2014-01-01

Systemic infection induces conserved physiological responses that include both resistance and ‘tolerance of infection’ mechanisms1. Temporary anorexia associated with an infection is often beneficial2,3 reallocating energy from food foraging towards resistance to infection4 or depriving pathogens of nutrients 5. It imposes, however, a stress on intestinal commensals, as they also experience reduced substrate availability and impacting host fitness due to the loss of caloric intake and colonization resistance (protection from additional infections)6. We hypothesized that the host might utilize internal resources to support the gut microbiota during the acute phase of the disease. Here we show that systemic exposure to Toll-like receptor (TLR) ligands causes rapid α1,2-fucosylation of the small intestine epithelial cells (IEC), which requires sensing of TLR agonists and production of IL-23 by dendritic cells, activation of innate lymphoid cells and expression of α1,2-Fucosyltransferase-2 (Fut2) by IL-22-stimulated IECs. Fucosylated proteins are shed into the lumen and fucose is liberated and metabolized by the gut microbiota, as shown by reporter bacteria and community-wide analysis of microbial gene expression. Fucose affects the expression of microbial metabolic pathways and reduces the expression of bacterial virulence genes. It also improves host tolerance of the mild pathogen Citrobacter rodentium. Thus, rapid IEC fucosylation appears to be a protective mechanism that utilizes the host's resources to maintain host-microbial interactions during pathogen-induced stress. PMID:25274297

Tendencia de los egresos hospitalarios por enfermedades infecciosas intestinales en niños en Argentina, 2005-2013.

PubMed

Degiuseppe, Juan I

2017-08-01

Acute diarrhea is one of the most serious public health problems in developing countries because it is generally associated with unfavorable living conditions. The objective of this study was to analyze trends in hospital discharges for intestinal infectious disease in children under age 5 recorded in official public hospitals from Argentina in the 2005-2013 period. This was an ecological, time-series study based on data provided by the Health Statistics and Information Department, at a national and regional level. Specific hospital discharge rates were estimated, and seasonal behavior and trends were analyzed in relation to this event. In Argentina, 2 521 729 patients under age 5 were discharged in this period; of these, 9.0% were diagnosed with intestinal infectious disease. Children under age 1 accounted for a third of hospitalizations; two annual peaks (summer and winter) were observed in the seasonality analysis. Overall, a downward trend was observed, with a mild increase in the 2007-2009 period. Rates were up to 3 or 4 times higher in Northwest and Northeast Argentina than in the Pampa region. Hospital discharges for intestinal infectious disease in the public subsector account for approximately 10% of all discharges of children under age 5. This event shows a seasonal pattern, with a slightly downward trend over the past years in spite of its heterogeneous distribution across the different Argentine regions. Sociedad Argentina de Pediatría

Low-nitrogen oxides combustion of dried sludge using a pilot-scale cyclone combustor with recirculation.

PubMed

Shim, Sung Hoon; Jeong, Sang Hyun; Lee, Sang-Sup

2015-04-01

Recently, numerical and experimental studies have been conducted to develop a moderate or intense low-oxygen dilution (MILD) combustion technology for solid fuels. The study results demonstrated that intense recirculation inside the furnace by high-momentum air is a key parameter to achieve the MILD combustion of solid fuels. However, the high-velocity air requires a significant amount of electricity consumption. A cyclone-type MILD combustor was therefore designed and constructed in the authors' laboratory to improve the recirculation inside the combustor. The laboratory-scale tests yielded promising results for the MILD combustion of dried sewage sludge. To achieve pilot-scale MILD combustion of dried sludge in this study, the effects of geometric parameters such as the venturi tube configuration, the air injection location, and the air nozzle diameter were investigated. With the optimized geometric and operational conditions, the pilot-scale cyclone combustor demonstrated successful MILD combustion of dried sludge at a rate of 75 kg/hr with an excess air ratio of 1.05. A horizontal cyclone combustor with recirculation demonstrated moderate or intense low-oxygen dilution (MILD) combustion of dried sewage sludge at a rate of 75 kg/hr. Optimizing only geometric and operational conditions of the combustor reduced nitrogen oxide (NOx) emissions to less than 75 ppm. Because the operating cost of the MILD combustor is much lower than that of the selective catalytic reduction (SCR) applied to the conventional combustor, MILD combustion technology with the cyclone type furnace is an eligible option for reducing NOx emissions from the combustion of dried sewage sludge.

Immune evasion of porcine enteric coronaviruses and viral modulation of antiviral innate signaling.

PubMed

Zhang, Qingzhan; Yoo, Dongwan

2016-12-02

Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are emerged and reemerging viruses in pigs, and together with transmissible gastroenteritis virus (TGEV), pose significant economic concerns to the swine industry. These viruses infect epithelial cells of the small intestine and cause watery diarrhea, dehydration, and a high mortality in neonatal piglets. Type I interferons (IFN-α/β) are major antiviral cytokines forming host innate immunity, and in turn, these enteric coronaviruses have evolved to modulate the host innate immune signaling during infection. Accumulating evidence however suggests that IFN induction and signaling in the intestinal epithelial cells differ from other epithelial cells, largely due to distinct features of the gut epithelial mucosal surface and commensal microflora, and it appears that type III interferon (IFN-λ) plays a key role to maintain the antiviral state in the gut. This review describes the recent understanding on the immune evasion strategies of porcine enteric coronaviruses and the role of different types of IFNs for intestinal antiviral innate immunity. Copyright © 2016 Elsevier B.V. All rights reserved.

Toxicological significance of azo dye metabolism by human intestinal microbiota

PubMed Central

Feng, Jinhui; Cerniglia, Carl E.; Chen, Huizhong

2018-01-01

Approximately 0.7 million tons of azo dyes are synthesized each year. Azo dyes are composed of one or more R1-N=N-R2 linkages. Studies have shown that both mammalian and microbial azoreductases cleave the azo bonds of the dyes to form compounds that are potentially genotoxic. The human gastrointestinal tract harbors a diverse microbiota comprised of at least several thousand species. Both water-soluble and water-insoluble azo dyes can be reduced by intestinal bacteria. Some of the metabolites produced by intestinal microbiota have been shown to be carcinogenic to humans although the parent azo dyes may not be classified as being carcinogenic. Azoreductase activity is commonly found in intestinal bacteria. Three types of azoreductases have been characterized in bacteria. They are flavin dependent NADH preferred azoreductase, flavin dependent NADPH preferred azoreductase, and flavin free NADPH preferred azoreductase. This review highlights how azo dyes are metabolized by intestinal bacteria, mechanisms of azo reduction, and the potential contribution in the carcinogenesis/mutagenesis of the reduction of the azo dyes by intestinal microbiota. PMID:22201895

Non-Hematopoietic MLKL Protects Against Salmonella Mucosal Infection by Enhancing Inflammasome Activation

PubMed Central

Yu, Shui-Xing; Chen, Wei; Liu, Zhen-Zhen; Zhou, Feng-Hua; Yan, Shi-Qing; Hu, Gui-Qiu; Qin, Xiao-Xia; Zhang, Jie; Ma, Ke; Du, Chong-Tao; Gu, Jing-Min; Deng, Xu-Ming; Han, Wen-Yu; Yang, Yong-Jun

2018-01-01

The intestinal mucosal barrier is critical for host defense against pathogens infection. Here, we demonstrate that the mixed lineage kinase-like protein (MLKL), a necroptosis effector, promotes intestinal epithelial barrier function by enhancing inflammasome activation. MLKL−/− mice were more susceptible to Salmonella infection compared with wild-type counterparts, with higher mortality rates, increased body weight loss, exacerbated intestinal inflammation, more bacterial colonization, and severe epithelial barrier disruption. MLKL deficiency promoted early epithelial colonization of Salmonella prior to developing apparent intestinal pathology. Active MLKL was predominantly expressed in crypt epithelial cells, and experiments using bone marrow chimeras found that the protective effects of MLKL were dependent on its expression in non-hematopoietic cells. Intestinal mucosa of MLKL−/− mice had impaired caspase-1 and gasdermin D cleavages and decreased interleukin (IL)-18 release. Moreover, administration of exogenous recombinant IL-18 rescued the phenotype of increased bacterial colonization in MLKL−/− mice. Thus, our results uncover the role of MLKL in enhancing inflammasome activation in intestinal epithelial cells to inhibit early bacterial colonization. PMID:29456533

Escherichia coli challenge and one type of smectite alter intestinal barrier of pigs

PubMed Central

2013-01-01

An experiment was conducted to determine how an E. coli challenge and dietary clays affect the intestinal barrier of pigs. Two groups of 32 pigs (initial BW: 6.9 ± 1.0 kg) were distributed in a 2 × 4 factorial arrangement of a randomized complete block design (2 challenge treatments: sham or E. coli, and 4 dietary treatments: control, 0.3% smectite A, 0.3% smectite B and 0.3% zeolite), with 8 replicates total. Diarrhea score, growth performance, goblet cell size and number, bacterial translocation from intestinal lumen to lymph nodes, intestinal morphology, and relative amounts of sulfo and sialo mucins were measured. The E. coli challenge reduced performance, increased goblet cell size and number in the ileum, increased bacterial translocation from the intestinal lumen to the lymph nodes, and increased ileal crypt depth. One of the clays (smectite A) tended to increase goblet cell size in ileum, which may indicate enhanced protection. In conclusion, E. coli infection degrades intestinal barrier integrity but smectite A may enhance it. PMID:24359581

Escherichia coli challenge and one type of smectite alter intestinal barrier of pigs.

PubMed

Almeida, Juliana Abranches Soares; Liu, Yanhong; Song, Minho; Lee, Jeong Jae; Gaskins, H Rex; Maddox, Carol Wolfgang; Osuna, Orlando; Pettigrew, James Eugene

2013-12-20

An experiment was conducted to determine how an E. coli challenge and dietary clays affect the intestinal barrier of pigs. Two groups of 32 pigs (initial BW: 6.9 ± 1.0 kg) were distributed in a 2 × 4 factorial arrangement of a randomized complete block design (2 challenge treatments: sham or E. coli, and 4 dietary treatments: control, 0.3% smectite A, 0.3% smectite B and 0.3% zeolite), with 8 replicates total. Diarrhea score, growth performance, goblet cell size and number, bacterial translocation from intestinal lumen to lymph nodes, intestinal morphology, and relative amounts of sulfo and sialo mucins were measured. The E. coli challenge reduced performance, increased goblet cell size and number in the ileum, increased bacterial translocation from the intestinal lumen to the lymph nodes, and increased ileal crypt depth. One of the clays (smectite A) tended to increase goblet cell size in ileum, which may indicate enhanced protection. In conclusion, E. coli infection degrades intestinal barrier integrity but smectite A may enhance it.

An enteric virus can replace the beneficial function of commensal bacteria

PubMed Central

Kernbauer, Elisabeth; Ding, Yi; Cadwell, Ken

2014-01-01

Intestinal microbial communities have profound effects on host physiology1. Whereas the symbiotic contribution of commensal bacteria is well established, the role of eukaryotic viruses that are present in the gastrointestinal tract under homeostatic conditions is undefined2,3. Here, we demonstrate that a common enteric RNA virus can replace the beneficial function of commensal bacteria in the intestine. Murine norovirus (MNV) infection of germfree or antibiotics-treated mice restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease. The presence of MNV also suppressed an expansion of group 2 innate lymphoid cells (ILCs) observed in the absence of bacteria, and induced transcriptional changes in the intestine associated with immune development and type I interferon (IFN) signaling. Consistent with this observation, the IFNα receptor was essential for the ability of MNV to compensate for bacterial depletion. Importantly, MNV infection offset the deleterious effect of antibiotics-treatment in models of intestinal injury and pathogenic bacterial infection. These data indicate that eukaryotic viruses have the capacity to support intestinal homeostasis and shape mucosal immunity akin to commensal bacteria. PMID:25409145

The lymphoscintigraphic manifestation of (99m)Tc-dextran lymphatic imaging in primary intestinal lymphangiectasia.

PubMed

Wen, Zhe; Tong, Guansheng; Liu, Yong; Meeks, Jacqui K; Ma, Daqing; Yang, Jigang

2014-05-01

The aim of this study was to analyze the imaging characteristics of (99m)Tc-dextran ((99m)Tc-DX) lymphatic imaging in the diagnosis of primary intestinal lymphangiectasia (PIL). Forty-one PIL patients were diagnosed as having PIL with the diagnosis being subsequently confirmed by laparotomy, endoscopy, biopsy, or capsule colonoscopy. Nineteen patients were male and 22 were female. A whole-body (99m)Tc-DX scan was performed at 10 min, 1 h, 3 h, and 6 h intervals after injection. The 10 min and 1 h postinjection intervals were considered the early phase, the 3 h postinjection interval was considered the middle phase, and the 6 h postinjection interval was considered the delayed phase. The imaging characteristics of (99m)Tc-DX lymphatic imaging in PIL were of five different types: (i) presence of dynamic radioactivity in the intestine, associated with radioactivity moving from the small intestine to the ascending and transverse colon; (ii) presence of delayed dynamic radioactivity in the intestine, no radioactivity or little radioactivity distributing in the intestine in the early phase, or significant radioactivity distributing in the intestine in the delayed phase; (iii) radioactivity distributing in the intestine and abdominal cavity; (iv) radioactivity distributing only in the abdominal cavity with no radioactivity in the intestines; and (v) no radioactivity distributing in the intestine and abdominal activity. (99m)Tc-DX lymphatic imaging in PIL showed different imaging characteristics. Caution should be exercised in the diagnosis of PIL using lymphoscintigraphy. Lymphoscintigraphy is a safe and accurate examination method and is a significant diagnostic tool in the diagnosis of PIL.

Prevalence and co-infection of intestinal parasites among thai rural residents at high-risk of developing cholangiocarcinoma: a cross-sectional study in a prospective cohort study.

PubMed

Songserm, Nopparat; Promthet, Supannee; Wiangnon, Surapon; Sithithaworn, Paiboon

2012-01-01

Intestinal parasitic infections (IPIs) are still important to the health of Thai rural residents. IPIs are the cause of many chronic diseases with, for example, opisthorchiasis resulting in progression to cholangiocarcinoma (CCA). This cross-sectional study in a prospective cohort study aimed to examine the prevalence and co- infection of intestinal parasites among Northeastern Thai rural residents, recruited into the Khon Kaen Cohort Study (KKCS), and who were residing in areas of high-risk for developing CCA. On recruitment, subjects had completed questionnaires and provided fecal samples for IPI testing using the formalin ethyl acetate concentration technique. Data on selected general characteristics and the results of the fecal tests were analysed. IPI test results were available for 18,900 of cohort subjects, and 38.50% were found to be positive for one or more types of intestinal parasite. The prevalence of Opisthorchis viverrini (O. viverrini) infection was the highest (45.7%), followed by intestinal flukes (31.9%), intestinal nematodes (17.7%), intestinal protozoa (3.02%), and intestinal cestodes (1.69%). The pattern of different infections was similar in all age groups. According to a mapping analysis, a higher CCA burden was correlated with a higher prevalence of O. viverrini and intestinal flukes and a greater intensity of O. viverrini. Both prevention and control programs against liver fluke and other intestinal parasites are needed and should be delivered simultaneously. We can anticipate that the design of future control and prevention programmes will accommodate a more community-orientated and participatory approach.

Probiotic Bifidobacterium breve Induces IL-10-Producing Tr1 Cells in the Colon

PubMed Central

Ueda, Yoshiyasu; Takahashi, Takuya; Asahara, Takashi; Tsuji, Hirokazu; Tsuji, Noriko M.; Kiyono, Hiroshi; Ma, Ji Su; Kusu, Takashi; Okumura, Ryu; Hara, Hiromitsu; Yoshida, Hiroki; Yamamoto, Masahiro; Nomoto, Koji; Takeda, Kiyoshi

2012-01-01

Specific intestinal microbiota has been shown to induce Foxp3+ regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103+ dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103+ DCs from Il10 −/−, Tlr2 −/−, and Myd88 −/− mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103+ DCs failed to induce IL-10 production from co-cultured Il27ra −/− T cells. B. breve treatment of Tlr2 −/− mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103+ DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4+ T cells from wild-type mice, but not Il10 −/− mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells. PMID:22693446

[Study on the relationship between vaginal and intestinal candida in patients with vulvovaginal candidiasis].

PubMed

Lin, Xiao-li; Li, Zhen; Zuo, Xu-lei

2011-07-01

To investigate the relationship between vaginal and intestinal candida in patients with vulvovaginal candidiasis by using microbiological and molecular methods. The samples of vaginal discharge and anal swabs were collected from 148 cases with vulvovaginal candidiasis, followed by fungal culture, identification, purification and genome DNA extraction. The genome sequences from respective locations were aligned and typed according to their homology analyzed by internal transcribed spacer (ITS) PCR and random amplified polymorphic DNA (RAPD) PCR. Patients with vulvovaginal infection or those with infections in intestine and vulvovagina were pooled respectively, while the recurrent incidences after local anti-fungal treatments were analyzed. Candida albicans is the dominant pathogen in 148 cases with vulvovaginal candidiasis (91.9%, 136/148); 33.1% (49/148) of patients with vulvovaginal candidiasis were infected in both intestine and vulvovagina. While 92% (22/24) of patients with intestinal and vaginal candida infection showed high homology. The recurrent rate of patients with vulvovaginal candidiasis complicated with concurrent intestinal candida infection (7/14) was significantly higher than that of solo vaginal infected patients [21% (6/29)] after vaginal treatment (P<0.05). The infection of vulvovaginal candidiasis is highly associated with the concurrent infection of intestinal candida. The recurrent rate is high in patients with vulvovaginal candidiasis with concurrent infection of intestinal candida after vaginal treatment. The general management to those patients infected by both vulvovaginal and intestinal candida is necessary in reducing the recurrence of the disease.

Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology

PubMed Central

Saxena, Kapil; Blutt, Sarah E.; Ettayebi, Khalil; Zeng, Xi-Lei; Broughman, James R.; Crawford, Sue E.; Karandikar, Umesh C.; Sastri, Narayan P.; Conner, Margaret E.; Opekun, Antone R.; Graham, David Y.; Qureshi, Waqar; Sherman, Vadim; Foulke-Abel, Jennifer; In, Julie; Kovbasnjuk, Olga; Zachos, Nicholas C.; Donowitz, Mark

2015-01-01

ABSTRACT Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate the cellular diversity and complex functions of human physiology and disease pathology. Human intestinal enteroid (HIE) cultures contain multiple intestinal epithelial cell types that comprise the intestinal epithelium (enterocytes and goblet, enteroendocrine, and Paneth cells) and are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE cultures as models for pathogenic infections in the small intestine by examining whether HIEs from different regions of the small intestine from different patients are susceptible to human rotavirus (HRV) infection. Little is known about HRVs, as they generally replicate poorly in transformed cell lines, and host range restriction prevents their replication in many animal models, whereas many animal rotaviruses (ARVs) exhibit a broader host range and replicate in mice. Using HRVs, including the Rotarix RV1 vaccine strain, and ARVs, we evaluated host susceptibility, virus production, and cellular responses of HIEs. HRVs infect at higher rates and grow to higher titers than do ARVs. HRVs infect differentiated enterocytes and enteroendocrine cells, and viroplasms and lipid droplets are induced. Heterogeneity in replication was seen in HIEs from different patients. HRV infection and RV enterotoxin treatment of HIEs caused physiological lumenal expansion detected by time-lapse microscopy, recapitulating one of the hallmarks of rotavirus-induced diarrhea. These results demonstrate that HIEs are a novel pathophysiological model that will allow the study of HRV biology, including host restriction, cell type restriction, and virus-induced fluid secretion. IMPORTANCE Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology and pathophysiology and the epithelial response, including host restriction of gastrointestinal infections such as HRV infection. HRVs remain a major worldwide cause of diarrhea-associated morbidity and mortality in children ≤5 years of age. Current in vitro models of rotavirus infection rely primarily on the use of animal rotaviruses because HRV growth is limited in most transformed cell lines and animal models. We demonstrate that HIEs are novel, cellularly diverse, and physiologically relevant epithelial cell cultures that recapitulate in vivo properties of HRV infection. HIEs will allow the study of HRV biology, including human host-pathogen and live, attenuated vaccine interactions; host and cell type restriction; virus-induced fluid secretion; cell-cell communication within the epithelium; and the epithelial response to infection in cultures from genetically diverse individuals. Finally, drug therapies to prevent/treat diarrheal disease can be tested in these physiologically active cultures. PMID:26446608

Primary intestinal lymphangiectasia successfully treated by segmental resections of small bowel.

PubMed

Kim, Na Rae; Lee, Suk-Koo; Suh, Yeon-Lim

2009-10-01

Primary intestinal lymphangiectasia is a rare cause of protein-losing enteropathy and usually presents with intermittent diarrhea or malnutrition. Diagnosis depends largely on its pathologic condition demonstrating greatly dilated lymphatics mainly in the lamina propria of the mucosa. We report a case of primary intestinal lymphangiectasia, of the diffuse type, presenting with abdominal pain and voluminous diarrhea in a previously healthy 8-year-old boy. He had periumbilical pain for 3 months before presentation. He was managed by segmental bowel resections and end-to-end anastomoses. The histopathologic condition of the resected small intestine showed lymphatic dilation limited mainly to the subserosa and mesentery but was not prominent in the mucosa. Abdominal pain and diarrhea subsided postoperatively. The present case is the fourth report describing a response to operative resection.

Imbalance of intestinal immune function in piglets infected by porcine circovirus type 2 during the fetal period.

PubMed

Mao, Yu; Li, Jin Jun; Liu, Yuan; Dong, Wei; Pang, Pei; Deng, Zhi Bang

2017-03-01

Porcine circovirus type 2- (PCV2-) associated reproductive disorders and enteritis have commonly been observed on PCV2-contaminated pig farms in recent years. In order to investigate disorders of intestinal immunity in piglets infected by PCV2 during the fetal period, 9 PCV2b-infected piglets and 6 non-infected piglets at one day of age were selected and euthanised prior to suckling. Samples of mesenteric lymph nodes (MLNs) and duodena were collected to investigate factors related to intestinal immunity and to detect lymphocytic apoptosis. The results indicated that there were no significant changes in the levels of IL-2, IL-10 and transforming growth factor-β (TGF-β) in the PCV2b-infected piglets but IFN-γ levels were significantly lower (P < 0.01) and IL-4 levels were significantly higher (P < 0.05) in infected piglets than in the controls. Furthermore, lymphocytic apoptosis increased in PCV2b-infected piglets and CD4+ to CD8+ ratios were lower in these piglets than in the controls. These findings suggest vertical transmission of PCV2b to fetuses, leading to an imbalance of intestinal immune function in piglets.

Activation of Intestinal Human Pregnane X Receptor Protects against Azoxymethane/Dextran Sulfate Sodium–Induced Colon Cancer

PubMed Central

Cheng, Jie; Fang, Zhong-Ze; Nagaoka, Kenjiro; Okamoto, Minoru; Qu, Aijuan; Tanaka, Naoki; Kimura, Shioko

2014-01-01

The role of intestinal human pregnane X receptor (PXR) in colon cancer was determined through investigation of the chemopreventive role of rifaximin, a specific agonist of intestinal human PXR, toward azoxymethane (AOM)/dextran sulfate sodium (DSS)–induced colon cancer. Rifaximin treatment significantly decreased the number of colon tumors induced by AOM/DSS treatment in PXR-humanized mice, but not wild-type or Pxr-null mice. Additionally, rifaximin treatment markedly increased the survival rate of PXR-humanized mice, but not wild-type or Pxr-null mice. These data indicated a human PXR–dependent therapeutic chemoprevention of rifaximin toward AOM/DSS-induced colon cancer. Nuclear factor κ-light-chain-enhancer of activated B cells–mediated inflammatory signaling was upregulated in AOM/DSS-treated mice, and inhibited by rifaximin in PXR-humanized mice. Cell proliferation and apoptosis were also modulated by rifaximin treatment in the AOM/DSS model. In vitro cell-based assays further revealed that rifaximin regulated cell apoptosis and cell cycle in a human PXR-dependent manner. These results suggested that specific activation of intestinal human PXR exhibited a chemopreventive role toward AOM/DSS-induced colon cancer by mediating anti-inflammation, antiproliferation, and proapoptotic events. PMID:25277138

Prevalence and Predictors of Intestinal Helminth Infections Among Human Immunodeficiency Virus Type 1–Infected Adults in an Urban African Setting

PubMed Central

Modjarrad, Kayvon; Zulu, Isaac; Redden, David T.; Njobvu, Lungowe; Freedman, David O.; Vermund, Sten H.

2009-01-01

Sub-Saharan Africa is disproportionately burdened by intestinal helminth and human immunodeficiency virus (HIV)-1 infection. Recent evidence suggests detrimental immunologic effects from concomitant infection with the two pathogens. Few studies, however, have assessed the prevalence of and predictors for intestinal helminth infection among HIV-1–infected adults in urban African settings where HIV infection rates are highest. We collected and analyzed sociodemographic and parasitologic data from 297 HIV-1–infected adults (mean age = 31.1 years, 69% female) living in Lusaka, Zambia to assess the prevalence and associated predictors of helminth infection. We found at least one type of intestinal helminth in 24.9% of HIV-infected adults. Thirty-nine (52.7%) were infected with Ascaris lumbricoides, and 29 (39.2%) were infected with hookworm. More than 80% were light-intensity infections. A recent visit to a rural area, food shortage, and prior history of helminth infection were significant predictors of current helminth status. The high helminth prevalence and potential for adverse interactions between helminths and HIV suggests that helminth diagnosis and treatment should be part of routine HIV care. PMID:16222025

Local Inflammatory Cues Regulate Differentiation and Persistence of CD8+ Tissue-Resident Memory T Cells.

PubMed

Bergsbaken, Tessa; Bevan, Michael J; Fink, Pamela J

2017-04-04

Many pathogens initiate infection at mucosal surfaces, and tissue-resident memory T (Trm) cells play an important role in protective immunity, yet the tissue-specific signals that regulate Trm differentiation are poorly defined. During Yersinia infection, CD8 + T cell recruitment to areas of inflammation within the intestine is required for differentiation of the CD103 - CD69 + Trm subset. Intestinal proinflammatory microenvironments have elevated interferon (IFN)-β and interleukin-12 (IL-12), which regulated Trm markers, including CD103. Type I interferon-receptor- or IL-12-receptor-deficient T cells functioned similarly to wild-type (WT) cells during infection; however, the inability of T cells to respond to inflammation resulted in defective differentiation of CD103 - CD69 + Trm cells and reduced Trm persistence. Intestinal macrophages were the main producers of IFN-β and IL-12 during infection, and deletion of CCR2 + IL-12-producing cells reduced the size of the CD103 - Trm population. These data indicate that intestinal inflammation drives phenotypic diversity and abundance of Trm cells for optimal tissue-specific immunity. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

[Effect of Psidium guajava leaf extract on alpha-glucosidase activity in small intestine of diabetic mouse].

PubMed

Wang, Bo; Liu, Heng-Chuan; Hong, Jun-Rong; Li, Hong-Gu; Huang, Cheng-Yu

2007-03-01

To investigate the inhibition effect of Psidium guajava linn (PGL), a leaf water-soluble extract, on the activities of alpha-glucosidases. The PGL water-soluble extract (PGL WE) was obtained by the procedure of distilled water immersion, filtration, extracted fluid concentration and dry of Psidium guajava leaf. The diabetes of Kunming mice was induced by intraperitoneal injection of Streptozotocin (STZ). The small intestinal mucosa of diabetic mice was scraped to make the homogenate for the preparation of alpha-glucosidases. In vitro, the homogenates were incubated with sucrose and maltose. The formed glucose represented the activities of alpha-glucosidases. The Lineweaver-Burk plot was applied to determine the type of alpha-glucosidase activity inhibited. The water-soluble extract from PGL significantly inhibited, in the dose-dependent manner, the activities of alpha-glucosidase from small intestinal mucosa of diabetic mice. The PGL extract inhibition concentration (IC50) to sucrase or maltase was 1.0 g/L or 3.0 g/L respectively. The mixed inhibition type was showed to be the competitive and non-competitive inhibition. The GPL water-soluble extract possesses the potential effect of inhibition on the alpha-glucosidase activity from the small intestinal mucosa of diabetic mouse.

p53 independent induction of PUMA mediates intestinal apoptosis in response to ischaemia–reperfusion

PubMed Central

Wu, Bin; Qiu, Wei; Wang, Peng; Yu, Hui; Cheng, Tao; Zambetti, Gerard P; Zhang, Lin; Yu, Jian

2007-01-01

Background The small intestine is highly sensitive to ischaemia–reperfusion (I/R) induced injury which is associated with high morbidity and mortality. Apoptosis, or programmed cell death, is a major mode of cell death occurring during I/R induced injury. However, the mechanisms by which I/R cause apoptosis in the small intestine are poorly understood. p53 upregulated modulator of apoptosis (PUMA) is a p53 downstream target and a member of the BH3‐only group of Bcl‐2 family proteins. It has been shown that PUMA plays an essential role in apoptosis induced by a variety of stimuli in different tissues through a mitochondrial pathway. Aims The role of PUMA in I/R induced injury and apoptosis in the small intestine was investigated. The mechanisms by which PUMA is regulated in I/R induced intestinal apoptosis were also studied. Methods Ischaemia was induced by superior mesenteric artery occlusion in the mouse small intestine. Induction of PUMA in response to ischaemia alone, or ischaemia followed by reperfusion (I/R), was examined. I/R induced intestinal apoptosis and injury were compared between PUMA knockout and wild‐type mice. The mechanisms of I/R induced and PUMA mediated apoptosis were investigated through analysis of caspase activation, cytosolic release of mitochondrial cytochrome c and alterations of the proapoptotic Bcl‐2 family proteins Bax and Bak. To determine whether PUMA is induced by reactive oxygen species and/or reactive nitrogen species generated by I/R, superoxide dismutase (SOD) and N‐nitro‐L‐arginine methyl ester (L‐NAME) were used to treat animals before I/R. To determine whether p53 is involved in regulating PUMA during I/R induced apoptosis, PUMA induction and apoptosis in response to I/R were examined in p53 knockout mice. Results PUMA was markedly induced following I/R in the mucosa of the mouse small intestine. I/R induced intestinal apoptosis was significantly attenuated in PUMA knockout mice compared with that in wild‐type mice. I/R induced caspase 3 activation, cytochrome c release, Bax mitochondrial translocation and Bak multimerisation were also inhibited in PUMA knockout mice. SOD or L‐NAME significantly blunted I/R induced PUMA expression and apoptosis. Furthermore, I/R induced PUMA expression and apoptosis in the small intestine were not affected in the p53 knockout mice. Conclusions Our data demonstrated that PUMA is activated by oxidative stress in response to I/R to promote p53 independent apoptosis in the small intestine through the mitochondrial pathway. Inhibition of PUMA is potentially useful for protecting against I/R induced intestinal injury and apoptosis. PMID:17127703

Helicobacter pylori and precancerous conditions of the stomach: the frequency of infection in a cross-sectional study of 79 consecutive patients with chronic antral gastritis in Yaoundé, Cameroon

PubMed Central

Ankouane, Firmin; Noah, Dominique Noah; Enyime, Félicien Ntoné; Ndjollé, Carole Menzy; Djapa, Roger Nsenga; Nonga, Bernadette Ngo; Njoya, Oudou; Ndam, Elie Claude Ndjitoyap

2015-01-01

Introduction The study aimed at determining the different types of precancerous conditions of the stomach and searches the frequency of Helicobacter pylori in these lesions in patients with chronic antral gastritis in Yaounde, Cameroon. Methods Five gastric biopsies were performed during upper gastrointestinal endoscopy for pathology and fixed in formol 10% before being coated in paraffin. Both the modified Giemsa and Periodic acid of Shift – Alkaline blue stains were used for the histological diagnosis of Helicobacter pylori infection. Hematoxylyn and eosin stain was used to determine the activity of gastritis, atrophic gastritis and intestinal metaplasia in accordance to the Sydney's classification of gastritis. Data were analysed using both the Epi info 6.04 and Excel 2007 softwares. Means and their standard deviations, medians and their interquartiles (IQR) were calculated. Proportions were established for qualitative variables and chi square analysis done in this study with a p value set at 0.05. Results Seventy-nine patients with chronic antral gastritis were enrolled, of which 43 (54.4%) were male, median age: 43 years (range from 21 to 70 years). The rate of atrophic gastritis was 74.7% (59/79). The activity of atrophic gastritis was mild in 47.5% (28/59) of cases, moderate in 47.5% (28/59) and severe in 5% (5/59). Intestinal metaplasia and follicular gastritis were present in 6.3% (5/79), and 10.1% (8/79), respectively. Concerning Helicobacter pylori infection, 71.2% (42/59) of patients with atrophic gastritis tested positive against 28.8% (17/59) who tested negative (p = 0.00003). Helicobacter pylori infection was related to the severity of gastric atrophy (p = 0.0001). Among patients with intestinal metaplasia and follicular gastritis, the proportion of those who tested positive for Helicobacter pylori infection was 80% (4/5), and 75% (6/8), respectively. There were no significant differences in the occurrence of atrophic gastritis according to age groups (p = 0.908). Conclusion This study concludes that atrophic gastritis, which is most often caused by Helicobacter pylori, is the most frequent precancerous condition of stomach in Cameroon. Routine gastric sampling for pathologic analysis is mandatory for effective diagnosis and surveillance of Helicobacter pylori infection and precancerous conditions of the stomach. PMID:26090010

Helicobacter pylori and precancerous conditions of the stomach: the frequency of infection in a cross-sectional study of 79 consecutive patients with chronic antral gastritis in Yaoundé, Cameroon.

PubMed

Ankouane, Firmin; Noah, Dominique Noah; Enyime, Félicien Ntoné; Ndjollé, Carole Menzy; Djapa, Roger Nsenga; Nonga, Bernadette Ngo; Njoya, Oudou; Ndam, Elie Claude Ndjitoyap

2015-01-01

The study aimed at determining the different types of precancerous conditions of the stomach and searches the frequency of Helicobacter pylori in these lesions in patients with chronic antral gastritis in Yaounde, Cameroon. Five gastric biopsies were performed during upper gastrointestinal endoscopy for pathology and fixed in formol 10% before being coated in paraffin. Both the modified Giemsa and Periodic acid of Shift - Alkaline blue stains were used for the histological diagnosis of Helicobacter pylori infection. Hematoxylyn and eosin stain was used to determine the activity of gastritis, atrophic gastritis and intestinal metaplasia in accordance to the Sydney's classification of gastritis. Data were analysed using both the Epi info 6.04 and Excel 2007 softwares. Means and their standard deviations, medians and their interquartiles (IQR) were calculated. Proportions were established for qualitative variables and chi square analysis done in this study with a p value set at 0.05. Seventy-nine patients with chronic antral gastritis were enrolled, of which 43 (54.4%) were male, median age: 43 years (range from 21 to 70 years). The rate of atrophic gastritis was 74.7% (59/79). The activity of atrophic gastritis was mild in 47.5% (28/59) of cases, moderate in 47.5% (28/59) and severe in 5% (5/59). Intestinal metaplasia and follicular gastritis were present in 6.3% (5/79), and 10.1% (8/79), respectively. Concerning Helicobacter pylori infection, 71.2% (42/59) of patients with atrophic gastritis tested positive against 28.8% (17/59) who tested negative (p=0.00003). Helicobacter pylori infection was related to the severity of gastric atrophy (p=0.0001). Among patients with intestinal metaplasia and follicular gastritis, the proportion of those who tested positive for Helicobacter pylori infection was 80% (4/5), and 75% (6/8), respectively. There were no significant differences in the occurrence of atrophic gastritis according to age groups (p=0.908). This study concludes that atrophic gastritis, which is most often caused by Helicobacter pylori, is the most frequent precancerous condition of stomach in Cameroon. Routine gastric sampling for pathologic analysis is mandatory for effective diagnosis and surveillance of Helicobacter pylori infection and precancerous conditions of the stomach.

Inclusion of thin target and source regions in alimentary and respiratory tract systems of mesh-type ICRP adult reference phantoms

NASA Astrophysics Data System (ADS)

Kim, Han Sung; Yeom, Yeon Soo; Tat Nguyen, Thang; Choi, Chansoo; Han, Min Cheol; Lee, Jai Ki; Kim, Chan Hyeong; Zankl, Maria; Petoussi-Henss, Nina; Bolch, Wesley E.; Lee, Choonsik; Qiu, Rui; Eckerman, Keith; Chung, Beom Sun

2017-03-01

It is not feasible to define very small or complex organs and tissues in the current voxel-type adult reference computational phantoms of the International Commission on Radiological Protection (ICRP), which limit dose coefficients for weakly penetrating radiations. To address the problem, the ICRP is converting the voxel-type reference phantoms into mesh-type phantoms. In the present study, as a part of the conversion project, the micrometer-thick target and source regions in the alimentary and respiratory tract systems as described in ICRP Publications 100 and 66 were included in the mesh-type ICRP reference adult male and female phantoms. In addition, realistic lung airway models were simulated to represent the bronchial (BB) and bronchiolar (bb) regions. The electron specific absorbed fraction (SAF) values for the alimentary and respiratory tract systems were then calculated and compared with the values calculated with the stylized models of ICRP Publications 100 and 66. The comparisons show generally good agreement for the oral cavity, oesophagus, and BB, whereas for the stomach, small intestine, large intestine, extrathoracic region, and bb, there are some differences (e.g. up to ~9 times in the large intestine). The difference is mainly due to anatomical difference in these organs between the realistic mesh-type phantoms and the simplified stylized models. The new alimentary and respiratory tract models in the mesh-type ICRP reference phantoms preserve the topology and dimensions of the voxel-type ICRP phantoms and provide more reliable SAF values than the simplified models adopted in previous ICRP Publications.

Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease

PubMed Central

Hayashi, Atsuko; Nomura, Hiroshi; Mochizuki, Ruriko; Ohnuma, Ayumu; Kimpara, Teiko; Suzuki, Kyoko; Mori, Etsuro

2015-01-01

Background/Aims We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). Methods A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. Results For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. Conclusions The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients. PMID:26483830

A HISTOLOGICAL STUDY OF TYPHOID FEVER

PubMed Central

Mallory, F. B.

1898-01-01

The typhoid bacillus produces a mild diffusible toxine, partly within the intestinal tract, partly within the blood and organs of the body. This toxine produces proliferation of endothelial cells which acquire for a certain length of time malignant properties. The new-formed cells are epithelioid in character, have irregular, lightly staining, eccentrically situated nuclei, abundant, sharply defined, acidophilic protoplasm, and are characterized by marked phagocytic properties. These phagocytic cells are produced most abundantly along the line of absorption from the intestinal tract, both in the lymphatic apparatus and in the blood-vessels. They are also produced by distribution of the toxine through the general circulation, in greatest numbers where the circulation is slowest. Finally, they are produced all over the body in the lymphatic spaces and vessels by absorption of the toxine eliminated from the blood-vessels. The swelling of the intestinal lymphoid tissue of the mesenteric lymph nodes, and of the spleen is due almost entirely to the formation of phagocytic cells. The necrosis of the intestinal lymphoid tissue is accidental in nature and is caused through occlusion of the veins and capillaries by fibrinous thrombi, which owe their origin to degeneration of phagocytic cells beneath the lining endothelium of the vessels. Two varieties of focal lesions occur in the liver: one consists of the formation of phagocytic cells in the lymph spaces and vessels around the portal vessels under the action of the toxine absorbed by the lymphatics; the other is due to obstruction of liver capillaries by phagocytic cells derived in small part from the lining endothelium of the liver capillaries, but chiefly by embolism through the portal circulation of cells originating from the endothelium of the blood-vessels of the intestine and spleen. The liver cells lying between the occluded capillaries undergo necrosis and disappear. Later the foci of cells degenerate and fibrin forms between them. Invasion with polymorphonuclear leucocytes is rare. Many of the phagocytic cells pass through the liver and lungs, and get into the general circulation. A few come from the abdominal lymphatics through the thoracic duct. PMID:19866884

Organ Transplantation: Frequently Asked Questions

MedlinePlus

... transplanted at the same time) intestine vascularized composite allografts (VCAs), such as face and hand transplantation Are ... including organ size, and condition, blood type and tissue type. UNOS generates a list of potential recipients. ...

Transgenic Expression of the Vitamin D Receptor Restricted to the Ileum, Cecum, and Colon of Vitamin D Receptor Knockout Mice Rescues Vitamin D Receptor-Dependent Rickets.

PubMed

Dhawan, Puneet; Veldurthy, Vaishali; Yehia, Ghassan; Hsaio, Connie; Porta, Angela; Kim, Ki-In; Patel, Nishant; Lieben, Liesbet; Verlinden, Lieve; Carmeliet, Geert; Christakos, Sylvia

2017-11-01

Although the intestine plays the major role in 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] action on calcium homeostasis, the mechanisms involved remain incompletely understood. The established model of 1,25(OH)2D3-regulated intestinal calcium absorption postulates a critical role for the duodenum. However, the distal intestine is where 70% to 80% of ingested calcium is absorbed. To test directly the role of 1,25(OH)2D3 and the vitamin D receptor (VDR) in the distal intestine, three independent knockout (KO)/transgenic (TG) lines expressing VDR exclusively in the ileum, cecum, and colon were generated by breeding VDR KO mice with TG mice expressing human VDR (hVDR) under the control of the 9.5-kb caudal type homeobox 2 promoter. Mice from one TG line (KO/TG3) showed low VDR expression in the distal intestine (<50% of the levels observed in KO/TG1, KO/TG2, and wild-type mice). In the KO/TG mice, hVDR was not expressed in the duodenum, jejunum, kidney, or other tissues. Growth arrest, elevated parathyroid hormone level, and hypocalcemia of the VDR KO mice were prevented in mice from KO/TG lines 1 and 2. Microcomputed tomography analysis revealed that the expression of hVDR in the distal intestine of KO/TG1 and KO/TG2 mice rescued the bone defects associated with systemic VDR deficiency, including growth plate abnormalities and altered trabecular and cortical parameters. KO/TG3 mice showed rickets, but less severely than VDR KO mice. These findings show that expression of VDR exclusively in the distal intestine can prevent abnormalities in calcium homeostasis and bone mineralization associated with systemic VDR deficiency. Copyright © 2017 Endocrine Society.

Differential expression of pancreatic protein and chemosensing receptor mRNAs in NKCC1-null intestine

PubMed Central

Bradford, Emily M; Vairamani, Kanimozhi; Shull, Gary E

2016-01-01

AIM: To investigate the intestinal functions of the NKCC1 Na+-K+-2Cl cotransporter (SLC12a2 gene), differential mRNA expression changes in NKCC1-null intestine were analyzed. METHODS: Microarray analysis of mRNA from intestines of adult wild-type mice and gene-targeted NKCC1-null mice (n = 6 of each genotype) was performed to identify patterns of differential gene expression changes. Differential expression patterns were further examined by Gene Ontology analysis using the online Gorilla program, and expression changes of selected genes were verified using northern blot analysis and quantitative real time-polymerase chain reaction. Histological staining and immunofluorescence were performed to identify cell types in which upregulated pancreatic digestive enzymes were expressed. RESULTS: Genes typically associated with pancreatic function were upregulated. These included lipase, amylase, elastase, and serine proteases indicative of pancreatic exocrine function, as well as insulin and regenerating islet genes, representative of endocrine function. Northern blot analysis and immunohistochemistry showed that differential expression of exocrine pancreas mRNAs was specific to the duodenum and localized to a subset of goblet cells. In addition, a major pattern of changes involving differential expression of olfactory receptors that function in chemical sensing, as well as other chemosensing G-protein coupled receptors, was observed. These changes in chemosensory receptor expression may be related to the failure of intestinal function and dependency on parenteral nutrition observed in humans with SLC12a2 mutations. CONCLUSION: The results suggest that loss of NKCC1 affects not only secretion, but also goblet cell function and chemosensing of intestinal contents via G-protein coupled chemosensory receptors. PMID:26909237

Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

PubMed

Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

2016-12-01

The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC 50  = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU 50  = 2.68 ± 0.75 %) or without (GU 50  = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

Association between intestinal permeability and faecal microbiota composition in Italian children with beta cell autoimmunity at risk for type 1 diabetes.

PubMed

Maffeis, Claudio; Martina, Alessia; Corradi, Massimiliano; Quarella, Sara; Nori, Nicole; Torriani, Sandra; Plebani, Mario; Contreas, Giovanna; Felis, Giovanna E

2016-10-01

Pancreatic organ-specific autoimmunity in subjects at risk for type 1 diabetes (T1D) is associated with increased intestinal permeability and an aberrant gut microbiota, but these factors have not yet been simultaneously investigated in the same subjects. Thus, the aim of this study was to assess both intestinal permeability and gut microbiota composition in an Italian sample of children at risk for T1D. Ten Italian children with beta cell autoimmunity at risk for T1D and 10 healthy children were involved in a case-control study. The lactulose/mannitol test was used to assess intestinal permeability. Analysis of microbiota composition was performed using polymerase chain reaction followed by denaturing gradient gel electrophoresis, based on the 16S rRNA gene. Intestinal permeability was significantly higher in children at risk for T1D than in healthy controls. Moreover, the gut microbiota of the former differed from that of the latter group: Three microorganisms were detected - Dialister invisus, Gemella sanguinis and Bifidobacterium longum - in association with the pre-pathologic state. The results of this study validated the hypothesis that increased intestinal permeability together with differences in microbiota composition are contemporaneously associated with the pre-pathological condition of T1D in a sample of Italian children. Further studies are necessary to confirm the microbial markers identified in this sample of children as well as to clarify the involvement of microbiota modifications in the mechanisms leading to increased permeability and the autoimmune mechanisms that promote diabetes onset. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Prolonged antibiotic treatment induces a diabetogenic intestinal microbiome that accelerates diabetes in NOD mice.

PubMed

Brown, Kirsty; Godovannyi, Artem; Ma, Caixia; Zhang, YiQun; Ahmadi-Vand, Zahra; Dai, Chaunbin; Gorzelak, Monika A; Chan, YeeKwan; Chan, Justin M; Lochner, Arion; Dutz, Jan P; Vallance, Bruce A; Gibson, Deanna L

2016-02-01

Accumulating evidence supports that the intestinal microbiome is involved in Type 1 diabetes (T1D) pathogenesis through the gut-pancreas nexus. Our aim was to determine whether the intestinal microbiota in the non-obese diabetic (NOD) mouse model played a role in T1D through the gut. To examine the effect of the intestinal microbiota on T1D onset, we manipulated gut microbes by: (1) the fecal transplantation between non-obese diabetic (NOD) and resistant (NOR) mice and (2) the oral antibiotic and probiotic treatment of NOD mice. We monitored diabetes onset, quantified CD4+T cells in the Peyer's patches, profiled the microbiome and measured fecal short-chain fatty acids (SCFA). The gut microbiota from NOD mice harbored more pathobionts and fewer beneficial microbes in comparison with NOR mice. Fecal transplantation of NOD microbes induced insulitis in NOR hosts suggesting that the NOD microbiome is diabetogenic. Moreover, antibiotic exposure accelerated diabetes onset in NOD mice accompanied by increased T-helper type 1 (Th1) and reduced Th17 cells in the intestinal lymphoid tissues. The diabetogenic microbiome was characterized by a metagenome altered in several metabolic gene clusters. Furthermore, diabetes susceptibility correlated with reduced fecal SCFAs. In an attempt to correct the diabetogenic microbiome, we administered VLS#3 probiotics to NOD mice but found that VSL#3 colonized the intestine poorly and did not delay diabetes. We conclude that NOD mice harbor gut microbes that induce diabetes and that their diabetogenic microbiome can be amplified early in life through antibiotic exposure. Protective microbes like VSL#3 are insufficient to overcome the effects of a diabetogenic microbiome.

Intestinal IFN-γ-producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease.

PubMed

Alfen, Johanna Sophie; Larghi, Paola; Facciotti, Federica; Gagliani, Nicola; Bosotti, Roberto; Paroni, Moira; Maglie, Stefano; Gruarin, Paola; Vasco, Chiara Maria; Ranzani, Valeria; Frusteri, Cristina; Iseppon, Andrea; Moro, Monica; Crosti, Maria Cristina; Gatti, Stefano; Pagani, Massimiliano; Caprioli, Flavio; Abrignani, Sergio; Flavell, Richard A; Geginat, Jens

2018-01-31

IL-10 is an anti-inflammatory cytokine required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type 1 regulatory T (T R 1) cells but is also produced by CD25 + regulatory T (Treg) cells. We aimed to identify and characterize human intestinal T R 1 cells and to investigate whether they are a relevant cellular source of IL-10 in patients with inflammatory bowel diseases (IBDs). CD4 + T cells isolated from the intestinal lamina propria of human subjects and mice were analyzed for phenotype, cytokine production, and suppressive capacities. Intracellular IL-10 expression by CD4 + T-cell subsets in the inflamed guts of patients with IBD (Crohn disease or ulcerative colitis) was compared with that in cells from noninflamed control subjects. Finally, the effects of proinflammatory cytokines on T-cell IL-10 expression were analyzed, and IL-1β and IL-23 responsiveness was assessed. Intestinal T R 1 cells could be identified by coexpression of CCR5 and programmed cell death protein 1 (PD-1) in human subjects and mice. CCR5 + PD-1 + T R 1 cells expressed IFN-γ and efficiently suppressed T-cell proliferation and transfer colitis. Intestinal IFN-γ + T R 1 cells, but not IL-7 receptor-positive T H cells or CD25 + Treg cells, showed lower IL-10 expression in patients with IBDs. T R 1 cells were responsive to IL-23, and IFN-γ + T R 1 cells downregulated IL-10 with IL-1β and IL-23. Conversely, CD25 + Treg cells expressed higher levels of IL-1 receptor but showed stable IL-10 expression. We provide the first ex vivo characterization of human intestinal T R 1 cells. Selective downregulation of IL-10 by IFN-γ + T R 1 cells in response to proinflammatory cytokines is likely to drive excessive intestinal inflammation in patients with IBDs. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Influence of bedding type on mucosal immune responses.

PubMed

Sanford, Amy N; Clark, Stephanie E; Talham, Gwen; Sidelsky, Michael G; Coffin, Susan E

2002-10-01

The mucosal immune system interacts with the external environment. In the study reported here, we found that bedding materials can influence the intestinal immune responses of mice. We observed that mice housed on wood, compared with cotton bedding, had increased numbers of Peyer's patches (PP) visible under a dissecting microscope. In addition, culture of lymphoid organs revealed increased production of total and virus-specific IgA by PP and mesenteric lymph node (MLN) lymphocytes from mice housed on wood, compared with cotton bedding. However, bedding type did not influence serum virus-specific antibody responses. These observations indicate that bedding type influences the intestinal immune system and suggest that this issue should be considered by mucosal immunologists and personnel at animal care facilities.

The formation of intestinal organoids in a hanging drop culture.

PubMed

Panek, Malgorzata; Grabacka, Maja; Pierzchalska, Malgorzata

2018-01-25

Recently organoids have become widely used in vitro models of many tissue and organs. These type of structures, originated from embryonic or adult mammalian intestines, are called "mini guts". They organize spontaneously when intestinal crypts or stem cells are embedded in the extracellular matrix proteins preparation scaffold (Matrigel). This approach has some disadvantages, as Matrigel is undefined (the concentrations of growth factors and other biologically active components in it may vary from batch to batch), difficult to handle and expensive. Here we show that the organoids derived from chicken embryo intestine are formed in a hanging drop without embedding, providing an attractive alternative for currently used protocols. Using this technique we obtained compact structures composed of contiguous organoids, which were generally similar to chicken organoids cultured in Matrigel in terms of morphology and expression of intestinal epithelial markers. Due to the simplicity, high reproducibility and throughput capacity of hanging drop technique our model may be applied in various studies concerning the gut biology.

Molecular Epidemiology of Human Intestinal Amoebas in Iran

PubMed Central

Hooshyar, H; Rostamkhani, P; Rezaian, M

2012-01-01

Many microscopic-based epidemiological surveys on the prevalence of human intestinal pathogenic and non-pathogenic protozoa including intestinal amoeba performed in Iran show a high prevalence of human intestinal amoeba in different parts of Iran. Such epidemiological studies on amoebiasis are confusing, mainly due to recently appreciated distinction between the Entamoeba histolytica, E. dispar and E. moshkovskii. Differential diagnosis can be done by some methods such as PCR-based methods, monoclonal antibodies and the analysis of isoenzyme typing, however the molecular study of these protozoa in Iran is low. Based on molecular studies, it seems that E. dispar is predominant species especially in the central and northern areas of Iran and amoebiasis due to E. histolytica is a rare infection in the country. It is suggested that infection with E. moshkovskii may be common among Iranians. Considering the importance of molecular epidemiology of amoeba in Iran and also the current data, the present study reviews the data currently available on the molecular distribution of intestinal human amoeba in Iran. PMID:23193500

Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity.

PubMed

Chng, Song Hui; Kundu, Parag; Dominguez-Brauer, Carmen; Teo, Wei Ling; Kawajiri, Kaname; Fujii-Kuriyama, Yoshiaki; Mak, Tak Wah; Pettersson, Sven

2016-04-12

Diet and microbiome derived indole derivatives are known to activate the ligand induced transcription factor, the Aryl hydrocarbon Receptor (AhR). While the current understanding of AhR biology has confirmed its role in mucosal lymphocytes, its function in intestinal antigen presenting cells (APCs) is poorly understood. Here, we report that Cre-mediated deletion of AhR in CD11c-expressing cells in C57/BL6 mice is associated with altered intestinal epithelial morphogenesis in vivo. Moreover, when co-cultured with AhR-deficient DCs ex vivo, intestinal organoids showed reduced SRY (sex determining region Y)-box 9 and increased Mucin 2 expression, which correlates with reduced Paneth cells and increased goblet cell differentiation, similar to the data obtained in vivo. Further, characterization of intestinal APC subsets, devoid of AhR, revealed an expression pattern associated with aberrant intrinsic Wnt pathway regulation. At a functional level, the loss of AhR in APCs resulted in a dysfunctional epithelial barrier, associated with a more aggressive chemically induced colitis compared to wild type animals. Our results are consistent with a model whereby the AhR signalling pathway may participate in the regulation of innate immunity through intestinal epithelium development and mucosal immunity.

Perinatal Survival of a Fetus with Intestinal Volvulus and Intussusception: A Case Report and Review of the Literature

PubMed Central

Ohuoba, Esohe; Fruhman, Gary; Olutoye, Oluyinka; Zacharias, Nikolaos

2013-01-01

Fetal intestinal volvulus is a rare life-threatening condition. Late diagnosis of volvulus contributes to high rate of morbidity and mortality. It has variable degrees of presentation and survival. Intrauterine volvulus may be complicated by intestinal atresia due to ischemic necrosis. To our knowledge, there are three reported cases of term fetal demise. We report a case of fetal intestinal volvulus with perinatal survival of the largest term infant described with this complication to date. The volvulus was associated with type 3A jejunal atresia and intestinal pathology was noted on prenatal ultrasound. The infant was born via urgent cesarean delivery at 376/7 weeks of gestation and underwent emergent exploratory laparotomy with resection of small bowel and primary end-to-end anastomosis. Intrauterine intestinal volvulus may be suspected on prenatal ultrasound but only definitively diagnosed postnatally. Signs of fetal distress and volvulus are rarely associated with reports of survival in the term fetus. We review reported cases of prenatally suspected volvulus in infants documented to survive past the neonatal period. As fetal volvulus and most intestinal atresias/stenoses manifest during the third trimester, we recommend that the limited fetal anatomical survey during growth ultrasounds at 32 to 36 weeks routinely include an assessment of the fetal bowel. PMID:24147247

Perinatal survival of a fetus with intestinal volvulus and intussusception: a case report and review of the literature.

PubMed

Ohuoba, Esohe; Fruhman, Gary; Olutoye, Oluyinka; Zacharias, Nikolaos

2013-10-01

Fetal intestinal volvulus is a rare life-threatening condition. Late diagnosis of volvulus contributes to high rate of morbidity and mortality. It has variable degrees of presentation and survival. Intrauterine volvulus may be complicated by intestinal atresia due to ischemic necrosis. To our knowledge, there are three reported cases of term fetal demise. We report a case of fetal intestinal volvulus with perinatal survival of the largest term infant described with this complication to date. The volvulus was associated with type 3A jejunal atresia and intestinal pathology was noted on prenatal ultrasound. The infant was born via urgent cesarean delivery at 37(6/7) weeks of gestation and underwent emergent exploratory laparotomy with resection of small bowel and primary end-to-end anastomosis. Intrauterine intestinal volvulus may be suspected on prenatal ultrasound but only definitively diagnosed postnatally. Signs of fetal distress and volvulus are rarely associated with reports of survival in the term fetus. We review reported cases of prenatally suspected volvulus in infants documented to survive past the neonatal period. As fetal volvulus and most intestinal atresias/stenoses manifest during the third trimester, we recommend that the limited fetal anatomical survey during growth ultrasounds at 32 to 36 weeks routinely include an assessment of the fetal bowel.

[Study of the association between socio-environmental factors and the prevalence of intestinal parasitosis in the suburbs of the city of Manaus in the state of Amazonas, Brazil].

PubMed

Visser, Silvia; Giatti, Leandro Luiz; Carvalho, Ricardo Augusto Chaves de; Guerreiro, Jose Camilo Hurtado

2011-08-01

This study assesses the association between socio-environmental factors and urban sanitation conditions with the prevalence of intestinal parasitosis in a community on the periphery of the city of Manaus. The study comprised a socio-environmental survey and a parasitological inquiry. A heterogeneous community was revealed with some socio-economic and environmental differences between the micro-areas evaluated, even though the urban sanitation conditions were found to be predominantly precarious. The prevalence of intestinal parasitosis was 44.2%. There was no significant difference between the micro-areas that could explain the occurrence of intestinal parasitosis. An association was found between intestinal parasitosis and residential building types, age bracket and the quality of the water used for personal hygiene and consumption in the home. Open air sewage was a risk factor associated with intestinal parasitosis (OR=6.72; p=0.034) and also with intestinal protozoa (OR=21.87; p=0.004). In terms of the presence of protozoa, two risk factors were verified: the dumping of sewage directly into the river system (OR=12.98; p=0.011) and the use of rudimentary cesspits (OR=9.54; p=0.019).

Distinct intestinal adaptation for vitamin B12 and bile acid absorption revealed in a new mouse model of massive ileocecal resection.

PubMed

Matsumoto, Yuka; Mochizuki, Wakana; Akiyama, Shintaro; Matsumoto, Taichi; Nozaki, Kengo; Watanabe, Mamoru; Nakamura, Tetsuya

2017-09-15

Ileocecal resection (ICR), one of several types of intestinal resection that results in short bowel syndrome (SBS), causes severe clinical disease in humans. We here describe a mouse model of massive ICR in which 75% of the distal small intestine is removed. We demonstrate that mice underwent 75% ICR show severe clinical signs and high mortality, which may recapitulate severe forms of human SBS, despite an adaptive response throughout the remnant intestine. By using this model, we also investigated whether the epithelium of the remnant intestine shows enhanced expression of factors involved in region-specific functions of the ileum. Cubn mRNA and its protein product, which play an essential role in vitamin B12 absorption in the ileum, are not compensatory up-regulated in any part of the remnant intestine, demonstrating a clear contrast with post-operative up-regulation of genes involved in bile acid absorption. Our study suggests that functional adaptation by phenotypical changes in the intestinal epithelium is not a general feature for nutrient absorption systems that are confined to the ileum. We also propose that the mouse model developed in this study will become a unique system to facilitate studies on SBS with ICR in humans. © 2017. Published by The Company of Biologists Ltd.

Oral Infection with Signature-Tagged Listeria monocytogenes Reveals Organ-Specific Growth and Dissemination Routes in Guinea Pigs

PubMed Central

Melton-Witt, Jody A.; Rafelski, Susanne M.; Portnoy, Daniel A.

2012-01-01

Listeria monocytogenes causes a serious food-borne disease due to its ability to spread from the intestine to other organs, a process that is poorly understood. In this study we used 20 signature-tagged wild-type clones of L. monocytogenes in guinea pigs in combination with extensive quantitative data analysis to gain insight into extraintestinal dissemination. We show that L. monocytogenes colonized the liver in all asymptomatic animals. Spread to the liver occurred as early as 4 h after ingestion via a direct pathway from the intestine to the liver. This direct pathway contributed significantly to the bacterial load in the liver and was followed by a second wave of dissemination via the mesenteric lymph nodes (indirect pathway). Furthermore, bacteria were eliminated in the liver, whereas small intestinal villi provided a niche for bacterial replication, indicating organ-specific differences in net bacterial growth. Bacteria were shed back from intestinal villi into the small intestinal lumen and reinfected the Peyer's patches. Together, these results support a novel dissemination model where L. monocytogenes replicates in intestinal villi, is shed into the lumen, and reinfects intestinal immune cells that traffic to liver and mesenteric lymph nodes, a process that occurs even during asymptomatic colonization. PMID:22083714

Microscopic mild focal cortical dysplasia in temporal lobe dual pathology: an electrocorticography study.

PubMed

Morales Chacón, L; Estupiñán, B; Lorigados Pedre, L; Trápaga Quincoses, O; García Maeso, I; Sanchez, A; Bender del Busto, J; Garcia, M E; Baez Martin, M; Zaldivar, M; Gómez, A; Orozco, S; Rocha Arrieta, L

2009-10-01

Associations between electrophysiological and histological findings might provide an insight into the epileptogenicity of mild focal cortical dysplasia (FCD) in patients with temporal lobe epilepsy (TLE) and a dual pathology. A total of 22 patients with pharmacoresistant TLE were included in the study, 16 of them with histologically confirmed hippocampal sclerosis (HS) associated with neocortical temporal mild Palmini Type-I FCD subtypes and 6 with HS. Intraoperative electrocorticography (ECoG) recordings were analysed for epileptiform discharge frequency and morphology. Associations between histological, and electrocorticography pattern findings in these patients were analysed. Electroclinical outcomes in these patients were also evaluated. Neocortical areas with mild Palmini Type-I FCD showed a significantly higher spike frequency (SF) recorded in the inferior temporal gyrus than those neocortical areas in patients with HS. There was a tendency to higher spike frequency and lower amplitude in neocortical areas with histopathologic subtype IB FCD in relation with IA during intraoperative ECoG. Post-SF excision and amplitude were significantly lower during neocortical post-excision intraoperative ECoG than during neocortical pre-excision recording. There was no difference found in the clinical outcome between patients with and without FCD. Intraoperative electrocorticographic interictal spike frequency recorded in the neocortical inferior temporal gyrus may help to characterize the histopathologic subtypes of mild Palmini Type-I FCD in patients with temporal lobe epilepsy (TLE) and a dual pathology. Our data support the epileptogenicity of neocortical mild FCD in TLE and assessments of ECoG patterns are relevant to determine the extent of the resection in these patients which can influence the electroclinical outcome.

Colonization of fish skin is vital for Vibrio anguillarum to cause disease.

PubMed

Weber, Barbara; Chen, Chang; Milton, Debra L

2010-02-01

Vibrio anguillarum causes a fatal haemorrhagic septicaemia in marine fish. During initial stages of infection, host surfaces are colonized; however, few virulence factors required for colonization of the host are identified. In this study, in vivo bioluminescent imaging was used to analyse directly the colonization of the whole rainbow trout animal by V. anguillarum. The wild type rapidly colonized both the skin and the intestines by 24 h; however, the bacterial numbers on the skin were significantly higher than in the intestines indicating that skin colonization may be important for disease to occur. Mutants defective for the anguibactin iron uptake system, exopolysaccharide transport, or Hfq, an RNA chaperone, were attenuated for virulence, did not colonize the skin, and penetrated skin mucus less efficiently than the wild type. These mutants, however, did colonize the intestines and were as resistant to 2% bile salts as is the wild type. Moreover, exopolysaccharide mutants were significantly more sensitive to lysozyme and antimicrobial peptides, while the Hfq and anguibactin mutants were sensitive to lysozyme compared with the wild type. Vibrio anguillarum encodes several mechanisms to protect against antimicrobial components of skin mucus enabling an amazingly abundant growth on the skin enhancing its disease opportunities. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

Pathological Type-2 Immune Response, Enhanced Tumor Growth, and Glucose Intolerance in Retnlβ (RELMβ) Null Mice: A Model of Intestinal Immune System Dysfunction in Disease Susceptibility.

PubMed

Wernstedt Asterholm, Ingrid; Kim-Muller, Ja Young; Rutkowski, Joseph M; Crewe, Clair; Tao, Caroline; Scherer, Philipp E

2016-09-01

Resistin, and its closely related homologs, the resistin-like molecules (RELMs) have been implicated in metabolic dysregulation, inflammation, and cancer. Specifically, RELMβ, expressed predominantly in the goblet cells in the colon, is released both apically and basolaterally, and is hence found in both the intestinal lumen in the mucosal layer as well as in the circulation. RELMβ has been linked to both the pathogenesis of colon cancer and type 2 diabetes. RELMβ plays a complex role in immune system regulation, and the impact of loss of function of RELMβ on colon cancer and metabolic regulation has not been fully elucidated. We therefore tested whether Retnlβ (mouse ortholog of human RETNLβ) null mice have an enhanced or reduced susceptibility for colon cancer as well as metabolic dysfunction. We found that the lack of RELMβ leads to increased colonic expression of T helper cell type-2 cytokines and IL-17, associated with a reduced ability to maintain intestinal homeostasis. This defect leads to an enhanced susceptibility to the development of inflammation, colorectal cancer, and glucose intolerance. In conclusion, the phenotype of the Retnlβ null mice unravels new aspects of inflammation-mediated diseases and strengthens the notion that a proper intestinal barrier function is essential to sustain a healthy phenotype. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Gastric cancer in young vs old Romanian patients: immunoprofile with emphasis on maspin and mena protein reactivity.

PubMed

Gurzu, Simona; Kadar, Zoltan; Sugimura, Haruhiko; Bara, Tivadar; Bara, Tivadar; Halmaciu, Ioana; Jung, Ioan

2015-03-01

Increasing number of early-onset gastric carcinomas (GCs) and controversial results regarding the differences among young and older patients with this type of cancer are the reasons why correlation of clinicopathological factors with molecular markers is necessary. The aim of our study was to compare the demographic, clinical and immunohistochemical (IHC) aspects in Romanian patients with GC diagnosed below and above 45 years old. In 191 samples provided from patients with GC, the clinicopathological parameters were correlated with a panel of 15 antibodies: E-cadherin, HER-2, VEGF, CD31, CD105, COX-2, maspin, bax, bcl-2, p53, Ki67, MLH-1, MSH-2, mena protein and vimentin. Compared to the conventional cases, GCs diagnosed below 45 years old were more frequently located at the gastroesophageal junction and presented a higher percentage of lymph node metastases. The diffuse type E-cadherin/mena/p53/Ki67/bax-negative cases that displayed nuclear maspin positivity were also more frequently in younger patients. The intestinal type early-onset GCs were the most angiogenic ones, the apoptotic rate being lower than in the intestinal type GCs of the aged. Compared to the conventional cases, in the early-onset GCs the nuclear maspin-mediated antiproliferative activity is more intense in diffuse type while the mena-dependent tumor cell proliferation is more characteristic for intestinal type GCs. © 2014 APMIS. Published by John Wiley & Sons Ltd.

Donor interleukin-22 and host type I interferon signaling pathway participate in intestinal graft-versus-host disease via STAT1 activation and CXCL10.

PubMed

Lamarthée, B; Malard, F; Gamonet, C; Bossard, C; Couturier, M; Renauld, J-C; Mohty, M; Saas, P; Gaugler, B

2016-03-01

Acute graft-versus-host disease (aGVHD) remains a major complication following allogeneic hematopoietic cell transplantation, limiting the success of this therapy. We previously reported that interleukin-22 (IL-22) participates to aGVHD development, but the underlying mechanisms of its contribution remain poorly understood. In this study, we analyzed the mechanism of the pathological function of IL-22 in intestinal aGVHD. Ex-vivo colon culture experiments indicated that IL-22 was able to induce Th1-like inflammation via signal transducer and activator of transcription factor-1 (STAT1) and CXCL10 induction in the presence of type I interferon (IFN). To evaluate a potential synergy between IL-22 and type I IFN in aGVHD, we transplanted recipient mice, either wild-type (WT) or type I IFN receptor deficient (IFNAR(-/-)), with bone marrow cells and WT or IL-22 deficient (IL-22(-/-)) T cells. We observed a decreased GVHD severity in IFNAR(-/-) recipient of IL-22(-/-) T cells, which was associated with a lower level of STAT1 activation and reduced CXCL10 expression in the large intestine. Finally, immunohistochemistry staining of STAT1 performed on gastrointestinal biopsies of 20 transplanted patients showed exacerbated STAT1 activation in gastrointestinal tissues of patients with aGVHD as compared with those without aGVHD. Thus, interfering with both IL-22 and type I IFN signaling may provide a novel approach to limit aGVHD.

Effects of dietary glucose and sodium chloride on intestinal glucose absorption of common carp (Cyprinus carpio L.).

PubMed

Qin, Chaobin; Yang, Liping; Zheng, Wenjia; Yan, Xiao; Lu, Ronghua; Xie, Dizhi; Nie, Guoxing

2018-01-08

The co-transport of sodium and glucose is the first step for intestinal glucose absorption. Dietary glucose and sodium chloride (NaCl) may facilitate this physiological process in common carp (Cyprinus carpio L.). To test this hypothesis, we first investigated the feeding rhythm of intestinal glucose absorption. Carps were fed to satiety once a day (09:00 a.m.) for 1 month. Intestinal samples were collected at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00. Result showed that food intake greatly enhanced sodium/glucose cotransporter 1 (SGLT1) and glucose transporter type 2 (GLUT2) expressions, and improved glucose absorption, with highest levels at 09:00 a.m.. Then we designed iso-nitrogenous and iso-energetic diets with graded levels of glucose (10%, 20%, 30%, 40% and 50%) and NaCl (0%, 1%, 3% and 5%), and submitted to feeding trial for 10 weeks. The expressions of SGLT1 and GLUT2, brush border membrane vesicles (BBMVs) glucose transport and intestinal villus height were determined after the feeding trial. Increasing levels of dietary glucose and NaCl up-regulated mRNA and protein levels of SGLT1 and GLUT2, enhanced BBMVs glucose transport in the proximal, mid and distal intestine. As for histological adaptive response, however, high-glucose diet prolonged while high-NaCl diet shrank intestinal villus height. Furthermore, we also found that higher mRNA levels of SGLT1 and GLUT2, higher glucose transport capacity of BBMVs, and higher intestinal villus were detected in the proximal and mid intestine, compared to the distal part. Taken together, our study indicated that intestinal glucose absorption in carp was primarily occurred in the proximal and mid intestine, and increasing levels of dietary glucose and NaCl enhanced intestinal glucose absorption in carp. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulation of bile acid homeostasis by the intestinal Diet1–FGF15/19 axis

PubMed Central

Reue, Karen; Lee, Jessica M.; Vergnes, Laurent

2015-01-01

Purpose of review Hepatic bile acid synthesis is controlled, in part, by a complex enterohepatic feedback regulatory mechanism. In this review, we focus on the role of the intestinal FGF15/19 hormone in modulating bile acid levels, and additional metabolic effects on glucose metabolism, non-alcoholic liver disease (NAFLD), and liver regeneration. We also highlight the newly identified intestinal protein, Diet1, which is a modulator of FGF15/19 levels. Recent findings Low FGF19 levels are associated with bile acid diarrhea and NAFLD. In contrast, high FGF19 levels are associated with diabetes remission following Roux-en-Y gastric bypass surgery, suggesting new therapeutic approaches against type 2 diabetes. The effect of FGF15/19 on liver plasticity is a double-edged sword: whereas elevated FGF15/19 levels improve survival of mice after partial hepatectomy, FGF19 mitogenic activity is associated with liver carcinoma. Finally, a recent study has identified Diet1, an intestinal factor that influences FGF15/19 levels in mouse intestine and human enterocytes. Diet1 represents the first factor shown to influence FGF15/19 levels at a post-transcriptional level. Summary The biological effects of FGF15/19 make it an attractive target for treating metabolic dysregulation underlying conditions such as fatty liver and type 2 diabetes. Further elucidation of the role of Diet1 in FGF15/19 secretion may provide a control point for pharmacological modulation of FGF15/19 levels. PMID:24535283

Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance.

PubMed

Saad, M J A; Santos, A; Prada, P O

2016-07-01

Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ∼100 trillion bacteria, which constitute the gut microbiota. Studies have shown that lean and overweight rodents and humans may present differences in the composition of their intestinal flora. Over the past 10 years, data from different sources have established a causal link between the intestinal microbiota and obesity/insulin resistance. It is important to emphasize that diet-induced obesity promotes insulin resistance by mechanisms independent and dependent on gut microbiota. In this review, we present several mechanisms that contribute to explaining the link between intestinal flora and insulin resistance/obesity. The LPS from intestinal flora bacteria can induce a chronic subclinical inflammatory process and obesity, leading to insulin resistance through activation of TLR4. The reduction in circulating SCFA may also have an essential role in the installation of reduced insulin sensitivity and obesity. Other mechanisms include effects of bile acids, branched-chain amino acids (BCAA), and some other lesser-known factors. In the near future, this area should open new therapeutic avenues for obesity/insulin resistance and its comorbidities. ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.

Regulation of human intestinal T-cell responses by type 1 interferon-STAT1 signaling is disrupted in inflammatory bowel disease.

PubMed

Giles, E M; Sanders, T J; McCarthy, N E; Lung, J; Pathak, M; MacDonald, T T; Lindsay, J O; Stagg, A J

2017-01-01

Type 1 interferon (IFN-1) promotes regulatory T-cell function to suppress inflammation in the mouse intestine, but little is known about IFN-1 in the human gut. We therefore assessed the influence of IFN-1 on CD4+ T-cells isolated from human colon tissue obtained from healthy controls or patients with inflammatory bowel disease (IBD). Immunofluorescent imaging revealed constitutive expression of IFNβ in human intestinal tissue, and colonic T-cells were responsive to exogenous IFN-1 as assessed by phosphorylation of signal transduction and activator of transcription 1 (pSTAT1) and induction of interferon stimulated genes (ISGs). Unlike their blood counterparts, intestinal T-cells from non-inflamed regions of IBD colon displayed enhanced responsiveness to IFN-1, increased frequency of pSTAT1+ cells, and greater induction of ISGs upon IFN-1 exposure in vitro. In healthy tissue, antibody neutralization of IFNβ selectively reduced T-cell production of the pro-regulatory cytokine interleukin-10 (IL-10) and increased IFNγ synthesis. In contrast, neutralization of IFNβ in IBD tissue cultures increased the frequency of T-cells producing inflammatory cytokines but did not alter IL-10 expression. These data support a role for endogenous IFN-1 as a context-dependent modulator of T-cell function that promotes regulatory activity in healthy human intestine, but indicate that the IFN-1/STAT1 pathway is dysregulated in inflammatory bowel disease.

ADAM10 Regulates Notch Function in Intestinal Stem Cells of Mice

PubMed Central

Tsai, Yu-Hwai; VanDussen, Kelli L.; Sawey, Eric T.; Wade, Alex W.; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G.; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C.; Samuelson, Linda C.; Dempsey, Peter J.

2014-01-01

BACKGROUND & AIMS ADAM10 is a cell surface sheddase that regulates physiological processes including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. METHODS We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10f/f mice) and conditional (Vil-CreER;Adam10f/f and Lgr5-CreER;Adam10f/f mice) deletion of ADAM10. We performed cell lineage tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26NICD) or mice with intestine-specific disruption of Notch (Rosa26DN-MAML), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. RESULTS Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26NICD and Rosa26DN-MAML mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage tracing experiments showed that ADAM10 is required for survival of Lgr5+ crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. CONCLUSIONS ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. PMID:25038433

ADHD and Other Associated Developmental Problems in Children with Mild Mental Retardation. The Use of the "Five-To-Fifteen" Questionnaire in a Population-Based Sample

ERIC Educational Resources Information Center

Lindblad, Ida; Gillberg, Christopher; Fernell, Elisabeth

2011-01-01

The aim was to examine the rates and types of parent reported neuropsychiatric problems in children and adolescents with mild mental retardation (MMR) (mild intellectual disability/UK) using the Five-To-Fifteen questionnaire (FTF). The target group comprised all pupils with clinically diagnosed MMR, aged between 7 and 15 years, attending the…

Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines.

PubMed

Camargo, A; Ferreira, S H

1971-06-01

BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF.

Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines

PubMed Central

Camargo, A.; Ferreira, S. H.

1971-01-01

BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF. PMID:5091164

Clinical classification of adult patients with chronic intestinal failure due to benign disease: An international multicenter cross-sectional survey.

PubMed

Pironi, Loris; Konrad, Denise; Brandt, Chrisoffer; Joly, Francisca; Wanten, Geert; Agostini, Federica; Chambrier, Cecile; Aimasso, Umberto; Zeraschi, Sarah; Kelly, Darlene; Szczepanek, Kinga; Jukes, Amelia; Di Caro, Simona; Theilla, Miriam; Kunecki, Marek; Daniels, Joanne; Serlie, Mireille; Poullenot, Florian; Wu, Jian; Cooper, Sheldon C; Rasmussen, Henrik H; Compher, Charlene; Seguy, David; Crivelli, Adriana; Pagano, Maria C; Hughes, Sarah-Jane; Guglielmi, Francesco W; Kozjek, Nada Rotovnik; Schneider, Stéphane M; Gillanders, Lyn; Ellegard, Lars; Thibault, Ronan; Matras, Przemysław; Zmarzly, Anna; Matysiak, Konrad; Van Gossum, Andrè; Forbes, Alastair; Wyer, Nicola; Taus, Marina; Virgili, Nuria M; O'Callaghan, Margie; Chapman, Brooke; Osland, Emma; Cuerda, Cristina; Sahin, Peter; Jones, Lynn; Lee, Andre D W; Bertasi, Valentino; Orlandoni, Paolo; Izbéki, Ferenc; Spaggiari, Corrado; Díez, Marta Bueno; Doitchinova-Simeonova, Maryana; Garde, Carmen; Serralde-Zúñiga, Aurora E; Olveira, Gabriel; Krznaric, Zeljko; Czako, Laszlo; Kekstas, Gintautas; Sanz-Paris, Alejandro; Jáuregui, Estrella Petrina; Murillo, Ana Zugasti; Schafer, Eszter; Arends, Jann; Suárez-Llanos, José P; Shaffer, Jon; Lal, Simon

2018-04-01

The aim of the study was to evaluate the applicability of the ESPEN 16-category clinical classification of chronic intestinal failure, based on patients' intravenous supplementation (IVS) requirements for energy and fluids, and to evaluate factors associated with those requirements. ESPEN members were invited to participate through ESPEN Council representatives. Participating centers enrolled adult patients requiring home parenteral nutrition for chronic intestinal failure on March 1st 2015. The following patient data were recorded though a structured database: sex, age, body weight and height, intestinal failure mechanism, underlying disease, IVS volume and energy need. Sixty-five centers from 22 countries enrolled 2919 patients with benign disease. One half of the patients were distributed in 3 categories of the ESPEN clinical classification. 9% of patients required only fluid and electrolyte supplementation. IVS requirement varied considerably according to the pathophysiological mechanism of intestinal failure. Notably, IVS volume requirement represented loss of intestinal function better than IVS energy requirement. A simplified 8 category classification of chronic intestinal failure was devised, based on two types of IVS (either fluid and electrolyte alone or parenteral nutrition admixture containing energy) and four categories of volume. Patients' IVS requirements varied widely, supporting the need for a tool to homogenize patient categorization. This study has devised a novel, simplified eight category IVS classification for chronic intestinal failure that will prove useful in both the clinical and research setting when applied together with the underlying pathophysiological mechanism of the patient's intestinal failure. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Small intestinal bacterial overgrowth syndrome

PubMed Central

Bures, Jan; Cyrany, Jiri; Kohoutova, Darina; Förstl, Miroslav; Rejchrt, Stanislav; Kvetina, Jaroslav; Vorisek, Viktor; Kopacova, Marcela

2010-01-01

Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO. PMID:20572300

Normal cadmium uptake in microcytic anemia mk/mk mice suggests that DMT1 is not the only cadmium transporter in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Tomohito; Momoi, Kanae; Hosoyamada, Makoto

2008-03-15

Divalent metal transporter 1 (DMT1) is a mammalian iron (Fe) transporter and also transports Cadmium (Cd) in vitro. This study compared Cd absorption in DMT1-dysfunctional MK/Rej-{sup mk}/{sub mk} mice (mk/mk mice) and in DMT1-functional, Fe-deficient wild-type (WT) mice, to clarify the role of DMT1 in intestinal Cd absorption in vivo. Mice were given 1 ppm CdCl{sub 2} aq in drinking water for 2 weeks, and the concentrations of Cd and Fe in liver, kidney, and intestinal epithelium were subsequently determined. The Fe concentration in intestinal epithelia of WT mice was decreased in proportion to the level of dietary Fe limitation,more » while Cd accumulation under the same conditions was increased. DMT1 mRNA expression in the small intestine of Fe-deficient WT mice was clearly increased compared to that in Fe-sufficient WT mice. Iron deficiency resulted in up-regulation of Cd uptake in the intestine of Fe-deficient WT mice. The mk/mk mice have a mutation in DMT1 and loss of its function led to decreased intestinal Fe concentration. However, intestinal Cd accumulation was the same as in WT mice and it was also increased in Fe-deficient situation. There is the possibility that an unknown Cd pathway has taken a role on Cd intestinal absorption in vivo and that this pathway is regulated by food Fe concentrations. Therefore, DMT1 is not the sole transporter of intestinal cadmium absorption in vivo.« less

Mother-to-Infant Transmission of Intestinal Bifidobacterial Strains Has an Impact on the Early Development of Vaginally Delivered Infant's Microbiota

PubMed Central

Makino, Hiroshi; Kushiro, Akira; Ishikawa, Eiji; Kubota, Hiroyuki; Gawad, Agata; Sakai, Takafumi; Oishi, Kenji; Martin, Rocio; Ben-Amor, Kaouther; Knol, Jan; Tanaka, Ryuichiro

2013-01-01

Objectives Bifidobacterium species are one of the major components of the infant's intestine microbiota. Colonization with bifidobacteria in early infancy is suggested to be important for health in later life. However, information remains limited regarding the source of these microbes. Here, we investigated whether specific strains of bifidobacteria in the maternal intestinal flora are transmitted to their infant's intestine. Materials and Methods Fecal samples were collected from healthy 17 mother and infant pairs (Vaginal delivery: 12; Cesarean section delivery: 5). Mother's feces were collected twice before delivery. Infant's feces were collected at 0 (meconium), 3, 7, 30, 90 days after birth. Bifidobacteria isolated from feces were genotyped by multilocus sequencing typing, and the transitions of bifidobacteria counts in infant's feces were analyzed by quantitative real-time PCR. Results Stains belonging to Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium catenulatum, Bifidobacterium longum subsp. longum, and Bifidobacterium pseudocatenulatum, were identified to be monophyletic between mother's and infant's intestine. Eleven out of 12 vaginal delivered infants carried at least one monophyletic strain. The bifidobacterial counts of the species to which the monophyletic strains belong, increased predominantly in the infant's intestine within 3 days after birth. Among infants delivered by C-section, monophyletic strains were not observed. Moreover, the bifidobacterial counts were significantly lower than the vaginal delivered infants until 7 days of age. Conclusions Among infants born vaginally, several Bifidobacterium strains transmit from the mother and colonize the infant's intestine shortly after birth. Our data suggest that the mother's intestine is an important source for the vaginal delivered infant's intestinal microbiota. PMID:24244304

Oligomeric states of the Shigella translocator protein IpaB provide structural insights into formation of the type III secretion translocon

PubMed Central

Dickenson, Nicholas E; Choudhari, Shyamal P; Adam, Philip R; Kramer, Ryan M; Joshi, Sangeeta B; Middaugh, C Russell; Picking, Wendy L; Picking, William D

2013-01-01

The Shigella flexneri Type III secretion system (T3SS) senses contact with human intestinal cells and injects effector proteins that promote pathogen entry as the first step in causing life threatening bacillary dysentery (shigellosis). The Shigella Type III secretion apparatus (T3SA) consists of an anchoring basal body, an exposed needle, and a temporally assembled tip complex. Exposure to environmental small molecules recruits IpaB, the first hydrophobic translocator protein, to the maturing tip complex. IpaB then senses contact with a host cell membrane, forming the translocon pore through which effectors are delivered to the host cytoplasm. Within the bacterium, IpaB exists as a heterodimer with its chaperone IpgC; however, IpaB's structural state following secretion is unknown due to difficulties isolating stable protein. We have overcome this by coexpressing the IpaB/IpgC heterodimer and isolating IpaB by incubating the complex in mild detergents. Interestingly, preparation of IpaB with n-octyl-oligo-oxyethylene (OPOE) results in the assembly of discrete oligomers while purification in N,N-dimethyldodecylamine N-oxide (LDAO) maintains IpaB as a monomer. In this study, we demonstrate that IpaB tetramers penetrate phospholipid membranes to allow a size-dependent release of small molecules, suggesting the formation of discrete pores. Monomeric IpaB also interacts with liposomes but fails to disrupt them. From these and additional findings, we propose that IpaB can exist as a tetramer having inherent flexibility, which allows it to cooperatively interact with and insert into host cell membranes. This event may then lay the foundation for formation of the Shigella T3SS translocon pore. PMID:23456854

Cetuximab Injection

MedlinePlus

... other medications to treat a certain type of cancer of the head and neck. Cetuximab is also used alone or in combination with other medications to treat a certain type of cancer of the colon (large intestine) or rectum that ...

Factors influencing growth and intestinal parasitic infections in preschoolers attending philanthropic daycare centers in Salvador, Northeast Region of Brazil.

PubMed

Lander, Rebecca L; Lander, Alastair G; Houghton, Lisa; Williams, Sheila M; Costa-Ribeiro, Hugo; Barreto, Daniel L; Mattos, Angela P; Gibson, Rosalind S

2012-11-01

Poor growth and intestinal parasitic infections are widespread in disadvantaged urban children. This cross-sectional study assessed factors influencing poor growth and intestinal parasites in 376 children aged three to six years in daycare centers in Salvador, in the Northeast Region of Brazil. Data was obtained from seven daycare centers on child weight, height, socio-economic status, health and intestinal parasites in stool samples. Prevalence of moderate underweight (< -1SD > -2SD), wasting and stunting was 12%, 16% and 6% respectively. Socioeconomic status, birth order, and maternal weight were predictors of poor anthropometric status. Almost 30% of children were infected with more than one intestinal parasite. Helminths (17.8%), notably Trichuris trichiura (12%) and Ascaris lumbricoides (10.5%), and protozoan Giardia duodenalis (13%) were the most common types of parasites detected. One percent of children had hookworm and Cryptosporidium sp. and 25% had non-pathogenic protozoan cysts. Boys from families with very low socio-economic status had lower linear growth and presented a greater risk of helminth infection. Deworming is considered an alternative for reducing the prevalence of intestinal parasitic infections in this age group.

Intestinal epithelial wound healing assay in an epithelial-mesenchymal co-culture system.

PubMed

Seltana, Amira; Basora, Nuria; Beaulieu, Jean-François

2010-01-01

Rapid and efficient healing of epithelial damage is critical to the functional integrity of the small intestine. Epithelial repair is a complex process that has largely been studied in cultured epithelium but to a much lesser extent in mucosa. We describe a novel method for the study of wound healing using a co-culture system that combined an intestinal epithelial Caco-2/15 cell monolayer cultured on top of human intestinal myofibroblasts, which together formed a basement membrane-like structure that contained many of the major components found at the epithelial-mesenchymal interface in the human intestine. To investigate the mechanism of restitution, small lesions were generated in epithelial cell monolayers on plastic or in co-cultures without disturbing the underlying mesenchymal layer. Monitoring of wound healing showed that repair was more efficient in Caco-2/15-myofibroblast co-cultures than in Caco-2/15 monolayers and involved the deposition of basement membrane components. Functional experiments showed that the addition of type I collagen or human fibronectin to the culture medium significantly accelerated wound closure on epithelial cell co-cultures. This system may provide a new tool to investigate the mechanisms that regulate wound healing in the intestinal epithelium.

Interactions Between Bacteria and the Gut Mucosa: Do Enteric Neurotransmitters Acting on the Mucosal Epithelium Influence Intestinal Colonization or Infection?

PubMed

Green, Benedict T; Brown, David R

2016-01-01

The intestinal epithelium is a critical barrier between the internal and external milieux of the mammalian host. Epithelial interactions between these two host environments have been shown to be modulated by several different, cross-communicating cell types residing in the gut mucosa. These include enteric neurons, whose activity is influenced by bacterial pathogens, and their secreted products. Neurotransmitters appear to influence epithelial associations with bacteria in the intestinal lumen. For example, internalization of Salmonella enterica and Escherichia coli O157:H7 into the Peyer's patch mucosa of the small intestine is altered after the inhibition of neural activity with saxitoxin, a neuronal sodium channel blocker. Catecholamine neurotransmitters, such as dopamine and norepinephrine, also alter bacterial internalization in Peyer's patches. In the large intestine, norepinephrine increases the mucosal adherence of E. coli. These neurotransmitter actions are mediated by well-defined catecholamine receptors situated on the basolateral membranes of epithelial cells rather than through direct interactions with luminal bacteria. Investigations of the involvement of neuroepithelial communication in the regulation of interactions between the intestinal mucosa and luminal bacteria will provide novel insights into the mechanisms underlying bacterial colonization and pathogenesis at mucosal surfaces.

Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases

PubMed Central

Opazo, Maria C.; Ortega-Rocha, Elizabeth M.; Coronado-Arrázola, Irenice; Bonifaz, Laura C.; Boudin, Helene; Neunlist, Michel; Bueno, Susan M.; Kalergis, Alexis M.; Riedel, Claudia A.

2018-01-01

The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases. PMID:29593681

Tolerance and efficacy of emamectin benzoate and ivermectin for the treatment of Pseudocapillaria tomentosa in laboratory zebrafish (Danio rerio).

PubMed

Collymore, Chereen; Watral, Virginia; White, Julie R; Colvin, Michael E; Rasmussen, Skye; Tolwani, Ravi J; Kent, Michael L

2014-10-01

Tolerance of adult zebrafish and efficacy of emamectin benzoate and ivermectin in eliminating Pseudocapillaria tomentosa infection were evaluated. In the tolerance study, behavioral changes, fecundity, histopathology, and mortality were evaluated for in-feed administration of emamectin (0.05, 0.10, and 0.25 mg/kg) and ivermectin (0.05 and 0.10 mg/kg). All doses of emamectin were well tolerated. Ivermectin 0.05 mg/kg administration resulted in mild behavioral changes and a transient decrease in fecundity. Ivermectin 0.10 mg/kg administration resulted in severe behavioral changes and some mortality. In the efficacy study, emamectin (0.05 and 0.25 mg/kg) and ivermectin (0.05 mg/kg) were evaluated for their efficacy in eliminating P. tomentosa infection. Emamectin reduced parasite burden in infected zebrafish, and ivermectin eliminated intestinal nematode infections. Despite a small margin of safety, ivermectin 0.05 mg/kg was effective at eliminating P. tomentosa infection in adult zebrafish. Higher doses or a longer course of treatment may be needed for complete elimination of P. tomentosa infection using emamectin. In this study, we propose two possible treatments for intestinal nematode infections in zebrafish.

Baccharis megapotamica var. weirii poisoning in water buffalo (Bubalus bubalis).

PubMed

Oliveira-Filho, José C; Carmo, Priscila M S; Lucena, Ricardo B; Pierezan, Felipe; Barros, Claudio S L

2011-05-01

An outbreak of an acute disease in buffalo (Bubalus bubalis) caused by the ingestion of Baccharis megapotamica var. weirii occurred in the southern region of Brazil. Ten out of 50 buffalo died 24-48 hr after being introduced into a pasture containing abundant amounts of the plant. Factors influencing the ingestion of the plant and consequent toxicosis included hunger, stress caused by shipment, and unfamiliarity with the plant. Clinical signs included serous ocular discharge, incoordination, mild bloat, and muscle trembling. One buffalo was necropsied. Gross findings included dehydration, abundant liquid in the rumen, reddening of the mucosa of forestomachs, abomasum, and intestine, and edema of the wall of the rumen. The main histologic lesions were superficial to full thickness degeneration and necrosis of the stratified epithelium lining the forestomachs, necrosis of the intestinal mucosa, and widespread lymphoid necrosis. A calf (Bos taurus) was fed a single dose of 5 g/kg/body weight of B. megapotamica var. weirii harvested from the same site where the buffalo died. Twenty hours after the administration of the plant this calf died with clinical signs and lesions similar to those observed in the naturally poisoned buffalo. © 2011 The Author(s)

Distinctive toxicity of TiO2 rutile/anatase mixed phase nanoparticles on Caco-2 cells.

PubMed

Gerloff, Kirsten; Fenoglio, Ivana; Carella, Emanuele; Kolling, Julia; Albrecht, Catrin; Boots, Agnes W; Förster, Irmgard; Schins, Roel P F

2012-03-19

Titanium dioxide has a long-standing use as a food additive. Micrometric powders are, e.g., applied as whiteners in confectionary or dairy products. Possible hazards of ingested nanometric TiO(2) particles for humans and the potential influence of varying specific surface area (SSA) are currently under discussion. Five TiO(2)-samples were analyzed for purity, crystallinity, primary particle size, SSA, ζ potential, and aggregation/agglomeration. Their potential to induce cytotoxicity, oxidative stress, and DNA damage was evaluated in human intestinal Caco-2 cells. Only anatase-rutile containing samples, in contrast to the pure anatase samples, induced significant LDH leakage or mild DNA damage (Fpg-comet assay). Evaluation of the metabolic competence of the cells (WST-1 assay) revealed a highly significant correlation between the SSA of the anatase samples and cytotoxicity. The anatase/rutile samples showed higher toxicity per unit surface area than the pure anatase powders. However, none of the samples affected cellular markers of oxidative stress. Our findings suggest that both SSA and crystallinity are critical determinants of TiO(2)-toxicity toward intestinal cells. © 2012 American Chemical Society

Sarcocystid organisms found in bile from a dog with acute hepatitis: a case report and review of intestinal and hepatobiliary Sarcocystidae infections in dogs and cats.

PubMed

Irvine, Katherine L; Walker, Julie M; Friedrichs, Kristen R

2016-03-01

Sarcocystidae is a family of coccidian protozoa from the phylum Apicomplexa that includes Toxoplasma, Neospora, Sarcocystis, Hammondia, and Besnoitia spp. All species undergo a 2-host sexual and asexual cycle. In the definitive host, replication is enteroepithelial, and infection is typically asymptomatic or less commonly causes mild diarrhea. Clinical disease is most frequently observed in the intermediate host, often as an aberrant infection, and is mostly associated with neurologic, muscular, or hepatic inflammation. Here, we review the literature regarding intestinal Sarcocystidae infections in dogs and cats, with emphasis on the life cycle stages and the available diagnostic assays and their limitations. We also report the diagnostic findings for an 11-year-old dog with acute neutrophilic hepatitis, biliary protozoa, and negative biliary culture. Although Toxoplasma and Neospora IgG titers were both high, PCR for these 2 organisms was negative for bile. The organisms were identified by 18S rDNA PCR as most consistent with Hammondia, either H heydorni or H triffittae. This is the first report of presumed Hammondia organisms being found in canine bile. © 2016 American Society for Veterinary Clinical Pathology.

Spontaneous, Experimentally Induced, and Transmissible AA Amyloidosis in Japanese Quail ( Coturnix japonica).

PubMed

Nakayama, Yumi; Kamiie, Junichi; Watanabe, Gen; Suzuki, Kazuhiko; Murakami, Tomoaki

2017-11-01

The authors describe a spontaneous case of amyloid A (AA) amyloidosis in an adult female Japanese quail ( Coturnix japonica). The bird developed AA amyloidosis secondary to chronic peritonitis caused by a Gram-negative bacillus infection. Mild amyloid deposition was also identified in the intestinal tract of apparently healthy adult individuals, suggesting that quail may develop intestinal amyloidosis with age. Based on these observations, it was hypothesized that quail can develop AA amyloidosis following inflammatory stimulation with lipopolysaccharide (LPS). Therefore, adult quail were repeatedly injected with LPS and the development of AA amyloidosis was confirmed. The amyloid deposition in this model increased when quail amyloid was intravenously injected as an amyloid-enhancing factor. The experiments were repeated with young quail, but amyloid deposits were not observed following LPS injections. However, AA amyloidosis did develop when quail amyloid was injected in addition to LPS. These results indicated that adult quail develop AA amyloidosis after inflammatory stimulation with LPS. Furthermore, quail AA amyloidosis was shown to have transmissibility regardless of age. Interestingly, the authors found that administration of chicken amyloid fibrils also induced AA amyloidosis in young quail. This is the first report of cross-species transmission of avian AA amyloidosis.

Characterizing the type and location of intracranial abnormalities in mild traumatic brain injury.

PubMed

Isokuortti, Harri; Iverson, Grant L; Silverberg, Noah D; Kataja, Anneli; Brander, Antti; Öhman, Juha; Luoto, Teemu M

2018-01-12

OBJECTIVE The incidence of intracranial abnormalities after mild traumatic brain injury (TBI) varies widely across studies. This study describes the characteristics of intracranial abnormalities (acute/preexisting) in a large representative sample of head-injured patients who underwent CT imaging in an emergency department. METHODS CT scans were systematically analyzed/coded in the TBI Common Data Elements framework. Logistic regression modeling was used to quantify risk factors for traumatic intracranial abnormalities in patients with mild TBIs. This cohort included all patients who were treated at the emergency department of the Tampere University Hospital (between 2010 and 2012) and who had undergone head CT imaging after suffering a suspected TBI (n = 3023), including 2766 with mild TBI and a reference group with moderate to severe TBI. RESULTS The most common traumatic lesions seen on CT scans obtained in patients with mild TBIs and those with moderate to severe TBIs were subdural hematomas, subarachnoid hemorrhages, and contusions. Every sixth patient (16.1%) with mild TBI had an intracranial lesion compared with 5 of 6 patients (85.6%) in the group with moderate to severe TBI. The distribution of different types of acute traumatic lesions was similar among mild and moderate/severe TBI groups. Preexisting brain lesions were a more common CT finding among patients with mild TBIs than those with moderate to severe TBIs. Having a past traumatic lesion was associated with increased risk for an acute traumatic lesion but neurodegenerative and ischemic lesions were not. A lower Glasgow Coma Scale score, male sex, older age, falls, and chronic alcohol abuse were associated with higher risk of acute intracranial lesion in patients with mild TBI. CONCLUSIONS These findings underscore the heterogeneity of neuropathology associated with the mild TBI classification. Preexisting brain lesions are common in patients with mild TBI, and the incidence of preexisting lesions increases with age. Acute traumatic lesions are fairly common in patients with mild TBI; every sixth patient had a positive CT scan. Older adults (especially men) who fall represent a susceptible group for acute CT-positive TBI.

The ROSAS Cohort: A Prospective, Longitudinal Study of Biomarkers for Alzheimer's Disease. Strategy, Methods and Initial Results.

PubMed

de Mauléon, A; Soto, M; Kiyasova, V; Delrieu, J; Guignot, I; Galtier, S; Lilamand, M; Cantet, C; Lala, F; Sastre, N; Andrieu, S; Pueyo, M; Ousset, P J; Vellas, B

2017-01-01

The aims of the Research Of biomarkers in Alzheimer's diseaSe (ROSAS) study were to determine the biofluid and imaging biomarkers permitting an early diagnosis of Alzheimer's disease and better characterisation of cognitive and behavioural course of the pathology. This paper outlines the overall strategy, methodology of the study, baseline characteristics of the population and first longitudinal results from the ROSAS cohort. Longitudinal prospective monocentric observational study performed at the Alzheimer's disease Research centre in Toulouse. A total of 387 patients were studied and analyzed in 3 groups: 184 patients with dementia of Alzheimer's type, 96 patients with memory disorders without dementia (Mild Cognitive Impairment) and 107 patients without abnormal memory tests (control group), and were followed up during 4 years. Patient's sociodemographic characteristics, risk factors, medical conditions, previous and current medications, neuropsychological assessment and overall cognitive status were recorded. Blood and urine samples were collected at every year, Magnetic Resonance Imaging were performed at inclusion, after one year of follow-up and at the end of the study. At baseline, three different groups of the cohort differed interestingly in age, level of education, and in percentage of ApoEε4 carriers whereas the history of cardiovascular and endocrine pathologies were similar among the groups. During the follow-up period (3-4 years) 42 mild cognitive impairment patients (43.8%) progressed to dementia, 7 controls progressed into mild cognitive impairment and 1 patient in the control group converted from mild cognitive impairment group to dementia of Alzheimer's type group. During the first year of follow up, the incidence of progression from mild cognitive impairment to dementia of Alzheimer's type was 12.7 per 100, during the second year 33.9 per 100 and 46.7 per 100 for the third year. This paper presents the baseline characteristics of the unique French prospective monocenter study in which the natural course of dementia of Alzheimer's type was evaluated. Future analysis of blood and urine samples collection from the ROSAS study will permit to identify possible biofluid biomarkers predicting the early stages of the dementia of Alzheimer's type and risk of progression from Mild Cognitive Impairment to Alzheimer's disease.

[Consumption of psychoactive drugs and exposure to bacterial toxins carried by food: a dangerous association].

PubMed

Corma-Gómez, Anaïs; López-Sepúlveda, Rocío; Capitán-Del Río, Inés; Sánchez Mariscal, María Dolores; López-Hernández, Begoña

2017-11-01

To describe and analyse from a clinical and epidemiological point of view, a food borne outbreak in a psychiatric institution in Granada, in 2015, and to examine whether treatment with psychoactive drugs constitutes a risk factor for the development of a food borne disease, analysing the degree of susceptibility according to the therapeutic group consumed. Ambispective cohort study. Residents were the unit of analysis. Our group carried out an active case search and a food survey. A search for other risks was developed as well as a food inspection. Location, time and individual variables were studied. A descriptive analysis was conducted (absolute and relative frequencies). Calculation of attack rates by building and by menu was made. Bi-variant analysis (Chi-square test, t-Student test) and relative risk were used as a measure of strength of association. For risk analysis of medication, a multivariate analysis using logistic regression was carried out. 18 cases with diarrhoea without fever were found (incubation period from 6 to 16hours). Cases were mild and self-limiting. The clinical manifestations, the temporal grouping of cases and the characteristics of the ingested foods, focussed suspicion on a bacterial toxin. Being equal in the rest of variables, the N03AF, and N03AG therapeutic groups confer greater risk of disease (odds ratio [OR]: 8.626; 95% confidence interval [95%CI]: 2.050-36.308; p=0.003; and OR: 14.516; 95%CI: 3.155-66.784; p=0.001, respectively). Decreased intestinal transit, caused by the administration of anticonvulsants, may increase exposure time of the intestinal mucosa to the toxin, increasing the risk of disease and suffering from complications. An additional hygienic effort should be made in this type of institution to prevent these pathologies. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Correlating levels of type III secretion and secreted proteins with fecal shedding of Escherichia coli O157:H7 in cattle.

PubMed

Sharma, V K; Sacco, R E; Kunkle, R A; Bearson, S M D; Palmquist, D E

2012-04-01

The locus of enterocyte effacement (LEE) of Escherichia coli O157:H7 (O157) encodes a type III secretion system (T3SS) for secreting LEE-encoded and non-LEE-encoded virulence proteins that promote the adherence of O157 to intestinal epithelial cells and the persistence of this food-borne human pathogen in bovine intestines. In this study, we compared hha sepB and hha mutants of O157 for LEE transcription, T3SS activity, adherence to HEp-2 cells, persistence in bovine intestines, and the ability to induce changes in the expression of proinflammatory cytokines. LEE transcription was upregulated in the hha sepB and hha mutant strains compared to that in the wild-type strain, but the secretion of virulence proteins in the hha sepB mutant was severely compromised. This reduced secretion resulted in reduced adherence of the hha sepB mutant to Hep-2 cells, correlating with a significantly shorter duration and lower magnitude of fecal shedding in feces of weaned (n = 4 per group) calves inoculated with this mutant strain. The levels of LEE transcription, T3SS activity, and adherence to HEp-2 cells were much lower in the wild-type strain than in the hha mutant, but no significant differences were observed in the duration or the magnitude of fecal shedding in calves inoculated with these strains. Examination of the rectoanal junction (RAJ) tissues from three groups of calves showed no adherent O157 bacteria and similar proinflammatory cytokine gene expression, irrespective of the inoculated strain, with the exception that interleukin-1β was upregulated in calves inoculated with the hha sepB mutant. These results indicate that the T3SS is essential for intestinal colonization and prolonged shedding, but increased secretion of virulence proteins did not enhance the duration and magnitude of fecal shedding of O157 in cattle or have any significant impact on the cytokine gene expression in RAJ tissue compared with that in small intestinal tissue from the same calves.

Expression, Distribution and Role of Aquaporin Water Channels in Human and Animal Stomach and Intestines

PubMed Central

Zhu, Cui; Chen, Zhuang; Jiang, Zongyong

2016-01-01

Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions. Aquaporin water channels (AQPs) represent a major transcellular route for water transport in the gastrointestinal tract. Until now, at least 11 AQPs (AQP1–11) have been found to be present in the stomach, small and large intestines. These AQPs are distributed in different cell types in the stomach and intestines, including gastric epithelial cells, gastric glands cells, absorptive epithelial cells (enterocytes), goblet cells and Paneth cells. AQP1 is abundantly distributed in the endothelial cells of the gastrointestinal tract. AQP3 and AQP4 are mainly distributed in the basolateral membrane of epithelial cells in the stomach and intestines. AQP7, AQP8, AQP10 and AQP11 are distributed in the apical of enterocytes in the small and large intestines. Although AQP-null mice displayed almost no phenotypes in gastrointestinal tracts, the alterations of the expression and localization of these AQPs have been shown to be associated with the pathology of gastrointestinal disorders, which suggests that AQPs play important roles serving as potential therapeutic targets. Therefore, this review provides an overview of the expression, localization and distribution of AQPs in the stomach, small and large intestine of human and animals. Furthermore, this review emphasizes the potential roles of AQPs in the physiology and pathophysiology of stomach and intestines. PMID:27589719

Expression, Distribution and Role of Aquaporin Water Channels in Human and Animal Stomach and Intestines.

PubMed

Zhu, Cui; Chen, Zhuang; Jiang, Zongyong

2016-08-29

Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions. Aquaporin water channels (AQPs) represent a major transcellular route for water transport in the gastrointestinal tract. Until now, at least 11 AQPs (AQP1-11) have been found to be present in the stomach, small and large intestines. These AQPs are distributed in different cell types in the stomach and intestines, including gastric epithelial cells, gastric glands cells, absorptive epithelial cells (enterocytes), goblet cells and Paneth cells. AQP1 is abundantly distributed in the endothelial cells of the gastrointestinal tract. AQP3 and AQP4 are mainly distributed in the basolateral membrane of epithelial cells in the stomach and intestines. AQP7, AQP8, AQP10 and AQP11 are distributed in the apical of enterocytes in the small and large intestines. Although AQP-null mice displayed almost no phenotypes in gastrointestinal tracts, the alterations of the expression and localization of these AQPs have been shown to be associated with the pathology of gastrointestinal disorders, which suggests that AQPs play important roles serving as potential therapeutic targets. Therefore, this review provides an overview of the expression, localization and distribution of AQPs in the stomach, small and large intestine of human and animals. Furthermore, this review emphasizes the potential roles of AQPs in the physiology and pathophysiology of stomach and intestines.

Loss of intestinal GATA4 prevents diet-induced obesity and promotes insulin sensitivity in mice

PubMed Central

Patankar, Jay V.; Chandak, Prakash G.; Obrowsky, Sascha; Pfeifer, Thomas; Diwoky, Clemens; Uellen, Andreas; Sattler, Wolfgang; Stollberger, Rudolf; Hoefler, Gerald; Heinemann, Akos; Battle, Michele; Duncan, Stephen; Kratky, Dagmar

2011-01-01

Transcriptional regulation of small intestinal gene expression controls plasma total cholesterol (TC) and triglyceride (TG) levels, which are major determinants of metabolic diseases. GATA4, a zinc finger domain transcription factor, is critical for jejunal identity, and intestinal GATA4 deficiency leads to a jejunoileal transition. Although intestinal GATA4 ablation is known to misregulate jejunal gene expression, its pathophysiological impact on various components of metabolic syndrome remains unknown. Here, we used intestine-specific GATA4 knockout (GATA4iKO) mice to dissect the contribution of GATA4 on obesity development. We challenged adult GATA4iKO mice and control littermates with a Western-type diet (WTD) for 20 wk. Our findings show that WTD-fed GATA4iKO mice are resistant to diet-induced obesity. Accordingly, plasma TG and TC levels are markedly decreased. Intestinal lipid absorption in GATA4iKO mice was strongly reduced, whereas luminal lipolysis was unaffected. GATA4iKO mice displayed a greater glucagon-like peptide-1 (GLP-1) release on normal chow and even after long-term challenge with WTD remained glucose sensitive. In summary, our findings show that the absence of intestinal GATA4 has a beneficial effect on decreasing intestinal lipid absorption causing resistance to hyperlipidemia and obesity. In addition, we show that increased GLP-1 release in GATA4iKO mice decreases the risk for development of insulin resistance. PMID:21177287

Prevalence of opportunistic intestinal parasitic infection among HIV infected patients who are taking antiretroviral treatment at Jimma Health Center, Jimma, Ethiopia.

PubMed

Zeynudin, A; Hemalatha, K; Kannan, S

2013-02-01

One of the major health problems among HIV sero-positive patients are superimposed infections due to the deficient immunity. Furthermore, intestinal parasitic (IP) infections, which are also one of the basic health problems in tropical regions, are common in these patients. Infection by opportunistic pathogens, including various forms of intestinal parasites has been the hall mark of HIV since the beginning of the epidemic. To study the prevalence of opportunistic intestinal parasitic infection among HIV patients who are taking antiretroviral treatment (ART) in Jimma, Ethiopia. Patient samples were diagnosed by examination of single stool specimen which was examined as fresh wet mounts, formal-ether concentration technique and modified Ziehl-Neelsen staining technique. Data was obtained from 91 study subjects selected by convenience sampling method. The overall prevalence of intestinal parasitic infections was found to be 39.56%. Eight types of intestinal parasites was identified, the most dominant being, Ascaris lumbricoides, 21.67%, Entamoeba histolytica, 15% and Cryptosporidium parvum 13.33%. The prevalence of opportunistic parasite was 15.38%, the prevalence of non-opportunistic parasite was 20.87% and the prevalence of both opportunistic and non opportunistic was 3.29%. The study indicated that intestinal parasites were still a problem in the study area. Data also showed that among the predisposing factors, habit of hand washing before meal, usage of latrine and duration after treatment was statistically associated with intestinal parasitic infections.

Soluble Dietary Fiber Ameliorates Radiation-Induced Intestinal Epithelial-to-Mesenchymal Transition and Fibrosis.

PubMed

Yang, Jianbo; Ding, Chao; Dai, Xujie; Lv, Tengfei; Xie, Tingbing; Zhang, Tenghui; Gao, Wen; Gong, Jianfeng; Zhu, Weiming; Li, Ning; Li, Jieshou

2017-11-01

Intestinal fibrosis is a late complication of pelvic radiotherapy. Epithelial-to-mesenchymal transition (EMT) plays an important role in tissue fibrosis. The aim of this study was to examine the effect of soluble dietary fiber on radiation-induced intestinal EMT and fibrosis in a mouse model. Apple pectin (4% wt/wt in drinking water) was administered to wild-type and pVillin-Cre-EGFP transgenic mice with intestinal fibrosis induced by a single dose of abdominal irradiation of 10 Gy. The effects of pectin on intestinal EMT and fibrosis, gut microbiota, and short-chain fatty acid (SCFA) concentration were evaluated. Intestinal fibrosis in late radiation enteropathy showed increased submucosal thickness and subepithelial collagen deposition. Enhanced green fluorescent protein (EGFP) + /vimentin + and EGFP + /α-smooth muscle actin (SMA) + coexpressing cells were most clearly observed at 2 weeks after irradiation and gradually decreased at 4 and 12 weeks. Pectin significantly attenuated the thickness of submucosa and collagen deposition at 12 weeks (24.3 vs 27.6 µm in the pectin + radiation-treated group compared with radiation-alone group, respectively, P < .05; 69.0% vs 57.1%, P < .001) and ameliorated EMT at 2 and 4 weeks. Pectin also modulated the intestinal microbiota composition and increased the luminal SCFA concentration. The soluble dietary fiber pectin protected the terminal ileum against radiation-induced fibrosis. This effect might be mediated by altered SCFA concentration in the intestinal lumen and reduced EMT in the ileal epithelium.

Effects of alfalfa meal on the intestinal microbial diversity and immunity of growing ducks.

PubMed

Jiang, J F; Song, X M; Wu, J L; Jiang, Y Q

2014-12-01

This study was conducted to investigate the effects of alfalfa meal diets on the intestinal microbial diversity and immunity of growing egg-type ducks. A total of 128 healthy 7-week-old female egg-type Shaoxing ducks were selected and randomly assigned into four dietary treatments: 0%, 3%, 6% and 9% alfalfa meal for 8 weeks. Each treatment consisted of four replicates of eight ducks each. Polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) was used to characterize the microbiota. The results showed that the DGGE fingerprints of the V6-V8 fragments of the 16S rRNA from the caeca and faeces of ducks fed 3%, 6% and 9% alfalfa meal had significantly higher microbiota species richness than those fed 0% alfalfa meal (p < 0.05). The Shannon-Weiner index of the microbiota from the caeca and faeces of ducks fed 3%, 6% and 9% alfalfa meal was significantly higher than those fed 0% alfalfa meal (p < 0.05). Molecular analysis of the caecal and faecal DNA extracts showed that the alfalfa meal diet promotes the intestinal microbial diversity, as indicated by their higher species richness and Shannon-Weiner index. However, the groups did not significantly differ in terms of average daily gain, feed intake and gain-to-feed ratio (p > 0.05), and the 3-9% alfalfa meal did not affect the growth performance of the growing egg-type ducks. The proliferation of T and B lymphocytes was significantly greater (p < 0.05) in the groups supplemented with 3%, 6% and 9% of alfalfa meal than the unsupplemented control group, and alfalfa meal promoted the lymphocytes proliferation of the growing egg-type ducks. Dietary alfalfa meal supplementation increases intestinal microbial community diversity and improves of the immune response growing egg-type ducks. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

PubMed

Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

2015-01-01

We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

Clinical and molecular epidemiology of Escherichia coli sequence type 131 among hospitalized patients colonized intestinally with fluoroquinolone-resistant E. coli.

PubMed

Han, Jennifer H; Johnston, Brian; Nachamkin, Irving; Tolomeo, Pam; Bilker, Warren B; Mao, Xiangqun; Clabots, Connie; Lautenbach, Ebbing; Johnson, James R

2014-11-01

This study examined molecular and epidemiologic factors associated with Escherichia coli sequence type 131 (ST131) among hospitalized patients colonized intestinally with fluoroquinolone (FQ)-resistant E. coli between 2002 and 2004. Among 86 patients, 21 (24%) were colonized with ST131. The proportion of ST131 isolates among colonizing isolates increased significantly over time, from 8% in 2002 to 50% in 2004 (P = 0.003). Furthermore, all 19 clonally related isolates were ST131. Future studies should identify potential transmissibility differences between ST131 and non-ST131 strains. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Oxidative Phosphorylation System in Gastric Carcinomas and Gastritis.

PubMed

Feichtinger, René G; Neureiter, Daniel; Skaria, Tom; Wessler, Silja; Cover, Timothy L; Mayr, Johannes A; Zimmermann, Franz A; Posselt, Gernot; Sperl, Wolfgang; Kofler, Barbara

2017-01-01

Switching of cellular energy production from oxidative phosphorylation (OXPHOS) by mitochondria to aerobic glycolysis occurs in many types of tumors. However, the significance of this switching for the development of gastric carcinoma and what connection it may have to Helicobacter pylori infection of the gut, a primary cause of gastric cancer, are poorly understood. Therefore, we investigated the expression of OXPHOS complexes in two types of human gastric carcinomas ("intestinal" and "diffuse"), bacterial gastritis with and without metaplasia, and chemically induced gastritis by using immunohistochemistry. Furthermore, we analyzed the effect of HP infection on several key mitochondrial proteins. Complex I expression was significantly reduced in intestinal type (but not diffuse) gastric carcinomas compared to adjacent control tissue, and the reduction was independent of HP infection. Significantly, higher complex I and complex II expression was present in large tumors. Furthermore, higher complex II and complex III protein levels were also obvious in grade 3 versus grade 2. No differences of OXPHOS complexes and markers of mitochondrial biogenesis were found between bacterially caused and chemically induced gastritis. Thus, intestinal gastric carcinomas, but not precancerous stages, are frequently characterized by loss of complex I, and this pathophysiology occurs independently of HP infection.

Glucose, epithelium, and enteric nervous system: dialogue in the dark.

PubMed

Pfannkuche, H; Gäbel, G

2009-06-01

The gastrointestinal epithelium is in close contact with the various components of the chymus, including nutrients, bacteria and toxins. The epithelial barrier has to decide which components are effectively absorbed and which components are extruded. In the small intestine, a nutrient like glucose is mainly absorbed by the sodium linked glucose cotransporter 1 (SGLT1) and the glucose transporter 2 (GLUT2). The expression and activity of both transport proteins is directly linked to the amount of intraluminal glucose. Besides the direct interaction between glucose and the enterocytes, glucose also stimulates different sensory mechanisms within the intestinal wall. The most important types of cells involved in the sensing of intraluminal contents are enteroendocrine cells and neurones of the enteric nervous system. Regarding glucosensing, a distinct type of enteroendocrine cells, the enterochromaffine (EC) cells are involved. Excitation of EC cells by intraluminal glucose results in the release of serotonin (5-HT), which modulates epithelial functions and activates enteric secretomotorneurones. Enteric neurones are not only activated by 5-HT, but also directly by glucose. The activation of different cell types and the subsequent crosstalk between these cells may trigger appropriate absorptive and secretory processes within the intestine.

Inhibitory effect of black tea and its combination with acarbose on small intestinal α-glucosidase activity.

PubMed

Satoh, Takashi; Igarashi, Masaki; Yamada, Shogo; Takahashi, Natsuko; Watanabe, Kazuhiro

2015-02-23

It is said that black tea is effective against type 2 diabetes mellitus because it can help modulate postprandial hyperglycemia. However, the mechanism underlying its therapeutic and preventive effects on type 2 diabetes mellitus is unclear. In this study, we focused on the effect of black tea on the carbohydrate digestion and absorption process in the gastrointestinal tract. We examined whether black tea can modulate postprandial hyperglycemia. The freeze-dried powder of the aqueous extract of black tea leaves (JAT) was used for in vitro studies of α-amylase activity, α-glucosidase activity, and glucose uptake by glucose transporters in Caco-2 cells; ex vivo studies of small intestinal α-glucosidase activity; and in vivo studies of oral sugar tolerance in GK rats, an animal model of nonobese type 2 diabetes mellitus. Half maximal inhibitory concentration values indicated that JAT significantly reduced α-glucosidase activity, but weakly reduced α-amylase activity. Kinetic studies of rat small intestinal α-glucosidase activity revealed that the combination of JAT and the α-glucosidase inhibitor, acarbose, showed a mixed-type inhibition. JAT had no effect on the uptake of 2'-deoxy-d-glucose by glucose transporter 2 (GLUT2) and the uptake of α-methyl-d-glucose by sodium-dependent glucose transporter 1 (SGLT1). In the oral sucrose tolerance test in GK rats, JAT reduced plasma glucose levels in a dose-dependent manner compared with the control group. The hypoglycemic action of JAT was also confirmed: JAT, in combination with acarbose, produced a synergistic inhibitory effect on plasma glucose levels in vivo. In contrast to the oral sucrose tolerance test, JAT showed no effect in the oral glucose tolerance test. JAT was demonstrated to inhibit the degradation of disaccharides into monosaccharides by α-glucosidase in the small intestine. Thereby indirectly preventing the absorption of the dietary source of glucose mediated by SGLT1 and GLUT2 transporters localized at the apical side of enterocytes in the small intestine. The results indicate that black tea could be useful as a functional food in the dietary therapy for borderline type 2 diabetes mellitus that could modulate postprandial hyperglycemia. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A multicenter, randomized, double-blind, placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirin-induced moderate-to-severe small intestinal damage.

PubMed

Watanabe, Toshio; Takeuchi, Toshihisa; Handa, Osamu; Sakata, Yasuhisa; Tanigawa, Tetsuya; Shiba, Masatsugu; Naito, Yuji; Higuchi, Kazuhide; Fujimoto, Kazuma; Yoshikawa, Toshikazu; Arakawa, Tetsuo

2015-01-01

Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant. We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy. We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks. The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated. High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy. UMIN Clinical Trials Registry UMIN000003463.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of High-Dose Rebamipide Treatment for Low-Dose Aspirin-Induced Moderate-to-Severe Small Intestinal Damage

PubMed Central

Watanabe, Toshio; Takeuchi, Toshihisa; Handa, Osamu; Sakata, Yasuhisa; Tanigawa, Tetsuya; Shiba, Masatsugu; Naito, Yuji; Higuchi, Kazuhide; Fujimoto, Kazuma; Yoshikawa, Toshikazu; Arakawa, Tetsuo

2015-01-01

Background Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant. Aim We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy. Methods We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks. Results The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated. Conclusions High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy. Trial Registration UMIN Clinical Trials Registry UMIN000003463 PMID:25874951

Acute high-intensity interval running increases markers of gastrointestinal damage and permeability but not gastrointestinal symptoms.

PubMed

Pugh, Jamie N; Impey, Samuel G; Doran, Dominic A; Fleming, Simon C; Morton, James P; Close, Graeme L

2017-09-01

The purpose of this study was to investigate the effects of high-intensity interval running on markers of gastrointestinal (GI) damage and permeability alongside subjective symptoms of GI discomfort. Eleven male runners completed an acute bout of high-intensity interval training (HIIT) (eighteen 400-m runs at 120% maximal oxygen uptake) where markers of GI permeability, intestinal damage, and GI discomfort symptoms were assessed and compared with resting conditions. Compared with rest, HIIT significantly increased serum lactulose/rhamnose ratio (0.051 ± 0.016 vs. 0.031 ± 0.021, p = 0.0047; 95% confidence interval (CI) = 0.006 to 0.036) and sucrose concentrations (0.388 ± 0.217 vs. 0.137 ± 0.148 mg·L -1 ; p < 0.001; 95% CI = 0.152 to 0.350). In contrast, urinary lactulose/rhamnose (0.032 ± 0.005 vs. 0.030 ± 0.005; p = 0.3; 95% CI = -0.012 to 0.009) or sucrose concentrations (0.169% ± 0.168% vs. 0.123% ± 0.120%; p = 0.54; 95% CI = -0.199 to 0.108) did not differ between HIIT and resting conditions. Plasma intestinal-fatty acid binding protein (I-FABP) was significantly increased (p < 0.001) during and in the recovery period from HIIT whereas no changes were observed during rest. Mild symptoms of GI discomfort were reported immediately and at 24 h post-HIIT, although these symptoms did not correlate to GI permeability or I-FABP. In conclusion, acute HIIT increased GI permeability and intestinal I-FABP release, although these do not correlate with symptoms of GI discomfort. Furthermore, by using serum sampling, we provide data showing that it is possible to detect changes in intestinal permeability that is not observed using urinary sampling over a shorter time-period.

TUMOR SUPPRESSER GENE P53 EXPRESSION IN PREMALIGNANT LESIONS AND GASTRIC CARCINOMA - PROGNOSTIC VALUE

PubMed Central

Vukobrat-Bijedić, Zora; Radović, Svjetlana; Husić-Selimović, Azra; Gornjaković, Srđan

2007-01-01

The aim of the study was to verify the presence of mutated tumor suppresser gene p53 in intestinal mucosa with histologically confirmed premalignant lesions and gastric carcinoma, and assess its prognostic value. The paper presents prospective study that included 50 patients with gastric adeno-carcinoma of intestinal type that were treated at Gastroenterohepa-tology Clinic, and 50 patients with histologically confirmed chronic atrophic H. pylori positive gastritis. In the mucosa biopsy samples, we analyzed presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes. We typed intestinal metaplasia immunohistochemically and confirmed the presence of p53 onco-protein in antigen positive gastric carcinoma cells, and evaluated its prognostic value. Our results suggest that H. pylori acts as an initiator of inflammatory processes in gastric mucosa, which are followed by emergence of precancerous lesions. p53 is expressed late in carcinogenesis (14%) and as such, may be considered as an indicator of transformation of premalignant into malignant lesion. PMID:17489760

Immunohistochemical study on the ontogenetic development of the regional distribution of peptide YY, pancreatic polypeptide, and glucagon-like peptide 1 endocrine cells in bovine gastrointestinal tract.

PubMed

Pyarokhil, Asadullah Hamid; Ishihara, Miyuki; Sasaki, Motoki; Kitamura, Nobuo

2012-04-10

The regional distribution and relative frequency of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and glucagon-like peptide 1 (GLP-1)-immunoreactive (IR) cells were determined immunohistochemically in the gastrointestinal tract at seven ontogenetic stages in pre- and postnatal cattle. Different frequencies of PYY-, PP-, and GLP-1-IR cells were found in the intestines at all stages; they were not found in the esophagus and stomach. The frequencies varied depending on the intestinal segment and the developmental stage. The frequencies of PYY- and PP-IR cells were lower in the small intestine and increased from ileum to rectum, whereas GLP-1-IR cells were more numerous in duodenum and jejunum, decreased in ileum and cecum, and increased again in colon and rectum. The frequencies also varied according to pre- and postnatal stages. All three cell types were most numerous in fetus, and decreased in calf and adult groups, indicating that the frequencies of these three types of endocrine cells decrease with postnatal development. The results suggest that these changes vary depending on feeding habits and adaptation of growth, secretion, and motility of intestine at different ontogenetic stages of cattle. Copyright © 2011 Elsevier B.V. All rights reserved.

Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease

PubMed Central

Brown, Kirsty; DeCoffe, Daniella; Molcan, Erin; Gibson, Deanna L.

2012-01-01

The gastrointestinal (GI) microbiota is the collection of microbes which reside in the GI tract and represents the largest source of non-self antigens in the human body. The GI tract functions as a major immunological organ as it must maintain tolerance to commensal and dietary antigens while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to host cell damage and/or autoimmunity. Evidence suggests that the composition of the intestinal microbiota can influence susceptibility to chronic disease of the intestinal tract including ulcerative colitis, Crohn’s disease, celiac disease and irritable bowel syndrome, as well as more systemic diseases such as obesity, type 1 diabetes and type 2 diabetes. Interestingly, a considerable shift in diet has coincided with increased incidence of many of these inflammatory diseases. It was originally believed that the composition of the intestinal microbiota was relatively stable from early childhood; however, recent evidence suggests that diet can cause dysbiosis, an alteration in the composition of the microbiota, which could lead to aberrant immune responses. The role of the microbiota and the potential for diet-induced dysbiosis in inflammatory conditions of the GI tract and systemic diseases will be discussed. PMID:23016134

Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments

PubMed Central

Goodell, Margaret A.; Nguyen, Hoang; Shroyer, Noah

2017-01-01

Somatic stem cells replenish many tissues throughout life to repair damage and to maintain tissue homeostasis. Stem cell function is frequently described as following a hierarchical model in which a single master cell undergoes self-renewal and differentiation into multiple cell types and is responsible for most regenerative activity. However, recent data from studies on blood, skin and intestinal epithelium all point to the concomitant action of multiple types of stem cells with distinct everyday roles. Under stress conditions such as acute injury, the surprising developmental flexibility of these stem cells enables them to adapt to diverse roles and to acquire different regeneration capabilities. This paradigm shift raises many new questions about the developmental origins, inter-relationships and molecular regulation of these multiple stem cell types. PMID:25907613

Insulin in human milk and the prevention of type 1 diabetes.

PubMed

Shehadeh, N; Shamir, R; Berant, M; Etzioni, A

2001-12-01

Although controversial, exclusive breast milk feeding was shown to exert a protective effect in preventing type 1 diabetes. In contrast, an early introduction of cow's milk-based formula in young infants may enhance the risk of disease, especially in genetically susceptible children, presumably by an increase of intestinal permeability to macromolecules such as bovine serum albumin and beta-casein, which may arouse autoimmunity. We have shown that human milk contains insulin in substantial concentrations, while insulin is barely detectable (if at all) in infant formulas. Orally administered insulin was demonstrated to promote gut maturation and to reduce intestinal permeability to macromolecules. Furthermore, oral insulin may induce tolerance to insulin and protect against the development of type 1 diabetes. We herewith raise a hypothesis that human milk is protective against the development of type 1 diabetes by virtue of the effects of its substantial content of insulin.

Study on a magnetic spiral-type wireless capsule endoscope controlled by rotational external permanent magnet

NASA Astrophysics Data System (ADS)

Ye, Bo; Zhang, Wei; Sun, Zhen-jun; Guo, Lin; Deng, Chao; Chen, Ya-qi; Zhang, Hong-hai; Liu, Sheng

2015-12-01

In this paper, the authors propose rotating an external permanent magnet (EPM) to manipulate the synchronous rotation of a magnetic spiral-type wireless capsule endoscope (WCE), and the synchronous rotation of the WCE is converted to its translational motion in intestinal tract. In order to preliminarily verify the feasibility of this method, a handheld actuator (HA) controlled by micro controller unit, a magnetic spiral-type WCE and a bracket were fabricated, theoretical analysis and simulations about the control distance of this method were performed, and in ex-vivo tests were examined in porcine small intestine to verify the control distance and control performances of this method. It was demonstrated that this method showed good performances in controlling the translational motion of the magnetic spiral-type WCE, and this method has great potential to be used in clinical application.

Neonate intestinal immune response to CpG oligodeoxynucleotide stimulation.

PubMed

Lacroix-Lamandé, Sonia; Rochereau, Nicolas; Mancassola, Roselyne; Barrier, Mathieu; Clauzon, Amandine; Laurent, Fabrice

2009-12-14

The development of mucosal vaccines is crucial to efficiently control infectious agents for which mucosae are the primary site of entry. Major drawbacks of these protective strategies are the lack of effective mucosal adjuvant. Synthetic oligodeoxynucleotides that contain several unmethylated cytosine-guanine dinucleotide (CpG-ODN) motifs are now recognized as promising adjuvants displaying mucosal adjuvant activity through direct activation of TLR9-expressing cells. However, little is known about the efficacy of these molecules in stimulating the intestinal immune system in neonates. First, newborn mice received CpG-ODN orally, and the intestinal cytokine and chemokine response was measured. We observed that oral administration of CpG-ODN induces CXC and CC chemokine responses and a cellular infiltration in the intestine of neonates as detected by immunohistochemistry. We next compared the efficiency of the oral route to intraperitoneal administration in stimulating the intestinal immune responses of both adults and neonates. Neonates were more responsive to TLR9-stimulation than adults whatever the CpG-ODN administration route. Their intestinal epithelial cells (IECs) indirectly responded to TLR9 stimulation and contributed to the CXC chemokine response, whereas other TLR9-bearing cells of the lamina-propria produced CC chemokines and Th1-type cytokines. Moreover, we showed that the intestine of adult exhibited a significantly higher level of IL10 at homeostasis than neonates, which might be responsible for the unresponsiveness to TLR9-stimulation, as confirmed by our findings in IL10-deficient mice. This is the first report that deciphers the role played by CpG-ODN in the intestine of neonates. This work clearly demonstrates that an intraperitoneal administration of CpG-ODN is more efficient in neonates than in adults to stimulate an intestinal chemokine response due to their lower IL-10 intestinal level. In addition we report the efficiency of the oral route at inducing intestinal chemokine responses in neonate that might be taken into consideration for further vaccine development against neonatal diseases.

Essential Oil from Myrica rubra Leaves Potentiated Antiproliferative and Prooxidative Effect of Doxorubicin and its Accumulation in Intestinal Cancer Cells.

PubMed

Ambrož, Martin; Hanušová, Veronika; Skarka, Adam; Boušová, Iva; Králová, Věra; Langhasová, Lenka; Skálová, Lenka

2016-01-01

Essential oil from the leaves of Myrica rubra, a subtropical Asian fruit tree traditionally used in folk medicines, has a significant antiproliferative effect in several intestinal cancer cell lines. Doxorubicin belongs to the most important cytostatics used in cancer therapy. The present study was designed to evaluate the effects of defined essential oil from M. rubra leaves on efficacy, prooxidative effect, and accumulation of doxorubicin in cancer cell lines and in non-cancerous cells. For this purpose, intestinal adenocarcinoma CaCo2 cells were used. Human fibroblasts (periodontal ligament) and a primary culture of rat hepatocytes served as models of non-cancerous cells. The results showed that the sole essential oil from M. rubra has a strong prooxidative effect in cancer cells while it acts as a mild antioxidant in hepatocytes. Combined with doxorubicin, the essential oil enhanced the antiproliferative and prooxidative effects of doxorubicin in cancer cells. At higher concentrations, synergism of doxorubicin and essential oil from M. rubra was proved. In non-cancerous cells, the essential oil did not affect the toxicity of doxorubicin and the doxorubicin-mediated reactive oxygen species formation. The essential oil increased the intracellular concentration of doxorubicin and enhanced selectively the doxorubicin accumulation in nuclei of cancer cells. Taken together, essential oil from M. rubra leaves could be able to improve the doxorubicin efficacy in cancer cells due to an increased reactive oxygen species production, and the doxorubicin accumulation in nuclei of cancer cells. Georg Thieme Verlag KG Stuttgart · New York.

Gastroenterology – Guidelines on Parenteral Nutrition, Chapter 15

PubMed Central

Schulz, R. J.; Bischoff, S. C.; Koletzko, B.

2009-01-01

In patients with Crohn's disease and ulcerative colitis parenteral nutrition (PN) is indicated when enteral nutrition is not possible or should be avoided for medical reasons. In Crohn's patients PN is indicated when there are signs/symptoms of ileus or subileus in the small intestine, scars or intestinal fistulae. PN requires no specific compounding for chronic inflammatory bowel diseases. In both diseases it should be composed of 55–60% carbohydrates, 25–30% lipids and 10–15% amino acids. PN helps in the correction of malnutrition, particularly the intake of energy, minerals, trace elements, deficiency of calcium, vitamin D, folic acid, vitamin B12, and zinc. Enteral nutrition is clearly superior to PN in severe, acute pancreatitis. An intolerance to enteral nutrition results in an indication for total PN in complications such as pseudocysts, intestinal and pancreatic fistulae, and pancreatic abscesses or pancreatic ascites. If enteral nutrition is not possible, PN is recommended, at the earliest, 5 days after admission to the hospital. TPN should not be routinely administered in mild acute pancreatitis or nil by moth status <7 days, due to high costs and an increased risk of infection. The energy requirements are between 25 and 35 kcal/kg body weight/day. A standard solution including lipids (monitoring triglyceride levels!) can be administered in acute pancreatitis. Glucose (max. 4–5 g/kg body weight/day) and amino acids (about 1.2–1.5 g/kg body weight/day) should be administered and the additional enrichment of TPN with glutamine should be considered in severe, progressive forms of pancreatitis. PMID:20049077

Insights into the protective role of solid lipid nanoparticles on rosmarinic acid bioactivity during exposure to simulated gastrointestinal conditions.

PubMed

Madureira, Ana Raquel; Campos, Débora A; Oliveira, Ana; Sarmento, Bruno; Pintado, Maria Manuela; Gomes, Ana Maria

2016-03-01

The evaluation of the digestion effects on bioactive solid lipid nanoparticles (SLN) was performed. For this purpose, witepsol and carnauba SLN loaded with rosmarinic acid (RA) were exposed to the simulated gastrointestinal tract (GIT) conditions prevailing in stomach and small intestine. The simulation of intestinal epithelium was made with a dialysis bag and intestinal cell culture lines. Changes on SLN physical properties, RA release and absorption profiles were followed at each step. Combination of digestion pH and enzymes showed a significant effect upon SLN physical properties. Zeta potential values increased at stomach conditions and decreased at small intestine simulation. Also, at intestine, SLN increased their sizes and released 40-60% of RA, maintaining its initial antioxidant activity values. Sustained release of 40% of RA from SLN was also observed in dialysis tube. At CaCo-2 cell line, both types of SLN showed similar absorbed RA % (ca. 30%). Nevertheless, in CaCo-2/HT29x mix cell lines, for carnauba SLN a lower adsorption RA % was observed than for witepsol SLN. Solid lipid nanoparticles protected RA bioactivity (in terms of antioxidant activity) until reaching the intestine. A controlled release of RA from SLN was achieved and a significant absorption was observed at intestinal cells. Overall, SLN produced with witepsol showed a higher stability than carnauba SLN. Copyright © 2015 Elsevier B.V. All rights reserved.

Intestinal tuft cells regulate the ATM mediated DNA Damage response via Dclk1 dependent mechanism for crypt restitution following radiation injury.

PubMed

Chandrakesan, Parthasarathy; May, Randal; Weygant, Nathaniel; Qu, Dongfeng; Berry, William L; Sureban, Sripathi M; Ali, Naushad; Rao, Chinthalapally; Huycke, Mark; Bronze, Michael S; Houchen, Courtney W

2016-11-23

Crypt epithelial survival and regeneration after injury require highly coordinated complex interplay between resident stem cells and diverse cell types. The function of Dclk1 expressing tuft cells regulating intestinal epithelial DNA damage response for cell survival/self-renewal after radiation-induced injury is unclear. Intestinal epithelial cells (IECs) were isolated and purified and utilized for experimental analysis. We found that small intestinal crypts of Villin Cre ;Dclk1 f/f mice were hypoplastic and more apoptotic 24 h post-total body irradiation, a time when stem cell survival is p53-independent. Injury-induced ATM mediated DNA damage response, pro-survival genes, stem cell markers, and self-renewal ability for survival and restitution were reduced in the isolated intestinal epithelial cells. An even greater reduction in these signaling pathways was observed 3.5 days post-TBI, when peak crypt regeneration occurs. We found that interaction with Dclk1 is critical for ATM and COX2 activation in response to injury. We determined that Dclk1 expressing tuft cells regulate the whole intestinal epithelial cells following injury through paracrine mechanism. These findings suggest that intestinal tuft cells play an important role in regulating the ATM mediated DNA damage response, for epithelial cell survival/self-renewal via a Dclk1 dependent mechanism, and these processes are indispensable for restitution and function after severe radiation-induced injury.

Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium.

PubMed

Murata, Yoji; Kotani, Takenori; Supriatna, Yana; Kitamura, Yasuaki; Imada, Shinya; Kawahara, Kohichi; Nishio, Miki; Daniwijaya, Edwin Widyanto; Sadakata, Hisanobu; Kusakari, Shinya; Mori, Munemasa; Kanazawa, Yoshitake; Saito, Yasuyuki; Okawa, Katsuya; Takeda-Morishita, Mariko; Okazawa, Hideki; Ohnishi, Hiroshi; Azuma, Takeshi; Suzuki, Akira; Matozaki, Takashi

2015-08-04

Intestinal epithelial cells contribute to regulation of intestinal immunity in mammals, but the detailed molecular mechanisms of such regulation have remained largely unknown. Stomach-cancer-associated protein tyrosine phosphatase 1 (SAP-1, also known as PTPRH) is a receptor-type protein tyrosine phosphatase that is localized specifically at microvilli of the brush border in gastrointestinal epithelial cells. Here we show that SAP-1 ablation in interleukin (IL)-10-deficient mice, a model of inflammatory bowel disease, resulted in a marked increase in the severity of colitis in association with up-regulation of mRNAs for various cytokines and chemokines in the colon. Tyrosine phosphorylation of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20, an intestinal microvillus-specific transmembrane protein of the Ig superfamily, was greatly increased in the intestinal epithelium of the SAP-1-deficient animals, suggesting that this protein is a substrate for SAP-1. Tyrosine phosphorylation of CEACAM20 by the protein tyrosine kinase c-Src and the consequent association of CEACAM20 with spleen tyrosine kinase (Syk) promoted the production of IL-8 in cultured cells through the activation of nuclear factor-κB (NF-κB). In addition, SAP-1 and CEACAM20 were found to form a complex through interaction of their ectodomains. SAP-1 and CEACAM20 thus constitute a regulatory system through which the intestinal epithelium contributes to intestinal immunity.

Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats.

PubMed

Goldstein, Jorge; Morris, Winston E; Loidl, César Fabián; Tironi-Farinati, Carla; Tironi-Farinatti, Carla; McClane, Bruce A; Uzal, Francisco A; Fernandez Miyakawa, Mariano E

2009-09-18

Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, it causes oedema of the lungs and brain by damaging the endothelial cells, inducing physiological and morphological changes. Although it is believed to compromise the intestinal barrier, thus entering the gut vasculature, little is known about the mechanism underlying this process. This study characterizes the effects of epsilon toxin on fluid transport and bioelectrical parameters in the small intestine of mice and rats. The enteropooling and the intestinal loop tests, together with the single-pass perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all used in combination with histological and ultrastructural analysis of mice and rat small intestine, challenged with or without C. perfringens epsilon toxin. Luminal epsilon toxin induced a time and concentration dependent intestinal fluid accumulation and fall of the transepithelial resistance. Although no evident histological changes were observed, opening of the mucosa tight junction in combination with apoptotic changes in the lamina propria were seen with transmission electron microscopy. These results indicate that C. perfringens epsilon toxin alters the intestinal permeability, predominantly by opening the mucosa tight junction, increasing its permeability to macromolecules, and inducing further degenerative changes in the lamina propria of the bowel.

In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury

PubMed Central

Rannou, Emilie; François, Agnès; Toullec, Aurore; Guipaud, Olivier; Buard, Valérie; Tarlet, Georges; Mintet, Elodie; Jaillet, Cyprien; Iruela-Arispe, Maria Luisa; Benderitter, Marc; Sabourin, Jean-Christophe; Milliat, Fabien

2015-01-01

The pathophysiological mechanism involved in side effects of radiation therapy, and especially the role of the endothelium remains unclear. Previous results showed that plasminogen activator inhibitor-type 1 (PAI-1) contributes to radiation-induced intestinal injury and suggested that this role could be driven by an endothelium-dependent mechanism. We investigated whether endothelial-specific PAI-1 deletion could affect radiation-induced intestinal injury. We created a mouse model with a specific deletion of PAI-1 in the endothelium (PAI-1KOendo) by a Cre-LoxP system. In a model of radiation enteropathy, survival and intestinal radiation injury were followed as well as intestinal gene transcriptional profile and inflammatory cells intestinal infiltration. Irradiated PAI-1KOendo mice exhibited increased survival, reduced acute enteritis severity and attenuated late fibrosis compared with irradiated PAI-1flx/flx mice. Double E-cadherin/TUNEL labeling confirmed a reduced epithelial cell apoptosis in irradiated PAI-1KOendo. High-throughput gene expression combined with bioinformatic analyses revealed a putative involvement of macrophages. We observed a decrease in CD68+cells in irradiated intestinal tissues from PAI-1KOendo mice as well as modifications associated with M1/M2 polarization. This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. PMID:26510580

[Cell renovation in the intestinal epithelium in aging].

PubMed

Gusel'nikova, E A; Konovalov, S S; Poliakova, V O; Kvetnoĭ, I M

2010-01-01

The ability to cell renovation of two basic cell types of intestinal mucosa is the important mechanism for the regulation and support of the gut physiological functions in aging and under the influence of the ecological negative factors. The study of the processes of cell renovation of the intestinal epithelial and neuroendocrine cells in physiological and radiological aging has a great interest, because the irradiation in the subletal doses could be considered as the model of artificial aging, and this fact enables studying of the radiological influence as the ecological factor, promoting the aging. In this study, the increase of cell proliferation in intestinal mucosa in physiological as well as artificial aging was observed. It was shown, that the total population of mitotic cells increases two times. These data testify about active participation of the mechanisms of cell renovation in the safety of gut functions during aging.

Intestinal adenocarcinoma in a herd of farmed Sika deer (Cervus nippon): a novel syndrome.

PubMed

Kelly, P A; Toolan, D; Jahns, H

2015-01-01

Intestinal adenocarcinomas were identified in 76 adult deer from a closed herd of 193 breeding animals grazing pasture heavily infested with bracken fern (Pteridium aquilinum). Tumors were observed postmortem in 32 animals with rapid weight loss, and similar neoplasms were detected in a further 44 clinically normal deer at "cull." Tumors were located in distal ileum, cecum, and proximal colon and presented as single (26%) or multiple (74%), variably sized, pale-gray, firm, poorly circumscribed neoplasms with associated intestinal strictures. Histopathologically tumors were well-differentiated, locally infiltrative, low-grade adenocarcinomas of tubular (51%), mucinous (33.5%), or mixed (15.5%) types. Extraintestinal metastases were not observed. The high incidence of intestinal adenocarcinoma within this herd suggests a specific and novel syndrome, and genetic and/or environmental factors may be involved in the pathogenesis. © The Author(s) 2014.

Diarrhoea-associated parasites in HIV-1 seropositive and sero-negative patients in a teaching hospital, Northwest Ethiopia.

PubMed

Andualem, Berhanu; Kassu, Afework; Moges, Feleke; Gedefaw, Molla; Diro, Ermias; Mengistu, Getahun; Andargie, Gashaw

2007-04-01

to determine the prevalence and type of intestinal parasites in HIV infected and uninfected patients with diarrhea. A cross-sectional study was conducted at Gondar University hospital, Northwest Ethiopia, between March 2003 and October 2004. A total 312 consecutive diarrheic patients were included in the study. Stool specimens were collected and examined for intestinal parasites following direct, formol-ether concentration and modified acid fast staining methods. Among the patients, 63.8% were found to be HIV seropositive. The prevalence of intestinal parasites in HIV seropositive and seronegative diarrheic patients was 30.6% and 33.6%, respectively. The most prevalent parasites were Strongyoides stercoralis (9.0%) and Entamoeba histolytica (8.3%) followed by Ascaris lumbricoides (5.4%) and Cryptosporidium species (5. 1%). The prevalence of intestinal parasites in diarrheic patients was very high. Institution of appropriate intervention measures are needed to reduce morbidity in such patients.

An unusual cause of small bowel obstruction in children: lentil soup bezoar

PubMed Central

Plataras, Christos; Sardianos, Nektarios; Vlatakis, Stephanos; Nikas, Konstantinos

2014-01-01

Bezoars are an unusual cause of acute intestinal obstruction in children. Most cases are trichobezoars in adolescent girls who swallow their hair. Lactobezoars are another unusual but occasionally reported cause of intestinal obstruction in neonates. Phytobezoars and food bolus bezoars are the least common types of intestinal obstruction that have been reported in children. Of the few paediatric cases that have been described, the majority involve persimmons. Moreover, all of these cases involve the ingestion of raw fibres or fruit that have not been cooked. We report a case of a girl who presented with acute ileal obstruction because of lentil soup bezoar. Given the wide use of this otherwise nutritional foodstuff, we highlight the danger from its inappropriate preparation to the health of children. This is the first reported case of intestinal obstruction caused by lentils in children and we hope to raise concern among paediatricians regarding this matter. PMID:24692381

Gastrointestinal granuloma due to Candida albicans in an immunocompetent cat.

PubMed

Duchaussoy, Anne-Claire; Rose, Annie; Talbot, Jessica J; Barrs, Vanessa R

2015-12-01

A 3.5 year-old cat was admitted to the University of Melbourne Veterinary Teaching Hospital for chronic vomiting. Abdominal ultrasonography revealed a focal, circumferential thickening of the wall of the duodenum extending from the pylorus aborally for 3 cm, and an enlarged gastric lymph node. Cytology of fine-needle aspirates of the intestinal mass and lymph node revealed an eosinophilic inflammatory infiltrate and numerous extracellular septate acute angle branching fungal-type hyphae. Occasional hyphae had globose terminal ends, as well as round to oval blastospores and germ tubes. Candida albicans was cultured from a surgical biopsy of the duodenal mass. No underlying host immunodeficiencies were identified. Passage of an abrasive intestinal foreign body was suspected to have caused intestinal mucosal damage resulting in focal intestinal candidiasis. The cat was treated with a short course of oral itraconazole and all clinical signs resolved.

Gastrointestinal granuloma due to Candida albicans in an immunocompetent cat

PubMed Central

Duchaussoy, Anne-Claire; Rose, Annie; Talbot, Jessica J.; Barrs, Vanessa R.

2015-01-01

A 3.5 year-old cat was admitted to the University of Melbourne Veterinary Teaching Hospital for chronic vomiting. Abdominal ultrasonography revealed a focal, circumferential thickening of the wall of the duodenum extending from the pylorus aborally for 3 cm, and an enlarged gastric lymph node. Cytology of fine-needle aspirates of the intestinal mass and lymph node revealed an eosinophilic inflammatory infiltrate and numerous extracellular septate acute angle branching fungal-type hyphae. Occasional hyphae had globose terminal ends, as well as round to oval blastospores and germ tubes. Candida albicans was cultured from a surgical biopsy of the duodenal mass. No underlying host immunodeficiencies were identified. Passage of an abrasive intestinal foreign body was suspected to have caused intestinal mucosal damage resulting in focal intestinal candidiasis. The cat was treated with a short course of oral itraconazole and all clinical signs resolved. PMID:26862475

[Dual role for prostaglandin D2 in intestinal epithelial homeostasis].

PubMed

Le Loupp, Anne-Gaelle; Bach-Ngohou, Kalyane; Bettan, Armel; Denis, Marc; Masson, Damien

2015-01-01

Prostaglandin D2 (PGD2) and derivatives are lipid mediators involved in the control of the intestinal epithelial barrier homeostasis. Their involvement in the pathophysiology of chronic inflammatory bowel disease (IBD) is still debated. Several results highlight the duality of PGD2 as an anti- or pro-inflammatory mediator. This duality seems to be related to a differential expression of its receptors by intestinal epithelial cells and the surrounding immunocompetent cells. The enteric glial cells from the enteric nervous system (ENS) express the lipocalin-type-prostaglandin D synthase and secrete PGD2 and 15d-PGJ2. The protective role of the ENS in the homeostatic control of the epithelial intestinal barrier and its involvement in the pathogenesis of IBD have already been demonstrated. Thus, these lipid mediators seem to be new actors of the neuro-glio-epithelial unit and could play a crucial role maintaining gut barrier integrity. © 2015 médecine/sciences – Inserm.

IL-6-Type Cytokine Signaling in Adipocytes Induces Intestinal GLP-1 Secretion.

PubMed

Wueest, Stephan; Laesser, Céline I; Böni-Schnetzler, Marianne; Item, Flurin; Lucchini, Fabrizio C; Borsigova, Marcela; Müller, Werner; Donath, Marc Y; Konrad, Daniel

2018-01-01

We recently showed that interleukin (IL)-6-type cytokine signaling in adipocytes induces free fatty acid release from visceral adipocytes, thereby promoting obesity-induced hepatic insulin resistance and steatosis. In addition, IL-6-type cytokines may increase the release of leptin from adipocytes and by those means induce glucagon-like peptide 1 (GLP-1) secretion. We thus hypothesized that IL-6-type cytokine signaling in adipocytes may regulate insulin secretion. To this end, mice with adipocyte-specific knockout of gp130, the signal transducer protein of IL-6, were fed a high-fat diet for 12 weeks. Compared with control littermates, knockout mice showed impaired glucose tolerance and circulating leptin, GLP-1, and insulin levels were reduced. In line, leptin release from isolated adipocytes was reduced, and intestinal proprotein convertase subtilisin/kexin type 1 ( Pcsk1 ) expression, the gene encoding PC1/3, which controls GLP-1 production, was decreased in knockout mice. Importantly, treatment with the GLP-1 receptor antagonist exendin 9-39 abolished the observed difference in glucose tolerance between control and knockout mice. Ex vivo, supernatant collected from isolated adipocytes of gp130 knockout mice blunted Pcsk1 expression and GLP-1 release from GLUTag cells. In contrast, glucose- and GLP-1-stimulated insulin secretion was not affected in islets of knockout mice. In conclusion, adipocyte-specific IL-6 signaling induces intestinal GLP-1 release to enhance insulin secretion, thereby counteracting insulin resistance in obesity. © 2017 by the American Diabetes Association.

Class B type I scavenger receptor is responsible for the high affinity cholesterol binding activity of intestinal brush border membrane vesicles

PubMed Central

Labonté, Eric D.; Howles, Philip N.; Granholm, Norman A.; Rojas, Juan C.; Davies, Joanna P.; Ioannou, Yiannis A.; Hui, David Y.

2007-01-01

Recent studies have documented the importance of Niemann Pick C1-like 1 protein (NPC1L1), a putative physiological target of the drug ezetimibe, in mediating intestinal cholesterol absorption. However, whether NPC1L1 is the high affinity cholesterol binding protein on intestinal brush border membranes is still controversial. In this study, brush border membrane vesicles (BBMV) from wild type and NPC1L1−/− mice were isolated and assayed for micellar cholesterol binding in the presence or absence of ezetimibe. Results confirmed the loss of the high affinity component of cholesterol binding when wild type BBMV preparations were incubated with antiserum against the class B type 1 scavenger receptor (SR-BI) in the reaction mixture similar to previous studies. Subsequently, second order binding of cholesterol was observed with BBMV from wild type and NPC1L1−/− mice. The inclusion of ezetimibe in these in vitro reaction assays resulted in the loss of the high affinity component of cholesterol interaction. Surprisingly, BBMVs from NPC1L1−/− mice maintained active binding of cholesterol. These results documented that SR-BI, not NPC1L1, is the major protein responsible for the initial high affinity cholesterol ligand binding process in the cholesterol absorption pathway. Additionally, ezetimibe may inhibit BBM cholesterol binding through targets such as SR-BI in addition to its inhibition of NPC1L1. PMID:17442616

Analysis of cell cycle-related proteins in gastric intramucosal differentiated-type cancers based on mucin phenotypes: a novel hypothesis of early gastric carcinogenesis based on mucin phenotype

PubMed Central

2010-01-01

Background Abnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. However, recent studies have shown that gastric cancer tumorigenesis was characterized by mucin expression. Thus, expression patterns of cell cycle-related proteins were investigated in the early phase of differentiated-type gastric cancers to ascertain any mechanistic relationships with mucin phenotypes. Methods Immunostaining for Cyclins D1, A, E, and p21, p27, p53 and β-catenin was used to examine impairments of the cell cycle in 190 gastric intramucosal differentiated-type cancers. Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10. A Ki-67 positive rate (PR) was also examined. Results Overexpressions of p53, cyclin D1 and cyclin A were significantly more frequent in a gastric phenotype than an intestinal phenotype. Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype. Reduction of p21 was a common feature of the gastric intramucosal differentiated-type cancers examined. Conclusions Our results suggest that the levels of some cell cycle regulators appear to be associated with mucin phenotypes of early gastric differentiated-type cancers. PMID:20525401

Mild aphasia: is this the place for an argument?

PubMed

Armstrong, Elizabeth; Fox, Sarah; Wilkinson, Ray

2013-05-01

Individuals with mild aphasia often report significant disruption to their communication despite seemingly minor impairment. This study explored this phenomenon through examining conversations of a person with mild aphasia engaging in argumentation--a skill she felt had significantly deteriorated after her stroke. A person with mild aphasia and her husband recorded 4 conversations involving topical issues. The discourse dynamics and lexical-grammatical content were analyzed using systemic functional linguistic (Halliday & Matthiessen, 2004) and conversation analysis (Sacks, Schegloff, & Jefferson, 1974) frameworks. The couple demonstrated similarities in the types of conversational moves, but the language of the person with aphasia was more nonspecific and simplified, manifesting in difficulties developing a logical argument and responding to the partner's line of argument. In addition, the nonaphasic speaker recurrently overlapped the aphasic speaker in order to request clarification of particular points, highlighting the types of behaviors that can occur in this form of higher level language activity. The complex argument task and the multilevel and multi-approach analysis are useful tools for examining persons with mild aphasia, revealing aspects that are often overlooked in standard tests. Treatment could incorporate more complex notions such as evaluative language and the role of overlap in complex conversations.