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Sample records for ameliorates intestinal radiation

  1. Orazipone, a locally acting immunomodulator, ameliorates intestinal radiation injury: A preclinical study in a novel rat model

    International Nuclear Information System (INIS)

    Boerma, Marjan; Wang, Junru; Richter, Konrad K.; Hauer-Jensen, Martin

    2006-01-01

    Purpose: Intestinal radiation injury (radiation enteropathy) is relevant to cancer treatment, as well as to radiation accidents and radiation terrorism scenarios. This study assessed the protective efficacy of orazipone, a locally-acting small molecule immunomodulator. Methods and Materials: Male rats were orchiectomized, a 4-cm segment of small bowel was sutured to the inside of the scrotum, a proximal anteperistaltic ileostomy was created for intraluminal drug administration, and intestinal continuity was re-established by end-to-side anastomosis. After three weeks postoperative recovery, the intestine in the 'scrotal hernia' was exposed locally to single-dose or fractionated X-radiation. Orazipone (30 mg/kg/day) or vehicle was administered daily through the ileostomy, either during and after irradiation, or only after irradiation. Structural, cellular, and molecular aspects of intestinal radiation toxicity were assessed two weeks after irradiation. Results: Orazipone significantly ameliorated histologic injury and transforming growth factor-β immunoreactivity levels, both after single-dose and fractionated irradiation. Intestinal wall thickness was significantly reduced after single-dose and nonsignificantly after fractionated irradiation. Mucosal surface area and numbers of mast cells were partially restored by orazipone after single-dose irradiation. Conclusions: This work (1) demonstrates the utility of the ileostomy rat model for intraluminal administration of response modifiers in single-dose and fractionated radiation studies; (2) shows that mucosal immunomodulation during and/or after irradiation ameliorates intestinal toxicity; and (3) highlights important differences between single-dose and fractionated radiation regimens

  2. Inhibition of Protease-activated Receptor 1 Ameliorates Intestinal Radiation Mucositis in a Preclinical Rat Model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Junru; Kulkarni, Ashwini [Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Chintala, Madhu [Schering-Plough Research Institute, Kenilworth, New Jersey (United States); Fink, Louis M. [Nevada Cancer Institute, Las Vegas, Nevada (United States); Hauer-Jensen, Martin, E-mail: mhjensen@life.uams.edu [Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Surgery Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas (United States)

    2013-01-01

    Purpose: To determine, using a specific small-molecule inhibitor of protease-activated receptor 1 (PAR1) signaling, whether the beneficial effect of thrombin inhibition on radiation enteropathy development is due to inhibition of blood clotting or to cellular (PAR1-mediated) thrombin effects. Methods and Materials: Rats underwent fractionated X-irradiation (5 Gy Multiplication-Sign 9) of a 4-cm small-bowel segment. Early radiation toxicity was evaluated in rats receiving PAR1 inhibitor (SCH602539, 0, 10, or 15 mg/kg/d) from 1 day before to 2 weeks after the end of irradiation. The effect of PAR1 inhibition on development of chronic intestinal radiation fibrosis was evaluated in animals receiving SCH602539 (0, 15, or 30 mg/kg/d) until 2 weeks after irradiation, or continuously until termination of the experiment 26 weeks after irradiation. Results: Blockade of PAR1 ameliorated early intestinal toxicity, with reduced overall intestinal radiation injury (P=.002), number of myeloperoxidase-positive (P=.03) and proliferating cell nuclear antigen-positive (P=.04) cells, and collagen III accumulation (P=.005). In contrast, there was no difference in delayed radiation enteropathy in either the 2- or 26-week administration groups. Conclusion: Pharmacological blockade of PAR1 seems to reduce early radiation mucositis but does not affect the level of delayed intestinal radiation fibrosis. Early radiation enteropathy is related to activation of cellular thrombin receptors, whereas platelet activation or fibrin formation may play a greater role in the development of delayed toxicity. Because of the favorable side-effect profile, PAR1 blockade should be further explored as a method to ameliorate acute intestinal radiation toxicity in patients undergoing radiotherapy for cancer and to protect first responders and rescue personnel in radiologic/nuclear emergencies.

  3. Bone marrow transplantation rescues intestinal mucosa after whole body radiation via paracrine mechanisms

    International Nuclear Information System (INIS)

    Chang, Ya Hui; Lin, Li-Mei; Lou, Chi-Wen; Chou, Chuan-Kai; Ch’ang, Hui-Ju

    2012-01-01

    Purpose: Our previous study reveals bone marrow transplantation (BMT) recruits host marrow-derived myelomonocytic cells to radiation-injured intestine, enhancing stromal proliferation, leading secondarily to epithelial regeneration. In this study, we propose BMT ameliorates intestinal damage via paracrine mechanisms. Materials and methods: Angiogenic cytokines within the intestinal mucosa of mice after whole body irradiation (WBI) with or without BMT were measured by cytokine array and ELISA. BM conditioned medium (BMCM) with or without treatment with neutralizing antibodies to angiogenic cytokines were continuously infused into mice for three days after radiation. Carrageenan was used to deplete myelomonocytic cells of mice. Results: BMT increased VEGF, bFGF and other angiogenic and chemotactic cytokines in the intestinal mucosa within 24 h after WBI. Infusion of BMCM ameliorated radiation-induced intestinal damage with improved stromal activity and prolonged survival of mice. Neutralization of bFGF, PDGF and other angiogenic cytokines within BMCM abolished the mitigating effect to the intestine. Pretreatment of carrageenan to recipient mice reversed some of the cytokine levels, including VEGF, bFGF and IGF within the intestinal mucosa after BMT. Conclusions: Our result suggests BMT recruits host myelomonocytic cells and enhances intestinal stroma proliferation after radiation by secreting cytokines enhancing angiogenesis and chemotaxis. Host myelomonocytic cells further uplift the paracrine effect to enhance intestinal mucosal recovery.

  4. Simvastatin Ameliorates Radiation Enteropathy Development After Localized, Fractionated Irradiation by a Protein C-Independent Mechanism

    International Nuclear Information System (INIS)

    Wang Junru; Boerma, Marjan; Fu Qiang; Kulkarni, Ashwini; Fink, Louis M.; Hauer-Jensen, Martin

    2007-01-01

    Purpose: Microvascular injury plays a key role in normal tissue radiation responses. Statins, in addition to their lipid-lowering effects, have vasculoprotective properties that may counteract some effects of radiation on normal tissues. We examined whether administration of simvastatin ameliorates intestinal radiation injury, and whether the effect depends on protein C activation. Methods and Materials: Rats received localized, fractionated small bowel irradiation. The animals were fed either regular chow or chow containing simvastatin from 2 weeks before irradiation until termination of the experiment. Groups of rats were euthanized at 2 weeks and 26 weeks for assessment of early and delayed radiation injury by quantitative histology, morphometry, and quantitative immunohistochemistry. Dependency on protein C activation was examined in thrombomodulin (TM) mutant mice with deficient ability to activate protein C. Results: Simvastatin administration was associated with lower radiation injury scores (p < 0.0001), improved mucosal preservation (p = 0.0009), and reduced thickening of the intestinal wall and subserosa (p = 0.008 and p = 0.004), neutrophil infiltration (p = 0.04), and accumulation of collagen I (p = 0.0003). The effect of simvastatin was consistently more pronounced for delayed than for early injury. Surprisingly, simvastatin reduced intestinal radiation injury in TM mutant mice, indicating that the enteroprotective effect of simvastatin after localized irradiation is unrelated to protein C activation. Conclusions: Simvastatin ameliorates the intestinal radiation response. The radioprotective effect of simvastatin after localized small bowel irradiation does not appear to be related to protein C activation. Statins should undergo clinical testing as a strategy to minimize side effects of radiation on the intestine and other normal tissues

  5. Curcumin Attenuates Gamma Radiation Induced Intestinal Damage in Rats

    International Nuclear Information System (INIS)

    EI-Tahawy, N.A.

    2009-01-01

    Small Intestine exhibits numerous morphological and functional alterations during radiation exposure. Oxidative stress, a factor implicated in the intestinal injury may contribute towards some of these alterations. The present work was designed to evaluate the efficacy of curcumin, a yellow pigment of turmeric on y-radiation-induced oxidative damage in the small intestine by measuring alterations in the level of thiobarbituric acid reactive substances (TSARS), serotonin metabolism, catecholamine levels, and monoamine oxidase (MAO) activity in parallel to changes in the architecture of intestinal tissues. In addition, monoamine level, MAO activity and TSARS level were determined in the serum. Curcumin was supplemented orally via gavages, to rats at a dose of (45 mg/ Kg body wt/ day) for 2 weeks pre-irradiation and the last supplementation was 30 min pre exposure to 6.5 Gy gamma radiations (applied as one shot dose). Animals were sacrificed on the 7th day after irradiation. The results demonstrated that, whole body exposure of rats to ionizing radiation has induced oxidative damage in small intestine obvious by significant increases of TSARS content, MAO activity and 5-hydroxy indole acetic acid (5-HIAA) and by significant decreases of serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (EPI) levels. In parallel histopathological studies of the small intestine of irradiated rats through light microscopic showed significant decrease in the number of villi, villus height, mixed sub mucosa layer with more fibres and fibroblasts. Intestinal damage was in parallel to significant alterations of serum MAO activity, TBARS, 5-HT, DA, NE and EPI levels. Administration of curcumin before irradiation has significantly improved the levels of monoamines in small intestine and serum of irradiated rats, which was associated with significant amelioration in MAO activity and TBARS contents

  6. Related radiation effects on the intestine and their treatment

    International Nuclear Information System (INIS)

    Bardychev, M.S.; Kurpeshcheva, A.K.; Kaplan, M.A.

    1978-01-01

    Late radiation injuries of the intestine are frequent after radiation therapy of malignant tumours of female genitalia and some other tumours due to which the intestine gets into the irradiation field. On the basis of the analysis of 80 patients with late radiation injuries of intestine which developed at remote terms after radiation therapy of cervix uteri cancer and corpus uteri (65 patients) and other tumours, peculiarities of the clinical course and treatment of radiation enterocolitis, rectosigmoidites and rectites are discussed. In 39 patients these injuries were concomitant with late radiation injuries of the skin and subcutaneous soft tissues. The clinical course of radiation unjuries of the intestine was defined by the character of the pathological process in the intestine and was more sharply marked in patients suffering from radiation enterocolites. It was established that one of the pathogenetic mechanisms of late radiation injuries of the intestine was a disorder of the absorption function of the intestine. Local treatment of radiation injuries of the intestine should be combined with a general one the important component of which is a parenteral diet

  7. Radiation-induced recurrent intestinal pseudo-obstruction

    International Nuclear Information System (INIS)

    Conklin, J.L.; Anuras, S.

    1981-01-01

    The syndrome of intestinal pseudo-obstruction is a complex of signs and symptoms of intestinal obstruction without evidence of mechanical obstruction of the intestinal lumen. A patient with radiation-induced intestinal pseudoobstruction is described. The patient is a 74-year old woman with a history of chronic diarrhea, recurrent episodes of crampy abdominal pain, nausea and vomiting since receiving a 13,000 rad radiation dose to the pelvis in 1954. She has been hospitalized on many occasions for symptoms and signs of bowel obstruction. Upper gastrointestinal contrast roentgenograms with small bowel follow-through done during these episodes revealed multiple dilated loops of small bowel with no obstructing lesion. Barium enemas revealed no obstructing lesion. Each episode resolved with conservative therapy. Other secondary causes for intestinal pseudo-obstruction were ruled out in our patient. She gave no history of familial gastrointestinal disorders. Although postirradiation motility abnormalities have been demonstrated experimentally this is the first report of radiation induced intestinal pseudo-obstruction

  8. Tissue response after radiation exposure. Intestine

    International Nuclear Information System (INIS)

    Otsuka, Kensuke; Tomita, Masanori; Yamauchi, Motohiro; Iwasaki, Toshiyasu

    2014-01-01

    Gastrointestinal syndrome followed by 'gut death' is due to intestinal disorders. This syndrome is induced by high-dose (>10 Gy) of ionizing radiation. Recovery from the gastrointestinal syndrome would depend on the number of survived clonogens and regeneration capability of crypts. These tissue alterations can be observed by high-dose radiation, however, cellular dynamics in crypts can be affected by low-dose radiation. For example, Potten et al. found that low-dose radiation induce apoptosis of intestinal stem cells, which produce all differentiated function cells. Recently, intestinal stem cells are characterized by molecular markers such as Lgr5. Since intestinal adenomas can be induced by deletion of Apc gene in Lgr5 + stem cells, it is widely recognized that Lgr5 + stem cells are the cell-of-origin of cancer. Duodenal Lgr5 + stem cells are known as radioresistant cells, however, we found that ionizing radiation significantly induces the turnover of colonic Lgr5 + stem cells. Combined with the knowledge of other radioresistant markers, stem-cell dynamics in tissue after irradiation are becoming clear. The present review introduces the history of gastrointestinal syndrome and intestinal stem cells, and discusses those future perspectives. (author)

  9. Radiodiagnosis of early radiation intestinal changes

    International Nuclear Information System (INIS)

    Volodina, G.I.; Abdulkhakova, D.A.

    1987-01-01

    X-ray examination of the colon in 102 patients and of the small intestine in 62 was performed during combined radiation therapy of cervical cancer and at different time after its discontinuation. Early radiation functional and morphological changes in the ileum and colon were detected. Radiation changes in the ileac mucosa were noted in 52% of the patients, changes of various degree in the rectal, sigmoid and cecal mucosa were noted in 41.2%. Moderate radiation changes in the ascending, descending and horizontal parts of the colon were noted in 10.7%. Early radiation intestinal injuries in the form of erosions and ulcers were revealed in 5.8% of the patients. In most of the patients radiation intestinal changes were without noticeable clinical manifestations. All these patients could be defined as a group at risk of developing late radiation changes

  10. Intestinal endocrine cells in radiation enteritis

    International Nuclear Information System (INIS)

    Pietroletti, R.; Blaauwgeers, J.L.; Taat, C.W.; Simi, M.; Brummelkamp, W.H.; Becker, A.E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were quantified by counting their number per unit length of muscularis mucosa. Results in radiation enteritis were compared with matched control specimens by using Student's t test. Chromogranin immunostaining showed a statistically significant increase of endocrine cells in radiation enteritis specimens compared with controls both in small and large intestine (ileum, 67.5 +/- 23.5 cells per unit length of muscularis mucosa in radiation enteritis versus 17.0 +/- 6.1 in controls; colon, 40.9 +/- 13.7 cells per unit length of muscularis mucosa in radiation enteritis versus 9.5 +/- 4.1 in controls--p less than 0.005 in both instances). Increase of endocrine cells was demonstrated also by Grimelius' staining; however, without reaching statistical significance. It is not clear whether or not the increase of endocrine cells in radiation enteritis reported in this study is caused by a hyperplastic response or by a sparing phenomenon. We should consider that increased endocrine cells, when abnormally secreting their products, may be involved in some of the clinical features of radiation enteropathy. In addition, as intestinal endocrine cells produce trophic substances to the intestine, their increase could be responsible for the raised risk of developing carcinoma of the intestine in long standing radiation enteritis

  11. Intestinal ameliorative effects of traditional Ogi-tutu, Vernonia amygdalina and Psidium guajava in mice infected with Vibrio cholera.

    Science.gov (United States)

    Shittu, Olufunke B; Ajayi, Olusola L; Bankole, Samuel O; Popoola, Temitope Os

    2016-06-01

    Cholera, a severe acute watery diarrhea caused by Vibrio cholerae is endemic in Nigeria with most cases occurring in the rural areas. In South West Nigeria, some individuals resort to alternative treatments such as Ogi-tutu, Psidium guajava and Vernonia amygdalina during infections. The effectiveness of these alternatives in the prevention and treatment of V. cholerae infection requires experimental investigation. This study was designed to investigate the ameliorative effects of Ogi-tutu, Vernonia amygdalina and Psidium guajava on intestinal histopathology of experimental mice infected with V. cholerae. Preliminary investigation of in vitro vibriocidal activities of these alternatives were carried out using agar cup diffusion assay. For ameliorative effects, adult mice were inoculated with 100 µl (106 cells) of Vibrio cholerae and dosed at 0 h (immediate prevention) and 4 h (treatment of infection) and their intestines were histopathologically evaluated. The histopathological changes were the same irrespective of the treated groups, but the lesions varied in extent and severity. The ameliorative effects in decreasing order were V. amygdalina > P. guajava > Ogi-tutu. V. amygdalina gave the best ameliorative effects in the prevention and treatment of V. cholerae infection.

  12. Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

  13. Surgical management of radiation injury to the small intestine

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    Swan, R.W.; Fowler, W.C. Jr., Boronow, R.C.

    1976-01-01

    Severe injury of the small intestine represents one of the most tragic complications of radiation of the pelvis and abdomen. Not uncommonly, patients die from the radiation or the treatment of its intestinal complications. More commonly, patients become intestinal cripples, secondary to chronic partial obstruction of the small intestine and malnutrition associated with the stagnant loop syndrome, as previously reported by one of us. Management results have been discouraging, usually because of a general lack of clinical recognition and understanding of radiation injury to the intestine. Medical management has not been satisfactory. It may provide temporary relief from symptoms, but not long-lasting. Surgical management, although frequently curative, has been associated with high death and morbidity rates. Many surgical procedures have been used in treating radiation injury to the small intestine. Generally, these fall into two categories: first, intestinal resection with primary anastomosis; and second, enteroenteric or enterocolic bypass. In the literature are reflected advocates for each method of surgical management.

  14. Saccharomyces boulardii ameliorates clarithromycin- and methotrexate-induced intestinal and hepatic injury in rats.

    Science.gov (United States)

    Duman, Deniz Güney; Kumral, Zarife Nigâr Özdemir; Ercan, Feriha; Deniz, Mustafa; Can, Güray; Cağlayan Yeğen, Berrak

    2013-08-28

    Saccharomyces boulardii is a probiotic used for the prevention of antibiotic-associated diarrhoea. We aimed to investigate whether S. boulardii could alter the effects of clarithromycin (CLA) and methotrexate (MTX) on oro-caecal intestinal transit and oxidative damage in rats. Rats were divided into two groups receiving a single dose of MTX (20 mg/kg) or CLA (20 mg/kg per d) for 1 week. Groups were treated with either saline or S. boulardii (500 mg/kg) twice per d throughout the experiment. The control group was administered only saline. Following decapitation, intestinal transit and inflammation markers of glutathione (GSH), malondialdehyde and myeloperoxidase were measured in intestinal and hepatic tissues. CLA and MTX increased intestinal transit, while S. boulardii treatment slowed down CLA-facilitated transit back to control level. Both MTX and CLA increased lipid peroxidation while depleting the antioxidant GSH content in the hepatic and ileal tissues. Conversely, lipid peroxidation was depressed and GSH levels were increased in the ileal and hepatic tissues of S. boulardii-treated rats. Increased ileal neutrophil infiltration due to MTX and CLA treatments was also reduced by S. boulardii treatment. Histological analysis supported that S. boulardii protected intestinal tissues against the inflammatory effects of both agents. These findings suggest that S. boulardii ameliorates intestinal injury and the accompanying hepatic inflammation by supporting the antioxidant state of the tissues and by inhibiting the recruitment of neutrophils. Moreover, a preventive effect on MTXinduced toxicity is a novel finding of S. boulardii, proposing it as an adjunct to chemotherapy regimens.

  15. Attenuative effects of G-CSF in radiation induced intestinal injury

    International Nuclear Information System (INIS)

    Kim, Joong Sun; Gong, Eun Ji; Kim, Sung Dae; Heo, Kyu; Ryoo, Seung Bum; Yang, Kwang Mo

    2011-01-01

    Granulocyte colony stimulating factor (G-CSF) has been reported to protect from radiationinduced myelosuppression. Growing evidence suggests that G-CSF also has many important non-hematopoietic functions in other tissues, including the intestine (Kim et al., 2010; Kim et al., 2011). However, little is known about the influence of G-CSF on intestinal injury. Examination 12 hours after radiation (5 Gy) revealed that the G-CSF treated mice were significantly protected from apoptosis of jejunal crypt, compared with radiation controls. G-CSF treatment attenuated intestinal morphological changes such as decreased survival crypt, the number of villi, villous shortening, crypt depth and length of basal lamina of 10 enterocytes compared with the radiation control 3.5 days after radiation (10 Gy). G-CSF attenuated the change of peripheral blood from radiation-induced myelosuppression and displayed attenuation of mortality in lethally-irradiated (10 Gy) mice. The present results support the suggestion that G-CSF administrated prior to radiation plays an important role in the survival of irradiated mice, possibly due to the protection of hematopoietic cells and intestinal stem cells against radiation. The results indicate that G-CSF protects from radiation-mediated intestinal damage and from hematopoietic injury. G-CSF treatment may be useful clinically in the prevention of injury following radiation.

  16. Temporary intestinal ischemia for radiation protection

    International Nuclear Information System (INIS)

    Lote, K.

    1983-01-01

    The most important determinant of cellular radiosensivity is the tissue oxygen content at the time of irradiation. The purpose of the present experimental work was to assess a new iscemia-inducing method in order to reduce normal tissue radiation damage during radiotherapy. Temporary ischemia was induced in a cat small intestine by degraded starch microspheres. Regional arterial and tissue blod flow immediately fell by 85% with subsequent normalization within 26 minutes after microsphere injection. No tendency of small vessel thrombosis caused by starch sphere embolization in combination with previous or current intestinal irradiation was detected. Starch sphere remenants were rapidly engulfed by, and persisted within tissue macrophages for 14 days without causing intestinal inflammatory reactions. In vitro studies showed that human platelets neither adhered to nor were aggregated by starch microspheres. The new method, wich occlude arteriolar vessels distal to the mesentric arterial arcades and thus largely excludes collateral blood flow, seems suited to provide effictive and selective feline small intestinal hypoxic radiation protection. This conclusion may also be valid in man

  17. Delayed radiation effects at the small and large intestine

    International Nuclear Information System (INIS)

    Wunder, S.

    1982-01-01

    The work deals with 56 patients treated within a period of 15 years for delayed radiation damage to the intestine. Gynecologic carcinomas were most frequently the basic disease. By the time the complaints occurred, which mostly took the form of an ileus, the radiation therapy dated back 4 months to 38 years. The mean age of the patients was 60 years. The report points out the diagnostical problem as well as clinical, radiographic and histological findings. Especially hydronephrosis and renal failure were observed as additional radiation sequelae. Whenever possible, resection of the intestinal segment concerned should be carried through. The portion of radiological patients who attracted the disorder was of 72 per cent, with a lethal result in 37 per cent. Half the patients died from an imperfect anastomosis followed by peritonitis. In 16 per cent of the patients recidivations of the malignant basic disease occurred. Whether treatment of radiation damage of the intestine is successful depends on the care taken to give a diagnosis and on the assessment of the intestinal segment damaged. As the actinic injury tends to aggravate early surgical intervention is recommended. Because the treatment of malignant tumours by irradiation is partly quite successful, injuries to the intestine must to some extent be put up with. (orig./MG) [de

  18. BVES Regulates Intestinal Stem Cell Programs and Intestinal Crypt Viability after Radiation

    Science.gov (United States)

    Reddy, Vishruth K.; Short, Sarah P.; Barrett, Caitlyn W.; Mittal, Mukul K.; Keating, Cody E.; Thompson, Joshua J.; Harris, Elizabeth I.; Revetta, Frank; Bader, David M.; Brand, Thomas; Washington, M. Kay; Williams, Christopher S.

    2016-01-01

    Blood Vessel Epicardial Substance (BVES/Popdc1) is a junctional-associated transmembrane protein that is underexpressed in a number of malignancies and regulates epithelial-to-mesenchymal transition. We previously identified a role for BVES in regulation of the Wnt pathway, a modulator of intestinal stem cell programs, but its role in small intestinal (SI) biology remains unexplored. We hypothesized that BVES influences intestinal stem cell programs and is critical to SI homeostasis after radiation injury. At baseline, Bves−/− mice demonstrated increased crypt height, as well as elevated proliferation and expression of the stem cell marker Lgr5 compared to wildtype (WT) mice. Intercross with Lgr5-EGFP reporter mice confirmed expansion of the stem cell compartment in Bves−/− mice. To examine stem cell function after BVES deletion, we employed ex vivo 3D-enteroid cultures. Bves−/− enteroids demonstrated increased stemness compared to WT, when examining parameters such as plating efficiency, stem spheroid formation, and retention of peripheral cystic structures. Furthermore, we observed increased proliferation, expression of crypt-base columnar “CBC” and “+4” stem cell markers, amplified Wnt signaling, and responsiveness to Wnt activation in the Bves−/− enteroids. Bves expression was downregulated after radiation in WT mice. Moreover, after radiation, Bves−/− mice demonstrated significantly greater small intestinal crypt viability, proliferation, and amplified Wnt signaling in comparison to WT mice. Bves−/− mice also demonstrated elevations in Lgr5 and Ascl2 expression, and putative damage-responsive stem cell populations marked by Bmi1 and TERT. Therefore, BVES is a key regulator of intestinal stem cell programs and mucosal homeostasis. PMID:26891025

  19. Effects of Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 in Radiation-Induced Intestinal Injury

    International Nuclear Information System (INIS)

    Abderrahmani, Rym; Francois, Agnes; Buard, Valerie; Benderitter, Marc; Sabourin, Jean-Christophe; Crandall, David L.; Milliat, Fabien

    2009-01-01

    Purpose: To investigate effects of plasminogen activator inhibitor 1 (PAI-1) genetic deficiency and pharmacological PAI-1 inhibition with PAI-039 in a mouse model of radiation-induced enteropathy. Methods and Materials: Wild-type (Wt) and PAI-1 -/- knockout mice received a single dose of 19 Gy to an exteriorized localized intestinal segment. Sham and irradiated Wt mice were treated orally with 1 mg/g of PAI-039. Histological modifications were quantified using a radiation injury score. Moreover, intestinal gene expression was monitored by real-time PCR. Results: At 3 days after irradiation, PAI-039 abolished the radiation-induced increase in the plasma active form of PAI-1 and limited the radiation-induced gene expression of transforming growth factor β1 (TGF-β1), CTGF, PAI-1, and COL1A2. Moreover, PAI-039 conferred temporary protection against early lethality. PAI-039 treatment limited the radiation-induced increase of CTGF and PAI-1 at 2 weeks after irradiation but had no effect at 6 weeks. Radiation injuries were less severe in PAI-1 -/- mice than in Wt mice, and despite the beneficial effect, 3 days after irradiation, PAI-039 had no effects on microscopic radiation injuries compared to untreated Wt mice. Conclusions: A genetic deficiency of PAI-1 is associated with amelioration of late radiation enteropathy. Pharmacological inhibition of PAI-1 by PAI-039 positively impacts the early, acute phase increase in plasma PAI-1 and the associated radiation-induced gene expression of inflammatory/extracellular matrix proteins. Since PAI-039 has been shown to inhibit the active form of PAI-1, as opposed to the complete loss of PAI-1 in the knockout animals, these data suggest that a PAI-1 inhibitor could be beneficial in treating radiation-induced tissue injury in acute settings where PAI-1 is elevated.

  20. Claudin-3 expression in radiation-exposed rat models: A potential marker for radiation-induced intestinal barrier failure

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Sehwan; Lee, Jong-geol; Bae, Chang-hwan; Lee, Seung Bum [National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Jang, Won-Suk; Lee, Sun-Joo [Laboratory of Experimental Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Lee, Seung-Sook [National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Department of Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Park, Sunhoo, E-mail: sunhoo@kcch.re.kr [National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Department of Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2015-01-02

    Highlights: • Irradiation increased intestinal bacterial translocation, accompanied by claudin protein expression in rats. • Neurotensin decreased the bacterial translocation and restored claudin-3 expression. • Claudin-3 can be used as a marker in evaluating radiation induced intestinal injury. - Abstract: The molecular events leading to radiation-induced intestinal barrier failure are not well known. The influence of the expression of claudin proteins in the presence and absence of neurotensin was investigated in radiation-exposed rat intestinal epithelium. Wistar rats were randomly divided into control, irradiation, and irradiation + neurotensin groups, and bacterial translocation to the mesenteric lymph node and expression of claudins were determined. Irradiation led to intestinal barrier failure as demonstrated by significant bacterial translocation. In irradiated terminal ilea, expression of claudin-3 and claudin-4 was significantly decreased, and claudin-2 expression was increased. Administration of neurotensin significantly reduced bacterial translocation and restored the structure of the villi as seen by histologic examination. Among the three subtype of claudins, only claudin-3 expression was restored. These results suggest that the therapeutic effect of neurotensin on the disruption of the intestinal barrier is associated with claudin-3 alteration and that claudin-3 could be used as a marker in evaluating radiation-induced intestinal injury.

  1. Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism

    Science.gov (United States)

    Yan, Fang; Cao, Hanwei; Cover, Timothy L.; Washington, M. Kay; Shi, Yan; Liu, LinShu; Chaturvedi, Rupesh; Peek, Richard M.; Wilson, Keith T.; Polk, D. Brent

    2011-01-01

    Probiotic bacteria can potentially have beneficial effects on the clinical course of several intestinal disorders, but our understanding of probiotic action is limited. We have identified a probiotic bacteria–derived soluble protein, p40, from Lactobacillus rhamnosus GG (LGG), which prevents cytokine-induced apoptosis in intestinal epithelial cells. In the current study, we analyzed the mechanisms by which p40 regulates cellular responses in intestinal epithelial cells and p40’s effects on experimental colitis using mouse models. We show that the recombinant p40 protein activated EGFR, leading to Akt activation. Activation of EGFR by p40 was required for inhibition of cytokine-induced apoptosis in intestinal epithelial cells in vitro and ex vivo. Furthermore, we developed a pectin/zein hydrogel bead system to specifically deliver p40 to the mouse colon, which activated EGFR in colon epithelial cells. Administration of p40-containing beads reduced intestinal epithelial apoptosis and disruption of barrier function in the colon epithelium in an EGFR-dependent manner, thereby preventing and treating DSS-induced intestinal injury and acute colitis. Furthermore, p40 activation of EGFR was required for ameliorating colon epithelial cell apoptosis and chronic inflammation in oxazolone-induced colitis. These data define what we believe to be a previously unrecognized mechanism of probiotic-derived soluble proteins in protecting the intestine from injury and inflammation. PMID:21606592

  2. Intestinal endocrine cells in radiation enteritis

    NARCIS (Netherlands)

    Pietroletti, R.; Blaauwgeers, J. L.; Taat, C. W.; Simi, M.; Brummelkamp, W. H.; Becker, A. E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were

  3. Protective effect of superoxide dismutase in radiation-induced intestinal inflammation

    International Nuclear Information System (INIS)

    Molla, Meritxell; Gironella, Meritxell; Salas, Antonio; Closa, Daniel; Biete, Albert; Gimeno, Mercedes; Coronel, Pilar; Pique, Josep M.; Panes, Julian

    2005-01-01

    Purpose: To analyze the therapeutic value of Cu/Zn-superoxide dismutase (SOD1) supplementation in an experimental model of radiation-induced intestinal inflammation and explore its mechanistic effects. Methods and materials: Mice were subjected to abdominal irradiation with 10 Gy or sham irradiation and studied 24 or 72 hours after radiation. Groups of mice were treated with 0.1, 4, or 6 mg/kg/day of SOD1 or vehicle. Leukocyte-endothelial cell interactions in intestinal venules were assessed by intravital microscopy. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression was determined with radiolabeled antibodies. Effects of SOD1 on histologic damage and levels of lipid hydroperoxides were also measured. Results: A significant increase in the flux of rolling leukocytes and number of firmly adherent leukocytes in intestinal venules was observed at 24 and 72 hours after irradiation. Treatment with SOD1 had no effect on leukocyte rolling but significantly and dose-dependently decreased firm leukocyte adhesion to intestinal venules. Treatment with SOD1 at doses that reduced leukocyte recruitment abrogated the increase in hydroperoxides in intestinal tissue and ICAM-1 upregulation in intestinal endothelial cells. The inflammatory score, but not a combined histology damage score, was also significantly reduced by SOD1. Conclusions: Treatment with SOD1 decreases oxidative stress and adhesion molecule upregulation in response to abdominal irradiation. This is associated with an attenuation of the radiation-induced intestinal inflammatory response

  4. Bile loss in the acute intestinal radiation syndrome in rats

    International Nuclear Information System (INIS)

    Geraci, J.P.; Dunston, S.G.; Jackson, K.L.; Mariano, M.S.; Holeski, C.; Eaton, D.L.

    1987-01-01

    The effects of bile duct ligation (BDL), choledochostomy, bile acid sequestering within the intestinal lumen by cholestyramine, and fluid and electrolyte replacement on survival time and development of diarrhea after whole-body exposure to doses of ionizing radiation that result in death from acute intestinal injury were studied. BDL significantly prolonged survival and delayed the onset of diarrhea after exposure to 137 Cs gamma rays, fission neutrons, or cyclotron-produced neutrons in the range of doses that produce intestinal death or death from a combination of intestinal and hematopoietic injuries. Cannulation of the bile duct with exteriorized bile flow (choledochostomy) to protect the irradiated intestine from the mucolytic action of bile salts did not duplicate the effect of BDL in increasing survival time. Choledochostomy without fluid replacement eliminated the occurrence of diarrhea in 15.4 Gy irradiated rats. Diarrhea did occur in irradiated animals with choledochostomy if they received duodenal injections of fluid and electrolytes to replace the fluid lost as a result of bile drainage. Duodenal injection of fluid and electrolytes had no significant effect on survival time in irradiated rats. Injection of fluid and electrolytes into the peritoneal cavity of irradiated rats resulted in an increase in survival time that was comparable to that observed after BDL. Addition of antibiotics to the peritoneally injected fluid and electrolytes further increased survival time (up to 9 days). This survival time approached that seen in animals receiving the same radiation dose but which had the intestine exteriorized and shielded to minimize radiation injury to the intestine. Postmortem histological examinations of the irradiated small intestine showed mucosal regeneration in these long-term survivors receiving fluid and antibiotic therapy

  5. Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

    International Nuclear Information System (INIS)

    Wang Junru; Zheng Huaien; Kulkarni, Ashwini; Ou Xuemei; Hauer-Jensen, Martin

    2006-01-01

    Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor β immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent

  6. Probiotics and Probiotic Metabolic Product Improved Intestinal Function and Ameliorated LPS-Induced Injury in Rats.

    Science.gov (United States)

    Deng, Bo; Wu, Jie; Li, Xiaohui; Men, Xiaoming; Xu, Ziwei

    2017-11-01

    In the present study, we sought to determine the effects of Bacillus subtilis (BAS) and Bacillus licheniformis (BAL) in rats after lipopolysaccharide (LPS)-induced acute intestinal inflammation. We also determined whether the B. subtilis metabolic product (BASM) is as effective as the live-cell probiotic. 60 male SD rats were randomly assigned to five groups and administered a diet containing 0.05% B. licheniformis (BAL group), 0.05% B. subtilis (BAS group), 0.5% B. subtilis metabolic product (BASM group), or a basic diet (PC group and NC group) for 40 days. On day 40, BAL, BAS, BASM, and NC groups were injected with 4 mg/kg body weight LPS. 4 h later, all rats were anesthetized and sacrificed. The results showed that the administration of B. licheniformis and B. subtilis improved intestinal function as evidenced by histology, increased enzyme activity, and mucosal thickness. They also increased the number of intraepithelial lymphocytes and decreased mucosal myeloperoxidase activity and plasma TNF-α. In addition, the cecal content of B. subtilis-treated rats had significantly increased microbial diversity, decreased numbers of Firmicutes, and increased numbers of Bacteroidetes as compared to rats fed basic diets. Similar to BAS group, the cecal content of B. licheniformis-treated rats decreased the number of Firmicutes. Administration of B. subtilis metabolic product had similar effects on intestinal function, inflammation response, and microbial diversity as B. subtilis but these effects were attenuated. In conclusion, administration of probiotic strains B. licheniformis or B. subtilis improved intestinal function, ameliorated the inflammation response, and modulated microflora after LPS-induced acute inflammation in rats. Non-living cells also exerted probiotic properties but live cells tended to function better.

  7. The protective effect of lycopene against radiation injury to the small intestine of abdominally radiated mice

    International Nuclear Information System (INIS)

    Itoh, Youko; Kurabe, Teruhisa; Ishiguchi, Tsuneo

    2004-01-01

    To reduce the side effects of radiotherapy, radioprotective effects of lycopene on villi and crypts in the small intestine of abdominally radiated mice (15 Gy) were examined with administration pre-, continuous and post-radiation. In the lycopene group, the ratio of the villus length to the crypt was significantly increased in comparison with the radiation only group at 2 days after radiation. At 7 days after radiation, the ratio of necrotic cells in crypt/total was significantly decreased and the ratio of necrotic cells in villus/total was significantly increased by lycopene administration, which indicated an acceleration of the recovery from the radiation injury with lycopene. Each lycopene administered group showed a significant radioprotective effect, with the pre-radiation administration inducing a smaller effect than that of continuous and post-radiation administration. Radiation induced apoptosis was also decreased by lycopene administration. It is concluded that pre-, continuous and post-radiation administration of lycopene protects against radiation injury of the small intestine and accelerate the recovery. (author)

  8. Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature

    Directory of Open Access Journals (Sweden)

    Abbaszadeh A.

    2017-06-01

    Full Text Available Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/ biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses

  9. Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

    International Nuclear Information System (INIS)

    Li Guanghui; Zhang Yaping; Tang Jinliang; Chen Zhengtang; Hu Yide; Wei Hong; Li Dezhi; Hao Ping; Wang Donglin

    2010-01-01

    Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-α, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-α, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.

  10. PAI-1-dependent endothelial cell death determines severity of radiation-induced intestinal injury.

    Directory of Open Access Journals (Sweden)

    Rym Abderrahmani

    Full Text Available Normal tissue toxicity still remains a dose-limiting factor in clinical radiation therapy. Recently, plasminogen activator inhibitor type 1 (SERPINE1/PAI-1 was reported as an essential mediator of late radiation-induced intestinal injury. However, it is not clear whether PAI-1 plays a role in acute radiation-induced intestinal damage and we hypothesized that PAI-1 may play a role in the endothelium radiosensitivity. In vivo, in a model of radiation enteropathy in PAI-1 -/- mice, apoptosis of radiosensitive compartments, epithelial and microvascular endothelium was quantified. In vitro, the role of PAI-1 in the radiation-induced endothelial cells (ECs death was investigated. The level of apoptotic ECs is lower in PAI-1 -/- compared with Wt mice after irradiation. This is associated with a conserved microvascular density and consequently with a better mucosal integrity in PAI-1 -/- mice. In vitro, irradiation rapidly stimulates PAI-1 expression in ECs and radiation sensitivity is increased in ECs that stably overexpress PAI-1, whereas PAI-1 knockdown increases EC survival after irradiation. Moreover, ECs prepared from PAI-1 -/- mice are more resistant to radiation-induced cell death than Wt ECs and this is associated with activation of the Akt pathway. This study demonstrates that PAI-1 plays a key role in radiation-induced EC death in the intestine and suggests that this contributes strongly to the progression of radiation-induced intestinal injury.

  11. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

    International Nuclear Information System (INIS)

    Cheng, Jian; Zhang, Lin; Dai, Weiqi; Mao, Yuqing; Li, Sainan; Wang, Jingjie; Li, Huanqing; Guo, Chuanyong; Fan, Xiaoming

    2015-01-01

    Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys 3 ]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation

  12. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jian; Zhang, Lin [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Dai, Weiqi [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Mao, Yuqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Li, Sainan [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Wang, Jingjie; Li, Huanqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Guo, Chuanyong [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Fan, Xiaoming, E-mail: xiaomingfan57@sina.com [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China)

    2015-02-27

    Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.

  13. Analysis of changes in intestinal microflora of irradiated mice. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mal' tsev, V.N.; Pinegin, B.V.; Korshunov, V.M.

    1977-01-01

    In experiments on 3 groups of CBA mice exposed to doses of 900, 600 and 300 R ..gamma..-rays, it was demonstrated that the integral severity of post-radiation microflora in the intestine can be determined by means of information index h, which takes into consideration all changes occurring in different representatives of the intestinal microflora. Differential analysis of the mechanisms of radioinduced changes in microflora indicates that it is based on a decrease in lactobacilli and increase in enterococcus, proteus, colibacillus and yeast in the small intestine, with increase in colibacillus, clostridia, proteus and enterococcus in the large intestine.

  14. Irf4-dependent CD103+CD11b+ dendritic cells and the intestinal microbiome regulate monocyte and macrophage activation and intestinal peristalsis in postoperative ileus

    DEFF Research Database (Denmark)

    Pohl, Judith Mira; Gutweiler, Sebastian; Thiebes, Stephanie

    2017-01-01

    and large intestinal POI suggested a potential role of the intestinal microbiota. Indeed, antibiotic treatment reduced iNOS levels and ameliorated POI. Conclusions: Our findings reveal that CD103+CD11b+ DCs and the intestinal microbiome are a prerequisite for the activation of intestinal monocytes...

  15. Radioprotective effects of sodium arginate on radiation induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Nakatsugawa, Shigekazu; Yukawa, Yutaka; Abe, Mitsuyuki.

    1988-05-01

    Effects of sodium arginate were examined on radiation-induced intestinal death of mice and on the pathological changes of the ileum after whole or partial abdominal X-irradiation. BALB/c male mice (SPF, 7 approx. 8 week old, 21 approx. 28 g body weight) were irradiated with various doses of 10 MV of X-rays under general anesthesia (dose rate : 4 Gy/min). A radiation field covers either 2.5 or 5.0 cm width of abdomen from the anus. Sterilized water or 5 % sodium arginate solution (0.2 ml/body) was daily given per os through a stomach tube until the death of mice or 15 approx. 21 days after X-ray exposure. Intestinal death was examined daily. In another experiment, mice were daily sacrificed and pathological specimens were made. In order to study the effects of sodium arginate on peripheral blood circulation in the ileum after X-ray exposure, the microangiograms with Ba contrast media were also taken. Sodium arginate showed statistically significant radioprotective effects on intestinal death after 14.5 approx. 15.0 Gy of X-ray irradiation to the abdomen through a radiation field of 5.0 cm width or after 18.0 Gy of X-irradiation to the abdomen through a field of 2.5 cm width. The pathological studies suggest that the drug may protect the surface of the intestine against infection and potentiate the recovery processes of the mucosal membrane. This may elucidate the possible mechanisms of radioprotective effects of sodium arginate on esophagitis or on rectal ulcer induced by radiotherapy.

  16. Radiation-induced intestinal lesions. Prognosis and surgical management

    International Nuclear Information System (INIS)

    Van Haecke, P.; Vitaux, J.; Michot, F.; Hay, J.-M.; Flamant, Y.; Maillard, J.-N.

    1981-01-01

    Thirteen patients with intestinal lesions consecutive to radiotherapy for carcinoma of the uterus were operated upon between 1973 and 1979. The small bowel was involved in 9 patients and the colon and rectum in 4 patients. Urinary tract lesions were associated in 3 patients of each group. Intestinal necrosis, progression of the lesions and extensive pelvic fibrosis were the only criteria of poor prognosis. Twenty-two operations were performed: 4 for urinary tract lesions and 18 for intestinal lesions. Five patients died during the immediate post-operative period and five died within 2 to 30 months after surgery, including 4 whose carcinoma recurred. The operative technique should be selected according to the extent and severity of radiation-induced damage, as determined by pre-operative examination and thorough exploration of the abdominal cavity once opened. Limited lesions of the small bowel can be treated by resection, but intestinal bypass with latero-lateral anastomosis seems to be preferable in cases with extensive lesions. Patients with colorectal lesions should have defunctioning colostomy prior to any other procedure dictated by the state of affairs. Multiple anastomosis, extensive resections and excessive dissections should be avoided [fr

  17. Prophylactic treatment with a potent corticosteroid cream ameliorates radiodermatitis, independent of radiation schedule

    DEFF Research Database (Denmark)

    Ulff, Eva; Maroti, Marianne; Serup, Jörgen

    2017-01-01

    BACKGROUND AND PURPOSE: The study will test the hypothesis that preventive topical steroid treatment instituted from start of radiotherapy can ameliorate acute radiation dermatitis. Subgroups of increased risk of dermatitis are included. MATERIAL AND METHODS: A double blinded randomized trial...... of acute radiation dermatitis in breast cancer patients treated with adjuvant RT, independent of RT schedule. Preventive application of a potent corticosteroid cream should be used in the routine and instituted at the start of RT....... schedules as well as for anatomical sites, skin type, breast size and BMI. Patients treated the irradiated area during the radiation period and two weeks following cessation of radiation. RESULTS: Patients receiving hypofraction RT developed less skin reactions than those treated with conventional RT...

  18. Natural compound methyl protodioscin protects against intestinal inflammation through modulation of intestinal immune responses

    OpenAIRE

    Zhang, Rongli; Gilbert, Shila; Yao, Xinsheng; Vallance, Jefferson; Steinbrecher, Kris; Moriggl, Richard; Zhang, Dongsheng; Eluri, Madhu; Chen, Haifeng; Cao, Huiqing; Shroyer, Noah; Denson, Lee; Han, Xiaonan

    2015-01-01

    Dioscoreaceae, a kind of yam plant, has been recommended for treatment of chronic inflammatory conditions. However, the mechanisms are poorly defined. Methyl protodioscin (MPD) is one of the main bioactive components in Dioscoreaceae. Here, we aim to determine the mechanisms by which MPD ameliorates intestinal inflammation. Surgical intestinal specimens were collected from inflammatory bowel diseases (IBD) patients to perform organ culture. Experimental colitis was induced in mice by dextran ...

  19. The influence of the microbial factor on the death of animals by intestinal radiation syndrome

    International Nuclear Information System (INIS)

    Kudryavtsev, V.D.; Kartasheva, A.L.; Tsyran, N.I.

    1979-01-01

    Data obtained in rats and mice irradiated with 900 - 1600 rad 60 Co gamma radiation point to an important role of the microbial factor in the 'intestinal death'. At the climax of the intestinal syndrome dysbacterial conditions developed violently in the intestinal content under predominance of putrefactive bacteria (Proteus). The application of kanamycin according to an elaborated pattern completely suppressed the proteus growth in the intestine and decreased considerably the content of obligatory representatives of the intestinal flora by which most of the animals could survive the time of 'intestinal death' (3rd to 5th day) after irradiation with relatively low doses (900 - 1200 rad). With increasing radiation doses (up to 1400 rad and more) the antibacterial therapy became uneffective because of the increasing importance of other lethal factors. The analysis of these results as well as literature data allow the conclusion that microbial intoxication plays a leading role in the death of the animals at the initial period and at the climax of the intestinal syndrome (3rd to 4th day). At the final stage of the development of the intestinal syndrome (5th day) septicaemia supervened. (author)

  20. Lack of protective effect of thromboxane synthetase inhibitor (CGS-13080) on single dose radiated canine intestine

    International Nuclear Information System (INIS)

    Barter, J.F.; Marlow, D.; Kamath, R.K.; Harbert, J.; Torrisi, J.R.; Barnes, W.A.; Potkul, R.K.; Newsome, J.T.; Delgado, G.

    1991-01-01

    The effect of a thromboxane A2 synthetase inhibitor (CGS-13080) on canine intestine was studied using a single dose of radiation, and radioactive microspheres were used to determine resultant blood flow. Thromboxane A2 causes vasospasm and platelet aggregation and may play a dominant role in radiation injury. However, there was no effect on the intestinal blood flow diminution occurring after radiation in this laboratory model using this thromboxane A2 synthetase inhibitor

  1. Surgical treatment of intestinal radiation injury

    International Nuclear Information System (INIS)

    Maekelae, J.Ne.; Nevasaari, K.; Kairaluoma, M.I.

    1987-01-01

    A review of 43 consecutive patients requiring operation for serious intestinal radiation injury was undertaken to elucidate the efficacy of surgical treatment. The most common site of radiation injury was the rectum (19 cases), followed by the small bowel (13 cases), the colon (7 cases), and the combination of these (4 cases). The overall operative mortality was 14%; morbidity, 47%; and the postoperative symptom-free period, 18 +/- 30 months. Colostomy (N = 20) carried the lowest risk of mortality, 0%, as compared with resection (N = 17) and bypass procedure (N = 6), which were accompanied by the mortalities of 24% and 33%, respectively. During the follow-up (3-13 years) 12 patients (28%) died of recurrent cancer and 9 patients (21%) of persistent radiation injury, which yielded an overall mortality of 65% after resection and 50% and 65% after bypass and colostomy procedures, respectively. Continuing radiation damage led to 15 late reoperations. Ten of these were performed after colostomy, four after resection, and one after bypass. We conclude that colostomy cannot be regarded as a preferred operative method, because it does not prevent the progression of radiation injury and because it is, for this reason, associated with a higher late-complication rate. A more radical surgery is recommended but with the limitation that the operative method must be adapted to the operative finding

  2. Caffeine ameliorates radiation-induced skin reactions in mice but does not influence tumour radiation response

    Energy Technology Data Exchange (ETDEWEB)

    Hebbar, S.A.; Mitra, A.K.; George, K.C.; Verma, N.C. [Radiation Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India)]. E-mail: ncverma@apsara.barc.ernet.in

    2002-03-01

    Intramuscular administration of caffeine at a dose of 80 mg kg{sup -1} body weight to the gastrocnemius muscles of Swiss mice 5 min prior to local irradiation (35 Gy) of the leg delayed the progression of radiation-induced skin reactions in such animals. While 90% epilation with reddening of the skin was noted in animals treated with radiation alone, animals pretreated with caffeine suffered only partial hair loss with slight reddening of the skin on the 16th and 20th days post-irradiation. Beyond the 28th day, damage scores in irradiated feet for both the groups were similar (score 3) and remained unchanged until the 32nd day and then decreased and disappeared completely in both treatment groups by the 40th day after irradiation. In addition, the effect of caffeine on the radiation response of a mouse fibrosarcoma was investigated. Results showed that intratumoral administration of caffeine at a dose of 80 mg kg{sup -1} body weight 5 min prior to local exposure of tumours to 10 Gy of {sup 60}Co {gamma}-rays did not influence the response of tumours to radiation. The present study thus showed that although caffeine ameliorated radiation-induced skin reactions in the mouse leg, it did not affect the tumour radiation response, indicating its potential application in cancer radiotherapy. (author)

  3. Intestinal cell proliferation following hyperthermia-radiation combinations

    International Nuclear Information System (INIS)

    Burholt, D.R.; Wilkinson, D.A.; Shrivastava, P.N.

    1987-01-01

    The present work is an investigation of the extent to which hyperthermia enhances x-ray induced inhibition of intestinal epithelial cell proliferation in mice. Hyperthermia was achieved by whole body immersion of anesthetized ice in a temperature controlled water bath (+-0.1 0 C). Post-treatment proliferative activity was monitored by determining the incorporation of /sup 3/H-TdR into intestinal crypt cells and by the counting of epithelial cell mitotic figures. Initial levels of cell kill were assessed by the microcolony crypt survival technique. All heat treatments were 41.5 0 C for 0.5h. Heat alone reduced the /sup 3/H-TdR incorporation to 50% of the control value by 2h post-treatment. This was followed by a return to control value by 10h and a slight hyperplasia at 24h. Heat either immediately before or after 2Gy abdominal field x-irradiation produced a prolonged period of depressed cell proliferation: /sup 3/H-TdR incorporation remained below control value for the first 24h. As the heat and radiation were separated in time from each other (up to 4h) the interaction between the two decreased. The development of thermotolerance was observed following the second and third treatment during either a heat-only or a heat-radiation multifraction treatments schedule with the treatment spaced 24h apart

  4. Mechanism for radiation-induced damage via TLR3 on the intestinal epithelium

    International Nuclear Information System (INIS)

    Takemura, Naoki; Uematsu, Satoshi

    2014-01-01

    When the small-intestinal epithelium is injured due to high-dose radiation exposure, radiation-induced gastrointestinal syndrome (GIS) such as absorption inhibition and intestinal bacterial infection occurs, and lead to subacute death. The authors immunologically analyzed the disease onset mechanism of GIS. In the small-intestinal mucosal epithelium, the intestinal epithelial stem cells of crypt structure and their daughter cells are renewed through proliferation and differentiation in the cycle of 3 or 4 days. When DNA is damaged by radiation, although p53 gene stops cell cycle and repairs DNA, cell death is induced if the repair is impossible. When stem cells perish, cell supply stops resulting in epithelial breakdown and fatal GIS. The authors analyzed the involvement in GIS of toll-like receptor (TLR) with the function of natural immunity, based on lethal γ-ray irradiation on KO mice and other methods. The authors found the mechanism, in which RNA that was leaked due to cell death caused by p53 gene elicits inflammation by activating TLR3, and leads to GIS through a wide range of cell death induction and stem cell extinction. The administration of a TLR3/RNA binding inhibitor before the irradiation of mice decreased crypt cell death and greatly improved survival rate. The administration one hour after the irradiation also showed improvement. The administration of the TLR3 specific inhibitor within a fixed time after the exposure is hopeful for the prevention of GIS, without affecting the DNA repair function of p53 gene. (A.O.)

  5. Clinical report of one case of intestinal form of acute radiation sickness

    International Nuclear Information System (INIS)

    Yu Changlin; Qiao Jianhui; Luo Weidong; Guo Mei; Wang Danhong; Sun Qiyun; Zhang Shi; Chen Jiankui; Li Xiaobing; Ai Huisheng

    2007-01-01

    Objective: To summarize the irradiation course, estimation of radiation dosage, clinical course, diagnosis and treatment of the patient A in a 60 Co radiation accident on October 21, 2004 in Jining, Shandong Province, China. Methods: According to the simulated test of the scene, chromosome aberration analysis, clinical course and tooth enamel ESR measurement, the total body dose of A was 20-25 Gy and diagnosed as intestinal form of acute radiation sickness. The patient was transferred to our hospital on day 3 post- irradiation, total environmental protection (TEP), antibiotics and emergency HLA-typing from his elder sister were given. On day 7 HLA haplo-identical peripheral blood stem cell transplantation was performed. Results: On day 10 post-transplant (+ 10 d), the counts of WBC began to increase and up to 5.1 x 10 9 /L on + 12 d. Bone marrow feature showed hematopoietic recovery of the three lineage blood cells. Continuous detection of the implantation ratio of donor's cells by STR-PCR showed stable 100% donor-derived chimera. On day 13, severe acute peritonitis and intestinal obstruction occurred; imipenem was much effective to control intestinal bacteria infection. Three days later, hematopoiesis reconstructed rapidly, peritonitis and intestinal obstruction were cured. On day 19, chest X-ray picture and CT scanning suggested that pulmonary mixed infection of bacteria and fungi appeared. The most severe skin irradiation burn damage occurred on day 25 which occupied the 14% of whole body skin surface. The functions of lung, heart and kidney were deteriorated sequentially. On day 30, tracheotomy had to be conducted and respirator was used. The patient died of multiple organ failure (MOF) on day 33. Conclusions: Patient A was exposed to relative well-distributed high dose and high dose rate of irradiation up to 20-25 Gy. This is the first case report of successful HLA haplo-identical peripheral blood stem cell transplantation for intestinal form of acute

  6. Low and high dose rate heavy ion radiation-induced intestinal and colonic tumorigenesis in APC1638N/+ mice

    Science.gov (United States)

    Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Fornace, Albert J.; Datta, Kamal

    2017-05-01

    Ionizing radiation (IR) is a recognized risk factor for colorectal cancer (CRC) and astronauts undertaking long duration space missions are expected to receive IR doses in excess of permissible limits with implications for colorectal carcinogenesis. Exposure to IR in outer space occurs at low doses and dose rates, and energetic heavy ions due to their high linear energy transfer (high-LET) characteristics remain a major concern for CRC risk in astronauts. Previously, we have demonstrated that intestinal tumorigenesis in a mouse model (APC1638N/+) of human colorectal cancer was significantly higher after exposure to high dose rate energetic heavy ions relative to low-LET γ radiation. The purpose of the current study was to compare intestinal tumorigenesis in APC1638N/+ mice after exposure to energetic heavy ions at high (50 cGy/min) and relatively low (0.33 cGy/min) dose rate. Male and female mice (6-8 weeks old) were exposed to either 10 or 50 cGy of 28Si (energy: 300 MeV/n; LET: 70 keV/μm) or 56Fe (energy: 1000 MeV/n; LET: 148 keV/μm) ions at NASA Space Radiation Laboratory in Brookhaven National Laboratory. Mice (n = 20 mice/group) were euthanized and intestinal and colon tumor frequency and size were counted 150 days after radiation exposure. Intestinal tumorigenesis in male mice exposed to 56Fe was similar for high and low dose rate exposures. Although male mice showed a decreasing trend at low dose rate relative to high dose rate exposures, the differences in tumor frequency between the two types of exposures were not statistically significant after 28Si radiation. In female mice, intestinal tumor frequency was similar for both radiation type and dose rates tested. In both male and female mice intestinal tumor size was not different after high and low dose rate radiation exposures. Colon tumor frequency in male and female mice after high and low dose rate energetic heavy ions was also not significantly different. In conclusion, intestinal and colonic tumor

  7. Radiation-induced intestinal neoplasia in a genetically-predisposed mouse (Min)

    International Nuclear Information System (INIS)

    Ellender, M.; Larder, S.M.; Harrison, J.D.; Cox, R.; Silver, A.R.J.

    1997-01-01

    A mouse lineage with inherited predisposition to multiple intestinal neoplasia (min) has been proposed as a model to study human colorectal cancer. Min mice are heterozygous for the adenomatous polyposis coli (Apc) gene implicated in human familial adenomatous polyposis (FAP). There is an increased risk of intestinal cancer in humans following radiation exposure and the min mouse model may be used to further our understanding of the molecular mechanisms involved. The present study showed a 2 Gy dose of x-rays doubles the tumour numbers in the murine gastrointestinal tract of F1 min heterozygotes. The distribution of tumours through the gut was also recorded. (authors)

  8. Protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury

    International Nuclear Information System (INIS)

    Shi, Jing; Wang, Lan; Lu, Yan; Ji, Yue; Wang, Yaqing; Dong, Ke; Kong, Xiangqing; Sun, Wei

    2017-01-01

    Radiation-induced gastrointestinal syndrome, including nausea, diarrhea and dehydration, contributes to morbidity and mortality after medical or industrial radiation exposure. No safe and effective radiation countermeasure has been approved for clinical therapy. In this study, we aimed to investigate the potential protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury. C57/BL6 mice were orally administered seabuckthorn pulp oil, seed oil and control olive oil once per day for 7 days before exposure to total-body X-ray irradiation of 7.5 Gy. Terminal deoxynucleotidyl transferase dUTP nick end labeling, quantitative real-time polymerase chain reaction and western blotting were used for the measurement of apoptotic cells and proteins, inflammation factors and mitogen-activated protein (MAP) kinases. Seabuckthorn oil pretreatment increased the post-radiation survival rate and reduced the damage area of the small intestine villi. Both the pulp and seed oil treatment significantly decreased the apoptotic cell numbers and cleaved caspase 3 expression. Seabuckthorn oil downregulated the mRNA level of inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8. Both the pulp and seed oils elevated the level of phosphorylated extracellular-signal-regulated kinase and reduced the levels of phosphorylated c-Jun N-terminal kinase and p38. Palmitoleic acid (PLA) and alpha linolenic acid (ALA) are the predominant components of pulp oil and seed oil, respectively. Pretreatment with PLA and ALA increased the post-radiation survival time. In conclusion, seabuckthorn pulp and seed oils protect against mouse intestinal injury from high-dose radiation by reducing cell apoptosis and inflammation. ALA and PLA are promising natural radiation countermeasure candidates.

  9. Intestinal ameliorative effects of traditional Ogi-tutu, Vernonia ...

    African Journals Online (AJOL)

    tutu, Vernonia amygdalina and Psidium guajava on intestinal histopathology of experimental mice infected with V. cholerae. Methods: Preliminary investigation of in vitro vibriocidal activities of these alternatives were carried out using agar cup ...

  10. Radiation, an ideal cytotoxic for the study of cell biology in the small intestine

    International Nuclear Information System (INIS)

    Potten, C.

    2003-01-01

    Epithelial tissues are highly polarised with the proliferative compartment sometimes subdivided into units of proliferation in many instances. My interests have been in trying to understand how many cellular constituents exist, what their function is and intercommunicants are that ensure appropriate steady state cell replacement rates. Radiation has proved to be a valuable tool to induce cell death, reproductive sterilisation, and regenerative proliferation in these systems, the responses to which can provide information on the number of regenerative cells (a function associated with stem cells). Such studies have helped define the epidermal proliferative units and the structurally similar units on the dorsal surface of the tongue. The radiation responses considered in conjunction with a wide range of cell kinetic lineage tracking and somatic mutation studies with complex mathematical modelling, provide insights into the functioning of the poliferative units (crypts) of the small intestine. Comparative studies have then been undertaken with the crypts in the large bowel. In the small intestine, which rarely develops cancer, various protective mechanisms have evolved to ensure the genetic integrity of the stem cell compartment. Stem cells in the small intestinal crypts have an intolerance of genotoxic damage (including that induced by very low doses of radiation), they do not undergo cell cycle arrest and repair but commit an altruistic p53 dependent cell suicide (apoptosis). This process is compromised in the large bowel by bcl-2 expression. Recent studies have suggested a second genome protection mechanism operating in the stem cells of the small intestinal crypts that may also have a p53 dependence. Such studies have allowed the cell lineages and genome protection mechanisms operating in the small intestinal crypts to be defined

  11. Is the use of antioxidants mixture ameliorating the double stress effect of radiation and hyperlipidaemia?

    International Nuclear Information System (INIS)

    Michael, M.I.; Amer, M.M.

    2010-01-01

    Radiation hazards, due to free radical generation, present an enormous challenge for biological and medical safety. In the same time, hyperlipidaemia represents one of the most important and recognized risk factor for atherosclerosis development as an event of accumulation of cells containing excess lipids within the arterial wall. Under normal physiological conditions, there is a critical balance in the generation of oxygen free radicals and antioxidant defense systems. In this study, we assumed that a subject encountered to both radiation and hyperlipidaemia oxidative stress and inquired if a mixture of three well known antioxidants can ameliorate this dramatically disorder. To answer the question, four groups of adult male albino rats were used; the control group (A) fed and drank ad libitum normal laboratory diet, the second group (B) fed normally and exposed to 5 Gy gamma radiation, the third group (C) fed high-fat diet (HFD) for two months then exposed to the same dose of radiation and the fourth group (D) subjected to the same treatment as group (C) and administrated a mixture of tryptophan (100 mg/kg b.w.), hawthorn extract (50 mg/100 g b.w.) and coenzyme Q10 (50 mg/kg b.w.) for one month. Body weight was recorded twice a week during the experimental period then all the animals were decapitated after one month and sera were collected to estimate total lipids, triglycerides, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), T3, T4, testosterone and corticosterone hormones besides glutathione. The results declared that radiation-hyperlipidaemia double stressors inadequately distorted the lipogram, hormonal and antioxidant status and the antioxidants mixture administrated could ameliorate these alterations and successfully brought back all the parameters investigated nearly to the control level.

  12. Inhibition of Epithelial TNF-α Receptors by Purified Fruit Bromelain Ameliorates Intestinal Inflammation and Barrier Dysfunction in Colitis.

    Science.gov (United States)

    Zhou, Zijuan; Wang, Liang; Feng, Panpan; Yin, Lianhong; Wang, Chen; Zhi, Shengxu; Dong, Jianyi; Wang, Jingyu; Lin, Yuan; Chen, Dapeng; Xiong, Yongjian; Peng, Jinyong

    2017-01-01

    Activation of the TNF-α receptor (TNFR) leads to an inflammatory response, and anti-TNF therapy has been administered to reduce inflammation symptoms and heal mucosal ulcers in inflammatory bowel disease (IBD). Bromelain, a complex natural mixture of proteolytic enzymes, has been shown to exert anti-inflammatory effects. This study aimed to investigate the effect of purified fruit bromelain (PFB)-induced inhibition of epithelial TNFR in a rat colitis model. Colitis was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Expression of TNFR1 and TNFR2 was measured by quantitative RT-PCR and western blotting. The effect of PFB on colitis was evaluated by examining the inflammatory response and intestinal epithelial barrier function. Our results showed that both TNFR1 and TNFR2 expression were significantly increased in a colitis model, and the increase was significantly reversed by PFB. Colitis symptoms, including infiltration of inflammatory cells, cytokine profiles, epithelial cell apoptosis, and epithelial tight junction barrier dysfunction were significantly ameliorated by PFB. Compared with fruit bromelain and stem bromelain complex, the inhibition of TNFR2 induced by PFB was stronger than that exhibited on TNFR1. These results indicate that PFB showed a stronger selective inhibitory effect on TNFR2 than TNFR1. In other words, purification of fruit bromelain increases its selectivity on TNFR2 inhibition. High expression of epithelial TNFRs in colitis was significantly counteracted by PFB, and PFB-induced TNFR inhibition ameliorated colitis symptoms. These results supply novel insights into potential IBD treatment by PFB.

  13. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    International Nuclear Information System (INIS)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G.; Castiglione, F.; Vanzi, E.; Bottoncetti, A.; Pupi, A.

    2011-01-01

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation

  14. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

    2011-10-15

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation

  15. Effects of Radiation on the Microbiota and Intestinal Inflammatory Disease

    Science.gov (United States)

    2017-09-01

    for immune cells associated with the intestine and their interactions with the normal microbial contents of the gut . 2. KEYWORDS Radiation, microbiome ...focal RT on bact/fung microbiota (COMPLETED) ☑Analysis: microbiome changes in irradiated guts + DSS (COMPLETED) CY17 Goal – RT-induced changes in gut ...sensitivity qAnalysis of microbiome changes in irradiated guts in other colitis models and infectious organisms (In Progress) qAnalysis of effects of

  16. Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young [Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwon, Kang-Beom [Department of Oriental Medical Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwak, Tae Hwan [PAEAN Biotechnology, 160 Techno-2 Street, Yuseong-gu, Daejeon 305-500 (Korea, Republic of); Choe, Seong-Kyu; Park, Raekil [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2015-11-27

    Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD{sup +}) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD{sup +} in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD{sup +} levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD{sup +} levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage. - Highlights: • NAD{sup +} acts as a cofactor for numerous enzymes including Sirtuins and PARP. • Up-regulation of SIRT1 could attenuate the cisplatin-induced intestinal damage. • Modulation of the cellular NAD{sup +} could be a promising therapeutic approach.

  17. Evidence from Animal Models: Is a Restricted or Conventional Intestinal Microbiota Composition Predisposing to Risk for High-LET Radiation Injury?

    Science.gov (United States)

    Maier, Irene; Schiestl, Robert H

    2015-06-01

    Intestinal microbiota affect cell responses to ionizing radiation at the molecular level and can be linked to the development of the immune system, controlled cell death or apoptosis. We have developed a microbiota mouse model and report here that high-linear energy transfer (LET) radiation induced the repair of chromosomal DNA lesions more efficiently in conventional than in restricted intestinal microbiota mice. Based on different phylotype densities after whole-body irradiation, bacterial indicator phylotypes were found to be more abundant in restricted in microbiota than in conventional microbiota. Genotoxic phenotypes of irradiated restricted and conventional microbiota mice were compared with ataxia telangiectasia-deficient restricted and conventional microbiota mice, respectively. Those indicator phylotypes, including Bacteroides (Gram-negative bacterium cTPY-13), Barnesiella intestinihominis and others, which were identified in nonirradiated restricted microbiota mice, increase in radiation-exposed conventional microbiota along with a reduction of persistent DNA double-strand breaks in blood lymphocytes. The dynamic change of phylotype abundances elucidated a feedback mechanism and effect of intestinal microbiota composition on the adaptive response to high-LET radiation. Several other bacterial phylotypes ( Helicobacter hepaticus , Helicobacter spp and others) were found to be more abundant in conventional than restricted microbiota. In this commentary, mouse models used in cancer research and radiotherapy for the study on the effects of intestinal microbiota composition on normal tissue radiation response are characterized and discussed. Highlights of this commentary: 1. Restricted microbiota phylotypes were correlated with persistent DNA double-strand breaks (DSBs) and were found to orchestrate onco-protective controlled cell death after radiation; 2. Restricted microbiota composition reduced proinflammatory extracellular-stimulated immune responses, but

  18. Examinations on cases of surgery for radiation-induced disorders of large intestine

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Tadaaki [Toho Univ., Tokyo (Japan). School of Medicine

    1996-11-01

    Author`s experience of surgery for radiation colitis was examined and discussed on the primary disease, radiation dose, major symptoms, surgical techniques, results and post-operative complication. Patients were 1 male and 21 females of the average age of 59.5 y. The primary diseases were bladder cancer for the male and uterine cancer for the females. The radiation dose ranged from 35-120 Gy and was 63.4 Gy in a mean. The symptoms for surgery were 14 ileuses, 4 intestinal hemorrhages, 1 perforation and 3 burrows. Colostomy was performed for 18 cases; enterostomy, 2; anastomosis, 1; and enterectomy, 1, which resulted in improvement of symptoms in 5 cases, 0, 1 and 1, respectively. The author concluded that radiation colitis should be treated preventively. (K.H.)

  19. Consequences of PAI-1 specific deletion in endothelium on radiation-induced intestinal damage

    International Nuclear Information System (INIS)

    Rannou, Emilie

    2015-01-01

    Radiation-induced injury to healthy tissues is a real public health problem, since they are one of the most limiting factors that restrict efficiency of radiation therapy. This problematic is also part of the French Cancer Plan 2014-2017, and involves clinical research. Concepts surrounding the development of radiation-induced damage have gradually evolved into a contemporary and integrated view of the pathogenesis, involving all compartments of target tissue. Among them, endothelium seems to be central in the sequence of interrelated events that lead to the development of radiation-induced damage, although there are rare concrete elements that support this concept. By using new transgenic mouse models, this PhD project provides a direct demonstration of an endothelium-dependent continuum in evolution of radiation-induced intestinal damage. Indeed, changes in the endothelial phenotype through targeted deletion of the gene SERPINE1, chosen because of its key role in the development of radiation enteritis, influences various parameters of the development of the disease. Thus, lack of PAI-1 secretion by endothelial cells significantly improves survival of the animals, and limits severity of early and late tissue damage after a localized small bowel irradiation. Furthermore, these mice partially KO for PAI-1 showed a decrease in the number of apoptotic intestinal stem cells in the hours following irradiation, a decrease in the macrophages infiltrate density one week after irradiation, and a change in the polarization of macrophages throughout the pathophysiological process. In an effort to protect healthy tissues from radiation therapy side effects, without hindering the cancer treatment, PAI-1 seems to be an obvious therapeutic target. Conceptually, this work represents the direct demonstration of the link between endothelium phenotype and radiation enteritis pathogenesis. (author)

  20. Salvia officinalis l. (sage) Ameliorates Radiation-Induced Oxidative Brain Damage In Rats

    International Nuclear Information System (INIS)

    Osman, N. N.; Abd El Azime, A.Sh.

    2013-01-01

    The present study was designed to investigate the oxidative stress and the role of antioxidant system in the management of gamma irradiation induced whole brain damage in rats . Also, to elucidate the potential role of Salvia officinalis (sage) in alleviating such negative effects. Rats were subjected to gamma radiation (6 Gy). Sage extract was daily given to rats during 14 days before starting irradiation and continued after radiation exposure for another 14 days. The results revealed that the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC) and nitric oxide (NO) content were significantly increased, while the activities of superoxide dismutase (SOD) and catalase (CAT) as well as the reduced glutathione (GSH) content were significantly decreased in the brain homogenate of irradiated rats. Additionally, brain acetylcholinesterase (AChE) as well as alkaline phosphatase (ALP), acid phosphatase (ACP) and lactate dehydrogenase (LDH) activities were significantly increased. On the other hand, the results showed that, administration of sage extract to rats was able to ameliorate the mentioned parameters and the values returned close to the normal ones. It could be concluded that sage extract, by its antioxidant constituents, could modulate radiation induced oxidative stress and enzyme activities in the brain.

  1. Amelioration of radiation induced oxidative stress using water soluble chitosan produced by Aspergillus niger

    International Nuclear Information System (INIS)

    EL-Sonbaty, S.M.; Swailam, H.M.; Noaman, E.

    2012-01-01

    Chitosan is a natural polysaccharide synthesized by a great number of living organisms and considered as a source of potential bioactive material and has many biological applications which are greatly affected by its solubility in neutral ph. In this study low molecular weight water soluble chitosan was prepared by chemical degradation of chitosan produced by Aspergillus niger using H 2 O 2 . Chitosan chemical structure was detected before and after treatment using FTIR spectrum, and its molecular weight was determined by its viscosity using viscometer. Its antioxidant activity against gamma radiation was evaluated in vivo using rats. Rats were divided into 4 groups; group 1: control, group 2: exposed to acute dose of gamma radiation (6 Gy), group 3: received water soluble chitosan, group 4: received water soluble chitosan then exposed to gamma radiation as group 2. Gamma radiation significantly increased malonaldehyde, decreased glutathione concentration, activity of superoxide dismutase, catalase, and glutatione peroxidase, while significantly increase the activity of alanine transferase, aspartate transferase, urea and creatinine concentration. Administration of water soluble chitosan has ameliorated induced changes caused by gamma radiation. It could be concluded that water soluble chitosan by scavenging free radicals directly or indirectly may act as a potent radioprotector against ionizing irradiation.

  2. Influence of intestinal early enteral nutrition therapy on intestinal barrier function and immune response of patients with radiation enteritis

    International Nuclear Information System (INIS)

    Liu Guohui; Kang Xin; Chen Gong; Wang Guangyi

    2012-01-01

    Objective: To investigate the influence of early enteral nutrition therapy on the intestinal barrier function and immune response of the patients with radiation enteritis (ER) so as to find a relatively simple and effective method to treat RE. Methods: Fifty-six patients with radiation enteritis (RE) diagnosed by colonoscopy, X-rays, and pathology were randomly divided into 2 equal groups: experimental group undergoing enteral nutrition therapy, and control group undergoing conventional therapy only. Peripheral blood samples were collected 1, 11, and 21 days after admission. Plasma diamine oxidase (DAO), D-lactic acid, endotoxin, and lactulose/mannitol (L/M) ratio, and levels of IgG, IgM, and IgA, and CD4/CD8 ratio were examined. Five cases from the experimental group and 5 cases from the control group underwent second-time operation because of incomplete intestinal obstruction, intestinal stenosis, or recurrent tumor respectively. The biopsy specimens of the terminal ileum or distal descending colon taken during the first and second operations underwent pathological examination. Peripheral blood samples were collected 1, 11, and 21 days after admission. Plasma diamine oxidase (DAO), D-lactic acid, endotoxin, and lactulose/mannitol (L/M) ratio, and levels of IgG, IgM, and IgA, and CD4/CD8 ratio were examined. Results: There were no significant differences in the intestinal function and blood immunological indices between these 2 groups. The levels of DAO, D-lactic acid, and endotoxin,and the L/M ratio 11 days after admission of the experiment group were all significantly lower than those of the control group (t=2.568, 2.427, 2.143, 2.443, P<0.05), and all those indices 21 days after admission of the experiment group were all much more significantly lower in comparison with the control group (t=6.019, 12.834, 7.837, 7.997, P<0.01). The levels of IgG, IgM, and IgA, and CD4/CD8 ratio 11 days after admission of the experimental group were all significantly higher than

  3. A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

    Science.gov (United States)

    2016-08-01

    intestine epithelial response is built into the Radiation- Induced Performance Decrement (RIPD) model (Anno et al., 1989, Anno et al., 1991). RIPD, a...compartments, simulating dose response with a multitarget single -hit model (Joiner, 2009). This theory proposes that one hit of radiation in n different... single -hit model was implemented to represent dose response. The dose response parameters (D0 and n) were chosen to match experimental data approximated

  4. Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract

    International Nuclear Information System (INIS)

    Sinha, Mahuya; Das, Dipesh Kr; Dey, Sanjit; Datta, Sanjukta; Ghosh, Santinath

    2012-01-01

    Protective effect of Moringa oleifera leaf extract (MoLE) against radiation-induced lipid peroxidation has been investigated. Swiss albino mice, selected from an inbred colony, were administered with MoLE (300 mg/kg body wt) for 15 days before exposing to a single dose of 5 Gy 60 Co-gamma radiation. After treatments, animals were necropsied at different post irradiation intervals (days 1, 7 and 15) and hepatic lipid peroxidation and reduced glutathione (GSH) contents were estimated to observe the relative changes due to irradiation and its possible amelioration by MoLE. It was observed that, MoLE treatment restored GSH in liver and prevented radiation induced augmentation in hepatic lipid peroxidation. Phytochemical analysis showed that MoLE possess various phytochemicals such as ascorbic acid, phenolics (catechin, epicatechin, ferulic acid, ellagic acid, myricetin) etc., which may play the key role in prevention of hepatic lipid peroxidation by scavenging radiation induced free radicals. (author)

  5. TREM-1 Promotes Pancreatitis-Associated Intestinal Barrier Dysfunction

    Directory of Open Access Journals (Sweden)

    Shengchun Dang

    2012-01-01

    Full Text Available Severe acute pancreatitis (SAP can cause intestinal barrier dysfunction (IBD, which significantly increases the disease severity and risk of mortality. We hypothesized that the innate immunity- and inflammatory-related protein-triggering receptor expressed on myeloid cells-1 (TREM-1 contributes to this complication of SAP. Thus, we investigated the effect of TREM-1 pathway modulation on a rat model of pancreatitis-associated IBD. In this study we sought to clarify the role of TREM-1 in the pathophysiology of intestinal barrier dysfunction in SAP. Specifically, we evaluated levels of serum TREM-1 and membrane-bound TREM-1 in the intestine and pancreas from an animal model of experimentally induced SAP. TREM-1 pathway blockade by LP17 treatment may suppress pancreatitis-associated IBD and ameliorate the damage to the intestinal mucosa barrier.

  6. Preventing subclinical necrotic enteritis through Lactobacillus johnsonii BS15 by ameliorating lipid metabolism and intestinal microflora in broiler chickens.

    Science.gov (United States)

    Qing, Xiaodan; Zeng, Dong; Wang, Hesong; Ni, Xueqin; Liu, Lei; Lai, Jing; Khalique, Abdul; Pan, Kangcheng; Jing, Bo

    2017-12-01

    Increasing studies have focused on the beneficial effects of Lactobacillus johnsonii in certain diseases. Here, we studied the prevention ability of a probiotic strain, L. johnsonii BS15 on subclinical necrotic enteritis (SNE), and its underlying mechanism. 180 male Cobb 500 chicks were randomly allotted into three groups and administrated with BS15 (1 × 10 6 cfu/g) or Man Rogosa Sharpe liquid medium throughout a 28-day experimental period. With the exception of the normal group, SNE infection was treated for the remaining experimental period after the chicks were fed with normal diet 14 days. Results showed that BS15 notably suppressed the SNE-induced loss of average daily gain and liver functional abnormality. Additionally, BS15 facilitated lipid metabolism of SNE boilers when the contents of peroxisome proliferator activated receptor γ and adipose triglyceride lipase in adipose tissue and serum high-density lipoprotein cholesterol decreased. BS15 also attenuated the hepatic lipid accumulation of stricken chicks by suppressing the genes expression of acetyl-CoA carboxylase, fatty acid synthase and sterol regulatory element binding protein-1c as well as stimulating the genes expression of peroxisome proliferator activated receptor α and carnitine palmitoyltransferase-1. Moreover, BS15 enhanced the development of SNE gut by improving the intestinal development and digestion as well as adjusting the gut microflora. Therefore, BS15 may provide a promising natural preventative strategy against SNE, which may be contributed to the amelioration of lipid metabolism and intestinal microflora.

  7. Protective Role of R-spondin1, an Intestinal Stem Cell Growth Factor, against Radiation-Induced Gastrointestinal Syndrome in Mice

    OpenAIRE

    Bhanja, Payel; Saha, Subhrajit; Kabarriti, Rafi; Liu, Laibin; Roy-Chowdhury, Namita; Roy-Chowdhury, Jayanta; Sellers, Rani S.; Alfieri, Alan A.; Guha, Chandan

    2009-01-01

    Background Radiation-induced gastrointestinal syndrome (RIGS) results from a combination of direct cytocidal effects on intestinal crypt and endothelial cells and subsequent loss of the mucosal barrier, resulting in electrolyte imbalance, diarrhea, weight loss, infection and mortality. Because R-spondin1 (Rspo1) acts as a mitogenic factor for intestinal stem cells, we hypothesized that systemic administration of Rspo1 would amplify the intestinal crypt cells and accelerate the regeneration of...

  8. Amelioration of radiation stress by antioxidants and prooxidants: role of redox transcription factors

    International Nuclear Information System (INIS)

    Sandur, Santosh Kumar

    2011-01-01

    The development of radiation countermeasures has emerged as a major area of research in radiation biology as ionizing radiation is finding wide applications in power generation, agriculture, food processing, disease diagnosis and therapy. Chemical agents used to alter tissue toxicity of radiation can be broadly divided into three categories based on the time of intervention in relation to radiation. These are: radioprotectors, mitigators, and therapeutic agents. Radiation causes injury to normal tissue by a dynamic process involving generation of reactive oxygen species (ROS), their interactions with bio-molecules, intracellular signaling, cell-to-cell communication, inflammatory responses, tissue repair and cell death. Most of the radiation-induced damage to bio-molecules is caused by the formation of free radicals resulting from the radiolysis of water. However, antioxidants that neutralize free radicals failed to reach clinic. At present, no agent, approved by the U.S. Food and Drug Administration, is available for the treatment of acute radiation syndrome (ARS), although amifostine is approved for prophylaxis of dry mouth (xerostomia) from radiotherapy of head and neck cancers. Therefore, researchers are employing new approaches to ameliorate radiation induced injury. Some of these include use of cytokines, NF-κB (Nuclear factor κB) activators, agents that induce G1 arrest, antibiotics and inhibitors of P53. We have used pro-oxidants to upregulate cytoprotective pathways as a novel strategy to protect against radiation induced hematopoietic syndrome. Different prooxidants including hydrogen peroxide, diethylmaleate, t-butylhydroperoxide and naphthoquinone and its derivatives protected lymphocytes against radiation induced cell death. Further studies were carried out with 1,4-naphthoquinone (NQ) to explore the molecular mechanism of the observed protection. Thiol containing antioxidants abrogated NQ mediated radioprotection in lymphocytes. Addition of NQ to

  9. Protective Effect of Vitamin E against Gamma Radiation Injury in Mice Histological and Ultrastructural Studies

    International Nuclear Information System (INIS)

    Abu Nour, S.M.; Abd EI Azeem, M.G.

    2009-01-01

    Vitamin E has been shown to ameliorate the effect of ionising radiation. The present study was designed to study the effect of high dose of gamma-radiation on the intestinal tissue of mice and the protective effect of the natural antioxidant vitamin E; a slow acting free radical scavenger. 24 adult albino male mice were divided into 4 groups (6 animals each). The first group represents the control group. The second experimental group received orally daily doses of vitamin E (100 mg/ kg body wt for 15 days). The third experimental group were exposed to 7 Gy gamma-rays as a single dose, while the fourth experimental group received vitamin E in the same dose before being irradiated. All animals were scarified and jejunal specimens were processed and prepared for histological and ultrastructural study after one day post irradiation. The results suggested that gamma-radiation induced different histological changes in the intestine of irradiated animals. Degeneration of the intestinal cells and microvilli were seen by light microscopic examination. SEM electron microscope (SEM) revealed haemorrhagic ulcerating tissues. In addition, the mitochondria were markedly swollen and loss of cristae, thickness of the terminal web zone was seen by transmission electron microscope. On the contrary, in animals treated with vitamin E, the intestinal tissues revealed structure almost similar to the control group. We conclude that vitamin E had protective effects against gamma-radiation induced oxidative stress

  10. Quantitation of the late effects of x radiation on the large intestine

    International Nuclear Information System (INIS)

    Black, W.C.; Gomez, L.S.; Yuhas, J.M.; Kligerman, M.M.

    1980-01-01

    A model for quantitating late effects of x radiation on the large intestine utilizing the rectum of the Sprague-Dawley rat is reported. This model was constructed prefatory to establishing relative biological effectiveness for negative pions as a component of preclinical trials at the Clinton P. Anderson Meson Physics Facility. The endpoint involves microscopic evaluation of the severity of the experimental lesion, compared with surgically resected bowel lesions we have studied following clinical radiation exposure of the bowel. Individual components of the overall lesion include mucosal ulceration, a typical epithelial regeneration, colitis cystica profunda, fibrosis, and vascular sclerosis. Dose response curves were established for animals receiving 1, 2, 5 and 10 fractions with groups sacrificed at both four and 12 months after completion of radiation exposures

  11. Relation between radiation-induced tissue injury and its carcinogenesis of the rat small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Tsubouchi, S [Aichi Cancer Center, Nagoya (Japan). Research Inst.; Matsuzawa, T

    1975-06-01

    This study was undertaken to make clear the relationships between radiation-induced tissue injury and its carcinogenesis in the rat small intestine. The abdomens of Wistar rats were irradiated locally with 1000 to 2000 rads. Approximately 2 months following irradiation, visible nodules were found in the intestines of the groups receiving irradiation. Nodule incidence was 80 to 100% in groups that received 1750 or 2000 rads, 50% in the 1500-rad groups, and 3% in the 1000-rad groups, respectively. The histology of the nodules within 70 days postirradiation, revealed adenomatous hyperplasia, including invasion of submucosa, muscle layers, and serosa of the small intestine accompanied by an area of fibrous tissue resulting from desmoplastic reaction by irradiation injury. The nodule within 140 to 300 days postirradiation induced advanced tissue injuried, that is, a polypoid lesion in histology and intestinal nodular adhesion in macroscopic anatomy. Running parallel with the advance of the above mentioned tissue injuries, the nodules in 3 out of 18 rat during 200 to 300 days postirradiation showed mucoid adenocarcinoma.

  12. Relation between radiation-induced tissue injury and its carcinogenesis of the rat small intestine

    International Nuclear Information System (INIS)

    Tsubouchi, Susumu; Matsuzawa, Taiju.

    1975-01-01

    This study was undertaken to make clear the relationships between radiation-induced tissue injury and its carcinogenesis in the rat small intestine. The abdomens of Wistar rats were irradiated locally with 1000 to 2000 rads. Approximately 2 months following irradiation, visible nodules were found in the intestines of the groups receiving irradiation. Nodule incidence was 80 to 100% in groups that received 1750 or 2000 rads, 50% in the 1500-rad groups, and 3% in the 1000-rad groups, respectively. The histology of the nodules within 70 days postirradiation, revealed adenomatous hyperplasia, including invasion of submucosa, muscle layers, and serosa of the small intestine accompanied by an area of fibrous tissue resulting from desmoplastic reaction by irradiation injury. The nodule within 140-300 days postirradiation induced advanced tissue injuried, that is, a polypoid lesion in histology and intestinal nodular adhesion in macroscopic anatomy. Running parallel with the advance of the above mentioned tissue injuries, the nodules in 3 out of 18 rat during 200-300 days postirradiation showed mucoid adenocarcinoma. (author)

  13. Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

    Directory of Open Access Journals (Sweden)

    Enjae Jung

    Full Text Available World conditions place large populations at risk from ionizing radiation (IR from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA. While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01. Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01. These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target.

  14. Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

    Science.gov (United States)

    Jung, Enjae; Perrone, Erin E; Brahmamdan, Pavan; McDonough, Jacquelyn S; Leathersich, Ann M; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Hotchkiss, Richard S; Coopersmith, Craig M

    2013-01-01

    World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target.

  15. Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Sang; Lee, Hae-June; Lee, Yoon-Jin [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Jeong, Jae-Hoon [Division of Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Kang, Seongman [Division of Life Sciences, Korea University, Seoul 136-701 (Korea, Republic of); Lim, Young-Bin, E-mail: yblim@kirams.re.kr [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2014-07-25

    Highlights: • UPR activation precedes caspase activation in irradiated IEC-6 cells. • Chemical ER stress inducers radiosensitize IEC-6 cells. • siRNAs that targeted ER stress responses ameliorate IR-induced cell death. • Chemical chaperons prevent cell death in irradiated IEC-6 cells. - Abstract: Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.

  16. RBE of 0,85 MeV neutrons in guinea pigs with intestinal form of radiation sickness

    International Nuclear Information System (INIS)

    Shaporov, V.N.; Sokolova, T.I.; Nasonova, T.A.; Aleshin, S.N.

    1989-01-01

    Relative biological effectiveness (RBE) coefficient of 0.85 MeV neutrons was 1.87 in comparison with 0.66 MeV γ-radiation ( 137 Cs) when estimated by the death rate of guinea pigs with intestinal form of radiation sickness. LD 50/5 was 5.9 and 11.06 respectively. Features of the mortality rate dynamics, clinical picture and pathoanatomical changes are discussed

  17. Acute and delayed radiation injuries in the small intestine and colon

    International Nuclear Information System (INIS)

    Heiss, H.

    1981-01-01

    The group of patients with severe actinic intestinal injuries consists of 67 patients, 46 female and 21 male. The main indication of irradiation were gynaecologic tumours with 67%. The irradiation was carried out with a telekobalt unit combined with radium. From the pathogenetic point of view, acute inflammation and necrobiotic processes in the intestinal mucosa and a restriction of the ability to regenerate are the main radiation-induced acute injuries; delayed injuries are mainly the narrowing and rarefaction of the vessels with lacking capillary budding. The cause of the completely different intervals of up to 26 years until the manifestation of the delayed injury remained unclear. The majority of the delayed symptoms were unspecific; therefore, the danger of misinterpretation was pointed out. A resection with primary anastomosis of the ends of the intestines is the goal to be reached operation-technically. The postoperative complication rate was 45.0%. The most frequent complications were the recurrence of a fistula and the formation of a new fistula, respectively, followed by anastomotic and wound insufficiency, and gastrointestinal bleedings. The postoperative lethality was 18.3%. The causes of death were, according to their frequency, peritonitis, acute failure of the coronary circulation, pneumonia, and massive bleedings. (orig./MG) [de

  18. Bax and Bak Do Not Exhibit Functional Redundancy in Mediating Radiation-Induced Endothelial Apoptosis in the Intestinal Mucosa

    International Nuclear Information System (INIS)

    Rotolo, Jimmy A.; Maj, Jerzy G.; Feldman, Regina; Ren, Decheng; Haimovitz-Friedman, Adriana; Cordon-Cardo, Carlos; Cheng, Emily H.-Y.; Kolesnick, Richard; Fuks, Zvi

    2008-01-01

    Purpose: To address in vivo the issue of whether Bax and Bak are functionally redundant in signaling apoptosis, capable of substituting for each other. Methods and Materials: Mice were exposed to whole-body radiation, and endothelial cell apoptosis was quantified using double immunostaining with TUNEL and anti-CD31 antibody. Crypt survival was determined at 3.5 days after whole-body radiation by the microcolony survival assay. Actuarial animal survival was calculated by the product-limit Kaplan-Meier method, and autopsies were performed to establish cause of death. Results: Radiation exposure of Bax- and Bak-deficient mice, both expressing a wild-type acid sphingomyelinase (ASMase) phenotype, indicated that Bax and Bak are both mandatory, though mutually independent, for the intestinal endothelial apoptotic response. However, neither affected epithelial apoptosis at crypt positions 4-5, indicating specificity toward endothelium. Furthermore, Bax deficiency and Bak deficiency each individually mimicked ASMase deficiency in inhibiting crypt lethality in the microcolony assay and in rescuing mice from the lethal gastrointestinal syndrome. Conclusions: The data indicate that Bax and Bak have nonredundant functional roles in the apoptotic response of the irradiated intestinal endothelium. The observation that Bax deficiency and Bak deficiency also protect crypts in the microcolony assay provides strong evidence that the microvascular apoptotic component is germane to the mechanism of radiation-induced damage to mouse intestines, regulating reproductive cell death of crypt stem cell clonogens

  19. Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: impact of a "Top-Down" approach to intestinal fibrosis in mice.

    Science.gov (United States)

    Johnson, Laura A; Luke, Amy; Sauder, Kay; Moons, David S; Horowitz, Jeffrey C; Higgins, Peter D R

    2012-03-01

    The natural history of Crohn's disease follows a path of progression from an inflammatory to a fibrostenosing disease, with most patients requiring surgical resection of fibrotic strictures. Potent antiinflammatory therapies reduce inflammation but do not appear to alter the natural history of intestinal fibrosis. The aim of this study was to determine the relationship between intestinal inflammation and fibrogenesis and the impact of a very early "top-down" interventional approach on fibrosis in vivo. In this study we removed the inflammatory stimulus from the Salmonella typhimurium mouse model of intestinal fibrosis by eradicating the S. typhimurium infection with levofloxacin at sequential timepoints during the infection. We evaluated the effect of this elimination of the inflammatory stimulus on the natural history of inflammation and fibrosis as determined by gross pathology, histopathology, mRNA expression, and protein expression. Fibrogenesis is preceded by inflammation. Delayed eradication of the inflammatory stimulus by antibiotic treatment represses inflammation without preventing fibrosis. Early intervention significantly ameliorates but does not completely prevent subsequent fibrosis. This study demonstrates that intestinal fibrosis develops despite removal of an inflammatory stimulus and elimination of inflammation. Early intervention ameliorates but does not abolish subsequent fibrosis, suggesting that fibrosis, once initiated, is self-propagating, suggesting that a very early top-down interventional approach may have the most impact on fibrostenosing disease. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  20. Edaravone ameliorates the adverse effects of valproic acid toxicity in small intestine.

    Science.gov (United States)

    Oktay, S; Alev, B; Tunali, S; Emekli-Alturfan, E; Tunali-Akbay, T; Koc-Ozturk, L; Yanardag, R; Yarat, A

    2015-06-01

    Valproic acid (VPA) is a drug used for the treatment of epilepsy, bipolar psychiatric disorders, and migraine. Previous studies have reported an increased generation of reactive oxygen species and oxidative stress in the toxic mechanism of VPA. Edaravone, a free radical scavenger for clinical use, can quench free radical reaction by trapping a variety of free radical species. In this study, effect of edaravone on some small intestine biochemical parameters in VPA-induced toxicity was investigated. Thirty seven Sprague Dawley female rats were randomly divided into four groups. The groups include control group, edaravone (30 mg(-1) kg(-1) day(-1)) given group, VPA (0.5 g(-1) kg(-1) day(-1)) given group, VPA + edaravone (in same dose) given group. Edaravone and VPA were given intraperitoneally for 7 days. Biochemical parameters such as malondialdehyde, as an index of lipid peroxidation(LPO), sialic acid (SA), glutathione levels and glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, catalase, myeloperoxidase, alkaline phosphatase (ALP), and tissue factor (TF) activities were determined in small intestine samples by colorimetric methods. Decreased small intestine antioxidant enzyme activities, increased LPO and SA levels, and increased activities of ALP and TF were detected in the VPA group. Based on our results edaravone may be suggested to reverse the oxidative stress and inflammation due to VPA-induced small intestine toxicity. © The Author(s) 2014.

  1. Synergistic effect of aluminum and ionizing radiation upon ultrastructure, oxidative stress and apoptotic alterations in Paneth cells of rat intestine.

    Science.gov (United States)

    Eltahawy, N A; Elsonbaty, S M; Abunour, S; Zahran, W E

    2017-03-01

    Environmental and occupational exposure to aluminum along with ionizing radiation results in serious health problems. This study was planned to investigate the impact of oxidative stress provoked by exposure to ionizing radiation with aluminum administration upon cellular ultra structure and apoptotic changes in Paneth cells of rat small intestine . Animals received daily aluminum chloride by gastric gavage at a dose 0.5 mg/Kg BW for 4 weeks. Whole body gamma irradiation was applied at a dose 2 Gy/week up to 8 Gy. Ileum malondialdehyde, advanced oxidative protein products, protein carbonyl and tumor necrosis factor-alpha were assessed as biomarkers of lipid peroxidation, protein oxidation and inflammation respectively along with superoxide dismutase, catalase, and glutathione peroxidase activities as enzymatic antioxidants. Moreover, analyses of cell cycle division and apoptotic changes were evaluated by flow cytometry. Intestinal cellular ultra structure was investigated using transmission electron microscope.Oxidative and inflammatory stresses assessment in the ileum of rats revealed that aluminum and ionizing radiation exposures exhibited a significant effect upon the increase in oxidative stress biomarkers along with the inflammatory marker tumor necrosis factor-α accompanied by a significant decreases in the antioxidant enzyme activities. Flow cytometric analyses showed significant alterations in the percentage of cells during cell cycle division phases along with significant increase in apoptotic cells. Ultra structurally, intestinal cellular alterations with marked injury in Paneth cells at the sites of bacterial translocation in the crypt of lumens were recorded. The results of this study have clearly showed that aluminum and ionizing radiation exposures induced apoptosis with oxidative and inflammatory disturbance in the Paneth cells of rat intestine, which appeared to play a major role in the pathogenesis of cellular damage. Furthermore, the

  2. Fish oil enhances recovery of intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplant.

    Directory of Open Access Journals (Sweden)

    Qiurong Li

    Full Text Available BACKGROUND: The intestinal chronic rejection (CR is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity. METHODS/PRINCIPAL FINDINGS: The luminal and mucosal microbiota composition of CR rats were characterized by DGGE analysis at 190 days after intestinal transplant. The specific bacterial species were determined by sequence analysis. Furthermore, changes in the localization of intestinal TJ proteins were examined by immunofluorescent staining. PCR-DGGE analysis revealed that gut microbiota in CR rats had a shift towards Escherichia coli, Bacteroides spp and Clostridium spp and a decrease in the abundance of Lactobacillales bacteria in the intestines. Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions. CONCLUSIONS/SIGNIFICANCE: Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation.

  3. Radiation-Induced Testicular Injury and Its Amelioration by Tinospora cordifolia (An Indian Medicinal Plant Extract

    Directory of Open Access Journals (Sweden)

    Priyanka Sharma

    2011-01-01

    Full Text Available The primary objective of this investigation is to determine the deleterious effects of sub lethal gamma radiation on testes and their possible inhibition by Tinospora cordifolia extract (TCE. For this purpose, one group of male Swiss albino mice was exposed to 7.5 Gy gamma radiation to serve as the irradiated control, while the other group received TCE (75 mg/kg b. wt./day orally for 5 consecutive days half an hr before irradiation to serve as experimental. Exposure of animals to 7.5 Gy gamma radiation resulted into significant decrease in body weight, tissue weight, testes- body weight ratio and tubular diameter up to 15 days of irradiation. Cent percent mortality was recorded by day 17th in irradiated control, whereas all animals survived in experimental group. TCE pretreatment rendered significant increase in body weight, tissue weight, testes- body weight ratio and tubular diameter at various intervals as compared to irradiated group. Radiation induced histological lesions in testicular architecture were observed more severe in irradiated control then the experimental. TCE administration before irradiation significantly ameliorated radiation induced elevation in lipid peroxidation and decline in glutathione concentration in testes. These observations indicate the radio- protective potential of Tinospora cordifolia root extract in testicular constituents against gamma irradiation in mice.

  4. Nigella sativa oil Ameliorates ionizing Radiation induced cellular injury in Male Albino Rats

    International Nuclear Information System (INIS)

    Mohamed, E.T.; El-Kady, A.A.

    2013-01-01

    Nigella sativa (NS), commonly known as black seed, is a plant spices in which thymoquinone is the main active ingredient isolated from the black seeds. The seeds of Nigella sativa are used in herbal medicine all over the world for the treatment and prevention of a number of diseases. The aim of this study was focused on investigating the possible protective effect of NS against gamma radiation induced nephrotoxicity and inflammatory changes in male albino rats. Twenty four albino rats were divided into four equal groups as follows: control group, irradiated group (animals subjected to whole body gamma irradiation at a dose of 6 Gy), treated group (rats treated with 0.2 ml/kg, i.p., NS oil for 4 weeks), and treated irradiated group (animals treated with 0.2 mL/kg, i.p., NS oil for 4 weeks then exposed to whole body gamma irradiation at a dose of 6 Gy). The obtained results revealed that the administration of Nigella sativa oil to irradiated rats significantly ameliorated the changes induced in kidney antioxidant system; catalase and glutathione peroxidase activities as well as reduced glutathione concentration. Also, NS oil restored the kidney function indices (urea and creatinine) near normal level when compared with their equivalent values in irradiated rats. In addition, the changes in serum tumor necrosis factor alpha (TNF-α), Interleukin-1β (IL-1β) and Interleukin-6 (IL-6) activities were markedly improved compared to the corresponding values of irradiated group. The histopathological results showed distinctive pattern of ischemic renal injury in irradiated group, while in treated- irradiated group the renal tissues showed relatively well-preserved architecture with or without focal degeneration. In conclusion, NS acts in the kidney as a potent scavenger of free radicals to prevent or ameliorates the toxic effects of gamma irradiation as shown in the biochemical and histopathological study and also NS oil might provide substantial protection against

  5. Treatment and prophylaxis with sucralfate ameliorates hypoxia/reoxygenation-induced intestinal injury in pup rats.

    Science.gov (United States)

    Sencan, Arzu Bostanci; Sencan, Aydin; Aktas, Safiye; Habif, Sara; Kabaroglu, Ceyda; Parildar, Zuhal; Karaca, Irfan

    2005-04-01

    Sucralfate is widely used as a cytoprotective agent in patients with peptic ulcer and other intestinal mucosal injury. The aim of this study is to investigate whether sucralfate has any effect on the prevention and treatment of hypoxia/reoxygenation-induced intestinal injury. Four groups of 10 1-day-old rat pups were studied. Hypoxia/reoxygenation (H/O)-induced intestinal injury was created. Group 1 was subjected to H/O just after birth and sacrificed at the end of the third day (Treatment Control). Group 2 was subjected to H/O just after birth and treated with sucralfate for 3 days. They were sacrificed at the end of the third day (Treatment). Group 3 was subjected to H/O on the third day after birth and then sacrificed (Prophylaxis Control). Group 4 was treated with sucralfate for the first 3 days, then H/O was created. Just after H/O, the pups were sacrificed (Prophylaxis). The intestinal tissues were harvested for histopathological investigation. Malondialdehyde (MDA) levels in the intestinal tissues were determined. The mucosal injury grades of the treatment and prophylaxis groups were significantly lower than those of control groups (p<0.05). The mean MDA level in the treatment and prophylaxis groups were 0.42+/-0.17 and 0.21+/-0.23 nmol/mg respectively. The MDA levels of both groups were significantly lower than in the control groups (p<0.05). The present study shows that sucralfate has beneficial effects in an experimental model of hypoxia/reoxygenation-induced intestinal injury.

  6. Transcriptional corepressor MTG16 regulates small intestinal crypt proliferation and crypt regeneration after radiation-induced injury.

    Science.gov (United States)

    Poindexter, Shenika V; Reddy, Vishruth K; Mittal, Mukul K; Williams, Amanda M; Washington, M Kay; Harris, Elizabeth; Mah, Amanda; Hiebert, Scott W; Singh, Kshipra; Chaturvedi, Rupesh; Wilson, Keith T; Lund, P Kay; Williams, Christopher S

    2015-03-15

    Myeloid translocation genes (MTGs) are transcriptional corepressors implicated in development, malignancy, differentiation, and stem cell function. While MTG16 loss renders mice sensitive to chemical colitis, the role of MTG16 in the small intestine is unknown. Histological examination revealed that Mtg16(-/-) mice have increased enterocyte proliferation and goblet cell deficiency. After exposure to radiation, Mtg16(-/-) mice exhibited increased crypt viability and decreased apoptosis compared with wild-type (WT) mice. Flow cytometric and immunofluorescence analysis of intestinal epithelial cells for phospho-histone H2A.X also indicated decreased DNA damage and apoptosis in Mtg16(-/-) intestines. To determine if Mtg16 deletion affected epithelial cells in a cell-autonomous fashion, intestinal crypts were isolated from Mtg16(-/-) mice. Mtg16(-/-) and WT intestinal crypts showed similar enterosphere forming efficiencies when cultured in the presence of EGF, Noggin, and R-spondin. However, when Mtg16(-/-) crypts were cultured in the presence of Wnt3a, they demonstrated higher enterosphere forming efficiencies and delayed progression to mature enteroids. Mtg16(-/-) intestinal crypts isolated from irradiated mice exhibited increased survival compared with WT intestinal crypts. Interestingly, Mtg16 expression was reduced in a stem cell-enriched population at the time of crypt regeneration. This is consistent with MTG16 negatively regulating regeneration in vivo. Taken together, our data demonstrate that MTG16 loss promotes radioresistance and impacts intestinal stem cell function, possibly due to shifting cellular response away from DNA damage-induced apoptosis and towards DNA repair after injury.

  7. Perioperative Alanyl-Glutamine-Supplemented Parenteral Nutrition in Chronic Radiation Enteritis Patients With Surgical Intestinal Obstruction: A Prospective, Randomized, Controlled Study.

    Science.gov (United States)

    Yao, Danhua; Zheng, Lei; Wang, Jian; Guo, Mingxiao; Yin, Jianyi; Li, Yousheng

    2016-04-01

    A prospective, randomized, controlled study was performed to evaluate the effects of perioperative alanyl-glutamine-supplemented parenteral nutrition (PN) support on the immunologic function, intestinal permeability, and nutrition status of surgical patients with chronic radiation enteritis (CRE)-induced intestinal obstruction. Patients who received 0.4 g/kg/d alanyl-glutamine and isonitrogenous PN were assigned to an alanyl-glutamine-supplemented PN (Gln-PN) group and a control group, respectively. Serum levels of alanine aminotransferase and glutamine, body fat mass (FM), immunologic function, and intestinal permeability were measured before and after surgery. Serum glutamine levels of the Gln-PN group significantly exceeded that of the control group (P nutrition state and intestinal motility of surgical patients with CRE-induced intestinal obstruction. © 2015 American Society for Parenteral and Enteral Nutrition.

  8. The tripeptide feG ameliorates systemic inflammatory responses to rat intestinal anaphylaxis

    Directory of Open Access Journals (Sweden)

    Davison Joseph S

    2002-08-01

    Full Text Available Abstract Background Food allergies are generally associated with gastrointestinal upset, but in many patients systemic reactions occur. However, the systemic effects of food allergies are poorly understood in experimental animals, which also offer the opportunity to explore the actions of anti-allergic drugs. The tripeptide D-phenylalanine-D-glutamate-Glycine (feG, which potentially alleviates the symptoms of systemic anaphylactic reactions, was tested to determine if it also reduced systemic inflammatory responses provoked by a gastric allergic reaction. Results Optimal inhibition of intestinal anaphylaxis was obtained when 100 μg/kg of feG was given 20 min before the rats were challenged with antigen. The increase in total circulating neutrophils and accumulation of neutrophils in the heart, developing 3 h and 24 h, respectively, after antigen challenge were reduced by both feG and dexamethasone. Both anti-inflammatory agents reduced the increase in vascular permeability induced by antigen in the intestine and the peripheral skin (pinna, albeit with different time courses. Dexamethasone prevented increases in vascular permeability when given 12 h before antigen challenge, whereas feG was effective when given 20 min before ingestion of antigen. The tripeptide prevented the anaphylaxis induced up regulation of specific antibody binding of a cell adhesion molecule related to neutrophil activation, namely CD49d (α4 integrin. Conclusions Aside from showing that intestinal anaphylaxis produces significant systemic inflammatory responses in non-intestinal tissues, our results indicate that the tripeptide feG is a potent inhibitor of extra-gastrointestinal allergic reactions preventing both acute (30 min and chronic (3 h or greater inflammatory responses.

  9. Surgical treatment of radiation induced injuries of the intestine

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, E.H.; Symmonds, R.E.

    1981-12-01

    In the patient who has received high dose irradiation of the pelvis and abdomen, all abdominopelvic operations should be avoided, unless it is absolutely essential. Persisting obstruction, hemorrhage, intestinal perforation with peritonitis and with abscess and fistula formation are valid indications for surgical intervention. Ninety-three patients have been operated upon for these complications after irradiation. Some anastomotic dehiscence occurred in ten patients. Six operative deaths occurred. Of the 93 patients, 65 were managed by means of complete resection of the involved segment of intestine, followed by restoration of intestinal continuity by means of an end-to-end anastomosis. This is the treatment of choice when the involved area can be safely resected. In the absence of actual intestinal necrosis and when segments of strictured small intestine are adherent deep in the pelvis, and intestinal bypass procedure may represent the treatment of choice. This was accomplished in 20 patients, two of whom eventually required a second operation for resection of the bypassed segment of intestine.

  10. Surgical treatment of radiation induced injuries of the intestine

    International Nuclear Information System (INIS)

    Schmitt, E.H.; Symmonds, R.E.

    1981-01-01

    In the patient who has received high dose irradiation of the pelvis and abdomen, all abdominopelvic operations should be avoided, unless it is absolutely essential. Persisting obstruction, hemorrhage, intestinal perforation with peritonitis and with abscess and fistula formation are valid indications for surgical intervention. Ninety-three patients have been operated upon for these complications after irradiation. Some anastomotic dehiscence occurred in ten patients. Six operative deaths occurred. Of the 93 patients, 65 were managed by means of complete resection of the involved segment of intestine, followed by restoration of intestinal continuity by means of an end-to-end anastomosis. This is the treatment of choice when the involved area can be safely resected. In the absence of actual intestinal necrosis and when segments of strictured small intestine are adherent deep in the pelvis, and intestinal bypass procedure may represent the treatment of choice. This was accomplished in 20 patients, two of whom eventually required a second operation for resection of the bypassed segment of intestine

  11. Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats

    OpenAIRE

    de Queiroz, Camila AA; Fonseca, Said Gonçalves C; Frota, Priscila B; Figueiredo, Ítalo L; Aragão, Karoline S; Magalhães, Carlos Emanuel C; de Carvalho, Cibele BM; Lima, Aldo Ângelo M; Ribeiro, Ronaldo A; Guerrant, Richard L; Moore, Sean R; Oriá, Reinaldo B

    2014-01-01

    Background WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc’s anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats. Methods Rats were undernourished using a northeastern Br...

  12. Intestinal complications following accelerated fractionated X-irradiation

    International Nuclear Information System (INIS)

    Hauer-Jensen, M.; Poulakos, L.; Osborne, J.W.

    1990-01-01

    Due to paucity of suitable animal models, it has been difficult to study the development of long-term intestinal complications following fractionated irradiation. We recently developed a model which allows multiple radiation exposures of a short segment of rat ileum without the need for repeated surgery. In the present series, this model was used to study the influence of shortening the total treatment time (accelerated fractionation) on development of radiation enteropathy. Male rats were orchiectomized and a short segment of distal ileum was transposed to the scrotum. Starting 3 weeks after surgery, the scrotum containing the intestinal segment was X-irradiated with 20 fractions of 2.8 Gy (total dose 56 Gy). Two fractionation schedules were compared: one fraction per day (total treatment time 26 days) and 3 fractions per day (total treatment time 7 days). Actuarial survival curves were obtained, and the degree of radiation injury was assessed 2, 8 and 26 weeks after the last radiation exposure using a semiquantitative histopathologic scoring system. There was no mortality from acute radiation injury in either treatment group. All animals of the 1-fraction/day group survived the observation period (26 weeks). In the 3-fraction/day group, there was significant mortality due to intestinal obstruction, and cumulative mortality at 26 weeks was 100%. Radiation injury, as assessed by the histopathologic scoring system, was also more pronounced in this group than in the 1-fraction/day group. We conclude that shortening the total treatment time significantly increases the severity of late intestinal complications. Our data are suggestive of an association between acute mucosal damage and chronic radiation injury of the small intestine. (orig.)

  13. Effect of certain natural antioxidants in protecting against damage caused by gamma radiation in ischemic rat intestine

    International Nuclear Information System (INIS)

    Hassan, T.A.A.

    2009-01-01

    Oxidative stress plays an important role in various clinical pathologies one of which is ischemia/reperfusion (I/R)- induced injury. Intestinal I/R enhances production of reactive oxygen species (ROS), inflammatory mediators and induces apoptosis. In other hand. the intestinal tract shows a high sensitivity to ionizing radiation due to a rapid cell turnover and is often implicated in radiation sickness the radiation damage may either be a consequence of a direct effect resulting in disruption of critical molecule (such as an enzyme or DNA) or an indirect effect through ionization of water molecules and formation of ROS. consequently, supplementation of antioxidants may be a beneficial approach to protect against cellular damages associated with oxidative stress. the current study was aimed to evaluate the possible protective effects of vitamin E (100 mg/kg p.o.), tomato extract (67 mg/kg. p.o.) and turmeric (100 mg/kg, p.o) against ileal injury induced in rats by total occlusion of the superior mesenteric artery for 30 min followed by reperfusion for another 30 min. Furthermore, this protective effect of the mentioned drugs was extended into injury that could happened in ileal tissues of rats exposed to (6 Gy) gamma radiation followed by intestinal I/R. Drugs were administered one daily for 14 consecutive days prior to the ischemic insult. Damage induced by I/R was manifested by depletion of ileal content of reduced glutathion (GSH) as well as Lactate dehydrogenas (LDH) activity, associated with elevation of ileal contents of thiobarbituric acid reactive substances (TBARS), nitrite, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Intestinal ischemic insults were exacerbated by radiation injury on comparing different untreated controls; except the ileal content of GSH which has elevated due to the preconditioning effect of irradiation. Vitamin E provided a significant protection against the decrease in LDH activity as well as the increase in TBARS

  14. Uric acid ameliorates indomethacin-induced enteropathy in mice through its antioxidant activity.

    Science.gov (United States)

    Yasutake, Yuichi; Tomita, Kengo; Higashiyama, Masaaki; Furuhashi, Hirotaka; Shirakabe, Kazuhiko; Takajo, Takeshi; Maruta, Koji; Sato, Hirokazu; Narimatsu, Kazuyuki; Yoshikawa, Kenichi; Okada, Yoshikiyo; Kurihara, Chie; Watanabe, Chikako; Komoto, Shunsuke; Nagao, Shigeaki; Matsuo, Hirotaka; Miura, Soichiro; Hokari, Ryota

    2017-11-01

    Uric acid is excreted from blood into the intestinal lumen, yet the roles of uric acid in intestinal diseases remain to be elucidated. The study aimed to determine whether uric acid could reduce end points associated with nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. A mouse model of NSAID-induced enteropathy was generated by administering indomethacin intraperitoneally to 8-week-old male C57BL/6 mice, and then vehicle or uric acid was administered orally. A group of mice treated with indomethacin was also concurrently administered inosinic acid, a uric acid precursor, and potassium oxonate, an inhibitor of uric acid metabolism, intraperitoneally. For in vitro analysis, Caco-2 cells treated with indomethacin were incubated in the presence or absence of uric acid. Oral administration of uric acid ameliorated NSAID-induced enteropathy in mice even though serum uric acid levels did not increase. Intraperitoneal administration of inosinic acid and potassium oxonate significantly elevated serum uric acid levels and ameliorated NSAID-induced enteropathy in mice. Both oral uric acid treatment and intraperitoneal treatment with inosinic acid and potassium oxonate significantly decreased lipid peroxidation in the ileum of mice with NSAID-induced enteropathy. Treatment with uric acid protected Caco-2 cells from indomethacin-induced oxidative stress, lipid peroxidation, and cytotoxicity. Uric acid within the intestinal lumen and in serum had a protective effect against NSAID-induced enteropathy in mice, through its antioxidant activity. Uric acid could be a promising therapeutic target for NSAID-induced enteropathy. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  15. A lactobacillus rhamnosus GG-derived soluble protein, p40, stimulates ligand release from intestinal epithelial cells to transactivate epidermal growth factor receptor

    Science.gov (United States)

    Protein p40, a Lactobacillus rhamnosus GG (LGG)-derived soluble protein, ameliorates intestinal injury and colitis, reduces apoptosis and preserves barrier function by activation of EGF receptor (EGFR) in intestinal epithelial cells. The aim of this study was to determine the mechanisms by which p40...

  16. Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC{sup 1638N/+} Mice

    Energy Technology Data Exchange (ETDEWEB)

    Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Strawn, Steve J.; Thakor, Hemang; Fan, Ziling [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States); Shay, Jerry W. [Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas (United States); Fornace, Albert J. [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States); Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah (Saudi Arabia); Datta, Kamal, E-mail: kd257@georgetown.edu [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States)

    2016-05-01

    Purpose: There are uncertainties associated with the prediction of colorectal cancer (CRC) risk from highly energetic heavy ion (HZE) radiation. We undertook a comprehensive assessment of intestinal and colonic tumorigenesis induced after exposure to high linear energy transfer (high-LET) HZE radiation spanning a range of doses and LET in a CRC mouse model and compared the results with the effects of low-LET γ radiation. Methods and Materials: Male and female APC{sup 1638N/+} mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, {sup 12}C, {sup 28}Si, or {sup 56}Fe radiation. For the >1 Gy HZE dose, we used γ-ray equitoxic doses calculated using relative biological effectiveness (RBE) determined previously. The mice were euthanized 150 days after irradiation, and intestinal and colon tumor frequency was scored. Results: The highest number of tumors was observed after {sup 28}Si, followed by {sup 56}Fe and {sup 12}C radiation, and tumorigenesis showed a male preponderance, especially after {sup 28}Si. Analysis showed greater tumorigenesis per unit of radiation (per cGy) at lower doses, suggesting either radiation-induced elimination of target cells or tumorigenesis reaching a saturation point at higher doses. Calculation of RBE for intestinal and colon tumorigenesis showed the highest value with {sup 28}Si, and lower doses showed greater RBE relative to higher doses. Conclusions: We have demonstrated that the RBE of heavy ion radiation-induced intestinal and colon tumorigenesis is related to ion energy, LET, gender, and peak RBE is observed at an LET of 69 keV/μm. Our study has implications for understanding risk to astronauts undertaking long duration space missions.

  17. Ellagitannins from pomegranate ameliorates 5-fluorouracil-induced intestinal mucositis in rats while enhancing its chemotoxicity against HT-29 colorectal cancer cells through intrinsic apoptosis induction.

    Science.gov (United States)

    Chen, Xiao-Xin; Lam, Kar Ho; Feng, Yibin; Xu, Kai; Sze, Stephen C W; Tang, Chi Wai; Leung, George P H; Lee, Calvin Kai-Fai; Shi, Jun; Yang, Zhijun; Li, Sheng-Tao; Zhang, Zhang-Jin; Zhang, Yanbo

    2018-06-19

    Worldwide, colorectal cancer (CRC) is a deleterious disease causing millions of death annually. 5-Fluorouracil (5-FU) is a first-line chemotherapy for CRC, but chemoresistance and gastrointestinal mucositis limit its efficacy. Polyphenol-rich foods are increasingly popular due to their potential beneficial role in cancer. Ellagitannins is a group of phenolic compounds commonly found in pomegranate, strawberries, raspberries, etc. The objective of this study was to explore whether ellagitannins from pomegranate (PETs) could ameliorate 5-FU-induced intestinal mucositis and enhance its efficacy against CRC. The results showed that PETs (100 mg/kg) counteracted 5-FU-induced intestinal mucositis in rats. The number of apoptotic cells per crypt was reduced from 1.50±0.21 to 0.85±0.18 (P<0.05). Moreover, PETs induced HT-29 CRC cell death through intrinsic apoptosis as demonstrated by dissipation of mitochondrial membrane potential, increased Bax to Bcl-2 ratio, and cleavage of caspase 9 and caspase 3. PETs and 5-FU combination treatments exhibited synergistic cytotoxicity against HT-29 cells with a weighted combination index of 0.3494. PETs (80 µg/mL) and 5-FU (40 µg/mL) treatments for 48 h induced 14.03±0.76% and 16.42±1.15% of HT-29 cells to undergo apoptosis while the combination treatment further increased apoptosis cells to 34.00±1.54% (P<0.05). Combination treatment of the cells also enhanced S phase cell cycle arrest as compared with PETs or 5-FU monotherapy (P<0.05). These results suggest that dietary ellagitannins from pomegranate could alleviate intestinal mucositis in rats induced by 5-FU while enhancing its toxicity against HT-29 cells through potentiation of apoptosis and cell cycle arrest.

  18. Radiation-induced hyperproliferation of intestinal crypts results in elevated genome instability with inactive p53-related genomic surveillance.

    Science.gov (United States)

    Zhou, Xin; Ma, Xiaofei; Wang, Zhenhua; Sun, Chao; Wang, Yupei; He, Yang; Zhang, Hong

    2015-12-15

    Radiation-induced hyperproliferation of intestinal crypts is well documented, but its potential tumorigenic effects remain elusive. Here we aim to determine the genomic surveillance process during crypt hyperproliferation, and its consequential outcome after ionizing radiation. Crypt regeneration in the intestine was induced by a single dose of 12Gy abdominal irradiation. γ-H2AX, 53BP1 and DNA-PKcs were used as DNA repair surrogates to investigate the inherent ability of intestinal crypt cells to recognize and repair double-strand breaks. Ki67 staining and the 5-bromo-2'-deoxyuridine incorporation assay were used to study patterns of cell proliferation in regenerating crypts. Staining for ATM, p53, Chk1 and Chk2 was performed to study checkpoint activation and release. Apoptosis was evaluated through H&E staining and terminal deoxynucleotidyl transferase (dUTP) nick-end labeling. The ATM-p53 pathway was immediately activated after irradiation. A second wave of DSBs in crypt cells was observed in regenerating crypts, accompanied with significantly increased chromosomal bridges. The p53-related genomic surveillance pathway was not active during the regeneration phase despite DSBs and chromosomal bridges in the cells of regenerating crypts. Non-homologous end joining (NHEJ) DSBs repair was involved in the DSBs repair process, as indicated by p-DNA-PKcs staining. Intestinal crypt cells retained hyperproliferation with inactive p53-related genomic surveillance system. NHEJ was involved in the resultant genomic instability during hyperproliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Effect of prior hyperthermia on subsequent thermal enhancement of radiation damage in mouse intestine

    International Nuclear Information System (INIS)

    Marigold, J.C.L.; Hume, S.P.

    1982-01-01

    Hyperthermia given in conjunction with X-rays results in a greater level of radiation injury than following X-rays alone, giving a thermal enhancement ratio (TER). The effect of prior hyperthermia ('priming') on TER was studied in the small intestine of mouse by giving 42.0 deg C for 1 hour at various times before the combined heat and X-ray treatments. Radiation damage was assessed by measuring crypt survival 4 days after radiation. TER was reduced when 'priming' hyperthermia was given 24-48 hours before the combined treatments. The reduction in effectiveness of the second heat treatment corresponded to a reduction in hyperthermal temperature of approximately 0.5 deg C, a value similar to that previously reported for induced resistance to heat given alone ('thermotolerance') (Hume and Marigold 1980). However, the time courses for development and decay of the TER response were much longer than those for 'thermotolerance', suggesting that different mechanisms are involved in thermal damage following heat alone and thermal enhancement of radiation damage

  20. Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

    International Nuclear Information System (INIS)

    Nomura, Takaharu

    2008-01-01

    Living organisms have developed complex biological system which protects themselves against environmental radiation, and irradiation with proper dose, dose-rate and irradiation time can stimulate their biological responses against oxidative stress evoked by the irradiation. Because reactive oxygen species are involved in various human diseases, non-toxic low dose/low dose-rate radiation can be utilized for the amelioration of such diseases. In this study, we used mouse experimental models for fatty liver, nephritis, diabetes, and ageing to elucidate the ameliorative effect of low dose/low dose-rate radiation in relation to endogenous antioxidant activity. Single irradiation at 0.5 Gy ameliorates carbon tetrachloride-induced fatty liver. The irradiation increases hepatic anti-oxidative system involving glutathione and glutathione peroxidase, suggesting that endogenous radical scavenger is essential for the ameliorative effect of low dose radiation on carbon tetrachloride-induced fatty liver. Single irradiation at 0.5 Gy ameliorates ferric nitrilotriacetate-induced nephritis. The irradiation increases catalase and decreases superoxide dismutase in kidney. The result suggests that low dose radiation reduced generation of hydroxide radical generation by reducing cellular hydroperoxide level. Single irradiation at 0.5 Gy at 12 week of age ameliorates incidence of type I diabetes in non-obese diabetic (NOD) mice through the suppression of inflammatory activity of splenocytes, and resultant apoptosis of β-cells in pancreas. The irradiation activities of superoxide dismutase and catalase, which coordinately diminish intracellular reactive oxygen species. Continuous irradiation at 0.70 mGy/hr from 10 week of age elongates life span, and suppresses alopecia in type II diabetesmice. The irradiation improved glucose clearance without affecting insulin-resistance, and increased pancreatic catalase activity. The results suggest that continuous low dose-rate irradiation protect

  1. Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation

    International Nuclear Information System (INIS)

    Gremy, O.

    2006-12-01

    The use of radiation therapy to treat abdominal and pelvic malignancies inevitably involves exposure of healthy intestinal tissues which are very radiosensitive. As a result, most patients experience symptoms such as abdominal pain, nausea and diarrhea. Such symptoms are associated with acute damage to intestine mucosa including radio-induced inflammatory processes. With a rat model of colorectal fractionated radiation, we have shown a gradual development of a colonic inflammation during radiation planning, without evident tissue injury. This radio-induced inflammation is characterized not only by the sur expressions of pro-inflammatory cytokines and chemokines, a NF-kB activation, but also by a repression of anti-inflammatory cytokines and the nuclear receptors PPARa and RXRa, both involved in inflammation control. This early inflammation is associated with a discreet neutrophil recruitment and a macrophage accumulation. Macrophages are still abnormally numerous in tissue 27 weeks after the last day of irradiation. Inflammatory process is the most often related to a specific immune profile, either a type Th1 leading to a cellular immune response, or a type Th2 for humoral immunity. According to our studies, a unique abdominal radiation in the rat induces an ileum inflammation and an immune imbalance resulting in a Th2-type profile. Inhibiting this profile is important as its persistence promotes chronic inflammation, predisposition to bacterial infections and fibrosis which is the main delayed side-effect of radiotherapy. The treatment of rats with an immuno-modulator compound, the caffeic acid phenethyl ester (C.A.P.E.), have the potential to both reduce ileal mucosal inflammation and inhibit the radio-induced Th2 status. In order to search new therapeutic molecular target, we has been interested in the PPARg nuclear receptor involved in the maintenance of colon mucosal integrity. In our abdominal irradiation model, we have demonstrated that the prophylactic

  2. De Novo Formation of Insulin-Producing “Neo-β Cell Islets” from Intestinal Crypts

    Directory of Open Access Journals (Sweden)

    Yi-Ju Chen

    2014-03-01

    Full Text Available The ability to interconvert terminally differentiated cells could serve as a powerful tool for cell-based treatment of degenerative diseases, including diabetes mellitus. To determine which, if any, adult tissues are competent to activate an islet β cell program, we performed an in vivo screen by expressing three β cell “reprogramming factors” in a wide spectrum of tissues. We report that transient intestinal expression of these factors—Pdx1, MafA, and Ngn3 (PMN—promotes rapid conversion of intestinal crypt cells into endocrine cells, which coalesce into “neoislets” below the crypt base. Neoislet cells express insulin and show ultrastructural features of β cells. Importantly, intestinal neoislets are glucose-responsive and able to ameliorate hyperglycemia in diabetic mice. Moreover, PMN expression in human intestinal “organoids” stimulates the conversion of intestinal epithelial cells into β-like cells. Our results thus demonstrate that the intestine is an accessible and abundant source of functional insulin-producing cells.

  3. Hepatocyte growth factor gene-modified adipose-derived mesenchymal stem cells ameliorate radiation induced liver damage in a rat model.

    Directory of Open Access Journals (Sweden)

    Jiamin Zhang

    Full Text Available Liver damage caused by radiotherapy is associated with a high mortality rate, but no established treatment exists. Adipose-derived mesenchymal stem cells (ADSCs are capable of migration to injured tissue sites, where they aid in the repair of the damage. Hepatocyte growth factor (HGF is critical for damage repair due to its anti-apoptotic, anti-fibrotic and cell regeneration-promoting effects. This study was performed to investigate the therapeutic effects of HGF-overexpressing ADSCs on radiation-induced liver damage (RILD. ADSCs were infected with a lentivirus encoding HGF and HGF-shRNA. Sprague-Dawley (SD rats received 60Gy of irradiation to induce liver injury and were immediately given either saline, ADSCs, ADSCs + HGF or ADSCs + shHGF. Two days after irradiation, a significant reduction in apoptosis was observed in the HGF-overexpressing ADSC group compared with the RILD group, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining. Scanning electron microscopy showed chromatin condensation after irradiation, which was ameliorated in the group that received ADSCs and was reversed in the group that received HGF-overexpressing ADSCs. HGF-overexpressing ADSCs ameliorated radiation- induced liver fibrosis through down regulation of α-SMA and fibronectin. Hepatocyte regeneration was significantly improved in rats treated with ADSCs compared with rats from the RILD group, as assessed by Ki-67 immunohistochemistry. Rats that received HGF-overexpressing ADSCs showed an even greater level of hepatocyte regeneration. HGF-overexpressing ADSCs completely blocked the radiation-induced increase in the enzymes ALT and AST. The effect of mitigating RILD was compromised in the ADSC + shHGF group compared with the ADSC group. Altogether, these results suggest that HGF-overexpressing ADSCs can significantly improve RILD in a rat model, which may serve as a valuable therapeutic alternative.

  4. Some regularities in the development of radiation tumors of the stomach and intestine

    International Nuclear Information System (INIS)

    Lebedeva, G.A.

    1978-01-01

    It was shown on dogs and rats that gastric and intestinal neoplasms arise under the influence of different kinds of radiation, these may be located in all portions of the stomach and bowel and are of a different histological origin. They are not infrequently primary multiple, mostly benign neoplasms which show multicentric growth. The frequency of tumors appearence, their localization, an average latent period, the degree of malignancy and multiplicity are conditioned by the amount of tissue dosage, the topography of their distribution in the alimentary tract and the level of whole-body irradiation. With the increased dosage of local irradiation the latent period and multiplicity are decreased, while the incidence of malignancy raises. The optimum levels of the tissue dosage and the time of maximum tumor appearance were determined for each type of radiation

  5. Clinical and experimental investigation on small intestinal injury following radiation therapy for carcinoma of uterine cervix

    International Nuclear Information System (INIS)

    Asakura, Midori

    1977-01-01

    Radiation injury of the small bowel was observed in 6 of 460 patients with carcinoma of uterine cervix who were treated by radiation between April 1966 and December 1973 at Tokyo Women's Medical College, Department of Radiology. Three of these 6 patients were treated conservatively and the other 3 others underwent surgery but died subsequently. Clinically and surgically these 6 patients showed marked adhesions of intestinal loops, which may be accounted for by the radiation injury of the small bowel. Clinical experience has shown that it is necessary to use a small radiation field to decrease small bowel injury from radiation. An experiment using abdominal radiation in mice confirmed that LD sub(50/30) is larger with a center split, maintaining equal integral doses. In adult dogs, severe small bowel obstruction was observed with over 4000 rad irradiation. Small bowel injury was milder in case with center split, intracavitary irradiation, and small radiation field. It was concluded that center split is one of the methods of preventing radiation injury of the small bowel. (Evans, J.)

  6. Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Yasuda, Takeshi [Radiation Emergency Medicine Research Program, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Fujita, Mayumi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Asada, Masahiro [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Meineke, Viktor [Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich (Germany); Imamura, Toru [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan)

    2014-02-01

    Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation with γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can protect the

  7. Apoptosis and mitosis in the small intestine at radiation injury

    International Nuclear Information System (INIS)

    Hashiguchi, Junichiro; Ito, Masahiro; Onizuka, Shinya; Sekine, Ichiro; Uchida, Shinji

    1990-01-01

    A single whole body irradiation was given at a dose rate of 0.298 Gy/min in 6-week-old male mice. Intestinal crypt apoptosis and mitosis cells were determined by delivering radiation doses of 0.4, 0.6, 1.0, 1.5, 2.0, 5.0, 10.0, and 20.0 Gy. The incidence of apoptosis was linearly increased in a dose-dependent manner up to 5.0 Gy, and thereafter, it was gradually decreased. There was a decreased tendency for mitosis with delivering higher radiation doses. The incidence of apoptosis rapidly increased 2 hours after irradiation with either 0.6 Gy or 2.0 Gy, and reached to the peak 4 hours later. It brought about a 18-fold and 28-fold increase for 0.6 Gy and 2.0 Gy, respectively, relative to that before irradiation. Mitosis cells decreased by half one hour after irradiation with 0.6 Gy, and then returned to the pre-irradiation value through synchronization 24 hours later. The number of cells positive to BrdU was 776 in the group of mice without irradiation and 479 in the group of mice irradiated with 2.0 Gy. (N.K.)

  8. Effects of the ionising radiations on the structure and the function of the intestinal epithelial cell

    International Nuclear Information System (INIS)

    Haton, C.

    2005-06-01

    The intestinal mucosa is a particularly radio-sensitive tissue and damage may occur following either accidental or therapeutic exposure. the deleterious actions of ionizing radiation are linked to the formation of sometimes overwhelming quantities of reactive oxygen species (R.O.S.). Production of R.O.S. is both direct and indirect from the secondary effects of irradiation. A better comprehension of the underlying mechanisms of injury will lead to more adapted therapeutic approaches to limit the harmful effects of irradiation. The homeostasis of the intestinal epithelium is regulated by three factors: proliferation, apoptosis and differentiation. these three factors were studied using the cell model, HT29, in order to analyze modulations of this balance after irradiation. our results, in agreement with other data, showed the establishment of mitotic delay. This arrest of proliferation was followed by apoptosis to be the major mechanism leading to cell death in this model. thus, for the first time, we have shown that irradiated intestinal epithelial cells preserve their capacity to differentiate. This indicates, although indirectly, that intestinal cells have and preserve an intrinsic capacity restore a functional epithelium. R.O.S. are considered as intermediates between the physical nature of radiations and biological responses. It seems essential to understand anti-oxidant mechanisms used by the cell for defence against the deleterious effects of R.O.S post exposure. This study of several anti-oxidant defence mechanisms of intestinal mucosa, was carried out in vivo in the mouse at different times following abdominal irradiation. We observed an early mitochondrial response in the hours following irradiation revealing this organelle as a particular target. We demonstrated a strong alteration of anti-oxidant capacity as revealed by a decrease in S.O.D.s, catalase and an increase of the G.P.X.s and M.T.s. A part of these modifications appeared to depend on an

  9. Cell-permeable intrinsic cellular inhibitors of apoptosis protect and rescue intestinal epithelial cells from radiation-induced cell death

    International Nuclear Information System (INIS)

    Matsuzaki-Horibuchi, Shiori; Yasuda, Takeshi; Sakaguchi, Nagako; Yamaguchi, Yoshihiro; Akashi, Makoto

    2015-01-01

    One of the important mechanisms for gastrointestinal (GI) injury following high-dose radiation exposure is apoptosis of epithelial cells. X-linked inhibitor of apoptosis (XIAP) and cellular IAP2 (cIAP2) are intrinsic cellular inhibitors of apoptosis. In order to study the effects of exogenously added IAPs on apoptosis in intestinal epithelial cells, we constructed bacterial expression plasmids containing genes of XIAP (full-length, BIR2 domain and BIR3-RING domain with and without mutations of auto-ubiquitylation sites) and cIAP2 proteins fused to a protein-transduction domain (PTD) derived from HIV-1 Tat protein (TAT) and purified these cell-permeable recombinant proteins. When the TAT-conjugated IAPs were added to rat intestinal epithelial cells IEC6, these proteins were effectively delivered into the cells and inhibited apoptosis, even when added after irradiation. Our results suggest that PTD-mediated delivery of IAPs may have clinical potential, not only for radioprotection but also for rescuing the GI system from radiation injuries. (author)

  10. Mixed Lactobacillus plantarum Strains Inhibit Staphylococcus aureus Induced Inflammation and Ameliorate Intestinal Microflora in Mice.

    Science.gov (United States)

    Ren, Dayong; Gong, Shengjie; Shu, Jingyan; Zhu, Jianwei; Rong, Fengjun; Zhang, Zhenye; Wang, Di; Gao, Liangfeng; Qu, Tianming; Liu, Hongyan; Chen, Ping

    2017-01-01

    Objective . Staphylococcus aureus is an important pathogen that causes intestinal infection. We examined the immunomodulatory function of single and mixed Lactobacillus plantarum strains, as well as their impacts on the structure of the microbiome in mice infected with Staphylococcus aureus . The experiment was divided into three groups: protection, treatment, and control. Serum IFN- γ and IL-4 levels, as well as intestinal sIgA levels, were measured during and 1 week after infection with Staphylococcus aureus with and without Lactobacillus plantarum treatment. We used 16s rRNA tagged sequencing to analyze microbiome composition. IFN- γ /IL-4 ratio decreased significantly from infection to convalescence, especially in the mixed Lactobacillus plantarum group. In the mixed Lactobacillus plantarum group the secretion of sIgA in the intestine of mice (9.4-9.7 ug/mL) was significantly higher than in the single lactic acid bacteria group. The dominant phyla in mice are Firmicutes , Bacteroidetes , and Proteobacteria . Treatment with mixed lactic acid bacteria increased the anti-inflammatory factor and the secretion of sIgA in the intestine of mice infected with Staphylococcus aureus and inhibited inflammation.

  11. Intestinal Microbiota-Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

    International Nuclear Information System (INIS)

    Ó Broin, Pilib; Vaitheesvaran, Bhavapriya; Saha, Subhrajit; Hartil, Kirsten; Chen, Emily I.; Goldman, Devorah; Fleming, William Harv; Kurland, Irwin J.; Guha, Chandan; Golden, Aaron

    2015-01-01

    Purpose: Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Methods and Materials: Groups of C57BL/6 mice (n=12 per group) were exposed to 0, 2, 4, 8, and 10.4 Gy of whole-body gamma radiation. At 24 hours after treatment, all animals were euthanized, and both plasma and liver biopsy samples were obtained, the latter being used to identify a distinct hepatic radiation injury response within plasma. A semiquantitative, untargeted metabolite/lipid profile was developed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which identified 354 biochemical compounds. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. Results: We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Conclusions: Plasma profiling of specific metabolites related to pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan-associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites particularly represent an attractive marker for radiation injury within blood plasma

  12. Intestinal Microbiota-Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

    Energy Technology Data Exchange (ETDEWEB)

    Ó Broin, Pilib [Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Department of Mathematical Sciences, Yeshiva University, New York, New York (United States); Vaitheesvaran, Bhavapriya [Department of Medicine, Diabetes Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Saha, Subhrajit [Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Hartil, Kirsten [Department of Medicine, Diabetes Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Chen, Emily I. [Department of Pharmacology, Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York (United States); Goldman, Devorah; Fleming, William Harv [Department of Medicine, Oregon Health and Science University, Portland, Oregon (United States); Kurland, Irwin J. [Department of Medicine, Diabetes Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Guha, Chandan, E-mail: cguha@montefiore.org [Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Golden, Aaron, E-mail: aaron.golden@einstein.yu.edu [Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States); Department of Mathematical Sciences, Yeshiva University, New York, New York (United States)

    2015-02-01

    Purpose: Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Methods and Materials: Groups of C57BL/6 mice (n=12 per group) were exposed to 0, 2, 4, 8, and 10.4 Gy of whole-body gamma radiation. At 24 hours after treatment, all animals were euthanized, and both plasma and liver biopsy samples were obtained, the latter being used to identify a distinct hepatic radiation injury response within plasma. A semiquantitative, untargeted metabolite/lipid profile was developed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which identified 354 biochemical compounds. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. Results: We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Conclusions: Plasma profiling of specific metabolites related to pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan-associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites particularly represent an attractive marker for radiation injury within blood plasma.

  13. Intestinal microbiota-derived metabolomic blood plasma markers for prior radiation injury.

    Science.gov (United States)

    Ó Broin, Pilib; Vaitheesvaran, Bhavapriya; Saha, Subhrajit; Hartil, Kirsten; Chen, Emily I; Goldman, Devorah; Fleming, William Harv; Kurland, Irwin J; Guha, Chandan; Golden, Aaron

    2015-02-01

    Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Groups of C57BL/6 mice (n=12 per group) were exposed to 0, 2, 4, 8, and 10.4 Gy of whole-body gamma radiation. At 24 hours after treatment, all animals were euthanized, and both plasma and liver biopsy samples were obtained, the latter being used to identify a distinct hepatic radiation injury response within plasma. A semiquantitative, untargeted metabolite/lipid profile was developed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which identified 354 biochemical compounds. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Plasma profiling of specific metabolites related to pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan-associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites particularly represent an attractive marker for radiation injury within blood plasma. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Effectiveness of Aloe vera leaf extract against low level exposure to gamma radiation induced injury in intestinal mucosa of Swiss mice

    International Nuclear Information System (INIS)

    Gehlot, Prashasnika; Saini, M.R.

    2004-01-01

    Full Text: Human beings can not deny the presence of all sorts of incoming radiations, which are detrimental to life. The small intestine represents one of the major dose limiting normal tissues in radiotherapy because of its high radio sensitivity. The purpose of this study was to determine the effects of Aloe vera, a potential radioprotector. Radioprotective efficacy of aloe vera leaf extract in intestinal mucosa in mice (1 g/kg body weight/day) was studied from 6h to day 20 after gamma irradiation (0.5 Gy(. Villus height, goblet cells/villus section, total cells are good parameters for the assessment of radiation damage. The mice selected from inbreed colony were divided into two groups. The first group was given Aloe vera extract orally for 15 consecutive days and served as experimental group. On 15th day, after 30 min of above treatment animals of both the groups were exposed to 0.5 Gy gamma irradiation and autopsied on 6, 12, 24 h and 5, 10, 20 days. Aloe vera pretreatment resulted in a significant increase (p<0.001) in villus height, total cells whereas globlet cells showed a significant decrease (p<0.001) from respective irradiated controls at each autospy day. The results suggest that Aloe vera pretreatment provides protection against radiation-induced alterations in intestinal mucosa of Swiss mice

  15. 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.

    Science.gov (United States)

    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

  16. Administration of Protein kinase D1 induce an immunomodulatory effect on lipopolysaccharide-induced intestinal inflammation in a co-culture model of intestinal epithelial Caco-2 cells and RAW 264.7 macrophage cells

    DEFF Research Database (Denmark)

    Nielsen, Ditte Søvsø Gundelund; Fredborg, Marlene; Andersen, Vibeke

    2017-01-01

    the effects of human PKD1 in relation to intestinal inflammation, using a co-culture model of intestinal epithelial Caco-2 cells and RAW264.7 macrophages. An inflammatory response was induced in the macrophages by lipopolysaccharide (LPS), upregulating the expression of tumour necrosis factor alpha (TNF......-α), interleukin- (IL-) 1β, and IL-6 besides increasing the secretion of TNF-α protein. The effect of administering PKD1 to Caco-2 was evaluated in relation to both amelioration of inflammation and the ability to suppress inflammation initiation. Administration of PKD1 (10–100 ng/ml) following induction...

  17. The histopathological comparison of L-carnitine with amifostine for protective efficacy on radiation-induced acute small intestinal toxicity

    Directory of Open Access Journals (Sweden)

    Murat Caloglu

    2012-01-01

    Full Text Available Background: The aim of the study was to compare the protective efficacy of l-carnitine (LC to amifostine on radiation-induced acute small intestine damage. Materials and Methods: Thirty, 4-week-old Wistar albino rats were randomly assigned to four groups - Group 1: control (CONT, n = 6, Group 2: irradiation alone (RT, n = 8, Group 3: amifostine plus irradiation (AMI+RT, n = 8, and Group 4: l-Carnitine plus irradiation (LC+RT, n = 8. The rats in all groups were irradiated individually with a single dose of 20 Gy to the total abdomen, except those in CONT. LC (300 mg/kg or amifostine (200 mg/kg was used 30 min before irradiation. Histopathological analysis of small intestine was carried out after euthanasia. Results: Pretreatment with amifostine reduced the radiation-induced acute degenerative damage (P = 0.009 compared to the RT group. Pretreatment with LC did not obtain any significant difference compared to the RT group. The vascular damage significantly reduced in both of the AMI+RT (P = 0.003 and LC+RT group (P = 0.029 compared to the RT group. The overall damage score was significantly lower in the AMI+RT group than the RT group (P = 0.009. There was not any significant difference between the LC+RT and RT group. Conclusions: Amifostine has a marked radioprotective effect against all histopathological changes on small intestinal tissue while LC has limited effects which are mainly on vascular structure.

  18. Daikenchuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors.

    Science.gov (United States)

    Endo, Mari; Hori, Masatoshi; Ozaki, Hiroshi; Oikawa, Tetsuro; Hanawa, Toshihiko

    2014-06-01

    Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal medicine, is prescribed for patients with postoperative ileus (POI) and adhesive bowel obstruction following abdominal surgery. Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI. In the present study, we investigated the effects of DKT in a mouse POI model and attempted to clarify the detailed mechanisms of action. Intestinal manipulation (IM) was applied to the distal ileum of mice. DKT was administered orally to the animals 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, cytokine mRNA expression and gastrointestinal motility were analyzed. We also investigated the effects of the α7nAChR antagonist methyllycaconitine citrate (MLA) on the DKT-mediated ameliorative action against POI, and we studied the effects of DKT on inflammatory activity in α7nAChR knockout mice. DKT treatment led to recovery of the delayed intestinal transit induced by IM. DKT significantly inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1. MLA significantly reduced the anti-inflammatory action of DKT, and the amelioration of macrophage infiltration by DKT was partially suppressed in α7nAChR knockout mice. In conclusion, in addition to the gastrointestinal prokinetic action, DKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency. The DKT-induced anti-inflammatory activity may be partly mediated by activation of α7nAChR.

  19. Comparison of the dose-response relationship of radiation-induced apoptosis in the hippocampal dentate gyrus and intestinal crypt of adult mice

    International Nuclear Information System (INIS)

    Kim, J. S.; Yang, M.; Kim, J.; Lee, D.; Kim, J. C.; Shin, T.; Kim, S. H.; Moon, C.

    2012-01-01

    The present study compared the dose-response curves for the frequency of apoptosis in mouse hippocampal dentate gyrus (DG) and intestinal crypt using whole-body gamma irradiation. The incidence of gamma-ray-induced apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end-labelling (TUNEL) method. TUNEL-positive apoptotic nuclei in the DG and intestinal crypt were increased in a dose-dependent pattern (0-2 Gy). The dose-response curves were linear-quadratic, with a significant relationship between the appearance of apoptosis and irradiation dose. The slopes of the dose-response curves in the DG were much steeper (∼5-6-fold) than those in the intestinal crypt within the range of 0-1 Gy exposure. Hippocampal DG might be a more effective and sensitive evaluation structure than the intestinal crypt to estimate the degree of radiation exposure in damaged organs of adult mice exposed to low irradiation dose. copy; The Author 2011. Published by Oxford Univ. Press. All rights reserved. (authors)

  20. Cellulose supplementation early in life ameliorates colitis in adult mice.

    Directory of Open Access Journals (Sweden)

    Dorottya Nagy-Szakal

    Full Text Available Decreased consumption of dietary fibers, such as cellulose, has been proposed to promote the emergence of inflammatory bowel diseases (IBD: Crohn disease [CD] and ulcerative colitis [UC] where intestinal microbes are recognized to play an etiologic role. However, it is not known if transient fiber consumption during critical developmental periods may prevent consecutive intestinal inflammation. The incidence of IBD peaks in young adulthood indicating that pediatric environmental exposures may be important in the etiology of this disease group. We studied the effects of transient dietary cellulose supplementation on dextran sulfate sodium (DSS colitis susceptibility during the pediatric period in mice. Cellulose supplementation stimulated substantial shifts in the colonic mucosal microbiome. Several bacterial taxa decreased in relative abundance (e.g., Coriobacteriaceae [p = 0.001], and other taxa increased in abundance (e.g., Peptostreptococcaceae [p = 0.008] and Clostridiaceae [p = 0.048]. Some of these shifts persisted for 10 days following the cessation of cellulose supplementation. The changes in the gut microbiome were associated with transient trophic and anticolitic effects 10 days following the cessation of a cellulose-enriched diet, but these changes diminished by 40 days following reversal to a low cellulose diet. These findings emphasize the transient protective effect of dietary cellulose in the mammalian large bowel and highlight the potential role of dietary fibers in amelioration of intestinal inflammation.

  1. Cellulose Supplementation Early in Life Ameliorates Colitis in Adult Mice

    Science.gov (United States)

    Nagy-Szakal, Dorottya; Hollister, Emily B.; Luna, Ruth Ann; Szigeti, Reka; Tatevian, Nina; Smith, C. Wayne; Versalovic, James; Kellermayer, Richard

    2013-01-01

    Decreased consumption of dietary fibers, such as cellulose, has been proposed to promote the emergence of inflammatory bowel diseases (IBD: Crohn disease [CD] and ulcerative colitis [UC]) where intestinal microbes are recognized to play an etiologic role. However, it is not known if transient fiber consumption during critical developmental periods may prevent consecutive intestinal inflammation. The incidence of IBD peaks in young adulthood indicating that pediatric environmental exposures may be important in the etiology of this disease group. We studied the effects of transient dietary cellulose supplementation on dextran sulfate sodium (DSS) colitis susceptibility during the pediatric period in mice. Cellulose supplementation stimulated substantial shifts in the colonic mucosal microbiome. Several bacterial taxa decreased in relative abundance (e.g., Coriobacteriaceae [p = 0.001]), and other taxa increased in abundance (e.g., Peptostreptococcaceae [p = 0.008] and Clostridiaceae [p = 0.048]). Some of these shifts persisted for 10 days following the cessation of cellulose supplementation. The changes in the gut microbiome were associated with transient trophic and anticolitic effects 10 days following the cessation of a cellulose-enriched diet, but these changes diminished by 40 days following reversal to a low cellulose diet. These findings emphasize the transient protective effect of dietary cellulose in the mammalian large bowel and highlight the potential role of dietary fibers in amelioration of intestinal inflammation. PMID:23437211

  2. Ameliorating role of chromium ingestion on biochemical, histological and trigluconate disorders induced by diabetes and / or gamma irradiation in pregnant albino rats and their fetuses

    International Nuclear Information System (INIS)

    RAMADAN, F.L.; REZK, R.G.

    2006-01-01

    Chromium is an essential trace element in human nutrition for the regulation of insulin action thereby influencing carbohydrate and lipid metabolism The aim of the present study was to evaluate the role of chromium intake on radiation-induced damage in diabetic mothers. Diabetes was induced in female rats by intraperitoneal injection of 150 mg/kg alloxan dissolved in saline. Pregnant diabetic mothers were received chromium (20 mg/kg) from the 1st up to the 19 th day of gestation. Meanwhile, pregnant diabetic rats were exposed to 0.3 Gy gamma radiation on the 6th and the 12 th day of gestation. Chromium treatment of diabetic mothers ameliorated radiation-induced damage, which was obvious by diminishing the increase of glucose, malonaldehyde (MDA), total cholesterol levels and by ameliorating the decrease of glutathione level in blood serum. In addition,chromium treatment ameliorated the radiation-induced changes in cholesterol levels of the fetuses. Moreover, chromium treatment led to the regeneration of the normal architecture of maternal hepatic cells and blood vessels. It could be concluded that chromium supplementation to diabetic mothers ameliorated the radiation-induced biochemical, histopathological and teratological disorders. Furthermore, the results obtained showed that chromium administration caused a significant protection to diabetic pregnant females against radiation-induced spontaneous abortion and embryo malformations

  3. Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Yasuda, Takeshi [Department of Radiation Emergency Medicine, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Asada, Masahiro; Motomura, Kaori; Suzuki, Masashi [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Zakrzewska, Malgorzata [Faculty of Biotechnology, University of Wroclaw (Poland); Imamura, Toru [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)

    2013-02-01

    Purpose: Human fibroblast growth factor-1 (FGF1) has radioprotective effects on the intestine, although its structural instability limits its potential for practical use. Several stable FGF1 mutants were created increasing stability in the order, wild-type FGF1, single mutants (Q40P, S47I, and H93G), Q40P/S47I, and Q40P/S47I/H93G. This study evaluated the contribution of the structural stability of FGF1 to its radioprotective effect. Methods and Materials: Each FGF1 mutant was administered intraperitoneally to BALB/c mice in the absence of heparin 24 h before or after total body irradiation (TBI) with {gamma}-rays at 8-12 Gy. Several radioprotective effects were examined in the jejunum. Results: Q40P/S47I/H93G could activate all subtypes of FGF receptors in vitro much more strongly than the wild-type without endogenous or exogenous heparin. Preirradiation treatment with Q40P/S47I/H93G significantly increased crypt survival more than wild-type FGF1 after TBI at 10 or 12 Gy, and postirradiation treatment with Q40P/S47I/H93G was effective in promoting crypt survival after TBI at 10, 11, or 12 Gy. In addition, crypt cell proliferation, crypt depth, and epithelial differentiation were significantly promoted by postirradiation treatment with Q40P/S47I/H93G. The level of stability of FGF1 mutants correlated with their mitogenic activities in vitro in the absence of heparin; however, preirradiation treatment with the mutants increased the crypt number to almost the same level as Q40P/S47I/H93G. When given 24 h after TBI at 10 Gy, all FGF1 mutants increased crypt survival more than wild-type FGF1, and Q40P/S47I/H93G had the strongest mitogenic effects in intestinal epithelial cells after radiation damage. Moreover, Q40P/S47I/H93G prolonged mouse survival after TBI because of the repair of intestinal damage. Conclusion: These findings suggest that the structural stability of FGF1 can contribute to the enhancement of protective effects against radiation-induced intestinal

  4. Alteration of the digestive motility linked with radiation-induced inflammatory processes in rats

    International Nuclear Information System (INIS)

    Picard, C.

    2000-12-01

    Exposure to ionizing radiation, whether accidental or for medical reasons, may lead to gastro-intestinal injury, characterized by nausea, vomiting, diarrhea and abdominal cramps. The aetiology of radiation-induced diarrhea remains to date unclear. In this study, we have investigated the acute effects of a 10 Gy abdominal irradiation on rat digestive functions. The objective of the first study was to evaluate the role of sensory afferent neurons, capsaicin-sensitive, on morphological changes and the inflammatory response following exposure. Three days after irradiation, we observed an inflammatory response characterized by neutrophils infiltration and mast cells de-granulation. No effect of capsaicin pre-treatment was seen on these parameters. However, neutrophils infiltration was increased as early as one day after irradiation in capsaicin-treated rats. No difference in severity of diarrhea was observed after denervation nor in morphological changes. These data demonstrate that abdominal irradiation results in diarrhea concomitant with an inflammatory response, and that sensory innervation does not play a major protective role. The objective of the rest of the work was in the first instance to characterize radiation-induced alterations of intestinal and colonic motility leading to diarrhea and secondly to evaluate the role of serotonin in such disorders. Perturbations in intestinal (MMC) and colonic (LSB) motor profiles were observed from the first day onwards. Migrating motor complexes (MMC) were completely disrupted at three days at the same time as the onset of diarrhea. In addition to inhibition of LSB, colonic fluid absorptive capacity was decreased and serotonin colonic tissue levels were increased three days after irradiation. Radiation-induced diarrhea was reduced by treatment with an antagonist of 5-HT 3 receptors, granisetron, as were alterations of colonic motility and serotonin tissue levels. However, this treatment did not significantly ameliorate

  5. The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation

    Science.gov (United States)

    Zaiss, Mario M.; Rapin, Alexis; Lebon, Luc; Dubey, Lalit Kumar; Mosconi, Ilaria; Sarter, Kerstin; Piersigilli, Alessandra; Menin, Laure; Walker, Alan W.; Rougemont, Jacques; Paerewijck, Oonagh; Geldhof, Peter; McCoy, Kathleen D.; Macpherson, Andrew J.; Croese, John; Giacomin, Paul R.; Loukas, Alex; Junt, Tobias; Marsland, Benjamin J.; Harris, Nicola L.

    2015-01-01

    Summary Intestinal helminths are potent regulators of their host’s immune system and can ameliorate inflammatory diseases such as allergic asthma. In the present study we have assessed whether this anti-inflammatory activity was purely intrinsic to helminths, or whether it also involved crosstalk with the local microbiota. We report that chronic infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb) altered the intestinal habitat, allowing increased short chain fatty acid (SCFA) production. Transfer of the Hpb-modified microbiota alone was sufficient to mediate protection against allergic asthma. The helminth-induced anti-inflammatory cytokine secretion and regulatory T cell suppressor activity that mediated the protection required the G protein-coupled receptor (GPR)-41. A similar alteration in the metabolic potential of intestinal bacterial communities was observed with diverse parasitic and host species, suggesting that this represents an evolutionary conserved mechanism of host-microbe-helminth interactions. PMID:26522986

  6. Amelioration of both early and late radiation-induced damage to pig skin by essential fatty acids

    International Nuclear Information System (INIS)

    Hopewell, J.W.; Van den Aardweg, G.J.M.J.; Morris, G.M.

    1994-01-01

    To evaluate the possible role of essential fatty acids, specifically gamma-linolenic and eicosapentaenoic acid, in the amelioration of early and late radiation damage to the skin. Skin sites on the flank of 22-25 kg female large white pigs were irradiated with either single or fractionated doses (20 F/28 days) of β-rays from 22.5 mm diameter 90 Sr/ 90 Y plaques at a dose rate of ∼3 Gy/min. Essential fatty acids were administered orally in the form of two open-quotes activeclose quotes oils, So-1100 and So-5407, which contained gamma-linolenic acid and a mixture of that oil with eicosapentaenoic acid, respectively. Oils (1.5-6.0 ml) were given daily for 4 weeks prior, both 4 weeks prior and 10-16 weeks after, or in the case of one single dose study, just for 10 weeks after irradiation. Control animals received a open-quotes placeboclose quotes oil, So-1129, containing no gamma linolenic acid or eicosapentaenoic acid over similar time scales before and after irradiation. Acute and late skin reactions were assessed visually and the dose-related incidence of a specific reaction used to compare the effects of different treatment schedules. A reduction in the severity of both the early and late radiation reactions in the skin was only observed when open-quotes activeclose quotes oils were given over the time course of the expression of radiation damage. Prior treatment with oils did not modify the radiation reaction. A 3.0 ml daily dose of either So-1100 or So-5407 given prior to, but also after irradiation with single and fractionated doses of β-rays produced the most significant modification to the radiation reactions, effects consistent with dose modification factors between 1.06-1.24 for the acute reactions of bright red erythema and/or moist desquamation, and of 1.14-1.35 for the late reactions of dusky/mauve erythema and dermal necrosis. 38 refs., 5 tabs

  7. Radiation enteritis

    International Nuclear Information System (INIS)

    Sato, Makoto; Sano, Masanori; Minakuchi, Naoki; Narisawa, Tomio; Takahashi, Toshio

    1981-01-01

    Radiation enteritis with severe complications including intestinal bleeding, fistula, and stenosis were treated surgically in 9 cases. These 9 cases included 7 cases of cancer of the uterine cervix and 2 single cases of seminoma and melanoma. The patients received 60 Co or Linac x-ray external irradiation with or without intracavitary irradiation by a radium needle. Radiation injury began with melena, vaginorectal fistula, and intestinal obstruction 3 to 18 months after irradiation. One patient with melena underwent colostomy and survived 2 years. One of the three patients with vaginorectal fistula who had colostomy survived 1.5 years. In intestinal obstruction, one patients had bypass operation and three patients had resection of the intestine and the other had both. Leakage was noted in one patient, but the others had favorable prognosis. (Ueda, J.)

  8. Sex-dependent Differences in Intestinal Tumorigenesis Induced in Apc1638N/+ Mice by Exposure to {gamma} Rays

    Energy Technology Data Exchange (ETDEWEB)

    Trani, Daniela [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Maastricht Radiation Oncology (MaastRO) Lab, GROW-School for Oncology and Developmental Biology, University of Maastricht (Netherlands); Moon, Bo-Hyun [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Kallakury, Bhaskar; Hartmann, Dan P. [Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Datta, Kamal [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Fornace, Albert J., E-mail: af294@georgetown.edu [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah (Saudi Arabia)

    2013-01-01

    Purpose: The purpose of the present study was to assess the effect of 1 and 5 Gy radiation doses and to investigate the interplay of gender and radiation with regard to intestinal tumorigenesis in an adenomatous polyposis coli (APC) mutant mouse model. Methods and Materials: Apc1638N/+ female and male mice were exposed whole body to either 1 Gy or 5 Gy of {gamma} rays and euthanized when most of the treated mice became moribund. Small and large intestines were processed to determine tumor burden, distribution, and grade. Expression of proliferation marker Ki-67 and estrogen receptor (ER)-{alpha} were also assessed by immunohistochemistry. Results: We observed that, with both 1 Gy and 5 Gy of {gamma} rays, females displayed reduced susceptibility to radiation-induced intestinal tumorigenesis compared with males. As for radiation effect on small intestinal tumor progression, although no substantial differences were found in the relative frequency and degree of dysplasia of adenomas in irradiated animals compared with controls, invasive carcinomas were found in 1-Gy- and 5-Gy-irradiated animals. Radiation exposure was also shown to induce an increase in protein levels of proliferation marker Ki-67 and sex-hormone receptor ER-{alpha} in both non tumor mucosa and intestinal tumors from irradiated male mice. Conclusions: We observed important sex-dependent differences in susceptibility to radiation-induced intestinal tumorigenesis in Apc1638N/+ mutants. Furthermore, our data provide evidence that exposure to radiation doses as low as 1 Gy can induce a significant increase in intestinal tumor multiplicity as well as enhance tumor progression in vivo.

  9. Ferulic acid ameliorates radiation induced duodenal inflammation

    International Nuclear Information System (INIS)

    Das, Ujjal; Manna, Krishnendu; Sengupta, Aaveri; Biswas, Sushobhan; Chakrabarty, Arpita; Dey, Sanjit

    2016-01-01

    Ionizing radiation creates oxidative stress followed by inflammation through reactive oxygen species (ROS) and altering the status of redox sensitive enzymes. In the current study we aimed to evaluate the effect of ferulic acid (FA) on increasing doses of ionizing radiation mediated oxidative stress and inflammation using in vivo murine duodenum. To delineate the hypothesis we exposed mice with 2.5, 5 and 10 Gy gamma radiation doses in presence and absence of the (FA). FA was administered orally at a fixed dose of 50mg/ kg bw for 5 days before radiation exposure. Different techniques such as biochemical assays, immune blot, and microscopic analysis for histopathology, flow cytometry and scanning electron microscopy were employed to achieve the goal

  10. Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation.

    Directory of Open Access Journals (Sweden)

    Eva Latorre

    Full Text Available TLR2 is a microbiota recognition receptor that has been described to contribute to intestinal homeostasis and to ameliorate inflammatory intestinal injury. In this context, serotonin (5-HT has shown to be an essential intestinal physiological neuromodulator that is also involved in intestinal inflammatory diseases. Since the interaction between TLR2 activation and the intestinal serotoninergic system remains non-investigated, our main aim was to analyze the effect of TLR2 on intestinal serotonin transporter (SERT activity and expression and the intracellular pathways involved. Caco-2/TC7 cells were used to analyze SERT and TLR2 molecular expression and SERT activity by measuring 5-HT uptake. The results showed that apical TLR2 activation inhibits SERT activity in Caco-2/TC7 cells mainly by reducing SERT protein level either in the plasma membrane, after short-term TLR2 activation or in both the plasma membrane and cell lysate, after long-term activation. cAMP/PKA pathway appears to mediate short-term inhibitory effect of TLR2 on SERT; however, p38 MAPK pathway has been shown to be involved in both short- and long-term TLR2 effect. Reciprocally, 5-HT long-term treatment yielded TLR2 down regulation in Caco-2/TC7 cells. Finally, results from in vivo showed an augmented intestinal SERT expression in mice Tlr2-/-, thus confirming our inhibitory effect of TLR2 on intestinal SERT in vitro. The present work infers that TLR2 may act in intestinal pathophysiology, not only by its inherent innate immune role, but also by regulating the intestinal serotoninergic system.

  11. Suggested classification of acute radiation sickness

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Guo; Mingyue, Zhu; Zhiqin, Zhao

    1984-08-01

    Acute radiation sickness is usually classified into three types. Over the last decade, we have been engaged in experimental studies on the classification of this syndrome. Our findings from these studies, however, point to the fact that between the hemopoietic and intestinal types, and between the intestinal and cerebral types there are transitive forms, namely, hemopoieto-intestinal type and cardio-vascular type, respectively. In this article the required radiation doses and the clinical courses of these transitive forms with special emphasis on their histological and clinical manifestations are described. In case of the hemopoieto-intestinal form, histological examination may reveal residual crypts and typical ''abnormal cells'' in the intestinal mucosa, and clinical manifestations include almost the whole spectrum of symptoms and signs of infection and hemorrhage. The watery stool in pink colour may be specific and helpful in diagnosis. In case of the cardio-vascular form, shock may occur immediately after exposure, and histological examination may show myocardial edema, hemorrhage, cell-infiltration and even necrosis. We propose that the acute radiation sickness should be divided into 5 forms, namely, hemopoietic, hemopoieto-intestinal, intestinal, cardio-vascular and cerebral types. Accurate diagnosis can only be made by taking an comprehensive view of radiation dose, clinical course, clinical manifestations and histological findings. (author).

  12. Protection of radiation-induced damage to the hematopoietic system, small intestine and salivary glands in rats by JNJ7777120 compound, a histamine H4 ligand.

    Directory of Open Access Journals (Sweden)

    Diego J Martinel Lamas

    Full Text Available Based on previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed at investigating the radioprotective potential of the H4R ligand, JNJ7777120, on ionizing radiation-induced injury and genotoxic damage in small intestine, salivary glands and hematopoietic tissue. For that purpose, rats were divided into 4 groups. JNJ7777120 and JNJ7777120-irradiated groups received a daily subcutaneous JNJ7777120 injection (10 mg/kg starting 24 h before irradiation. Irradiated groups received a single dose of 5 Gy on whole-body using Cesium-137 source and were sacrificed 3 or 30 days after irradiation. Tissues were removed, fixed, stained with hematoxylin and eosin or PAS staining and histological characteristics were evaluated. Proliferative and apoptotic markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate DNA damage. Submandibular gland (SMG function was evaluated by methacholine-induced salivation. Results indicate that JNJ7777120 treatment diminished mucosal atrophy and preserved villi and the number of crypts after radiation exposure (240±8 vs. 165±10, P<0.01. This effect was associated to a reduced apoptosis and DNA damage in intestinal crypts. JNJ7777120 reduced radiation-induced aplasia, preserving medullar components and reducing formation of micronucleus and also it accelerated bone marrow repopulation. Furthermore, it reduced micronucleus frequency in peripheral blood (27±8 vs. 149±22, in 1,000 erythrocytes, P<0.01. JNJ7777120 completely reversed radiation-induced reduced salivation, conserving glandular mass with normal histological appearance and reducing apoptosis and atrophy of SMG. JNJ7777120 exhibits radioprotective effects against radiation-induced cytotoxic and genotoxic damages in small intestine, SMG and hematopoietic tissues and, thus, could be of clinical value for patients undergoing radiotherapy.

  13. Differential intestinal anti-inflammatory effects of Lactobacillus fermentum and Lactobacillus salivarius in DSS mouse colitis: impact on microRNAs expression and microbiota composition.

    Science.gov (United States)

    Rodríguez-Nogales, Alba; Algieri, Francesca; Garrido-Mesa, Jose; Vezza, Teresa; Utrilla, M Pilar; Chueca, Natalia; Garcia, Federico; Olivares, Mónica; Rodríguez-Cabezas, M Elena; Gálvez, Julio

    2017-11-01

    To compare the intestinal anti-inflammatory effects of two probiotics Lactobacillus fermentum and Lactobacillus salivarius in mouse colitis, focusing on their impact on selected miRNAs and microbiota composition. Male C57BL/6J mice were randomly assigned to four groups (n = 10): non-colitic, DSS colitic and two colitic groups treated with probiotics (5 × 10 8 CFU/mouse/day). Both probiotics ameliorated macroscopic colonic damage. They improved the colonic expression of markers involved in the immune response, and the expression of miR-155 and miR-223. L. fermentum also restored miR-150 and miR-143 expression, also linked to the preservation of the intestinal barrier function. Besides, these beneficial effects were associated with the amelioration of the microbiota dysbiosis and a recovery of the SCFAs- and lactic acid-producing bacterial populations, although only L. fermentum improved Chao richness, Pielou evenness and Shannon diversity. Moreover, L. fermentum also restored the Treg cell population in MLNs and the Th1/Th2 cytokine balance. Both probiotics exerted intestinal anti-inflammatory effects in DSS-mouse colitis, maybe due to their ability to restore the intestinal microbiota homeostasis and modulate the immune response. L. fermentum showed a greater beneficial effect compared to L. salivarius, which makes it more interesting for future studies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Berberine ameliorates collagen-induced arthritis in rats by suppressing Th17 cell responses via inducing cortistatin in the gut.

    Science.gov (United States)

    Yue, Mengfan; Xia, Yufeng; Shi, Can; Guan, Chunge; Li, Yunfan; Liu, Rui; Wei, Zhifeng; Dai, Yue

    2017-09-01

    Berberine, an isoquinoline alkaloid, has been reported to ameliorate various autoimmune diseases including rheumatoid arthritis by oral administration. However, its mechanism remains mysterious due to an extremely low bioavailability. The fact that berberine readily accumulates in the gut, the largest endocrine organ in the body, attracted us to explore its anti-arthritic mechanism in view of the induction of intestinal immunosuppressive neuropeptides. In this study, berberine (200 mg·kg -1 , i.g.) was shown to ameliorate collagen-induced arthritis in rats, which was manifested by the reduction of clinical signs and joint destruction, as well as marked down-regulation of Th17 cell frequency and interleukin-17 level in blood. In contrast, an intravenous injection of berberine failed to affect arthritis in rats, implying that its anti-arthritic effect was gut-dependent. Further studies revealed that oral berberine selectively elevated the levels of cortistatin, of five gut-derived neuropeptides tested, in the intestines and sera of arthrititic rats. Antagonists of ghrelin/growth hormone secretagogue receptor 1 (a subtype of cortistatin receptor) almost completely abolished the ameliorative effect of berberine on arthritis and Th17 cell responses in rats. In vitro, berberine showed a moderate ability to promote the expression of cortistatin in nerve cells, which was strengthened when the nerve cells were cocultured with enteroendocrine cells to induce an autocrine/paracrine environment. In summary, oral berberine exerted anti-arthritic effect through inhibiting the Th17 cell response, which was closely associated with the induction of cortistatin generation from gut through augmenting autocrine/paracrine action between enteric nerve cells and endocrine cells. © 2017 Federation of European Biochemical Societies.

  15. Changing aspects of radiation enteropathy

    International Nuclear Information System (INIS)

    Morgenstern, L.; Hart, M.; Lugo, D.; Friedman, N.B.

    1985-01-01

    Fifty-two patients with radiation enteropathy secondary to radiation for abdominal or pelvic malignant neoplasms are described. This series (1977 to 1984) is compared with a series of 50 patients from the same institution over an earlier period (1961 to 1977). Intestinal obstruction was the principal complication in both series; 96% of the patients underwent either intestinal resection or anastomotic bypass of the affected segment. Changes that have occurred since the last report are as follows: changes in source of radiation energy (linear accelerator); less evidence of mucosal damage; increased serosal reaction (''serosal peel''); and increased use of elemental diets, parenteral nutrition, and long intestinal tubes in surgical management. Since postoperative radiation injury occurs most frequently in the pelvis, new developments for the exclusion of small bowel from the pelvis during radiation are reviewed. Changes in fractionation of radiation dosage should also be considered in patients with enteric symptoms during radiation therapy

  16. Elemental diets in the prophylaxis and therapy for intestinal lesions: an update

    International Nuclear Information System (INIS)

    Bounous, G.

    1989-01-01

    The recognition of potentially noxious physiologic substances in the intestinal milieu prompted the use of an elemental semihydrolyzed formula diet in the prophylaxis of experimental acute ischemic enteropathy. Elemental diets have been used in the management of a variety of digestive diseases. An elemental diet protects the intestinal mucosa of rodents from radiation injury and facilitates mucosal healing. Clinical trials have shown the benefits of this form of treatment in the prevention of acute radiation enteropathy and in the therapy for delayed radiation enteropathy and Crohn's disease.90 references

  17. Damage to the surface of the small intestinal villus: an objective scale of assessment of the effects of single and fractionated radiation doses

    Energy Technology Data Exchange (ETDEWEB)

    Carr, K.E.; Watt, C. (Glasgow Univ. (UK). Dept. of Anatomy); Hamlet, R.; Nias, A.H.W. (Glasgow Inst. of Radiotherapeutics and Oncology (UK))

    1983-07-01

    Scanning electron microscopy has been used to compare damage to mouse small intestinal mucosa after irradiation with different doses of photons and neutrons. Various stages of the collapse of villous structure seen after radiation include the production of conical and rudimentary villi and a flattened mucosa. A scale is proposed to relate radiation to villous damage. Points from this scale are taken to produce comparative ratios for equivalent damage produced by different radiation conditions. RBE values are quoted for neutron, X and gamma radiation given as single or fractionated irradiation doses and as whole or partial body irradiation. The relationship between the stroma in intravillous pegs and that of the pericryptal compartment is explored.

  18. Damage to the surface of the small intestinal villus: an objective scale of assessment of the effects of single and fractionated radiation doses

    International Nuclear Information System (INIS)

    Carr, K.E.; Watt, C.

    1983-01-01

    Scanning electron microscopy has been used to compare damage to mouse small intestinal mucosa after irradiation with different doses of photons and neutrons. Various stages of the collapse of villous structure seen after radiation include the production of conical and rudimentary villi and a flattened mucosa. A scale is proposed to relate radiation to villous damage. Points from this scale are taken to produce comparative ratios for equivalent damage produced by different radiation conditions. RBE values are quoted for neutron, X and gamma radiation given as single or fractionated irradiation doses and as whole or partial body irradiation. The relationship between the stroma in intravillous pegs and that of the pericryptal compartment is explored. (author)

  19. A suggested classification of acute radiation sickness

    International Nuclear Information System (INIS)

    Guo Yao; Zhu Mingyue; Zhao Zhiqin

    1984-01-01

    Acute radiation sickness is usually classified into three types. Over the last decade, we have been engaged in experimental studies on the classification of this syndrome. Our findings from these studies, however, point to the fact that between the hemopoietic and intestinal types, and between the intestinal and cerebral types there are transitive forms, namely, hemopoieto-intestinal type and cardio-vascular type, respectively. In this article the required radiation doses and the clinical courses of these transitive forms with special emphasis on their histological and clinical manifestations are described. In case of the hemopoieto-intestinal form, histological examination may reveal residual crypts and typical ''abnormal cells'' in the intestinal mucosa, and clinical manifestations include almost the whole spectrum of symptoms and signs of infection and hemorrhage. The watery stool in pink colour may be specific and helpful in diagnosis. In case of the cardio-vascular form, shock may occur immediately after exposure, and histological examination may show myocardial edema, hemorrhage, cell-infiltration and even necrosis. We propose that the acute radiation sickness should be divided into 5 forms, namely, hemopoietic, hemopoieto-intestinal, intestinal, cardio-vascular and cerebral types. Accurate diagnosis can only be made by taking an comprehensive view of radiation dose, clinical course, clinical manifestations and histological findings. (author)

  20. ESPEN guidelines on chronic intestinal failure in adults

    DEFF Research Database (Denmark)

    Pironi, Loris; Arends, Jann; Bozzetti, Federico

    2016-01-01

    : The following topics were addressed: management of HPN; parenteral nutrition formulation; intestinal rehabilitation, medical therapies, and non-transplant surgery, for short bowel syndrome, chronic intestinal pseudo-obstruction, and radiation enteritis; intestinal transplantation; prevention/treatment of CVC-related...... organ failure. Home parenteral nutrition (HPN) is the primary treatment for CIF. No guidelines (GLs) have been developed that address the global management of CIF. These GLs have been devised to generate comprehensive recommendations for safe and effective management of adult patients with CIF. METHODS......: The GLs were developed by the Home Artificial Nutrition & Chronic Intestinal Failure Special Interest Group of ESPEN. The GRADE system was used for assigning strength of evidence. Recommendations were discussed, submitted to Delphi rounds, and accepted in an online survey of ESPEN members. RESULTS...

  1. Plasma citrulline levels predict intestinal toxicity in patients treated with pelvic radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Onal, Cem; Kotek, Ayse; Arslan, Gungor; Topkan, Erkan (Dept. of Radiation Oncology, Baskent Univ. Faculty of Medicine, Adana (Turkey)), E-mail: hcemonal@hotmail.com; Unal, Birsel (Dept. of Biochemistry, Baskent Univ. Faculty of Medicine, Ankara (Turkey)); Yavuz, Aydin; Yavuz, Melek (Dept. of Radiation Oncology, Akdeniz Univ. Faculty of Medicine, Antalya (Turkey))

    2011-11-15

    Background. Radiotherapy (RT) for abdominal and pelvic malignancies often causes severe small bowel toxicity. Citrulline concentrations are known to decrease with intestinal failure. We thus evaluated the feasibility of plasma citrulline levels in predicting radiation-induced intestinal toxicity. Material and methods. Fifty-three patients (36 prostate cancer, 17 endometrial cancer) who received 45 Gy pelvic RT using conventional fractionation were prospectively evaluated. Patients with prostate cancer received an additional 25-30.6 Gy conformal boost. Plasma citrulline levels were assessed on day 0, mid- (week 3) and post-RT (week 8), and four months post-RT. Dose-volume histogram, citrulline concentration changes, and weekly intestinal toxicity scores were analyzed. Results. Mean age was 63 years (range: 43-81 years) and mean baseline citrulline concentration was 38.0 +- 10.1 mumol/l. Citrulline concentrations were significantly reduced at week 3 (27.4 +- 5.9 mumol/l; p < 0.0001), treatment end (29.9 +- 8.8 mumol/l; p < 0.0001), and four months post-treatment (34.3 +- 12.1; p 0.01). The following factor pairs were significantly positively correlated: Citrulline concentration/mean bowel dose during, end of treatment, and four months post-RT; dose-volume parameters/citrulline change groups; cumulative mean radiation dose/intestinal toxicity at end and four months post-RT; citrulline changes/intestinal toxicity during and end of RT. Citrulline concentration changes significantly differed during treatment according to RTOG intestinal toxicity grades (p < 0.0001). Although the citrulline changes differed significantly within RTOG intestinal toxicity grades (p = 0.003), the difference between Grade 0 and Grade 1 did not differ significantly at the end of the treatment. At four months after RT, no significant differences were apparent. Conclusion. Citrulline-based assessment scores are objective and should be considered in measuring radiation-induced intestinal toxicity

  2. Plasma citrulline levels predict intestinal toxicity in patients treated with pelvic radiotherapy

    International Nuclear Information System (INIS)

    Onal, Cem; Kotek, Ayse; Arslan, Gungor; Topkan, Erkan; Unal, Birsel; Yavuz, Aydin; Yavuz, Melek

    2011-01-01

    Background. Radiotherapy (RT) for abdominal and pelvic malignancies often causes severe small bowel toxicity. Citrulline concentrations are known to decrease with intestinal failure. We thus evaluated the feasibility of plasma citrulline levels in predicting radiation-induced intestinal toxicity. Material and methods. Fifty-three patients (36 prostate cancer, 17 endometrial cancer) who received 45 Gy pelvic RT using conventional fractionation were prospectively evaluated. Patients with prostate cancer received an additional 25-30.6 Gy conformal boost. Plasma citrulline levels were assessed on day 0, mid- (week 3) and post-RT (week 8), and four months post-RT. Dose-volume histogram, citrulline concentration changes, and weekly intestinal toxicity scores were analyzed. Results. Mean age was 63 years (range: 43-81 years) and mean baseline citrulline concentration was 38.0 ± 10.1 μmol/l. Citrulline concentrations were significantly reduced at week 3 (27.4 ± 5.9 μmol/l; p < 0.0001), treatment end (29.9 ± 8.8 μmol/l; p < 0.0001), and four months post-treatment (34.3 ± 12.1; p 0.01). The following factor pairs were significantly positively correlated: Citrulline concentration/mean bowel dose during, end of treatment, and four months post-RT; dose-volume parameters/citrulline change groups; cumulative mean radiation dose/intestinal toxicity at end and four months post-RT; citrulline changes/intestinal toxicity during and end of RT. Citrulline concentration changes significantly differed during treatment according to RTOG intestinal toxicity grades (p < 0.0001). Although the citrulline changes differed significantly within RTOG intestinal toxicity grades (p = 0.003), the difference between Grade 0 and Grade 1 did not differ significantly at the end of the treatment. At four months after RT, no significant differences were apparent. Conclusion. Citrulline-based assessment scores are objective and should be considered in measuring radiation-induced intestinal toxicity

  3. The Circadian Clock Gene BMAL1 Coordinates Intestinal RegenerationSummary

    Directory of Open Access Journals (Sweden)

    Kyle Stokes

    2017-07-01

    Full Text Available Background & Aims: The gastrointestinal syndrome is an illness of the intestine caused by high levels of radiation. It is characterized by extensive loss of epithelial tissue integrity, which initiates a regenerative response by intestinal stem and precursor cells. The intestine has 24-hour rhythms in many physiological functions that are believed to be outputs of the circadian clock: a molecular system that produces 24-hour rhythms in transcription/translation. Certain gastrointestinal illnesses are worsened when the circadian rhythms are disrupted, but the role of the circadian clock in gastrointestinal regeneration has not been studied. Methods: We tested the timing of regeneration in the mouse intestine during the gastrointestinal syndrome. The role of the circadian clock was tested genetically using the BMAL1 loss of function mouse mutant in vivo, and in vitro using intestinal organoid culture. Results: The proliferation of the intestinal epithelium follows a 24-hour rhythm during the gastrointestinal syndrome. The circadian clock runs in the intestinal epithelium during this pathologic state, and the loss of the core clock gene, BMAL1, disrupts both the circadian clock and rhythmic proliferation. Circadian activity in the intestine involves a rhythmic production of inflammatory cytokines and subsequent rhythmic activation of the JNK stress response pathway. Conclusions: Our results show that a circadian rhythm in inflammation and regeneration occurs during the gastrointestinal syndrome. The study and treatment of radiation-induced illnesses, and other gastrointestinal illnesses, should consider 24-hour timing in physiology and pathology. Keywords: Intestine, Circadian Rhythms, Gastrointestinal Syndrome, TNF, Intestinal Stem Cells

  4. Recent Advances in Intestinal Stem Cells.

    Science.gov (United States)

    McCabe, Laura R; Parameswaran, Narayanan

    2017-09-01

    The intestine is a dynamic organ with rapid stem cell division generating epithelial cells that mature and apoptose in 3-5 days. Rapid turnover maintains the epithelial barrier and homeostasis. Current insights on intestinal stem cells (ISCs) and their regulation are discussed here. The Lgr5+ ISCs maintain intestinal homeostasis by dividing asymmetrically, but also divide symmetrically to extinguish or replace ISCs. Following radiation or mucosal injury, reserve BMI1+ ISCs as well as other crypt cells can de-differentiate into Lgr5+ ISCs. ISC niche cells, including Paneth, immune and myofibroblast cells secrete factors that regulate ISC proliferation. Finally, several studies indicate that the microbiome metabolites regulate ISC growth. ISC cells can be plastic and integrate a complexity of environmental/niche cues to trigger or suppress proliferation as needed.

  5. Radiation effects on diamine oxidase activities in intestine and plasma of the rat

    International Nuclear Information System (INIS)

    Ely, M.J.; Speicher, J.M.; Snyder, S.L.; Catravas, G.N.

    1985-01-01

    Diamine oxidase (DAO; EC 1.4.3.6) activity was measured in plasma and ileal tissue homogenates prepared from male Sprague-Dawley rats sacrificed at 1-15 days after acute whole-body irradiation with 14.5-MeV electrons. Animals irradiated with 1 Gy showed no significant changes in plasma and ileal DAO activities through day 13 relative to nonirradiated controls. Animals irradiated with 5, 10 and 12 Gy displayed marked declines in ileal DAO, with levels reaching a nadir on day 3. This was paralleled by a decrease in plasma DAO activity in all three dose groups. Recovery of ileal and plasma DAO levels was later seen as early as day 4 in animals irradiated with 5 and 10 Gy doses, but animals receiving 12 Gy did not survive beyond day 3. A further study highlights the relationship between radiation dose and levels of plasma and mucosal DAO on day 3, the time of maximum decrease at all doses tested. Mucosal DAO activity decreased almost linearly with doses up to 6 Gy. Plasma DAO levels closely paralleled the dose dependency of the mucosal levels. These data suggest that plasma DAO activity might be useful as a readily measurable marker of intestinal epithelial injury and recovery after acute radiation exposure

  6. Modification of radiation induced intestinal lesions by Aegle marmelos fruit extract, an Indian medicinal plant

    International Nuclear Information System (INIS)

    Agrawal, Annapurna; Jahan, Swafiya; Goyal, R.K.

    2012-01-01

    Recently, some plant extracts have been screened out against radiation and found to be quite promising. Aegle marmelos (Bael), belonging to family Rutaceae, fruits are very good source of proteins which form 5.12% of the edible portion. It is claimed to be useful in treating pain, fever, inflammation, respiratory disorders, cardiac disorders, dysentery and diarrhea. The ripe fruit is used for the treatment of digestive and stomachic complications. Aegle marmelos is a useful medicine for herbalist and it holds a reputed position in Ayurvedic system of medicine. Protection of intestinal constituents by Aegle marmelos extract (AME) was studied after exposure to 6 Gy gamma radiations in mice. For this purpose, Swiss albino mice were divided in various groups. Group I was administered with double distilled water (DDW), volume equal to AME (100 mg/kg body wt./animal), by oral gavage to serve as normal. Group II was administered orally AME extract once daily at a dose of 100 mg/kg b.wt./animal for 5 consecutive days. Group III was exposed to 6 Gy gamma radiations to serve as irradiated control. Group IV was treated with AME, orally for 5 consecutive days (as in Group-II), and were exposed to gamma radiation half an hour after the last administration of AME on day 5. Animals from all these group autopsied on 12 hrs, days 1, 3, 7, 15 and 30 post-treatment intervals

  7. Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats.

    Science.gov (United States)

    de Queiroz, Camila A A; Fonseca, Said Gonçalves C; Frota, Priscila B; Figueiredo, Italo L; Aragão, Karoline S; Magalhães, Carlos Emanuel C; de Carvalho, Cibele B M; Lima, Aldo Ângelo M; Ribeiro, Ronaldo A; Guerrant, Richard L; Moore, Sean R; Oriá, Reinaldo B

    2014-08-05

    WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc's anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats. Rats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation. Oral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea.

  8. Treatment-time-dependence models of early and delayed radiation injury in rat small intestine

    International Nuclear Information System (INIS)

    Denham, James W.; Hauer-Jensen, Martin; Kron, Tomas; Langberg, Carl W.

    2000-01-01

    Background: The present study modeled data from a large series of experiments originally designed to investigate the influence of time, dose, and fractionation on early and late pathologic endpoints in rat small intestine after localized irradiation. The objective was to obtain satisfactory descriptions of the regenerative response to injury together with the possible relationships between early and late endpoints. Methods: Two- and 26-week pathologic radiation injury data in groups of Sprague-Dawley rats irradiated with 27 different fractionation schedules were modeled using the incomplete repair (IR) version of the linear-quadratic model with or without various time correction models. The following time correction models were tested: (1) No time correction; (2) A simple exponential (SE) regenerative response beginning at an arbitrary time after starting treatment; and (3) A bi-exponential response with its commencement linked to accumulated cellular depletion and fraction size (the 'intelligent response model' [INTR]). Goodness of fit of the various models was assessed by correlating the predicted biological effective dose for each dose group with the observed radiation injury score. Results: (1) The incomplete repair model without time correction did not provide a satisfactory description of either the 2- or 26-week data. (2) The models using SE time correction performed better, providing modest descriptions of the data. (3) The INTR model provided reasonable descriptions of both the 2- and 26-week data, confirming a treatment time dependence of both early and late pathological endpoints. (4) The most satisfactory descriptions of the data by the INTR model were obtained when the regenerative response was assumed to cease 2 weeks after irradiation rather than at the end of irradiation. A fraction-size-dependent delay of the regenerative response was also suggested in the best fitting models. (5) Late endpoints were associated with low-fractionation sensitivity

  9. D-xylose test of resorption as a method to determine radiation side effects in small intestine

    International Nuclear Information System (INIS)

    Koest, S.; Keinert, K.; Glaser, F.H.

    1998-01-01

    Background: The D-xylose test is the most important method to determine a disorder of carbohydrates resorption in proximal small intestine. The application is based on an impaired resorption due to pathological change of small intestine surface, leading to a decreased blood level or decreased excretion in urine. Patients and Method: D-xylose test was applied in 91 patients before, shortly after, 1/2 and 1 year after radiotherapy. All patients received an abdominal radiotherapy. We determined the blood level of D-xylose by a capillary blood sample 1 hour after oral D-xylose administration. Results: A significant decrease of the mean blood level of D-xylose to 1.88 mmol/l was determined after radiotherapy in comparison with 2.17 mmol/l before radiotherapy. Half a year after radiotherapy the mean blood level of D-xylose returned to normal. Regarding a threshold value of D-xylose blood level of 1.70 mmol/l 29 patients (32%) showed a pathologically decreased D-xylose resorption after radiotherapy. Twenty out of the 29 patients already showed a normal resorption half a year after the determination of the resorption disorder, 5 patients after 1 year and 4 patients after 1 1/2 years. There was no correlation between the detection of a disorder of D-xylose resorption and of a loss of body weight. The acute clinical side effects seemed to be more marked in connection with a disorder of D-xylose resorption, but this correlation is not significant. Eleven or 14 of the 29 patients, respectively, with pathologically decreased D-xylose resorption only had complaints of lower or upper gastrointestinal tract, respectively, and 10 patients did not have abdominal complaints at all. Conclusions: The D-xylose test is an important and simple method for determination of radiogen induced carbohydrate malabsorption in proximal small intestine. By means of its radiation side effects on small intestine can also be determined in patients who are otherwise free of complaints. (orig.) [de

  10. The prevention of radiation-induced DNA damage and apoptosis in human intestinal epithelial cells by salvianic acid A

    Directory of Open Access Journals (Sweden)

    Yanjun Zhang

    2014-07-01

    Full Text Available The topic of radiation always provokes public debate, and the uses of radiation for therapeutic and other purposes have always been associated with some anxiety. Salvia miltiorrhiza Bunge has been widely used for the treatment of various diseases including cerebrovascular diseases, coronary artery diseases, and myocardial infarction. Salvianolic acid A (SAA d (+-(3,4-dihydroxyphenyl lactic acid is the principal effective, watersoluble constituent of Salvia miltiorrhiza Bunge. In our present study, radiation-induced DNA damage and apoptosis in human intestinal epithelial cells (HIEC in the presence and absence of SAA were examined. We investigated the effects of SAA on ROS formation and the activity of enzymatic antioxidants (SOD, the lipid peroxidative index and the levels of non-enzymatic antioxidant (GSH. Finally, we investigated whether the reduction of radiation-induced cell death caused by SAA might be related to mitochondria-dependent apoptosis. Present findings indicate that SAA is a promising radioprotective agent with a strong antioxidant activity. SAA exerted its protective action on the proliferative activity of HIEC cells as evidenced by decreased cytotoxicity after exposure to γ-radiation. It is possible that SAA achieved its radioprotective action, at least in part, by enhancing DNA repair and the activity of antioxidant enzymes, by scavenging ROS and by inhibiting the mitochondria-dependent apoptotic pathway.

  11. Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

    International Nuclear Information System (INIS)

    Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.; Barnes, M.; DeLuca, A.M.; Terrill, R.; Matthews, D.; Johnstone, P.A.S.; Anderson, W.J.; Bollinger, B.K.

    1994-01-01

    The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through a 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses ≥30 Gy. Radiation changes were present in the aorta and vena cava at doses ≥40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs

  12. Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

    Energy Technology Data Exchange (ETDEWEB)

    Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.; Barnes, M.; DeLuca, A.M.; Terrill, R.; Matthews, D.; Johnstone, P.A.S. [National Institutes of Health, Bethesda, MD (United States); Anderson, W.J. [Terre Haute Center for Medical Education, IN (United States); Bollinger, B.K. [National Naval Medical Center, Bethesda, MD (United States)

    1994-07-01

    The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through a 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses {ge}30 Gy. Radiation changes were present in the aorta and vena cava at doses {ge}40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs.

  13. Differential proteiomic analysis of mouse intestinal epithelium irradiated by γ-ray

    International Nuclear Information System (INIS)

    Zhang Bo; Su Yongping; Liu Xiaohong; Ai Guoping; Ran Xinze; Wei Yongjiang; Wang Junping; Cheng Tianmin

    2003-01-01

    Objective: For elucidating the molecular mechanism of reconstruction of intestinal epithelium damaged by ionizing radiation, the proteomes of murine intestinal epithelium from normal and irradiated mice were compared by 2-D electrophoresis. Methods: Histopathologic sections of whole small intestine made from BALB/c mice 3 h and 72 h after total-body irradiation were stained with hematoxylin-eosin. Intestinal epithelial cells were isolated from normal and irradiated mice. The total protein samples prepared by one-step method were used in 2-D electrophoresis, the protein maps were compared and the differential spots were detected with PDQuest analysis software. Twenty-eight different spots were cut off from the gels, digested in gel with trypsin, measured with MALDI-TOF-MS and searched in database. Results: Small intestinal epithelium was damaged as early as 3 h after irradiation, and reconstructed 72 h later. After Coomassie-staining, the 2-DE image analysis by PDQuest software detected 638 ± 39 protein spots in normal mice group, 566 ± 32 spots in 3 hours post irradiation group, and 591 ± 29 spots in 3 days post irradiation group. The 2-DE images showed that proteomes of intestinal epithelium were altered with γ-irradiation. The proteins identified by peptide mass fingerprinting involved in cellular events, including signal transduction, metabolism and oxidative stress responses. Conclusions: Gamma-irradiation can induce the protein expression of intestinal epithelium. The technique of 2-D electrophoresis is a useful tool in the study of molecular mechanism of radiation damage

  14. The protective effects of black garlic extract for blood and intestinal mucosa to irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Do Young; KIm, Joon Sun; Choi, Hyeong Seok [Dongnam Institute of Radiological and Medical Sciences Cancer Center, Busan (Korea, Republic of); Choi, Jun Hyeok; Park, Won Suk; Min, Byung In [Inje University, Kimhae (Korea, Republic of)

    2016-03-15

    The radiation has been utilized in a number of fields, even though the use of plenty cause a variety of side effects. This study was confirmed for radiation protective effects of aged garlic to contribute to the prevention of disasters that are radiation exposure. We studied the Complete Blood cell Count(CBC) and the small intestine after feeding aged garlic extract into Sprague Dawley Rat which irradiated X-ray beam 7 and 13 Gy. Garlic extract was administered to the results in the experimental group showed a notable difference in the CBC of platelets (p<0.05), red blood cells (p<0.05) and early damaged white blood cells (p<0.05). In addition, it was confirmed that experimental group's small intestine crypt is more survival than irradiation group significantly. And experimental group has small intestine villi length almost similar to the normal group. result of the aged garlic study will be able to be of great benefit for the radiation relevant emergency management.

  15. The protective effects of black garlic extract for blood and intestinal mucosa to irradiation

    International Nuclear Information System (INIS)

    Jung, Do Young; KIm, Joon Sun; Choi, Hyeong Seok; Choi, Jun Hyeok; Park, Won Suk; Min, Byung In

    2016-01-01

    The radiation has been utilized in a number of fields, even though the use of plenty cause a variety of side effects. This study was confirmed for radiation protective effects of aged garlic to contribute to the prevention of disasters that are radiation exposure. We studied the Complete Blood cell Count(CBC) and the small intestine after feeding aged garlic extract into Sprague Dawley Rat which irradiated X-ray beam 7 and 13 Gy. Garlic extract was administered to the results in the experimental group showed a notable difference in the CBC of platelets (p<0.05), red blood cells (p<0.05) and early damaged white blood cells (p<0.05). In addition, it was confirmed that experimental group's small intestine crypt is more survival than irradiation group significantly. And experimental group has small intestine villi length almost similar to the normal group. result of the aged garlic study will be able to be of great benefit for the radiation relevant emergency management

  16. Intestinal Failure: New Definition and Clinical Implications.

    Science.gov (United States)

    Kappus, Matthew; Diamond, Sarah; Hurt, Ryan T; Martindale, Robert

    2016-09-01

    Intestinal failure (IF) is a state in which the nutritional demands of the body are not met by the gastrointestinal absorptive surface. It is a long-recognized complication associated with short bowel syndrome, which results in malabsorption after significant resection of the intestine for many reasons or functional dysmotility. Etiologies have included Crohn's disease, vascular complications, and the effects of radiation enteritis, as well as the effects of intestinal obstruction, dysmotility, or congenital defects. While IF has been long-recognized, it has historically not been uniformly defined, which has made both recognition and management challenging. This review examines the previous definitions of IF as well as the newer definition and classification of IF and how it is essential to IF clinical guidelines.

  17. Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis.

    Science.gov (United States)

    Shailubhai, Kunwar; Palejwala, Vaseem; Arjunan, Krishna Priya; Saykhedkar, Sayali; Nefsky, Bradley; Foss, John A; Comiskey, Stephen; Jacob, Gary S; Plevy, Scott E

    2015-11-06

    To evaluate the effect of orally administered plecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models. The cyclic guanosine monophosphate (cGMP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cell-based assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid (5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium (DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic (TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout (TCRα(-/-)) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity. Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C (GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cGMP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs (0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity (P < 0.05) and disease activity index (P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα(-/-) mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. This is the first-ever study reporting

  18. Growth Hormone Protects the Intestine Preserving Radiotherapy Efficacy on Tumors: A Short-Term Study.

    Directory of Open Access Journals (Sweden)

    Victor Caz

    Full Text Available The efficacy of radiotherapy on tumors is hampered by its devastating adverse effects on healthy tissue, particularly that of the gastrointestinal tract. These effects cause acute symptoms that are so disruptive to patients that they can lead to interruption of the radiotherapy program. These adverse effects could limit the intensity of radiation received by the patient, resulting in a sublethal dose to the tumor, thus increasing the risk of tumor resistance. The lack of an effective treatment to protect the bowel during radiation therapy to allow higher radiation doses that are lethal to the tumor has become a barrier to implementing effective therapy. In this study, we present a comparative analysis of both intestinal and tumor tissue in regard to the efficacy and the preventive impact of a short-term growth hormone (GH treatment in tumor-bearing rats as a protective agent during radiotherapy. Our data show that the exogenous administration of GH improved intestinal recovery after radiation treatment while preserving the therapeutic effect against the tumor. GH significantly increased proliferation in the irradiated intestine but not in the irradiated tumors, as assessed by Positron Emission Tomography and the proliferative markers Ki67, cyclin D3, and Proliferating Cell Nuclear Antigen. This proliferative effect was consistent with a significant increase in irradiated intestinal villi and crypt length. Furthermore, GH significantly decreased caspase-3 activity in the intestine, whereas GH did not produce this effect in the irradiated tumors. In conclusion, short-term GH treatment protects the bowel, inducing proliferation while reducing apoptosis in healthy intestinal tissue and preserving radiotherapy efficacy on tumors.

  19. Modulatory effect of fenugreek seed mucilage and spent turmeric on intestinal and renal disaccharidases in streptozotocin induced diabetic rats.

    Science.gov (United States)

    Kumar, G Suresh; Shetty, A K; Salimath, P V

    2005-06-01

    To elucidate the effect of feeding fenugreek seed mucilage and spent turmeric (10%) on disaccharidases activities, the specific activities of intestinal and renal disaccharidases viz., sucrase, maltase and lactase were measured in streptozotocin induced diabetic rats. Specific activities of intestinal disaccharidases were increased significantly during diabetes and amelioration of these activities during diabetes was clearly visible by supplementing fenugreek seed mucilage and spent turmeric in the diet. However during diabetes renal disaccharidases activities were significantly lower than those in the control rats. Fenugreek seed mucilage and spent turmeric supplementations were beneficial in alleviating the reduction in maltase activity during diabetes, however not much change in the activities of sucrase and lactase was observed upon feeding. This positive influence of feeding fenugreek seed mucilage and spent turmeric on intestinal and renal disaccharidases clearly indicates their beneficial role in the management of diabetes.

  20. The acetate switch of an intestinal pathogen disrupts host insulin signaling and lipid metabolism.

    Science.gov (United States)

    Hang, Saiyu; Purdy, Alexandra E; Robins, William P; Wang, Zhipeng; Mandal, Manabendra; Chang, Sarah; Mekalanos, John J; Watnick, Paula I

    2014-11-12

    Vibrio cholerae is lethal to the model host Drosophila melanogaster through mechanisms not solely attributable to cholera toxin. To examine additional virulence determinants, we performed a genetic screen in V. cholerae-infected Drosophila and identified the two-component system CrbRS. CrbRS controls transcriptional activation of acetyl-CoA synthase-1 (ACS-1) and thus regulates the acetate switch, in which bacteria transition from excretion to assimilation of environmental acetate. The resultant loss of intestinal acetate leads to deactivation of host insulin signaling and lipid accumulation in enterocytes, resulting in host lethality. These metabolic effects are not observed upon infection with ΔcrbS or Δacs1 V. cholerae mutants. Additionally, uninfected flies lacking intestinal commensals, which supply short chain fatty acids (SCFAs) such as acetate, also exhibit altered insulin signaling and intestinal steatosis, which is reversed upon acetate supplementation. Thus, acetate consumption by V. cholerae alters host metabolism, and dietary acetate supplementation may ameliorate some sequelae of cholera. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. The Protective Role of Ginkgo Biloba against Radiation Induced Injury on Rat Gastro-intestinal Tract

    International Nuclear Information System (INIS)

    El-Ghazaly, M.A.; Gharib, O.A.; El-Sheikh, M.M.; Khayyal, M.T.

    2015-01-01

    Ginkgo Biloba extract (EGb 761) is an antioxidant substance exhibits a wide variety of biological activities. The present study was performed to evaluate oxidative stress and inflammatory parameters of gastrointestinal injury induced by exposing rats to acute doses of γ-rays and the potential value of EGb 761 in preventing changes in these parameters. Male albino rats were treated orally with the extract in a dose of 100 mg/ kg for 7 successive days before whole body exposure to acute radiation levels of 2 and 6 Gray (Gy). Control groups were run concurrently. The rats were sacrificed 3 days after irradiation. Various inflammatory mediators and biochemical parameters were determined in the stomach and intestine. Both tissues were also examined histopathologically. Exposure to radiation led to dose dependent changes in the level of oxidative stress biomarkers (elevation of thiobarbituric acid reactive substance (TBARS) and nitrite associated with a glutathione (GSH) decrease as well as in the level of inflammatory parameters (elevation of Tumour necrosis factorα (TNF-α) and myeloperoxidase (MPO) associated with depletion of prostaglandin E 2 (PGE 2 ). Pre-treatment with EGb 761 protected against the changes in both oxidative stress biomarkers and inflammatory mediators. EGb 761 exerted a protective effect against the radiation induced gastrointestinal damage, possibly through its anti-inflammatory and anti-oxidant properties.

  2. Differentiation and functional maturation of bone marrow-derived intestinal epithelial T cells expressing membrane T cell receptor in athymic radiation chimeras

    International Nuclear Information System (INIS)

    Mosley, R.L.; Styre, D.; Klein, J.R.

    1990-01-01

    The thymus dependency of murine intestinal intraepithelial lymphocytes (IEL) was studied in an athymic F1----parent radiation chimera model. IEL, although not splenic or lymph node lymphocytes, from athymic chimeras displayed normal levels of cells bearing the class-specific T cell Ag, CD4 and CD8; the TCR-associated molecule, CD3; and the Thy-1 Ag. Moreover, two-color flow cytometric analyses of IEL from athymic mice demonstrated regulated expression of T cell Ag characteristic of IEL subset populations from thymus-bearing mice. In immunoprecipitation experiments, surface TCR-alpha beta or TCR-gamma delta were expressed on IEL, although not on splenic lymphocytes, from athymic chimeras. That IEL from athymic chimeras constituted a population of functionally mature effector cells activated in situ, similar to IEL from thymus-bearing mice, was demonstrated by the presence of CD3-mediated lytic activity of athymic lethally irradiated bone marrow reconstituted IEL. These data provide compelling evidence that intestinal T cells do not require thymic influence for maturation and development, and demonstrate that the microenvironment of the intestinal epithelium is uniquely adapted to regulate IEL differentiation

  3. Surgical results in cases of intestinal radiation injury

    Energy Technology Data Exchange (ETDEWEB)

    Deguchi, Hisatsugu; Ozawa, Tetsuro; Wada, Toshihiro; Tsugu, Yukio (Toho Univ., Tokyo (Japan). School of Medicine)

    1991-05-01

    Surgical procedures were performed on 25 patients suffering from late-phase intestinal tract disorders induced by irradiation. The primary diseases of these cases were almost exclusively gynecological in nature, such as cancer of the uterine cervix. Symptoms observed in these cases were overwhelming ileus followed by melena, fistulation and free perforation, as well as combination thereof. The most common portion involved was the recto-sigmoidal colon, followed by the ileo-cecum and ileum. As for the relationship of symptoms to the disordered portion, ileus was seen mainly in cases of disorders at the ileocecal portion; melena was observed exclusively in cases of disorders at the rectosigmoidal colon; fistulation was manifested mainly as recto-vaginal fistula or ileo-sigmoidal fistula; free perforation was observed at both the ileum and sigmoidal colon. Colostomy was the most frequent surgical method applied. Only 3 cases were able to undergo enterectomy. Other cases were subjected to enteroanastomosis or enterostomy. In most cases it was nearly in possible to excise the disordered portions. As for the effect of surgical procedures on symptoms, cases of melena or fistulation were all subjected to colostomy; the majority of these cases showed improvement in symptoms. Moreover, a high improvement ratio was obtained in cases of ileus which were subjected to enterectomy and enteroanastomosis. Cases of free perforation showed high improvement ratio irrespective of the surgical procedure given. As for postoperative complications, one case of free perforation at the ileum showed anastomotic leakage after partial resection. For cases suffering from late-phase intestinal tract disorders induced by irradiation, immediate resection of the disordered intestinal tract and anastomosis are ideal. However, conservative operations must be considered, based on the focal condition. (author).

  4. The circadian rhythm for the number and sensitivity of radiation-induced apoptosis in the crypts of mouse small intestine

    International Nuclear Information System (INIS)

    Ijiri, K.; Potten, C.S.

    1990-01-01

    Survival curves were constructed from dose-incidence curves for apoptosis in the crypts of mouse small intestine, using the number of apoptotic cells after high doses (N M ) as maximum cell population size. The mean lethal doses (D 0 ) for the dose range 0-0.5 Gy were calculated for each time of day. A circadian rhythm in both D 0 and N M values was detected, indicating that both the number and sensitivity of radiation-induced apoptosis were changing throughout the day. (author)

  5. Arsenic Induced Toxicity in Broiler Chicks and Its Amelioration with Ascorbic Acid: Clinical, Hematological and Pathological Study

    Directory of Open Access Journals (Sweden)

    Rabia Sharaf, Ahrar Khan*, Muhammad Zargham Khan, Iftikhar Hussain, Rao Zahid Abbas, S. T. Gul, Fazal Mahmood and Muhammad Kashif Saleemi

    2013-07-01

    Full Text Available This study was conducted to observe the arsenic (As toxicity lesions in birds and to know either Vit C ameliorates these toxic effects or not. One-day-old broilers chicks (n=72 procured from a local hatchery were randomly divided into four equal groups. First group was kept as control and second group was given As (50 mg/kg BW via crop tubing. Third group received in addition to As, Vit C (250 mg/kg BW whereas fourth group received only Vit C. Killing by neck dislocation of randomly selected six birds from each group was carried out on experimental days 0, 16 and 32 for collection of blood and tissues specimens. Arsenic treated birds showed clinical signs of toxicity throughout the experiment than all other groups. These clinical signs included decreased body weight and feed intake, dullness, open mouth breathing, increased thirst, ruffled feathers, pale comb, skin irritation and watery diarrhea which were not significant in any other group. As treated group showed a significant (P<0.05 decrease in hematological parameters. Severe gross and histopathological changes were observed in intestines, spleen and lungs of birds fed with As than all other groups. Decreased height of villi of middle portion of small intestines was also observed in As treated birds. Villi height in Vit C treated group increased as compared to control group. It was concluded that As induces severe toxic effects in broiler birds; however, these toxic effects can be partially ameliorated by Vit C.

  6. Stress responsive miR-31 is a major modulator of mouse intestinal stem cells during regeneration and tumorigenesis.

    Science.gov (United States)

    Tian, Yuhua; Ma, Xianghui; Lv, Cong; Sheng, Xiaole; Li, Xiang; Zhao, Ran; Song, Yongli; Andl, Thomas; Plikus, Maksim V; Sun, Jinyue; Ren, Fazheng; Shuai, Jianwei; Lengner, Christopher J; Cui, Wei; Yu, Zhengquan

    2017-09-05

    Intestinal regeneration and tumorigenesis are believed to be driven by intestinal stem cells (ISCs). Elucidating mechanisms underlying ISC activation during regeneration and tumorigenesis can help uncover the underlying principles of intestinal homeostasis and disease including colorectal cancer. Here we show that miR-31 drives ISC proliferation, and protects ISCs against apoptosis, both during homeostasis and regeneration in response to ionizing radiation injury. Furthermore, miR-31 has oncogenic properties, promoting intestinal tumorigenesis. Mechanistically, miR-31 acts to balance input from Wnt, BMP, TGFβ signals to coordinate control of intestinal homeostasis, regeneration and tumorigenesis. We further find that miR-31 is regulated by the STAT3 signaling pathway in response to radiation injury. These findings identify miR-31 as a critical modulator of ISC biology, and a potential therapeutic target for a broad range of intestinal regenerative disorders and cancers.

  7. Intestinal lymphangiectasia secondary to radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Rao, S.S.; Dundas, S.; Holdsworth, C.D.

    1987-01-01

    We report a case of intestinal lymphangiectasia secondary to radiotherapy and chemotherapy. The patient also had small bowel bacterial overgrowth and pancreatic insufficiency. Lymphatic ectasia as a histological feature has been described previously in association with postradiotherapy malabsorption, but radiation-induced lymphangiectasia producing clinical manifestations has hitherto not been reported. Replacement of dietary long-chain fats with medium-chain triglycerides, pancreatic enzyme supplements, and a short course of oxytetracycline, resulted in dramatic clinical improvement. The possibility of intestinal lymphangiectasia should be borne in mind in patients with postradiotherapy malabsorption. A low serum albumin and lymphocyte count should draw attention to this possibility

  8. Radiation enteritis. Evaluation of surgical cases

    Energy Technology Data Exchange (ETDEWEB)

    Sato, M.; Sano, M.; Minakuchi, N.; Narisawa, T.; Takahashi, T. (Akita Univ. (Japan))

    1981-09-01

    Radiation enteritis with severe complications including intestinal bleeding, fistula, and stenosis were treated surgically in 9 cases. These 9 cases included 7 cases of cancer of the uterine cervix and 2 single cases of seminoma and melanoma. The patients received /sup 60/Co or Linac x-ray external irradiation with or without intracavitary irradiation by a radium needle. Radiation injury began with melena, vaginorectal fistula, and intestinal obstruction 3 to 18 months after irradiation. One patient with melena underwent colostomy and survived 2 years. One of the three patients with vaginorectal fistula who had colostomy survived 1.5 years. In intestinal obstruction, one patients had bypass operation and three patients had resection of the intestine and the other had both. Leakage was noted in one patient, but the others had favorable prognosis.

  9. PAF-Myc-Controlled Cell Stemness Is Required for Intestinal Regeneration and Tumorigenesis.

    Science.gov (United States)

    Kim, Moon Jong; Xia, Bo; Suh, Han Na; Lee, Sung Ho; Jun, Sohee; Lien, Esther M; Zhang, Jie; Chen, Kaifu; Park, Jae-Il

    2018-03-12

    The underlying mechanisms of how self-renewing cells are controlled in regenerating tissues and cancer remain ambiguous. PCNA-associated factor (PAF) modulates DNA repair via PCNA. Also, PAF hyperactivates Wnt/β-catenin signaling independently of PCNA interaction. We found that PAF is expressed in intestinal stem and progenitor cells (ISCs and IPCs) and markedly upregulated during intestinal regeneration and tumorigenesis. Whereas PAF is dispensable for intestinal homeostasis, upon radiation injury, genetic ablation of PAF impairs intestinal regeneration along with the severe loss of ISCs and Myc expression. Mechanistically, PAF conditionally occupies and transactivates the c-Myc promoter, which induces the expansion of ISCs/IPCs during intestinal regeneration. In mouse models, PAF knockout inhibits Apc inactivation-driven intestinal tumorigenesis with reduced tumor cell stemness and suppressed Wnt/β-catenin signaling activity, supported by transcriptome profiling. Collectively, our results unveil that the PAF-Myc signaling axis is indispensable for intestinal regeneration and tumorigenesis by positively regulating self-renewing cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.

    Science.gov (United States)

    Phillips, Matthew C; Dheer, Rishu; Santaolalla, Rebeca; Davies, Julie M; Burgueño, Juan; Lang, Jessica K; Toborek, Michal; Abreu, Maria T

    2018-01-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo. We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Successful Mitigation of Delayed Intestinal Radiation Injury Using Pravastatin is not Associated with Acute Injury Improvement or Tumor Protection

    International Nuclear Information System (INIS)

    Haydont, Valerie; Gilliot, Olivier; Rivera, Sofia; Bourgier, Celine; Francois, Agnes; Aigueperse, Jocelyne; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine

    2007-01-01

    Purpose: To investigate whether pravastatin mitigates delayed radiation-induced enteropathy in rats, by focusing on the effects of pravastatin on acute cell death and fibrosis according to connective tissue growth factor (CTGF) expression and collagen inhibition. Methods and Materials: Mitigation of delayed radiation-induced enteropathy was investigated in rats using pravastatin administered in drinking water (30 mg/kg/day) 3 days before and 14 days after irradiation. The ileum was irradiated locally after surgical exteriorization (X-rays, 19 Gy). Acute apoptosis, acute and late histologic alterations, and late CTGF and collagen deposition were monitored by semiquantitative immunohistochemistry and colorimetric staining (6 h, 3 days, 14 days, 15 weeks, and 26 weeks after irradiation). Pravastatin antitumor action was studied in HT-29, HeLa, and PC-3 cells by clonogenic cell survival assays and tumor growth delay experiments. Results: Pravastatin improved delayed radiation enteropathy in rats, whereas its benefit in acute and subacute injury remained limited (6 h, 3 days, and 14 days after irradiation). Delayed structural improvement was associated with decreased CTGF and collagen deposition but seemed unrelated to acute damage. Indeed, the early apoptotic index increased, and severe subacute structural damage occurred. Pravastatin elicited a differential effect, protecting normal intestine but not tumors from radiation injury. Conclusion: Pravastatin provides effective protection against delayed radiation enteropathy without interfering with the primary antitumor action of radiotherapy, suggesting that clinical transfer is feasible

  12. Echinacea and Parsley Oil Ameliorate the Changes Induced by gamma-radiation in Uterus, Ovaries and Bone Marrow of Female Rats

    International Nuclear Information System (INIS)

    Ramadan, F.L.; Othman, A.

    2013-01-01

    The aim of the present study was to evaluate the role of Echinacea and parsley oil some biochemical, histological and bone marrow abnormalities, induced by g-irradiation exposure. Echinacea and parsley oil were orally administrated to female rats (50 mg /100 g b.wt./ day and 0.2 ml/100g b.wt./day, respectively) 7 days before and during exposure to radiation for 3 weeks since female rats were submitted to fractionated whole body gamma-radiation 1 Gy every week up to 3 Gy total dose. The results obtained revealed that treatment with Echinacea and parsley oil induced significant amelioration to the harmful effect of radiation on red blood corpuscles (RBCs), white blood corpuscles (WBCs), haemoglobin concentration (Hb), calcium level (Ca), in addition to estradiol (E2) and progesterone (p4) hormones in serum. Moreover, the treatment with Echinacea and parsley oil diminished the increase in urea, uric acid, creatinine and alkaline phosphatase (ALP) levels recorded in the serum of irradiated rats. Our findings demonstrated that exposure to g-radiation caused an increase in the apoptotic cells, while the treatment with Echinacea and parsley oil decreased the apoptotic cells and increased the alive cells in the bone marrow of female rats. Histological observations of the ovary and uterus sections showed that radiation induced deformation in the follicular tissue, dis organization of granulosa cells, abnormal Graafian follicle which appeared without ova, haemorrhage, dilated blood vessels and vacuolation ovarian tissue. Also, the uterus of female rats showed increase in endometrium thickness, decreased muscularis thickness and muscle fibres appeared with pyknotic nuclei. All these changes were obviously improved in animals supplied with echinacea and parsley oil. It could be concluded that Echinacea and parsley oil could be useful and adjunct for maintaining the integrity of biochemical changes, restored the original histological architecture of the ovary and uterus and

  13. Curcumin and Chronic Kidney Disease (CKD: Major Mode of Action through Stimulating Endogenous Intestinal Alkaline Phosphatase

    Directory of Open Access Journals (Sweden)

    Siddhartha S. Ghosh

    2014-12-01

    Full Text Available Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa, has significant anti-inflammatory properties. Chronic kidney disease (CKD, an inflammatory disease, can lead to end stage renal disease resulting in dialysis and transplant. Furthermore, it is frequently associated with other inflammatory disease such as diabetes and cardiovascular disorders. This review will focus on the clinically relevant inflammatory molecules that play a role in CKD and associated diseases. Various enzymes, transcription factors, growth factors modulate production and action of inflammatory molecules; curcumin can blunt the generation and action of these inflammatory molecules and ameliorate CKD as well as associated inflammatory disorders. Recent studies have shown that increased intestinal permeability results in the leakage of pro-inflammatory molecules (cytokines and lipopolysaccharides from gut into the circulation in diseases such as CKD, diabetes and atherosclerosis. This change in intestinal permeability is due to decreased expression of tight junction proteins and intestinal alkaline phosphatase (IAP. Curcumin increases the expression of IAP and tight junction proteins and corrects gut permeability. This action reduces the levels of circulatory inflammatory biomolecules. This effect of curcumin on intestine can explain why, despite poor bioavailability, curcumin has potential anti-inflammatory effects in vivo and beneficial effects on CKD.

  14. In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury

    Science.gov (United States)

    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

  15. Amelioration of radiation induced DNA damage and biochemical alterations by Punica Granatum (L) extracts and synthetic ellagic acid in Swiss albino mice

    International Nuclear Information System (INIS)

    Satheesh Kumar Bhandary, B.; Sharmila, K.P.; Suchetha Kumari, N.; Vadisha Bhat, S.; Sherly, Sharmila; Sanjeev, Ganesh

    2013-01-01

    Radiation therapy has been used in cancer treatment for many decades; Although effective in killing tumor cells, ROS produced in radiotherapy threaten the integrity and survival of surrounding normal cells. ROS are scavenged by radioprotectors before they can interact with biochemical molecules, thus reducing harmful effects of radiation. The pomegranate, Punica granatum L., an ancient, mystical, and highly distinctive fruit, is the predominant member of the Punicaceae family. It is used in several systems of medicine for a variety of ailments. The objective of the present study was to investigate the protective effects of ethanolic extracts of pomegranate whole fruit (EPWF) and seeds (EPS) and Synthetic Ellagic acid (EA) against Electron Beam Radiation (EBR) induced DNA damage and biochemical alterations in Swiss Albino mice. The extracts and synthetic compound were assessed for its radical scavenging property by DPPH radical scavenging and Ferric Reducing Antioxidant Power assays. The animals were treated with 200 mg/kg body wt. of pomegranate extracts and Ellagic acid for 15 days before exposure to 6 Gy of EBR. Radiation induced DNA damage was assessed by comet assay in the peripheral blood lymphocytes of mice. The biochemical estimations were carried out in the serum and RBC lysate of the animals. The plant extracts and synthetic compound exhibited good radical scavenging and reducing properties.The pretreated animals before irradiation caused a reduction in the comet length, olive tail moment, % DNA in tail when compared to irradiated group. The biochemical parameters such as lipid peroxidation was significantly depleted in the treated groups when compared to irradiated group followed by significant elevation in reduced glutathione. Our findings indicate the ameliorating effects of pomegranate extracts and synthetic ellagic acid on radiation induced DNA damage and biochemical changes in mice may be due to its free radical scavenging and increased antioxidant

  16. Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats.

    Science.gov (United States)

    Turan, Inci; Ozacmak, Hale Sayan; Ozacmak, V Haktan; Barut, Figen; Araslı, Mehmet

    2017-11-15

    Oxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats. Four groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10mg/kg) was administered intraperitoneally before reperfusion period. After 180min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry. The treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-γ, and IL-1α were brought back to the sham control levels by the treatment as well. Our findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. [Adult intestinal malrotation associated with intestinal volvulus].

    Science.gov (United States)

    Hernando-Almudí, Ernesto; Cerdán-Pascual, Rafael; Vallejo-Bernad, Cristina; Martín-Cuartero, Joaquín; Sánchez-Rubio, María; Casamayor-Franco, Carmen

    Intestinal malrotation is a congenital anomaly of the intestinal rotation and fixation, and usually occurs in the neonatal age. Description of a clinical case associated with acute occlusive symptoms. A case of intestinal malrotation is presented in a previously asymptomatic woman of 46 years old with an intestinal obstruction, with radiology and surgical findings showing an absence of intestinal rotation. Intestinal malrotation in adults is often asymptomatic, and is diagnosed as a casual finding during a radiological examination performed for other reasons. Infrequently, it can be diagnosed in adults, associated with an acute abdomen. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  18. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10−/− mice by attenuating the activation of T cells and promoting their apoptosis

    International Nuclear Information System (INIS)

    Singh, Udai P.; Singh, Narendra P.; Singh, Balwan; Price, Robert L.; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

    2012-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptor induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10 −/− mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10 −/− mice. After JWH-133 treatment, the percentage of CD4 + T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells declined in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) of mice with chronic colitis. JWH-133 was also effective in ameliorating dextran sodium sulfate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodo-pravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, and suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD. -- Highlights: ► JWH-133, a cannnabinoid receptor-2 agonist ameliorates experimental colitis. ► JWH-133 suppressed inflammation and toxicity to colon

  19. Coniferyl aldehyde attenuates radiation enteropathy by inhibiting cell death and promoting endothelial cell function.

    Science.gov (United States)

    Jeong, Ye-Ji; Jung, Myung Gu; Son, Yeonghoon; Jang, Jun-Ho; Lee, Yoon-Jin; Kim, Sung-Ho; Ko, Young-Gyo; Lee, Yun-Sil; Lee, Hae-June

    2015-01-01

    Radiation enteropathy is a common complication in cancer patients. The aim of this study was to investigate whether radiation-induced intestinal injury could be alleviated by coniferyl aldehyde (CA), an HSF1-inducing agent that increases cellular HSP70 expression. We systemically administered CA to mice with radiation enteropathy following abdominal irradiation (IR) to demonstrate the protective effects of CA against radiation-induced gastrointestinal injury. CA clearly alleviated acute radiation-induced intestinal damage, as reflected by the histopathological data and it also attenuated sub-acute enteritis. CA prevented intestinal crypt cell death and protected the microvasculature in the lamina propria during the acute and sub-acute phases of damage. CA induced HSF1 and HSP70 expression in both intestinal epithelial cells and endothelial cells in vitro. Additionally, CA protected against not only the apoptotic cell death of both endothelial and epithelial cells but also the loss of endothelial cell function following IR, indicating that CA has beneficial effects on the intestine. Our results provide novel insight into the effects of CA and suggest its role as a therapeutic candidate for radiation-induced enteropathy due to its ability to promote rapid re-proliferation of the intestinal epithelium by the synergic effects of the inhibition of cell death and the promotion of endothelial cell function.

  20. Major intestinal complications of radiotherapy. Management and nutrition

    Energy Technology Data Exchange (ETDEWEB)

    Deitel, M.; To, T.B.

    1987-12-01

    Hospitalization was required in 57 patients for intestinal injuries following radiotherapy for carcinoma of the cervix, endometrium, ovary, bladder, rectum, and other primary sites. Intestinal complications included stenosis, perforation, rectal ulcer, and rectovaginal, ileovaginal, and ileovesical fistula; 27 patients had multiple intestinal complications. Operation was necessary in 33 patients, as follows: bowel resections, 18; colostomy alone, five; adhesiolysis, five; ileocolic bypass, three; and Hartmann's procedure for sigmoid perforation, two. Five anastomotic leaks and six postoperative deaths occurred. Causes of death among the remaining patients included residual cancer (ten), de novo bowel cancer (two), radiation injury (four), and unrelated causes (six). Resection to uninvolved bowel, omental wrap of anterior resection anastomosis, avoidance of unnecessary adhesiolysis, and long-tube orientation seemed to contribute to successful operations. Nutritional support was used for repletion, post-operative fistulas, and short-gut syndrome.

  1. Major intestinal complications of radiotherapy. Management and nutrition

    International Nuclear Information System (INIS)

    Deitel, M.; To, T.B.

    1987-01-01

    Hospitalization was required in 57 patients for intestinal injuries following radiotherapy for carcinoma of the cervix, endometrium, ovary, bladder, rectum, and other primary sites. Intestinal complications included stenosis, perforation, rectal ulcer, and rectovaginal, ileovaginal, and ileovesical fistula; 27 patients had multiple intestinal complications. Operation was necessary in 33 patients, as follows: bowel resections, 18; colostomy alone, five; adhesiolysis, five; ileocolic bypass, three; and Hartmann's procedure for sigmoid perforation, two. Five anastomotic leaks and six postoperative deaths occurred. Causes of death among the remaining patients included residual cancer (ten), de novo bowel cancer (two), radiation injury (four), and unrelated causes (six). Resection to uninvolved bowel, omental wrap of anterior resection anastomosis, avoidance of unnecessary adhesiolysis, and long-tube orientation seemed to contribute to successful operations. Nutritional support was used for repletion, post-operative fistulas, and short-gut syndrome

  2. Significance of endothelial dysfunction in the pathogenesis of early and delayed radiation enteropathy

    Institute of Scientific and Technical Information of China (English)

    Junru Wang; Marjan Boerma; Qiang Fu; Martin Hauer-Jensen

    2007-01-01

    This review summarizes the current state of knowledge regarding the role of endothelial dysfunction in the pathogenesis of early and delayed intestinal radiation toxicity and discusses various endothelial-oriented interventions aimed at reducing the risk of radiation enteropathy. Studies published in the biomedical literature during the past four decades and cited in PubMed, as well as clinical and laboratory data from our own research program are reviewed. The risk of injury to normal tissues limits the cancer cure rates that can be achieved with radiation therapy. During treatment of abdominal and pelvic tumors, the intestine is frequently a major dose-limiting factor. Microvascular injury is a prominent feature of both early (inflammatory), as well as delayed (fibroproliferative) radiation injuries in the intestine and in many other normal tissues. Evidence from our and other laboratories suggests that endothelial dysfunction, notably a deficiency of endothelial thrombomodulin, plays a key role in the pathogenesis of these radiation responses. Deficient levels of thrombomodulin cause loss of vascular thromboresistance, excessive activation of cellular thrombin receptors by thrombin, and insufficient activation of protein C, a plasma protein with anticoagulant, anti-inflammatory, and cytoprotective properties. These changes are presumed to be critically involved in many aspects of early intestinal radiation toxicity and may sustain the fibroproliferative processes that lead to delayed intestinal dysfunction, fibrosis, and clinical complications. In conclusion, injury of vascular endothelium is important in the pathogenesis of the intestinal radiation response. Endothelial-oriented interventions are appealing strategies to prevent or treat normal tissue toxicity associated with radiation treatment of cancer.

  3. On factors modifying reparative regeneration of epithelial tissue of small intestine in the presence of intestinal syndrome

    International Nuclear Information System (INIS)

    Kudryavtsev, V.D.

    1980-01-01

    In experiments on Wistar rats irradiated in dosages of 1000 and 1200 rad, the possibility of reparative regeneration of cryptae was demonstrated in the case when ''intestinal death'' was prevented by therapeutic means (kanamycin mixed with Ringer-Lock's solution). Shielding of part of the abdomen and extensive bone marrow region, and transplantation of homologous bone marrow elicit a stimulatory effect on postradiation recovery of small intestine epithelial tissue. When radiation dose increases up to 1400 rad reepithelization of the exposed region occurs only with the protection of 50-60% of the abdomen. The regenerating cryptae do not appear after irradiation of the whole body or whole abdomen though life expectancy of rats increases up to 6-7 days due to the therapeutic cure

  4. Postirradiational changes in hematologic parameters and in intestinal microflora in rats

    International Nuclear Information System (INIS)

    Benova, K.; Striskova, K.; Dvorak, P.

    2007-01-01

    A decrease in the defense capacity of the body combined with penetration of intestinal microorganisms through the intestinal wall causes severe, often lethal complications of the acute radiation disease. We followed the clinical symptoms, the changes of hematological parameters and the changes of the composition of intestinal microflora in laboratory rats irradiated by a single, whole-body dose of 15 Gy gamma-rays. An increase of the common microflora in duodenum, liver and in oral cave and leucopenia in peripheral blood have been observe in all time intervals followed. The changes in red blood cells were characterized by anemia, manifesting clinically in hemorrhages and bloody diarrhea. (authors)

  5. Response of intestinal cells of differing topographical and hierarchical status to ten cytotoxic drugs and five sources of radiation

    International Nuclear Information System (INIS)

    Ijiri, K.; Potter, C.S.

    1983-01-01

    The spatial distribution of cell death among the epithelial cells lining the adult mouse small intestinal mucosa at various times after a range of doses of 10 different drugs as well as after internal or external irradiation (#betta# particles from tritium, #betta#- and X-rays and neutrons) has been recorded. Cell death, expressed as pycnosis or apoptosis, has been recorded for each cell position up the side of the crypts of the small intestine. Adriamycin and the various forms of radiation tend to kill cells preferentially at cell position 4-5 i.e. on cells very early in the lineage, probably stem cells. Isopropyl-methane-sulphonate, nitrogen mustard and possibly Actinomycin-D act on cell position 6-7, while 5-fluorouracil, Myleran, cyclophosphamide, and cycloheximide tend to kill cells at cell position 7-9. Vincristine and hydroxyurea are the 2 agents that exhibit a specificity for cells highest up the crypt, i.e. latest in transit population of the cell lineage by acting on cell positions 10 or 11. The data also suggest that normal healthy cells continue to migrate up the crypt and onto the villus in spite of considerable cell death and reduced cell production. (author)

  6. Response of intestinal cells of differing topographical and hierarchical status to ten cytotoxic drugs and five sources of radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ijiri, K; Potter, C S [Christie Hospital and Holt Radium Inst., Manchester (UK). Paterson Labs.

    1983-02-01

    The spatial distribution of cell death among the epithelial cells lining the adult mouse small intestinal mucosa at various times after a range of doses of 10 different drugs as well as after internal or external irradiation (..beta.. particles from tritium, ..gamma..- and X-rays and neutrons) has been recorded. Cell death, expressed as pycnosis or apoptosis, has been recorded for each cell position up the side of the crypts of the small intestine. Adriamycin and the various forms of radiation tend to kill cells preferentially at cell position 4-5 i.e. on cells very early in the lineage, probably stem cells. Isopropyl-methane-sulphonate, nitrogen mustard and possibly Actinomycin-D act on cell position 6-7, while 5-fluorouracil, Myleran, cyclophosphamide, and cycloheximide tend to kill cells at cell position 7-9. Vincristine and hydroxyurea are the 2 agents that exhibit a specificity for cells highest up the crypt, i.e. latest in transit population of the cell lineage by acting on cell positions 10 or 11. The data also suggest that normal healthy cells continue to migrate up the crypt and onto the villus in spite of considerable cell death and reduced cell production.

  7. The AT1 Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation-Induced Cognitive Impairment

    International Nuclear Information System (INIS)

    Robbins, Mike E.; Payne, Valerie B.S.; Tommasi, Ellen B.S.; Diz, Debra I.; Hsu, Fang-Chi; Brown, William R.; Wheeler, Kenneth T.; Olson, John; Zhao Weiling

    2009-01-01

    Purpose: We hypothesized that administration of the angiotensin type 1 (AT1) receptor antagonist, L-158,809, to young adult male rats would prevent or ameliorate fractionated whole-brain irradiation (WBI)-induced cognitive impairment. Materials and Methods: Groups of 80 young adult male Fischer 344 x Brown Norway (F344xBN) rats, 12-14 weeks old, received either: (1) fractionated WBI; 40 Gy of γ rays in 4 weeks, 2 fractions/week, (2) sham-irradiation; (3) WBI plus L-158,809 (20 mg/L drinking water) starting 3 days prior, during, and for 14, 28, or 54 weeks postirradiation; and (4) sham-irradiation plus L-158,809 for 14, 28, or 54 weeks postirradiation. An additional group of rats (n = 20) received L-158,809 before, during, and for 5 weeks postirradiation, after which they received normal drinking water up to 28 weeks postirradiation. Results: Administration of L-158,809 before, during, and for 28 or 54 weeks after fractionated WBI prevented or ameliorated the radiation-induced cognitive impairment observed 26 and 52 weeks postirradiation. Moreover, giving L-158,809 before, during, and for only 5 weeks postirradiation ameliorated the significant cognitive impairment observed 26 weeks postirradiation. These radiation-induced cognitive impairments occurred without any changes in brain metabolites or gross histologic changes assessed at 28 and 54 weeks postirradiation, respectively. Conclusions: Administering L-158,809 before, during, and after fractionated WBI can prevent or ameliorate the chronic, progressive, cognitive impairment observed in rats at 26 and 52 weeks postirradiation. These findings offer the promise of improving the quality of life for brain tumor patients

  8. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10{sup −/−} mice by attenuating the activation of T cells and promoting their apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Udai P.; Singh, Narendra P. [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Singh, Balwan [National Primate Research Center, Emory University, Atlanta GA 30329 (United States); Price, Robert L. [Department of Cell and Developmental Biology, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Mitzi [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Prakash S., E-mail: Prakash.Nagarkatti@uscmed.sc.edu [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States)

    2012-01-15

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptor induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10{sup −/−} mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10{sup −/−} mice. After JWH-133 treatment, the percentage of CD4{sup +} T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells declined in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) of mice with chronic colitis. JWH-133 was also effective in ameliorating dextran sodium sulfate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodo-pravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, and suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD. -- Highlights: ► JWH-133, a cannnabinoid receptor-2 agonist ameliorates experimental colitis. ► JWH-133 suppressed inflammation and

  9. Radiation Protection Dosimetry

    International Nuclear Information System (INIS)

    Kramer, H.M.; Schnuer, K.

    1992-01-01

    The contributions presented during the seminar provided clear evidence that radiation protection of the patient plays an increasingly important role for manufacturers of radiological equipment and for regulatory bodies, as well as for radiologists, doctors and assistants. The proceedings of this seminar reflect the activities and work in the field of radiation protection of the patient and initiate further action in order to harmonize dosimetric measurements and calculations, to ameliorate education and training, to improve the technical standards of the equipment and to give a push to a more effective use of ionising radiation in the medical sector

  10. Effects of cancer, radiotherapy and cytotoxic drugs on intestinal structure and function

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, M T; Spector, M H; Ladman, A J [New Mexico Univ., Albuquerque (USA)

    1979-09-01

    Intestinal malabsorption and the structural changes in the small intestine in relation to cancer, radiotherapy and cytotoxic drugs are reviewed. Primary intestinal malignancies are often associated with malabsorption; further studies have shown that tumours outside the gastrointestinal tract may also be accompanied by changes in intestinal structure resulting in malabsorption. Abdominal radiotherapy of cancer patients has been shown to result in ultrastructural changes in the small intestine, a decrease in intestinal enzyme activity and malabsorption of nutrients. The effects of cytotoxic drugs on the small intestinal structure and function are reviewed in more detail. The drugs discussed include the alkylating agents such as nitrogen mustard, cyclophosphamide, iphosphamide, 1,3-bis (2-chloroethyl)-1-nitrosourea and 1(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea. The effects of antimetabolites such as aminopterin, methotrexate, 5-fluoracil, cytosine arabinoside and 6-mercaptorpurine are also reviewed. Other drugs discussed were adriamycin, vincrinstine sulfate, vinblastine and hydroxyurea. Studies of the effects of combination chemotherapy on small intestinal structure and function are also described. It is concluded that chemotherapeutic drugs and radiation therapy may aggravate a malabsorptive state in view of their toxicity to the small intestinal cell, or may by themselves be responsible for malabsorption with resultant increase in cachexia and weight loss.

  11. Effects of cancer, radiotherapy and cytotoxic drugs on intestinal structure and function

    International Nuclear Information System (INIS)

    Shaw, M.T.; Spector, M.H.; Ladman, A.J.

    1979-01-01

    Intestinal malabsorption and the structural changes in the small intestine in relation to cancer, radiotherapy and cytotoxic drugs are reviewed. Primary intestinal malignancies are often associated with malabsorption; further studies have shown that tumours outside the gastrointestinal tract may also be accompanied by changes in intestinal structure resulting in malabsorption. Abdominal radiotherapy of cancer patients has been shown to result in ultrastructural changes in the small intestine, a decrease in intestinal enzyme activity and malabsorption of nutrients. The effects of cytotoxic drugs on the small intestinal structure and function are reviewed in more detail. The drugs discussed include the alkylating agents such as nitrogen mustard, cyclophosphamide, iphosphamide, 1,3-bis (2-chloroethyl)-1-nitrosourea and 1(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea. The effects of antimetabolites such as aminopterin, methotrexate, 5-fluoracil, cytosine arabinoside and 6-mercaptorpurine are also reviewed. Other drugs discussed were adriamycin, vincrinstine sulfate, vinblastine and hydroxyurea. Studies of the effects of combination chemotherapy on small intestinal structure and function are also described. It is concluded that chemotherapeutic drugs and radiation therapy may aggravate a malabsorptive state in view of their toxicity to the small intestinal cell, or may by themselves be responsible for malabsorption with resultant increase in cachexia and weight loss. (UK)

  12. Daikenchuto ameliorates muscle hypercontractility in a murine T-cell-mediated persistent gut motor dysfunction model.

    Science.gov (United States)

    Akiho, Hirotada; Nakamura, Kazuhiko

    2011-01-01

    Low-grade inflammation and immunological alterations are evident in functional gastrointestinal disorders such as irritable bowel syndrome (IBS). We evaluated the effects of daikenchuto (DKT), a pharmaceutical grade Japanese herbal medicine, on the hypercontractility of intestinal smooth muscle persisting after acute inflammation induced by a T-cell-activating anti-CD3 antibody (αCD3). BALB/c mice were injected with αCD3 (12.5 μg, i.p.), and DKT (2.7 g/kg) was administered orally once daily for 1 week. The contraction of isolated small intestinal muscle strips and muscle cells was examined on day 7 after αCD3 injection. The gene and protein expressions in the small intestines were evaluated by real-time PCR and multiplex immunoassays, respectively, on days 1, 3 and 7 after αCD3 injection. αCD3 injection resulted in significant increases in carbachol-evoked contractility in the muscle strips and isolated smooth muscle cells on day 7. DKT ameliorated the αCD3-induced muscle hypercontractility on day 7 in both the muscle strips and smooth muscle cells. αCD3 injection rapidly up- and downregulated the mRNA and protein expressions of pro- and anti-inflammatory cytokines, respectively. Although the influence of DKT on the mRNA expressions was moderate, the protein expressions of IL-13 and IL-17 were significantly decreased. We observed changes in the intestinal muscle contractility in muscle strips and muscle cells following resolution of inflammation in a T-cell-mediated model of enteropathy. The observed modulation of cytokine expression and function by DKT may lead to the development of new pharmacotherapeutic strategies aimed at a wide variety of gut motor dysfunction disorders. Copyright © 2011 S. Karger AG, Basel.

  13. Bone Marrow Derivation of Interstitial Cells of Cajal in Small Intestine Following Intestinal Injury

    Directory of Open Access Journals (Sweden)

    Dengqun Liu

    2010-01-01

    Full Text Available Interstitial cells of Cajal (ICCs in gastrointestinal tract are specialized cells serving as pacemaker cells. The origin of ICCs is currently not fully characterized. In this work, we aimed to study whether bone marrow-derived cells (BMDCs could contribute to the origin of ICCs in the muscular plexus of small intestine using GFP-C57BL/6 chimeric mice.Engraftment of BMDCs in the intestine was investigated for GFP expression. GFP positive bone marrow mononuclear cells reached a proportion of 95.65%±3.72% at different times in chimerism. Donor-derived cells distributed widely in all the layers of the gastrointestinal tract. There were GFP positive BMDCs in the myenteric plexus, which resembled characteristics of ICCs, including myenteric location, c-Kit positive staining, and ramified morphology. Donor-derived ICCs in the myenteric plexus contributed to a percentage ranging 9.25%±4.9% of all the ICCs in the myenteric plexus. In conclusion, here we described that donor-derived BMDCs might differentiate into gastrointestinal ICCs after radiation injury, which provided an alternative source for the origin of the ICCs in the muscular plexus of adult intestine. These results further identified the plasticity of BMDCs and indicated therapeutic implications of BMDCs for the gastrointestinal dysmotility caused by ICCs disorders.

  14. Surgical management of radiation enteritis

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, S.; Hujita, Y.; Watanabe, K.; Honda, I.; Yamamoto, H.; Yamada, S. [Chiba Cancer Center, Chiba City (Japan)

    1994-12-31

    In the past 21 years, The group have examined various disease states involving the ileum after radiation therapy for cervical cancers in this institution. Surgery was required in 7 cases of stenosis in the intestine, 5 cases of fistulization, and 5 cases of perforation, totally 17, and these cases were subjected to resection of the lesion site of the intestine, or exclusion or bypass surgery. Anastomoses were made between irradiated portions of intestine in most cases, but no sutural insufficiency at the anastomotic site was observed. These observations indicated possible avoidance of resection of a large portion of the intestine in anastomosis.

  15. AMELIORATIVE EFFECT OF GAMMA RADIATION ON SODIUM CHLORIDE STRESSED TOMATO PLANT GROWTH IN SOIL INFESTED WITH FUSARIUM OXYSPORUM F.SP. LYCOPERSICI

    International Nuclear Information System (INIS)

    RIZK, M.A.; BOTROS, H.W.

    2009-01-01

    The present study was carried out to investigate the influence of saline stress and/or gamma radiation on the tomato seedlings development, mycelial growth and sporulation of Fusarium oxysporum. Irradiation of the fungus ameliorated the detrimental effect of salinity and improved the percentage of seedlings emergence and increased the root and shoot lengths and dry weight of tomato seedlings. Also, coupling salinity with irradiation significantly increased the mycelial growth in soil and biomass gain of Fusarium oxysporum up to 2 kGy, above which the growth and sporulation were hardly affected and completely suppressed at 5 kGy. On the other hand, exposure of the tomato seeds up to 4 Gy counteracted the suppressive effect of salinity and increased the growth parameters in presence or absence of the fungus. Fusarium oxysporum f.sp. lycopersici appeared to be tolerant to salinity up to 4.8 EC (millimohse) and highly sensitive to irradiation dose 5 kGy.

  16. Ameliorating effect of hawthorn ( Crataegus oxyacantha ) and ...

    African Journals Online (AJOL)

    Ameliorating effect of hawthorn ( Crataegus oxyacantha ) and physical exercise on ... Conclusion: Crataegus oxyacantha extract has shown positive affect to ameliorate on ... Key words: Crataegus oxyacantha, physical activity, epilepsy, gerbil, ...

  17. Alteration of the digestive motility linked with radiation-induced inflammatory processes in rats; Alterations de la motricite digestive associees aux processus inflammatoires induits par les rayonnements ionisants chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Picard, C

    2000-12-01

    Exposure to ionizing radiation, whether accidental or for medical reasons, may lead to gastro-intestinal injury, characterized by nausea, vomiting, diarrhea and abdominal cramps. The aetiology of radiation-induced diarrhea remains to date unclear. In this study, we have investigated the acute effects of a 10 Gy abdominal irradiation on rat digestive functions. The objective of the first study was to evaluate the role of sensory afferent neurons, capsaicin-sensitive, on morphological changes and the inflammatory response following exposure. Three days after irradiation, we observed an inflammatory response characterized by neutrophils infiltration and mast cells de-granulation. No effect of capsaicin pre-treatment was seen on these parameters. However, neutrophils infiltration was increased as early as one day after irradiation in capsaicin-treated rats. No difference in severity of diarrhea was observed after denervation nor in morphological changes. These data demonstrate that abdominal irradiation results in diarrhea concomitant with an inflammatory response, and that sensory innervation does not play a major protective role. The objective of the rest of the work was in the first instance to characterize radiation-induced alterations of intestinal and colonic motility leading to diarrhea and secondly to evaluate the role of serotonin in such disorders. Perturbations in intestinal (MMC) and colonic (LSB) motor profiles were observed from the first day onwards. Migrating motor complexes (MMC) were completely disrupted at three days at the same time as the onset of diarrhea. In addition to inhibition of LSB, colonic fluid absorptive capacity was decreased and serotonin colonic tissue levels were increased three days after irradiation. Radiation-induced diarrhea was reduced by treatment with an antagonist of 5-HT{sub 3} receptors, granisetron, as were alterations of colonic motility and serotonin tissue levels. However, this treatment did not significantly ameliorate

  18. Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in radiation exposed small intestinal mucosa of the rat

    International Nuclear Information System (INIS)

    Kwag, Hyon Joo; Lee, Kyoung Ja; Rhee, Chung Sik

    2003-01-01

    The matrix metalloproteinases (MMPs) are a family of enzymes whose main function is the degradation of the extracellular matrix. Several studies have revealed that MMPs and TIMPs are related to the wound healing process and in photoaging caused by ultraviolet irradiation. However, the expressions of MMP and TIMP after irradiation have not, to the best of our knowledge, been studied. This study investigates the expressions of MMP-2 and TIMP-2 in rat intestinal mucosa following irradiation. The entire abdomen of Sprague-Dawley rats was irradiated using a single dose method. The rats were sacrificed on day 1, 2, 3, 5, 7 and 14 following irradiation. Histopathological observations were made using hematoxilin and eosin staining. The expressions of MMP-2 and TIMP-2 were examined using immunohistochemistry, immunoblotting and ELISA. Radiation induced damage, associated with atrophic villi, and infiltration of inflammatory cells was observed from the first postirradiation day, and severe tissue damage was observed on the second and the third postirradiation days. An increase in mitosis and the number of regenerating crypts, as evidence of regeneration, were most noticeable on the fifth postirradiation day. From the immunohistochemistry, the MMP-2 expression was observed from the first postirradiation day, but was most conspicuous on the third and the fifth postirradiation days. The TIMP-2 expression was most conspicuous on the fifth postirradiation day. From the immunoblotting, the MMP-2 expression was strongly positive on the third postirradiation day, and that of TIMP-2 showed a strong positive response on the fifth postirradiation day. In ELISA, tests, the expressions of MMP-2 and TIMP-2. were increased in the postirradiation groups compared to those of the normal controls, and showed a maximum increase on the fifth postirradiation day. These results were statistically significant. The expressions of MMP-2 and TIMP-2 were increased in the intestinal mucosa of the rats

  19. Creatine maintains intestinal homeostasis and protects against colitis.

    Science.gov (United States)

    Turer, Emre; McAlpine, William; Wang, Kuan-Wen; Lu, Tianshi; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Murray, Anne R; Beutler, Bruce

    2017-02-14

    Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N -ethyl- N -nitrosourea-mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted ( Gatm c/c ) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatm c/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatm c/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury.

  20. Lactobacillus kefiranofaciens M1 isolated from milk kefir grains ameliorates experimental colitis in vitro and in vivo.

    Science.gov (United States)

    Chen, Y P; Hsiao, P J; Hong, W S; Dai, T Y; Chen, M J

    2012-01-01

    Lactobacillus kefiranofaciens M1, isolated from and identified in Taiwanese milk kefir grain, has demonstrated immune-modulating activity. In the present study, we further investigated the effects of Lb. kefiranofaciens M1 on intestinal epithelial cells in vitro and on dextran sodium sulfate (DSS)-induced colitis in vivo. The possible mechanisms regarding the cytokine products and intestinal epithelial barrier restoration as well as the putative receptor for the protective effects of Lb. kefiranofaciens M1 were investigated. In vitro results indicated that Lb. kefiranofaciens M1 could strengthen the epithelial barrier function in vitro by increasing the transepithelial electrical resistance (TEER) and significantly upregulated the level of the chemokine CCL-20 at both the apical and basolateral sites. The in vivo effects of Lb. kefiranofaciens M1 on the regulation of intestinal physiology indicate that this strain could ameliorate DSS-induced colitis with a significant attenuation of the bleeding score and colon length shortening. Production of proinflammatory cytokines was decreased and that of the antiinflammatory cytokine IL-10 was increased in the DSS-treated mice given Lb. kefiranofaciens M1. The putative receptor for the protective effects of Lb. kefiranofaciens M1 was toll-like receptor 2 (TLR2), which was involved in probiotic-induced cytokine production in vitro and in attenuation of the bleeding score and colon length shortening in vivo. In this study, the kefir lactobacillus Lb. kefiranofaciens M1 clearly demonstrated an anticolitis effect. Based on these results, Lb. kefiranofaciens M1 has the potential to be applied in fermented dairy products as an alternative therapy for intestinal disorders. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. Effects of cytotoxic chemotherapeutic agents on split-dose repair in intestinal crypt cells

    International Nuclear Information System (INIS)

    Phillips, Theodore L.; Ross, Glenda Y.

    1997-01-01

    Purpose: Many cancer chemotherapeutic agents interact with radiation to enhance the amount of radiation damage observed in both tumor and normal tissues. It is important to predict this interaction and to determine the effect of drug on sublethal damage repair. To evaluate for effects in rapid renewing normal tissues, the intestinal crypt cell in vivo assay is an excellent one to employ. These studies investigate the effect of eleven cancer chemotherapeutic drugs on split-dose repair in the intestinal crypt cell of the mouse. Methods and Materials: LAF1 male mice, age 10-12 weeks, were exposed to whole-body irradiation with orthovoltage x-rays delivered as a single dose or as equally divided doses delivered with intervals between the two exposures of 2 to 24 h. In the experimental group, the cancer chemotherapeutic agent was administered intraperitoneally 2 h before the first radiation dose. At 3.6 days after the second irradiation, the mice were sacrificed; the jejunum was removed, fixed, and sectioned for light microscopy. The number of regenerating crypts were counted and corrected to represent the number of surviving cells per circumference. Results: Of the eleven drugs tested, only carmustine eliminated split-dose repair. Cisplatin delayed repair, and methotrexate caused marked synchronization obliterating the observation of split-dose repair. Conclusions: Most cytotoxic chemotherapeutic agents do not inhibit sublethal damage repair in intestinal crypt cells when given 2 h before the first radiation exposure. Absence of the initial increase in survival seen with split-dose radiation is noted with carmustine and high-dose methotrexate

  2. Use of Coffee Pulp and Minerals for Natural Soil Ameliorant

    Directory of Open Access Journals (Sweden)

    Pujiyanto Pujiyanto

    2007-05-01

    Full Text Available In coffee plantation, solid waste of coffee pulp is usually collected as heap nearby processing facilities for several months prior being used as compost. The practice is leading to the formation of odor and liquid which contaminate the environment. Experiments to evaluate the effect of natural soil ameliorant derived from coffee pulp and minerals were conducted at The Indonesian Coffee and Cocoa Research Institute in Jember, East Java. The experiments were intended to optimize the use of coffee pulp to support farming sustainability and minimize negative impacts of solid waste disposal originated from coffee cherry processing. Prior to applications, coffee pulp was hulled to organic paste. The paste was then mixed with 10% minerals (b/b. Composition of the minerals was 50% zeolite and 50% rock phosphate powder. The ameliorant was characterized for their physical and chemical properties. Agronomic tests were conducted on coffee and cocoa seedling. The experiments were arranged according to Randomized Completely Design with 2 factors, consisted of natural ameliorant and inorganic fertilizer respectively. Natural ameliorant derived from coffee pulp was applied at 6 levels: 0, 30, 60, 90, 120 and 150 g dry ameliorant/seedling of 3 kg soil, equivalent to 0, 1, 2, 3, 4 and 5% (b/b of ameliorant respectively. Inorganic fertilizer was applied at 2 levels: 0 and 2 g fertilizer/application of N-P-K compound fertilizer of 15-15-15 respectively. The inorganic fertilizer was applied 4 times during nursery of coffee and cocoa. The result of the experiment indicated that coffee pulp may be used as natural soil ameliorant. Composition of ameliorant of 90% coffee pulp and 10% of minerals has good physical and chemical characteristics for soil amelioration. The composition has high water holding capacity; cations exchange capacity, organic carbon and phosphorus contents which are favorable to increase soil capacity to support plant growth. Application of

  3. 16,16-dimethyl prostaglandin E2 increases survival of murine intestinal stem cells when given before photon radiation

    International Nuclear Information System (INIS)

    Hanson, W.R.; Thomas, C.

    1983-01-01

    A variety of prostaglandins (PG) protect the gastric and intestinal mucosa when given before damaging agents as absolute ethanol, acidified taurocholate, boiling water, or nonsteroidal anti-inflammatory agents (NSAI). A synthetic prostaglandin, 16,16-dimethyl PGE 2 , shown to be cytoprotective at physiologic levels to the above agents was given to mice 1 h before or 15 min after 137 Cs gamma(γ) whole-body irradiation. The survival of intestinal stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased when 16,16-dimethyl PGE 2 was given before but not after 137 Cs γ irradiation. The maximum degree of 16,16-dimethyl PGE 2 -induced radioprotection was seen when the drug was given 1 h before irradiation. No radioprotection was seen when the interval between drug and irradiation was 3 h or longer. When the time between 16,16-dimethyl PGE 2 and irradiation was kept at 1 h, the degree of radioprotection was dependent on the PG drug dose. There was a steep rise in the number of surviving cells at low doses of PG. These results imply that tumors which secrete PGE 2 may in part be protected from the lethal effects of ionizing photon radiation

  4. Clinical experience in 89 consecutive cases of chronic radiation enterocolitis

    Directory of Open Access Journals (Sweden)

    Ming-Cheng Chen

    2011-02-01

    Conclusions: We confirmed that as compared with recently developed innovative techniques, early primitive radiotherapy techniques were associated with more severe radiotherapy complications that required surgery. Smoking may enhance patients’ vulnerability to severe radiation injury. Surgery for radiation-induced intestinal obstruction, intestinal fistula and perforation is warranted because QOL, serum albumin level and body mass index were similar between the surgical and nonsurgical groups.

  5. Radiobiology of intestinal epithelium stem cells

    International Nuclear Information System (INIS)

    Konoplyannikova, O.A.

    1988-01-01

    After a single or three-fold whole body irradiation of mice with a dose of 4 Gy and the time interval for the proliferation to be restored (5 days or 3 weeks) the survival curve for stem cells of small intestine epithelium with regard to radiation dose was the same as that for non-preirradiated mice. This indicated that the proliferative potential of stem cells in these experimental conditions was not reduced

  6. Intestinal Cancer

    Science.gov (United States)

    ... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

  7. Counter-Radiation Balm and its Medical Properties at Radiation Injuries and Functional Disorders in Gastrointestinal Tract

    International Nuclear Information System (INIS)

    Melkadze, R.; Shalamberidze, M.

    2006-01-01

    It has been shown that the Counter-Radiation Balm (CRB) is fairly effective in normalization of secretory phenomena and eubiotic state of the digestive tract in conditions of their functional disorders induced by various causes. The CRB has normalizing effect on an intestional flora during experimental dysbacterioses, induced with irradiation and starvation. This holds true in both bone marrow- and mixed patterns of acute radiation disease (ARD). The CRB somewhat decreases a toxic constituent of ARD, increases colonization resistance of the intestine to external microbial invasions and precludes extension of intestinal area for conditionally-pathogene flora. (author)

  8. Prostaglandis and radiation

    International Nuclear Information System (INIS)

    Romantsev, E.F.; Blokhina, V.D.; Zhulanova, Z.I.; Koshcheenko, I.N.; Nikol'skij, A.V.; Filippovich, I.V.

    1984-01-01

    It was established that some biochemical distortions in the brain of animals, subjected to superlethal doses of ionizing radiation don't develope; the starting mechanisms of a radiation damage can be fundamentally another, as compared to the medullar and intestinal forms of radiation sickness. It enables to assume that observed changes in activity of prostaglandin-synthetase system during irradiation by 250 Gr dose are based on earlier formed changes in membrane permeability and distortion of receptor cell activity. Investigations of the effect of radiation damage modificators give additional information when studying the primary biochemical processes, initiating radiation sickness

  9. Role of Some Antioxidants in Ameliorating Disturbances Caused by Gamma Radiation in Female Rats

    International Nuclear Information System (INIS)

    El-Sherbiny, E. M.; Bayomi, M. M.; Addel-Aziz, S. M.

    2007-01-01

    The aim of this research is to investigate the role of supplemental antioxidant vitamins against some sex hormone and trace element disturbances in female rats 1 hour post exposure to 7.0 Gy of gamma radiation as a single dose using 60 Co source. Vitamins C and E were orally administered daily for 2 weeks in doses of 100 mg/kg and 25 mg/kg body weight, respectively. Total number of 48 female albino rats were equally divided into 4 groups; irradiated group (n = 12), vitamin C administered group (n = 12), vitamin E administered group (n = 12) and rats administered vitamin C followed immediately by vitamin E (n =12) post irradiation, in addition to the normal control group (n = 10). The results of this study revealed a significant reduction in serum estradiol level and highly significant reductions in serum progesterone level, zinc and selenium concentrations of female rats exposed to gamma rays, compared to control. Concerning groups administered vitamins, rats administered vitamin C showed a significant improvement in estradiol and progesterone levels, reaching the levels of control group and a non-significant improvement in serum zinc and selenium concentrations was recorded. Vitamin E administered group revealed a high significant increase in serum estradiol level accompanied with an improvement in progesterone, whereas a significant decrease in zinc was found and a significant amelioration in selenium concentration was recorded in comparison with control values. Administration of vitamin E followed immediately by vitamin C resulted in a significant increase in estradiol level and a remarkable improvement in the level of progesterone. Slight significant reduction in zinc was noticed, whereas selenium concentrations were reached normal levels in both E and C and and E groups in comparison with the other groups

  10. Total Glucosides of Paeony Promote Intestinal Motility in Slow Transit Constipation Rats through Amelioration of Interstitial Cells of Cajal.

    Directory of Open Access Journals (Sweden)

    Feiye Zhu

    Full Text Available Using an atropine-diphenoxylate-induced slow transit constipation (STC model, this study explored the effects of the total glucosides of paeony (TGP in the treatment of STC and the possible mechanisms.A prospective experimental animal study.The constipation model was set up in rats with an oral gavage of atropine-diphenoxylate and then treated with the TGP. The volume and moisture content of the faeces were observed and the intestinal kinetic power was evaluated. Meanwhile, the colorimetric method and enzyme linked immunosorbent assay (ELISA were employed to determine the changes of nitric oxide (NO, nitric oxide synthase (NOS, vasoative intestinal peptide (VIP and the P substance (SP in the serum, respectively. The protein expressions of c-kit and stem cell factor (SCF were assessed by immunohistochemical analysis and western blot, respectively, and the mRNA level of c-kit was measured by a reverse transcription polymerase chain reaction (RT-PCR.The TGP attenuated STC responses in terms of an increase in the fecal volume and moisture content, an enhancement of intestinal transit rate and the reduction of NO, NOS and VIP in the serum. In addition, the c-kit, a labeling of interstitial cells of Cajal (ICC increased at both protein and mRNA levels. SCF, which serves as a ligand of c-kit also increased at protein level.The analysis of our data indicated that the TGP could obviously attenuate STC through improving the function of ICC and blocking the inhibitory neurotransmitters such as NO, NOS and VIP.

  11. Total Glucosides of Paeony Promote Intestinal Motility in Slow Transit Constipation Rats through Amelioration of Interstitial Cells of Cajal

    Science.gov (United States)

    Zhu, Feiye; Xu, Shan; Zhang, Yongsheng; Chen, Fangming; Ji, Jinjun; Xie, Guanqun

    2016-01-01

    Objectives Using an atropine-diphenoxylate-induced slow transit constipation (STC) model, this study explored the effects of the total glucosides of paeony (TGP) in the treatment of STC and the possible mechanisms. Study Design A prospective experimental animal study. Methods The constipation model was set up in rats with an oral gavage of atropine-diphenoxylate and then treated with the TGP. The volume and moisture content of the faeces were observed and the intestinal kinetic power was evaluated. Meanwhile, the colorimetric method and enzyme linked immunosorbent assay (ELISA) were employed to determine the changes of nitric oxide (NO), nitric oxide synthase (NOS), vasoative intestinal peptide (VIP) and the P substance (SP) in the serum, respectively. The protein expressions of c-kit and stem cell factor (SCF) were assessed by immunohistochemical analysis and western blot, respectively, and the mRNA level of c-kit was measured by a reverse transcription polymerase chain reaction (RT-PCR). Results The TGP attenuated STC responses in terms of an increase in the fecal volume and moisture content, an enhancement of intestinal transit rate and the reduction of NO, NOS and VIP in the serum. In addition, the c-kit, a labeling of interstitial cells of Cajal (ICC) increased at both protein and mRNA levels. SCF, which serves as a ligand of c-kit also increased at protein level. Conclusion The analysis of our data indicated that the TGP could obviously attenuate STC through improving the function of ICC and blocking the inhibitory neurotransmitters such as NO, NOS and VIP. PMID:27478893

  12. Intestinal Anti-inflammatory Effects of Outer Membrane Vesicles from Escherichia coli Nissle 1917 in DSS-Experimental Colitis in Mice

    Directory of Open Access Journals (Sweden)

    María-José Fábrega

    2017-07-01

    Full Text Available Escherichia coli Nissle 1917 (EcN is a probiotic strain with proven efficacy in inducing and maintaining remission of ulcerative colitis. However, the microbial factors that mediate these beneficial effects are not fully known. Gram-negative bacteria release outer membrane vesicles (OMVs as a direct pathway for delivering selected bacterial proteins and active compounds to the host. In fact, vesicles released by gut microbiota are emerging as key players in signaling processes in the intestinal mucosa. In the present study, the dextran sodium sulfate (DSS-induced colitis mouse model was used to investigate the potential of EcN OMVs to ameliorate mucosal injury and inflammation in the gut. The experimental protocol involved pre-treatment with OMVs for 10 days before DSS intake, and a 5-day recovery period. Oral administration of purified EcN OMVs (5 μg/day significantly reduced DSS-induced weight loss and ameliorated clinical symptoms and histological scores. OMVs treatment counteracted altered expression of cytokines and markers of intestinal barrier function. This study shows for the first time that EcN OMVs can mediate the anti-inflammatory and barrier protection effects previously reported for this probiotic in experimental colitis. Remarkably, translation of probiotics to human healthcare requires knowledge of the molecular mechanisms involved in probiotic–host interactions. Thus, OMVs, as a non-replicative bacterial form, could be explored as a new probiotic-derived therapeutic approach, with even lower risk of adverse events than probiotic administration.

  13. Effects of medium-chain triglycerides on intestinal morphology and energy metabolism of intrauterine growth retarded weanling piglets.

    Science.gov (United States)

    Zhang, Li-Li; Zhang, Hao; Li, Yue; Wang, Tian

    2017-06-01

    It has been shown that there is a relationship between intrauterine growth retardation (IUGR) and postnatal intestinal damage involved in energy deficits. Therefore, the present study was conducted to investigate the effect of medium-chain triglycerides (MCT) on the intestinal morphology, intestinal function and energy metabolism of piglets with IUGR. At weaning (21 ± 1.1 d of age), 24 IUGR piglets and 24 normal birth weight (NBW) piglets were selected according to their birth weights (BW) (IUGR: 0.95 ± 0.04 kg BW; NBW: 1.58 ± 0.04 kg BW) and their weights at the time of weaning (IUGR: 5.26 ± 0.15 kg BW; NBW: 6.98 ± 0.19 kg BW). The piglets were fed a diet of either long-chain triglycerides (LCT) (containing 5% LCT) or MCT (containing 1% LCT and 4% MCT) for 28 d. Then, the piglets' intestinal morphology, biochemical parameters and mRNA abundance related to intestinal damage and energy metabolism were determined. IUGR was found to impair intestinal morphology, with evidence of decreased villus height and increased crypt depth; however, these negative effects of IUGR were ameliorated by MCT treatment. IUGR piglets showed compromised intestinal digestion and absorption functions when compared with NBW piglets. However, feeding MCT increased the maltase activity in the jejunum and alleviated IUGR-induced reductions in plasma d-xylose concentrations and jejunal sucrase activity. IUGR decreased the efficiency of the piglets' intestinal energy metabolism; however, piglets fed an MCT diet exhibited increased adenosine triphosphate (ATP) concentrations and ATP synthase F1 complex beta polypeptide expression, as well as decreased adenosine monophosphate-activated kinase alpha 1 expression in the jejunum of piglets. In addition, up-regulation of the piglets' citrate synthase and succinate dehydrogenase levels was found to occur following MCT treatment at both the activity and the transcriptional levels of the jejunum. Therefore, it can be postulated that

  14. Extra-intestinal findings on magnetic resonance enterography in children with inflammatory bowel disease

    International Nuclear Information System (INIS)

    Sheybani, E.F.; Sheikh, N.; Chavhan, G.B.; Greer, M.-L.C.

    2016-01-01

    Aim: To determine the occurrence of extra-intestinal findings on magnetic resonance enterography (MRE) in a large cohort of children with known or suspected inflammatory bowel disease, characterise those findings, determine the technique and frequency of follow-up imaging, and associated costs. Materials and methods: Imaging reports from 757 MRE examinations in 671 children with known or suspected IBD from 2011 through 2012 were analysed retrospectively. Reported extra-intestinal findings were categorised by two radiologists in consensus as normal, normal variants or commonly seen findings without clinical significance, or abnormal. Prior imaging reports of the patients with abnormal findings were reviewed to identify which findings were new or substantially changed. Subsequent imaging examinations, their associated costs, and additional work-up of extra-intestinal findings were recorded in each group. Results: A total of 403 extra-intestinal findings were reported in 290 MRE (38.3%) examinations performed in 269 children (40.1%). Of these, 189 (46.9%) findings were abnormal and new or significantly changed from prior imaging, 88 (21.8%) were abnormal and stable, 50 (12.4%) were normal variants or commonly seen findings with no clinical significance, and 76 (18.9%) were normal. Abnormal findings included 34.7% associated with IBD and 65.3% considered unrelated. Follow-up imaging was performed for 69 (17.1%) mostly abnormal findings in 94 patients (8.3%). Magnetic resonance imaging (51%) and ultrasound (28%) were the most commonly utilised imaging methods. Conclusion: MRE identifies a large number of previously unknown extra-intestinal abnormalities in children with known or suspected IBD, most unrelated to IBD. Although <10% of children having MRE undergo subsequent imaging of extra-intestinal abnormalities, given the rapid uptake of MRE in the paediatric population, emphasis should be given to avoiding techniques utilising ionising radiation at follow

  15. Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice.

    Directory of Open Access Journals (Sweden)

    Subhrajit Saha

    Full Text Available Nuclear accidents and terrorism presents a serious threat for mass casualty. While bone-marrow transplantation might mitigate hematopoietic syndrome, currently there are no approved medical countermeasures to alleviate radiation-induced gastrointestinal syndrome (RIGS, resulting from direct cytocidal effects on intestinal stem cells (ISC and crypt stromal cells. We examined whether bone marrow-derived adherent stromal cell transplantation (BMSCT could restitute irradiated intestinal stem cells niche and mitigate radiation-induced gastrointestinal syndrome.Autologous bone marrow was cultured in mesenchymal basal medium and adherent cells were harvested for transplantation to C57Bl6 mice, 24 and 72 hours after lethal whole body irradiation (10.4 Gy or abdominal irradiation (16-20 Gy in a single fraction. Mesenchymal, endothelial and myeloid population were characterized by flow cytometry. Intestinal crypt regeneration and absorptive function was assessed by histopathology and xylose absorption assay, respectively. In contrast to 100% mortality in irradiated controls, BMSCT mitigated RIGS and rescued mice from radiation lethality after 18 Gy of abdominal irradiation or 10.4 Gy whole body irradiation with 100% survival (p<0.0007 and p<0.0009 respectively beyond 25 days. Transplantation of enriched myeloid and non-myeloid fractions failed to improve survival. BMASCT induced ISC regeneration, restitution of the ISC niche and xylose absorption. Serum levels of intestinal radioprotective factors, such as, R-Spondin1, KGF, PDGF and FGF2, and anti-inflammatory cytokines were elevated, while inflammatory cytokines were down regulated.Mitigation of lethal intestinal injury, following high doses of irradiation, can be achieved by intravenous transplantation of marrow-derived stromal cells, including mesenchymal, endothelial and macrophage cell population. BMASCT increases blood levels of intestinal growth factors and induces regeneration of the irradiated

  16. Intestinal tract diseases

    International Nuclear Information System (INIS)

    Rozenshtraukh, L.S.

    1985-01-01

    Roentgenoanatomy and physiology of the small intestine are described. Indications for radiological examinations and their possibilities in the diagnosis of the small intestine diseases are considered.Congenital anomalies and failures in the small intestine development, clinical indications and diagnosis methods for the detection of different aetiology enteritis are described. Characteristics of primary malabsorption due to congenital or acquired inferiority of the small intestine, is provided. Radiological picture of intestinal allergies is described. Clinical, morphological, radiological pictures of Crohn's disease are considered in detail. Special attention is paid to the frequency of primary and secondary tuberculosis of intestinal tract. The description of clinical indications and frequency of benign and malignant tumours of the small intestine, methods for their diagnosis are given. Radiological pictures of parasitogenic and rare diseases of the small intestine are presented. Changes in the small intestine as a result of its reaction to pathological processes, developing in other organs and systems of the organism, are described

  17. Cloning of radiation-induced new gene RS1 expressed in mouse intestinal epithelium by enhanced RACE

    International Nuclear Information System (INIS)

    Wang Fengchao; Wang Junping; Su Yongping; Gao Jinsheng; Lou Shufen; Liu Xiaohong; Ren Jiong; Zhang Bo

    2003-01-01

    Objective: To obtain full-length cDNA of radiation-induced new gene RS1 expressed in mouse intestinal epithelium. Methods: The tissue expression profile of RS1 was analyzed by semi-quantitative RT-PCR to find the target tissue which highly expresses RS1. The total RNA extracted from the corresponding tissue was taken as the template for reverse-transcription. Enhanced RACE PCR was used to clone the full-length cDNA of RS1, including enrichment of the target gene through biotin-labeled probe for magnetic bead purification and nested PCR. Results: About a 2 kb long 3' end was successfully cloned and cloning of the 5' end proceeded well. Conclusion: The result is consistent with our experiment design. The set of combined techniques has been identified with the cloning of full-length cDNA from EST sequence especially when the optimal gene-specific primers are not available or the expression level of target gene is low

  18. Role of plasminogen activator inhibitor type-1 in radiation-induced normal tissues injury

    International Nuclear Information System (INIS)

    Abderrahmani, R.

    2010-01-01

    Radiotherapy is an essential tool for cancer treatment, but there is a balance between benefits and risks related to the use of ionizing radiation: the objective is to deliver a maximum dose to the tumour to destroy or to sterilize it while protecting surrounding normal tissues. Radio-induced damages to normal tissues are therefore a limiting factor when increasing the dose delivered to the tumour. One of the objectives of this research thesis is to bring to the fore a relationship between the initiation of lesions and the development of late damages, more particularly in the intestine, and to identify the involved molecular actors and their inter-connectivity. After a first part presenting ionizing radiation, describing biological effects of ionizing radiation and their use in radiotherapy, presenting the intestine and the endothelium and discussing the intestine radio-sensitivity, discussing the radio-induced intestine damages and radiotherapy-induced complications, and presenting the plasminogen activator inhibitor (PAI-1) and its behaviour in presence of ionizing radiation, two articles are reproduced. The first one addresses the effect of a pharmacological inhibition and of genetic deficiency in PAI-1 on the evolution of radio-induced intestine lesions. The second one discusses the fact that radio-induced PAI-1-related death of endothelial cells determines the severity of early radio-induced intestine lesions

  19. Dietary enhancement of intestinal radioresistance during fractionated irradiation

    International Nuclear Information System (INIS)

    Pageau, R.; St-Pierre, C.

    1978-01-01

    Rats fed laboratory chow or elemental diet 3 were given fractions of 240 rads of 60 Co γ radiation abdominally (1200 rads/week) until all animals had died. Changes in appetite, body weight, and mortality were monitored as a function of the cumulative dose received. More radiation was needed in the diet-fed group to achieve both 0 and 100% mortality, a difference of 37% at the mean lethal dose level. Both groups developed similar progressive anorexia but the diet-fed animals lost weight more slowly. Data indicate that basic intestinal radioresistance is enhanced by feeding the elemental diet

  20. Improvement for Amelioration Inventory Model with Weibull Distribution

    Directory of Open Access Journals (Sweden)

    Han-Wen Tuan

    2017-01-01

    Full Text Available Most inventory models dealt with deteriorated items. On the contrary, just a few papers considered inventory systems under amelioration environment. We study an amelioration inventory model with Weibull distribution. However, there are some questionable results in the amelioration paper. We will first point out those questionable results in the previous paper that did not derive the optimal solution and then provide some improvements. We will provide a rigorous analytical work for different cases dependent on the size of the shape parameter. We present a detailed numerical example for different ranges of the sharp parameter to illustrate that our solution method attains the optimal solution. We developed a new amelioration model and then provided a detailed analyzed procedure to find the optimal solution. Our findings will help researchers develop their new inventory models.

  1. Proposal to integrate the service on radiation hygiene at the primary health care services for workers exposed to ionizing radiation

    International Nuclear Information System (INIS)

    Frometa Suarez, Ileana; Lopez Pumar, Georgina; Gonzalez Amil, Melva

    1998-01-01

    The National Health System implemented in the last few years a new pattern of primary attention for workers by creating doctors offices in work centers. At the same time, the Ministry of Public Health (MINSAP) carries the medical surveillance of the staff exposed to ionizing radiation. This work proposes a program to integrate the consulting room on radiation hygiene to primary health care services for workers that work with ionizing radiation sources, aiming to ameliorate and improve them

  2. Stem cell injury and restitution after ionizing irradiation in intestine, liver, salivary gland, mesenteric lymph node

    International Nuclear Information System (INIS)

    Lee, Jae Hyun; Cho, Kyung Ja; Lee, Sun Joo; Jang, Won Suk

    1998-01-01

    There is little information about radiation injury on stem cell resident in other organs. In addition there is little experimental model in which radiation plays a role on proliferation stem cell in adult organ. This study was carried out to evaluate the early response of tissue injury and restitution in intestine, liver, salivary gland and lymph node, and to develop in vivo model to investigate stem cell biology by irradiation. The study is to assay the early response to radiation and setup an animal model for radiation effect on cellular response. Duodenal intestine, liver, submandibular salivary gland and mesenteric lymph node were selected to compare apoptosis and proliferating cell nuclear antigen (PCNA) expression to radiosensitivity. For the effect of radiation on cellular responses, rats were irradiated during starvation. Conclusionly, this study showed the value of apoptosis in detection system for evaluating cellular damage against radiation injury. Because apoptosis was regularly inducted depending on tissue-specific pattern, dose and time sequence as well as cellular activity. Furthermore in vivo model in the study will be helped in the further study to elucidate the relationship between radiation injury and starvation or malnutrition. (author). 22 refs., 6 figs

  3. 16,16-dimethyl prostaglandin E/sub 2/ increases survival of murine intestinal stem cells when given before photon radiation

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, W.R.; Thomas, C.

    1983-11-01

    A variety of prostaglandins (PG) protect the gastric and intestinal mucosa when given before damaging agents as absolute ethanol, acidified taurocholate, boiling water, or nonsteroidal anti-inflammatory agents (NSAI). A synthetic prostaglandin, 16,16-dimethyl PGE/sub 2/, shown to be cytoprotective at physiologic levels to the above agents was given to mice 1 h before or 15 min after /sup 137/Cs gamma(..gamma..) whole-body irradiation. The survival of intestinal stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased when 16,16-dimethyl PGE/sub 2/ was given before but not after /sup 137/Cs ..gamma.. irradiation. The maximum degree of 16,16-dimethyl PGE/sub 2/-induced radioprotection was seen when the drug was given 1 h before irradiation. No radioprotection was seen when the interval between drug and irradiation was 3 h or longer. When the time between 16,16-dimethyl PGE/sub 2/ and irradiation was kept at 1 h, the degree of radioprotection was dependent on the PG drug dose. There was a steep rise in the number of surviving cells at low doses of PG. These results imply that tumors which secrete PGE/sub 2/ may in part be protected from the lethal effects of ionizing photon radiation.

  4. Exposed persons at the Chernobyl Atomic Power Station accident: acute radiation effects

    International Nuclear Information System (INIS)

    Gus'kova, A.K.; Baranov, A.E.; Barabanova, A.V.

    1987-01-01

    Observation made over 115 patients with acute radiation sickness due to exposure external γ- and β-rays confirmed high efficiency of the earlier proposed principles of prognostication of the degree of severity by clinical manifestations of the primary disease response and those of separate syndromes, using the methods of hematological and cytogenetic analyses. Out of 115 victims, 56 persons had radiation burns (RB), 17 intestinal syndrome (IS), 80 - oropharengeal syndrome (ORS), 7 - interstitial radiation pneumonitis (IRP). In thanatogenesis, of prime importance were: RB (more than 40% of the body surface) - 19 persons and IRP - 7 persons. A severe course of intestinal and oropharengeal syndromes was combined with other fatal manifestations of radiation injury. Early isolation of patients (2-4 stages), selective decontamination of the intestine, prescription of a wide spectrum antibiotics, antimycotic and antiviral drugs, as well as γ-globulin could practically remove the risk of the development of fatal infectious complications during a medullary andtransitory forms of radiation sickness

  5. Surgical management of radiation enterocolitis

    International Nuclear Information System (INIS)

    Ieda, Katsuyuki; Katsumi, Masaharu; Ura, Shinzoh

    1980-01-01

    We reviewed 17 cases of severe radiation enterocolitis caused by tele-cobalt treatment for pelvic malignancies. They consisted of six males and nine females, ranging from 32 to 77 years old. The duration between the completion of radiation and the onset of symptoms varied from two months to ten years. Only two cases of them were treated conservatively and the other 15 cases were managed surgically. Six cases of the latter underwent an urgent surgery because of severe obstructive symptoms. Totally, 19 injuries to the intestine were revealed. The ileum was involved in eight patients, the rectum in seven and the sigmoid colon in four. Operative procedures carried out were intestinal resection with primary anastomosis in seven, colostomy alone in six and bypass operation in three. The resected segments of the ileum measured 40 cm long in two and 70 cm, 90 cm and 100 cm long in three respectively and the resected segments of the colon measured 15 cm and 45 cm long respectively. Three out of the seven cases with bowel resection were reconstructed with Gambee's single layer anastomosis and four with Albert-Lembert's two layer anastomosis. Type of anastomosis was end-to-end in six and end-to-side in one. Three cases underwent bypass operations because the injured intestines were densely adhered to the surroundings. Only one minor leakage occurred in seven primary anastomosis. Radiation doses ranged from 3000 to 9300 R. There was no relation between doses and severity of damage, clinical symptoms and site of injuries. There was no malignant findings around the damaged intestine. Many of the literatures report a high anastomotic leak in radiation enterocolitis, primary anastomosis can be carried out more safely if wide resection and reasonable anastomosis are performed. (author)

  6. Protective effect of an herbal preparation (HemoHIM) on radiation-induced intestinal injury in mice.

    Science.gov (United States)

    Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Park, Hae-Ran; Jung, Uhee; Jang, Jong Sik; Jo, Sung Kee

    2009-12-01

    The protective properties of an herbal preparation (HemoHIM) against intestinal damage were examined by evaluating its effects on jejunal crypt survival, morphological changes, and apoptosis in gamma-irradiated mice. The mice were whole-body irradiated with 12 Gy for the examination of jejunal crypt survival and any morphological changes and with 2 Gy for the detection of apoptosis and Ki-67 labeling. Irradiation was conducted using (60)Co gamma-rays. HemoHIM treatment was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36 and 12 hours pre-irradiation and 30 minutes post-irradiation or orally at a dosage of 250 mg/kg of body weight/day for 7 or 11 days before necropsy. The HemoHIM-treated group displayed a significant increase in survival of jejunal crypts, when compared to the irradiation controls. HemoHIM treatment decreased intestinal morphological changes such as crypt depth, villus height, mucosal length, and basal lamina length of 10 enterocytes after irradiation. Furthermore, the administration of HemoHIM protected intestinal cells from irradiation-induced apoptosis. These results suggested that HemoHIM may be therapeutically useful to reduce intestinal injury following irradiation.

  7. Intestinal Surgery.

    Science.gov (United States)

    Desrochers, André; Anderson, David E

    2016-11-01

    A wide variety of disorders affecting the intestinal tract in cattle may require surgery. Among those disorders the more common are: intestinal volvulus, jejunal hemorrhage syndrome and more recently the duodenal sigmoid flexure volvulus. Although general principles of intestinal surgery can be applied, cattle has anatomical and behavior particularities that must be known before invading the abdomen. This article focuses on surgical techniques used to optimize outcomes and discusses specific disorders of small intestine. Diagnoses and surgical techniques presented can be applied in field conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Experimental study on the hydroxyproline content of enteroanastomoses established in irradiated intestines of rats

    International Nuclear Information System (INIS)

    Winter, S.

    1984-01-01

    Cross-bred Sprague-Dawley rats were subjected to percutaneous X-irradiation of the rectosigmoid using a split-dose regimen and focal dose of 50 Gy. One day as well as one, two and four months after the cessation of irradiation a termino-terminal anastomosis was established in the area exposed to radiation. On days, 3, 7, 14 and 21 after surgery those parts of the intestine, which had been united by anastomosis, were removed in order to determine the hydroxyproline content of the latter. Further determinations were made in specimens of the tissue 1 cm above the anastomosis and carried out before surgery, after intraperitoneal injection of the anaesthetic alone or in animals subjected to laparatomy including intestinal exposure, where no anastomosis was established. In general, the collagen levels determined in colon anastomoses of irradiated or non-irradiated intestines of rats did not point to any adverse effects from radiation on the healing process. This result appears to be largely consistent with the experiences so far gained at the clinical level in the preoperative irradiation of colon carcinomas. (orig./MG) [de

  9. Down-regulation of NF-κB DNA binding activity by Angelica Sinensis to ameliorate radiation-induced pulmonary injury in mouse model

    International Nuclear Information System (INIS)

    Cao Zhen; Xie Conghua; Zhou Fuxiang; Luo Zhiguo; Zhou Yunfeng; Hang Guang

    2008-01-01

    Objective: To study the trend of NF-kB binding activity during the course of radiation-induced pulmonary injury (RPI), and to evaluate the intervention effect of Angelica Sinensis on it. Methods: Adult female C57BL/6J mice were randomly divided into 4 groups: blank control group (N group), Angelica Sinensis control group (A group), irradiation group (NX group) and irradiation group with Angelica Sinensis intervention (AX group). All mice from the NX and AX groups underwent single fraction of 12 Gy γ-ray delivered to the whole thorax. All mice were intraperitoneally injected 25% Angelica Sinensis injection (20 ml/kg) or identical volume Normal Sodiumdaily injection initiated 1 week before irradiation, lasted till 2 weeks after irradiation. Mice were sacrificed at designated time points (1, 24, 72 h, 1, 2, 4, 8, 16 and 24 weeks), and the whole lungs were removed freshly. HE and Masson staining were performed to provide histopathologic evidence and to evaluate the collagen deposit situation respectively. The immunohistochemical staining of NF-κB P65 protein was performed to identify the location as well as the relative content of P65 protein. The DNA binding activity of NF-κB was detected by TransAM TM ELISA assay. Results: HE and Masson staining manifested that visible pathological alterations began at 2 weeks, typical interstitial pneumonitis were showed at 4 and 8 weeks, collagen deposition was visible from 16 weeks. The NF-κB binding activity detection and the immunohistochemical half-quantity analysis showed two-phase elevation, at 24 h and 8 weeks. Preventive application of Angelica Sinensis revealed prominently ameliorative effect for RPI, with pathological improvement, decreased immunohistochemical staining and lower NF-κB binding activity in both peaks. Conclusions: During the development process of RPI, NF-κB binding activity shows two-phase elevation. Chinese medicine Angelica Sinensis can down-regulate the elevation, showing noted ameliorative effect

  10. Intervention of ginger or propolis ameliorates methotrexate-induced ileum toxicity.

    Science.gov (United States)

    Abdul-Hamid, Manal; Salah, Marwa

    2016-02-01

    The long-term clinical use of methotrexate (MTX) is restricted due to its severe intestinal toxicity. The protective effect of ginger or propolis on the toxicity induced by MTX is relatively less understood, so the possible protective effect of ginger or propolis, used separately, was investigated. A total of 60 male albino rats were divided into six groups as follows: (1) control group; (2) ginger group; (3) propolis group; (4) MTX group; (5) ginger + MTX group; and (6) propolis + MTX group. The present results show that MTX caused ileum injury, including shortening and fusion of the villi, inflammatory cell infiltration and goblet cell depletion. Administration of ginger or propolis ameliorated the MTX-induced ileum injury as shown by histological, immunohistochemical and ultrastructural investigations and statistical analysis. This is revealed by intact villi, which shows marked increase in brown colouration of proliferating cell nuclear antigen positive nuclei in the crypts region, improvement in the number of goblet cells and brush border length of ileum. The current results conclude the efficacy and safety of ginger and propolis, which may be due to their antioxidant properties. © The Author(s) 2013.

  11. Impact of Intestinal Microbiota on Intestinal Luminal Metabolome

    Science.gov (United States)

    Matsumoto, Mitsuharu; Kibe, Ryoko; Ooga, Takushi; Aiba, Yuji; Kurihara, Shin; Sawaki, Emiko; Koga, Yasuhiro; Benno, Yoshimi

    2012-01-01

    Low–molecular-weight metabolites produced by intestinal microbiota play a direct role in health and disease. In this study, we analyzed the colonic luminal metabolome using capillary electrophoresis mass spectrometry with time-of-flight (CE-TOFMS) —a novel technique for analyzing and differentially displaying metabolic profiles— in order to clarify the metabolite profiles in the intestinal lumen. CE-TOFMS identified 179 metabolites from the colonic luminal metabolome and 48 metabolites were present in significantly higher concentrations and/or incidence in the germ-free (GF) mice than in the Ex-GF mice (p metabolome and a comprehensive understanding of intestinal luminal metabolome is critical for clarifying host-intestinal bacterial interactions. PMID:22724057

  12. A study of the small intestine as a limiting normal tissue in radiotherapy

    International Nuclear Information System (INIS)

    Hamlet, R.

    1980-09-01

    The thesis describes intestinal crypt survival and scanning electron microscopy of the mucosa of the small intestine after single whole doses of neutron or gamma irradiation. The results demonstrate that scanning electron microscopy of the surface mucosa of the intestine, although difficult to quantitate, is a much more sensitive indicator of intestinal damage at low dose levels than the more standard methods involving the enumeration of surviving crypts of Lieberkuhn in a section of intestine. The results also show that the morphology of the jejunal mucosa follows a different pattern following neutron irradiation than after gamma irradiation. Survival and surface morphology after fractionated x and gamma irradiation is also discussed. There was lack of correlation between damage expressed in terms of crypt survival of mucosal damage in two out of three schedules. an investigation of the alternating fractionation formula of the Cumulative Radiation Effect model is discussed, together with possible reasons underlying differences between predictions and experimental results, and an assessment of the formula in general use. (U.K.)

  13. Small Intestine Disorders

    Science.gov (United States)

    ... disease Crohn's disease Infections Intestinal cancer Intestinal obstruction Irritable bowel syndrome Ulcers, such as peptic ulcer Treatment of disorders of the small intestine depends on the cause.

  14. Elemental diet as prophylaxis against radiation injury. Histological and ultrastructural studies

    International Nuclear Information System (INIS)

    McArdle, A.H.; Wittnich, C.; Freeman, C.R.; Duguid, W.P.

    1985-01-01

    The authors investigated whether elemental diet feeding would protect the intestine from radiation injury. Five dogs were fed an elemental diet for three days before receiving pelvic irradiation (500 rad/day for four days) and were maintained on the diet during the days of irradiation. These dogs were compared with five dogs that were fed normal kennel ration, but were treated similarly otherwise. One day and five days following completion of the radiation treatment, the dogs were anesthetized and a biopsy specimen of terminal ileum was taken for histologic and electron microscopic studies. In the dogs fed the elemental diet, there was no significant damage to the intestine seen on histological examination, and electron microscopy disclosed elongated microvilli and no organelle damage. However, both histological and electron microscopic examination of the intestine from dogs maintained on normal kennel ration showed that severe damage had occurred from the irradiation procedure. It seems, therefore, that the feeding of an elemental diet to dogs as a prophylaxis can afford protection to the intestine from the acute phase of radiation injury

  15. Roux-en-Y Gastric Bypass Surgery Suppresses Hepatic Gluconeogenesis and Increases Intestinal Gluconeogenesis in a T2DM Rat Model.

    Science.gov (United States)

    Yan, Yong; Zhou, Zhou; Kong, Fanzhi; Feng, Suibin; Li, Xuzhong; Sha, Yanhua; Zhang, Guangjun; Liu, Haijun; Zhang, Haiqing; Wang, Shiguang; Hu, Cheng; Zhang, Xueli

    2016-11-01

    Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and intestinal morphological adaption, as well as hepatic and intestinal gluconeogenesis. Twenty adult male T2DM rats induced by high-fat diet and low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, and serum lipid profiles were assessed to evaluate metabolic changes. Intestinal sections were stained with hematoxylin and eosin (H&E) for light microscopy examination. The messenger RNA (mRNA) and protein expression levels of key regulatory enzymes of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase)] were determined through reverse-transcription PCR (RT-PCR) and Western blotting, respectively. RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum triglyceride (TG) and free fatty acid (FFA) levels. The jejunum and ileum exhibited a marked increase in the length and number of intestinal villi after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK and G6Pase in the liver and upregulated expression of these enzymes in the jejunum and ileum tissues. RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The small intestine shows hyperplasia and hypertrophy after RYGB. Meanwhile, our study demonstrated that the reduced hepatic gluconeogenesis and increased intestinal gluconeogenesis may contribute to improved glucose homeostasis after RYGB.

  16. Ameliorative percutaneous lumbar discectomy

    International Nuclear Information System (INIS)

    Xiao Chengjiang; Su Huanbin; He Xiaofeng; Li Yanhao

    2005-01-01

    Objective: To ameliorate the percutaneous lumbar discectomy (APLD) for improving the effectiveness and amplifying the indicative range of PLD. Methods: To ameliorate percutaneous punctured route based on classic PLD and discectomy of extracting pulp out of the herniated disc with special pulpforceps. The statistical analysis of the therapeutic results on 750 disc protrusions of 655 cases undergone APLD following up from 6 to 54 months retrospectively. Results: The effective ratios were excellent in 40.2%, good for 46.6% and bad of 13.3%. No occurrance of intervertebral inflammation and paradiscal hematoma, there were only 1 case complicated with injuried cauda equina, and 4 cases with broken appliance within disc. Conclusions: APLD is effective and safe, not only indicative for inclusion disc herniation, but also for noninclusion herniation. (authors)

  17. Effect of lactic acid bacteria on the intestinal production of lactate and short-chain fatty acids, and the absorption of lactose

    DEFF Research Database (Denmark)

    Hove, H; Nordgaard-Andersen, I; Mortensen, P B

    1994-01-01

    (10) cells), but did not influence the concentrations and productions of DL-lactate and short-chain fatty acids in the ileostomic outputs and incubates. Large amounts of ingested lactic acid bacteria (4.2 x 10(10) cells) did not ameliorate lactose malabsorption measured by the breath-hydrogen test in 12...... lactose malabsorbers. This study shows that ingested lactic acid bacteria are indeed present in the colon, but it does not support the theory that they change the pattern of colonic fermentation or the degree of intestinal lactose malabsorption....

  18. Effects of intraoperative electron irradiation in the dog on cell turnover in intact and surgically-anastomosed aorta and intestine

    International Nuclear Information System (INIS)

    Sindelar, W.F.; Morrow, B.M.; Travis, E.L.; Tepper, J.; Merkel, A.B.; Kranda, K.; Terrill, R.

    1983-01-01

    Adults dogs were subjected to laparotomy and intraoperative electron irradiation after division and reanastomosis of aorta or after construction of a blind loop of small intestine having a transverse suture line and an end-to-side anastomosis. Dogs received intraoperative irradiation of both intact and anastomosed aorta or intestine in doses of 0, 2000, 3000, or 4500 rad. Animals were sacrificed at seven days or three months following treatment. At 24 hours prior to sacrifice, dogs received 5 mCi tritiated thymidine intravenously. Irradiated and non-irradiated segments of aorta and small intestine, including intact and anastomotic regions, were analyzed for tritiated thymidine incorporation and were subjected to autoradiography. Incorporation studies showed diminution in tritiated thymidine uptake by irradiated portions of aorta and small intestine, in both intact and anastomotic regions. Autoradiograms revealed that irradiated areas of intact or anastomotic aorta or intestine had diminished labeling of stromal cells, suggesting a lowered cell proliferative capacity of irradiated tissue compared to non-irradiated portions. Inflammatory cells showed similar labeling indices in irradiated and non-irradiated tissues, both intact and surgically-manipulated, suggesting that irradiation does not significantly affect a subsequent local inflammatory response. Radiation-induced decreases in tritiated thymidine incoporation in irradiated aorta and small intestine were generally more marked at seven days than at three months following irradiation, suggesting that radiation-induced depression of cell turnover rates decreases with time

  19. Gastrointestinal function in chronic radiation enteritis -effects of loperamide-N-oxide

    International Nuclear Information System (INIS)

    Yeoh, E.K.; Horowitz, M.; Russo, A.; Muecke, T.; Chatterton, B.E.; Robb, T.

    1993-01-01

    The effects of loperamide-N-oxide, a new peripheral opiate agonist precursor, on gastrointestinal function were evaluated in 18 patients with diarrhoea caused by radiation enteritis. Each patient was given loperamide-N-oxide and placebo for 14 days, separated by a washout period of 14 days. Gastrointestinal symptoms; absorption of bile acid, vitamin B12, lactose, and fat; gastric emptying; small intestinal and whole gut transit; and intestinal permeability were measured during placebo and loperamide-N-oxide phases. Data were compared with those obtained in 18 normal subjects. In the patient, in addition to an increased frequency of bowel actions there was reduced bile acid absorption, higher prevalence of lactose malabsorption associated with a reduced dietary intake of dairy products and faster small intestinal and whole gut transit when compared with the normal subjects. There was no significant difference in gastric emptying between the two groups. Treatment with loperamide-N-oxide was associated with a reduced frequency of bowel actions, slower small intestinal and total gut transit, more rapid gastric emptying improved absorption of bile acid and increased permeability to 51 Cr EDTA. These observations indicate that: (1) diarrhoea caused by chronic radiation enteritis is associated with more rapid intestinal transit and a high prevalence of bile acid and lactose malabsorption, and (2) loperamide-N-oxide slows small intestinal transit, increases bile acid absorption, and is effective in the treatment of diarrhoea associated with chronic radiation enteritis. (Author)

  20. Crypt base columnar stem cells in small intestines of mice are radioresistant

    NARCIS (Netherlands)

    Hua, G.; Thin, T.H.; Feldman, R.; Haimovitz-Friedman, A.; Clevers, H.; Fuks, Z.; Kolesnick, R.

    2012-01-01

    BACKGROUND & AIMS: Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that

  1. The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology.

    Science.gov (United States)

    Yu, Huimin; Hasan, Nesrin M; In, Julie G; Estes, Mary K; Kovbasnjuk, Olga; Zachos, Nicholas C; Donowitz, Mark

    2017-02-10

    The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases. However, this model is reductionist and lacks many of the complexities of normal intestine. Consequently, it is not yet possible to predict how great the advances using this model will be for understanding human physiology and pathophysiology, nor how the model will be modified to include multiple other intestinal cell types and physical forces necessary to more closely approximate normal intestine. This review describes recent studies using mini-intestines, which have readdressed previously established models of normal intestinal transport physiology and newly examined intestinal pathophysiology. The emphasis is on studies with human enteroids grown either as three-dimensional spheroids or two-dimensional monolayers. In addition, comments are provided on mouse studies in cases when human studies have not yet been described.

  2. Alleviation of acute radiation damages by post-irradiation treatments

    International Nuclear Information System (INIS)

    Kurishita, A.; Ono, T.

    1992-01-01

    Radiation induced hematopoietic and gastro-intestinal damages in mice were tried to alleviate experimentally by post-treatment. Combined treatment of OK-432 and aztreonam clearly prevented the radiation induced sepsis and elevated the survival rate in mice; the survival was 80% in the OK-432 plus aztreonam group while it was 55% in the group treated with OK-432 alone and 0% with saline. Irsogladine maleate, an anti-ulcer drug, increased the survival rate of jejunal crypt stem cells with a clear dose-related trend. The D 0 for irsogladine maleate was 2.8 Gy although it was 2.3 Gy for saline, These findings suggest that some conventional drugs are effective for radiation induced hematopoietic and gastro-intestinal damages and the possibility that they can be applied for people exposed to radiation accidentally. (author)

  3. Effects of the ionising radiations on the structure and the function of the intestinal epithelial cell; Effets des rayonnements ionisants sur la structure et la fonction de la cellule epitheliale intestinale

    Energy Technology Data Exchange (ETDEWEB)

    Haton, C

    2005-06-15

    The intestinal mucosa is a particularly radio-sensitive tissue and damage may occur following either accidental or therapeutic exposure. the deleterious actions of ionizing radiation are linked to the formation of sometimes overwhelming quantities of reactive oxygen species (R.O.S.). Production of R.O.S. is both direct and indirect from the secondary effects of irradiation. A better comprehension of the underlying mechanisms of injury will lead to more adapted therapeutic approaches to limit the harmful effects of irradiation. The homeostasis of the intestinal epithelium is regulated by three factors: proliferation, apoptosis and differentiation. these three factors were studied using the cell model, HT29, in order to analyze modulations of this balance after irradiation. our results, in agreement with other data, showed the establishment of mitotic delay. This arrest of proliferation was followed by apoptosis to be the major mechanism leading to cell death in this model. thus, for the first time, we have shown that irradiated intestinal epithelial cells preserve their capacity to differentiate. This indicates, although indirectly, that intestinal cells have and preserve an intrinsic capacity restore a functional epithelium. R.O.S. are considered as intermediates between the physical nature of radiations and biological responses. It seems essential to understand anti-oxidant mechanisms used by the cell for defence against the deleterious effects of R.O.S post exposure. This study of several anti-oxidant defence mechanisms of intestinal mucosa, was carried out in vivo in the mouse at different times following abdominal irradiation. We observed an early mitochondrial response in the hours following irradiation revealing this organelle as a particular target. We demonstrated a strong alteration of anti-oxidant capacity as revealed by a decrease in S.O.D.s, catalase and an increase of the G.P.X.s and M.T.s. A part of these modifications appeared to depend on an

  4. The radiological features of chronic radiation enteritis

    International Nuclear Information System (INIS)

    Mendelson, R.M.; Nolan, D.J.

    1985-01-01

    The radiological findings, using a single-contrast barium infusion technique, are described in a series of 13 patients with chronic radiation enteritis. The signs include evidence of submucosal thickening, single or multiple stenoses, adhesions and sinus or fistula formation. A combination of these signs characterises the condition. This technique is particularly suited to the investigation of radiation enteritis because of its ability to distend maximally the small intestine. A cause, stenosis and/or adhesions, was demonstrated in the eight of the 13 patients presenting with intermittent small-intestinal obstruction. Three patients had diarrhoea as their predominant complaint and a fistula was demonstrated in two. (author)

  5. The effect of 60Co γ-radiation and hydroxyurea on the in vivo chain growth of DNA in crypt cells of the small intestine of the mouse

    International Nuclear Information System (INIS)

    Johanson, K.J.; Rydberg, B.

    1977-01-01

    DNA chain growth has been studied in small intestinal crypt cells of the mouse in vivo using a sensitive method. The method was designed primarily to study radiation-induced DNA-breaks and their repair; but since there were breaks in DNA at the replicating fork, it was also possible to study DNA chain growth after a 3 H-thymidine pulse. It was found that DNA chain growth was not depressed by 200 rad of 60 Co γ-radiation. This finding supports the hypothesis that irradiation interferes mainly with the initiation of new replicons in mammalian cells affecting DNA chain growth only at higher doses. Hydroxyurea at sufficient dosage, however, depressed or even stopped DNA chain growth in mouse crypt cells in vivo. (author)

  6. Therapeutic effects of Glucagon-Like Peptide-2 on experimental radiation enteritis in rat

    International Nuclear Information System (INIS)

    Torres, S.

    2007-01-01

    Radiation enteritis in patients treated by abdominal and pelvic radiotherapy is characterized by acute mucosal disruption and chronic intestinal fibrosis. Using a model of localized intestinal irradiation in the rat, we showed remote intestinal dysfunction outside the irradiation field along the whole gut, probably associated with perturbations in the systems regulating intestinal functions. Based on the hypothesis of consequential late effects, acute administration of Glucagon-Like Peptide-2, a growth factor with specific trophic effect on the intestinal mucosa, limited the apparition of both acute and chronic radiation enteritis. This suggests that therapeutic strategies targeting the severity of acute tissue damage may also limit chronic sequelae. The study of GLP-2 effects on epithelial cells in co-culture with either subepithelial myo-fibroblasts or enteric nervous system emphasized the problem of the modelization of complex systems in vitro, and suggested a synergic action from these different actors in vivo. (author)

  7. Radiation enteropathy and leucocyte-endothelial cell reactions in a refined small bowel model

    Directory of Open Access Journals (Sweden)

    Osman Nadia

    2004-09-01

    Full Text Available Abstract Background Leucocyte recruitment and inflammation are key features of high dose radiation-induced tissue injury. The inflammatory response in the gut may be more pronounced following radiotherapy due to its high bacterial load in comparison to the response in other organs. We designed a model to enable us to study the effects of radiation on leucocyte-endothelium interactions and on intestinal microflora in the murine ileum. This model enables us to study specifically the local effects of radiation therapy. Method A midline laparotomy was performed in male C57/Bl6 mice and a five-centimetre segment of ileum is irradiated using the chamber. Leucocyte responses (rolling and adhesion were then analysed in ileal venules 2 – 48 hours after high dose irradiation, made possible by an inverted approach using intravital fluorescence microscopy. Furthermore, intestinal microflora, myeloperoxidase (MPO and cell histology were analysed. Results The highest and most reproducible increase in leucocyte rolling was exhibited 2 hours after high dose irradiation whereas leucocyte adhesion was greatest after 16 hours. Radiation reduced the intestinal microflora count compared to sham animals with a significant decrease in the aerobic count after 2 hours of radiation. Further, the total aerobic counts, Enterobacteriaceae and Lactobacillus decreased significantly after 16 hours. In the radiation groups, the bacterial count showed a progressive increase from 2 to 24 hours after radiation. Conclusion This study presents a refinement of a previous method of examining mechanisms of radiation enteropathy, and a new approach at investigating radiation induced leucocyte responses in the ileal microcirculation. Radiation induced maximum leucocyte rolling at 2 hours and adhesion peaked at 16 hours. It also reduces the microflora count, which then starts to increase steadily afterwards. This model may be instrumental in developing strategies against pathological

  8. Clinical and nutritional implications of radiation enteritis

    Energy Technology Data Exchange (ETDEWEB)

    Beer, W.H.; Fan, A.; Halsted, C.H.

    1985-01-01

    The clinical and nutritional significance of radiation enteritis was assessed in eight patients with chronic diarrhea which followed curative doses of radiotherapy for pelvic malignancies. Steatorrhea, found in seven malnourished patients, was ascribed to ileal disease or previous surgery, or to bacterial contamination of the small intestine. Lactose intolerance, assessed by breath hydrogen excretion after oral lactose and by jejunal lactase levels, was found in six patients. In a subgroup of five patients, the administration of two different defined formula liquid diets by nasoduodenal infusion decreased fecal fluid and energy losses by about one-half. Compared to Vivonex-HN, the infusion of Criticare-HN was associated with greater likelihood of intestinal gas production but a three-fold greater utilization of protein. Intestinal malabsorption and malnutrition in radiation enteritis has diverse etiologies. Whereas nutritional support by liquid diet limits fecal fluid and energy losses, these diets differ significantly in clinical tolerance and biologic value.

  9. Clinical and nutritional implications of radiation enteritis

    International Nuclear Information System (INIS)

    Beer, W.H.; Fan, A.; Halsted, C.H.

    1985-01-01

    The clinical and nutritional significance of radiation enteritis was assessed in eight patients with chronic diarrhea which followed curative doses of radiotherapy for pelvic malignancies. Steatorrhea, found in seven malnourished patients, was ascribed to ileal disease or previous surgery, or to bacterial contamination of the small intestine. Lactose intolerance, assessed by breath hydrogen excretion after oral lactose and by jejunal lactase levels, was found in six patients. In a subgroup of five patients, the administration of two different defined formula liquid diets by nasoduodenal infusion decreased fecal fluid and energy losses by about one-half. Compared to Vivonex-HN, the infusion of Criticare-HN was associated with greater likelihood of intestinal gas production but a three-fold greater utilization of protein. Intestinal malabsorption and malnutrition in radiation enteritis has diverse etiologies. Whereas nutritional support by liquid diet limits fecal fluid and energy losses, these diets differ significantly in clinical tolerance and biologic value

  10. Bile components and lecithin supplemented to plant based diets do not diminish diet related intestinal inflammation in Atlantic salmon.

    Science.gov (United States)

    Kortner, Trond M; Penn, Michael H; Bjӧrkhem, Ingemar; Måsøval, Kjell; Krogdahl, Åshild

    2016-09-07

    , and other combinations of supplements might prevent or ameliorate inflammation in the distal intestine.

  11. The effect of anaesthesia on the radiosensitivity of rat intestine, foot skin and R-1 tumours

    International Nuclear Information System (INIS)

    Kal, H.B.; Gaiser, J.F.

    1980-01-01

    A comparison has been made of the effects of Nembutal (sodium pentobarbital) and Ethrane (2-chloro-1,1,2-trifluoroethyldifluoromethyl ether) anaesthesia on the radiation responses of rat intestine, foot skin and R-1 rhabdomyosarcoma. Single-dose experiments under Nembutal or short-lasting Ethrane anaesthesia resulted in equivalent radiosensitivities for the R-1 sarcoma and foot skin, whereas Ethrane induced radiosensitization in the intestine. In the Ethrane anaesthesia lasting 3 hours, and in the split-dose experiments, Ethrane inhibited repair of radiation-induced damage in the R-1 sarcoma and in the foot skin. It is therefore recommended that the use of Ethrane as an anaesthetic should be avoided in experiments designed to investigate repair of damage in fractionated studies or during protracted irradiation treatments. (UK)

  12. Intestinal Lymphangiectasia

    Science.gov (United States)

    ... Overview of Crohn Disease Additional Content Medical News Intestinal Lymphangiectasia (Idiopathic Hypoproteinemia) By Atenodoro R. Ruiz, Jr., MD, ... Overview of Malabsorption Bacterial Overgrowth Syndrome Celiac Disease Intestinal ... Intolerance Short Bowel Syndrome Tropical Sprue Whipple ...

  13. Using of Coffee and Cardamom Mixture to Ameliorate Oxidative Stress Induced in irradiated Rats

    International Nuclear Information System (INIS)

    Hamza, R.G.; Osman, N.N.

    2013-01-01

    Human exposure to ionizing radiation induced overproduction of free radicals leading to oxidative stress. This study aimed to evaluate the possibility of using of coffee and cardamom mixture; as natural antioxidant compounds ; to ameliorate oxidative stress in rats induced by exposure to ionizing radiation. Phenolic contents in coffee and essential oils in cardamom were identified by using HPLC chromatography and GC/MS analysis. Four groups of adult male rats were used; the control group (A), the second group (B) received orally the mixture extract of coffee and cardamom (60 mg/100g body weight) for 8 weeks, the third group (C) irradiated (6 Gy) and the fourth group (D) received orally the mixture extract for 8 weeks and exposed to radiation at the 4th week. The results revealed that the administration of mixture extract of coffee and cardamom to rats significantly reduced the damage effect induced by irradiation via the adjustment of the antioxidant status, decreasing of malondialdehyde content and the subsequent amending of different biochemical parameters as well as some hormones. Accordingly, it is possible to indicate that coffee-cardamom reduced the radiation exposure induced oxidative stress.

  14. Amelioration of radiation damage to haemopoiesis by Ivastimul, given after irradiation to mice protected by peroral cystamine

    International Nuclear Information System (INIS)

    Vacek, A.; Rotkovska, D.; Bartonickova, A.; Kautska, J.

    1992-01-01

    Combined radioprotection by preirradiation peroral cystamine and postirradiation Ivastimul administration was examined in sublethally and lethally whole-body gamma-irradiated mice. Enhancement of haemopoietic recovery and increased survival of irradiated mice was demonstrated for a single dose of Ivastimul administered after irradiation. The ameliorative influence of combined radioprotection may be explained by haemopoietic stem cell protection by cystamine and haemopoietic stimulation mediated by Ivastimul. (author) 2 tabs., 3 figs., 20 refs

  15. The performance of maize crop during acid amelioration with ...

    African Journals Online (AJOL)

    Tanzania Journal of Science ... This study evaluated acid ameliorative potential and their effects on maize growth of four organic residues namely wild spikenard, cordia, cowpea and pigeon peas ... The finding suggests different acid ameliorating potential of residues, pigeon peas and cordia being the most effective.

  16. Intestinal parasites : associations with intestinal and systemic inflammation

    NARCIS (Netherlands)

    Zavala, Gerardo A; García, Olga P; Camacho, Mariela; Ronquillo, Dolores; Campos-Ponce, Maiza; Doak, Colleen; Polman, Katja; Rosado, Jorge L

    2018-01-01

    AIMS: Evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school-aged children with high rates of obesity. METHODS AND RESULTS: Plasma concentrations of CRP, leptin, TNF-α, IL-6 and IL-10 were measured as systemic inflammation markers and

  17. Radioprotective effects of natural β-carotene on villi and crypts in abdominally radiated mice

    International Nuclear Information System (INIS)

    Kurabe, Teruhisa; Itoh, Youko; Matsumura, Eijin; Nakamura, Atsushi; Ayakawa, Yoshio

    2002-01-01

    The protective effect of β-carotene against radiation injury to the small intestine of abdominally radiated mice (15 Gy) was examined with administration given pre-radiation, during (pre- and post-) radiation, and post-radiation. In the β-carotene group, the ratio of villus length to crypt was significantly greater in comparison with the radiation only group at 2 days after radiation. At 7 days after radiation, the ratio of necrotic cells in the crypt vs. the total was significantly lower, and the ratio of necrotic cells in the villus vs. the total was significantly greater with β-carotene administration, which indicated that β-carotene accelerated recovery from radiation injury. Each group administered β-carotene showed a significant radioprotective effect, with pre-radiation administration yielding a smaller effect than administration during radiation and post-radiation. It is concluded that pre-, during, and post-radiation administration of β-carotene protected against radiation injury of the small intestine and accelerated recovery from it. (author)

  18. Nopal feeding reduces adiposity, intestinal inflammation and shifts the cecal microbiota and metabolism in high-fat fed rats.

    Science.gov (United States)

    Moran-Ramos, Sofia; He, Xuan; Chin, Elizabeth L; Tovar, Armando R; Torres, Nimbe; Slupsky, Carolyn M; Raybould, Helen E

    2017-01-01

    Nopal is a cactus plant widely consumed in Mexico that has been used in traditional medicine to aid in the treatment of type-2 diabetes. We previously showed that chronic consumption of dehydrated nopal ameliorated hepatic steatosis in obese (fa/fa) rats; however, description of the effects on other tissues is sparse. The aim of the present study was to investigate the effects of nopal cladode consumption on intestinal physiology, microbial community structure, adipose tissue, and serum biochemistry in diet-induced obese rats. Rats were fed either a normal fat (NF) diet or a HF diet containing 4% of dietary fiber from either nopal or cellulose for 6 weeks. Consumption of nopal counteracted HF-induced adiposity and adipocyte hypertrophy, and induced profound changes in intestinal physiology. Nopal consumption reduced biomarkers of intestinal inflammation (mRNA expression of IL-6) and oxidative stress (ROS), modfied gut microbiota composition, increasing microbial diversity and cecal fermentation (SCFA), and altered the serum metabolome. Interestingly, metabolomic analysis of dehydrated nopal revealed a high choline content, which appeared to generate high levels of serum betaine, that correlated negatively with hepatic triglyceride (TAG) levels. A parallel decrease in some of the taxa associated with the production of trimethylamine, suggest an increase in choline absorption and bioavailability with transformation to betaine. The latter may partially explain the previously observed effect of nopal on the development of hepatic steatosis. In conclusion, this study provides new evidence on the effects of nopal consumption on normal and HF-diet induced changes in the intestine, the liver and systemic metabolism.

  19. Nopal feeding reduces adiposity, intestinal inflammation and shifts the cecal microbiota and metabolism in high-fat fed rats.

    Directory of Open Access Journals (Sweden)

    Sofia Moran-Ramos

    Full Text Available Nopal is a cactus plant widely consumed in Mexico that has been used in traditional medicine to aid in the treatment of type-2 diabetes. We previously showed that chronic consumption of dehydrated nopal ameliorated hepatic steatosis in obese (fa/fa rats; however, description of the effects on other tissues is sparse. The aim of the present study was to investigate the effects of nopal cladode consumption on intestinal physiology, microbial community structure, adipose tissue, and serum biochemistry in diet-induced obese rats. Rats were fed either a normal fat (NF diet or a HF diet containing 4% of dietary fiber from either nopal or cellulose for 6 weeks. Consumption of nopal counteracted HF-induced adiposity and adipocyte hypertrophy, and induced profound changes in intestinal physiology. Nopal consumption reduced biomarkers of intestinal inflammation (mRNA expression of IL-6 and oxidative stress (ROS, modfied gut microbiota composition, increasing microbial diversity and cecal fermentation (SCFA, and altered the serum metabolome. Interestingly, metabolomic analysis of dehydrated nopal revealed a high choline content, which appeared to generate high levels of serum betaine, that correlated negatively with hepatic triglyceride (TAG levels. A parallel decrease in some of the taxa associated with the production of trimethylamine, suggest an increase in choline absorption and bioavailability with transformation to betaine. The latter may partially explain the previously observed effect of nopal on the development of hepatic steatosis. In conclusion, this study provides new evidence on the effects of nopal consumption on normal and HF-diet induced changes in the intestine, the liver and systemic metabolism.

  20. Amelioration of radiation-induced pulmonary fibrosis by a water-soluble bifunctional sulfoxide radiation mitigator (MMS350).

    Science.gov (United States)

    Kalash, Ronny; Epperly, Michael W; Goff, Julie; Dixon, Tracy; Sprachman, Melissa M; Zhang, Xichen; Shields, Donna; Cao, Shaonan; Franicola, Darcy; Wipf, Peter; Berhane, Hebist; Wang, Hong; Au, Jeremiah; Greenberger, Joel S

    2013-11-01

    A water-soluble ionizing radiation mitigator would have considerable advantages for the management of acute and chronic effects of ionizing radiation. We report that a novel oxetanyl sulfoxide (MMS350) is effective both as a protector and a mitigator of clonal mouse bone marrow stromal cell lines in vitro, and is an effective in vivo mitigator when administered 24 h after 9.5 Gy (LD100/30) total-body irradiation of C57BL/6NHsd mice, significantly improving survival (P = 0.0097). Furthermore, MMS350 (400 μM) added weekly to drinking water after 20 Gy thoracic irradiation significantly decreased: expression of pulmonary inflammatory and profibrotic gene transcripts and proteins; migration into the lungs of bone marrow origin luciferase+/GFP+ (luc+/GFP+) fibroblast progenitors (in both luc+ marrow chimeric and luc+ stromal cell line injected mouse models) and decreased radiation-induced pulmonary fibrosis (P < 0.0001). This nontoxic and orally administered small molecule may be an effective therapeutic in clinical radiotherapy and as a counter measure against the acute and chronic effects of ionizing radiation.

  1. Intestinal Obstruction

    Science.gov (United States)

    ... Colostomy ) is required to relieve an obstruction. Understanding Colostomy In a colostomy, the large intestine (colon) is cut. The part ... 1 What Causes Intestinal Strangulation? Figure 2 Understanding Colostomy Gastrointestinal Emergencies Overview of Gastrointestinal Emergencies Abdominal Abscesses ...

  2. A case of ileo-cutaneou fistula due to radiation enteritis

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Tsukasa; Oguchi, Yoshiro; Nakaba, Hiroyuki [Kure National Hospital, Hiroshima (Japan); and others

    1992-07-01

    Radiation enteritis can cause late complications including stenosis, perforation, fistulization, and bleeding, which sometimes necessitate surgical treatment, but a complication of ileocutaneous fistula is rarely reported. In this paper, an excellent result of an operation for ileocutaneous fistula due to radiation enteritis is described. A 68-year-old woman had undergone extended total histerectomy and radiation therapy on uterine cervical cancer. After the operation and the radiation therapy, frequent abdominal pain bothered her and then the intestinal fistula ensued resulted in the fistulization. The fistula was located between two stenotic lesions of the intestine caused by radiation enteritis. Resection of ileum including the two stenotic lesion and the fistula and end-to-end anastomosis relieved the symptoms and the treatment course has been satisfactory. The two stenotic lesions were resected because it was suggested that the two stenotic lesions directly led the fistulization. She is now followed asymptomatically. (author).

  3. An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse.

    Science.gov (United States)

    Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A; Borrelli, Francesca

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for "CBD botanical drug substance," on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

  4. An orally active Cannabis extract with high content in cannabidiol attenuates chemical induced intestinal inflammation and hypermotility in the mouse

    Directory of Open Access Journals (Sweden)

    Ester Pagano

    2016-10-01

    Full Text Available Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD, here named CBD BDS for CBD botanical drug substance, on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS. Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol. The amounts of CBD in the colon, brain and liver after the oral treatments were measured by HPLC coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion or orally (only at one dose. In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

  5. Amebiasis intestinal Intestinal amebiasis

    Directory of Open Access Journals (Sweden)

    JULIO CÉSAR GÓMEZ

    2007-03-01

    Full Text Available Entamoeba histolytica es el patógeno intestinal más frecuente en nuestro medio -después de Giardia lamblia-, una de las principales causas de diarrea en menores de cinco años y la cuarta causa de muerte en el mundo debida a infección por protozoarios. Posee mecanismos patogénicos complejos que le permiten invadir la mucosa intestinal y causar colitis amebiana. El examen microscópico es el método más usado para su identificación pero la existencia de dos especies morfológicamente iguales, una patógena ( E. histolytica y una no patógena ( Entamoeba dispar, ha llevado al desarrollo de otros métodos de diagnóstico. El acceso al agua potable y los servicios sanitarios adecuados, un tratamiento médico oportuno y el desarrollo de una vacuna, son los ejes para disminuir la incidencia y mortalidad de esta entidad.Entamoeba histolytica is the most frequent intestinal pathogen seen in our country, after Giardia lamblia, being one of the main causes of diarrhea in children younger than five years of age, and the fourth leading cause of death due to infection for protozoa in the world. It possesses complex pathogenic mechanisms that allow it to invade the intestinal mucosa, causing amoebic colitis. Microscopy is the most used method for its identification, but the existence of two species morphologically identical, the pathogen one ( E. histolytica, and the non pathogen one ( E. dispar, have taken to the development of other methods of diagnosis. The access to drinkable water and appropriate sanitary services, an opportune medical treatment, and the development of a vaccine are the axes to diminish the incidence and mortality of this entity.

  6. Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo-Obstruction in 6 Dogs.

    Science.gov (United States)

    Zacuto, A C; Pesavento, P A; Hill, S; McAlister, A; Rosenthal, K; Cherbinsky, O; Marks, S L

    2016-01-01

    Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo-obstruction in humans and animals. To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Six client-owned dogs. Retrospective case series. Medical records were reviewed to describe signalment, clinicopathologic and imaging findings, histopathologic diagnoses, treatment, and outcome. All biopsy specimens were reviewed by a board-certified pathologist. Median age of dogs was 5.4 years (range, 15 months-9 years). Consistent clinical signs included vomiting (6/6), regurgitation (2/6), and small bowel diarrhea (3/6). Median duration of clinical signs before presentation was 13 days (range, 5-150 days). Diagnostic imaging showed marked gastric distension with dilated small intestines in 4/6 dogs. Full-thickness intestinal biopsies were obtained in all dogs by laparotomy. Histopathology of the stomach and intestines disclosed mononuclear inflammation, myofiber degeneration and necrosis, and fibrosis centered within the region of myofiber loss in the intestinal muscularis propria. All dogs received various combinations of immunomodulatory and prokinetic treatment, antimicrobial agents, antiemetics, and IV fluids, but none of the dogs showed a clinically relevant improvement with treatment. Median survival was 19 days after diagnosis (range, 3-270 days). Intestinal leiomyositis is a cause of intestinal pseudo-obstruction and must be diagnosed by full-thickness intestinal biopsy. This disease should be considered in dogs with acute and chronic vomiting, regurgitation, and small bowel diarrhea. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  7. The intestinal complement system in inflammatory bowel disease: Shaping intestinal barrier function.

    Science.gov (United States)

    Sina, Christian; Kemper, Claudia; Derer, Stefanie

    2018-06-01

    The complement system is part of innate sensor and effector systems such as the Toll-like receptors (TLRs). It recognizes and quickly systemically and/or locally respond to microbial-associated molecular patterns (MAMPs) with a tailored defense reaction. MAMP recognition by intestinal epithelial cells (IECs) and appropriate immune responses are of major importance for the maintenance of intestinal barrier function. Enterocytes highly express various complement components that are suggested to be pivotal for proper IEC function. Appropriate activation of the intestinal complement system seems to play an important role in the resolution of chronic intestinal inflammation, while over-activation and/or dysregulation may worsen intestinal inflammation. Mice deficient for single complement components suffer from enhanced intestinal inflammation mimicking the phenotype of patients with chronic inflammatory bowel disease (IBD) such as Crohn's disease (CD) or ulcerative colitis (UC). However, the mechanisms leading to complement expression in IECs seem to differ markedly between UC and CD patients. Hence, how IECs, intestinal bacteria and epithelial cell expressed complement components interact in the course of IBD still remains to be mostly elucidated to define potential unique patterns contributing to the distinct subtypes of intestinal inflammation observed in CD and UC. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. The role of natural growth stimulators in regulation of regeneration processes in small intestinal epithelium after irradiation

    International Nuclear Information System (INIS)

    Dziekiewicz, M.

    1996-01-01

    In this paper, basing on recently published data, the influence of growth factors on small intestine epithelium regeneration after irradiation is presented. Our knowledge of growth control in the small intestine mucosa may become an accepted mode of radio-, chemotherapy and the treatment of acute radiation sickness in the future. Results of recent studies suggest that there are different factors which can modulate the process of epithelium regeneration. Some of them such as gastrin, enteroglucagon, CCK, EGF, FGF, TGF and IL-11 are able to enhance this process. In addition, other factor-PGE-2 is responsible for not only stimulation of small intestine epithelium growth but radioprotection as well. (author)

  9. Modulatory role of allopurinol on xanthine oxidoreductase system and antioxidant status in irradiated rats

    International Nuclear Information System (INIS)

    Zahran, A.M.; Azab, Kh.Sh.; Abbady, M.I.

    2006-01-01

    Allopurinol is a xanthine oxidase (XO) inhibitor, used for management of hyperuricaema. It acts on purine catabolism without disrupting the biosynthesis of purine. The present work was conducted to examine the role of xanthine oxidase inhibitor (allopurinol) in minimizing radiation injuries in male albino rats. Allopurinol was given to rats via intraperitoneal (i.p) injection at a dose of 30 mg/kg body wt/day for 7 successive days before starting irradiation and 14 successive days during and in between exposure to gamma radiation. Rats were exposed to whole body gamma radiation, delivered as 1 Gy every other day up to total dose 8 Gy. Results demonstrate that treatment with allopurinol by the regime assumed in the present study minimized significantly the amount of thiobarbituric acid reactive substances (TBARS), product of lipid peroxidation, in liver, intestine and plasma. This effect was associated with significant amelioration in xanthine oxidoreductase (XOR) system as observed on the 1st and 7th days post last radiation fraction. The severity of changes in antioxidant parameters namely: superoxide dismutase (SOD), Catalase (CAT) and reduced glutathione (GSH) were less manifested in liver, intestine and blood as compared to irradiated rats. The levels of nitric oxide (NO) were significantly improved in plasma and the two investigated tissues as compared to irradiated rats. A significant decrease in plasma uric acid concentration was recorded on the 1st and 7th days post last allopurinol dose. However, significant amelioration was recorded in the plasma uric acid of rats treated with allopurinol before and during radiation exposure as compared to irradiated rats. Accordingly, it could be concluded that XO inhibitor (allopurinol) play a significant role in minimizing the tissue damages upon exposure to ionizing radiation via preventing the over production of reactive oxygen species (ROS) in irradiated cells through the XOR system of irradiation rats

  10. Changes in the carbohydrate-energy metabolism with radiation-induced intestine syndrome

    International Nuclear Information System (INIS)

    Kendysh, I.N.; Grozdov, S.P.

    1981-01-01

    A local exposure of the rat abdomen in a dose of 3.6 cC/kg decreases the oxygen uptake, oxidation of glucose and fatty acids, glucose tolerance and insulin resistance, and also causes a trend toward lactic acidosis. These changes in the carbohydrate-energy metabolism are normalized with the administration of insulin and dichloracetate, and they may be interpreted as consequences of a shock provoked by a massive predominant injury to the intestine [ru

  11. [Treatment of children with intestinal failure: intestinal rehabilitation, home parenteral nutrition or small intestine transplantation?

    NARCIS (Netherlands)

    Neelis, E.G.; Oers, H.A. van; Escher, J.C.; Damen, G.M.; Rings, E.H.; Tabbers, M.M.

    2014-01-01

    Intestinal failure is characterised by inadequate absorption of food or fluids, which is caused by insufficient bowel surface area or functioning. Children with chronic intestinal failure are dependent on parenteral nutrition (PN), which can be provided at home (HPN). In the Netherlands, HPN for

  12. Unusual Presentation of Postradiation Sarcoma With Subsequent Intestinal Metastasis Revealed by 18F-FDG PET/CT.

    Science.gov (United States)

    Lee, Tse-Hao; Chang, Cheng-Pei; Wu, Yuan-Hung; Huang, Wen-Sheng

    2017-10-01

    Radiation-related sarcoma is a rare but serious complication for patients after receiving radiation therapy initially for their primary malignancy. However, it usually takes several years and needs enough in-field radiation dose to develop this sarcoma. We describe a 60-year-old man with right axillary sarcoma revealed by whole-body F-FDG PET/CT 1 year after chemoradiotherapy, which presented ultrashort latency period and did not match the consensus definition of radiation-related sarcoma. Besides, metastatic sarcoma to small intestine was accidentally noted in the F-FDG PET/CT image.

  13. Severe small bowel radiation enteritis

    International Nuclear Information System (INIS)

    Jaen, J.; Santos, J.A.; Carrion, J.R.; Garcia, P.

    1989-01-01

    We have during recent years observed 8 patients with serious radiation injury to the small intestine. As the cases are quite illustrative, their symptomatology is briefly reported and the treatment and possible predisposing factors are analysed. (orig./MG)

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

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Eiichi [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Hosokawa, Masaya [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Faculty of Human Sciences, Tezukayama Gakuin University, Osaka (Japan); Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Tsukiyama, Katsushi; Yamada, Yuichiro [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Department of Internal Medicine, Division of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita (Japan); Seino, Yutaka [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Kansai Electric Power Hospital, Osaka (Japan); Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); CREST of Japan Science and Technology Cooperation (JST), Kyoto (Japan)

    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 glucose 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

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

    International Nuclear Information System (INIS)

    Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya

    2011-01-01

    Research highlights: → Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. → Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. → 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 β 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 glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [ 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 [ 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

  16. Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium.

    Directory of Open Access Journals (Sweden)

    Nicholas Lahar

    Full Text Available The intestinal crypt-niche interaction is thought to be essential to the function, maintenance, and proliferation of progenitor stem cells found at the bases of intestinal crypts. These stem cells are constantly renewing the intestinal epithelium by sending differentiated cells from the base of the crypts of Lieberkühn to the villus tips where they slough off into the intestinal lumen. The intestinal niche consists of various cell types, extracellular matrix, and growth factors and surrounds the intestinal progenitor cells. There have recently been advances in the understanding of the interactions that regulate the behavior of the intestinal epithelium and there is great interest in methods for isolating and expanding viable intestinal epithelium. However, there is no method to maintain primary human small intestinal epithelium in culture over a prolonged period of time. Similarly no method has been published that describes isolation and support of human intestinal epithelium in an in vivo model. We describe a technique to isolate and maintain human small intestinal epithelium in vitro from surgical specimens. We also describe a novel method to maintain human intestinal epithelium subcutaneously in a mouse model for a prolonged period of time. Our methods require various growth factors and the intimate interaction between intestinal sub-epithelial myofibroblasts (ISEMFs and the intestinal epithelial cells to support the epithelial in vitro and in vivo growth. Absence of these myofibroblasts precluded successful maintenance of epithelial cell formation and proliferation beyond just a few days, even in the presence of supportive growth factors. We believe that the methods described here can be used to explore the molecular basis of human intestinal stem cell support, maintenance, and growth.

  17. Dose-dependent effects of Lactobacillus rhamnosus on serum interleukin-17 production and intestinal T-cell responses in pigs challenged with Escherichia coli.

    Science.gov (United States)

    Zhu, Yao-Hong; Li, Xiao-Qiong; Zhang, Wei; Zhou, Dong; Liu, Hao-Yu; Wang, Jiu-Feng

    2014-03-01

    The mechanism underlying the dose effect of probiotics on ameliorating diarrhea has not been fully elucidated. Here, low (1 × 10(9) CFU/ml) or high (1 × 10(11) CFU/ml) doses of Lactobacillus rhamnosus ATCC 7469 were administered orally to piglets for 1 week before F4 (K88)-positive enterotoxigenic Escherichia coli (F4(+) ETEC) challenge. Administration of a low, but not a high, dose of L. rhamnosus decreased the percentage of CD3(+) CD4(+) CD8(-) T cells in the peripheral blood. Notably, transiently increased serum concentrations of interleukin-17A (IL-17A) were observed after F4(+) ETEC challenge in pigs pretreated with a high dose of L. rhamnosus. Administration of L. rhamnosus increased the percentage of the small intestinal lamina propria CD3(+) CD4(+) CD8(-) cells and Peyer's patch CD3(+) CD4(-) CD8(-) and CD3(-) CD4(-) CD8(+) cells. The percentage of ileal intraepithelial CD3(+) CD4(-) CD8(+) cells increased only in the high-dose piglets. Administration of L. rhamnosus downregulated expression of ileal IL-17A after F4(+) ETEC challenge but had no effect on expression of gamma interferon (IFN-γ), IL-12, IL-4, and FOXP3 mRNA in the small intestine. Expression of jejunal IL-2, ileal transforming growth factor β1 (TGF-β1), and ileal IL-10 was upregulated in the low-dose piglets after F4(+) ETEC challenge. Our findings suggest that amelioration of infectious diarrhea in piglets by L. rhamnosus is associated with the generation of lamina propria CD3(+) CD4(+) CD8(-) T cells, the expansion of Peyer's patch CD3(+) CD4(-) CD8(-) and CD3(-) CD4(-) CD8(+) cells, and the attenuation of F4(+) ETEC-induced increase in CD3(+) CD4(+) CD8(+) T cells in the small intestine. However, consumption of high doses of L. rhamnosus may increase levels of serum IL-17A after F4(+) ETEC challenge, thus eliciting a strong proinflammatory response.

  18. Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease.

    Science.gov (United States)

    Schwiertz, Andreas; Spiegel, Jörg; Dillmann, Ulrich; Grundmann, David; Bürmann, Jan; Faßbender, Klaus; Schäfer, Karl-Herbert; Unger, Marcus M

    2018-02-12

    Intestinal inflammation and increased intestinal permeability (both possibly fueled by dysbiosis) have been suggested to be implicated in the multifactorial pathogenesis of Parkinson's disease (PD). The objective of the current study was to investigate whether fecal markers of inflammation and impaired intestinal barrier function corroborate this pathogenic aspect of PD. In a case-control study, we quantitatively analyzed established fecal markers of intestinal inflammation (calprotectin and lactoferrin) and fecal markers of intestinal permeability (alpha-1-antitrypsin and zonulin) in PD patients (n = 34) and controls (n = 28, group-matched for age) by enzyme-linked immunosorbent assay. The study design controlled for potential confounding factors. Calprotectin, a fecal marker of intestinal inflammation, and two fecal markers of increased intestinal permeability (alpha-1-antitrypsin and zonulin) were significantly elevated in PD patients compared to age-matched controls. Lactoferrin, as a second fecal marker of intestinal inflammation, showed a non-significant trend towards elevated concentrations in PD patients. None of the four fecal markers correlated with disease severity, PD subtype, dopaminergic therapy, or presence of constipation. Fecal markers reflecting intestinal inflammation and increased intestinal permeability have been primarily investigated in inflammatory bowel disease so far. Our data indicate that calprotectin, alpha-1-antitrypsin and zonulin could be useful non-invasive markers in PD as well. Even though these markers are not disease-specific, they corroborate the hypothesis of an intestinal inflammation as contributing factor in the pathogenesis of PD. Further investigations are needed to determine whether calprotectin, alpha-1-antitrypsin and zonulin can be used to define PD subgroups and to monitor the effect of interventions in PD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Intestinal cytochromes P450 regulating the intestinal microbiota and its probiotic profile

    Directory of Open Access Journals (Sweden)

    Eugenia Elefterios Venizelos Bezirtzoglou

    2012-09-01

    Full Text Available Cytochromes P450 (CYPs enzymes metabolize a large variety of xenobiotic substances. In this vein, a plethora of studies were conducted to investigate their role, as cytochromes are located in both liver and intestinal tissues. The P450 profile of the human intestine has not been fully characterized. Human intestine serves primarily as an absorptive organ for nutrients, although it has also the ability to metabolize drugs. CYPs are responsible for the majority of phase I drug metabolism reactions. CYP3A represents the major intestinal CYP (80% followed by CYP2C9. CYP1A is expressed at high level in the duodenum, together with less abundant levels of CYP2C8-10 and CYP2D6. Cytochromes present a genetic polymorphism intra- or interindividual and intra- or interethnic. Changes in the pharmacokinetic profile of the drug are associated with increased toxicity due to reduced metabolism, altered efficacy of the drug, increased production of toxic metabolites, and adverse drug interaction. The high metabolic capacity of the intestinal flora is due to its enormous pool of enzymes, which catalyzes reactions in phase I and phase II drug metabolism. Compromised intestinal barrier conditions, when rupture of the intestinal integrity occurs, could increase passive paracellular absorption. It is clear that high microbial intestinal charge following intestinal disturbances, ageing, environment, or food-associated ailments leads to the microbial metabolism of a drug before absorption. The effect of certain bacteria having a benefic action on the intestinal ecosystem has been largely discussed during the past few years by many authors. The aim of the probiotic approach is to repair the deficiencies in the gut flora and establish a protective effect. There is a tentative multifactorial association of the CYP (P450 cytochrome role in the different diseases states, environmental toxic effects or chemical exposures and nutritional status.

  20. Healing of the suture line in the irradiated small intestine

    International Nuclear Information System (INIS)

    Da Costa, S.A.

    1989-01-01

    With the help of data from literature the author goes more deeply into the aetiology, treatment and possible prevention of lesions of the small intestine related to preceding irradiation. In a clinical retrospective study at twenty patients who, after irradiation of the abdominal and pelvic areas, have been submitted to abdominal surgery, the relation is studied between predistion factors for gastrointestinal complications after irradiation, the surgeries applied in case of small-intestine problems and postoperative complications. The third part of the thesis covers an experimental part in which the healing process of suture line in the terminal ileum has been studied after resection and reanastomosis in previously irradiated bowel of the rat. It was investigated whether differences occurred in the healing process of suture line after various periods - 4, 10 and 40 weeks, after irradiation. Also comparison took place with a control group which underwent a similar procedure with the exception of the radiation treatment, which was simulated in this group. In a second experiment it was investigated if the healing process of suture line depends on the type of anastomosis. An end-to-end anastomosis was chosen versus side-to-side anastomosis. Also in this experiment an irradiated group was compared with a control group. Furthermore a method was developed for performing micro-angiographies of the rat intestine in order to demonstrate obliteration of blood vessels in irradiated intestine and to assess neovascularization in the intestinal wall at the suture line. (author). 84 refs.; 18 figs.; 27 tabs

  1. A note on inventory model for ameliorating items with time dependent second order demand rate

    Directory of Open Access Journals (Sweden)

    Gobinda Chandra Panda

    2013-03-01

    Full Text Available Background: This paper is concerned with the development of ameliorating inventory models. The ameliorating inventory is the inventory of goods whose utility increases over the time by ameliorating activation. Material and Methods: This study is performed according to two areas: one is an economic order quantity (EOQ model for the items whose utility is ameliorating in accordance with Weibull distribution, and the other is a partial selling quantity (PSQ model developed for selling the surplus inventory accumulated by ameliorating activation with linear demand. The aim of this paper was to develop a mathematical model for inventory type concerned in the paper. Numerical examples were presented show the effect of ameliorating rate on inventory polices.  Results and Conclusions:  The inventory model for items with Weibull ameliorating is developed. For the case of small ameliorating rate (less than linear demand rate, EOQ model is developed, and for the case where ameliorating rate is greater than linear demand rate, PSQ model is developed.  .  

  2. [Myosin B ATPase activity of the intestinal smooth muscle in intestinal obstruction].

    Science.gov (United States)

    Takamatsu, H

    1983-06-01

    Intestinal smooth myosin B was prepared from muscle layers around the lesion in dogs with experimental colonic stenosis and in patients with congenital intestinal obstruction. Mg2+-ATPase activity of the myosin B was compared between the proximal dilated segment and distal segment to obstruction. Experimental colonic stenosis: In early period after surgery, proximal colons showed higher activity of myosin B ATPase than distal colons, decreasing to less than distal colon as time passed. Congenital intestinal obstruction: In three cases, whose atresia might have occurred at earlier period of gestation, proximal bowels showed less activity of myosin B ATPase than distal bowels. However, in two cases, whose atresia might have occurred at later period of gestation, and two cases with intestinal stenosis, proximal bowels indicated higher activity of myosin B ATPase than distal bowels. These data suggested that the contractibility of the proximal intestine was depending on the duration of obstruction, and it was depressed in the former patients and was accelerated in the latter patients. These results suggested that the extensive resection of dilated proximal bowel in the congenital atresia is not always necessary to obtain good postoperative intestinal dynamics at the operation of the atresial lesions which may be induced at later period of gestation. They also suggested that surgery for intestinal obstruction should be performed before the depression of intestinal contractibility to get good bowel function.

  3. Surgical managements of radiation enteritis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Tsuguo; Naito, Kazuyo; Noomi, Shinppachiro; Kurioka, Hideaki; Yamagishi, Hisakazu (Kyoto Prefectural Univ. of Medicine (Japan))

    1983-02-01

    Radiation injury to the digestive tract was surgically treated in 22 cases. Six of them died shortly after surgery. Major symptoms were ileus or perforative peritonitis in 20 of the 22 cases, and surgery was performed for ileal lesion in 18 cases, indicating the significance of lesions in the small intestine. Seven patients underwent resection of the injured portion of the intestinal tract and anastomotic reconstruction in one stage, but 3 of them died from rupture of sutures. It was highly probable that anastomosis was made using an injured portion of the intestine. Intraoperative judgement of intestinal injury is made by palpation and inspection. If judgement is difficult, an artificial anus should be constructed first, and anastomotic reconstruction should be done in the 2nd stage. Since delayed injury of this disease is an ischemic change due to vascular obliteration, conservative therapy never leads to complete recovery, but active resection and anastomosis seem to produce a satisfactory result.

  4. Surgical managements of radiation enteritis

    International Nuclear Information System (INIS)

    Tanaka, Tsuguo; Naito, Kazuyo; Noomi, Shinppachiro; Kurioka, Hideaki; Yamagishi, Hisakazu

    1983-01-01

    Radiation injury to the digestive tract was surgically treated in 22 cases. Six of them died shortly after surgery. Major symptoms were ileus or perforative peritonitis in 20 of the 22 cases, and surgery was performed for ileal lesion in 18 cases, indicating the significance of lesions in the small intestine. Seven patients underwent resection of the injured portion of the intestinal tract and anastomotic reconstruction in one stage, but 3 of them died from rupture of sutures. It was highly probable that anastomosis was made using an injured portion of the intestine. Intraoperative judgement of intestinal injury is made by palpation and inspection. If judgement is difficult, an artificial anus should be constructed first, and anastomotic reconstruction should be done in the 2nd stage. Since delayed injury of this disease is an ischemic change due to vascular obliteration, conservative therapy never leads to complete recovery, but active resection and anastomosis seem to produce a satisfactory result. (Chiba, N.)

  5. [Congenital intestinal lymphangiectasia].

    Science.gov (United States)

    Popović, Dugan D j; Spuran, Milan; Alempijević, Tamara; Krstić, Miodrag; Djuranović, Srdjan; Kovacević, Nada; Damnjanović, Svetozar; Micev, Marjan

    2011-03-01

    Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortuous, dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and medication are required for disease control. A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue. Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm. Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-protein diet containing medium-chain fatty acids, somatotropin and supportive therapy. Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of the disease and adequate treatment can prevent development of various complications.

  6. The Protective Effect of Curcumin versus Sodium Nitroprusside on Intestinal Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Dalia M Saleh

    2014-04-01

    Full Text Available Objective: Intestinal ischemia/reperfusion (I/R injury is a signi and #64257;cant complication in abdominal vascular surgery. Various treatment modalities have been applied, however, the role of nitric oxide (NO in this type of injury is still controversial. Aim of the work: To compare the protective effect of curcumin vs sodium nitroprusside (SNP, NO donor on intestine and remote organs following intestinal I/R injury. Methods: Rats were divided into 4 groups (sham-control, I/R, curcumin+I/R, SNP+I/R. I/R was induced by 30 min clamping the superior mesenteric artery (SMA then 60 min reperfusion. Rats were pretreated with either curcumin (80 mg/kg/day with food for one week or SNP (5 mg/kg, i.p prior to I/R. Intestinal levels of malondialdehyde (MDA, Nitrite/nitrate, superoxide dismutase (SOD and reduced glutathione (GSH were measured. The sections from jejunum, lungs and liver were stained with hematoxylin and eosin (H and E for histopathological examination. Immunohistochemical stains for eNOS expression in the jejunum and cleaved caspase-3 for apoptosis in the lungs and liver were done. Results: I/R resulted in both local and remote organs in and #64258;ammation associated with signi and #64257;cant increase in MDA and nitrate/nitrite and significant decrease in SOD and GSH levels. These histological and biochemical changes were improved by pretreatment with curcumin and to less extent by SNP. Immunohistochemical examination showed significant decrease in eNOS activity in the I/R group which was improved by curcumin pretreatment not by SNP. Liver apoptosis was improved by curcumin while lung apoptosis was improved by SNP. Conclusion: Curcumin ameliorates I/R-induced local and remote organs damage through its anti-inflammatory and antiapoptotic effect. SNP may be beneficial in I/R injury but not as significant as curcumin. [J Interdiscipl Histopathol 2014; 2(2.000: 74-87

  7. Amelioration and reforestation of sulfurous mine soils in Lusatia (eastern Germany)

    International Nuclear Information System (INIS)

    Katzur, J.; Haubold-Rosar, M.

    1996-01-01

    In Germany nearly 1.550 km 2 have been claimed by brown coal mining until now. Mine soils formed of carboniferous and sulfurous overburden are classified as sulfurous mine soils. They remain vegetation-free for decades and may be cultivated only after soil amelioration. The objective of amelioration is a sustained improvement of soil reaction. Lime requirement for the achievement of a certain pH-value is calculated from acid-base-balance (SBB). Lime fertilizers and base-rich brown coal ashes are used for amelioration. As ashes have several advantages, their application is recommended. The ameliorative application of lime fertilizer or brown coal ash should be incorporated intensively into the soil to a depth of 60 cm, better 100 cm. Amelioration includes a mineral fertilization with N, P and K. Afforestation with Pinus sylvestris, Pinus nigra, Larix decidua, Larix eurolepis. Tilia cordata, Quercus rubra and Quercus petraea on ameliorated mine soils show surprising good results. Multi-species stands have very positive effects on soil formation. Raw humus is formed under pine and larch, and under deciduous trees moder and mull with higher bioactivity and better development of water and nutrient balance in the topsoil are found. 55 refs., 6 figs., 4 tabs

  8. Cell Survival in irradiation mouse intestine is increased by DNA-Binding radioprotectors

    International Nuclear Information System (INIS)

    Coultas, P.; Martin, R.

    1996-01-01

    Crypt survival in the mouse intestine has been used to examine effects of bisbenzimide radioprotectors. Intravenous delivery has been used for the present study in which the effects of methyl proamine (MP), a second generation Hoechst 33342 analogue have been examined. Recent results using the lung model suggest that MP is both more potent as a protector and less toxic than H 33342. The rapid nature of the crypt microcolony survival assay in mouse intestine provides an efficient way to examining factors which could impinge on the extent of radioprotection, for example, the interval between protector administration and radiation exposure. The data clearly show that for MP at 100 mg/kg, there is substantially increased crypt survival equivalent to a dose modification of about 1.33. The crypt scoring methods used indicate that protection is throughout the small intestine and preliminary data indicate that colon is also protected to a similar or slightly greater extent

  9. Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation; Caracterisation et modulation pharmacologique de l'inflammation intestinale induite par les rayonnements ionisants

    Energy Technology Data Exchange (ETDEWEB)

    Gremy, O

    2006-12-15

    The use of radiation therapy to treat abdominal and pelvic malignancies inevitably involves exposure of healthy intestinal tissues which are very radiosensitive. As a result, most patients experience symptoms such as abdominal pain, nausea and diarrhea. Such symptoms are associated with acute damage to intestine mucosa including radio-induced inflammatory processes. With a rat model of colorectal fractionated radiation, we have shown a gradual development of a colonic inflammation during radiation planning, without evident tissue injury. This radio-induced inflammation is characterized not only by the sur expressions of pro-inflammatory cytokines and chemokines, a NF-kB activation, but also by a repression of anti-inflammatory cytokines and the nuclear receptors PPARa and RXRa, both involved in inflammation control. This early inflammation is associated with a discreet neutrophil recruitment and a macrophage accumulation. Macrophages are still abnormally numerous in tissue 27 weeks after the last day of irradiation. Inflammatory process is the most often related to a specific immune profile, either a type Th1 leading to a cellular immune response, or a type Th2 for humoral immunity. According to our studies, a unique abdominal radiation in the rat induces an ileum inflammation and an immune imbalance resulting in a Th2-type profile. Inhibiting this profile is important as its persistence promotes chronic inflammation, predisposition to bacterial infections and fibrosis which is the main delayed side-effect of radiotherapy. The treatment of rats with an immuno-modulator compound, the caffeic acid phenethyl ester (C.A.P.E.), have the potential to both reduce ileal mucosal inflammation and inhibit the radio-induced Th2 status. In order to search new therapeutic molecular target, we has been interested in the PPARg nuclear receptor involved in the maintenance of colon mucosal integrity. In our abdominal irradiation model, we have demonstrated that the prophylactic

  10. Radiation dose estimates for oral agents used in upper gastrointestinal disease

    International Nuclear Information System (INIS)

    Siegel, J.A.; Wu, R.K.; Knight, L.C.; Zelac, R.E.; Stern, H.S.; Malmud, L.S.

    1983-01-01

    Radiation dosimetry was calculated for a number of orally administered radiopharmaceuticals used for study of upper gastrointestinal function. These include: Tc-99m sulfur colloid in water, in a cooked egg, and in chicken liver labeled in vivo; In-111 DTPA; Tc-99m DTPA; In-113m DTPA; Tc-99m ovalbumin in cooked egg; and In-111 colloid in chicken liver labeled in vivo. Radiation burdens to the stomach, small intestine, upper and lower large intestine, ovaries, testes, and total body are calculated for each preparation

  11. Autophagy and tight junction proteins in the intestine and intestinal diseases

    Directory of Open Access Journals (Sweden)

    Chien-An A. Hu

    2015-09-01

    Full Text Available The intestinal epithelium (IE forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens (bacteria, fungi and virus and antigens. The apical intercellular tight junctions (TJ are responsible for the paracellular barrier function and regulate trans-epithelial flux of ions and solutes between adjacent cells. Increased intestinal permeability caused by defects in the IE TJ barrier is considered an important pathogenic factor for the development of intestinal inflammation, diarrhea and malnutrition in humans and animals. In fact, defects in the IE TJ barrier allow increased antigenic penetration, resulting in an amplified inflammatory response in inflammatory bowel disease (IBD, necrotizing enterocolitis and ischemia-reperfusion injury. Conversely, the beneficial enhancement of the intestinal TJ barrier has been shown to resolve intestinal inflammation and apoptosis in both animal models of IBD and human IBD. Autophagy (self-eating mechanism is an intracellular lysosome-dependent degradation and recycling pathway essential for cell survival and homeostasis. Dysregulated autophagy has been shown to be directly associated with many pathological processes, including IBD. Importantly, the crosstalk between IE TJ and autophagy has been revealed recently. We showed that autophagy enhanced IE TJ barrier function by increasing transepithelial resistance and reducing the paracellular permeability of small solutes and ions, which is, in part, by targeting claudin-2, a cation-selective, pore-forming, transmembrane TJ protein, for lysosome (autophagy-mediated degradation. Interestingly, previous studies have shown that the inflamed intestinal mucosa in patients with active IBD has increased claudin-2 expression. In addition, inflammatory cytokines (for example, tumor necrosis factor-α, interleukin-6

  12. Gene expression analyses of the small intestine of pigs in the ex-evacuation zone of the Fukushima Daiichi Nuclear Power Plant.

    Science.gov (United States)

    Morimoto, Motoko; Kato, Ayaka; Kobayashi, Jin; Okuda, Kei; Kuwahara, Yoshikazu; Kino, Yasushi; Abe, Yasuyuki; Sekine, Tsutomu; Fukuda, Tomokazu; Isogai, Emiko; Fukumoto, Manabu

    2017-11-15

    After the accident at the Fukushima Daiichi Nuclear Power Plant, radioactive contaminants were released over a widespread area. Monitoring the biological effects of radiation exposure in animals in the ex-evacuation zone should be continued to understand the health effects of radiation exposure in humans. The present study aimed to clarify the effects of radiation by investigating whether there is any alteration in the morphology and gene expressions of immune molecules in the intestine of pigs and inobuta (wild boar and domestic pig hybrid) in the ex-evacuation zone in 2012. Gene expression analysis was performed in small intestine samples from pigs, which were collected from January to February 2012, in the ex-evacuation zone. Pigs lived freely in this zone, and their small intestine was considered to be affected by the dietary intake of radioactive contaminants. Several genes were selected by microarray analysis for further investigation using real-time polymerase chain reaction. IFN-γ, which is an important inflammatory cytokine, and TLR3, which is a pattern recognize receptor for innate immune system genes, were highly elevated in these pigs. The expressions of the genes of these proteins were associated with the radiation level in the muscles. We also examined the alteration of gene expressions in wild boars 5 years after the disaster. The expression of IFN-γ and TLR3 remained high, and that of Cyclin G1, which is important in the cell cycle, was elevated. We demonstrated that some changes in gene expression occurred in the small intestine of animals in the ex-evacuation zone after radiation. It is difficult to conclude that these alterations are caused by only artificial radionuclides from the Fukushima Daiichi Nuclear Power Plant. However, the animals in the ex-evacuation zone might have experienced some changes owing to radioactive materials, including contaminated soil, small animals, and insects. We need to continue monitoring the effects of long

  13. Congenital intestinal lymphangiectasia

    Directory of Open Access Journals (Sweden)

    Popović Dušan Đ.

    2011-01-01

    Full Text Available Background. Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortous, dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and medication are required for disease control. Case report. A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue. Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm. Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-protein diet containing medium-chain fatty acids, somatotropin and suportive therapy. Conclusion. Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of the disease and adequate treatment can prevent development of various complications.

  14. Experimental study of some homeostatic parameters at late times after exposure to radiation

    International Nuclear Information System (INIS)

    Chertkov, K.S.; Andrianova, I.E.; Atamanova, O.M.; Filimonova, G.I.; Nesterova, T.A.; Sbitneva, M.F.; Glushkov, V.A.; Chotij, V.G.; Stejmatskaya, Z.A.

    1994-01-01

    Following radiation damage from LD 50 - LD 97 , changes in blood, immune and endocrine parameters were revealed and followed up in dogs at the time of late effects development, 3-18 months after exposure. The changes result from post-radiation immunodeficiency and resemble those observed in residents of radioactive contaminate areas or in men participated in Chernobyl accident amelioration

  15. Intestine transplantation

    Directory of Open Access Journals (Sweden)

    Tadeja Pintar

    2011-02-01

    Conclusion: Intestine transplantation is reserved for patients with irreversible intestinal failure due to short gut syndrome requiring total paranteral nutrition with no possibility of discontinuation and loss of venous access for patient maintenance. In these patients complications of underlying disease and long-term total parenteral nutrition are present.

  16. Daikenchuto, a Kampo medicine, regulates intestinal fibrosis associated with decreasing expression of heat shock protein 47 and collagen content in a rat colitis model.

    Science.gov (United States)

    Inoue, Ken; Naito, Yuji; Takagi, Tomohisa; Hayashi, Natsuko; Hirai, Yasuko; Mizushima, Katsura; Horie, Ryusuke; Fukumoto, Kohei; Yamada, Shinya; Harusato, Akihito; Hirata, Ikuhiro; Omatsu, Tatsushi; Yoshida, Naohisa; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Handa, Osamu; Konishi, Hideyuki; Wakabayashi, Naoki; Yagi, Nobuaki; Ichikawa, Hiroshi; Kokura, Satoshi; Yoshikawa, Toshikazu

    2011-01-01

    Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time-course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor β1 (TGF-β1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with α-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-β1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.

  17. Surgical management of radiation enterocolitis

    International Nuclear Information System (INIS)

    Sakaguchi, Masahiro; Katsumi, Masaharu; Ishimoto, Kiwao; Yamamoto, Shinji; Yukawa, Hirofumi; Koh, Kenzo; Yamaguchi, Kazuya; Ohta, Masataka; Hayashido, Motonori

    1986-01-01

    Radiotherapy for malignant tumors is effective and established. However, there are many complications in radiotherapy. A typical complication is radiation enterocolitis. It is difficult to treat severe histological damage to the irradiated tissues. This paper reports our experience with 26 patients with radiation enterocolitis for whom surgical treatment was given during a period of 16 years in our surgical department. The most frequent original disease requiring irradiation was cancer of the cervix uteri (15 cases) which was followed by cancer of the urinary bladder (7 cases). All of these patients had received external 60 Co irradiation. The ileum was the most frequent site of the lesion, followed by the rectum, sigmoid and descending colon. The period between the end of irradiation and the onset of enterocolitis ranged from 2 months to 10 years, with an average of 28 months. The main symptoms were intestinal obstruction in the ileum, and melena and fistula in the rectum and sigmoid colon. Intestinal resection was performed in 10 patients, a bypass operation in 4, and colostomy in 12. As to types of intestinal suture in these cases, Gambee's single layer method was thought useful from our experience. Colostomy as surgical management of melena and fistula did not yield satisfactory results. (author)

  18. Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases

    Science.gov (United States)

    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

  19. Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Maria C. Opazo

    2018-03-01

    Full Text Available 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.

  20. Ameliorative effects of selenium and zinc

    African Journals Online (AJOL)

    Methidathion-induced hematological, biochemical and hepatohistological alterations in rat: Ameliorative effects of selenium and zinc. L Barkat, A Boumendjel, C Abdennour, MS Boulakoud, A El Feki, M Messarah ...

  1. Intestinal Permeability: The Basics

    Directory of Open Access Journals (Sweden)

    Ingvar Bjarnason

    1995-01-01

    Full Text Available The authors review some of the more fundamental principles underlying the noninvasive assessment of intestinal permeability in humans, the choice of test markers and their analyses, and the practical aspects of test dose composition and how these can be changed to allow the specific assessment of regional permeability changes and other intestinal functions. The implications of increased intestinal permeability in the pathogenesis of human disease is discussed in relation to findings in patients with Crohn’s disease. A common feature of increased intestinal permeability is the development of a low grade enteropathy, and while quantitatively similar changes may be found in Crohn’s disease these seem to predict relapse of disease. Moreover, factors associated with relapse of Crohn’s disease have in common an action to increase intestinal permeability. While increased intestinal permeability does not seem to be important in the etiology of Crohn’s disease it may be a central mechanism in the clinical relapse of disease.

  2. Protective mechanisms and acclimation to solar ultraviolet-B radiation in Oenothera stricta

    Science.gov (United States)

    Robberecht, R.; Caldwell, M. M.

    1981-01-01

    Plant adaptations ameliorating or repairing the damaging effects of ultraviolet-B (UV-B) radiation on plant tissue were investigated. The degree of phenotype plasticity in UV protective mechanisms and acclimation in relation to the natural solar UV-B radiation flux and in an enhanced UV-B irradiance environment was also examined. Mechanisms by which plants avoid radiation, adaptations altering the path of radiation incident on the leaf, and repair processes were considered. Attenuation of UV-B by tissues, UV-B irradiation into the leaf, and the effects of UV-B on photosynthesis were investigated.

  3. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure

    NARCIS (Netherlands)

    Korpela, K.; Mutanen, A.; Salonen, A.; Savilahti, E.; Vos, de W.M.; Pakarinen, M.P.

    2017-01-01

    BACKGROUND: Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. METHODS: We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent

  4. Amelioration of some biochemical parameters in irradiated male albino rats by garlic

    International Nuclear Information System (INIS)

    El-masry, F.S.H.; El-sayed, N.M.; Hussein, A.H.

    2005-01-01

    Garlic extract has various medical effects on the treatment of many diseases as hypertension, atherosclerosis, inflammation and diabetes. The alteration of the biochemical parameters in blood serum of irradiated rats may play an important role in determining the pathogenesis of radiation exposure. Many of the damaging effects of ionizing radiation are mediated by reactive free radicals. This study was designed to evaluate the protective role of garlic against gamma irradiation (5Gy) induced biochemical disorders in rats. Samples were collected at 1, 7 and 14 days post-irradiation. Lipid peroxide content (malondialdehyde), cholesterol, HDL-C, LDL-C, fatty acids, glucose, insulin, glycogen, haemoglobin, ferritin andiron were estimated.Garlic was orally administered to rats (100 mg/kg body weight) for 14 days before exposure to single dose of gamma irradiation at dose level 5 Gy. The data revealed significant increase in the levels of lipid peroxide, cholesterol, LDL-cholesterol, fatty acids, insulin, glucose and iron accompanied with significant decrease in the levels of HDL-cholesterol, glycogen, haemoglobin and ferritin due to radiation exposure. Administration of garlic alone to the rats caused nonsignificant changes in the estimated parameters indicating its safe use, but the treatment with garlic to rats before radiation exposure ameliorated the changes induced by gamma irradiation and tended to normalize their levels.It could be concluded that garlic administration may has a beneficial role in restoring the biochemical disorders induced by 5 Gy gamma irradiation

  5. Intestinal ischemia-reperfusion injury augments intestinal mucosal injury and bacterial translocation in jaundiced rats.

    Science.gov (United States)

    Yüksek, Yunus Nadi; Kologlu, Murat; Daglar, Gül; Doganay, Mutlu; Dolapci, Istar; Bilgihan, Ayse; Dolapçi, Mete; Kama, Nuri Aydin

    2004-01-01

    The aim of this study was to evaluate local effects and degree of bacterial translocation related with intestinal ischemia-reperfusion injury in a rat obstructive jaundice model. Thirty adult Sprague-Dawley rats (200-250 g) were divided into three groups; including Group 1 (jaundice group), Group 2 (jaundice-ischemia group) and Group 3 (ischemia group). All rats had 2 laparotomies. After experimental interventions, tissue samples for translocation; liver and ileum samples for histopathological examination, 25 cm of small intestine for mucosal myeloperoxidase and malondialdehyde levels and blood samples for biochemical analysis were obtained. Jaundiced rats had increased liver enzyme levels and total and direct bilirubin levels (p<0.05). Intestinal mucosal myeloperoxidase and malondialdehyde levels were found to be high in intestinal ischemia-reperfusion groups (p<0.05). Intestinal mucosal damage was more severe in rats with intestinal ischemia-reperfusion after bile duct ligation (p<0.05). Degree of bacterial translocation was also found to be significantly high in these rats (p<0.05). Intestinal mucosa is disturbed more severely in obstructive jaundice with the development of ischemia and reperfusion. Development of intestinal ischemia-reperfusion in obstructive jaundice increases bacterial translocation.

  6. Intestinal lymphangiectasia in children

    Science.gov (United States)

    Isa, Hasan M.; Al-Arayedh, Ghadeer G.; Mohamed, Afaf M.

    2016-01-01

    Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification. PMID:26837404

  7. Effects of radiation on the human gastrointestinal tract

    International Nuclear Information System (INIS)

    Novak, J.M.; Collins, J.T.; Donowitz, M.; Farman, J.; Sheahan, D.G.; Spiro, H.M.

    1979-01-01

    Radiation therapy directed at the abdomen may damage the digestive tract, the type and extent of injury depending on the dose of the radiation and the radiation sensitivity of the gut. Characteristic early changes are manifest in the mucosa of the gut: for later ulceration, changes in the collagen tissues and particularly in the vascular channels occur. This paper describes and characterizes injuries to the esophagus, stomach, small intestine and colon. It emphasizes the importance of recognizing radiation-induced damage to the gut which may occur early or late after radiation

  8. Chemoprotective Effect of Taurine on Potassium Bromate-Induced DNA Damage, DNA-Protein Cross-Linking and Oxidative Stress in Rat Intestine

    Science.gov (United States)

    Ahmad, Mir Kaisar; Khan, Aijaz Ahmed; Ali, Shaikh Nisar; Mahmood, Riaz

    2015-01-01

    Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. It induces multiple organ toxicity in humans and experimental animals and is a probable human carcinogen. The present study reports the protective effect of dietary antioxidant taurine on KBrO3-induced damage to the rat intestine. Animals were randomly divided into four groups: control, KBrO3 alone, taurine alone and taurine+ KBrO3. Administration of KBrO3 alone led to decrease in the activities of intestinal brush border membrane enzymes while those of antioxidant defence and carbohydrate metabolism were also severely altered. There was increase in DNA damage and DNA-protein cross-linking. Treatment with taurine, prior to administration of KBrO3, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. Histological studies supported these biochemical results showing extensive intestinal damage in KBrO3-treated animals and greatly reduced tissue injury in the taurine+ KBrO3 group. These results show that taurine ameliorates bromate induced tissue toxicity and oxidative damage by improving the antioxidant defence, tissue integrity and energy metabolism. Taurine can, therefore, be potentially used as a therapeutic/protective agent against toxicity of KBrO3 and related compounds. PMID:25748174

  9. Parsley oil boosting anti oxidation capacity in irradiated rats

    International Nuclear Information System (INIS)

    Abbady, M.M.; Osman, S.A.A.; Abu-Ghadeer, A.R.M.

    1999-01-01

    Many synthetic antioxidant components have shown toxic and/or mutagenic effects, which have directed most of the attention on the naturally occurring antioxidants. The present study aims to evaluate the possible antioxidant effects of parsley on levels of lipid peroxides, glutathione (GSH) and superoxide dismutase (SOD) in blood and certain tissues (liver, spleen and intestine) of whole body gamma irradiated rats (4.5 Gy). Parsley oil was orally administrated to rats (100 mg/kg bod. wt) for 7 days before radiation exposure. The data showed that parsley significantly ameliorates the decrease in the antioxidant system (GSH and SOD) and the increase in the lipid peroxides level caused by radiation exposure

  10. Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation; Caracterisation et modulation pharmacologique de l'inflammation intestinale induite par les rayonnements ionisants

    Energy Technology Data Exchange (ETDEWEB)

    Gremy, O

    2006-12-15

    The use of radiation therapy to treat abdominal and pelvic malignancies inevitably involves exposure of healthy intestinal tissues which are very radiosensitive. As a result, most patients experience symptoms such as abdominal pain, nausea and diarrhea. Such symptoms are associated with acute damage to intestine mucosa including radio-induced inflammatory processes. With a rat model of colorectal fractionated radiation, we have shown a gradual development of a colonic inflammation during radiation planning, without evident tissue injury. This radio-induced inflammation is characterized not only by the sur expressions of pro-inflammatory cytokines and chemokines, a NF-kB activation, but also by a repression of anti-inflammatory cytokines and the nuclear receptors PPARa and RXRa, both involved in inflammation control. This early inflammation is associated with a discreet neutrophil recruitment and a macrophage accumulation. Macrophages are still abnormally numerous in tissue 27 weeks after the last day of irradiation. Inflammatory process is the most often related to a specific immune profile, either a type Th1 leading to a cellular immune response, or a type Th2 for humoral immunity. According to our studies, a unique abdominal radiation in the rat induces an ileum inflammation and an immune imbalance resulting in a Th2-type profile. Inhibiting this profile is important as its persistence promotes chronic inflammation, predisposition to bacterial infections and fibrosis which is the main delayed side-effect of radiotherapy. The treatment of rats with an immuno-modulator compound, the caffeic acid phenethyl ester (C.A.P.E.), have the potential to both reduce ileal mucosal inflammation and inhibit the radio-induced Th2 status. In order to search new therapeutic molecular target, we has been interested in the PPARg nuclear receptor involved in the maintenance of colon mucosal integrity. In our abdominal irradiation model, we have demonstrated that the prophylactic

  11. Intestinal pseudo-obstruction

    Science.gov (United States)

    ... Staying in bed for long periods of time (bedridden). Taking drugs that slow intestinal movements. These include ... be tried: Colonoscopy may be used to remove air from the large intestine. Fluids can be given ...

  12. Preventive Effect of TU-100 on a Type-2 Model of Colitis in Mice: Possible Involvement of Enhancing Adrenomedullin in Intestinal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Atsushi Kaneko

    2013-01-01

    Full Text Available Purpose. Crohn's disease (CD and ulcerative colitis (UC, the two major forms of inflammatory bowel disease (IBD, have histopathologically and immunologically different characteristics. We previously reported that a traditional Japanese medicine, daikenchuto (TU-100, ameliorated a trinitrobenzenesulfonic acid- (TNBS- induced type-1 model colitis exhibiting histopathological features of CD through adrenomedullin (ADM enhancement. Our current aims were to examine whether TU-100 ameliorates a type-2 model colitis that histologically resembles UC and identify the active ingredients. Methods. TU-100 was administered orally to mice with oxazolone- (OXN- induced type-2 model colitis. The morbidity was evaluated by body weight loss and the macroscopic score of colonic lesions. ADM was quantified using an EIA kit. Results. TU-100 prevented weight loss and colon ulceration. ADM production by intestinal epithelial cells was increased by TU-100 addition. Screening to identify active ingredients showed that [6]-shogaol and hydroxy α-sanshool enhanced ADM production. Conclusions. TU-100 exerted a protective effect in OXN-induced type-2 model colitis, indicating that TU-100 may be a beneficial agent for treatment of UC.

  13. Radiation-induced gastrointestinal toxicity. Pathophysiologie, approaches to treatment and prophylaxis

    International Nuclear Information System (INIS)

    Classen, J.; Belka, C.; Paulsen, F.; Budach, W.; Hoffmann, W.; Bamberg, M.

    1998-01-01

    Background: Gastrointestinal toxicity is frequently observed during radiotherapy of malignancies in the abdomen and pelvis. The proposed pathophysiology of radiation enteritis is complex and a variety of different treatment strategies have been suggested for the management of acute radiation-induced diarrhea. Material and methods: Data are presented from an extensive review of the current literature. Results: Radiation-induced diarrhea results from a variety of different pathophysiological mechanisms including malabsorption of bile salts and lactose, imbalances in local bacterial flora and changes in the intestinal patterns of motility. Up to date acute radiation diarrhea is predominantly treated symptomatically using opioide derivates (loperamide) or adsorbants of bile salts such as smectite. Clinical trials have been performed using L. acidophilus, smectite or sucralfate for diarrhea prophylaxis with moderate reduction of acute symptoms. Conclusions: Further evaluation of strategies for diarrhea prophylaxis is warranted. Due to the complex nature of radiation enteritis a multimodal approach taking into account alterations in intestinal motility patterns, malabsorption of bile salts and an imbalance of mucosal bacterial flora may offer new perspectives. (orig.) [de

  14. MR imaging of the gastro-intestinal tract in children

    Energy Technology Data Exchange (ETDEWEB)

    Hoermann, Marcus [Medical University of Vienna/General Hospital, Department of General and Paediatric Radiology, Waehringerguertel 18-20, A-1090 Vienna (Austria)], E-mail: marcus.hoermann@meduniwien.ac.at

    2008-11-15

    MR imaging (MRI) is an established method for the evaluation of particularly inflammatory bowel disease in adults, as well as for acute abdominal pain in pregnant women. Despite the fact that MRI is ideally suited for the evaluation of children the method is still not established in these patients. The value of MRI in Crohn's disease, ulcerative colitis and appendicitis as well as intestinal tumors and malformations has been documented in children. There will be more indications in the future depending on the development of new imaging techniques, faster sequences, stronger gradients and increasing availability. Furthermore, the radiologist's attention must be drawn to decrease the radiation burden in children and to replace ionizing techniques especially in chronic disease with the need for repeated follow-up studies and in younger children. This review will discuss some general considerations for the use of MRI in evaluating the paediatric gastro-intestinal tract.

  15. Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo?Obstruction in 6 Dogs

    OpenAIRE

    Zacuto, A.C.; Pesavento, P.A.; Hill, S.; McAlister, A.; Rosenthal, K.; Cherbinsky, O.; Marks, S.L.

    2015-01-01

    Background Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo?obstruction in humans and animals. Objective To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Animals Six client?owned dogs. Methods Retrospective case series. Medical records were reviewed to de...

  16. Vascular lesions following radiation

    International Nuclear Information System (INIS)

    Fajardo, L.F.; Berthrong, M.

    1988-01-01

    The special radiation sensitivity of the vascular system is mainly linked to that of endothelial cells, which are perhaps the most radiation-vulnerable elements of mesenchymal tissues. Within the vascular tree, radiation injures most often capillaries, sinusoids, and small arteries, in that order. Lesions of veins are observed less often, but in certain tissues the veins are regularly damaged (e.g., intestine) or are the most affected structures (i.e., liver). Large arteries do suffer the least; however, when significant damage does occur in an elastic artery (e.g., thrombosis or rupture), it tends to be clinically significant and even fatal. Although not always demonstrable in human tissues, radiation vasculopathy generally is dose and time dependent. Like other radiation-induced lesions, the morphology in the vessels is not specific, but it is characteristic enough to be often recognizable. Vascular injury, especially by therapeutic radiation is not just a morphologic marker. It is a mediator of tissue damage; perhaps the most consistent pathogenetic mechanism in delayed radiation injury

  17. Diffused and sustained inhibitory effects of intestinal electrical stimulation on intestinal motility mediated via sympathetic pathway.

    Science.gov (United States)

    Zhao, Xiaotuan; Yin, Jieyun; Wang, Lijie; Chen, Jiande D Z

    2014-06-01

    The aims were to investigate the energy-dose response effect of intestinal electrical stimulation (IES) on small bowel motility, to compare the effect of forward and backward IES, and to explore the possibility of using intermittent IES and mechanism of IES on intestinal motility. Five dogs implanted with a duodenal cannula and one pair of intestinal serosal electrodes were studied in five sessions: 1) energy-dose response study; 2) forward IES; 3) backward IES; 4) intermittent IES vs. continuous IES; 5) administration of guanethidine. The contractile activity and tonic pressure of the small intestine were recorded. The duration of sustained effect after turning off IES was manually calculated. 1) IES with long pulse energy dose dependently inhibited contractile activity and tonic pressure of the small intestine (p intestine depended on the energy of IES delivered (p intestine. 5) Guanethidine blocked the inhibitory effect of IES on intestinal motility. IES with long pulses inhibits small intestinal motility; the effect is energy-dose dependent, diffused, and sustained. Intermittent IES has the same efficacy as the continuous IES in inhibiting small intestinal motility. Forward and backward IES have similar inhibitory effects on small bowel motility. This IES-induced inhibitory effect is mediated via the sympathetic pathway. © 2013 International Neuromodulation Society.

  18. 27 CFR 24.304 - Chaptalization (Brix adjustment) and amelioration record.

    Science.gov (United States)

    2010-04-01

    ... ameliorates juice or wine, or both, shall maintain a record of the operation and the transaction date. Records...; however, if liquid sugar or invert sugar syrup is used, the quantity of water in such sugar is included as... to be held after that date for completion. When the amelioration of wine included in the record for...

  19. Influence of ionizing radiation on gastrointestinal peptide levels

    Energy Technology Data Exchange (ETDEWEB)

    Wysocki, J.; Esposito, V.; Linard, C. [CEA Fontenay-aux-Roses, 92 (France). Inst. de Protection et de Surete Nucleaire

    1997-03-01

    Exposure of the gut to ionising radiation may induce gastrointestinal damage and dysfunction. Early effects such as nausea, vomiting and diarrhea, anorexia may be observed within the first 24 h after irradiation. Such symptoms are seen even with doses as low as 1 Gy. later effects and the onset of the gastrointestinal syndrome are seen at higher doses (10 Gy) and include gastric emptying inhibition, intestinal hemorrhages, disturbances in water and electrolytes balance and septicemia. The severity of which depends on the nature, dose and dose rate received. The mechanism underlying these changes was unclear; it has long been known that exposure to ionising radiation affects intestinal morphology usually because of inhibition of mitotic activity at the level of the crypt enterocyst. The various physiological functions of the gastrointestinal tract are controlled by a wide variety of agents as neurotransmitters, neuropeptides. Radiation induces alterations in hormonal release and response. The present study carried out in the rat focuses on Gastrin Releasing Peptide (GRP), a gastrointestinal neuropeptide present in the central nervous system and in the gut endocrine cells were released into blood. The GRP controls food intake, pancreatic enzyme secretions, gastric emptying, intestinal motility and cellular proliferation. The aim was to investigate the effects of gamma and neutron/gamma on plasma and gastrointestinal tissue levels of GRP

  20. Intestinal lymphangiectasia in adults.

    Science.gov (United States)

    Freeman, Hugh James; Nimmo, Michael

    2011-02-15

    Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial

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

    Science.gov (United States)

    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

  2. The CT signs of intestinal volvulus

    International Nuclear Information System (INIS)

    Ji Jiansong; Wang Zufei; Xu Zhaolong; Lv Guijian; Xu Min; Zhao Zhongwei; Su Jinliang; Zhou Limin

    2005-01-01

    Objective: To improve the accuracy rate of spiral CT diagnosing intestinal volvulus. Methods: To analysis the CT findings of 9 cases of intestinal volvulus proved by operation, the main reconstruction techniques were multiplanar reformation (MPR) and sliding thin-slab maximum intensity projection (STS-MIP). Results: All the 9 cases were diagnosed accurately, the main signs were 'whirlpool' of intestine (6 cases) and vessels (9 cases),'target loop' (2 cases),'beak'(6 cases). Conclusion: 'Whirlpool' of vessels is a specific sign to diagnose intestinal volvulus, 'target loop', reduced enhancement of intestinal wall and ascites are the reliable signs to strangulated intestinal obstruction. Spiral CT and reconstructions have important value to diagnose the intestinal volvulus. (authors)

  3. Advances in radiation biology: Relative radiation sensitivities of human organ systems. Volume 12

    International Nuclear Information System (INIS)

    Lett, J.T.; Altman, K.I.; Ehmann, U.K.; Cox, A.B.

    1987-01-01

    This volume is a thematically focused issue of Advances in Radiation Biology. The topic surveyed is relative radiosensitivity of human organ systems. Topics considered include relative radiosensitivities of the thymus, spleen, and lymphohemopoietic systems; relative radiosensitivities of the small and large intestine; relative rediosensitivities of the oral cavity, larynx, pharynx, and esophagus; relative radiation sensitivity of the integumentary system; dose response of the epidermal; microvascular, and dermal populations; relative radiosensitivity of the human lung; relative radiosensitivity of fetal tissues; and tolerance of the central and peripheral nervous system to therapeutic irradiation

  4. Advances in radiation biology: Relative radiation sensitivities of human organ systems. Volume 12

    Energy Technology Data Exchange (ETDEWEB)

    Lett, J.T.; Altman, K.I.; Ehmann, U.K.; Cox, A.B.

    1987-01-01

    This volume is a thematically focused issue of Advances in Radiation Biology. The topic surveyed is relative radiosensitivity of human organ systems. Topics considered include relative radiosensitivities of the thymus, spleen, and lymphohemopoietic systems; relative radiosensitivities of the small and large intestine; relative rediosensitivities of the oral cavity, larynx, pharynx, and esophagus; relative radiation sensitivity of the integumentary system; dose response of the epidermal; microvascular, and dermal populations; relative radiosensitivity of the human lung; relative radiosensitivity of fetal tissues; and tolerance of the central and peripheral nervous system to therapeutic irradiation.

  5. The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model.

    Science.gov (United States)

    Kwak, Dong Shin; Lee, Oh Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon

    2016-05-23

    DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.

  6. Pathogenesis and symptomatics of the acute radiation syndrome

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Haen, M.; Carbonell, F.

    1980-01-01

    The pathogenesis and symptomatics of the acute radiation syndrome are discussed. Diagnosis and therapy would be impossible without detailed knowledge in these fields. The concept of acute radiation syndrome is explained, and a pathophysiological analysis of the various forms of radiation syndrome - haematological, intestinal and affecting the central nervous system is attempted. The developments in the diagnosis and therapy of acute radiation syndrome since its first description - 35 years ago - are reviewed. Today, whole-body doses of 100 rd and more can be treated by radiotherapy. (orig./MG) [de

  7. Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid

    Directory of Open Access Journals (Sweden)

    Zadeh Mojgan

    2012-03-01

    Full Text Available Abstract Background The cellular and molecular mechanisms of inflammatory bowel disease are not fully understood; however, data indicate that uncontrolled chronic inflammation induced by bacterial gene products, including lipoteichoic acid (LTA, may trigger colonic inflammation resulting in disease pathogenesis. LTA is a constituent glycolipid of Gram-positive bacteria that shares many inflammatory properties with lipopolysaccharide and plays a critical role in the pathogenesis of severe inflammatory responses via Toll-like receptor 2. Accordingly, we elucidate the role of LTA in immune stimulation and induced colitis in vivo. Methods To better understand the molecular mechanisms utilized by the intestinal microbiota and their gene products to induce or subvert inflammation, specifically the effect(s of altered surface layer protein expression on the LTA-mediated pro-inflammatory response, the Lactobacillus acidophilus surface layer protein (Slp genes encoding SlpB and SlpX were deleted resulting in a SlpB- and SlpX- mutant that continued to express SlpA (assigned as NCK2031. Results Our data show profound activation of dendritic cells by NCK2031, wild-type L. acidophilus (NCK56, and purified Staphylococcus aureus-LTA. In contrary to the LTA-deficient strain NCK2025, the LTA-expressing strains NCK2031 and NCK56, as well as S. aureus-LTA, induce pro-inflammatory innate and T cell immune responses in vivo. Additionally, neither NCK2031 nor S. aureus-LTA supplemented in drinking water protected mice from DSS-colitis, but instead, induced significant intestinal inflammation resulting in severe colitis and tissue destruction. Conclusions These findings suggest that directed alteration of two of the L. acidophilus NCFM-Slps did not ameliorate LTA-induced pro-inflammatory signals and subsequent colitis.

  8. Neutron and X-ray effects on small intestine summarized by using a mathematical model or paradigm

    International Nuclear Information System (INIS)

    Carr, K.E.; McCullough, J.S.; Nunn, S.; Hume, S.P.; Nelson, A.C.

    1991-01-01

    The responses of intestinal tissues to ionizing radiation can be described by comparing irradiated cell populations qualitatively or quantitatively with corresponding controls. This paper describes quantitative data obtained from resin-embedded sections of neutron-irradiated mouse small intestine at different times after treatment. Information is collected by counting cells or structures present per complete circumference. The data are assessed by using standard statistical tests, which show that early mitotic arrest precedes changes in goblet, absorptive, endocrine and stromal cells and a decrease in crypt numbers. The data can also produce ratios of irradiated:control figures for cells or structural elements. These ratios, along with tissue area measurements, can be used to summarize the structural damage as a composite graph and table, including a total figure, known as the Morphological Index. This is used to quantify the temporal response of the wall as a whole and to compare the effects of different qualities of radiation, here X-ray and cyclotron-produced neutron radiations. It is possible that such analysis can be used predictively along with other reference data to identify the treatment, dose and time required to produce observed tissue damage. (author)

  9. Longitudinal Study of Intestinal Symptoms and Fecal Continence in Patients With Conformal Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Geinitz, Hans; Thamm, Reinhard; Keller, Monika; Astner, Sabrina T.; Heinrich, Christine; Scholz, Christian; Pehl, Christian; Kerndl, Simone; Prause, Nina; Busch, Raymonde; Molls, Michael; Zimmermann, Frank B.

    2011-01-01

    Purpose: To prospectively assess the intestinal symptoms and fecal continence in patients who had undergone conformal radiotherapy (CRT) for prostate cancer. Methods and Materials: A total of 78 men who had undergone definitive CRT for prostate cancer were evaluated. The patients were assessed before, during (treatment Weeks 4 and 6), and 2, 12, and 24 months after CRT completion. The intestinal symptoms and fecal continence were evaluated with comprehensive standardized questionnaires. Results: The intestinal symptoms were mostly intermittent, with only a small minority of patients affected daily. Defecation pain, fecal urge, and rectal mucous discharge increased significantly during therapy. Defecation pain and rectal mucous discharge had returned to baseline levels within 8 weeks and 1 year after CRT, respectively. However, fecal urge remained significantly elevated for ≤1 year and then returned toward the pretreatment values. The prevalence of rectal bleeding was significantly elevated 2 years after CRT. Fecal continence deteriorated during CRT and remained impaired at 1 year after treatment. Incontinence was mostly minor, occurring less than once per week and predominantly affecting incontinence for gas. Conclusion: Intestinal symptoms and fecal incontinence increased during prostate CRT. Except for rectal bleeding, the intestinal symptoms, including fecal incontinence, returned to baseline levels within 1-2 years after CRT. Thus, the rate of long-term late radiation-related intestinal toxicity was low.

  10. Late intestinal adverse effects of radiotherapy for uterine cervical cancer

    International Nuclear Information System (INIS)

    Tsukada, Seiji; Yamamoto, Yasuaki; Kaneko, Toru; Maruhashi, Toshihiro; Takahashi, Takeshi

    1993-01-01

    We investigated the incidence and clinical appearance of late adverse intestinal effects in 88 patients treated with postoperative radiotherapy and 46 patients treated with radiotherapy alone for uterine cervical cancer. In the postoperative radiotherapy group, colitis, ileus and bowel fistules were seen in 13 patients (14.8%), 8 (9.1%), and 3 (3.4%) of the patients, respectively. Of these patients, 11 (12.5%) needed to have surgical therapy for these adverse effects. In the radiation alone group, 18 patients (39.1%) had colitis and 2 (4.3%) had ileus; of them, 2 patients (4.3%) needed to have surgical therapy. The higher incidence of so severe adverse effects as to require surgical therapy in the postoperative radiotherapy group indicates that adhesion caused by operation might have caused the occurrence of these adverse effects. Four of a total of 134 patients died of causes which might be attributable to irradiation. In 61 patients treated by radical hysterectomy without postoperative radiotherapy, intestinal adverse effects were not found. These results indicate that late intestinal adverse effects after radiotherapy are likely to occur in some cases very severely; therefore, careful consideration is necessary in the decision to use radiotherpay for uterine cervical cancer. (J.P.N.)

  11. Foreign body-associated intestinal pyogranuloma resulting in intestinal obstruction in four dogs.

    Science.gov (United States)

    Papazoglou, L G; Tontis, D; Loukopoulos, P; Patsikas, M N; Hermanns, W; Kouti, V; Timotheou, T; Liapis, I; Tziris, N; Rallis, T S

    2010-04-17

    Intestinal obstruction resulting from an intramural foreign body-associated pyogranuloma was diagnosed in four dogs. Vomiting and weight loss were the main clinical signs. On physical examination, a mass in the abdomen was detected in three dogs. Abdominal radiography demonstrated the presence of soft tissue opacity in three of the dogs and gas-filled dilated intestinal loops in all four dogs. Abdominal ultrasonography showed hyperkinetic fluid-filled dilated intestinal loops and a hypoechoic small intestinal mass in all the dogs. Exploratory coeliotomy confirmed the presence of a jejunal mass, which was removed by resection and anastomosis in all the dogs. In one of the dogs a linear foreign body was also found cranial to the mass and was removed through a separate enterotomy incision. The lesions were diagnosed as foreign body-associated intestinal pyogranulomas on histological examination. Three dogs recovered without complications, but the fourth showed signs of septic peritonitis four days after surgery and was euthanased at the owner's request. The other three dogs remained disease-free 12 to 42 months after surgery.

  12. Radiation sensitivity of foodborne pathogens in meat byproducts with different packaging

    International Nuclear Information System (INIS)

    Yong, Hae In; Kim, Hyun-Joo; Nam, Ki Chang; Kwon, Joong Ho; Jo, Cheorun

    2015-01-01

    The aim of this study was to determine radiation sensitivity of Escherichia coli O157:H7 and Listeria monocytogenes in edible meat byproducts. Seven beef byproducts (heart, liver, lung, lumen, omasum, large intestine, and small intestine) and four pork byproducts (heart, large intestine, liver, and small intestine) were used. Electron beam irradiation significantly reduced the numbers of pathogenic microorganisms in meat byproducts and no viable cells were detected in both aerobically- and vacuum-packaged samples irradiated at 4 kGy. Meat byproducts packed under vacuum had higher D 10 value than the ones packed aerobically. No significant difference was observed between the D 10 values of E. coli O157:H7 and L. monocytogenes inoculated in either aerobically or vacuum packaged samples. These results suggest that low-dose electron beam irradiation can significantly decrease microbial numbers and reduce the risk of meat byproduct contamination by the foodborne pathogens. - Highlights: • Radiation sensitivities of pathogens in meat byproduct were tested. • Electron beam irradiation of 3 or 4 kGy reduced pathogens by> 9 log • The D 10 values were lower in the aerobic-packaging than under vacuum condition

  13. Protective mechanisms and acclimation to solar ultraviolet-b radiation in oenothera stricta. Final report

    International Nuclear Information System (INIS)

    Robberecht, R.; Caldwell, M.M.

    1981-12-01

    Plant adaptations ameliorating or repairing the damaging effects of ultraviolet-B (UV-B) radiation on plant tissue were investigated. The degree of phenotype plasticity in UV protective mechanisms and acclimation in relation to the natural solar UV-B radiation flux and in an enhanced UV-B irradiance environment was also examined. Mechanisms by which plants avoid radiation, adaptations altering the path of radiation incident on the leaf, and repair processes were considered. Attenuation of UV-B by tissues, UV-B irradiation into the leaf, and the effects of UV-B on photosynthesis were investigated

  14. Dose-Dependent Effects of Lactobacillus rhamnosus on Serum Interleukin-17 Production and Intestinal T-Cell Responses in Pigs Challenged with Escherichia coli

    Science.gov (United States)

    Zhu, Yao-Hong; Li, Xiao-Qiong; Zhang, Wei; Zhou, Dong; Liu, Hao-Yu

    2014-01-01

    The mechanism underlying the dose effect of probiotics on ameliorating diarrhea has not been fully elucidated. Here, low (1 × 109 CFU/ml) or high (1 × 1011 CFU/ml) doses of Lactobacillus rhamnosus ATCC 7469 were administered orally to piglets for 1 week before F4 (K88)-positive enterotoxigenic Escherichia coli (F4+ ETEC) challenge. Administration of a low, but not a high, dose of L. rhamnosus decreased the percentage of CD3+ CD4+ CD8− T cells in the peripheral blood. Notably, transiently increased serum concentrations of interleukin-17A (IL-17A) were observed after F4+ ETEC challenge in pigs pretreated with a high dose of L. rhamnosus. Administration of L. rhamnosus increased the percentage of the small intestinal lamina propria CD3+ CD4+ CD8− cells and Peyer's patch CD3+ CD4− CD8− and CD3− CD4− CD8+ cells. The percentage of ileal intraepithelial CD3+ CD4− CD8+ cells increased only in the high-dose piglets. Administration of L. rhamnosus downregulated expression of ileal IL-17A after F4+ ETEC challenge but had no effect on expression of gamma interferon (IFN-γ), IL-12, IL-4, and FOXP3 mRNA in the small intestine. Expression of jejunal IL-2, ileal transforming growth factor β1 (TGF-β1), and ileal IL-10 was upregulated in the low-dose piglets after F4+ ETEC challenge. Our findings suggest that amelioration of infectious diarrhea in piglets by L. rhamnosus is associated with the generation of lamina propria CD3+ CD4+ CD8− T cells, the expansion of Peyer's patch CD3+ CD4− CD8− and CD3− CD4− CD8+ cells, and the attenuation of F4+ ETEC-induced increase in CD3+ CD4+ CD8+ T cells in the small intestine. However, consumption of high doses of L. rhamnosus may increase levels of serum IL-17A after F4+ ETEC challenge, thus eliciting a strong proinflammatory response. PMID:24389928

  15. The Effect of Reflexology on the Pain-Insomnia-Fatigue Disturbance Cluster of Breast Cancer Patients During Adjuvant Radiation Therapy.

    Science.gov (United States)

    Tarrasch, Ricardo; Carmel-Neiderman, Narin N; Ben-Ami, Sarah; Kaufman, Bella; Pfeffer, Raphi; Ben-David, Merav; Gamus, Dorit

    2018-01-01

    To evaluate the effects of reflexology treatment on quality of life, sleep disturbances, and fatigue in breast cancer patients during radiation therapy. A total of 72 women with breast cancer (stages 1-3) scheduled for radiation therapy were recruited. Women were allocated upon their preference either to the group receiving reflexology treatments once a week concurrently with radiotherapy and continued for 10 weeks or to the control group (usual care). The Lee Fatigue Scale, General Sleep Disturbance Scale, and Multidimensional Quality of Life Scale Cancer were completed by each patient in both arms at the beginning of the radiation treatment, after 5 weeks, and after 10 weeks of reflexology treatment. The final analysis included 58 women. The reflexology treated group demonstrated statistically significant lower levels of fatigue after 5 weeks of radiation therapy (p fatigue, quality of sleep, pain, and quality of life in breast cancer patients during radiation therapy. Reflexology prevented the decline in quality of life and significantly ameliorated the fatigue and quality of sleep of these patients. An encouraging trend was also noted in amelioration of pain levels.

  16. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure.

    Science.gov (United States)

    Korpela, Katri; Mutanen, Annika; Salonen, Anne; Savilahti, Erkki; de Vos, Willem M; Pakarinen, Mikko P

    2017-02-01

    Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent phylogenetic microarray analysis. The microbiota was related to histological liver injury, fecal markers of intestinal inflammation, matrix metalloproteinase 9 and calprotectin, and disease characteristics. Overabundance of Lactobacilli, Proteobacteria, and Actinobacteria was observed in IF, whereas bacteria related to Clostridium clusters III, IV, and XIVa along with overall diversity and richness were reduced. Patients were segregated into 3 subgroups based on dominating bacteria: Clostridium cluster XIVa, Proteobacteria, and bacteria related to Lactobacillus plantarum. In addition to liver steatosis and fibrosis, Proteobacteria were associated with prolonged current parenteral nutrition (PN) as well as liver and intestinal inflammation. Lactobacilli were related to advanced steatosis and fibrosis mostly after weaning off PN without associated inflammation. In multivariate permutational analysis of variance, liver steatosis, bowel length, PN calories, and antibiotic treatment best explained the microbiota variation among patients with IF. Intestinal microbiota composition was associated with liver steatosis in IF and better predicted steatosis than duration of PN or length of the remaining intestine. Our results may be explained by a model in which steatosis is initiated during PN in response to proinflammatory lipopolysaccharides produced by Proteobacteria and progresses after weaning off PN, as the L plantarum group Lactobacilli becomes dominant and affects lipid metabolism by altering bile acid signaling.

  17. GPR81, a Cell-Surface Receptor for Lactate, Regulates Intestinal Homeostasis and Protects Mice from Experimental Colitis.

    Science.gov (United States)

    Ranganathan, Punithavathi; Shanmugam, Arulkumaran; Swafford, Daniel; Suryawanshi, Amol; Bhattacharjee, Pushpak; Hussein, Mohamed S; Koni, Pandelakis A; Prasad, Puttur D; Kurago, Zoya B; Thangaraju, Muthusamy; Ganapathy, Vadivel; Manicassamy, Santhakumar

    2018-03-01

    At mucosal sites such as the intestine, the immune system launches robust immunity against invading pathogens while maintaining a state of tolerance to commensal flora and ingested food Ags. The molecular mechanisms underlying this phenomenon remain poorly understood. In this study, we report that signaling by GPR81, a receptor for lactate, in colonic dendritic cells and macrophages plays an important role in suppressing colonic inflammation and restoring colonic homeostasis. Genetic deletion of GPR81 in mice led to increased Th1/Th17 cell differentiation and reduced regulatory T cell differentiation, resulting in enhanced susceptibility to colonic inflammation. This was due to increased production of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) and decreased expression of immune regulatory factors (IL-10, retinoic acid, and IDO) by intestinal APCs lacking GPR81. Consistent with these findings, pharmacological activation of GPR81 decreased inflammatory cytokine expression and ameliorated colonic inflammation. Taken together, these findings identify a new and important role for the GPR81 signaling pathway in regulating immune tolerance and colonic inflammation. Thus, manipulation of the GPR81 pathway could provide novel opportunities for enhancing regulatory responses and treating colonic inflammation. Copyright © 2018 by The American Association of Immunologists, Inc.

  18. Intestinal Irradiation and Fibrosis in a Th1-Deficient Environment

    International Nuclear Information System (INIS)

    Linard, Christine; Billiard, Fabienne; Benderitter, Marc

    2012-01-01

    Purpose: Changes in the Th1/Th2 immune balance may play a role in increasing the incidence of radiation-induced toxicity. This study evaluates the consequences of Th1 deficiency on intestinal response (fibrosis and T cell trafficking) to abdominal irradiation and examines in mucosa and mesenteric lymph nodes (MLN) the differential involvement of the two Th1 pathways, T-bet/STAT1 and IL-12/STAT4, in controlling this balance in mice. Methods and Materials: Using T-bet-deficient mice (T-bet −/− ), we evaluated the mRNA and protein expression of the Th1 pathways (IFN-γ, T-bet/STAT1, and IL-12/STAT4) and the CD4 + and CD8 + populations in ileal mucosa and MLN during the first 3 months after 10 Gy abdominal irradiation. Results: The T-bet-deficient mice showed an increased fibrotic response to radiation, characterized by higher TGF-β1, col3a1 expression, and collagen deposition in mucosa compared with wild-type mice. This response was associated with drastically lower expression of IFN-γ, the hallmark Th1 cytokine. Analysis of the Th1 expression pathways, T-bet/STAT1 and IL-12/STAT4, showed their equal involvement in the failure of Th1 polarization. A minimal IFN-γ level depended on the IL-23-p19/STAT4 level. In addition, the radiation-induced deficiency in the priming of Th1 by IFN-γ was related to the defective homing capacity of CD8 + cells in the mucosa. Conclusion: Irradiation induces Th2 polarization, and the Th2 immune response may play a role in potentiating irradiation-induced intestinal collagen deposition.

  19. Radioprotection of the intestinal crypts of mice by recombinant human interleukin-1 alpha

    International Nuclear Information System (INIS)

    Wu, S.G.; Miyamoto, T.

    1990-01-01

    Recombinant human interleukin-1 alpha (rHIL-1 alpha or IL-1) protected the intestinal crypt cells of mice against X-ray-induced damage. The survival of crypt cells measured in terms of their ability to form colonies of regenerating duodenal epithelium in situ was increased when IL-1 was given either before or after irradiation. The maximum degree of radioprotection was seen when the drug was given between 13 and 25 h before irradiation. The IL-1 dose producing maximum protection was about 6.3 micrograms/kg. This is the first report indicating that the cytokine IL-1 has a radioprotective effect in the intestine. The finding suggests that IL-1 may be of potential value in preventing radiation injury to the gut in the clinic

  20. Primary intestinal lymphangiectasia.

    Science.gov (United States)

    Suresh, N; Ganesh, R; Sankar, Janani; Sathiyasekaran, Malathi

    2009-10-01

    Primary intestinal lymphangiectasia (PIL) is a rare disease of intestinal lymphatics presenting with hypoproteinemia, bilateral lower limb edema, ascites, and protein losing enteropathy. We report a series of 4 children from Chennai, India presenting with anasarca, recurrent diarrhea, hypoproteinemia and confirmatory features of PIL on endoscopy and histopathology.

  1. Si-Jun-Zi Decoction Treatment Promotes the Restoration of Intestinal Function after Obstruction by Regulating Intestinal Homeostasis

    Directory of Open Access Journals (Sweden)

    Xiangyang Yu

    2014-01-01

    Full Text Available Intestinal obstruction is a common disease requiring abdominal surgery with significant morbidity and mortality. Currently, an effective medical treatment for obstruction, other than surgical resection or decompression, does not exist. Si-Jun-Zi Decoction is a famous Chinese medicine used to replenish qi and invigorate the functions of the spleen. Modern pharmacological studies show that this prescription can improve gastrointestinal function and strengthen immune function. In this study, we investigated the effects of a famous Chinese herbal formula, Si-Jun-Zi Decoction, on the restoration of intestinal function after the relief of obstruction in a rabbit model. We found that Si-Jun-Zi Decoction could reduce intestinal mucosal injury while promoting the recovery of the small intestine. Further, Si-Jun-Zi Decoction could regulate the intestinal immune system. Our results suggest that Si-Jun-Zi Decoction promotes the restoration of intestinal function after obstruction by regulating intestinal homeostasis. Our observations indicate that Si-Jun-Zi Decoction is potentially a therapeutic drug for intestinal obstruction.

  2. Epinephrine Injection effect on serotonin metabolism in small intestines of gamma irradiated rats

    International Nuclear Information System (INIS)

    Saada, H.N.; Mahdy, A.M.

    1997-01-01

    The response of serotonin metabolism to epinephrine injection was examined in the small intestine of normal and whole body gamma irradiated rats. The data revealed that a single dose of 6 Gy induced decrease in serotonin content associated with increase of monoaminoxidase activity (MAO), and 5-hydroxyindol acetic acid (5-HIAA); at one and four hours, and one, three and seven days after exposure. Intraperitoneal administration of epinephrine to normal unirradiated rats at a dose of 0.2 mug/g increased serotonin content, decreased (MAO) activity, and (5-HIAA) level, one and four hours after treatment. No significant changes were recorded later. Injection of epinephrine to rats, 15 minutes before irradiation, resulted in no significant changes of serotonin content, MAO activity and 5-HIAA level at one, four hours and one day after irradiation. At three and seven days, the changes were less significant. The results obtained suggest that the effect of epinephrine on serotonin and 5-HIAA levels in the small intestine of rats is mediated by the opposing effect of epinephrine on the radiation induced increase of intestinal MAO activity

  3. The effect of interstitial 125I seeds implantation on intestinal wall: a pathological observation in experimental dogs

    International Nuclear Information System (INIS)

    Ning Houfa; Zhang Fenglian; Shen An; Cao Guiwen; Cui Xinjiang

    2010-01-01

    Objective: To observe the radiation injury of the bowel wall due to the implantation of interstitial 125 I seeds in experimental dogs. Methods: A total of 12 healthy male dogs were randomly and equally divided into 3 experimental groups and 1 control group, with 3 dogs in each group.In the experimental groups, two 125 I seeds with the active radiation dose of 0.8mCi were symmetrically implanted under the serous membrane of the dog's small intestinal wall. The dogs were fed for 14 days (group A), for one month (group B) and for two months (group C) respectively when the animals were scheduled to be sacrificed. The dogs' general condition was observed till they were sacrificed. The seed-implanting intestinal segments were then removed and dyed with HE staining method for electronic microscopic exam. The histopathologic findings were recorded and the results were compared between four groups. Results: No obvious histopathological changes were found in the dog's bowel wall 14 days after the implantation. One month after the procedure cellular injury was observed under electronic microscope, and two months after the operation partial fibrosis of the intestinal wall appeared but no ulceration or perforation occurred. Conclusion: The implantation of 125 I seeds can cause reversible cellular injuries of the intestinal wall in experimental dogs, the degree of the damage reaches its peak at one month after the implant when the partial fibrosis of bowel wall becomes evident. However, the seeds do not cause any serious complications, such as ulceration or perforation. (authors)

  4. Gastric and intestinal surgery.

    Science.gov (United States)

    Fossum, Theresa W; Hedlund, Cheryl S

    2003-09-01

    Gastric surgery is commonly performed to remove foreign bodies and correct gastric dilatation-volvulus and is less commonly performed to treat gastric ulceration or erosion, neoplasia, and benign gastric outflow obstruction. Intestinal surgery, although commonly performed by veterinarians, should never be considered routine. The most common procedures of the small intestinal tract performed in dogs and cats include enterotomy and resection/anastomosis. Surgery of the large intestine is indicated for lesions causing obstruction, perforations, colonic inertia, or chronic inflammation.

  5. Intestinal epithelium in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Mehmet eCoskun

    2014-08-01

    Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.

  6. Radiation-injured bowel

    Energy Technology Data Exchange (ETDEWEB)

    Localio, S.A.; Pachter, H.L.; Gouge, T.H.

    1979-01-01

    Radiation enteropathy is an insidious, progressive disease that is seen with increasing frequency. Serious disabilities may develop after years of gestation. Those patients who require surgery are treated by control of sepsis, correction of metabolic abnormalities, and reversal of protein/calorie malnutrition prior to definitive surgery. The treatment of choice is resection with anastomosis, but recurrences may occur many years later in intestine grossly normal at the time of surgery.

  7. Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Scanff, P.; Souidi, M.; Grison, S.; Griffiths, N.M.; Gourmelon, P.

    2004-01-01

    The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. Basal hepatic secretion was increased only for taurocholate, in accordance with the marked increase of CYP8B1 activity in the liver. The results are clearly demonstrate that concomitantly with radiation-induced intestinal bile acid malabsorption, hepatic bile acid synthesis and secretion are also changed. A current working model for pathophysiological changes in enterohepatic recycling after irradiation is thus proposed. (author)

  8. Abdominal radiation causes bacterial translocation

    International Nuclear Information System (INIS)

    Guzman-Stein, G.; Bonsack, M.; Liberty, J.; Delaney, J.P.

    1989-01-01

    The purpose of this study was to determine if a single dose of radiation to the rat abdomen leads to bacterial translocation into the mesenteric lymph nodes (MLN). A second issue addressed was whether translocation correlates with anatomic damage to the mucosa. The radiated group (1100 cGy) which received anesthesia also was compared with a control group and a third group which received anesthesia alone but no abdominal radiation. Abdominal radiation lead to 100% positive cultures of MLN between 12 hr and 4 days postradiation. Bacterial translocation was almost nonexistent in the control and anesthesia group. Signs of inflammation and ulceration of the intestinal mucosa were not seen until Day 3 postradiation. Mucosal damage was maximal by Day 4. Bacterial translocation onto the MLN after a single dose of abdominal radiation was not apparently dependent on anatomical, histologic damage of the mucosa

  9. Assessment of changes of some functions of Ukrainian acid soils after chemical amelioration

    Directory of Open Access Journals (Sweden)

    Zapko Yurij

    2014-09-01

    Full Text Available The objective of the article was to determine the effectiveness of lime of different origin for chemical amelioration of soils and examine its impact on soil functions such as productivity, habitat, regulation of water quality, and the protective buffer biogeocenotic screen. Limy ameliorants were applied in small local field experiment on Luvic Chernozem, and experiment with lysimeter columns was carried out on Albic Luvisol. The number of the main groups of microflora and enzymatic activity of soil was determined in soil samples taken for the analysis from the root zone. Research concerning the influence of natural and industrial origin ameliorants on soil as habitat showed the correlation of sugar beets productivity with soil biogenic. The increase of biomultiplicity of soil microbiota after addition of a cement dust and negative influence of red sludge on soil as habitat for living organisms was observed. Research involving the influence of ameliorants on soil by lime as the protective buffer biogeocenotic screen was carried out using lysimeter columns. It was stated that the addition of limy ameliorants reduces mobility of heavy metals.

  10. Biochar from commercially cultivated seaweed for soil amelioration

    Science.gov (United States)

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-04-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum - brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma - red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity.

  11. Ghrelin Ameliorates Asthma by Inhibiting Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Fu, Tian; Wang, Lei; Zeng, Qingdi; Zhang, Yan; Sheng, Baowei; Han, Liping

    2017-12-01

    This study aimed to confirm the ameliorative effect of ghrelin on asthma and investigate its mechanism. The murine model of asthma was induced by ovalbumin (OVA) treatment and assessed by histological pathology and airway responsiveness to methacholine. The total and differential leukocytes were counted. Tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 levels in bronchoalveolar lavage fluid were quantified by commercial kits. The protein levels in pulmonary tissues were measured by Western blot analysis. Ghrelin ameliorated the histological pathology and airway hyperresponsiveness in the OVA-induced asthmatic mouse model. Consistently, OVA-increased total and differential leukocytes and levels of tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 in bronchoalveolar lavage fluid were significantly attenuated by ghrelin. Ghrelin prevented the increased protein levels of the endoplasmic reticulum stress markers glucose regulated protein 78 and CCAAT/enhancer binding protein homologous protein and reversed the reduced levels of p-Akt in asthmatic mice. Ghrelin might prevent endoplasmic reticulum stress activation by stimulating the Akt signaling pathway, which attenuated inflammation and ameliorated asthma in mice. Ghrelin might be a new target for asthma therapy. Copyright © 2017. Published by Elsevier Inc.

  12. Biochar from commercially cultivated seaweed for soil amelioration

    Science.gov (United States)

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-01-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum – brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma – red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity. PMID:25856799

  13. Diagnosis of intestinal and extra intestinal amoebiasis

    International Nuclear Information System (INIS)

    Lopez, Myriam Consuelo; Quiroz, Damian Arnoldo; Pinilla, Analida Elizabeth

    2007-01-01

    The objective is to carry out a review of the national and international literature as of the XXth century in order to update the advances for the diagnosis of complex odd Entamoeba histolytic / Entamoeba dispar and that of intestinal and extra intestinal amoebiasis that may be of use to the scientific community. As well as to unify the diagnostic criteria of this parasitosis known as a public health problem, and as a consequence of that, optimize the quality of population care. Data source: there was a systematic search for the scientific literature Publisher in Spanish and English since 1960 until today, this selection started on the first semester of 2006 until 2007, in the development of the line on intestinal and extra-intestinal amoebiasis of the Medical School of the National University of Colombia. A retrospective search process was carried out, systematically reviewing the most relevant articles as well as the products of this research line. In deciding how to make this article, there was a continuous search in different data bases such as Medline, SciELO and other bases in the library of the National University of Colombia, as well as other classical books related to the subject. For that purpose the terms amoebiasis, odd Entamoeba histolytic, Entamoeba, diagnosis, epidemiology, dysentery, amoebic liver abscess, were used. Studies selection: titles and abstracts were reviewed to select the original publications and the most representative ones related to this article's subject. Data extraction: the articles were classified according to the subject, the chronology and the authors according to the scientific contribution to solve the problem. Synthesis of the data: in the fi rst instance, a chronological critical analysis was carried out to order and synthesize the progress made in the diagnosis until confirmation of the experts' agreements in the field of amoebiasis was obtained throughout the world. Conclusion: this article summarizes what has taken place

  14. Intestinal transplantation: The anesthesia perspective.

    Science.gov (United States)

    Dalal, Aparna

    2016-04-01

    Intestinal transplantation is a complex and challenging surgery. It is very effective for treating intestinal failure, especially for those patients who cannot tolerate parenteral nutrition nor have extensive abdominal disease. Chronic parental nutrition can induce intestinal failure associated liver disease (IFALD). According to United Network for Organ Sharing (UNOS) data, children with intestinal failure affected by liver disease secondary to parenteral nutrition have the highest mortality on a waiting list when compared with all candidates for solid organ transplantation. Intestinal transplant grafts can be isolated or combined with the liver/duodenum/pancreas. Organ Procurement and Transplantation Network (OPTN) has defined intestinal donor criteria. Living donor intestinal transplant (LDIT) has the advantages of optimal timing, short ischemia time and good human leukocyte antigen matching contributing to lower postoperative complications in the recipient. Thoracic epidurals provide excellent analgesia for the donors, as well as recipients. Recipient management can be challenging. Thrombosis and obstruction of venous access maybe common due to prolonged parenteral nutrition and/or hypercoaguability. Thromboelastography (TEG) is helpful for managing intraoperative product therapy or thrombosis. Large fluid shifts and electrolyte disturbances may occur due to massive blood loss, dehydration, third spacing etc. Intestinal grafts are susceptible to warm and cold ischemia and ischemia-reperfusion injury (IRI). Post-reperfusion syndrome is common. Cardiac or pulmonary clots can be monitored with transesophageal echocardiography (TEE) and treated with recombinant tissue plasminogen activator. Vasopressors maybe used to ensure stable hemodynamics. Post-intestinal transplant patients may need anesthesia for procedures such as biopsies for surveillance of rejection, bronchoscopy, endoscopy, postoperative hemorrhage, anastomotic leaks, thrombosis of grafts etc. Asepsis

  15. Presentation of a nationwide multicenter registry of intestinal failure and intestinal transplantation

    NARCIS (Netherlands)

    Neelis, E. G.; Roskott, A. M.; Dijkstra, G.; Wanten, G. J.; Serlie, M. J.; Tabbers, M. M.; Damen, G.; Olthof, E. D.; Jonkers, C. F.; Kloeze, J. H.; Ploeg, R. J.; Imhann, F.; Nieuwenhuijs, V. B.; Rings, E. H. H. M.

    Background & aims: Exact data on Dutch patients with chronic intestinal failure (CIF) and after intestinal transplantation (ITx) have been lacking. To improve standard care of these patients, a nationwide collaboration has been established. Objectives of this study were obtaining an up-to-date

  16. Presentation of a nationwide multicenter registry of intestinal failure and intestinal transplantation

    NARCIS (Netherlands)

    Neelis, E.G.; Roskott, A.M.; Dijkstra, G.; Wanten, G.J.A.; Serlie, M.J.; Tabbers, M.M.; Damen, G.M.; Olthof, E.D.; Jonkers, C.F.; Kloeze, J.H.; Ploeg, R.J.; Imhann, F.; Nieuwenhuijs, V.B.; Rings, E.H.

    2016-01-01

    BACKGROUND & AIMS: Exact data on Dutch patients with chronic intestinal failure (CIF) and after intestinal transplantation (ITx) have been lacking. To improve standard care of these patients, a nationwide collaboration has been established. Objectives of this study were obtaining an up-to-date

  17. Portulaca oleracea Linn seed extract ameliorates hydrogen ...

    African Journals Online (AJOL)

    Portulaca oleracea Linn seed extract ameliorates hydrogen ... induced cell death by inhibiting oxidative stress and ROS generation. Keywords: ... culture medium; therefore the stock solutions of ... acetic acid (1 %) and ethanol (50 %) to extract.

  18. Intestinal Stem Cell Markers in the Intestinal Metaplasia of Stomach and Barrett's Esophagus.

    Directory of Open Access Journals (Sweden)

    Bo Gun Jang

    Full Text Available Gastric intestinal metaplasia (IM is a highly prevalent preneoplastic lesion; however, the molecular mechanisms regulating its development remain unclear. We have previously shown that a population of cells expressing the intestinal stem cell (ISC marker LGR5 increases remarkably in IM. In this study, we further investigated the molecular characteristics of these LGR5+ cells in IM by examining the expression profile of several ISC markers. Notably, we found that ISC markers-including OLFM4 and EPHB2-are positively associated with the CDX2 expression in non-tumorous gastric tissues. This finding was confirmed in stomach lesions with or without metaplasia, which demonstrated that OLFM4 and EPHB2 expression gradually increased with metaplastic progression. Moreover, RNA in situ hybridization revealed that LGR5+ cells coexpress several ISC markers and remained confined to the base of metaplastic glands, reminiscent to that of normal intestinal crypts, whereas those in normal antral glands expressed none of these markers. Furthermore, a large number of ISC marker-expressing cells were diffusely distributed in gastric adenomas, suggesting that these markers may facilitate gastric tumorigenesis. In addition, Barrett's esophagus (BE-which is histologically similar to intestinal metaplasia-exhibited a similar distribution of ISC markers, indicating the presence of a stem cell population with intestinal differentiation potential. In conclusion, we identified that LGR5+ cells in gastric IM and BE coexpress ISC markers, and exhibit the same expression profile as those found in normal intestinal crypts. Taken together, these results implicate an intestinal-like stem cell population in the pathogenesis of IM, and provide an important basis for understanding the development and maintenance of this disease.

  19. Stem-cell-specific endocytic degradation defects lead to intestinal dysplasia in Drosophila

    Directory of Open Access Journals (Sweden)

    Péter Nagy

    2016-05-01

    Full Text Available UV radiation resistance-associated gene (UVRAG is a tumor suppressor involved in autophagy, endocytosis and DNA damage repair, but how its loss contributes to colorectal cancer is poorly understood. Here, we show that UVRAG deficiency in Drosophila intestinal stem cells leads to uncontrolled proliferation and impaired differentiation without preventing autophagy. As a result, affected animals suffer from gut dysfunction and short lifespan. Dysplasia upon loss of UVRAG is characterized by the accumulation of endocytosed ligands and sustained activation of STAT and JNK signaling, and attenuation of these pathways suppresses stem cell hyperproliferation. Importantly, the inhibition of early (dynamin-dependent or late (Rab7-dependent steps of endocytosis in intestinal stem cells also induces hyperproliferation and dysplasia. Our data raise the possibility that endocytic, but not autophagic, defects contribute to UVRAG-deficient colorectal cancer development in humans.

  20. Non-Meckel Small Intestine Diverticulitis

    Directory of Open Access Journals (Sweden)

    Shamim Ejaz

    2017-08-01

    Full Text Available Non-Meckel small intestine diverticulitis can have many manifestations and its management is not well-defined. We report 4 unselect cases of small intestine diverticulitis; all patients were seen by the same physician at the Emergency Center at The University of Texas MD Anderson Cancer Center between 1999 and 2014. The median age at diagnosis of these patients was 82 years (range, 76–87 years. All 4 patients presented with acute onset of abdominal pain, and computed tomography scans showed characteristics of small intestine diverticulitis unrelated to cancer. Most of the diverticula were found in the region of the duodenum and jejuno-ileal segments of the small intestine. The patients, even those with peripancreatic inflammation and localized perforation, were treated conservatively. Non-Meckel diverticulitis can be overlooked in the initial diagnosis because of the location of the diverticulosis, the age of the patient, and the rarity of the disease. Because patients with non-Meckel small intestine diverticulitis can present with acute abdominal pain, non-Meckel small intestine diverticulitis should be considered in the differential diagnosis of patients with acute abdominal pain, and computed tomography scans can help identify the condition. Because of the rarity of non-Meckel small intestine diverticulitis, few studies have been published, and the data are inconclusive about how best to approach these patients. Our experience with these 4 elderly patients indicates that non-Meckel small intestine diverticulitis can be treated conservatively, which avoids the potential morbidity and mortality of a surgical approach.

  1. Dyslipidaemia--hepatic and intestinal cross-talk.

    LENUS (Irish Health Repository)

    Tomkin, Gerald H

    2010-06-01

    Cholesterol metabolism is tightly regulated with the majority of de novo cholesterol synthesis occurring in the liver and intestine. 3 Hydroxy-3-methylglutaryl coenzyme A reductase, a major enzyme involved in cholesterol synthesis, is raised in both liver and intestine in diabetic animals. Niemann PickC1-like1 protein regulates cholesterol absorption in the intestine and facilitates cholesterol transport through the liver. There is evidence to suggest that the effect of inhibition of Niemann PickC1-like1 lowers cholesterol through its effect not only in the intestine but also in the liver. ATP binding cassette proteins G5\\/G8 regulate cholesterol re-excretion in the intestine and in the liver, cholesterol excretion into the bile. Diabetes is associated with reduced ATP binding cassette protein G5\\/G8 expression in both the liver and intestine in animal models. Microsomal triglyceride transfer protein is central to the formation of the chylomicron in the intestine and VLDL in the liver. Microsomal triglyceride transfer protein mRNA is increased in diabetes in both the intestine and liver. Cross-talk between the intestine and liver is poorly documented in humans due to the difficulty in obtaining liver biopsies but animal studies are fairly consistent in showing relationships that explain in part mechanisms involved in cholesterol homeostasis.

  2. Presentation of a nationwide multicenter registry of intestinal failure and intestinal transplantation

    NARCIS (Netherlands)

    Neelis, E. G.; Roskott, A. M.; Dijkstra, G.; Wanten, G. J.; Serlie, M. J.; Tabbers, M. M.; Damen, G.; Olthof, E. D.; Jonkers, C. F.; Kloeze, J. H.; Ploeg, R. J.; Imhann, F.; Nieuwenhuijs, V. B.; Rings, E. H. H. M.

    2016-01-01

    Exact data on Dutch patients with chronic intestinal failure (CIF) and after intestinal transplantation (ITx) have been lacking. To improve standard care of these patients, a nationwide collaboration has been established. Objectives of this study were obtaining an up-to-date prevalence of CIF and

  3. Sucralfate protects intestinal epithelial cells from radiation-induced apoptosis in rats

    International Nuclear Information System (INIS)

    Matsuu-Matsuyama, Mutsumi; Shichijo, Kazuko; Okaichi, Kumio

    2006-01-01

    Radiotherapy for malignant pelvic disease is often followed by acute radiation colitis (ARC). It has been reported that sucralfate treatment has a protective effect against ARC, though the mechanisms of action are unknown. The effects of sucralfate on X-ray radiation-induced apoptosis was studied at 4 Gy in the colonic crypt cells of rats. Sucralfate enemas given prior to radiation resulted in the following: reduction in number of apoptotic colonic crypt cells; reduction in number of caspase-3 positive cells; decreases in p53 accumulation and p21 expression; decreases of Bax/Bcl-2 ratio. The protective effects of sucralfate against ARC may be partially due to the suppression of radiation-induced apoptosis by way of p53 in the colon and the protection of the colonic epithelial stem cell region. (author)

  4. Treatment of Radiation Induced Biological Changes by Bone Marrow Transplantation

    International Nuclear Information System (INIS)

    El-Missiry, M.A.; Shehata, G.; Roushdy, H.M; Fayed, Th.A.

    1999-01-01

    Preventing the propagation of radiation induced oxidative damage has been a subject of considerable investigations. The ultimate goal of the present study is to use bone marrow cells to ameliorate or to treat the radiation sickness. Transplantation of bone marrow cell has shown promising results in the present experimental radiation treatment. In this report, suspension of bone marrow cells was injected into rats 12 h. after exposure to 4.5 Gy whole body gamma irradiation. Significant results were recorded on the successful control of the radiation induced disorders in a number of biochemical parameters including certain enzymatic and nonenzymatic antioxidants (superoxide dismutase and glutathione) and certain parameters related to kidney function including creatinine, urea as well as Atpase Activity in blood serum, urine and kidney tissue

  5. Ileal perforation induced by acute radiation injury under gefitinib treatment

    International Nuclear Information System (INIS)

    Muraoka, Takayuki; Tsukuda, Kazunori; Toyooka, Shinichi

    2011-01-01

    Enteritis is one of the side effects of radiotherapy to the abdominal cavity. Radiation enteritis involves damage to mucous membranes in the acute phase and to stromal tissues in the late phase. Perforation of the intestine tends to occur in the late phase, and rarely in the acute phase. However, we describe here a case of intestinal perforation occurring in the acute phase after irradiation in a patient who received gefitinib treatment. Gefitinib, one of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), is widely used to treat non-small cell lung cancer (NSCLC) patients, but is simultaneously known to inhibit wound healing. We suspect that gefitinib may affect regeneration of the small intestinal mucosa injured by irradiation. A 76-year-old woman had NSCLC with metastases to the 5th lumbar, sacral, and right iliac bones. To control the pain from bone metastasis, anterior-posterior opposing portal irradiation (total 35 Gy) was started, and was completed over 22 days. On day 25 after starting radiotherapy, the patient began to take gefitinib. On day 35, she presented with acute peritonitis, and an emergency laparotomy was performed. The terminal ileum was affected by radiation enteritis and there were two pin-hole perforations. In the surgical specimen, no cancerous lesions were detected, and immunohistochemical staining of phosphorylated EGFR (pEGFR) was negative. pEGFR has an important role in mucous membrane repair after irradiation. Intestinal perforation in the acute phase of radiation enteritis may be associated with impaired mucosal repair mechanisms due to the use of an EGFR-TKI such as gefitinib, as evidenced by the absence of pEGFR. (author)

  6. Intestinal Irradiation and Fibrosis in a Th1-Deficient Environment

    Energy Technology Data Exchange (ETDEWEB)

    Linard, Christine, E-mail: christine.linard@irsn.fr [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-Roses (France); Billiard, Fabienne; Benderitter, Marc [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-Roses (France)

    2012-09-01

    Purpose: Changes in the Th1/Th2 immune balance may play a role in increasing the incidence of radiation-induced toxicity. This study evaluates the consequences of Th1 deficiency on intestinal response (fibrosis and T cell trafficking) to abdominal irradiation and examines in mucosa and mesenteric lymph nodes (MLN) the differential involvement of the two Th1 pathways, T-bet/STAT1 and IL-12/STAT4, in controlling this balance in mice. Methods and Materials: Using T-bet-deficient mice (T-bet{sup -/-}), we evaluated the mRNA and protein expression of the Th1 pathways (IFN-{gamma}, T-bet/STAT1, and IL-12/STAT4) and the CD4{sup +} and CD8{sup +} populations in ileal mucosa and MLN during the first 3 months after 10 Gy abdominal irradiation. Results: The T-bet-deficient mice showed an increased fibrotic response to radiation, characterized by higher TGF-{beta}1, col3a1 expression, and collagen deposition in mucosa compared with wild-type mice. This response was associated with drastically lower expression of IFN-{gamma}, the hallmark Th1 cytokine. Analysis of the Th1 expression pathways, T-bet/STAT1 and IL-12/STAT4, showed their equal involvement in the failure of Th1 polarization. A minimal IFN-{gamma} level depended on the IL-23-p19/STAT4 level. In addition, the radiation-induced deficiency in the priming of Th1 by IFN-{gamma} was related to the defective homing capacity of CD8{sup +} cells in the mucosa. Conclusion: Irradiation induces Th2 polarization, and the Th2 immune response may play a role in potentiating irradiation-induced intestinal collagen deposition.

  7. Black ginseng extract ameliorates hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Evelyn Saba

    2016-04-01

    Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  8. Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration.

    Science.gov (United States)

    Schall, K A; Holoyda, K A; Grant, C N; Levin, D E; Torres, E R; Maxwell, A; Pollack, H A; Moats, R A; Frey, M R; Darehzereshki, A; Al Alam, D; Lien, C; Grikscheit, T C

    2015-08-01

    Loss of significant intestinal length from congenital anomaly or disease may lead to short bowel syndrome (SBS); intestinal failure may be partially offset by a gain in epithelial surface area, termed adaptation. Current in vivo models of SBS are costly and technically challenging. Operative times and survival rates have slowed extension to transgenic models. We created a new reproducible in vivo model of SBS in zebrafish, a tractable vertebrate model, to facilitate investigation of the mechanisms of intestinal adaptation. Proximal intestinal diversion at segment 1 (S1, equivalent to jejunum) was performed in adult male zebrafish. SBS fish emptied distal intestinal contents via stoma as in the human disease. After 2 wk, S1 was dilated compared with controls and villus ridges had increased complexity, contributing to greater villus epithelial perimeter. The number of intervillus pockets, the intestinal stem cell zone of the zebrafish increased and contained a higher number of bromodeoxyuridine (BrdU)-labeled cells after 2 wk of SBS. Egf receptor and a subset of its ligands, also drivers of adaptation, were upregulated in SBS fish. Igf has been reported as a driver of intestinal adaptation in other animal models, and SBS fish exposed to a pharmacological inhibitor of the Igf receptor failed to demonstrate signs of intestinal adaptation, such as increased inner epithelial perimeter and BrdU incorporation. We describe a technically feasible model of human SBS in the zebrafish, a faster and less expensive tool to investigate intestinal stem cell plasticity as well as the mechanisms that drive intestinal adaptation. Copyright © 2015 the American Physiological Society.

  9. Small Intestinal Infections.

    Science.gov (United States)

    Munot, Khushboo; Kotler, Donald P

    2016-06-01

    Small intestinal infections are extremely common worldwide. They may be bacterial, viral, or parasitic in etiology. Most are foodborne or waterborne, with specific etiologies differing by region and with diverse pathophysiologies. Very young, very old, and immune-deficient individuals are the most vulnerable to morbidity or mortality from small intestinal infections. There have been significant advances in diagnostic sophistication with the development and early application of molecular diagnostic assays, though these tests have not become mainstream. The lack of rapid diagnoses combined with the self-limited nature of small intestinal infections has hampered the development of specific and effective treatments other than oral rehydration. Antibiotics are not indicated in the absence of an etiologic diagnosis, and not at all in the case of some infections.

  10. Intestinal microbiota in healthy adults: temporal analysis reveals individual and common core and relation to intestinal symptoms.

    Directory of Open Access Journals (Sweden)

    Jonna Jalanka-Tuovinen

    Full Text Available While our knowledge of the intestinal microbiota during disease is accumulating, basic information of the microbiota in healthy subjects is still scarce. The aim of this study was to characterize the intestinal microbiota of healthy adults and specifically address its temporal stability, core microbiota and relation with intestinal symptoms. We carried out a longitudinal study by following a set of 15 healthy Finnish subjects for seven weeks and regularly assessed their intestinal bacteria and archaea with the Human Intestinal Tract (HIT Chip, a phylogenetic microarray, in conjunction with qPCR analyses. The health perception and occurrence of intestinal symptoms was recorded by questionnaire at each sampling point.A high overall temporal stability of the microbiota was observed. Five subjects showed transient microbiota destabilization, which correlated not only with the intake of antibiotics but also with overseas travelling and temporary illness, expanding the hitherto known factors affecting the intestinal microbiota. We identified significant correlations between the microbiota and common intestinal symptoms, including abdominal pain and bloating. The most striking finding was the inverse correlation between Bifidobacteria and abdominal pain: subjects who experienced pain had over five-fold less Bifidobacteria compared to those without pain. Finally, a novel computational approach was used to define the common core microbiota, highlighting the role of the analysis depth in finding the phylogenetic core and estimating its size. The in-depth analysis suggested that we share a substantial number of our intestinal phylotypes but as they represent highly variable proportions of the total community, many of them often remain undetected.A global and high-resolution microbiota analysis was carried out to determine the temporal stability, the associations with intestinal symptoms, and the individual and common core microbiota in healthy adults. The

  11. Lactobacillus reuteri strains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF-κB signaling in the intestine.

    Science.gov (United States)

    Liu, Yuying; Fatheree, Nicole Y; Mangalat, Nisha; Rhoads, Jon Marc

    2012-03-15

    Necrotizing enterocolitis (NEC) is the leading gastrointestinal cause of mortality and morbidity in the premature infant. Premature infants have a delay in intestinal colonization by commensal bacteria and colonization with potentially pathogenic organisms. Lactobacillus reuteri is a probiotic that inhibits enteric infections, modulates the immune system, and may be beneficial to prevent NEC. In previous studies, L. reuteri strains DSM 17938 and ATCC PTA 4659 differentially modulated inflammation in vitro; however, the strains had equivalent anti-inflammatory responses in LPS feeding-induced ileitis in neonatal rats in vivo. The impact of these two strains in the prevention of NEC has not been previously investigated. NEC was induced in newborn rats by orogastric formula feeding and exposure to hypoxia. L. reuteri was added to the formula to prevent NEC. NEC score, Toll-like receptor (TLR)-signaling genes, phospho-IκB activity, and cytokine levels in the intestine were examined. Both strains significantly increased survival rate and decreased the incidence and severity of NEC, with optimal effects from DSM 17938. In response to probiotic, mRNA expression of IL-6, TNF-α, TLR4, and NF-κB was significantly downregulated, while mRNA levels of anti-inflammatory cytokine IL-10 were significantly upregulated. In parallel, L. reuteri treatment led to decrease intestinal protein levels of TLR4 and cytokine levels of TNF-α and IL-1β in newborn rats with NEC. Both strains significantly inhibited not only intestinal LPS-induced phospho-IκB activity in an ex vivo study but also decreased the levels of phospho-IκB in the intestines of NEC rat model. Cow milk formula feeding produced a similar but milder proinflammatory profile in the intestine that was also ameliorated by 17938. Our studies demonstrate that each of the two L. reuteri strains has potential therapeutic value in our NEC model and in enteritis associated with cow milk feeding. These results support the

  12. Small Intestine Cancer—Health Professional Version

    Science.gov (United States)

    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.

  13. Parenteral Nutrition and Intestinal Failure.

    Science.gov (United States)

    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.

  14. Determination of Intestine Inflammation Markers in Diagnostic Search in Children with Intestinal Diseases

    Directory of Open Access Journals (Sweden)

    N.V. Pavlenko

    2016-08-01

    Full Text Available Introduction. Prevalence of bowel diseases in children is the second, trailing only the diseases of gastroduodenal zone and growing in recent years. Actual one is the problem of differential diagnosis of functional and inflammatory intestinal diseases using non-invasive methods on the prehospital stage and as a screening. Objective. Comparative analysis of fecal markers of the bowel inflammation (lactoferrine and calprotectine with endoscopy and morphology of intestinal mucosa in children. Matherials and methods. 49 children aged 6–18 years were examined. All patients underwent endoscopic and morphological study of the intestine, coprotest, determination of fecal markers of bowel inflammation (lactoferrin and calprotectine. Results. It is shown that in young children, the intestinal mucosa mainly hadn’t endoscopic changes, coprotest and morphological examination didn’t reveal the signs of inflammation, fecal intestinal inflammation markers were negative (p < 0.05. In the group of older children, moderate or marked catarrhal changes were found endoscopically, coprotest results were typical of inflammation in the intestines, it was morphologically proved the presence of chronic inflammation of the mucous membrane of the colon with signs of atrophy, the results of lactoferrin and calprotectine determination were positive (p < 0.05. Conclusion. The findings suggest that the evaluation of calprotectine and lactoferrin can be used in pediatric patients because of its non-invasiveness as diagnostic screening for the selection of patients for the further endoscopic examination and diagnostic search.

  15. Intestinal spirochetosis and colon diverticulosis Espiroquetose intestinal e diverticulose do cólon

    Directory of Open Access Journals (Sweden)

    Marcus Aurelho de Lima

    2005-02-01

    Full Text Available A case of intestinal spirochetosis in a 62-year-old white male is reported. The condition was characterized by chronic flatulence and episodes of intestinal hemorrhage, in addition to the evidence of hypotonic diverticular disease, with a large number of slender organisms in the colon epithelium and cryptae. Spirochetes were demonstrated by Whartin-Starry stain. The serologic tests for syphilis and HIV were positive. Spirochetosis was treated with penicillin G, and the patient remains free of intestinal complaints 20 months later.Um caso de espiroquetose intestinal é relatado em um homem branco de 62 anos. A condição foi caracterizada por flatulência crônica e episódios de hemorragia intestinal, além da evidência de doença diverticular hipotônica dos cólons, com numerosos organismos filamentosos no epitélio e nas criptas do cólon. Os espiroquetas foram demonstrados pela coloração de Whartin-Starry. Os testes sorológicos para sífilis e HIV foram positivos. A espiroquetose foi tratada com penicilina G e o paciente permanece sem queixas intestinais após 20 meses.

  16. Medical treatment of radiation injuries-Current US status

    Energy Technology Data Exchange (ETDEWEB)

    Jarrett, D.G. [OSA - CBD and CDP, 3050 Defense Pentagon, Room 3C257, Washington, DC 20301-3050 (United States)], E-mail: david.jarrett@us.army.mil; Sedlak, R.G.; Dickerson, W.E. [Uniformed Services University, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States); Reeves, G.I. [Northrop Grumman IT, 8211 Terminal Road, Lorton, VA 22079-1421 (United States)

    2007-07-15

    A nuclear incident or major release of radioactive materials likely would result in vast numbers of patients, many of whom would require novel therapy. Fortunately, the numbers of radiation victims in the United States (USA) have been limited to date. If a mass-casualty situation occurs, there will be a need to perform rapid, accurate dose estimates and to provide appropriate medications and other treatment to ameliorate radiation injury. The medical management of radiation injury is complex. Radiation injury may include acute radiation sickness (ARS) from external and/or internal radiation exposure, internal organ damage from incorporated radioactive isotopes, and cutaneous injury. Human and animal data have shown that optimal medical care may nearly double the survivable dose of ionizing radiation. Current treatment strategies for radiation injuries are discussed with concentration on the medical management of the hematopoietic syndrome. In addition, priority areas for continuing and future research into both acute deterministic injuries and also long-term stochastic sequelae of radiation exposure have been identified. There are several near-term novel therapies that appear to offer excellent prognosis for radiation casualties, and these are also described.

  17. Intestinal epithelium in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet

    2014-01-01

    The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...... of inflammatory bowel disease (IBD). Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets....

  18. Epithelial apoptosis in mechanistically distinct methods of injury in the murine small intestine

    Science.gov (United States)

    Vyas, Dinesh; Robertson, Charles M; Stromberg, Paul E; Martin, James R.; Dunne, W. Michael; Houchen, Courtney W; Barrett, Terrence A; Ayala, Alfred; Perl, Mario; Buchman, Timothy G; Coopersmith, Craig M

    2007-01-01

    Gut epithelial apoptosis is involved in the pathophysiology of multiple diseases. This study characterized intestinal apoptosis in three mechanistically distinct injuries with different kinetics of cell death. FVB/N mice were subjected to gamma radiation, Pseudomonas aeruginosa pneumonia or injection of monoclonal anti-CD3 antibody and sacrificed 4, 12, or 24 hours post-injury (n=10/time point). Apoptosis was quantified in the jejunum by hematoxylin and eosin (H&E), active caspase-3, terminal deoxynucleotidyl transferase dUTP-mediated nick end labeling (TUNEL), in situ oligoligation reaction (ISOL,) cytokeratin 18, and annexin V staining. Reproducible results were obtained only for H&E, active caspase-3, TUNEL and ISOL, which were quantified and compared against each other for each injury at each time point. Kinetics of injury were different with early apoptosis highest following radiation, late apoptosis highest following anti CD3, and more consistent levels following pneumonia. ISOL was the most consistent stain and was always statistically indistinguishable from at least 2 stains. In contrast, active caspase-3 demonstrated lower levels of apoptosis, while the TUNEL assay had higher levels of apoptosis in the most severely injured intestine regardless of mechanism of injury. H&E was a statistical outlier more commonly than any other stain. This suggests that regardless of mechanism or kinetics of injury, ISOL correlates to other quantification methods of detecting gut epithelial apoptosis more than any other method studied and compares favorably to other commonly accepted techniques of quantifying apoptosis in a large intestinal cross sectional by balancing sensitivity and specificity across a range of times and levels of death. PMID:17357092

  19. Ameliorative Effect of Different Concentration of Mushroom ...

    African Journals Online (AJOL)

    Prof. Ogunji

    ameliorative effect of mushroom in the post-experimental stage. Samples of liver and ... except in the liver which showed mild periportal chronic inflammatory cell. However, the .... alcohol for 12 hours and through absolute alcohol to remove ...

  20. Radiation in dental practice: awareness, protection and recommendations.

    Science.gov (United States)

    Praveen, B N; Shubhasini, A R; Bhanushree, R; Sumsum, P S; Sushma, C N

    2013-01-01

    Radiation is the transmission of energy through space and matter. There are several forms of radiation, including ionizing and nonionizing. X-rays are the ionizing radiation used extensively in medical and dental practice. Even though they provide useful information and aid in diagnosis, they also have the potential to cause harmful effects. In dentistry, it is mainly used for diagnostic purposes and in a dental set-up usually the practicing dentist exposes, processes and interprets the radiograph. Even though such exposure is less, it is critical to reduce the exposure to the dental personnel and patients in order to prevent the harmful effects of radiation. Several radiation protection measures have been advocated to ameliorate these effects. A survey conducted in the Bengaluru among practicing dentists revealed that radiation protection awareness was very low and the necessary measures taken to reduce the exposure were not adequate. The aim of the article is to review important parameters that must be taken into consideration in the clinical set-up to reduce radiation exposure to patients and dental personnel.

  1. Primary intestinal lymphangiectasia (Waldmann's disease).

    Science.gov (United States)

    Vignes, Stéphane; Bellanger, Jérôme

    2008-02-22

    Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool alpha1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective

  2. Primary intestinal lymphangiectasia (Waldmann's disease

    Directory of Open Access Journals (Sweden)

    Bellanger Jérôme

    2008-02-01

    Full Text Available Abstract Primary intestinal lymphangiectasia (PIL is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other

  3. A etiological factors in mechanical intestinal obstruction

    International Nuclear Information System (INIS)

    Asad, S.; Khan, H.; Khan, I.A.; Ghaffar, S.; Rehman, Z.U.

    2012-01-01

    Background: Intestinal obstruction occurs when the normal flow of intestinal contents is interrupted. The most frequent causes of intestinal obstruction are postoperative adhesions and hernias, which cause extrinsic compression of the intestine. Less frequently, tumours or strictures of the bowel can cause intrinsic blockage. Objective of the study was to find out the various a etiological factors of mechanical intestinal obstruction and to evaluate the morbidity and mortality in adult patients presenting to Surgical 'A' unit of Ayub teaching hospital with mechanical intestinal obstruction. Methods: This cross-sectional study was conducted from March 2009 to September, 2009. All patients presenting with intestinal obstruction and were above the age of 12 years were included in the study. Patients with non-mechanical obstruction were excluded from the study and those who responded to conservative measures were also excluded. Results: A total of 36 patients with age ranging from 12 to 80 years (Mean age 37.72+-19.74 years) and male to female ratio of 1.77:1, were treated for mechanical intestinal obstruction. The most common cause for mechanical intestinal obstruction was adhesions (36.1%). Intestinal tuberculosis was the second most common cause (19.4%), while hernias and sigmoid volvulus affected 13.9% patients each. Malignancies were found in 5.6% cases. Conclusion: Adhesions and Tuberculosis are the leading causes of mechanical intestinal obstruction in Pakistan. Although some patients can be treated conservatively, a substantial portion requires immediate surgical intervention. (author)

  4. The extent of intestinal failure-associated liver disease in patients referred for intestinal rehabilitation is associated with increased mortality: an analysis of the pediatric intestinal failure consortium database.

    Science.gov (United States)

    Javid, Patrick J; Oron, Assaf P; Duggan, Christopher; Squires, Robert H; Horslen, Simon P

    2017-09-05

    The advent of regional multidisciplinary intestinal rehabilitation programs has been associated with improved survival in pediatric intestinal failure. Yet, the optimal timing of referral for intestinal rehabilitation remains unknown. We hypothesized that the degree of intestinal failure-associated liver disease (IFALD) at initiation of intestinal rehabilitation would be associated with overall outcome. The multicenter, retrospective Pediatric Intestinal Failure Consortium (PIFCon) database was used to identify all subjects with baseline bilirubin data. Conjugated bilirubin (CBili) was used as a marker for IFALD, and we stratified baseline bilirubin values as CBili4 mg/dL. The association between baseline CBili and mortality was examined using Cox proportional hazards regression. Of 272 subjects in the database, 191 (70%) children had baseline bilirubin data collected. 38% and 28% of patients had CBili >4 mg/dL and CBili 4 mg/dL, prematurity, race, and small bowel atresia. On regression analysis controlling for age, prematurity, and diagnosis, the risk of mortality was increased by 3-fold for baseline CBili 2-4 mg/dL (HR 3.25 [1.07-9.92], p=0.04) and 4-fold for baseline CBili >4 mg/dL (HR 4.24 [1.51-11.92], p=0.006). On secondary analysis, CBili >4 mg/dL at baseline was associated with a lower chance of attaining enteral autonomy. In children with intestinal failure treated at intestinal rehabilitation programs, more advanced IFALD at referral is associated with increased mortality and decreased prospect of attaining enteral autonomy. Early referral of children with intestinal failure to intestinal rehabilitation programs should be strongly encouraged. Treatment Study, Level III. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. [An experimental assessment of methods for applying intestinal sutures in intestinal obstruction].

    Science.gov (United States)

    Akhmadudinov, M G

    1992-04-01

    The results of various methods used in applying intestinal sutures in obturation were studied. Three series of experiments were conducted on 30 dogs--resection of the intestine after obstruction with the formation of anastomoses by means of double-row suture (Albert--Shmiden--Lambert) in the first series (10 dogs), by a single-row suture after V. M. Mateshchuk [correction of Mateshuku] in the second series, and bu a single-row stretching suture suggested by the author in the third series. The postoperative complications and the parameters of physical airtightness of the intestinal anastomosis were studied in dynamics in the experimental animals. The results of the study: incompetence of the anastomosis sutures in the first series 6, in the second 4, and in the third series one. Adhesions occurred in all animals of the first and second series and in 2 of the third series. Six dogs of the first series died, 4 of the second, and one of the third. Study of the dynamics of the results showed a direct connection of the complications with the parameters of the physical airtightness of the anastomosis, and the last-named with the method of the intestinal suture. Relatively better results were noted in formation of the anastomosis by means of our suggested stretshing continuous suture passed through the serous, muscular, and submucous coats of the intestine.

  6. Update on small intestinal stem cells

    OpenAIRE

    Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-01-01

    Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to id...

  7. The plain film roentgenographic findings in diagnosis of intestinal volvulus

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Gyung Ho; Seo, Yeon Hee; Sohn, Myung Hee; Kim, Chong Soo; Choi, Ki Chul; Jeon, Doo Sung [Chunbuk National University College of Medicine, Chunju (Korea, Republic of)

    1988-08-15

    intestine, the findings of the simple plain abdomen showed unusual ectopic position of small bowel, interlocking of loop in erect view, radiating stripes converging toward the center of the torsion, disarrangement of dilated loop in erect film, fixation of the dilated loop and long fluid level, and intramural gas. In 24 cases of the sigmoid vovulus, the findings of simple plain adbomen showed inverted U shaped shadow and midline crease (typical vend inner sign), single dilated without midline crease, and upright U shaped shadow with midline crease. In 2 cases of cecal volvulus, the findings of ectopic position of cecum with dilatation and distended small bowel with fluid level. In the 3 cases of compound volvulus, the findings of dilatation of sigmoid colon with displacement to the right side of the abdomen, the presence of dilated small bowel loop in the left lower abdomen, and dilated sigmoid with tapering off-shoot around the encircling ileal loop (signet-ring appearance)

  8. The plain film roentgenographic findings in diagnosis of intestinal volvulus

    International Nuclear Information System (INIS)

    Chung, Gyung Ho; Seo, Yeon Hee; Sohn, Myung Hee; Kim, Chong Soo; Choi, Ki Chul; Jeon, Doo Sung

    1988-01-01

    intestine, the findings of the simple plain abdomen showed unusual ectopic position of small bowel, interlocking of loop in erect view, radiating stripes converging toward the center of the torsion, disarrangement of dilated loop in erect film, fixation of the dilated loop and long fluid level, and intramural gas. In 24 cases of the sigmoid vovulus, the findings of simple plain adbomen showed inverted U shaped shadow and midline crease (typical vend inner sign), single dilated without midline crease, and upright U shaped shadow with midline crease. In 2 cases of cecal volvulus, the findings of ectopic position of cecum with dilatation and distended small bowel with fluid level. In the 3 cases of compound volvulus, the findings of dilatation of sigmoid colon with displacement to the right side of the abdomen, the presence of dilated small bowel loop in the left lower abdomen, and dilated sigmoid with tapering off-shoot around the encircling ileal loop (signet-ring appearance).

  9. Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

    Directory of Open Access Journals (Sweden)

    Ozkan Onal

    2015-01-01

    Full Text Available Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF intraperitoneally (ip for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD, catalase (CAT, glutathioneperoxidase (GSH-Px, malondyaldehide (MDA, and protein carbonyl (PCO were analyzed in tissue samples. Total oxidant status (TOS, and total antioxidant capacity (TAC were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy

  10. Pharmacological Inhibition of Monoacylglycerol O-Acyltransferase 2 Improves Hyperlipidemia, Obesity, and Diabetes by Change in Intestinal Fat Utilization

    Science.gov (United States)

    Take, Kazumi; Mochida, Taisuke; Maki, Toshiyuki; Satomi, Yoshinori; Hirayama, Megumi; Nakakariya, Masanori; Amano, Nobuyuki; Adachi, Ryutaro; Sato, Kenjiro; Kitazaki, Tomoyuki; Takekawa, Shiro

    2016-01-01

    Monoacylglycerol O-acyltransferase 2 (MGAT2) catalyzes the synthesis of diacylglycerol (DG), a triacylglycerol precursor and potential peripheral target for novel anti-obesity therapeutics. High-throughput screening identified lead compounds with MGAT2 inhibitory activity. Through structural modification, a potent, selective, and orally bioavailable MGAT2 inhibitor, compound A (compA), was discovered. CompA dose-dependently inhibited postprandial increases in plasma triglyceride (TG) levels. Metabolic flux analysis revealed that compA inhibited triglyceride/diacylglycerol resynthesis in the small intestine and increased free fatty acid and acyl-carnitine with shorter acyl chains than originally labelled fatty acid. CompA decreased high-fat diet (HFD) intake in C57BL/6J mice. MGAT2-null mice showed a similar phenotype as compA-treated mice and compA did not suppress a food intake in MGAT2 KO mice, indicating that the anorectic effects were dependent on MGAT2 inhibition. Chronic administration of compA significantly prevented body weight gain and fat accumulation in mice fed HFD. MGAT2 inhibition by CompA under severe diabetes ameliorated hyperglycemia and fatty liver in HFD-streptozotocin (STZ)-treated mice. Homeostatic model assessments (HOMA-IR) revealed that compA treatment significantly improved insulin sensitivity. The proximal half of the small intestine displayed weight gain following compA treatment. A similar phenomenon has been observed in Roux-en-Y gastric bypass-treated animals and some studies have reported that this intestinal remodeling is essential to the anti-diabetic effects of bariatric surgery. These results clearly demonstrated that MGAT2 inhibition improved dyslipidemia, obesity, and diabetes, suggesting that compA is an effective therapeutic for obesity-related metabolic disorders. PMID:26938273

  11. Pharmacological Inhibition of Monoacylglycerol O-Acyltransferase 2 Improves Hyperlipidemia, Obesity, and Diabetes by Change in Intestinal Fat Utilization.

    Directory of Open Access Journals (Sweden)

    Kazumi Take

    Full Text Available Monoacylglycerol O-acyltransferase 2 (MGAT2 catalyzes the synthesis of diacylglycerol (DG, a triacylglycerol precursor and potential peripheral target for novel anti-obesity therapeutics. High-throughput screening identified lead compounds with MGAT2 inhibitory activity. Through structural modification, a potent, selective, and orally bioavailable MGAT2 inhibitor, compound A (compA, was discovered. CompA dose-dependently inhibited postprandial increases in plasma triglyceride (TG levels. Metabolic flux analysis revealed that compA inhibited triglyceride/diacylglycerol resynthesis in the small intestine and increased free fatty acid and acyl-carnitine with shorter acyl chains than originally labelled fatty acid. CompA decreased high-fat diet (HFD intake in C57BL/6J mice. MGAT2-null mice showed a similar phenotype as compA-treated mice and compA did not suppress a food intake in MGAT2 KO mice, indicating that the anorectic effects were dependent on MGAT2 inhibition. Chronic administration of compA significantly prevented body weight gain and fat accumulation in mice fed HFD. MGAT2 inhibition by CompA under severe diabetes ameliorated hyperglycemia and fatty liver in HFD-streptozotocin (STZ-treated mice. Homeostatic model assessments (HOMA-IR revealed that compA treatment significantly improved insulin sensitivity. The proximal half of the small intestine displayed weight gain following compA treatment. A similar phenomenon has been observed in Roux-en-Y gastric bypass-treated animals and some studies have reported that this intestinal remodeling is essential to the anti-diabetic effects of bariatric surgery. These results clearly demonstrated that MGAT2 inhibition improved dyslipidemia, obesity, and diabetes, suggesting that compA is an effective therapeutic for obesity-related metabolic disorders.

  12. A case of radiation enteritis with perforated peritonitis caused by a piece of eggshell

    International Nuclear Information System (INIS)

    Kitamura, Hirotaka; Maeda, Kazuya; Miyanaga, Tamonn; Doden, Kenji; Hattori, Masakazu; Hashizume, Yasuo

    2011-01-01

    The patient was a woman in her sixties who had received radiation therapy for cancer of uterine cervix 7 years earlier and had been suffering from diarrhea for these several years. The patient was seen at our emergency clinic because of a 5 hour-history of lower abdominal pain at the beginning of July 2010. An abdominal CT scan showed free air and ascites. A high density structure 1.5 cm in size was identified within the small intestine, but its relation with the perforation was obscure. Emergency operation was done with the most likely diagnosis of intestinal perforation and general peritonitis. When the lower abdomen was opened by midline incision, about 200 ml of cloudy ascites was observed and the ileum became white in color and hard resulting from the radiation therapy. A perforation was identified in the ileum about 15 cm distant from the ileocecal valve, and a 1.5-cm sized thin and hard material was palpated within the intestine at the same portion. Ilececal resection including the perforated portion was performed and functional end-to-end anastomosis was made at a grossly normal area. There was a piece of eggshell 1.5-cm in size in the perforated portion in the resected specimen. From this together with histopathologial findings, perforation of the small intestine caused by a piece of eggshell associated with radiation enteritis was finally diagnosed. Small bowel perforation must be kept in mind as a possible late complication of radiation therapy, however, no cases of small bowel perforation caused by eggshell have been reported so far. This rare case is reported here, with a review of the literature. (author)

  13. Very late onset small intestinal B cell lymphoma associated with primary intestinal lymphangiectasia and diffuse cutaneous warts

    OpenAIRE

    Bouhnik, Y; Etienney, I; Nemeth, J; Thevenot, T; Lavergne-Slove, A; Matuchansky, C

    2000-01-01

    As only a handful of lymphoma cases have been reported in conjunction with primary intestinal lymphangiectasia, it is not yet clear if this association is merely fortuitous or related to primary intestinal lymphangiectasia induced immune deficiency. We report on two female patients, 50 and 58 years old, who developed small intestinal high grade B cell lymphoma a long time (45 and 40 years, respectively) after the initial clinical manifestations of primary intestinal lymphangiectasia. They pre...

  14. The effect of fucoidan on intestinal flora and intestinal barrier function in rats with breast cancer.

    Science.gov (United States)

    Xue, Meilan; Ji, Xinqiang; Liang, Hui; Liu, Ying; Wang, Bing; Sun, Lingling; Li, Weiwei

    2018-02-21

    Recent research studies have shown that the intestinal flora are related to the occurrence and progress of breast cancer. This study investigates the effect of fucoidan on intestinal flora and intestinal barrier function in rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancers. Sixty female Sprague-Dawley rats were randomly assigned to the control group, the model group, and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg per kg bw (body weight), respectively. Intestinal histopathological analysis was performed and 16S rDNA high-throughput sequencing was used to provide an overview of the intestinal flora composition. The contents of d-lactic acid (d-LA), diamine oxidase (DAO) and endotoxin in plasma were detected by ELISA. Expression levels of the tight junction (TJ) proteins, phosphorylated p38 MAPK and ERK1/2 were measured using western blotting. Our results suggested that the intestinal wall of the model group was damaged. However, after fucoidan intervention, the villi were gradually restored. ELISA showed that the levels of plasma endotoxin, d-LA and DAO decreased in the F1 and F2 groups compared to those in the model group. Fucoidan treatment also increased the expressions of ZO-1, occludin, claudin-1 and claudin-8. Furthermore, the expression levels of phosphorylated p38 MAPK and ERK1/2 were upregulated in fucoidan treatment groups. The results of 16S rDNA high-throughput sequencing indicated that fucoidan increased the diversity of the intestinal microbiota and induced changes in microbial composition, with the increased Bacteroidetes/Firmicutes phylum ratio. In conclusion, the supplement of fucoidan could improve the fecal microbiota composition and repair the intestinal barrier function. The study suggested the use of fucoidan as an intestinal flora modulator for potential prevention of breast cancer.

  15. Risks Associated with High-Dose Lactobacillus rhamnosus in an Escherichia coli Model of Piglet Diarrhoea: Intestinal Microbiota and Immune Imbalances

    Science.gov (United States)

    Yue, Yuan; Cai, Zheng-Xing; Lu, Qing-Ping; Zhang, Lu; Weng, Xiao-Gang; Zhang, Fan-Jian; Zhou, Dong; Yang, Jin-Cai; Wang, Jiu-Feng

    2012-01-01

    Probiotic could be a promising alternative to antibiotics for the prevention of enteric infections; however, further information on the dose effects is required. In this study, weanling piglets were orally administered low- or high-dose Lactobacillus rhamnosus ACTT 7469 (1010 CFU/d or 1012 CFU/d) for 1 week before F4 (K88)-positive Escherichia coli challenge. The compositions of faecal and gastrointestinal microbiota were recorded; gene expression in the intestines was assessed by real-time PCR; serum tumour necrosis factor-α (TNF-α) concentrations and intestinal Toll-like receptor 4 (TLR4) were detected by ELISA and immunohistochemistry, respectively. Unexpectedly, high-dose administration increased the incidence of diarrhoea before F4+ETEC challenge, despite the fact that both doses ameliorated F4+ETEC-induced diarrhoea with increased Lactobacillus and Bifidobacterium counts accompanied by reduced coliform shedding in faeces. Interestingly, L. rhamnosus administration reduced Lactobacillus and Bifidobacterium counts in the colonic contents, and the high-dose piglets also had lower Lactobacillius and Bacteroides counts in the ileal contents. An increase in the concentration of serum TNF-α induced by F4+ETEC was observed, but the increase was delayed by L. rhamnosus. In piglets exposed to F4+ETEC, jejunal TLR4 expression increased at the mRNA and protein levels, while jejunal interleukin (IL)-8 and ileal porcine β-defensins 2 (pBD2) mRNA expression increased; however, these increases were attenuated by administration of L. rhamnosus. Notably, expression of jejunal TLR2, ileal TLR9, Nod-like receptor NOD1 and TNF-α mRNA was upregulated in the low-dose piglets after F4+ETEC challenge, but not in the high-dose piglets. These findings indicate that pretreatment with a low dose of L. rhamnosus might be more effective than a high dose at ameliorating diarrhoea. There is a risk that high-dose L. rhamnosus pretreatment may negate the preventative effects, thus

  16. [Morphological changes of the intestine in experimental acute intestinal infection in the treatment of colloidal silver].

    Science.gov (United States)

    Polov'ian, E S; Chemich, N D; Moskalenko, R A; Romaniuk, A N

    2012-06-01

    At the present stage of infectionist practice in the treatment of acute intestinal infections caused by opportunistic microorganisms, colloidal silver is used with a particle size of 25 nm as an alternative to conventional causal therapy. In 32 rats, distributed in 4 groups of 8 animals each (intact; healthy, got colloidal silver; with a modeled acute intestinal infection in the basic treatment and with the addition of colloidal silver), histological examination was performed of small and large intestine of rats. Oral administration of colloidal silver at a dose of 0.02 mg/day to intact rats did not lead to changes in morphometric parameters compared to the norm, and during early convalescence in rats with acute intestinal infections were observed destructive and compensatory changes in the intestine, which depended on the treatment regimen. With the introduction of colloidal silver decreased activity of the inflammatory process and the severity of morphological changes in tissues of small and large intestine, indicating that the positive effect of study drug compared with baseline therapy.

  17. Activated STAT5 Confers Resistance to Intestinal Injury by Increasing Intestinal Stem Cell Proliferation and Regeneration

    Directory of Open Access Journals (Sweden)

    Shila Gilbert

    2015-02-01

    Full Text Available Intestinal epithelial stem cells (IESCs control the intestinal homeostatic response to inflammation and regeneration. The underlying mechanisms are unclear. Cytokine-STAT5 signaling regulates intestinal epithelial homeostasis and responses to injury. We link STAT5 signaling to IESC replenishment upon injury by depletion or activation of Stat5 transcription factor. We found that depletion of Stat5 led to deregulation of IESC marker expression and decreased LGR5+ IESC proliferation. STAT5-deficient mice exhibited worse intestinal histology and impaired crypt regeneration after γ-irradiation. We generated a transgenic mouse model with inducible expression of constitutively active Stat5. In contrast to Stat5 depletion, activation of STAT5 increased IESC proliferation, accelerated crypt regeneration, and conferred resistance to intestinal injury. Furthermore, ectopic activation of STAT5 in mouse or human stem cells promoted LGR5+ IESC self-renewal. Accordingly, STAT5 promotes IESC proliferation and regeneration to mitigate intestinal inflammation. STAT5 is a functional therapeutic target to improve the IESC regenerative response to gut injury.

  18. Stem cell factor enhances the survival of murine intestinal stem cells after photon irradiation

    International Nuclear Information System (INIS)

    Leigh, B.R.; Khan, W.; Hancock, S.L.

    1995-01-01

    Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic cell is clinically relevant. Gastrointestinal toxicity is common during and after abdominal and pelvic radiation therapy and limits the radiation dose in these regions. As observed with bone marrow, the administration of SCF to mice prior to TBI enhanced the survival of mouse duodenal crypt stem cells. The maximum enhancement of survival was seen when 100 μ/kg of SCF was given intraperitoneally 8 h before irradiation. This regimen increased the survival of duodenal crypt stem cells after 12.0 Gy TBI from 22.5 ± 0.7 per duodenal cross section for controls to 30.0 ± 1.7 after treatment with SCF (P=0.03). The TBI dose producing 50% mortality of 6 days (LD 50/6 ) was increased from 14.9 Gy for control mice to 19.0 Gy for mice treated with SCF (dose modification factor = 1.28). These findings demonstrate that SCF (dose modification factor = 1.28). These findings demonstrate that SCF has radioprotective effects on a non-hematopoietic stem cell population and suggest that SCF may be of clinical value in preventing radiation injury to the intestine. 29 refs., 4 figs

  19. Lipo sarcoma in small intestine

    International Nuclear Information System (INIS)

    Rodriguez Iglesias, J.; Pineyro Gutierrez, A.; Taroco Medeiros, L.; Fein Kolodny, C.; Navarrete Pedocchi, H.

    1987-01-01

    A case is presented by primitive liposarcoma in small intestine , an extensive bibliographical review foreigner and national in this case. It detach the exceptional of the intestinal topography of the liposarcomas; and making stress in the relative value of the computerized tomography and ultrasonography in the diagnose of the small intestine tumors . As well as in the sarcomas of another topography, chemo and radiotherapy associated to the exeresis surgery, it can be of benefit [es

  20. [Intrauterine intestinal volvulus].

    Science.gov (United States)

    Gawrych, Elzbieta; Chojnacka, Hanna; Wegrzynowski, Jerzy; Rajewska, Justyna

    2009-07-01

    Intrauterine intestinal volvulus is an extremely rare case of acute congenital intestinal obstruction. The diagnosis is usually possible in the third trimester of a pregnancy. Fetal midgut volvulus is most likely to be recognized by observing a typical clockwise whirlpool sign during color Doppler investigation. Multiple dilated intestinal loops with fluid levels are usually visible during the antenatal ultrasound as well. Physical and radiographic findings in the newborn indicate intestinal obstruction and an emergency surgery is required. The authors describe intrauterine volvulus in 3 female newborns in which surgical treatment was individualized. The decision about primary or delayed anastomosis after resection of the gangrenous part of the small bowel was made at the time of the surgery and depended on the general condition of the newborn, as well as presence or absence of meconium peritonitis. Double loop jejunostomy was performed in case of two newborns, followed by a delayed end-to-end anastomosis. In case of the third newborn, good blood supply of the small intestine after untwisting and 0.25% lignocaine injections into mesentery led to the assumption that the torsion was not complete and ischemia was reversible. In the two cases of incomplete rotation the cecum was sutured to the left abdominal wall to prevent further twisting. The postoperative course was uneventful and oral alimentation caused no problems. Physical development of all these children has been normal (current age: 1-2 years) and the parents have not observed any disorders or problems regarding passage of food through the alimentary canal. Prompt antenatal diagnosis of this surgical emergency and adequate choice of intervention may greatly reduce mortality due to intrauterine volvulus.

  1. Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice

    Directory of Open Access Journals (Sweden)

    Matias Russo

    2016-07-01

    Full Text Available The purpose of this study was to determine whether the administration of the feruloyl esterase (FE-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group, CR diet Group (CR Group and CR diet plus L. fermentum Group (CR-Lf Group. CR diet was administered during 45 days and CRL1446 strain was given in the dose of 108 cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020 than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025, total cholesterol (p = 0.005 and glucose (p < 0.0001 levels and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006 parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions.

  2. Protection from radiation-induced enteropathy by elemental diet feeding: The role of free radicals

    International Nuclear Information System (INIS)

    McArdle, A.H.; Duong, M.N.

    1991-01-01

    Free radicals have been implicated in intestinal reperfusion injury following ischemia and in epithelial cell damage resulting from ionizing radiation. Elemental diets (ED) have been shown to afford significant prophylaxis to the intestine from these injuries. The purpose of the present study was to investigate whether ED alters the activity of the defense mechanisms necessary for free radical removal. Six female dogs, fed on normal dog chow, had a 30 cm resection of terminal ileum to form Thiry-Vella loops. The main intestine was biopsied and anastomosed. Two weeks later, biopsies were taken from the lips of the loops. Following this, the loops were fed daily with ED another 2 weeks and biopsied again. The dogs were then placed on ED for 3 days before and during 4 days of pelvic irradiation, and the loops also were fed ED daily; after which the animals were again anesthetized, and the loops and main intestine were biopsied. All biopsies were processed for histology, and assayed for xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GSP) and catalase (CAT). The XO and SOD pathway of free oxygen radical generation and scavenging are not affected by radiation. However, ED lowers both XO and SOD activity and may result in a reduced production of peroxides. The significantly increased activity of GSP and CAT when ED is fed improves the scavenging capacity of the free hydroxyl radicals generated by the radiation, and is an important adjunct to an understanding of ED prophylaxis

  3. Should WOC nurses measure health-related quality of life in patients undergoing intestinal ostomy surgery?

    Science.gov (United States)

    Pittman, Joyce; Kozell, Kathryn; Gray, Mikel

    2009-01-01

    literature review revealed sufficient research to conclude that intestinal stoma surgery impairs HRQOL. Multiple factors, including the underlying reason for an ostomy, presence and severity of ostomy complications, presence and severity of comorbid conditions, sexual function, age, and ability to pay for ostomy supplies influence the magnitude of this effect. HRQOL tends to be most severely impaired during the immediate postoperative period. It usually improves most dramatically by the third postoperative month, and it continues to improve more gradually over the first postoperative year. A systematic review revealed 2 randomized clinical trials demonstrating that at least 2 nursing interventions improve HRQOL in persons with intestinal ostomies. A separate systematic review identified 4 instruments for measuring HRQOL in the research setting. There is sufficient research-based evidence to conclude that intestinal ostomy surgery exerts a clinically relevant impact on HRQOL, and that nursing interventions can ameliorate this effect. While a small number of instruments exist, including several that have proved valid and reliable in the research setting, no instrument has yet been adapted for routine in the clinical setting.

  4. Effects of ionizing radiation on the activity of the major hepatic enzymes implicated in bile acid biosynthesis in the rat

    International Nuclear Information System (INIS)

    Souidi, M.; Scanff, P.; Grison, St.; Gourmelon, P.; Aigueperse, J.

    2007-01-01

    In the days following high-dose radiation exposure, damage to small intestinal mucosa is aggravated by changes in the bile acid pool reaching the gut. Intestinal bile acid malabsorption, as described classically, may be associated with altered hepatic bile acid biosynthesis, which was the objective of this work. The activity of the main rate-limiting enzymes implicated in the bile acid biosynthesis were evaluated in the days following an 8-Gy γ Co 60 total body irradiation of rats, with concomitant determination of biliary bile acid profiles and intestinal bile acid content. Modifications of biliary bile acid profiles, observed as early as the first post-irradiation day, were most marked at the third and fourth day, and resulted in an increased hydrophobicity index. In parallel, the intestinal bile acids' content was enhanced and hepatic enzymatic activities leading to bile acids were changed. A marked increase of sterol 12-hydroxylase and decrease of oxy-sterol 7-hydroxylase activity was observed at day 3, whereas both cholesterol 7-hydroxylase and oxy-sterol 7-hydroxylase activities were decreased at day 4 after irradiation. These results show, for the first time, radiation-induced modifications of hepatic enzymatic activities implicated in bile acid biosynthesis and suggest that they are mainly a consequence of radiation-altered intestinal absorption, which induces a physiological response of the entero-hepatic bile acid recirculation. (authors)

  5. Exercise and the gastro-intestinal tract

    African Journals Online (AJOL)

    on perfonnance and me value of cardiovascular training in improving performance in aerobic sports is well recognised. The role of me gastro-intestinal tracr, bom as a limiting and sustaining facror in aerobic exercises, is less well appreciared. Gastro-intestinal symptoms. The spectrum of gastro-intestinal effecrs of exercise ...

  6. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Directory of Open Access Journals (Sweden)

    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  7. The effect of 45Ca on the intestine of Indian desert gerbil (Meriones hurrianae, Jerdon)

    International Nuclear Information System (INIS)

    Gupta, N.K.; Kumar, A.

    1981-01-01

    Indian desert gerbils (Meriones hurrianae, Jerdon) were given 45 Ca intraperitoneally at the doses of 0.5 and 1.0 μCi/g. b.wt. The animals were autopsied at the intervals of 1, 3, 5, 7 and 14 d following their treatment with the isotope. The animals did not show any discernible symptoms of radiation sickness characteristically seen in case of GI syndrome. The intestine (jejunum) shows maximum damage at 3 d posttreatment. The changes include inhibited mitosis, chromatolysis and vacuolation of crypt nuclei, shortening of villi, i.e. decrease in the number of cells per villus, decrease in the number of goblet cells, hyperemia and lymphocytic infiltration. The cells lining the apical parts of villi show less or no damage. The Paneth's cells lose their property of staining. At day 5 posttreatment, a trend towards normalization is observed. However, relapse of damage is observed at 7 d posttreatment and near normal structure of the intestine is seen at the last interval studied i.e. 14 d posttreatment. The response of the intestine is dose dependent. (author)

  8. Changes in mast cells during acute radiation sickness(a morphometric study)

    International Nuclear Information System (INIS)

    Datsenko, A.V.; Shikhodyrov, V.V.

    1985-01-01

    Changes in the morphometric parameters of rat mast cells during acute radiation sickness have been studied. The most significant deviation of the quantitative indices of mast cells from the control values were noted at the height of the bone-marrow, at the terminal stage of the intestinal, and during the first few hours of the cerebral forms of acute radiation sickness

  9. Epidermal Growth Factor and Intestinal Barrier Function

    Directory of Open Access Journals (Sweden)

    Xiaopeng Tang

    2016-01-01

    Full Text Available Epidermal growth factor (EGF is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.

  10. Thyroid hormone regulation of adult intestinal stem cells: Implications on intestinal development and homeostasis.

    Science.gov (United States)

    Sun, Guihong; Roediger, Julia; Shi, Yun-Bo

    2016-12-01

    Organ-specific adult stem cells are essential for organ homeostasis, tissue repair and regeneration. The formation of such stem cells often takes place during postembryonic development, a period around birth in mammals when plasma thyroid hormone concentration is high. The life-long self-renewal of the intestinal epithelium has made mammalian intestine a valuable model to study the function and regulation and adult stem cells. On the other hand, much less is known about how the adult intestinal stem cells are formed during vertebrate development. Here, we will review some recent progresses on this subject, focusing mainly on the formation of the adult intestine during Xenopus metamorphosis. We will discuss the role of thyroid hormone signaling pathway in the process and potential molecular conservations between amphibians and mammals as well as the implications in organ homeostasis and human diseases.

  11. Isotopic identification of intestinal strangulation

    International Nuclear Information System (INIS)

    Anderson, M.C.; Selby, J.B.

    1982-01-01

    A small series of eleven dogs prepared with a strangulating segment of jejunum demonstrated that a radionuclide, 99 mTc-labelled albumin, concentrates in the lumen and bowel wall of the affected intestinal segment. Modern scanning equipment accurately localized the strangulating loop. This technique has the potential of identifying patients with intestinal obstruction, in whom strangulation is a factor, prior to the development of impaired arterial inflow and frank gangrene. These findings confirmed earlier obstructions that were reported when nuclear scanning instrumentation was less sophisticated. Identification of patients at risk for intestinal strangulation requires a high index of suspicion. Excruciating cramping abdominal pain out of proportion to physical findings, roentgenogram evidence, and laboratory studies should alert the physician to the possibility of intestinal ischemia and closed loop obstruction. Radionuclide scanning in such cases may be of assistance in defining or excluding the diagnosis of a strangulating mechanism. The test is simple, relatively economical, and represents a low risk procedure to patients. It would have no place when the classic physical and laboratory findings of intestinal infarction are present

  12. Isotopic identification of intestinal strangulation

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, M.C.; Selby, J.B.

    1982-12-01

    A small series of eleven dogs prepared with a strangulating segment of jejunum demonstrated that a radionuclide, /sup 99/mTc-labelled albumin, concentrates in the lumen and bowel wall of the affected intestinal segment. Modern scanning equipment accurately localized the strangulating loop. This technique has the potential of identifying patients with intestinal obstruction, in whom strangulation is a factor, prior to the development of impaired arterial inflow and frank gangrene. These findings confirmed earlier obstructions that were reported when nuclear scanning instrumentation was less sophisticated. Identification of patients at risk for intestinal strangulation requires a high index of suspicion. Excruciating cramping abdominal pain out of proportion to physical findings, roentgenogram evidence, and laboratory studies should alert the physician to the possibility of intestinal ischemia and closed loop obstruction. Radionuclide scanning in such cases may be of assistance in defining or excluding the diagnosis of a strangulating mechanism. The test is simple, relatively economical, and represents a low risk procedure to patients. It would have no place when the classic physical and laboratory findings of intestinal infarction are present.

  13. Some biochemical characteristics of a toxic substance isolated from organs of lethally irradiated animals in the course of the intestinal syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Meter, J D; Sirota, N S [Tsentral' nyj Nauchno-Issledovatel' skij Rentgeno-Radiologicheskij Inst., Leningrad (USSR)

    1976-05-01

    A toxic substance isolated from organs of lethally irradiated (1300 rads) animals in the period when intestinal syndrome has developed is classified according to the parameters under study (namely, the molecular weight, UV-absorption curve, extinction coefficient, specific monosaccharides, the presence and percentage of KDA, etc.) as lipopolysaccharide of Escherichia coli, the main inhabitant of the gastroenteric tract of mice. That endotoxins (sensitivity to which is increased in this period of radiation sickness) are detected in the blood and organs of lethally irradiated animals, might indicate their participation in the pathogenesis of the intestinal syndrome.

  14. Some biochemical characteristics of a toxic substance isolated from organs of lethally irradiated animals in the course of the intestinal syndrome

    International Nuclear Information System (INIS)

    Meter, J.D.; Sirota, N.S.

    1976-01-01

    A toxic substance isolated from organs of lethally irradiated (1300 rads) animals in the period when intestinal syndrome has developed is classified according to the parameters under study (namely, the molecular weight, UV-absorption curve, extinction coefficient, specific monosaccharides, the presence and percentage of KDA, etc.) as lipopolysaccharide of Escherichia coli, the main inhabitant of the gastroenteric tract of mice. That endotoxins (sensitivity to which is increased in this period of radiation sickness) are detected in the blood and organs of lethally irradiated animals, might indicate their participation in the pathogenesis of the intestinal syndrome

  15. Acute and chronic radiation syndrome in domestic animals

    International Nuclear Information System (INIS)

    Nuessel, M.

    1974-11-01

    The paper reports on the incidence and the clinical picture of the radiation syndrome in domestic animals, especially in pigs which are often used in animal experiments. The following parameters which influence the radiation reaction are discussed: type of irradiation (whole-body, partial-body and local irradiation), mean lethal radiation dose, radiation quality and RBE, age and individual radiosensitivity. The auther then describes the various symptoms of the radiation syndrome and the lesions which lead to death (death due to intestinal lesions, death following changes in the central nervous system). The next few chapters treat the symptoms manifested after chronic and internal irradiation. The paper closes with some remarks on the usability of irradiated animals for human consumption. (MG/AK) [de

  16. Cholinesterase response in the rhabdomyosarcoma tumor and small intestine of the BALB/c mice and the radioprotective actions of exogenous ATP after lethal dose of neutron radiation

    International Nuclear Information System (INIS)

    Szeinfeld, D.; De Villiers, N.

    1993-01-01

    The rhabdomyosarcoma tumors were subjected to different doses of 2.0, 3.8 and 7.0 Gy from a neutron beam facility p(66 MeV)/Be. Elevated levels of cholinesterase activity are observed in which there is a correlation between the different doses of neutron radiation and the augmentation response of this enzyme. The increase of cholinesterase activity after 7 Gy neutron irradiation as a feature of involvement in the homeostatic mechanism maintaining the proper choline/acetylcholine ratio in the cell is also observed at 1 and 24 h in both tissues, rhabdomyosarcoma and small intestine. The activity of the enzyme after neutron irradiation with prior administration of ATP showed smaller increases when compared with increase observed after neutron irradiation alone. Moreover in the present work the protective mechanism of ATP in the response of cholinesterase activity is marked differential between both, normal and tumoral tissue and correlated inversely with the administered of the following concentrations of exogenous ATP (8, 25, 80, 250, and 700 mg/kg body weight) prior to exposure to 7 Gy neutron radiation. These results reflect the radioprotective ability of exogenous ATP to exert a number of metabolic adaptations as a defense mechanism in which the cell exposed to neutron radiation could remain viable because the injury is potentially repairable. (orig.) [de

  17. Sucralfate does not ameliorate acute radiation proctitis: randomised study and meta-analysis.

    Science.gov (United States)

    Hovdenak, N; Sørbye, H; Dahl, O

    2005-09-01

    During pelvic radiotherapy, many patients develop radiation-induced gastrointestinal symptoms, which may interfere with treatment. Prophylaxis during radiotherapy should ideally prevent acute reaction and the development of delayed injury. Sucralfate, an aluminium sucrose octasulphate, has been used for acute and delayed radiation side-effects. However, conflicting results have been published. We report here a prospective, randomised, placebo-controlled study of prophylactic sucralfate during pelvic radiotherapy. In addition, a meta-analysis of available data from the literature has been carried out. Fifty-one patients with localised pelvic tumours scheduled for curative conformal pelvic radiotherapy (total dose 64-70 Gy over 6.5-7 weeks in 2 Gy daily fractions) were included. Peroral sucralfate 2 g three times daily, or identically appearing placebo tablets, was given during the course of radiotherapy. Symptom registration, endoscopy and biopsies were carried out immediately before radiotherapy, 2 weeks and 6 weeks into the treatment course, and 2 weeks after completing radiotherapy. Mucosal cup forceps biopsies were obtained through a rigid proctoscope. Graded endoscopic appearance and quantitative histology were registered. On the basis of previously published negative reports, an unplanned interim analysis of 44 evaluable patients showed significantly increased diarrhoea in the sucralfate group and the trial was stopped. No difference was seen in other symptoms, endoscopic appearance or histology. A meta-analysis comprising five published studies showed no statistically significant beneficial effect of sucralfate on acute symptoms. Sucralfate cannot be recommended for prophylaxis of acute radiation proctopathy and may even worsen the symptoms.

  18. Small intestine aspirate and culture

    Science.gov (United States)

    ... ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to check for infection ...

  19. Prenatal intestinal volvulus: look for cystic fibrosis.

    Science.gov (United States)

    Chouikh, Taieb; Mottet, Nicolas; Cabrol, Christelle; Chaussy, Yann

    2016-12-21

    Intestinal volvulus is a life-threatening emergency requiring prompt surgical management. Prenatal intestinal volvulus is rare, and most are secondary to intestinal atresia, mesenteric defect or without any underlying cause. Cystic fibrosis (CF) is known to cause digestive tract disorders. After birth, 10-15% of newborns with CF may develop intestinal obstruction within a few days of birth because of meconial ileus. 1 This obstruction is a result of dehydrated thickened meconium obstructing the intestinal lumen. We report two cases of fetuses with prenatal diagnosis of segmental volvulus in whom CF was diagnosed. 2016 BMJ Publishing Group Ltd.

  20. Role of Cardamom (Elettaria cardamomum) in Ameliorating Radiation Induced Oxidative Stress In Rats

    International Nuclear Information System (INIS)

    Darwish, M.M.; Abd El Azime, A. Sh.

    2013-01-01

    Radiation is one of the most widespread sources of environmental stress in living environment which cause oxidative stress and metabolic changes. The present study aims to evaluate the antioxidant effect of Cardamom (Elettaria cardamomum) on gamma radiation-induced oxidative damage in liver and heart tis sues. The study was conducted on forty (40) rats which were classified into four equal groups. Group1: Control group, Group. 2: rats given cardamom in basal diet.Group3: Irradiated rats, rats were subjected to whole body gamma irradiation at 6 Gy delivere d as single exposure dose. Group 4: irradiated +cardamom: rats receiving cardamom for 4 weeks and irradiated. The animals were scarified 24h after irradiation. Irradiated animals had significant increase in oxidative stress markers in liver and heart tissues expressed by significant increase of malondialdehyde (MDA) content associated to significant depletion of superoxide dismutase (SOD) , catalase (CAT) activities, and reduced glutathione (GSH) content . Hepatic and cardiac changes included significant increases of serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) , total cholesterol(TC), triacylglycerol(TAG), low-density lipoprotein cholesterol(LDL-C), and iron concentration. While, a significant decre ase in high-density lipoprotein-cholesterol (HDL-C), manganese and copper were observed. Addition of cardamom to the basal diet prior to gamma radiation, improved the tested parameters . So it is a therapeutic alternative for oxidative stress, hyperlipidaemia and trace elements changes. . The data obtained in this study suggest that cardamom may prevent liver and heart from radiation-induced damage.

  1. Telescoping Intestine in an Adult

    Directory of Open Access Journals (Sweden)

    Khaldoon Shaheen

    2013-01-01

    Full Text Available Protrusion of a bowel segment into another (intussusception produces severe abdominal pain and culminates in intestinal obstruction. In adults, intestinal obstruction due to intussusception is relatively rare phenomenon, as it accounts for minority of intestinal obstructions in this population demographic. Organic lesion is usually identifiable as the cause of adult intussusceptions, neoplasms account for the majority. Therefore, surgical resection without reduction is almost always necessary and is advocated as the best treatment of adult intussusception. Here, we describe a rare case of a 44-year-old male with a diffuse large B-cell lymphoma involving the terminal ileum, which had caused ileocolic intussusception and subsequently developed intestinal obstruction requiring surgical intervention. This case emphasizes the importance of recognizing intussusception as the initial presentation for bowel malignancy.

  2. Epinephrine ameliorating response of serum proteins and protein fractions to whole body gamma irradiation in albino rats

    International Nuclear Information System (INIS)

    Mohamed, M.A.; Saada, H.N.; Roushdy, H.M.; Awad, O.M.; El-Sayed, M.M.; Azab, Kh.Sh.

    1997-01-01

    The present study was carried out to investigate the role of epinephrine in modifying the radiation induced effects on serum protein as presented by total protein, protein fractions and albumin/globulin (A/G) ratio in adult albino rats. Epinephrine was intraperitoneally injected at a concentration of 200 M/g body weight, 15 min, pre-9 or just after 0 whole body gamma-irradiation of rats at a dose of 6 Gy (single dose). Studies have been undertaken at periods of 1 hr, 4 hrs, 1,3 and 7 days after irradiation. Data of the present study revealed that whole body gamma-irradiation induced significant decreased in the total content of serum protein and albumin at 1,3 and 7 days post radiation exposure alpha 1-globulin significantly increased only on the 1 st hr post-irradiation, however alpha 1-globulin significantly increased along all the experimental periods. B-globulin insignificantly changed after irradiation but gamma-globulin significantly decreased during the experimental periods. These changes were associated with significant decreases in A/G ratio at 3 and 7 days post-irradiation. Administration of epinephrine pre-or after radiation exposure produced some amelioration in the radiation induced changes in the studied parameters. So, it could be concluded that epinephrine plays a beneficial radioprotective role through its pharmacologic properties

  3. Intestinal volvulus in cetaceans.

    Science.gov (United States)

    Begeman, L; St Leger, J A; Blyde, D J; Jauniaux, T P; Lair, S; Lovewell, G; Raverty, S; Seibel, H; Siebert, U; Staggs, S L; Martelli, P; Keesler, R I

    2013-07-01

    Intestinal volvulus was recognized as the cause of death in 18 cetaceans, including 8 species of toothed whales (suborder Odontoceti). Cases originated from 11 institutions from around the world and included both captive (n = 9) and free-ranging (n = 9) animals. When the clinical history was available (n = 9), animals consistently demonstrated acute dullness 1 to 5 days prior to death. In 3 of these animals (33%), there was a history of chronic gastrointestinal illness. The pathological findings were similar to those described in other animal species and humans, and consisted of intestinal volvulus and a well-demarcated segment of distended, congested, and edematous intestine with gas and bloody fluid contents. Associated lesions included congested and edematous mesentery and mesenteric lymph nodes, and often serofibrinous or hemorrhagic abdominal effusion. The volvulus involved the cranial part of the intestines in 85% (11 of 13). Potential predisposing causes were recognized in most cases (13 of 18, 72%) but were variable. Further studies investigating predisposing factors are necessary to help prevent occurrence and enhance early clinical diagnosis and management of the condition.

  4. The protective effects of resveratral on acute radiation injury in mice

    International Nuclear Information System (INIS)

    Yan Hao; Wang Hui; Zhang Heng

    2014-01-01

    Objective: To study the protective function of resveratrol on radiation-induced small intestine injury and lethal effect in mice. Methods: Mice were randomly divided into three groups: irradiation (IR) control, IR only, and IR+ resveratrol. 15 mice each group were irradiated on abdomen with 7.2 Gy γ-rays for cell lethal assay and 8 mice each group were irradiated with 6.5 Gy for small intestine injury assay. For the IR+ resveratrol group, the mouse was given resveratrol by intragastric administration 24 h before irradiation and then was fed with resveratrol daily for 5 days. The control and IR alone groups were fed with placebo. After 30 days of IR, mouse survival rate was detected. For small intestine injury experiments, 24 h after IR, the mice were terminated and the small intestines were treated with HE and immunohistochemical staining. Results: Compared with the irradiation group, resveratrol increased mouse survival by 33.3%, decreased apoptosis in intestinal crypt cells (t = 17.35, P < 0.05), and increased Ki67 expression (t = 13.62, P < 0.05). Conclusion: Resveratrol could protect small intestine injury from ionizing irradiation. (authors)

  5. Update on small intestinal stem cells.

    Science.gov (United States)

    Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-08-07

    Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to identify the integrating signals from the surrounding niche, supporting a model whereby distinct cell populations facilitate homeostatic vs injury-induced regeneration.

  6. A Mimicker of Gallbladder Carcinoma: Cystic Gastric Heterotopia with Intestinal Metaplasia

    Directory of Open Access Journals (Sweden)

    Gonca ÖZGÜN

    2017-01-01

    Full Text Available Heterotopic gastric mucosa in the gallbladder is an unusual entity and is usually clinically silent. We report a 75-year-old female patient who presented with intermittent upper abdomial pain radiating to the back. Abdominal imaging studies showed a sessile polypoid lesion and a gallstone in the gallbladder. Gallbladder carcinoma was suspected and cholecystectomy performed. Intraoperative frozen section examination suggested mucinous tumor, suspicious for malignancy. However, the permanent sections revealed aberrant gastric tissue consisted of gastric pyloric and fundic glands of heterotopic gastric mucosa with intestinal metaplasia in the gallbladder.

  7. A Mimicker of Gallbladder Carcinoma: Cystic Gastric Heterotopia with Intestinal Metaplasia.

    Science.gov (United States)

    Özgün, Gonca; Adim, Şaduman Balaban; Uğraş, Nesrin; Kiliçturgay, Sadık

    2017-01-01

    Heterotopic gastric mucosa in the gallbladder is an unusual entity and is usually clinically silent. We report a 75-year-old female patient who presented with intermittent upper abdomial pain radiating to the back. Abdominal imaging studies showed a sessile polypoid lesion and a gallstone in the gallbladder. Gallbladder carcinoma was suspected and cholecystectomy performed. Intraoperative frozen section examination suggested mucinous tumor, suspicious for malignancy. However, the permanent sections revealed aberrant gastric tissue consisted of gastric pyloric and fundic glands of heterotopic gastric mucosa with intestinal metaplasia in the gallbladder.

  8. Short Bowel Syndrome, a Case of Intestinal Rehabilitation

    Directory of Open Access Journals (Sweden)

    Dianna Ramírez Prada

    2015-05-01

    Full Text Available Case: The objective is to present the successful experience of multidisciplinary management of a patient with short bowel syndrome and intestinal failure with progression to intestinal adaptation. This is a newly born premature with intestinal atresia type IV with multiple intestinal atresia who evolved to intestinal failure and required managed with prolonged parenteral nutritional support, multiple antibiotic schemes, prebiotics, multivitamins, enteral nutrition with elemental formula to achieve their adaptation intestinal until lead to a normal diet. The evolution of these patients intestinal failure is a challenge for the health team, as it not only involves the surgical management of your condition if not basic nutritional support, fluid and electrolyte balance, hepatic dysfunction cholestasis associated infections etc. Discussion: Short bowel syndrome with progression to intestinal failure in children is a condition whose prevalence is increasing worldwide, thanks to advances in neonatal intensive care, neonatal surgery, and nutritional support of patients with conditions such as gastroschisis, omphalocele and necrotizing enterocolitis. Despite the limitations of our health system, it is possible to offer a multidisciplinary and integrated to lead to intestinal adaptation treatment.

  9. Precision cut intestinal slices are an appropriate ex vivo model to study NSAID-induced intestinal toxicity in rats

    NARCIS (Netherlands)

    Niu, Xiaoyu; de Graaf, Inge A. M.; van der Bij, Hendrik A.; Groothuis, Geny M. M.

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used therapeutic agents, however, they are associated with a high prevalence of intestinal side effects. In this investigation, rat precision cut intestinal slices (PCIS) were evaluated as an ex vivo model to study NSAID-induced intestinal

  10. INFANTS’ INTESTINAL COLICS. MODERN DATA

    Directory of Open Access Journals (Sweden)

    N.I. Ursova

    2011-01-01

    Full Text Available The article analyzes modern data on infants’ intestinal colics. Peculiarities of nutrition, intestinal microbiocenose in healthy infants, methods of colcs’ correction are discussed. Author describes the principles of probiotics choice based on their clinical effectiveness in infants. Milk formula «Nan Comfort» can be useful in prophylaxis and treatment of functional disorders of gastrointestinal tract in children.Key words: infants, gastrointestinal tract, anatomy, physiology, intestinal colics, nutrition, probiotics.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 125–131

  11. Role of intestinal bacteria in gliadin-induced changes in intestinal mucosa: study in germ-free rats.

    Directory of Open Access Journals (Sweden)

    Jana Cinova

    Full Text Available BACKGROUND AND AIMS: Celiac disease (CD is a chronic inflammatory disorder of the small intestine that is induced by dietary wheat gluten proteins (gliadins in genetically predisposed individuals. The overgrowth of potentially pathogenic bacteria and infections has been suggested to contribute to CD pathogenesis. We aimed to study the effects of gliadin and various intestinal bacterial strains on mucosal barrier integrity, gliadin translocation, and cytokine production. METHODOLOGY/PRINCIPAL FINDINGS: Changes in gut mucosa were assessed in the intestinal loops of inbred Wistar-AVN rats that were reared under germ-free conditions in the presence of various intestinal bacteria (enterobacteria and bifidobacteria isolated from CD patients and healthy children, respectively and CD-triggering agents (gliadin and IFN-γ by histology, scanning electron microscopy, immunofluorescence, and a rat cytokine antibody array. Adhesion of the bacterial strains to the IEC-6 rat cell line was evaluated in vitro. Gliadin fragments alone or together with the proinflammatory cytokine interferon (IFN-γ significantly decreased the number of goblet cells in the small intestine; this effect was more pronounced in the presence of Escherichia coli CBL2 and Shigella CBD8. Shigella CBD8 and IFN-γ induced the highest mucin secretion and greatest impairment in tight junctions and, consequently, translocation of gliadin fragments into the lamina propria. Shigella CBD8 and E. coli CBL2 strongly adhered to IEC-6 epithelial cells. The number of goblet cells in small intestine increased by the simultaneous incubation of Bifidobacterium bifidum IATA-ES2 with gliadin, IFN-γ and enterobacteria. B. bifidum IATA-ES2 also enhanced the production of chemotactic factors and inhibitors of metalloproteinases, which can contribute to gut mucosal protection. CONCLUSIONS: Our results suggest that the composition of the intestinal microbiota affects the permeability of the intestinal mucosa

  12. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines.

    Science.gov (United States)

    Drago, Sandro; El Asmar, Ramzi; Di Pierro, Mariarosaria; Grazia Clemente, Maria; Tripathi, Amit; Sapone, Anna; Thakar, Manjusha; Iacono, Giuseppe; Carroccio, Antonio; D'Agate, Cinzia; Not, Tarcisio; Zampini, Lucia; Catassi, Carlo; Fasano, Alessio

    2006-04-01

    Little is known about the interaction of gliadin with intestinal epithelial cells and the mechanism(s) through which gliadin crosses the intestinal epithelial barrier. We investigated whether gliadin has any immediate effect on zonulin release and signaling. Both ex vivo human small intestines and intestinal cell monolayers were exposed to gliadin, and zonulin release and changes in paracellular permeability were monitored in the presence and absence of zonulin antagonism. Zonulin binding, cytoskeletal rearrangement, and zonula occludens-1 (ZO-1) redistribution were evaluated by immunofluorescence microscopy. Tight junction occludin and ZO-1 gene expression was evaluated by real-time polymerase chain reaction (PCR). When exposed to gliadin, zonulin receptor-positive IEC6 and Caco2 cells released zonulin in the cell medium with subsequent zonulin binding to the cell surface, rearrangement of the cell cytoskeleton, loss of occludin-ZO1 protein-protein interaction, and increased monolayer permeability. Pretreatment with the zonulin antagonist FZI/0 blocked these changes without affecting zonulin release. When exposed to luminal gliadin, intestinal biopsies from celiac patients in remission expressed a sustained luminal zonulin release and increase in intestinal permeability that was blocked by FZI/0 pretreatment. Conversely, biopsies from non-celiac patients demonstrated a limited, transient zonulin release which was paralleled by an increase in intestinal permeability that never reached the level of permeability seen in celiac disease (CD) tissues. Chronic gliadin exposure caused down-regulation of both ZO-1 and occludin gene expression. Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.

  13. Kaiso overexpression promotes intestinal inflammation and potentiates intestinal tumorigenesis in Apc(Min/+) mice.

    Science.gov (United States)

    Pierre, Christina C; Longo, Joseph; Mavor, Meaghan; Milosavljevic, Snezana B; Chaudhary, Roopali; Gilbreath, Ebony; Yates, Clayton; Daniel, Juliet M

    2015-09-01

    Constitutive Wnt/β-catenin signaling is a key contributor to colorectal cancer (CRC). Although inactivation of the tumor suppressor adenomatous polyposis coli (APC) is recognized as an early event in CRC development, it is the accumulation of multiple subsequent oncogenic insults facilitates malignant transformation. One potential contributor to colorectal carcinogenesis is the POZ-ZF transcription factor Kaiso, whose depletion extends lifespan and delays polyp onset in the widely used Apc(Min/+) mouse model of intestinal cancer. These findings suggested that Kaiso potentiates intestinal tumorigenesis, but this was paradoxical as Kaiso was previously implicated as a negative regulator of Wnt/β-catenin signaling. To resolve Kaiso's role in intestinal tumorigenesis and canonical Wnt signaling, we generated a transgenic mouse model (Kaiso(Tg/+)) expressing an intestinal-specific myc-tagged Kaiso transgene. We then mated Kaiso(Tg/+) and Apc(Min/+) mice to generate Kaiso(Tg/+):Apc(Min/+) mice for further characterization. Kaiso(Tg/+):Apc(Min/+) mice exhibited reduced lifespan and increased polyp multiplicity compared to Apc(Min/+) mice. Consistent with this murine phenotype, we found increased Kaiso expression in human CRC tissue, supporting a role for Kaiso in human CRC. Interestingly, Wnt target gene expression was increased in Kaiso(Tg/+):Apc(Min/+) mice, suggesting that Kaiso's function as a negative regulator of canonical Wnt signaling, as seen in Xenopus, is not maintained in this context. Notably, Kaiso(Tg/+):Apc(Min/+) mice exhibited increased inflammation and activation of NFκB signaling compared to their Apc(Min/+) counterparts. This phenotype was consistent with our previous report that Kaiso(Tg/+) mice exhibit chronic intestinal inflammation. Together our findings highlight a role for Kaiso in promoting Wnt signaling, inflammation and tumorigenesis in the mammalian intestine. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Scanning electron microscopy of mouse intestinal mucosa after cobalt 60 and D-T neutron irradiation

    International Nuclear Information System (INIS)

    Hamlet, R.; Carr, K.R.; Toner, P.G.; Nias, A.H.W.

    1976-01-01

    The stem-cell population of the intestinal crypt is an important model system in experimental radiobiology. Standardized techniques have been developed to allow quantitation of the response of crypt cells to radiation injury following doses of 0 to 2 krad of D-T neutrons or 60 Co γ rays. These techniques rely on the identification of regenerating crypt cells three-and-a-half days after irradiation. The results were expressed as the number of regenerating crypts per circumference of small intestine, as determined by conventional histological examination; the more profound the injury, the smaller the the crypt count. The practical relevance of crypt-counting techniques to clinical radiotherapy is limited by their relative insensitivity; the dose levels commonly used in fractionated radiotherapy produced no detectable response. Scanning electron microscopy of the mucosal surface provided a more sensitive measure of radiation injury. The earliest detectable changes occurred at the level of 300 rad of γ radiation, well below the threshold of the crypt-counting technique. At around 1,000 rad, where the first drop in crypt counts occurred, there were well-marked morphological changes which became more severe with increasing dose levels. Some differences have been observed between the morphological effects of γ and neutron irradiation at points of radiobiological equivalence in terms of crypt counts (using RBE value of about 2). The changes observed may reflect more than the disruption of epithelial cell kinetics. Mucosal morphology is the total expression of many different biological parameters of which the regenerative ability of the crypt cells is only one. The surface microanatomy of the gut may be the most sensitive indicator of radiation injury which is conveniently available for study. (author)

  15. Scanning electron microscopy of mouse intestinal mucosa after cobalt 60 and D-T neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, R [Belvidere Hospital, Glasgow (UK). Institute of Radiotherapeutics and Oncology; Carr, K R; Toner, P G; Nias, A H.W.

    1976-07-01

    The stem-cell population of the intestinal crypt is an important model system in experimental radiobiology. Standardized techniques have been developed to allow quantitation of the response of crypt cells to radiation injury following doses of 0 to 2 krad of D-T neutrons or /sup 60/Co ..gamma.. rays. These techniques rely on the identification of regenerating crypt cells three-and-a-half days after irradiation. The results were expressed as the number of regenerating crypts per circumference of small intestine, as determined by conventional histological examination; the more profound the injury, the smaller the the crypt count. The practical relevance of crypt-counting techniques to clinical radiotherapy is limited by their relative insensitivity; the dose levels commonly used in fractionated radiotherapy produced no detectable response. Scanning electron microscopy of the mucosal surface provided a more sensitive measure of radiation injury. The earliest detectable changes occurred at the level of 300 rad of ..gamma.. radiation, well below the threshold of the crypt-counting technique. At around 1,000 rad, where the first drop in crypt counts occurred, there were well-marked morphological changes which became more severe with increasing dose levels. Some differences have been observed between the morphological effects of ..gamma.. and neutron irradiation at points of radiobiological equivalence in terms ofCrypt counts (using RBE value of about 2). The changes observed may reflect more than the disruption of epithelial cell kinetics. Mucosal morphology is the total expression of many different biological parameters of which the regenerative ability of the crypt cells is only one. The surface microanatomy of the gut may be the most sensitive indicator of radiation injury which is conveniently available for study.

  16. Search for the lowest irradiation dose from literatures on radiation-induced cancer in gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Yoshizawa, Y; Kusama, T [Tokyo Univ. (Japan). Faculty of Medicine

    1976-05-01

    A survey of past case reports about radiation-induced cancer in the gastrointestinal tract was carried out with the main object of finding the lowest irradiation dose. Search of the literature published since 1923 revealed 80 cases of radiation-induced large intestine cancer and one case of stomach cancer. The cases of radiation-induced cancer in the large intestine had received radiation for the treatment of non-malignant conditions, fibroma, ovarial cyste, myoma, endometritis and duodenal ulcer. The lowest irradiation dose was estimated at 460 rads. Adenocarcinoma was the histopathological finding in all cases of radiation-induced cancer in the caecum, colon and rectum, and squamous cell carcinoma in the cases of anal cancer. The latent period ranged from 1 to 31 years, with the average of 13.6 years. There were some reports of statistical studies of radiation-induced stomach cancer. Three groups were the subjects of these studies. The first group was composed of atomic bomb survivors, the second of patients who had undergone radiation treatment for ankylosing spondilitis, and the third of duodenal ulcer patients subjected to radiation treatment for the purpose of suppressing gastric acid secretion. These statistical studies showed no significant increase of the incidence of stomach cancer in the irradiated groups.

  17. Search for the lowest irradiation dose from literatures on radiation-induced cancer in gastrointestinal tract

    International Nuclear Information System (INIS)

    Yoshizawa, Yasuo; Kusama, Tomoko

    1976-01-01

    A survey of past case reports about radiation-induced cancer in the gastrointestinal tract was carried out with the main object of finding the lowest irradiation dose. Search of the literature published since 1923 revealed 80 cases of radiation-induced large intestine cancer and one case of stomach cancer. The cases of radiation-induced cancer in the large intestine had received radiation for the treatment of non-malignant conditions, fibroma, ovarial cyste, myoma, endometritis and duodenal ulcer. The lowest irradiation dose was estimated at 460 rads. Adenocarcinoma was the histopathological finding in all cases of radiation-induced cancer in the caecum, colon and rectum, and squamous cell carcinoma in the cases of anal cancer. The latent period ranged from 1 to 31 years, with the average of 13.6 years. There were some reports of statistical studies of radiation-induced stomach cancer. Three groups were the subjects of these studies. The first group was composed of atomic bomb survivors, the second of patients who had undergone radiation treatment for ankylosing spondilitis, and the third of duodenal ulcer patients subjected to radiation treatment for the purpose of suppressing gastric acid secretion. These statistical studies showed no significant increase of the incidence of stomach cancer in the irradiated groups. (auth.)

  18. Small intestinal sulphoxidation of albendazole.

    Science.gov (United States)

    Villaverde, C; Alvarez, A I; Redondo, P; Voces, J; Del Estal, J L; Prieto, J G

    1995-05-01

    1. The in vitro sulphoxidation of Albendazole (ABZ) by rat intestinal microsomes has been examined. The results revealed intestinal sulphoxidation of ABZ by intestinal microsomes in a NADPH-dependent enzymatic system. The kinetic constants for sulphoxidase activity were Vmax = 46 pmol/min/mg protein and Michaelis constant Km = 6.8 microM. 2. The possible effect of inducers (Arochlor 1254 and ABZ pretreatment) and inhibitors (erythromycin, methimazole, carbon monoxide and fenbendazole), was also studied. In rat pretreated with Arochlor 1254, Vmax was 52 pmol/min/mg protein, whereas oral administration of ABZ increased the intestinal sulphoxidation of the drug, Vmax being 103 pmol/min/mg protein. 3. Erythromycin did not change the enzymatic bioconversion of ABZ, but methimazole and carbon monoxide inhibited the enzyme activity by approximately 60 and 30% respectively. Fenbendazole (a structural analogue of ABZ) was a competitive inhibitor of the sulphoxidation process, characterized by a Ki or 69 microM. 4. These data demonstrate that the intestinal enzymes contributing to the initial sulphoxidation of ABZ may be similar to the hepatic enzymes involved in the biotransformation process by the P450 and FMO systems, a conclusion that needs to be further established.

  19. Small intestine diverticuli

    International Nuclear Information System (INIS)

    Pomakov, P.; Risov, A.

    1991-01-01

    The routine method of contrast matter passage applied to 850 patients with different gastrointestinal diseases proved inefficient to detect any small-intestinal diverticuli. The following modiffications of the method have been tested in order to improve the diagnostic possibilities of the X-ray: study at short intervals, assisted passage, enteroclysm, pharmacodynamic impact, retrograde filling of the ileum by irrigoscopy. Twelve diverticuli of the small-intestinal loops were identified: 5 Meckel's diverticuli, 2 solitary of which one of the therminal ileum, 2 double diverticuli and 1 multiple diverticulosis of the jejunum. The results show that the short interval X-ray examination of the small intestines is the method of choice for identifying local changes in them. The solitary diverticuli are not casuistic scarcity, its occurrence is about 0.5% at purposeful X-ray investigation. The assisted passage method is proposed as a method of choice for detection of the Meckel's diverticulum. 5 figs., 3 tabs. 18 refs

  20. Effect of gamma radiation on the growth, survival, hematology and histological parameters of rainbow trout (Oncorhynchus mykiss) larvae

    Energy Technology Data Exchange (ETDEWEB)

    Oujifard, Amin, E-mail: oujifard.amin@gmail.com [Fisheries Department, Faculty of Agriculture and Natural Resources, Persian Gulf University, Borazjan, Bushehr (Iran, Islamic Republic of); Amiri, Roghayeh [Department of Veterinary, Agricultural Medical and Industrial Research School, Nuclear Science and Technology Research Institute, AEOI, Karaj (Iran, Islamic Republic of); Shahhosseini, Gholamreza [Fisheries Department, Faculty of Natural Resources and Marine Sciences, TarbiatModares University, Noor, Mazandaran (Iran, Islamic Republic of); Davoodi, Reza [Fisheries Department, Faculty of Agriculture and Natural Resources, Persian Gulf University, Borazjan, Bushehr (Iran, Islamic Republic of); Moghaddam, Jamshid Amiri [Fisheries Department, Faculty of Natural Resources and Marine Sciences, TarbiatModares University, Noor, Mazandaran (Iran, Islamic Republic of)

    2015-08-15

    Highlights: • Incrementing of gamma radiation reveals the negative effects on fish larvae. • Radiation adversely affected the weight, blood cells and intestinal morphology of the larvae. • No mortality was observed at low dosage of gamma radiation on fish larvae. - Abstract: Effects of low (1, 2.5 and 5 Gy) and high doses (10, 20 and 40 Gy) of gamma radiation were examined on the growth, survival, blood parameters and morphological changes of the intestines of rainbow trout (Oncorhynchus mykiss) larvae (103 ± 20 mg) after 12 weeks of exposure. Negative effects of gamma radiation on growth and survival were observed as radiation level and time increased. Changes were well documented at 10 and 20 Gy. All the fish were dead at the dose of 40 Gy. In all the treatments, levels of red blood cells (RBC), hematocrit (HCT) and hemoglobin (HB) were significantly (P < 0.05) declined as the irradiation levels increased, whereas the amount of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) did not change. No significant differences (P > 0.05) were found in the levels of white blood cells (WBC), lymphocytes and monocytes. Destruction of the intestinal epithelium cells was indicated as the irradiation levels increased to 1 Gy and above. The highest levels of growth, survival, specific growth rate (SGR), condition factor (CF) and protein efficiency rate (PER) were obtained in the control treatment. The results showed that gamma rays can be a potential means for damaging rainbow trout cells.

  1. Effect of gamma radiation on the growth, survival, hematology and histological parameters of rainbow trout (Oncorhynchus mykiss) larvae

    International Nuclear Information System (INIS)

    Oujifard, Amin; Amiri, Roghayeh; Shahhosseini, Gholamreza; Davoodi, Reza; Moghaddam, Jamshid Amiri

    2015-01-01

    Highlights: • Incrementing of gamma radiation reveals the negative effects on fish larvae. • Radiation adversely affected the weight, blood cells and intestinal morphology of the larvae. • No mortality was observed at low dosage of gamma radiation on fish larvae. - Abstract: Effects of low (1, 2.5 and 5 Gy) and high doses (10, 20 and 40 Gy) of gamma radiation were examined on the growth, survival, blood parameters and morphological changes of the intestines of rainbow trout (Oncorhynchus mykiss) larvae (103 ± 20 mg) after 12 weeks of exposure. Negative effects of gamma radiation on growth and survival were observed as radiation level and time increased. Changes were well documented at 10 and 20 Gy. All the fish were dead at the dose of 40 Gy. In all the treatments, levels of red blood cells (RBC), hematocrit (HCT) and hemoglobin (HB) were significantly (P < 0.05) declined as the irradiation levels increased, whereas the amount of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) did not change. No significant differences (P > 0.05) were found in the levels of white blood cells (WBC), lymphocytes and monocytes. Destruction of the intestinal epithelium cells was indicated as the irradiation levels increased to 1 Gy and above. The highest levels of growth, survival, specific growth rate (SGR), condition factor (CF) and protein efficiency rate (PER) were obtained in the control treatment. The results showed that gamma rays can be a potential means for damaging rainbow trout cells

  2. Extract Against Toxic Sodium The Protective Role of Grape Seed Proanthocyanidins Nitrites and Gamma Irradiation Induced Histological Changes in Intestine and Urinary Bladder of Male Albino Rats

    International Nuclear Information System (INIS)

    Abd El- Azeem, M.G.; El-Nashar, D.E.M.

    2010-01-01

    Proanthocyanidins (a grape seed extract) possess a broad spectrum of biological activities. The present study was performed to investigate the effect of gamma radiation exposure and toxic sodium nitrites induced oxidative stress on the intestine and urinary bladder histologically and also to evaluate the possible protective role of proanthocyanidins. Seventy adult male albino rats, each weighing 95-105 g were used and divided into 7 groups as follows: The first group represents the control group. The second experimental group were exposed to 7 Gy gamma-rays as a single dose and sacrificed on the 7th day. The third experimental group received by a stomach tube daily 50 mg/kg b.wt of sodium nitrite for 4 weeks. The fourth experimental group received proanthocyanidins, Grape seed extracts (antioxidant) (100 mg/kg) body wt.) daily for seven days before irradiation and the continued for 14 days post irradiation. The fifth group of animals received grape seed extract after being exposed to gamma radiation for two weeks, while the sixth experimental group received the same antioxidant for seven days before and after received sodium nitrite (50 mg/kg) daily for 4 weeks. Finally, the seventh experimental groups was treated with the same antioxidant in same dose and time after received sodium nitrite for 4 weeks. The animals were then sacrificed on the end of each experimental duration. The results revealed that both gamma-radiation and sodium nitrite induced different histological changes in the intestine and urinary bladder of irradiated and sodium nitrite received animals. The effect of gamma radiation exposure showed marked degeneration of intestinal villi, vaculation in the lining epithelium cells and karyolytic nuclei. In addition, using sodium nitrite lead to necrosis of intestinal glandular cells. The effect of gamma radiation on urinary bladder was presented by, hyperplasia and vaculation of mucosal epithelium, congestion of blood capillaries. Rats from nitrite

  3. Pyrolysis temperature influences ameliorating effects of biochars on acidic soil.

    Science.gov (United States)

    Wan, Qing; Yuan, Jin-Hua; Xu, Ren-Kou; Li, Xing-Hui

    2014-02-01

    The biochars were prepared from straws of canola, corn, soybean, and peanut at different temperatures of 300, 500, and 700 °C by means of oxygen-limited pyrolysis.Amelioration effects of these biochars on an acidic Ultisol were investigated with incubation experiments, and application rate of biochars was 10 g/kg. The incorporation of these biochars induced the increase in soil pH, soil exchangeable base cations, base saturation, and cation exchange capacity and the decrease in soil exchangeable acidity and exchangeable Al. The ameliorating effects of biochars on acidic soil increased with increase in their pyrolysis temperature. The contribution of oxygen-containing functional groups on the biochars to their ameliorating effects on the acidic soil decreased with the rise in pyrolysis temperature, while the contribution from carbonates in the biochars changed oppositely. The incorporation of the biochars led to the decrease in soil reactive Al extracted by 0.5mol/L CuCl2, and the content of reactive Al was decreased with the increase in pyrolysis temperature of incorporated biochars. The biochars generated at 300 °C increased soil organically complexed Al due to ample quantity of oxygen-containing functional groups such as carboxylic and phenolic groups on the biochars, while the biochars generated at 500 and 700 °C accelerated the transformation of soil exchangeable Al to hydroxyl-Al polymers due to hydrolysis of Al at higher pH. Therefore, the crop straw-derived biochars can be used as amendments for acidic soils and the biochars generated at relatively high temperature have great ameliorating effects on the soils.

  4. Megacystis microcolon intestinal hypoperistalsis syndrome

    Science.gov (United States)

    Hiradfar, Mehran; Shojaeian, Reza; Dehghanian, Paria; Hajian, Sara

    2013-01-01

    Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a multisystemic disorder in which impaired intestinal motor activity causes recurrent symptoms of intestinal obstruction in the absence of mechanical occlusion, associated with bladder distention without distal obstruction of the urinary tract. MMIHS and prune belly syndrome may overlap in most of the clinical features and discrimination of these two entities is important because the prognosis, management and consulting with parents are completely different. MMIHS outcome is very poor and in this article we present two neonates with MMIHS that both died in a few days. PMID:23729700

  5. Antibiotic concentrations in intestinal mucosa.

    Science.gov (United States)

    Malmborg, A S

    1985-01-01

    The concentrations in the intestinal mucosa after the initial dose of cefoxitin, piperacillin and clindamycin have been studied. The antibiotics were given at the induction of anesthesia as prophylaxis to patients undergoing elective colorectal surgery. The concentrations of the antibiotics in serum and intestinal mucosa taken during the operation were determined by the microbiological agar diffusion method. Therapeutic concentrations in intestinal mucosa were maintained during the major part of the operation period. The mean mucosa/serum concentration ratios were for cefoxitin 0.4, for piperacillin 0.5 and for clindamycin 1.2.

  6. Ameliorative effect of Lentinus squarrosulus mycomeat against ...

    African Journals Online (AJOL)

    Ameliorative effect of Lentinus squarrosulus mycomeat against Pseudomonas aeruginosa infection using albino rat as animal model. ... Morphological appearance and behavior of the rats were used as the assessment method for adverse reactions. After a period of 26 days, the rats were sacrificed with the liver, spleen and ...

  7. Efficacy of Royal Jelly in Modulating Radiation-Induced Liver Damage in Rats Subjected to Low Level of Gamma Radiation

    International Nuclear Information System (INIS)

    Ibrahim, N.K.

    2010-01-01

    Royal Jelly (RJ) is bee product, rich in proteins, vitamins, enzymes, minerals, hormones (trace elements of testosterone), lipids, glucides, niacin, pantothenic acid, biotin, inositol and folic acid, which may be beneficial in neutralizing the free oxygen radicals. The present study was carried out evaluate the radio-protective effect of Royal Jelly exposure of male Swiss albino rats to 1 Gy for 5 times day post day. Royal jelly was supplemented by gavage to rats at a dose of 150 mg/ kg body wt/ day for successive 10 days through exposure to gamma radiation 1 Gy x 5 time day post day. The dose of royal jelly is equivalent to daily human nutritional supplementation quantity. The result revealed that whole body gamma-irradiation of rats produced significant decrease in plasma total protein, albumin and globulin contents and significant increase in plasma alanine transaminase (ALT) and aspartate transaminase (AST) activity. However, plasma testosterone significantly decrease and follicle-stimulating hormone (FSH) and luteinising hormone (LH) significantly increased. Cholesterol (TC), triacyleglycerol (TAC), superoxide dismutase (SOD) and glutathione per oxidise (GSHPx) decreased whereas, malondialdehde (MDA) increased. Oral administration of the RJ exerted a noticeable amelioration of the radiation induced hormonal and biochemical changes according to the results of the present study. It could be concluded that RJ possess anti-oxidative potential that may protect the liver against ?-radiation induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the limitation of culprit free radicals and the amelioration of oxidative stress and also due to the synergistic relationship between the natural components found in RJ

  8. Deciphering the porcine intestinal microRNA transcriptome

    Directory of Open Access Journals (Sweden)

    Keller Andreas

    2010-04-01

    Full Text Available Abstract Background While more than 700 microRNAs (miRNAs are known in human, a comparably low number has been identified in swine. Because of the close phylogenetic distance to humans, pigs serve as a suitable model for studying e.g. intestinal development or disease. Recent studies indicate that miRNAs are key regulators of intestinal development and their aberrant expression leads to intestinal malignancy. Results Here, we present the identification of hundreds of apparently novel miRNAs in the porcine intestine. MiRNAs were first identified by means of deep sequencing followed by miRNA precursor prediction using the miRDeep algorithm as well as searching for conserved miRNAs. Second, the porcine miRNAome along the entire intestine (duodenum, proximal and distal jejunum, ileum, ascending and transverse colon was unraveled using customized miRNA microarrays based on the identified sequences as well as known porcine and human ones. In total, the expression of 332 intestinal miRNAs was discovered, of which 201 represented assumed novel porcine miRNAs. The identified hairpin forming precursors were in part organized in genomic clusters, and most of the precursors were located on chromosomes 3 and 1, respectively. Hierarchical clustering of the expression data revealed subsets of miRNAs that are specific to distinct parts of the intestine pointing to their impact on cellular signaling networks. Conclusions In this study, we have applied a straight forward approach to decipher the porcine intestinal miRNAome for the first time in mammals using a piglet model. The high number of identified novel miRNAs in the porcine intestine points out their crucial role in intestinal function as shown by pathway analysis. On the other hand, the reported miRNAs may share orthologs in other mammals such as human still to be discovered.

  9. Oral curcumin has anti-arthritic efficacy through somatostatin generation via cAMP/PKA and Ca(2+)/CaMKII signaling pathways in the small intestine.

    Science.gov (United States)

    Yang, Yan; Wu, Xin; Wei, Zhifeng; Dou, Yannong; Zhao, Di; Wang, Ting; Bian, Difei; Tong, Bei; Xia, Ying; Xia, Yufeng; Dai, Yue

    2015-01-01

    Curcumin (CUR) has been proven to be clinically effective in rheumatoid arthritis (RA) therapy, but its low oral bioavailability eclipses existent evidence that attempts to explain the underlying mechanism. Small intestine, the only organ exposed to a relatively high concentration of CUR, is the main site that generates gut hormones which are involved in the pathogenesis of RA. This study aims at addressing the hypothesis that one or more gut hormones serve as an intermediary agent for the anti-arthritic action of CUR. The protein and mRNA levels of gut hormones in CUR-treated rats were analyzed by ELISA and RT-PCR. Somatostatin (SOM) depletor and receptor antagonist were used to verify the key role of SOM in CUR-mediated anti-arthritic effect. The mechanisms underlying CUR-induced upregulation of SOM levels were explored by cellular experiments and immunohistochemical staining. The data showed that oral administration of CUR (100 mg/kg) for consecutive two weeks in adjuvant-induced arthritis rats still exhibited an extremely low plasma exposure despite of a dramatic amelioration of arthritis symptoms. When injected intraperitoneally, CUR lost anti-arthritic effect in rats, suggesting that it functions in an intestine-dependent manner. CUR elevated SOM levels in intestines and sera, and SOM depletor and non-selective SOM receptor antagonist could abolish the inhibitory effect of CUR on arthritis. Immunohistochemical assay demonstrated that CUR markedly increased the number of SOM-positive cells in both duodenum and jejunum. In vitro experiments demonstrated that CUR could augment SOM secretion from intestinal endocrine cells, and this effect could be hampered by either MEK1/2 or Ca(2+)/calmodulin-dependent kinase II (CAMKII) inhibitor. In summary, oral administration of CUR exhibits anti-arthritic effect through augmenting SOM secretion from the endocrine cells in small intestines via cAMP/PKA and Ca(2+)/CaMKII signaling pathways. Copyright © 2015 Elsevier Ltd

  10. Murine P-glycoprotein deficiency alters intestinal injury repair and blunts lipopolysaccharide-induced radioprotection.

    Science.gov (United States)

    Staley, Elizabeth M; Yarbrough, Vanisha R; Schoeb, Trenton R; Daft, Joseph G; Tanner, Scott M; Steverson, Dennis; Lorenz, Robin G

    2012-09-01

    P-glycoprotein (P-gp) has been reported to increase stem cell proliferation and regulate apoptosis. Absence of P-gp results in decreased repair of intestinal epithelial cells after chemical injury. To further explore the mechanisms involved in the effects of P-gp on intestinal injury and repair, we used the well-characterized radiation injury model. In this model, injury repair is mediated by production of prostaglandins (PGE(2)) and lipopolysaccharide (LPS) has been shown to confer radioprotection. B6.mdr1a(-/-) mice and wild-type controls were subjected to 12 Gy total body X-ray irradiation and surviving crypts in the proximal jejunum and distal colon were evaluated 3.5 days after irradiation. B6.mdr1a(-/-) mice exhibited normal baseline stem cell proliferation and COX dependent crypt regeneration after irradiation. However, radiation induced apoptosis was increased and LPS-induced radioprotection was blunted in the C57BL6.mdr1a(-/-) distal colon, compared to B6 wild-type controls. The LPS treatment induced gene expression of the radioprotective cytokine IL-1α, in B6 wild-type controls but not in B6.mdr1a(-/-) animals. Lipopolysaccharid-induced radioprotection was absent in IL-1R1(-/-) animals, indicating a role for IL-1α in radioprotection, and demonstrating that P-gp deficiency interferes with IL-1α gene expression in response to systemic exposure to LPS.

  11. Evaluation value of intestinal flora detection for intestinal mucosal inflammation and immune response in patients with ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Yan Zou

    2017-09-01

    Full Text Available Objective: To study the evaluation value of intestinal flora detection for intestinal mucosal inflammatory response and immune response in patients with ulcerative colitis. Methods: The patients who were diagnosed with ulcerative colitis in Zigong Fifth People’s Hospital between March 2015 and February 2017 were selected as the UC group, and those who were diagnosed with colonic polyps were selected as the control group. Fresh excreta were collected to detect the number of intestinal flora, and the diseased intestinal mucosa tissue was collected to detect the expression of inflammatory response molecules and immune cell transcription factors. Results: enterococcus contents in intestinal tract and TLR4, NF-kB, TNF-α, HMGB-1, T-bet and RORC mRNA expression levels in intestinal mucosa of UC group were significantly higher than those of control group while bifidobacteria contents in intestinal tract and SOCS2, SOCS3, Foxp3 and GATA-3 mRNA expression levels were significantly lower than those of control group; TLR4, NF-kB, TNF-α, HMGB-1, T-bet and RORC mRNA expression levels in intestinal mucosa of UC patients with grade II and grade III flora disturbance were significantly higher than those of UC patients with normal flora and grade I flora disturbance while SOCS2, SOCS3, Foxp3 and GATA-3 mRNA expression levels were significantly lower than those of UC patients with normal flora and grade I flora disturbance; TLR4, NF-kB, TNF-α, HMGB-1, T-bet and RORC mRNA expression levels in intestinal mucosa of UC patients with grade III flora disturbance were significantly higher than those of UC patients with grade II flora disturbance while SOCS2, SOCS3, Foxp3 and GATA-3 mRNA expression levels were significantly lower than those of UC patients with grade II flora disturbance. Conclusion: The intestinal flora disturbance in patients with ulcerative colitis can result in inflammatory response activation and immune response disorder.

  12. Intestinal perfusion in the study of intestinal absorption

    International Nuclear Information System (INIS)

    Baker, S.J.

    1976-01-01

    Several techniques for studying absorption by means of intestinal perfusion have been developed. While the principle is simple, the practice is complicated by absorption of the solvent and by excretion of fluid into the lumen. To improve reliability a ''marker'' is incorporated into the system; it should behave as nearly as possible like the nutrient of interest, except that it should be unabsorbable. A great many markers, including several labelled with radionuclides, have been developed for use with numerous nutrients, and perfusion methods using double or triple tubes or occlusive balloons have been tested. The perfusion technique is too complicated for routine diagnostic use, but it offers at present the only possibility of studying the function of defined sections of the small intestine in the intact human. (author)

  13. The jagged-2/notch-1/hes-1 pathway is involved in intestinal epithelium regeneration after intestinal ischemia-reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Guoqing Chen

    Full Text Available Notch signaling plays a critical role in the maintenance of intestinal crypt epithelial cell proliferation. The aim of this study was to investigate the role of Notch signaling in the proliferation and regeneration of intestinal epithelium after intestinal ischemia reperfusion (I/R injury.Male Sprague-Dawley rats were subjected to sham operation or I/R by occlusion of the superior mesenteric artery (SMA for 20 min. Intestinal tissue samples were collected at 0, 1, 2, 4, and 6 h after reperfusion. Proliferation of the intestinal epithelium was evaluated by immunohistochemical staining of proliferating nuclear antigen (PCNA. The mRNA and protein expression levels of Notch signaling components were examined using Real-time PCR and Western blot analyses. Immunofluorescence was also performed to detect the expression and location of Jagged-2, cleaved Notch-1, and Hes-1 in the intestine. Finally, the γ-secretase inhibitor DAPT and the siRNA for Jagged-2 and Hes-1 were applied to investigate the functional role of Notch signaling in the proliferation of intestinal epithelial cells in an in vitro IEC-6 culture system.I/R injury caused increased intestinal crypt epithelial cell proliferation and increased mRNA and protein expression of Jagged-2, Notch-1, and Hes-1. The immunofluorescence results further confirmed increased protein expression of Jagged-2, cleaved Notch-1, and Hes-1 in the intestinal crypts. The inhibition of Notch signaling with DAPT and the suppression of Jagged-2 and Hes-1 expression using siRNA both significantly inhibited the proliferation of IEC-6 cells.The Jagged-2/Notch-1/Hes-1 signaling pathway is involved in intestinal epithelium regeneration early after I/R injury by increasing crypt epithelial cell proliferation.

  14. Intestinal morphological effect of brachytherapy of low rate of dose, administrated in therapeutic form and its clinical manifestations in uterine cervix tumors

    International Nuclear Information System (INIS)

    Mendoza, Carmen; Contreras, Manuel

    2005-01-01

    Brachytherapy is effective to eradicate cancer in the cervix, in order to obtain the control of disease we use high dose with vesical and rectum toxicity. The objective is to investigate if brachytherapy by itself is the cause of intestinal damage, to know in addition if the intensity of the clinic manifestations is in direct relation to the given radiation dose and this gets worse when it is received in several applications. Hypothesis: The intensity of the radiation with brachytherapy of low rate of dose is proportional to the degree of clinical manifestations and morphologic damage of the intestine. A prospective analysis was made inpatients with cancer of cervix from september 2000 to june 2004. Each patient who enters to the department of brachytherapy of the hospital must be done laboratory examination that includes plaque and coagulation test before being accepted. We use the clinical card and a table in order to register data concerning teletherapy, implants of brachytherapy of low rate of dose, symptoms of intestinal toxicity and details of colonoscopia. Subsequent to the hospitable discharge the patient is sent to gastroenterology for clinical evaluation and to realize colonoscopia. From september 2000 to june 2004, 540 patients entered, 80 patients (15%) displayed intestinal manifestations, all received teletherapy and brachytherapy, nobody else received brachytherapy in exclusive form and only one patient (0.1%) received the total of the dose in 2 applications. The equipment of teletherapy Primus with energy of 6 and 18 Mv and implants of brachytherapy Manchester were used (70/55 patients). 79 (98%) patients received dose between 85-75 Gy in one single application, 58 (72%) received the total of the dose to the tumor, 21 (26%) in vaginal mucosa. Discussion: Brachytherapy is the cause of the damages in the intestinal mucosa. (The author)

  15. Alternative Functional In Vitro Models of Human Intestinal Epithelia

    Directory of Open Access Journals (Sweden)

    Amanda L Kauffman

    2013-07-01

    Full Text Available Physiologically relevant sources of absorptive intestinal epithelial cells are crucial for human drug transport studies. Human adenocarcinoma-derived intestinal cell lines, such as Caco-2, offer conveniences of easy culture maintenance and scalability, but do not fully recapitulate in vivo intestinal phenotypes. Additional sources of renewable physiologically relevant human intestinal cells would provide a much needed tool for drug discovery and intestinal physiology. We sought to evaluate and compare two alternative sources of human intestinal cells, commercially available primary human intestinal epithelial cells (hInEpCs and induced pluripotent stem cell (iPSC-derived intestinal cells to Caco-2, for use in in vitro transwell monolayer intestinal transport assays. To achieve this for iPSC-derived cells, our previously described 3-dimensional intestinal organogenesis method was adapted to transwell differentiation. Intestinal cells were assessed by marker expression through immunocytochemical and mRNA expression analyses, monolayer integrity through Transepithelial Electrical Resistance (TEER measurements and molecule permeability, and functionality by taking advantage the well-characterized intestinal transport mechanisms. In most cases, marker expression for primary hInEpCs and iPSC-derived cells appeared to be as good as or better than Caco-2. Furthermore, transwell monolayers exhibited high TEER with low permeability. Primary hInEpCs showed molecule efflux indicative of P-glycoprotein transport. Primary hInEpCs and iPSC-derived cells also showed neonatal Fc receptor-dependent binding of immunoglobulin G variants. Primary hInEpCs and iPSC-derived intestinal cells exhibit expected marker expression and demonstrate basic functional monolayer formation, similar to or better than Caco-2. These cells could offer an alternative source of human intestinal cells for understanding normal intestinal epithelial physiology and drug transport.

  16. Apoptosis induced by high- and low-LET radiations

    International Nuclear Information System (INIS)

    Hendry, J.H.; Potten, C.S.; Merritt, A.

    1995-01-01

    Cell death after irradiation occurs by apoptosis in certain cell populations in tissues. The phenomenon also occurs after high linear energy transfer (LET) irradiation, and the relative biological effectiveness (RBE) is 3 to 4 (with respect to low-LET radiation and apoptosis in intestinal crypts) for neutrons with energies of 14 MeV and up to 600 MeV. It is thought that p53 plays a role in the phenomenon, as radiation-induced apoptosis is not observed in p53-null animals. (orig.)

  17. An intestinal Trojan horse for gene delivery.

    Science.gov (United States)

    Peng, Haisheng; Wang, Chao; Xu, Xiaoyang; Yu, Chenxu; Wang, Qun

    2015-03-14

    The intestinal epithelium forms an essential element of the mucosal barrier and plays a critical role in the pathophysiological response to different enteric disorders and diseases. As a major enteric dysfunction of the intestinal tract, inflammatory bowel disease is a genetic disease which results from the inappropriate and exaggerated mucosal immune response to the normal constituents in the mucosal microbiota environment. An intestine targeted drug delivery system has unique advantages in the treatment of inflammatory bowel disease. As a new concept in drug delivery, the Trojan horse system with the synergy of nanotechnology and host cells can achieve better therapeutic efficacy in specific diseases. Here, we demonstrated the feasibility of encapsulating DNA-functionalized gold nanoparticles into primary isolated intestinal stem cells to form an intestinal Trojan horse for gene regulation therapy of inflammatory bowel disease. This proof-of-concept intestinal Trojan horse will have a wide variety of applications in the diagnosis and therapy of enteric disorders and diseases.

  18. Radioimmunoassay studies of intestinal calcium-binding protein in the pig. 2. The distribution of intestinal CaBP in pig tissues

    International Nuclear Information System (INIS)

    Arnold, B.M.; Kuttner, M.; Willis, D.M.; Hitchman, A.J.W.; Harrison, J.E.; Murray, T.M.

    1975-01-01

    Using a specific radioimmunoassay for porcine intestinal calcium-binding protein (CaBP), we have measured the concentration of CaBP in the various tissues and organs of normal pigs. Intestinal CaBP was present in highest concentration in the upper small intestine, with lower concentrations in the distal small intestine. Intestinal CaBP was also found, in lower concentrations, in kidney, liver, thyroid, pancreas, and blood. In all other tissues, including parathyroid, bone, skeletal muscle, and brain, CaBP immunoreactivity was undetectable or less than in blood. The elution profile of calcium-binding activity and immunoreactivity from gel filtration analysis of kidney and parathyroid extracts suggest that the calcium-binding protein in the parathyroid gland, and the major calcium-binding protein(s) in the kidney, are chemically and immunochemically different from intestinal CaBP. (author)

  19. Radioimmunoassay studies of intestinal calcium-binding protein in the pig. II. The distribution of intestinal CaBP in pig tissues

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, B M; Kuttner, M; Willis, D M; Hitchman, A J.W.; Harrison, J E; Murray, T M [Toronto Univ., Ontario (Canada). Dept. of Medicine

    1975-12-01

    Using a specific radioimmunoassay for porcine intestinal calcium-binding protein (CaBP), we have measured the concentration of CaBP in the various tissues and organs of normal pigs. Intestinal CaBP was present in highest concentration in the upper small intestine, with lower concentrations in the distal small intestine. Intestinal CaBP was also found, in lower concentrations, in kidney, liver, thyroid, pancreas, and blood. In all other tissues, including parathyroid, bone, skeletal muscle, and brain, CaBP immunoreactivity was undetectable or less than in blood. The elution profile of calcium-binding activity and immunoreactivity from gel filtration analysis of kidney and parathyroid extracts suggest that the calcium-binding protein in the parathyroid gland, and the major calcium-binding protein(s) in the kidney, are chemically and immunochemically different from intestinal CaBP.

  20. Parenteral nutrition in intestinal failure

    Directory of Open Access Journals (Sweden)

    Kurkchubasche AG

    2015-01-01

    Full Text Available Arlet G Kurkchubasche,1 Thomas J Herron,2 Marion F Winkler31Department of Surgery and Pediatrics, 2Department of Surgery, Alpert Medical School of Brown University, 3Department of Surgery/Nutritional Support Service, Rhode Island Hospital, Providence, RI, USAAbstract: Intestinal failure is a consequence of extensive surgical resection resulting in anatomic loss and/or functional impairment in motility or absorptive capacity. The condition is clinically characterized by the inability to maintain fluid, energy, protein, electrolyte, or micronutrient balance when on a conventionally accepted, normal diet. Parenteral nutrition (PN is the cornerstone of management until intestinal adaptation returns the patient to a PN-independent state. Intestinal length, residual anatomic segments and motility determine the need for and duration of parenteral support. The goals of therapy are to provide sufficient nutrients to enable normal growth and development in children, and support a healthy functional status in adults. This review addresses indications for PN, the formulation of the PN solution, patient monitoring, and considerations for prevention of PN-associated complications. With the ultimate goal of achieving enteral autonomy, the important role of diet, pharmacologic interventions, and surgery is discussed.Keywords: intestinal failure, short-bowel syndrome, parenteral nutrition, home nutrition support, intestinal rehabilitation

  1. Transcriptome Analysis of Three Sheep Intestinal Regions reveals Key Pathways and Hub Regulatory Genes of Large Intestinal Lipid Metabolism.

    Science.gov (United States)

    Chao, Tianle; Wang, Guizhi; Ji, Zhibin; Liu, Zhaohua; Hou, Lei; Wang, Jin; Wang, Jianmin

    2017-07-13

    The large intestine, also known as the hindgut, is an important part of the animal digestive system. Recent studies on digestive system development in ruminants have focused on the rumen and the small intestine, but the molecular mechanisms underlying sheep large intestine metabolism remain poorly understood. To identify genes related to intestinal metabolism and to reveal molecular regulation mechanisms, we sequenced and compared the transcriptomes of mucosal epithelial tissues among the cecum, proximal colon and duodenum. A total of 4,221 transcripts from 3,254 genes were identified as differentially expressed transcripts. Between the large intestine and duodenum, differentially expressed transcripts were found to be significantly enriched in 6 metabolism-related pathways, among which PPAR signaling was identified as a key pathway. Three genes, CPT1A, LPL and PCK1, were identified as higher expression hub genes in the large intestine. Between the cecum and colon, differentially expressed transcripts were significantly enriched in 5 lipid metabolism related pathways, and CEPT1 and MBOAT1 were identified as hub genes. This study provides important information regarding the molecular mechanisms of intestinal metabolism in sheep and may provide a basis for further study.

  2. Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.

    Directory of Open Access Journals (Sweden)

    Nicole J W de Wit

    Full Text Available Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, we explored the applicability of in vitro (human Caco-2 cells and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP technique to study the effect of food compounds. In vitro digested yellow (YOd and white onion extracts (WOd were used as model food compounds and transcriptomics was applied to obtain more insight into which extent mode of actions depend on the model. The three intestine models shared 9,140 genes which were used to compare the responses to digested onions between the models. Unsupervised clustering analysis showed that genes up- or down-regulated by WOd in human Caco-2 cells and rat intestine slices were similarly regulated by YOd, indicating comparable modes of action for the two onion species. Highly variable responses to onion were found in the pig SISP model. By focussing only on genes with significant differential expression, in combination with a fold change > 1.5, 15 genes showed similar onion-induced expression in human Caco-2 cells and rat intestine slices and 2 overlapping genes were found between the human Caco-2 and pig SISP model. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions in all three models. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Taken together, our data indicate that each of the in vitro and ex vivo intestine models used in this study, taking into account their limitations, can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies.

  3. Whole cell Deinococcus radiodurans ameliorates salt stress in Indian mustard through pyrroloquinoline quinone

    International Nuclear Information System (INIS)

    Srivastava, A.K.; Jadhav, P.; Suprasanna, P.; Rajpurohit, Y.S.; Misra, H.S.

    2015-01-01

    Salinity stress is considered as one of the major abiotic stresses limiting crop productivity. A variety of symbiotic and non-symbiotic bacteria are currently being used worldwide with the aim to boost built-in defense system in plants. Deinococcus radiodurans is a highly desiccation and radiation tolerant bacterium which synthesizes PQQ (pyrroloquinoline quinone) that has been shown to have a versatile role in crop productivity and as a general stress response regulator in bacteria and mammals. PQQ also acts as scavenger of reactive oxygen species and hence, can module redox signaling, one of the major regulator of stress tolerance in plants. In view of this, present research was conducted to evaluate the potential of whole cell D. radiodurans for ameliorating salt stress in plants. The soil colonization with wild-type cells led to partial amelioration of salt stress. The PQQ mutant showed an intermediate phenotype between wild-type seedlings and those grown on non-colonized soils which confirmed that the effects are largely associated with PQQ. The differential phenotype was also correlated with ROS level and ABA accumulation. The flame photometry data showed that there was no significant reduction in water soluble Na + level in control plant and those treated with either wild-type or PQQ mutant. Further, the elevated levels of antioxidant enzymes and reduced ascorbate in the plants treated with bacterial cells indicated its positive role in oxidative stress management. Although, the exact molecular basis to these effects is yet to be understood, present findings support the use of whole cell D. radiodurans for managing the growth and productivity of Indian mustard in salt affected fields. (author)

  4. Enrichment, Distribution of Vanadium-Containing Protein in Vanadium-Enriched Sea Cucumber Apostichopus japonicus and the Ameliorative Effect on Insulin Resistance.

    Science.gov (United States)

    Liu, Yanjun; Zhou, Qingxin; Zhao, Yanlei; Wang, Yiming; Wang, Yuming; Wang, Jingfeng; Xu, Jie; Xue, Changhu

    2016-05-01

    Sea cucumbers are a potential source of natural organic vanadium that may improve insulin resistance. In this work, vanadium was accumulated rapidly in blood, body wall, and intestine by sea cucumber Apostichopus japonicus. Furthermore, water-soluble vanadium-containing proteins, the main form of the organic vanadium, were tentatively accumulated and isolated by a bioaccumulation experiment. It was also designed to evaluate the beneficial effect of vanadium-containing proteins (VCPs) from sea cucumber rich in vanadium on the development of hyperglycemia and insulin resistance in C57BL/6J mice fed with a high-fat high-sucrose diet (HFSD). HFSD mice treated with VCPs significantly decreased fasting blood glucose, serum insulin, and HOMA-IR values as compared to HFSD mice, respectively. Serum adiponectin, resistin, TNF-α, and leptin levels in insulin-resistant mice were dramatically reduced by a VCP supplement. These results show an ameliorative effect on insulin resistance by treatment with VCPs. Such compound seems to be a valuable therapy to achieve and/or maintain glycemic control and therapeutic agents in the treatment arsenal for insulin resistance and type 2 diabetes.

  5. Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol ...

    African Journals Online (AJOL)

    Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol-Induced Hepatotoxicity In Rats. ... Nigerian Quarterly Journal of Hospital Medicine ... the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure.

  6. Effect of Gamma radiation on microbial population of natural casings

    International Nuclear Information System (INIS)

    Trigo, M.J.; Fraqueza, M.J.

    1998-01-01

    The high microbial load of fresh and dry natural casings increases the risk of meat product contamination with pathogenic microorganims, agents of foodborn diseases. The aim of this work is to evaluate the killing effect of gamma radiation on the resident microbial population of pork and beef casings, to improve their hygiene and safety. Portions of fresh pork (small intestine and colon) and dry beef casings were irradiated in a Cobalt 60 source with absorbed doses of 1, 2, 5 and 10 kGy. The D 10 values of total aerobic microorganisms in the pork casings were 1.65 kGy for colon and 1.54 kGy for small intestine. The D 10 value found in beef dry casings (small intestine) was 10.17 kGy. Radurization with 5 kGy was able to reduce, at least, 6 logs the coliform bacteria in pork casings. The killing effect over faecal Streptococci was 4 logs for pork fresh casings and 2 logs for beef dry casings. Gamma radiation with 5 kGy proved to be a convenient method to reduce substantially the microbial population of pork fresh casings. Otherwise, the microbial population of beef dry casings still resisted to 10 kGy

  7. Interactions between the intestinal microbiota and innate lymphoid cells

    Science.gov (United States)

    Chen, Vincent L; Kasper, Dennis L

    2014-01-01

    The mammalian intestine must manage to contain 100 trillion intestinal bacteria without inducing inappropriate immune responses to these microorganisms. The effects of the immune system on intestinal microorganisms are numerous and well-characterized, and recent research has determined that the microbiota influences the intestinal immune system as well. In this review, we first discuss the intestinal immune system and its role in containing and maintaining tolerance to commensal organisms. We next introduce a category of immune cells, the innate lymphoid cells, and describe their classification and function in intestinal immunology. Finally, we discuss the effects of the intestinal microbiota on innate lymphoid cells. PMID:24418741

  8. ACUTE INTESTINAL INFECTIONS: THERAPEUTICAL TACTICS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    A.N. Surkov

    2011-01-01

    Full Text Available Acute intestinal infections are quite common among children. Their clinical presentations include intoxication syndrome (drowsiness, low appetite, fever etc, infectious toxic syndrome (toxicosis with exicosis, neurotoxicosi, hypovolemic or infectious-toxic shockand diarrhea syndrome. Sometimes intestinal infections can be quite severe and even lethal. However disease duration and outcome depend on timelines and adequacy of prescribed treatment. Main guidelines of intestinal infections treatment include probiotics. That is why the right choice of probiotics is important for a pediatrician. The article contains basic information upon etiopathogenesis, classification, diagnostic criteria and acute pediatric intestinal infections treatment guidelines.Key words: acute intestinal infections, etiopathogenesis, diagnostic criteria, treatment, probiotics, children. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (6: 141–147

  9. Hippo signalling directs intestinal fate

    DEFF Research Database (Denmark)

    le Bouteiller, Marie Catherine M; Jensen, Kim Bak

    2015-01-01

    Hippo signalling has been associated with many important tissue functions including the regulation of organ size. In the intestinal epithelium differing functions have been proposed for the effectors of Hippo signalling, YAP and TAZ1. These are now shown to have a dual role in the intestinal...

  10. Mathematical modelling of the death rate dynamics in mammals with intestinal form of radiation sicleness

    International Nuclear Information System (INIS)

    Smirnova, O.A.

    1990-01-01

    A mathematical models has been developed to describe the death rate dynamics in irradiated mammals. The model links statistical biometric functions with statistical and dynamic characteristics of the organism's 'critical' system. There is an agreement between the results of modelling and experiments with respect to death rate dynamics of small laboratory animals subjected to acute and chronic irradiation with doses and dose-rates at which small intestine epithelium is 'ctitical'

  11. The small intestine and colon: Scintigraphic quantitation of motility in health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Kamm, M.A. (Saint Mark' s Hospital, London (United Kingdom). Medical Physiology Unit)

    1992-10-01

    Radioisotopes allow accurate quantitation of the pattern and effectiveness of the transit of chyme through the small and large intestines. Abnormalities of small bowel transit can be demonstrated in patients with the irritable bowel syndrome, and patients with chronic idiopathic intestinal pseudo-obstruction due to either a visceral myopathy or neuropathy. In the colon, radioisotopic studies of transit have demonstrated the site of delayed transit in some severely constipated patients. In patients with these disorders of transit, functional studies may influence the choice of medical or surgical therapy although there are few prospective studies which have established their worth in this context. Radioisotope studies can also be utilised to study the effectiveness of delivery of drugs to the small and large bowel, and to study the adequacy of rectal evacuation in patients with a defaecatory disturbance. The low radiation dose and possibility of frequent observations make radioisotope studies valuable for clinical and research studies in functional gastrointestinal disorders. (orig.).

  12. The small intestine and colon: Scintigraphic quantitation of motility in health and disease

    International Nuclear Information System (INIS)

    Kamm, M.A.

    1992-01-01

    Radioisotopes allow accurate quantitation of the pattern and effectiveness of the transit of chyme through the small and large intestines. Abnormalities of small bowel transit can be demonstrated in patients with the irritable bowel syndrome, and patients with chronic idiopathic intestinal pseudo-obstruction due to either a visceral myopathy or neuropathy. In the colon, radioisotopic studies of transit have demonstrated the site of delayed transit in some severely constipated patients. In patients with these disorders of transit, functional studies may influence the choice of medical or surgical therapy although there are few prospective studies which have established their worth in this context. Radioisotope studies can also be utilised to study the effectiveness of delivery of drugs to the small and large bowel, and to study the adequacy of rectal evacuation in patients with a defaecatory disturbance. The low radiation dose and possibility of frequent observations make radioisotope studies valuable for clinical and research studies in functional gastrointestinal disorders. (orig.)

  13. Radiation research contracts: Biological effects of small radiation doses

    International Nuclear Information System (INIS)

    Hug, O.

    1959-01-01

    According to its Statute the IAEA has to fulfil a dual function - to help individual countries in solving their specific problems and to undertake tasks in the common interest of all its Member States. With this latter aim in mind the Agency has placed a number of research contracts with national research institutes. The purpose and scope of two of them is described below by the scientists responsible for their execution. The Agency has contributed to this work by putting at the institutes' disposal scientists from its own staff apparatus and financial aid.IAEA placed a research contract concerning the effects of small radiation doses on cells, in particular on nervous cells, with the Pharmacological Institute of the University of Vienna. This Institute appeared well suited to deal with the problem owing to the type of its previous research work. The Director, Prof. Franz Bruecke, and his collaborator Dr. Otto Kraupp, have long been interested in the functioning of the nervous system and in the influence of different drugs upon it. It was particularly fortunate that the electrical properties and functions of cells had been measured by a method specially developed at this Institute. From the above mentioned observations one could expect that instantaneous reactions of cells to radiation would also lead to changes of the electrical status. Consequently, this method is now being applied to the research undertaken for IAEA. Different cells of plants and animals, ranging from algae to muscle fibres of mammals, were chosen as objects. So far changes of potentials-had been observed only during irradiation with very high doses. During these investigations another useful test for small radiation doses was developed, namely the measurement of the through-flow of an artificial blood solution through the blood vessels of an intestinal loop. It was observed that a few seconds after irradiation the flow rate diminishes, and returns to its normal level only when irradiation ends

  14. Radiation research contracts: Biological effects of small radiation doses

    Energy Technology Data Exchange (ETDEWEB)

    Hug, O

    1959-01-15

    According to its Statute the IAEA has to fulfil a dual function - to help individual countries in solving their specific problems and to undertake tasks in the common interest of all its Member States. With this latter aim in mind the Agency has placed a number of research contracts with national research institutes. The purpose and scope of two of them is described below by the scientists responsible for their execution. The Agency has contributed to this work by putting at the institutes' disposal scientists from its own staff apparatus and financial aid.IAEA placed a research contract concerning the effects of small radiation doses on cells, in particular on nervous cells, with the Pharmacological Institute of the University of Vienna. This Institute appeared well suited to deal with the problem owing to the type of its previous research work. The Director, Prof. Franz Bruecke, and his collaborator Dr. Otto Kraupp, have long been interested in the functioning of the nervous system and in the influence of different drugs upon it. It was particularly fortunate that the electrical properties and functions of cells had been measured by a method specially developed at this Institute. From the above mentioned observations one could expect that instantaneous reactions of cells to radiation would also lead to changes of the electrical status. Consequently, this method is now being applied to the research undertaken for IAEA. Different cells of plants and animals, ranging from algae to muscle fibres of mammals, were chosen as objects. So far changes of potentials-had been observed only during irradiation with very high doses. During these investigations another useful test for small radiation doses was developed, namely the measurement of the through-flow of an artificial blood solution through the blood vessels of an intestinal loop. It was observed that a few seconds after irradiation the flow rate diminishes, and returns to its normal level only when irradiation ends

  15. Duodenal-jejunal bypass surgery up-regulates the expression of the hepatic insulin signaling proteins and the key regulatory enzymes of intestinal gluconeogenesis in diabetic Goto-Kakizaki rats.

    Science.gov (United States)

    Sun, Dong; Wang, Kexin; Yan, Zhibo; Zhang, Guangyong; Liu, Shaozhuang; Liu, Fengjun; Hu, Chunxiao; Hu, Sanyuan

    2013-11-01

    Duodenal-jejunal bypass (DJB), which is not routinely applied in metabolic surgery, is an effective surgical procedure in terms of type 2 diabetes mellitus resolution. However, the underlying mechanisms are still undefined. Our aim was to investigate the diabetic improvement by DJB and to explore the changes in hepatic insulin signaling proteins and regulatory enzymes of gluconeogenesis after DJB in a non-obese diabetic rat model. Sixteen adult male Goto-Kakizaki rats were randomly divided into DJB and sham-operated groups. The body weight, food intake, hormone levels, and glucose metabolism were measured. The levels of protein expression and phosphorylation of insulin receptor-beta (IR-β) and insulin receptor substrate 2 (IRS-2) were evaluated in the liver. We also detected the expression of key regulatory enzymes of gluconeogenesis [phosphoenoylpyruvate carboxykinase-1 (PCK1), glucose-6-phosphatase-alpha (G6Pase-α)] in small intestine and liver. DJB induced significant diabetic improvement with higher postprandial glucagons-like peptide 1, peptide YY, and insulin levels, but without weight loss. The DJB group exhibited increased expression and phosphorylation of IR-β and IRS-2 in liver, up-regulated the expression of PCK1 and G6Pase-α in small intestine, and down-regulated the expression of these enzymes in liver. DJB is effective in up-regulating the expression of the key proteins in the hepatic insulin signaling pathway and the key regulatory enzymes of intestinal gluconeogenesis and down-regulating the expression of the key regulatory enzymes of hepatic gluconeogenesis without weight loss. Our study helps to reveal the potential role of hepatic insulin signaling pathway and intestinal gluconeogenesis in ameliorating insulin resistance after metabolic surgery.

  16. Intestinal leiomyoma

    Science.gov (United States)

    ... most often found when a person has an upper gastrointestinal (GI) endoscopy or colonoscopy for another reason. Rarely, these tumors can cause bleeding, blockage or rupture of the intestines If this ...

  17. Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation

    International Nuclear Information System (INIS)

    Yamamoto, Tetsuo; Kinoshita, Manabu; Shinomiya, Nariyoshi; Hiroi, Sadayuki; Sugasawa, Hidekazu; Majima, Takashi; Seki, Shuhji; Matsushita, Yoshitaro; Saitoh, Daizoh

    2010-01-01

    While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome. (author)

  18. Role of ghrelin in small intestinal motility following pediatric intracerebral hemorrhage in mice.

    Science.gov (United States)

    Zan, Jieyu; Song, Lei; Wang, Jiejie; Zou, Rong; Hong, Fei; Zhao, Jinhua; Cheng, Yijun; Xu, Ming

    2017-11-01

    Small intestinal motility (SIM) disorder is a common complication following pediatric intracerebral hemorrhage (ICH), leading to a poor prognosis in patients. Previous studies have shown that ghrelin is involved in SIM in various diseases; however, the role of ghrelin in pediatric ICH‑induced SIM disorder remains to be elucidated. The present study was designed to investigate the association between ghrelin and SIM post‑ICH, and to examine the effect of exogenous ghrelin administration on SIM in vivo. An ICH model was induced in mice by autologous blood infusion. Neurobehavioral deficits were evaluated using a Rotarod test, forelimb placing test, and corner turn test. Intestinal mucosal damage was examined using hematoxylin and eosin staining. SIM was measured using charcoal meal staining. An enzyme‑linked immunosorbent assay was used to evaluate serum levels of ghrelin and nitric oxide (NO). Reverse transcription‑quantitative polymerase chain reaction and western blot analyses were performed to determine the levels of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) at the mRNA and protein levels. Nω‑nitro‑L‑arginine methyl ester hydrochloride (L‑NAME), L‑arginine, atropine, phentolamine and propranolol were used to manipulate the putative pathways induced by ghrelin. Neurological dysfunction was observed post‑ICH. ICH caused damage to the intestinal mucosa and delayed SIM. Serum levels of ghrelin increased between 3 h and 3 days, peaking at 12 h, and showed a significant negative correlation with SIM post‑ICH. Ghrelin administration dose‑dependently attenua-ted ICH‑induced SIM disorder. Ghrelin also decreased NO levels by downregulating the mRNA and protein expression levels of iNOS, but not those of nNOS or eNOS, post‑ICH. Consistently, the effect was enhanced by L‑NAME and weakened by L‑arginine, respectively. The protective effect of ghrelin was

  19. Functional characterization of folic acid transport in the intestine of the laying hen using the everted intestinal sac model.

    Science.gov (United States)

    Tactacan, G B; Rodriguez-Lecompte, J C; Karmin, O; House, J D

    2011-01-01

    Absorption at the level of the intestine is likely a primary regulatory mechanism for the deposition of dietary supplemented folic acid into the chicken egg. Therefore, factors affecting the intestinal transport of folic acid in the laying hen may influence the level of egg folate concentrations. To this end, a series of experiments using intestinal everted sacs were conducted to characterize intestinal folic acid absorption processes in laying hens. Effects of naturally occurring folate derivatives (5-methyl and 10-formyltetrahydrofolate) as well as heme on folic acid absorption were also investigated. Folic acid absorption was measured based on the rate of uptake of (3)H-labeled folic acid in the everted sac from various segments of the small and large intestines. Folic acid concentration, incubation length, and pH condition were optimized before the performance of uptake experiments. The distribution profile of folic acid transport along the intestine was highest in the upper half of the small intestine. Maximum uptake rate (nmol·100 g tissue(-1)·min(-1)) was observed in the duodenum (20.6 ± 1.9) and jejunum (22.3 ± 2.0) and decreased significantly in the ileum (15.3 ± 1.1) and cecum (9.3 ± 0.9). Transport increased proportionately (P methyl and 10-formyltetrahydrofolate as well as heme impeded folic acid uptake, reducing intestinal folic acid absorption when added at concentrations ranging from 0 to 100 µM. Overall, these data indicated the presence of a folic acid transport system in the entire intestine of the laying hen. Uptake of folic acid in the cecum raises the likelihood of absorption of bacterial-derived folate.

  20. Regulation of intestinal homeostasis by innate immune cells.

    Science.gov (United States)

    Kayama, Hisako; Nishimura, Junichi; Takeda, Kiyoshi

    2013-12-01

    The intestinal immune system has an ability to distinguish between the microbiota and pathogenic bacteria, and then activate pro-inflammatory pathways against pathogens for host defense while remaining unresponsive to the microbiota and dietary antigens. In the intestine, abnormal activation of innate immunity causes development of several inflammatory disorders such as inflammatory bowel diseases (IBD). Thus, activity of innate immunity is finely regulated in the intestine. To date, multiple innate immune cells have been shown to maintain gut homeostasis by preventing inadequate adaptive immune responses in the murine intestine. Additionally, several innate immune subsets, which promote Th1 and Th17 responses and are implicated in the pathogenesis of IBD, have recently been identified in the human intestinal mucosa. The demonstration of both murine and human intestinal innate immune subsets contributing to regulation of adaptive immunity emphasizes the conserved innate immune functions across species and might promote development of the intestinal innate immunity-based clinical therapy.

  1. Antibiotics can ameliorate circulatory complications of liver cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn Stæhr; Schaffalitzky de Muckadell, Ove B

    2011-01-01

    . This review focuses on how broad spectrum antibiotics can ameliorate the haemodynamic consequences of bacterial translocation. It is possible that the use of broad spectrum antibiotics in the future may be used to prevent other complications of liver cirrhosis than spontaneous bacterial peritonitis...

  2. Effect of radiation on glucose absorption in the nouse jejunum in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Overgaard, J.; Matsui, Masasuke (Danish Cancer Society, Aarhus (Denmark). Department of Experimental Clinical Oncology)

    1990-05-01

    In an attempt to develop a clinical assay for intestinal damage, the relationship between radiation dose and glucose absorpion in the jejunum has been investigated. Lightly anesthetised C3D2F1 mice had their upper abdomen irradiated. The intestine was exteriorized and a 10-cm segment of the jejunum was isolated and included in a closed circuit perfusion loop. An isotonic solution containing 2 mg/ml D-glucose was perfused in 2 h and the rate of glucose absorption calculated. The absorption decreased as a function of dose and time after irradiation with the most prominent reduction after 4-5 days, returning to normal within a week after irradiation. A dose-response relationship was found after single doses between 5 and 17.5 Gy. Split-dose recovery of approximately 7.5. Gy was fond within 2-4 h. This absorption insufficiency was only found to be present acutely, and no late abnormalities were seen for times greater than 12 months after irradiation. The results correlated with other functional endpoints such as absorptive surface. This assay seems suitable to demonstrate (acute) functional intestinal radiation damage and has obvious clinical applicability. (author). 31 refs.; 6 figs.; 1 tab.

  3. A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices

    NARCIS (Netherlands)

    Westerhout, J.; Steeg, E. van de; Grossouw, D.; Zeijdner, E.E.; Krul, C.A.M.; Verwei, M.; Wortelboer, H.M.

    2014-01-01

    A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption,

  4. Regional specialization within the intestinal immune system

    DEFF Research Database (Denmark)

    Mowat, Allan M.; Agace, William Winston

    2014-01-01

    The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly...... implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout...... the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease...

  5. Granulocyte Colony-Stimulating Factor in the Treatment of Acute Radiation Syndrome: A Concise Review

    Directory of Open Access Journals (Sweden)

    Michal Hofer

    2014-04-01

    Full Text Available This article concisely summarizes data on the action of one of the principal and best known growth factors, the granulocyte colony-stimulating factor (G-CSF, in a mammalian organism exposed to radiation doses inducing acute radiation syndrome. Highlighted are the topics of its real or anticipated use in radiation accident victims, the timing of its administration, the possibilities of combining G-CSF with other drugs, the ability of other agents to stimulate endogenous G-CSF production, as well as of the capability of this growth factor to ameliorate not only the bone marrow radiation syndrome but also the gastrointestinal radiation syndrome. G-CSF is one of the pivotal drugs in the treatment of radiation accident victims and its employment in this indication can be expected to remain or even grow in the future.

  6. Intestinal metaplasia induced by x-irradiation in rat

    International Nuclear Information System (INIS)

    Watanabe, Hiromitsu; Terada, Yoritaka; Fujii, Isao; Yamamoto, Yukiko; Takizawa, Shoichi

    1978-01-01

    Total 400 rad of x-ray was given in 100 or 150 rad doses to the whole body of rats at intervals of one week, and one year and a half later, rats were killed. Disaccharidase was formed in most of animals, intestinal metaplasia only with goblet cells occurred in 65% of animals, and that with intestinal type of lacuna occurred in 36% of them. When 500 rad of x-ray was irradiated to each part of stomach day after day up to the total dose of 3,000 rad, biochemical intestinal metaplasia already occurred one week after the irradiation, and intestinal type lacuna occurred 2 months after the irradiation. Intestinal type lacuna was recognized in all animals killed 499 days after the irradiation, and intestinal metaplasia with Paneth's cells occurred in 6 out of 11 cases (56%). When a dose of 1,000 rad was irradiated to stomach three times at intervals of 2 days up to the total of 3,000 rad, much intestinal type lacuna was recognized 2 months after the irradiation, gastric adenoid cancerous changes appeared 4 months after, and gastric adenoid cancer occurred 6 months after. The above-mentioned results clarified that even if x-ray of a small dose was irradiated, intestinal metaplasia occurred, and that the period from the irradiation to occurrence of intestinal metaplasia was shortened by increasing a dose of x-ray. It was also clarified that not only intestinal metaplasia but also gastric adenoic cancer occurred due to a great amount of x-ray irradiation. (Ueda, J.)

  7. Intestinal metaplasia induced by x-irradiation in rat

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, H; Terada, Y; Fujii, I; Yamamoto, Y; Takizawa, S [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

    1978-04-01

    Total 400 rad of x-ray was given in 100 or 150 rad doses to the whole body of rats at intervals of one week, and one year and a half later, rats were killed. Disaccharidase was formed in most of animals, intestinal metaplasia only with goblet cells occurred in 65% of animals, and that with intestinal type of lacuna occurred in 36% of them. When 500 rad of x-ray was irradiated to each part of stomach day after day up to the total dose of 3,000 rad, biochemical intestinal metaplasia already occurred one week after the irradiation, and intestinal type lacuna occurred 2 months after the irradiation. Intestinal type lacuna was recognized in all animals killed 499 days after the irradiation, and intestinal metaplasia with Paneth's cells occurred in 6 out of 11 cases (56%). When a dose of 1,000 rad was irradiated to stomach three times at intervals of 2 days up to the total of 3,000 rad, much intestinal type lacuna was recognized 2 months after the irradiation, gastric adenoid cancerous changes appeared 4 months after, and gastric adenoid cancer occurred 6 months after. The above-mentioned results clarified that even if x-ray of a small dose was irradiated, intestinal metaplasia occurred, and that the period from the irradiation to occurrence of intestinal metaplasia was shortened by increasing a dose of x-ray. It was also clarified that not only intestinal metaplasia but also gastric adenoic cancer occurred due to a great amount of x-ray irradiation.

  8. Intestinal sclerosis with pseudo-obstruction in three dogs.

    Science.gov (United States)

    Moore, R; Carpenter, J

    1984-04-01

    Intestinal sclerosis causing chronic intestinal pseudo-obstruction was diagnosed in 3 dogs. The pseudo-obstruction was characterized by vomiting and weight loss of 2 weeks' to 3 months' duration. A patent intestinal lumen was determined by contrast radiography and verified at surgery. Intestinal biopsy revealed diffuse atrophy, fibrosis, and mononuclear cell infiltration of the tunica muscularis. Each dog was euthanatized because of a progressive, deteriorating clinical course.

  9. Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

    Energy Technology Data Exchange (ETDEWEB)

    Horita, Nobukatsu [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Tsuchiya, Kiichiro, E-mail: kii.gast@tmd.ac.jp [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Hayashi, Ryohei [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Department of Gastroenterology and Metabolism, Hiroshima University (Japan); Fukushima, Keita; Hibiya, Shuji; Fukuda, Masayoshi; Kano, Yoshihito; Mizutani, Tomohiro; Nemoto, Yasuhiro; Yui, Shiro [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Okamoto, Ryuichi; Nakamura, Tetsuya [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Watanabe, Mamoru [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan)

    2014-11-28

    Highlights: • Lentivirus mixed with Matrigel enables direct infection of intestinal organoids. • Our original approach allows the marking of a single stem cell in a crypt. • Time-lapse imaging shows the dynamics of a single stem cell. • Our lentivirus transgene system demonstrates plural long-lived stem cells in a crypt. - Abstract: Background and aims: The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour. Methods: Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence. Results: We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids. Conclusions: The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus.

  10. Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

    International Nuclear Information System (INIS)

    Horita, Nobukatsu; Tsuchiya, Kiichiro; Hayashi, Ryohei; Fukushima, Keita; Hibiya, Shuji; Fukuda, Masayoshi; Kano, Yoshihito; Mizutani, Tomohiro; Nemoto, Yasuhiro; Yui, Shiro; Okamoto, Ryuichi; Nakamura, Tetsuya; Watanabe, Mamoru

    2014-01-01

    Highlights: • Lentivirus mixed with Matrigel enables direct infection of intestinal organoids. • Our original approach allows the marking of a single stem cell in a crypt. • Time-lapse imaging shows the dynamics of a single stem cell. • Our lentivirus transgene system demonstrates plural long-lived stem cells in a crypt. - Abstract: Background and aims: The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour. Methods: Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence. Results: We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids. Conclusions: The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus

  11. Radiation proctitis and its surgical problems

    Energy Technology Data Exchange (ETDEWEB)

    Ichikawa, Hideyuki; Hayashi, Shiro; Yasuna, Osamu; Yamaura, Yoshinori

    1985-01-01

    Radiation proctitis was investigated in terms of clinico-pathological findings, the method of treatment and therapeutic results in 11 patients (7 with cervical cancer, 1 with ovarian cancer, and 3 with cancer of the bladder). Four of the patients with cervical cancer were treated with 4,136-5,000 rad of WCo combined with brachytherapy of WCo or TXCs, one patient with 6,000 rad of WCo alone, one with 3,000 rad of x-ray alone, and one with 4,900 rad of x-ray combined with brachytherapy of TXCs. A patient with ovarian cancer was treated with 6,000 rad of x-ray and three patients with cancer of the bladder were treated with 4,200-6,330 rad of x-ray. Radiation proctitis developed early (4 months to 1 year after therapy) in 8 patients and late (4 years to 19 years after therapy) in the other 3 patients. Common symptoms were melena, constipation and sensation of gastric fullness. According to the Sherman's classification, proctitis was grade III or IV (showing constriction, ulcer or fistula) in all patients. Although the lesion could be resected in one patient, only colostomy was performed in the other 10 patients. It is recommended that care should be taken in deciding the method of exposure to the pelvic viscera and exposure doses for the prevention of radiation proctitis, and that intestinal lesions should be resected before far-advanced intestinal disturbance developes. (Namekawa, K.).

  12. Immunization with intestinal microbiota-derived Staphylococcus aureus and Escherichia coli reduces bacteria-specific recolonization of the intestinal tract.

    Science.gov (United States)

    Garfias-López, Julio Adrián; Castro-Escarpuli, Graciela; Cárdenas, Pedro E; Moreno-Altamirano, María Maximina Bertha; Padierna-Olivos, Juan; Sánchez-García, F Javier

    2018-04-01

    A wide array of microorganisms colonizes distinctive anatomical regions of animals, being the intestine the one that harbors the most abundant and complex microbiota. Phylogenetic analyses indicate that it is composed mainly of bacteria, and that Bacterioidetes and Firmicutes are the most represented phyla (>90% of the total eubacteria) in mice and humans. Intestinal microbiota plays an important role in host physiology, contributing to digestion, epithelial cells metabolism, stimulation of intestinal immune responses, and protection against intestinal pathogens. Changes in its composition may affect intestinal homeostasis, a condition known as dysbiosis, which may lead to non-specific inflammation and disease. The aim of this work was to analyze the effect that a bacteria-specific systemic immune response would have on the intestinal re-colonization by that particular bacterium. Bacteria were isolated and identified from the feces of Balb/c mice, bacterial cell-free extracts were used to immunize the same mice from which bacteria came from. Concurrently with immunization, mice were subjected to a previously described antibiotic-based protocol to eliminate most of their intestinal bacteria. Serum IgG and feces IgA, specific for the immunizing bacteria were determined. After antibiotic treatment was suspended, specific bacteria were orally administered, in an attempt to specifically re-colonize the intestine. Results showed that parenteral immunization with gut-derived bacteria elicited the production of both anti-bacterial IgG and IgA, and that immunization reduces bacteria specific recolonization of the gut. These findings support the idea that the systemic immune response may, at least in part, determine the bacterial composition of the gut. Copyright © 2018. Published by Elsevier B.V.

  13. The mucosal firewalls against commensal intestinal microbes.

    Science.gov (United States)

    Macpherson, Andrew J; Slack, Emma; Geuking, Markus B; McCoy, Kathy D

    2009-07-01

    Mammals coexist with an extremely dense microbiota in the lower intestine. Despite the constant challenge of small numbers of microbes penetrating the intestinal surface epithelium, it is very unusual for these organisms to cause disease. In this review article, we present the different mucosal firewalls that contain and allow mutualism with the intestinal microbiota.

  14. The mechanism of circulatory disturbances in the small intestinal wall and their role in the development of intestinal syndrome

    International Nuclear Information System (INIS)

    Kudryavtsev, V.D.; Sushkevich, L.N.

    1980-01-01

    The mechanism of vascular disorders in the wall of the small intestine, the possibility of correcting them and their significance in the development of the intestinal syndrome were analysed. The experiments in which Wistar rats were irradiated with 10 Gy yielded information on the blood flow in the small intestine, on the number of regenerating crypts, on the blood plasma volume and on arterial blood pressure. The data obtained justify to speak of an important influence of disturbances in general hemodynamics on the microcirculation in the entire organ. Reaction that fail to take place or paradoxic changes in the blood flow of tissue after injection of vasoactive substances also illustrate the significance of direct intestinal vascular damage for adversely affecting compensatory adaptation mechanisms. Markedly disturbed blood supply to the tissue and the resultant deterioration of tissue trophism at the level of an intestinal syndrome not only intensify radiogenic destructive processes in epitheliocytes, but also prevent to a certain extent the regeneration of mucous membrane of the small intestine. The possibility of achieving partial restoration of blood vessel speed in the small intestine of irradiated rats is shown if the loss of intravascular fluid is parenterally replaced with Ringer's or hemodilution solution. (author)

  15. Cytokine Tuning of Intestinal Epithelial Function

    Directory of Open Access Journals (Sweden)

    Caroline Andrews

    2018-06-01

    Full Text Available The intestine serves as both our largest single barrier to the external environment and the host of more immune cells than any other location in our bodies. Separating these potential combatants is a single layer of dynamic epithelium composed of heterogeneous epithelial subtypes, each uniquely adapted to carry out a subset of the intestine’s diverse functions. In addition to its obvious role in digestion, the intestinal epithelium is responsible for a wide array of critical tasks, including maintaining barrier integrity, preventing invasion by microbial commensals and pathogens, and modulating the intestinal immune system. Communication between these epithelial cells and resident immune cells is crucial for maintaining homeostasis and coordinating appropriate responses to disease and can occur through cell-to-cell contact or by the release or recognition of soluble mediators. The objective of this review is to highlight recent literature illuminating how cytokines and chemokines, both those made by and acting on the intestinal epithelium, orchestrate many of the diverse functions of the intestinal epithelium and its interactions with immune cells in health and disease. Areas of focus include cytokine control of intestinal epithelial proliferation, cell death, and barrier permeability. In addition, the modulation of epithelial-derived cytokines and chemokines by factors such as interactions with stromal and immune cells, pathogen and commensal exposure, and diet will be discussed.

  16. Lynch syndrome-related small intestinal adenocarcinomas.

    Science.gov (United States)

    Jun, Sun-Young; Lee, Eui-Jin; Kim, Mi-Ju; Chun, Sung Min; Bae, Young Kyung; Hong, Soon Uk; Choi, Jene; Kim, Joon Mee; Jang, Kee-Taek; Kim, Jung Yeon; Kim, Gwang Il; Jung, Soo Jin; Yoon, Ghilsuk; Hong, Seung-Mo

    2017-03-28

    Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas.

  17. A comparative study on the metabolism of Epimedium koreanum Nakai-prenylated flavonoids in rats by an intestinal enzyme (lactase phlorizin hydrolase) and intestinal flora.

    Science.gov (United States)

    Zhou, Jing; Chen, Yan; Wang, Ying; Gao, Xia; Qu, Ding; Liu, Congyan

    2013-12-24

    The aim of this study was to compare the significance of the intestinal hydrolysis of prenylated flavonoids in Herba Epimedii by an intestinal enzyme and flora. Flavonoids were incubated at 37 °C with rat intestinal enzyme and intestinal flora. HPLC-UV was used to calculate the metabolic rates of the parent drug in the incubation and LC/MS/MS was used to determine the chemical structures of metabolites generated by different flavonoid glycosides. Rates of flavonoid metabolism by rat intestinal enzyme were quicker than those of intestinal flora. The sequence of intestinal flora metabolic rates was icariin>epimedin B>epimedin A>epimedin C>baohuoside I, whereas the order of intestinal enzyme metabolic rates was icariin>epimedin A>epimedin C>epimedin B>baohuoside I. Meanwhile, the LC/MS/MS graphs showed that icariin produced three products, epimedin A/B/C had four and baohuoside I yielded one product in incubations of both intestinal enzyme and flora, which were more than the results of HPLC-UV due to the fact LC/MS/MS has lower detectability and higher sensitivity. Moreover, the outcomes indicated that the rate of metabolization of flavonoids by intestinal enzyme were faster than those of intestinal flora, which was consistent with the HPLC-UV results. In conclusion, the metabolic pathways of the same components by intestinal flora and enzyme were the same. What's more, an intestinal enzyme such as lactase phlorizin hydrolase exhibited a more significant metabolic role in prenylated flavonoids of Herba Epimedi compared with intestinal flora.

  18. Plasma intestinal fatty acid binding protein (I-FABP) concentrations increase following intestinal ischemia in pigs

    NARCIS (Netherlands)

    Niewold, T.A.; Meinen, M.; Meulen, van der J.

    2004-01-01

    Intestinal fatty acid binding protein (I-FABP) is an intracellular epithelial protein in the intestinal mucosa of many animals. IFABP appears in the circulation following epithelial damage, and in humans, is proven to be a parameter for damage to the mucosa. In this paper, an ELISA test designed for

  19. [Primary intestinal lymphangiectasia (Waldmann's disease)].

    Science.gov (United States)

    Vignes, S; Bellanger, J

    2017-08-31

    Primary intestinal lymphangiectasia (PIL), Waldmann's disease, is a rare disorder of unknown etiology characterized by dilated intestinal lacteals leading to lymph leakage into the small-bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. The main symptom is bilateral lower limb edema. Edema may be moderate to severe including pleural effusion, pericarditis or ascites. Protein-losing enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance and diagnosis by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of biopsies. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Several B-cell lymphomas of the gastrointestinal tract or with extra-intestinal localizations were reported in PIL patients. A long-term strictly low-fat diet associated with medium-chain triglyceride and liposoluble vitamin supplementation is the cornerstone of PIL medical management. Octreotide, a somatostatin analog, have been proposed with an inconsistent efficacy in association with diet. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. A prolonged clinical and biological follow-up is recommended. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  20. Intestinal circulation during inhalation anesthesia

    International Nuclear Information System (INIS)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-01-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86 Rb and 9-microns spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO 2 ) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines