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Sample records for decreases acute mucosal

  1. Dexmedetomidine decreases the oral mucosal blood flow.

    Science.gov (United States)

    Kawaai, Hiroyoshi; Yoshida, Kenji; Tanaka, Eri; Togami, Kohei; Tada, Hitoshi; Ganzberg, Steven; Yamazaki, Shinya

    2013-12-01

    There is an abundance of blood vessels in the oral cavity, and intraoperative bleeding can disrupt operations. There have been some interesting reports about constriction of vessels in the oral cavity, one of which reported that gingival blood flow in cats is controlled by sympathetic α-adrenergic fibres that are involved with vasoconstriction. Dexmedetomidine is a sedative and analgesic agent that acts through the α-2 adrenoceptor, and is expected to have a vasoconstrictive action in the oral cavity. We have focused on the relation between the effects of α-adrenoceptors by dexmedetomidine and vasoconstriction in oral tissues, and assessed the oral mucosal blood flow during sedation with dexmedetomidine. The subjects comprised 13 healthy male volunteers, sedated with dexmedetomidine in a loading dose of 6 μg/kg/h for 10 min and a continuous infusion of 0.7 μg/kg/h for 32 min. The mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), and palatal mucosal blood flow (PMBF) were measured at 0, 5, 10, 12, 22, and 32 min after the start of the infusion. The HR, CO, and PBMF decreased significantly during the infusion even though there were no differences in the SV. The SVR increased significantly but the PMBF decreased significantly. In conclusion, PMBF was reduced by the mediating effect of dexmedetomidine on α-2 adrenoceptors.

  2. Mucosal Immunity and acute viral gastroenteritis.

    Science.gov (United States)

    Rose, Markus A

    2014-01-01

    Acute gastroenteritis is a major killer of the very young worldwide. Rotavirus is the most common intestinal virus, causing acute gastroenteritis and extra-intestinal complications especially in young and chronically ill subjects. As early as 1991, the WHO recommended as high priority the development of a vaccine against rotavirus, the major pathogen causing enteric infections. Since the introduction of rotavirus vaccines for infant immunization programmes in different parts of the world in 2006, vaccination against rotavirus has resulted in substantial declines in severe gastroenteritis. The oral rotavirus vaccines RotaTeq(®) and Rotarix(®) are excellent examples for their unique features and principles of mucosal immunization. We elaborate on rotavirus immunity and the success of rotavirus vaccination and aspects also beyond infants' acute gastroenteritis.

  3. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    Directory of Open Access Journals (Sweden)

    Minmin Li

    2015-01-01

    Full Text Available The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2 and cyclooxygenase- (COX- 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

  4. Prevention of acute gastric mucosal lesions by Solcoseryl.

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    Brzozowski, T; Radecki, T; Sendur, R; Gustaw, P; Konturek, S J

    1987-04-01

    Solcoseryl, a deproteinized extract from calf blood containing various biologically active substances, has been reported to promote the healing of skin wounds and gastric ulceration In this study, the gastroprotective effects of Solcoseryl vis-a-vis acute gastric mucosal damage were examined in rats. Solcoseryl significantly reduced the formation of acute lesions induced by intragastric application of absolute ethanol or acidified taurocholate and by water immersion and restraint stress, but failed to affect those caused by acidified aspirin. Since Solcoseryl did not offer protection in the absence of mucosal prostaglandins (PG) e.g. in aspirin-induced gastric damage, it is likely that PG may be involved in the observed gastroprotective activity of the drug. Solcoseryl failed to affect gastric acid or pepsin secretion, but increased mucosal blood flow. Thus PG generated by Solcoseryl might contribute to the maintenance of the observed mucosal microcirculation and the prevention of lesion formation by corrosive substances and stress conditions.

  5. A critical role of gastric mucosal ascorbic acid in the progression of acute gastric mucosal lesions induced by compound 48/80 in rats

    Institute of Scientific and Technical Information of China (English)

    Yoshio Kamiya; Yoshiji Ohta; Yoichiro Imai; Tomiyasu Arisawa; Hiroshi Nakano

    2005-01-01

    AIM: To study the role of gastric mucosal ascorbic acid(AA) in the progression of acute gastric mucosal lesions induced by compound 48/80 (C48/80), a mast cell degranulator, in rats.METHODS: C48/80 (0.75 mg/kg) was intraperitoneally injected to fasted Wistar rats. Oral administration of AA (10, 50 or 100 mg/kg) was performed 0.5 h after C48/80treatment. Determinations for gastric mucosal lesion severity and blood flow, and assays for gastric mucosal total AA, reduced AA, oxidized AA, vitamin E, thiobarbituric acid reactive substances (TBARS), adherent mucus, nitrite/nitrate (NOx), non-protein SH (NPSH), and myeloperoxidase(MPO), and serum total AA, reduced AA, oxidized AA,and NOx were conducted 0.5 and 3 h after C48/80treatment.RESULTS: Gastric mucosal lesions occurred 0.5 h after C48/80 treatment and progressed at 3 h. Gastric mucosal blood flow decreased 0.5 h after C48/80 treatment but the decrease was recovered at 3 h. Gastric mucosal total AA, reduced AA, vitamin E, and adherent mucus concentrations decreased 3 h after C48/80 treatment.Gastric mucosal oxidized AA concentration remained unchanged after C48/80 treatment. Gastric mucosal NPSH concentration decreased 0.5 h after C48/80 treatment,but the decrease was recovered at 3 h. Gastric mucosal TBARS concentration and MPO activity increased 0.5 h after C48/80 treatment and further increased at 3 h.Serum total AA and reduced AA concentrations increased 0.5 h after C48/80 treatment and further increased at 3 h, while serum oxidized AA concentration increased at 0.5 h. Serum and gastric mucosal NOx concentrations increased 3 h after C48/80 treatment. AA administration to C48/80-treated rats at 0.5 h after the treatment prevented the gastric mucosal lesion progression and the changes in gastric mucosal total AA, reduced AA, vitamin E, adherent mucus, NOx, and TBARS concentrations and MPO activity and serum NOx concentration found at 3 h after the treatment dose-dependently. The AA administration to C48/80-treated

  6. Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80

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    Sena Lee

    2014-04-01

    Full Text Available The protective effect of ginsenoside Re, isolated from ginseng berry, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (C48/80. Ginsenoside Re (20 mg/kg or 100 mg/kg was orally administered 0.5 h prior to C48/80 treatment. Ginsenoside Re dose-dependently prevented gastric mucosal lesion development 3 h after C48/80 treatment. Increases in the activities of myeloperoxidase (MPO; an index of neutrophil infiltration and xanthine oxidase (XO and the content of thiobarbituric acid reactive substances (TBARS; an index of lipid peroxidation and decreases in the contents of hexosamine (a marker of gastric mucus and adherent mucus, which occurred in gastric mucosal tissues after C48/80 treatment, were significantly attenuated by ginsenoside Re. The elevation of Bax expression and the decrease in Bcl2 expression after C48/80 treatment were also attenuated by ginsenoside Re. Ginsenoside Re significantly attenuated all these changes 3 h after C48/80 treatment. These results indicate that orally administered ginsenoside Re protects against C48/80-induced acute gastric mucosal lesions in rats, possibly through its stimulatory action on gastric mucus synthesis and secretion, its inhibitory action on neutrophil infiltration, and enhanced lipid peroxidation in the gastric mucosal tissue.

  7. Acute appendicitis following endoscopic mucosal resection of cecal adenoma.

    Science.gov (United States)

    Nemoto, Yukako; Tokuhisa, Junya; Shimada, Nagasato; Gomi, Tatsuya; Maetani, Iruru

    2015-07-21

    Endoscopic mucosal resection (EMR) allows the removal of flat or sessile lesions, laterally spreading tumors, and carcinoma of the colon or the rectum limited to the mucosa or the superficial submucosa. Acute appendicitis is the most common abdominal emergency requiring emergency surgery, and it is also a rare complication of diagnostic colonoscopy and therapeutic endoscopy, including EMR. In the case presented here, a 53-year-old female underwent colonoscopy due to a positive fecal occult blood test and was diagnosed with cecal adenoma. She was referred to our hospital and admitted for treatment. The patient had no other symptoms. EMR was performed, and 7 h after the surgery, the patient experienced right -lower abdominal pain. Laboratory tests performed the following day revealed a WBC count of 16000/mm(3), a neutrophil count of 14144/mm(3), and a C-reactive protein level of 2.20 mg/dL, indicating an inflammatory response. Computed tomography also revealed appendiceal wall thickening and swelling, so acute appendicitis following EMR was diagnosed. Antibiotics were initiated leading to total resolution of the symptoms, and the patient was discharged on the sixth post-operative day. Pathological analysis revealed a high-grade cecal tubular adenoma. Such acute appendicitis following EMR is extremely rare, and EMR of the cecum may be a rare cause of acute appendicitis.

  8. Acute effects of Helicobacter pylori extracts on gastric mucosal blood flow in the mouse

    Institute of Scientific and Technical Information of China (English)

    Johanna Henriksn(a)s; Christer Atuma; Mia Phillipson; Stellan Sandler; Lars Engstrand; Lena Holm

    2009-01-01

    AIM: To investigate the mechanisms underlying the reduction in gastric blood flow induced by a luminal water extract of Helicobacter pylori (HPE). METHODS: The stomachs of isoflurane-anesthetized mice were exteriorized, and the mucosal surface exposed. Blood flow was measured with the laser Doppler technique, and systemic arterial blood pressure monitored. C57BL/6 mice were exposed to water extract produced from H pylori strain 88-23. To investigate the role of a nerve- or iNOS-mediated pathway, we used intraluminal lidocaine and iNOS-/-mice. Blood flow response to the endogenous nitric oxide synthase inhibitor asymmetric dimethyl arginine (ADMA) was also assessed. RESULTS: In wild-type mice, HPE decreased mucosal blood flow by approximately 30%. This reduction was abolished in iNOS-deficient mice, and by pre-treatment with lidocaine. Luminally applied ADMA resulted in reduction in blood flow similar to that observed in wildtype mice exposed to HPE. CONCLUSION: A H pylori water extract reduces gastric mucosal blood flow acutely through iNOS- and nerve-mediated pathways.

  9. Effects of traditional Chinese medicine on intestinal mucosal permeability in early phase of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    CHEN Hong; LI Fei; JIA Jian-guo; DIAO Yong-peng; LI Zong-xin; SUN Jia-bang

    2010-01-01

    Background Traditional Chinese medicine has been used widely for many years in China to treat acute pancreatitis.We have investigated the effects of Dachengqi decoction on intestinal mucosal permeability and outcome in patients with severe acute pancreatitis (SAP).Methods Forty patients with sustained SAP that required admission to the surgical intensive care unit were enrolled prospectively in the study. All of these patients were divided randomly into the Dachengqi decoction group (n=20) and control group (n=20) on admission. Intestinal permeability was assessed by measuring absorption of two metabolically inert markers, lactulose (L) and mannitol (M), which were administered orally. Serum concentrations of endotoxin (lipopolysaccharide, LPS) and the ratio of lactulose to mannitol in urine (L/M) were detected in all patients.Results Compared with those in the control group, urinary L/M ratio decreased significantly in the Dachengqi decoction group on the 7th day after admission (P=0.001). Also, serum concentrations of LPS were reduced on the 5th and 7th day after admission (P=0.006, P=0.008, respectively). Incidence of multiple organ dysfunction syndrome (MODS) and pancreatic infection was significantly lower in the Dachengqi decoction group compared with those in the control group (P=0.038, P=0.025, respectively).Conclusion Dachengqi decoction may promote the recovery of intestinal mucosal permeability and decrease the incidence of MODS and pancreatic infection in patients with SAP.

  10. Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Xiao-chang LIU; Qiao MEI; Jian-ming XU; Jing HU

    2009-01-01

    Aim:To investigate the effect of balsalazine treatment on intestinal mucosal permeability in dextran sulfate sodium (DSS)-induced colitis and to determine the mechanism of the balsalazine-induced changes.Methods:Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS.Balsalazine was administered intragastrically at doses of 42,141,and 423 mg/kg.The disease activity index (DAI) score was evaluated and colon tissue was collected for the assessment of histological changes.The amount of malondialdehyde (MDA) in the colon was determined,along with the activity of myeloperoxidase (MPO),superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor (TNF)-α and interferon (IFN)-Y.The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue.Results:Balsalazine was found to reduce the DAI score and the histological index (HI) score,decrease the MDA content and the activity of MPO,and increase the activity of SOD and GSH-Px in colitis mice.At the same time,balsalazine ameliorated microvillus and tight junction structure,resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-α and IFN-Y in colitis mice.Conclusion:In colitis mice,the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability.The mechanism of this effect is partly associated with balsalazine's antioxidative and anti-inflammatory effects.

  11. Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia:a case-control study

    Institute of Scientific and Technical Information of China (English)

    Dorina Lauritano; Massimo Petruzzi; Dario Di Stasio; Alberta Lucchese

    2014-01-01

    The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition (P50.002), duration of mucositis (P50.003) and the average grade of mucositis (P50.03). The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering from leukaemia.

  12. Palifermin and Chlorhexidine Mouthwashes in Prevention of Chemotherapy-Induced Mucositis in Children with Acute Lymphocytic Leukemia: a Randomized Controlled Trial.

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    Gholizadeh, Narges; Mehdipoor, Masoumeh; Sajadi, Hasan; Moosavi, Mahdieh-Sadat

    2016-12-01

    Over the past three decades, significant improvements have been achieved in the survival of children with cancer. However, the considerable morbidity which occurs as a result of chemotherapy often restricts the treatment intensity. One of the important dose-limiting and costly adverse effects of cancer therapy is mucositis. Children with hematological malignancies are greatly at risk of developing mucositis. This study aimed to assess the effectiveness of palifermin in preventing mucositis in children with acute lymphocytic leukemia (ALL) who undergo chemotherapy. In this clinical trial, 90 children with ALL were randomized to receive chlorhexidine (n=45) or palifermin (n=45). One group received 60 μg/ kg/ day palifermin as an intravenous bolus once daily for 3 days before and 3 days after the chemotherapy. Chlorhexidine mouthwash was administered once daily for 3 days before and 3 days after the chemotherapy. The world health organization (WHO) oral toxicity scale was employed for grading the mucositis. The data were analyzed by using two-way ANOVA. The two groups were matched for age and gender. The study groups were significantly different in terms of mucositis grading (P values after 1 and 2 week therapy were 0.00). Palifermin decreased the incidence and severity of chemotherapy-induced mucositis. Palifermin reduces the oral mucositis in children with ALL. Several mechanisms of action are suggested for keratinocyte growth factor (such as palifermin) including promotion of cell proliferation and cytoprotection, restraining the apoptosis, and changing the cytokine profile.

  13. Relative defects in mucosal immunity predict acute graft-versus-host disease.

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    August, Keith J; Chiang, K-Y; Qayed, Muna; Dulson, Ashley; Worthington-White, Diana; Cole, Conrad R; Horan, John T

    2014-07-01

    Impairment of gut mucosal immunity by the transplant process could facilitate translocation of commensal bacteria and thereby augment the graft-versus-host response. To begin to assess the influence of gut mucosal immunity on the development of acute graft-versus-host disease (GVHD), we conducted a prospective study in 24 pediatric allogeneic hematopoietic cell transplant recipients, assessing 4 fecal markers of mucosal immunity: calprotectin, soluble CD8 (sCD8), soluble intracellular adhesion molecule 1, and β-defensin-2. Stool samples were collected prospectively on transplant days 0, +5, +10, and +15 and analyzed by ELISA. Lower levels on day +5 (calprotectin and β-defensin-2) and day +10 (calprotectin, β-defensin-2, and sCD8) were associated with subsequent acute GVHD. The most striking difference was with calprotectin on day +10. Patients with levels below 424 mg/kg had an incidence of 77.8%, whereas those with levels above this threshold had a cumulative incidence of 0% (P = .002). Relative defects in gut mucosal immunity may be important in the pathogenesis of acute GVHD.

  14. CELECOXIB - Chemoradiation therapy for reducing mucositis and other acute side effects in advance head and neck carcinoma

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    Izadi Sh

    2009-02-01

    Full Text Available "nBackground: Chemo-radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay or interruption of treatment plan, cyclo-oxygenase 2 (COX2 is an inducible enzyme primarily expressed in inflamed and tumoral tissues. COX-2 inhibitors have shown promise to reduce chemoradiation induce toxicities. We conducted a phase III, randomized double blind clinical trial to evaluate the toxicity and efficacy of celecoxib, a selective COX2 inhibitor, administered concurrently with chemoradiation for locally advanced head and neck cancer. Here in we report the first report about the role of COX-2 inhibitor in acute toxicicities. "nMethods: Patients with stage III/IV (locally advance head and neck carcinoma who referred to department of radiation-oncology were eligible. Patients were treated with chemotherapy with cisplatin concurrently with radiation (60-70Gy. Celecoxib (100mg qid was started at the first day of radiotherapy and was given for a total of 8 weeks. Acute toxicities were evaluated every week by WHO scale. "nResults: One hundred twenty two patients were enrolled into the study, (61 patients for each group. In repeated mesurment analysis of variance there is a significant difference in the time of onset of grade II acute toxicities between the two groups; The mucositis, dysphagia, epidermitis and oral pain score changed significantly over the typical five weeks in two groups but these changes were more sever in placebo group (p=0.0001. In the analysis of the overall changes in the following laboratory parame-ters: WBC, hemoglobin and platelet showed that these parameters decreased over time in both groups without a significant difference between groups. "nConclusion: The results of these study showed that the use of a COX-2 inhibitor (celecoxib that is a safe and inexpensive drug may reduce acute toxicities of chemoradiation specially

  15. Depletion of mucosal substance P in acute otitis media

    DEFF Research Database (Denmark)

    Cayé-Thomasen, Per; Schmidt, Peter Thelin; Hermansson, Ann

    2004-01-01

    OBJECTIVE: The neuropeptide substance P (SP) is an inducer of neurogenic inflammation and bone resorption in the middle ear. Resorption of the bone tissue structures surrounding the middle ear cavity is a distinct feature of the initial stage of acute otitis media (AOM), which may be due to nerve...

  16. Mucosal reactive oxygen species decrease virulence by disrupting Campylobacter jejuni phosphotyrosine signaling.

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    Corcionivoschi, Nicolae; Alvarez, Luis A J; Sharp, Thomas H; Strengert, Monika; Alemka, Abofu; Mantell, Judith; Verkade, Paul; Knaus, Ulla G; Bourke, Billy

    2012-07-19

    Reactive oxygen species (ROS) play key roles in mucosal defense, yet how they are induced and the consequences for pathogens are unclear. We report that ROS generated by epithelial NADPH oxidases (Nox1/Duox2) during Campylobacter jejuni infection impair bacterial capsule formation and virulence by altering bacterial signal transduction. Upon C. jejuni invasion, ROS released from the intestinal mucosa inhibit the bacterial phosphotyrosine network that is regulated by the outer-membrane tyrosine kinase Cjtk (Cj1170/OMP50). ROS-mediated Cjtk inactivation results in an overall decrease in the phosphorylation of C. jejuni outer-membrane/periplasmic proteins, including UDP-GlcNAc/Glc 4-epimerase (Gne), an enzyme required for N-glycosylation and capsule formation. Cjtk positively regulates Gne by phosphorylating an active site tyrosine, while loss of Cjtk or ROS treatment inhibits Gne activity, causing altered polysaccharide synthesis. Thus, epithelial NADPH oxidases are an early antibacterial defense system in the intestinal mucosa that modifies virulence by disrupting bacterial signaling.

  17. EFFECT OF HELICOBACTER PYLORI INFECTION ON ACUTE STRESS-RELATED GASTRIC MUCOSAL DAMAGE OF SERIOUSLY ILL PATIENTS

    Institute of Scientific and Technical Information of China (English)

    赵超; 肖文; 叶光福; 周建平; 周其璋

    2002-01-01

    Emergency endoscopy studies have shown that the most of seriously ill patients develop acute stress-related mucosal damage and ulceration within 24 hours of admission, which manifest the upper gastrointestinal tract

  18. Palifermin and Chlorhexidine Mouthwashes in Prevention of Chemotherapy-Induced Mucositis in Children with Acute Lymphocytic Leukemia: a Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Narges Gholizadeh

    2016-12-01

    Full Text Available Statement of the Problem: Over the past three decades, significant improvements have been achieved in the survival of children with cancer. However, the considerable morbidity which occurs as a result of chemotherapy often restricts the treatment intensity. One of the important dose-limiting and costly adverse effects of cancer therapy is mucositis. Children with hematological malignancies are greatly at risk of developing mucositis. Purpose: This study aimed to assess the effectiveness of palifermin in preventing mucositis in children with acute lymphocytic leukemia (ALL who undergo chemotherapy. Materials and Method: In this clinical trial, 90 children with ALL were randomized to receive chlorhexidine (n=45 or palifermin (n=45. One group received 60 μg/ kg/ day palifermin as an intravenous bolus once daily for 3 days before and 3 days after the chemotherapy. Chlorhexidine mouthwash was administered once daily for 3 days before and 3 days after the chemotherapy. The world health organization (WHO oral toxicity scale was employed for grading the mucositis. The data were analyzed by using two-way ANOVA. Results: The two groups were matched for age and gender. The study groups were significantly different in terms of mucositis grading (P values after 1 and 2 week therapy were 0.00. Palifermin decreased the incidence and severity of chemotherapy-induced mucositis. Conclusion: Palifermin reduces the oral mucositis in children with ALL. Several mechanisms of action are suggested for keratinocyte growth factor (such as palifermin including promotion of cell proliferation and cytoprotection, restraining the apoptosis, and changing the cytokine profile. Keywords ● Oral Mucositis ● Palifermin ● Leukemia

  19. Gastroprotection studies of Schiff base zinc (II derivative complex against acute superficial hemorrhagic mucosal lesions in rats.

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    Shahram Golbabapour

    Full Text Available BACKGROUND: The study was carried out to assess the gastroprotective effect of the zinc (II complex against ethanol-induced acute hemorrhagic lesions in rats. METHODOLOGY/PRINCIPAL FINDING: The animals received their respective pre-treatments dissolved in tween 20 (5% v/v, orally. Ethanol (95% v/v was orally administrated to induce superficial hemorrhagic mucosal lesions. Omeprazole (5.790×10(-5 M/kg was used as a reference medicine. The pre-treatment with the zinc (II complex (2.181×10(-5 and 4.362×10(-5 M/kg protected the gastric mucosa similar to the reference control. They significantly increased the activity levels of nitric oxide, catalase, superoxide dismutase, glutathione and prostaglandin E2, and decreased the level of malondialdehyde. The histology assessments confirmed the protection through remarkable reduction of mucosal lesions and increased the production of gastric mucosa. Immunohistochemistry and western blot analysis indicated that the complex might induced Hsp70 up-regulation and Bax down-regulation. The complex moderately increased the gastroprotectiveness in fine fettle. The acute toxicity approved the non-toxic characteristic of the complex (<87.241×10(-5 M/kg. CONCLUSION/SIGNIFICANCE: The gastroprotective effect of the zinc (II complex was mainly through its antioxidant activity, enzymatic stimulation of prostaglandins E2, and up-regulation of Hsp70. The gastric wall mucus was also a remarkable protective mechanism.

  20. Altered mucosal immune response after acute lung injury in a murine model of Ataxia Telangiectasia.

    Science.gov (United States)

    Eickmeier, Olaf; Kim, Su Youn; Herrmann, Eva; Döring, Constanze; Duecker, Ruth; Voss, Sandra; Wehner, Sibylle; Hölscher, Christoph; Pietzner, Julia; Zielen, Stefan; Schubert, Ralf

    2014-05-29

    Ataxia telangiectasia (A-T) is a rare but devastating and progressive disorder characterized by cerebellar dysfunction, lymphoreticular malignancies and recurrent sinopulmonary infections. In A-T, disease of the respiratory system causes significant morbidity and is a frequent cause of death. We used a self-limited murine model of hydrochloric acid-induced acute lung injury (ALI) to determine the inflammatory answer due to mucosal injury in Atm (A-T mutated)- deficient mice (Atm(-/-)). ATM deficiency increased peak lung inflammation as demonstrated by bronchoalveolar lavage fluid (BALF) neutrophils and lymphocytes and increased levels of BALF pro-inflammatory cytokines (e.g. IL-6, TNF). Furthermore, bronchial epithelial damage after ALI was increased in Atm(-/-) mice. ATM deficiency increased airway resistance and tissue compliance before ALI was performed. Together, these findings indicate that ATM plays a key role in inflammatory response after airway mucosal injury.

  1. Ligustrazine alleviates gastric mucosal injur y in a rat model of acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Sheng-Chun Dang; Jian-Xin Zhang; Jian-Guo Qu; Xue-Qing Wang; Xin Fan

    2007-01-01

    BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inlfammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inlfammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group C);ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood lfow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score;meanwhile, the levels of serum interleukin-1β(IL-1β) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood lfow in group P was signiifcantly lower than that in group C (P CONCLUSIONS: Decreased gastric blood lfow and increased inlfammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.

  2. Higher levels of mucosal antibody to pneumococcal vaccine candidate proteins are associated with reduced acute otitis media caused by Streptococcus pneumoniae in young children.

    Science.gov (United States)

    Xu, Q; Casey, J R; Pichichero, M E

    2015-09-01

    Mucosal immunity has a crucial role in controlling human respiratory tract infections. This study characterizes the naturally acquired mucosal antibody levels to three Streptococcus pneumoniae (Spn) protein antigens, pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and pneumolysin (Ply), and assesses the association of the mucosal antibody levels with occurrence of acute otitis media (AOM) caused by Spn. Both nasopharyngeal (NP) immunoglobulin G (IgG) and IgA levels to all three proteins slightly decreased in children from 6 to 9 months of age and then gradually increased through 24 months of age. Spn NP colonization was associated with higher mucosal antibody levels to all three proteins. However, children with Spn AOM had 5-8-fold lower IgG and 3-6-fold lower IgA levels to the three proteins than children without AOM but asymptomatically colonized with Spn. Antigen-specific antibody levels in the middle ear fluid (MEF) were correlated with antibody levels in the NP. Children with AOM caused by Spn had lower antibody levels in both the MEF and NP than children with AOM caused by other pathogens. These results indicate that higher naturally acquired mucosal antibody levels to PhtD, PcpA and Ply are associated with reduced AOM caused by Spn.

  3. Acute mucosal radiation reactions in patients with head and neck cancer. Patterns of mucosal healing on the basis of daily examinations

    Energy Technology Data Exchange (ETDEWEB)

    Wygoda, A.; Skladowski, K.; Rutkowski, T.; Hutnik, M.; Golen, M.; Pilecki, B.; Przeorek, W.; Lukaszczyk-Widel, B. [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice (Poland). 1st Dept. of Radiation Oncology

    2012-08-15

    Purpose: The goal of this research was to evaluate the healing processes of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer. Materials and methods: In 46 patients with oral and oropharyngeal cancer patients irradiated with conventional (n = 25) and accelerated (n = 21) dose fractionation AMRR was evaluated daily during and after radiotherapy. Complex of morphological and functional symptoms according to the Dische score were collected daily until complete healing. Results: Duration of healing after the end of radiotherapy ranged widely (12-70 days). It was on the average 8 days longer for accelerated than for conventional radiotherapy (p = 0.016). Duration of dysphagia was also longer for accelerated irradiation (11 days, p = 0.027). Three types of morphological symptoms were observed as the last symptom at the end of AMRR healing: spotted and confluent mucositis, erythema, and edema. Only a slight correlation between healing duration and area of irradiation fields (r = 0.23) was noted. In patients with confluent mucositis, two morphological forms of mucosal healing were observed, i.e., marginal and spotted. The spotted form was noted in 71% of patients undergoing conventional radiotherapy and in 38% of patients undergoing accelerated radiotherapy. The symptoms of mucosal healing were observed in 40% patients during radiotherapy. Conclusion: The wide range of AMRR healing reflects individual potential of mucosa recovery with longer duration for accelerated radiotherapy. Two morphological forms of confluent mucositis healing were present: marginal and spotted. Healing of AMRR during radiotherapy can be observed in a significant proportion of patients. (orig.)

  4. Effect of ecoimmunonutrition supports on maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background One of the major causes of death in severe acute pancreatitis (SAP) is severe infection owing to bacterial translocation. Some clinical studies suggested that ecoimmunonutrition (EIN) as a new strategy had better treatment effect on SAP patients. But the experiment studies on the precise mechanism of the effect of EIN were less reported. In this study, we mainly investigated the effects of EIN on bacterial translocation in SAP model of dogs.Methods SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in healthy hybrid dogs. The SAP dogs were supported with either parenteral nutrition (PN) or elemental enteral nutrition (EEN) or EIN. The levels of serum amylase, serum aminotransferase and plasma endotoxin were detected before and after pancreatitis induction. On the 7th day after nutrition supports, peritoneal fluid, mesenteric lymph nodes (MLN), liver, and pancreas were collected for bacterial culture with standard techniques to observe the incidence of bacterial translocation. Pathology changes of pancreas were analyzed by histopathologic grading and scoring of the severity of pancreas, and the degree of intestinal mucosal damage was assessed by measuring mucosal thickness, villus height, and crypt depth of ileum.Results Compared with PN and EEN, EIN significantly decreased the levels of serum amylase, serum aminotransferase, plasma endotoxin, and the incidence of bacterial translocation. Furthermore, compared with the others, the histology scores of inflammation in pancreas and the ileum injury (ileum mocosa thickness, villus height, and crypt depth) were significantly alleviated by EIN (P<0.05). Moreover, concerning liver function, the serum levels of alanine aminotransferase, aspartate aminotransferase and albumin were ameliorating significantly in the EIN group.Conclusion Our results suggested that EIN could maintain the integrity of intestinal mucosal barrier and reducing the incidence of bacterial translocation

  5. [Changes of Intestinal Mucosal Barrier and Intestinal Flora in Rats with Severe Acute Pancreatitis].

    Science.gov (United States)

    Li, Yan; Wu, Hao; Deng, Yiyun; Liao, Ruyi; Xi, Lili; Yao, Ping

    2015-04-01

    This paper is to explore changes of intestinal mucosal barrier, intestinal flora, and bacterial translocation in rats with severe acute pancreatitis (SAP). Twenty four male SD rats were randomly divided into the control group (n = 10) and the experimental group (n = 14). The model of severe acute pancreatitis of rats was induced by the method of injecting adversely 5% sodium taurocholate into the common biliary-pancreatic duct. All of the rats were killed after 24 hours and the level of the serum amylase and the plasma endotoxin was determined after that. The pathological changes of pancreas and small intestine were observed through hematoxylin-eosin staining (HE staining) and the abdominal viscera bacterial translocation rates were tested. With the method of real-time polymerase chain reaction (RT-PCR) the quantity of the intestinal flora was analyzed. In the control group, the level of Escherichia coli, Lactobacillus and Bifidobacterium were 2.08 ± 1.29, 11.04 ± 7.55 and 12.21 ± 4.95, respectively. On the contrast, the level of Escherichia coli in the cecum contents was much higher (9.72 ± 3.58, P intestines were also significantly higher (P intestinal mucosal barrier was severely damaged and the dysbacteriosis occurs in the intestinal canal. And these might relate to the occurrence and development of multiple organ infection.

  6. Effects of Atractylodis Rhizoma Pharmacopuncture on an Acute Gastric Mucosal Lesion Induced by Compound 48/80 in Rats

    Directory of Open Access Journals (Sweden)

    Lee Yun-Kyu

    2012-03-01

    Full Text Available Objectives: This study was designed to investigate the protective effects of Atractylodis Rhizoma pharmacopuncture (ARP against acute gastric mucosal lesions induced by compound 48/80 in rats. Methods: The ARP was injected in Joksamni (ST36 and Jungwan (CV12 1 hr before treatment with compound 48/80. The animals were sacrificed under anesthesia 3 hrs after treatment with compound 48/80. The stomachs were removed, and the amounts of gastric adherent mucus, gastric mucosal hexosamine, thiobarbituric acid reactive substances (TBARS, xanthine oxidase (XO, and superoxide dismutase (SOD were measured. Also, histological examination were performed. Results: Gastric adherent mucus, gastric mucosal hexosamine and histological defects of gastric mucosa declined significantly after ARP treatment. Changes in gastric mucosal TBARS were also reduced by ARP treatment, but this result was not statistically significant. ARP treatment did not change the XO and the SOD activities. Conclusions: ARP showed protective effects for acute gastric mucosal lesions induced by compound 48/80 in rats. These results suggest that ARP may have protective effects for gastritis.

  7. Effect of adjuvant lactulose enema therapy on outcome and intestinal mucosal barrier function in patients with acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Ling Gao; Ming-Quan Li

    2016-01-01

    Objective:To analyze the effect of adjuvant lactulose enema therapy on outcome and intestinal mucosal barrier function in patients with acute pancreatitis.Methods: A total of 98 patients with acute pancreatitis were randomly divided into observation group and control group, control group received conventional symptomatic treatment, observation group received symptomatic treatment + adjuvant lactulose enema therapy, and differences in levels of inflammatory cytokines, RAAS system-related molecules and mucosal barrier function-related indexes in serum as well as intestinal flora quantity in stool samples were compared between two groups after treatment.Results:Serum inflammatory cytokines IL-1β, IL-6, IL-8, PCT and TNF-α levels of enema group were significantly lower than those of control group; serum RAAS system molecules R, AngI, AngII and ALD levels were significantly lower than those of control group; serum mucosal barrier function indexes D-lactate, LPS, I-FABP and DAO levels were significantly lower than those of control group; the quantity of bifidobacterium and lactobacillus in stool samples were significantly more than those of control group while the quantity of enterobacterium, enterococcus and E. coli were significantly lower than those of control group.Conclusion:Adjuvant lactulose enema therapy can promote the improvement of acute pancreatitis, and restore patients’ intestinal mucosal barrier function.

  8. Oral hygiene care of patients with oral cancer during postoperative irradiation. An alleviating effect on acute radiation mucositis

    Energy Technology Data Exchange (ETDEWEB)

    Katsura, Kouji; Masuko, Noriko; Hayashi, Takafumi [Niigata Univ. (Japan). School of Dentistry; Sugita, Tadashi; Sakai, Kunio; Tsuchida, Emiko; Matsumoto, Yasuo; Sasamoto, Ryuta

    2000-09-01

    To evaluate the effect of oral hygiene care of patients with oral cancer on alleviating acute radiation mucositis. Eighteen patients receiving postoperative radiotherapy for tongue and oral floor cancer were evaluated. Radiotherapy was given in 2 Gy per fraction, 5 times a week for a total dose of 50 Gy in most patients. Radiation field included the tongue and oral floor. During radiotherapy, 8 patients were treated by dento-maxillofacial radiologists with special concern on oral hygiene (oral hygiene group) and the remaining 10 patients were treated with routine dental care (standard medication group). Mucositis were evaluated using JCOG grade and EORTC/RTOG score by radiotherapists or dento-maxillofacial radiologists at 10 Gy intervals. Oral hygiene plans comprised motivation to maintain oral hygiene and establishing the habits of oral self care 4 times per day. Once a week, oral hygiene and oral cleaning of patients were checked by dento-maxillofacial radiologists. Oral self care included mechanical tooth brushing and a chemical mouthwash. No patients with grade 3 and score 4 mucositis were noted in the oral hygiene group. Severe mucositis occurred less frequently in the oral hygiene group than in the standard medication group. Interruption of radiotherapy due to severe mucositis did not occur in the oral hygiene group. On the other hand, interruption of radiotherapy occurred in four patients in the standard medication group, and in three it was due to severe oral pain. Our results suggested that our method of oral hygiene was more effective for alleviating acute radiation mucositis than other methods so far reported. In addition, our method is considered to be useful in preventing rampant dental caries and severe periodontitis due to the xerostomia induced by radiotherapy. (author)

  9. Human Gastric Mucosal Hydrophobicity Does dot Decrease with Helicobacter Pylori Infection or Chronological Age

    Directory of Open Access Journals (Sweden)

    Mohammed S Al-Marhoon

    2005-01-01

    Full Text Available BACKGROUND AND AIMS: Infection with cytotoxin-associated gene A (cagA Helicobacter pylori is associated with severe gastric diseases. Previous studies in humans have reported a decreased gastric hydrophobicity with H pylori infection. The aim of the present study was to differentiate between the effect of cagA+ and cagA- strains on gastric mucus hydrophobicity.

  10. Acutely decreased thermoregulatory energy expenditure or decreased activity energy expenditure both acutely reduce food intake in mice.

    Directory of Open Access Journals (Sweden)

    Karl J Kaiyala

    Full Text Available Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1 increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2 exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21 °C to 28 °C rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40 ± 1% and dark cycle energy expenditure (15 ± 3% at normal ambient temperature (21 °C. Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65 ± 7%, thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14 ± 2% at 21 °C; 21 ± 4% at 28 °C, while food intake was reduced during the dark cycle (0.9 ± 0.1 g in mice housed at 28 °C, but during the light cycle (0.3 ± 0.1 g in mice housed at 21 °C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R(2 = 0.51, p<0.01. We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure.

  11. Prediction of Acute Radiation Mucositis using an Oral Mucosal Dose Surface Model in Carbon Ion Radiotherapy for Head and Neck Tumors.

    Directory of Open Access Journals (Sweden)

    Atsushi Musha

    Full Text Available To evaluate the dose-response relationship for development of acute radiation mucositis (ARM using an oral mucosal dose surface model (OMDS-model in carbon ion radiotherapy (C-ion RT for head and neck tumors.Thirty-nine patients receiving C-ion RT for head and neck cancer were evaluated for ARM (once per week for 6 weeks according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.0, and the Radiation Therapy Oncology Group (RTOG scoring systems. The irradiation schedule typically used was 64 Gy [relative biological effectiveness (RBE] in 16 fractions for 4 weeks. Maximum point doses in the palate and tongue were compared with ARM in each patient.The location of the ARM coincided with the high-dose area in the OMDS-model. There was a clear dose-response relationship between maximum point dose and ARM grade assessed using the RTOG criteria but not the CTCAE. The threshold doses for grade 2-3 ARM in the palate and tongue were 43.0 Gy(RBE and 54.3 Gy(RBE, respectively.The OMDS-model was useful for predicting the location and severity of ARM. Maximum point doses in the model correlated well with grade 2-3 ARM.

  12. Divergent mucosal and systemic responses in children in response to acute otitis media.

    Science.gov (United States)

    Verhoeven, D; Pichichero, M E

    2014-10-01

    Acute otitis media (AOM), induced by respiratory bacteria, is a significant cause of children seeking medical attention worldwide. Some children are highly prone to AOMs, suffering three to four recurrent infections per year (prone). We previously determined that this population of children could have diminished anti-bacterial immune responses in peripheral blood that could fail to limit bacterial colonization in the nasopharynx (NP). Here, we examined local NP and middle ear (ME) responses and compared them to peripheral blood to examine whether the mucosa responses were similar to the peripheral blood responses. Moreover, we examined differences in effector cytokine responses between these two populations in the NP, ME and blood compartments at the onset of an AOM caused by either Streptococcus pneumoniae or non-typeable Haemophilus influenzae. We found that plasma effector cytokines patterned antigen-recall responses of CD4 T cells, with lower responses detected in prone children. ME cytokine levels did not mirror blood, but were more similar to the NP. Interferon (IFN)-γ and interleukin (IL)-17 in the NP were similar in prone and non-prone children, while IL-2 production was higher in prone children. The immune responses diverged in the mucosal and blood compartments at the onset of a bacterial ME infection, thus highlighting differences between local and systemic immune responses that could co-ordinate anti-bacterial immune responses in young children.

  13. Oral Pseudoephedrine Decreases the Rate of Trans-mucosal Nitrous Oxide Exchange for the Middle Ear

    Science.gov (United States)

    Teixeira, Miriam S.; Alper, Cuneyt M.; Martin, Brian S; Cullen Doyle, Brendan M.; Doyle, William J.

    2015-01-01

    Objective Determine if oral pretreatment with a vasoconstrictor decreases the blood to middle-ear exchange-rate of the perfusion-limited gas, Nitrous Oxide (N2O). Study Design Randomized, double-blind, crossover study. Methods Ten adult subjects with and 10 without past middle-ear disease completed paired experimental sessions, identical but for oral pretreatment with either pseudoephedrine HCL or lactose placebo. At each session, subjects were fitted with a non-rebreathing mask and breathed room air for 20 minutes (acclimation period), 50% N2O:50% O2 for 20 minutes (experimental period) and 100% O2 for 10 minutes (recovery period). Throughout, heart-rate, blood-pressure and O2 saturation were monitored and bilateral middle-ear pressures were recorded by tympanometry every minute. The primary outcome was the slope of the middle-ear pressure-time function for the experimental period which estimates the volume N2O exchange-rate. Using repeated measures ANOVA, the effects of Group (disease history), Treatment (active vs. placebo) and Period (1 vs. 2) on the recorded vital signs, and of Group, Treatment and Ear (left/right) on the middle-ear pressure-time slope were evaluated for statistical significance. Results Statistically significant effects of Period on O2 saturation (Period 2>Period 1) and of Treatment on heart-rate (Active>Placebo) were documented. Only Treatment was statistically significant for the middle-ear pressure-time slope with a shallower slope characterizing the active treatment session. Conclusion The volume exchange-rate across the middle-ear mucosa of perfusion-limited gases can be modulated pharmacologically. Theoretically, similar drugs can be used to reduce the requisite Eustachian tube opening efficiency for adequate middle-ear pressure regulation. PMID:26152838

  14. Antibody blockade of IL-17 family cytokines in immunity to acute murine oral mucosal candidiasis.

    Science.gov (United States)

    Whibley, Natasha; Tritto, Elaine; Traggiai, Elisabetta; Kolbinger, Frank; Moulin, Pierre; Brees, Dominique; Coleman, Bianca M; Mamo, Anna J; Garg, Abhishek V; Jaycox, Jillian R; Siebenlist, Ulrich; Kammüller, Michael; Gaffen, Sarah L

    2016-06-01

    Antibodies targeting IL-17A or its receptor, IL-17RA, are approved to treat psoriasis and are being evaluated for other autoimmune conditions. Conversely, IL-17 signaling is critical for immunity to opportunistic mucosal infections caused by the commensal fungus Candida albicans, as mice and humans lacking the IL-17R experience chronic mucosal candidiasis. IL-17A, IL-17F, and IL-17AF bind the IL-17RA-IL-17RC heterodimeric complex and deliver qualitatively similar signals through the adaptor Act1. Here, we used a mouse model of acute oropharyngeal candidiasis to assess the impact of blocking IL-17 family cytokines compared with specific IL-17 cytokine gene knockout mice. Anti-IL-17A antibodies, which neutralize IL-17A and IL-17AF, caused elevated oral fungal loads, whereas anti-IL-17AF and anti-IL-17F antibodies did not. Notably, there was a cooperative effect of blocking IL-17A, IL-17AF, and IL-17F together. Termination of anti-IL-17A treatment was associated with rapid C. albicans clearance. IL-17F-deficient mice were fully resistant to oropharyngeal candidiasis, consistent with antibody blockade. However, IL-17A-deficient mice had lower fungal burdens than anti-IL-17A-treated mice. Act1-deficient mice were much more susceptible to oropharyngeal candidiasis than anti-IL-17A antibody-treated mice, yet anti-IL-17A and anti-IL-17RA treatment caused equivalent susceptibilities. Based on microarray analyses of the oral mucosa during infection, only a limited number of genes were associated with oropharyngeal candidiasis susceptibility. In sum, we conclude that IL-17A is the main cytokine mediator of immunity in murine oropharyngeal candidiasis, but a cooperative relationship among IL-17A, IL-17AF, and IL-17F exists in vivo. Susceptibility displays the following hierarchy: IL-17RA- or Act1-deficiency > anti-IL-17A + anti-IL-17F antibodies > anti-IL-17A or anti-IL-17RA antibodies > IL-17A deficiency.

  15. Role of acute elevation of portal venous pressure by exogenous glucagon on gastric mucosal injury in rats with portal hypertension.

    Science.gov (United States)

    Tsui, C P; Sung, Joseph J Y; Leung, Felix W

    2003-07-18

    Time-course studies revealed the increased susceptibility of the gastric mucosa to noxious injury in portal hypertension correlates with the level of elevated portal venous pressure and hyperglucagonemia. Whether acute elevation of portal venous pressure by exogenous glucagon aggravates such injury is not known. We tested the hypothesis that glucagon in a dose sufficient to acutely elevate portal venous pressure aggravates noxious injury of the gastric mucosa in rats with portal hypertension. Infusion of a portal hypotensive dose of somatostatin should reverse these changes. In anesthetized rats with portal vein ligation, glucagon, somatostatin or the combination was administered intravenously in a randomized, coded fashion. Acidified ethanol-induced gastric mucosal injury was determined. Portal venous pressure and gastric mucosal perfusion and oxygenation (reflectance spectrophotometry) were monitored to confirm the effects of the respective intravenous treatments. Exogenous glucagon exacerbated acidified ethanol-induced gastric mucosal injury. The exacerbation was attenuated by somatostatin. These changes paralleled the portal hypertensive and hypotensive effects of glucagon and somatostatin, respectively. Our data suggest that a unique mechanism is triggered with the onset of portal hypertension. In an antagonistic manner, glucagon and somatostatin modulate this novel mechanism that controls portal venous pressure and susceptibility of the gastric mucosa to noxious injury.

  16. Peak heart rate decreases with increasing severity of acute hypoxia

    DEFF Research Database (Denmark)

    Lundby, C; Araoz, M; Van Hall, Gerrit

    2001-01-01

    The purpose of the present study was to investigate the degree to which peak heart rate is reduced during exhaustive exercise in acute hypoxia. Five sea-level lowlanders performed maximal exercise at normobaric normoxia and at three different levels of hypobaric hypoxia (barometric pressures of 518......, 459, and 404 mmHg) in a hypobaric chamber and while breathing 9% O(2) in N(2). These conditions were equivalent to altitudes of 3300, 4300, 5300, and 6300 m above sea level, respectively. At 4300 m, maximal exercise was also repeated after 4 and 8 h. Peak heart rate (HR) decreased from 191 (182...

  17. Mucosal immunization with PsaA protein, using chitosan as a delivery system, increases protection against acute otitis media and invasive infection by Streptococcus pneumoniae.

    Science.gov (United States)

    Xu, J-H; Dai, W-J; Chen, B; Fan, X-Y

    2015-03-01

    As infection with Streptococcus pneumoniae (mainly via the mucosal route) is a leading cause of acute otitis media, sinus and bacterial pneumonia, the mucosal immunity plays an important role in the prevention of pneumococcal diseases. Therefore, intranasal vaccination may be an effective immunization strategy, but requires appropriate mucosal vaccine delivery systems. In this work, chitosan was used as a mucosal delivery system to form chitosan-PsaA nanoparticles based on ionotropic gelation methods and used to immunize BALB/c mice intranasally. Compared to mice immunized with naked PsaA, levels of IFN-γ, IL-17A and IL-4 in spleen lymphocytes, the systemic (IgG in serum) and mucosal (IgA in mucosal lavage) specific antibodies were enhanced significantly in mice inoculated with chitosan-PsaA. Furthermore, increased protection against acute otitis media following middle ear challenge with pneumococcus serotype 14, and improved survival following intraperitoneal challenge with pneumococcus serotype 3 or serotype 14, was found in the mice immunized with chitosan-PsaA nanoparticles. Thus, intranasal immunization with chitosan-PsaA can successfully induce mucosal and systemic immune responses and increase protection against pneumococcal acute otitis media and invasive infections. Hence, intranasal immunization with PsaA protein, based on chitosan as a delivery system, is an efficient immunization strategy for preventing pneumococcal infections.

  18. Acute Toxicity and Gastroprotective Role of M. pruriens in Ethanol-Induced Gastric Mucosal Injuries in Rats

    Science.gov (United States)

    Hassandarvish, Pouya; Abdul Majid, Nazia; Hadi, A. Hamid A.; Nordin, Noraziah; Abdulla, Mahmood A.

    2013-01-01

    The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions. PMID:23781513

  19. Acute Toxicity and Gastroprotective Role of M. pruriens in Ethanol-Induced Gastric Mucosal Injuries in Rats

    Directory of Open Access Journals (Sweden)

    Shahram Golbabapour

    2013-01-01

    Full Text Available The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC. The reference control was administered omeprazole orally (20 mg/kg. The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg and the experimental groups (62.5, 125, 250, and 500 mg/kg. After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg and could enhance defensive mechanisms against hemorrhagic mucosal lesions.

  20. Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions

    Institute of Scientific and Technical Information of China (English)

    Li Zhu; Zhong Cheng Yang; Ao Li; De Chang Cheng

    2000-01-01

    AIM To investigate the changes of gastric acid production and its mechanism in shock period of severe burn in rats.METHODS A rat model with 30% TBSA fullthickness burn injury was employed and the gastric acid production, together with gastric mucosal blood flow (GMBF) and energy charge ( EC ) were measured serially within 48h postburn.RESULTS The gastric acid production in the acute shock period was markedly inhibited after severe burn injury. At the 3rd h postburn, the gastric juice volume, total acidity and acid output were already significantly decreased (P<0.01), and reached the lowest point,0.63mL/L ± 0.20mL/L, 10.81mmol/L ±2.58mmol/L and 2.23 mmol/h ± 0.73mmol/h respectively, at the 12th h postburn. Although restored to some degree 24 h after thermal injury, the variables above were still statistically lower, compared with those of control animals at the 48th h postburn. The GMBF and EC were also significantly reduced after severe burns, consistent with the trend of gastric acid production changes.CONCLUSION Gastric acid production, as well as GMBF and EC was predominantly decreased in the early postburn stage, suggesting that gastric mucosal ischemia and hypoxia with resultant disturbance in energy metabolism, but not gastric acid proper, might be the decisive factor in the pathogenesis of AGML after thermal injury, and that the preventive use of anti-acid drugs during burn shock period was unreasonable in some respects. Therefore,taking effective measures to improve gastric mucosal blood perfusion as early as possible postburn might be more preferable for the AGML prevention and treatment.

  1. Protective effect of Matricaria chamomilla on ethanol-induced acute gastric mucosal injury in rats.

    Science.gov (United States)

    Cemek, Mustafa; Yilmaz, Ezgi; Büyükokuroğlu, Mehmet Emin

    2010-07-01

    The antiulcerogenic and antioxidant properties of Matricaria chamomilla L. (Compositae) hydroalcoholic extract (MCE) on ethanol-induced gastric mucosal injury were investigated in rats. After the induction of gastric mucosal injury, all groups were sacrificed; the gastric ulcer index was calculated, and malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood and gastric tissue, and serum ascorbic acid, retinol, and beta-carotene levels were measured in all groups. Pretreatment with MCE at some doses significantly reduced gastric lesions. Again, some doses of MCE significantly reduced the MDA, and significantly increased GSH levels in gastric tissue or whole blood. Serum beta-carotene and retinol levels were significantly higher in the 200 mg/kg MCE-administered group with respect to control. As a result, MCE clearly has a protective effect against ethanol-induced gastric mucosal lesions, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in antioxidant activity.

  2. Grape seed extract dose-responsively decreases disease severity in a rat model of mucositis; concomitantly enhancing chemotherapeutic effectiveness in colon cancer cells.

    Science.gov (United States)

    Cheah, Ker Yeaw; Howarth, Gordon Stanley; Bastian, Susan Elaine Putnam

    2014-01-01

    Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells. Female Dark Agouti rats were gavaged with grape seed extract (400-1000 mg/kg) or water (day 3-11) and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg) or saline (control) on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) assay. Compared with 5-Fluorouracil controls, grape seed extract (400-1000 mg/kg) significantly decreased the histological damage score (PGrape seed extract (1000 mg/kg) increased jejunal crypt depth by 25% (PGrape seed extract (600 mg/kg) decreased myeloperoxidase activity by 55% (PGrape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10-25 ug/mL) significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (PGrape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells.

  3. Grape seed extract dose-responsively decreases disease severity in a rat model of mucositis; concomitantly enhancing chemotherapeutic effectiveness in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Ker Yeaw Cheah

    Full Text Available OBJECTIVE: Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells. DESIGN: Female Dark Agouti rats were gavaged with grape seed extract (400-1000 mg/kg or water (day 3-11 and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg or saline (control on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl-2,5-diphenyl-tetrazolium bromide assay. RESULTS: Compared with 5-Fluorouracil controls, grape seed extract (400-1000 mg/kg significantly decreased the histological damage score (P<0.05 in the jejunum. Grape seed extract (1000 mg/kg increased jejunal crypt depth by 25% (P<0.05 in 5-Fluorouracil treated rats compared to 5-Fluorouracil controls, and attenuated the 5-Fluorouracil -induced reduction of mucosal thickness (25%, P<0.05. Grape seed extract (600 mg/kg decreased myeloperoxidase activity by 55% (P<0.01 compared to 5-Fluorouracil controls. Grape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10-25 ug/mL significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (P<0.05 in Caco-2 cells and was more potent than 5-Fluorouracil at 50-100 µg/mL. CONCLUSION: Grape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells.

  4. Serum vitamin D levels decrease in children with acute urticaria.

    Science.gov (United States)

    Ozdemir, B; Köksal, B T; Karakaş, N M; Ozbek, O Y

    Acute urticaria is an immune-inflammatory disease, characterised by acute immune activation. There has been increasing evidence showing that vitamin D deficiency is associated with increased incidence and severity of immune-inflammatory disorders. The aim of this study was to evaluate serum vitamin D levels in acute urticaria. We enrolled 30 children with acute urticaria and 30 control subjects. Concentrations of 25-hydroxyvitamin D [25(OH)D], a biomarker of vitamin D status, were measured in serum of acute urticaria patients and compared with the control group. There were no significant differences in baseline variables (age, gender, weight) between the groups. Vitamin D deficiency (urticaria than in control patients. Serum 25(OH)D levels were significantly lower in the study group compared to those in the control group (13.1±4.3 vs 28.2±7.4ng/mL, purticaria and serum vitamin D levels (purticaria and an inverse relationship with disease duration. These findings may open up the possibility of the clinical use of vitamin D as a contributing factor in the pathogenesis of acute urticaria and a predictive marker for disease activity in acute urticaria. A potential role of vitamin D in pathogenesis and additive therapy in acute urticaria needs to be examined. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  5. Mucosal invasion by fusobacteria is a common feature of acute appendicitis in Germany, Russia, and China

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    Alexander Swidsinski

    2012-01-01

    Full Text Available Background/Aim: To investigate the geographic occurrence of mucosa-invading Fusobacteria in acute appendicitis. Patients and Methods: Carnoy- and formalin-fixated appendices from Germany, Russia, and China were comparatively investigated. Bacteria were detected using fluorescent in situ hybridization. Cecal biopsies from patients with inflammatory bowel disease and other conditions were used as disease controls. Results: Fusobacteria represented mainly by Fusobacterium nucleatum were the major invasive component in bacterial infiltrates in acute appendicitis but were completely absent in controls. The occurrence of invasive Fusobacteria in Germany, Russia, and China was the same. The detection rate in Carnoy-fixated material was 70-71% and in formalin-fixated material was 30-36%. Conclusions: Acute appendicitis is a polymicrobial infectious disease in which F. nucleatum and other Fusobacteria play a key role.

  6. Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats

    Institute of Scientific and Technical Information of China (English)

    Fatih Mehmet Birdane; Mustafa Cemek; Yavuz Osman Birdane; (I)lhami Gül(c)in; Mehmet Emin Büyükokuro(g)lu

    2007-01-01

    AIM: To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats.METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated;whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid,retinol and β-carotene levels were measured in all the groups.RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage.This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 ± 2.81 vs 13.15 ± 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid,retinol and β-carotene levels.CONCLUSION: FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity.

  7. Protective effects of alginate-chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. (Zuojin Pill) against ethanol-induced acute gastric mucosal injury in rats.

    Science.gov (United States)

    Wang, Qiang-Song; Zhu, Xiao-Ning; Jiang, Heng-Li; Wang, Gui-Fang; Cui, Yuan-Lu

    2015-01-01

    Zuojin Pill (ZJP), a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in a ratio of 6:1 (w/w) and was first recorded in "Danxi's experiential therapy" for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss.) Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the mucoadhesive microspheres loaded with alkaloids reduce the inflammatory response by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), downregulating the mRNA expression of inducible nitric oxide synthase, TNF-α, and IL-1β in gastric mucosa. All the results indicate that mucoadhesive microspheres loaded with alkaloids could not only increase the residence time of alkaloids in rat stomach, but also exert gastroprotective effects through reducing the inflammatory response on ethanol-induced gastric mucosal damage. Thus, these

  8. Meditation acutely improves psychomotor vigilance, and may decrease sleep need

    Directory of Open Access Journals (Sweden)

    Passafiume Jason

    2010-07-01

    Full Text Available Abstract Background A number of benefits from meditation have been claimed by those who practice various traditions, but few have been well tested in scientifically controlled studies. Among these claims are improved performance and decreased sleep need. Therefore, in these studies we assess whether meditation leads to an immediate performance improvement on a well validated psychomotor vigilance task (PVT, and second, whether longer bouts of meditation may alter sleep need. Methods The primary study assessed PVT reaction times before and after 40 minute periods of mediation, nap, or a control activity using a within subject cross-over design. This study utilized novice meditators who were current university students (n = 10. Novice meditators completed 40 minutes of meditation, nap, or control activities on six different days (two separate days for each condition, plus one night of total sleep deprivation on a different night, followed by 40 minutes of meditation. A second study examined sleep times in long term experienced meditators (n = 7 vs. non-meditators (n = 23. Experienced meditators and controls were age and sex matched and living in the Delhi region of India at the time of the study. Both groups continued their normal activities while monitoring their sleep and meditation times. Results Novice meditators were tested on the PVT before each activity, 10 minutes after each activity and one hour later. All ten novice meditators improved their PVT reaction times immediately following periods of meditation, and all but one got worse immediately following naps. Sleep deprivation produced a slower baseline reaction time (RT on the PVT that still improved significantly following a period of meditation. In experiments with long-term experienced meditators, sleep duration was measured using both sleep journals and actigraphy. Sleep duration in these subjects was lower than control non-meditators and general population norms, with no apparent

  9. Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection.

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    Saurabh Mehandru

    2006-12-01

    Full Text Available BACKGROUND: During acute and early HIV-1 infection (AEI, up to 60% of CD4(+ T cells in the lamina propria of the lower gastrointestinal (GI tract are lost as early as 2-4 wk after infection. Reconstitution in the peripheral blood during therapy with highly active antiretroviral therapy (HAART is well established. However, the extent of immune reconstitution in the GI tract is unknown. METHODS AND FINDINGS: Fifty-four AEI patients and 18 uninfected control participants underwent colonic biopsy. Forty of the 54 AEI patients were followed after initiation of antiretroviral therapy (18 were studied longitudinally with sequential biopsies over a 3-y period after beginning HAART, and 22 were studied cross sectionally after 1-7 y of uninterrupted therapy. Lymphocyte subsets, markers of immune activation and memory in the peripheral blood and GI tract were determined by flow cytometry and immunohistochemistry. In situ hybridization was performed in order to identify persistent HIV-1 RNA expression. Of the patients studied, 70% maintained, on average, a 50%-60% depletion of lamina propria lymphocytes despite 1-7 y of HAART. Lymphocytes expressing CCR5 and both CCR5 and CXCR4 were persistently and preferentially depleted. Levels of immune activation in the memory cell population, CD45RO+ HLA-DR+, returned to levels seen in the uninfected control participants in the peripheral blood, but were elevated in the GI tract of patients with persistent CD4+ T cell depletion despite therapy. Rare HIV-1 RNA-expressing cells were detected by in situ hybridization. CONCLUSIONS: Apparently suppressive treatment with HAART during acute and early infection does not lead to complete immune reconstitution in the GI mucosa in the majority of patients studied, despite immune reconstitution in the peripheral blood. Though the mechanism remains obscure, the data suggest that there is either viral or immune-mediated accelerated T cell destruction or, possibly, alterations in T

  10. Effect of acid secretion blockade on acute gastric mucosal lesions induced by Tityus serrulatus scorpion toxin in anaesthetized rats.

    Science.gov (United States)

    Melo, Júnio Rios; de Araújo, Gnana Keith Marques; da Luz, Magda Maria Profeta; da Conceição, Sérgio Alexandre; Lisboa, Felipe Assis; Moraes-Santos, Tasso; Cunha-Melo, José Renan

    2006-10-01

    Scorpion venom (TX) promotes gastric acid and pepsin secretion leading to acute gastric mucosal lesions (AGML), when injected in animals. The goal of the present study was to observe the effects of acid gastric secretion blockers over the incidence of TX-induced AGML in vivo. To verify this model, we used male albino rats, fasted 18-20 h (n=122) and anaesthetized with urethane (1.4 g/kg, i.p.). Their trachea and left femoral vein were both cannulated; the first to avoid airway obstructions during scorpion intoxication and the second for administration of saline, TX and acid blockers. Following the surgical procedure, the animals were divided in 10 groups of at least 10 animals each. Control groups were injected with NaCl 0.9% 1 ml/kg (n=10) or TX 375 microg/kg (n=32). Test groups (n=10, each) received atropine 5 mg/kg, cimetidine 10mg/kg, ranitidine 2.5mg/kg, ranitidine 5mg/kg, omeprazol 1 mg/kg, omeprazol 4 mg/kg, octreotide 80 and octreotide 100 microg/kg 10 min before the TX was injected. After 1h of intoxication, the stomach was resected for macroscopic study and the gastric secretion was collected for volume, pH and acid output assessment. We observed that all blockers were able to completely or partially prevent the TX-induced acid secretion as well as the AGML (p<0.05). Our data suggest the TX-induced AGML can be prevented by different class of acid blockers injected before the intoxication.

  11. Protective effects of alginate–chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. (Zuojin Pill against ethanol-induced acute gastric mucosal injury in rats

    Directory of Open Access Journals (Sweden)

    Wang QS

    2015-11-01

    Full Text Available Qiang-Song Wang,1,2,* Xiao-Ning Zhu,1,* Heng-Li Jiang,1,* Gui-Fang Wang,3 Yuan-Lu Cui1 1Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 2Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, 3Pharmacy Department, Baokang Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Zuojin Pill (ZJP, a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. in a ratio of 6:1 (w/w and was first recorded in “Danxi’s experiential therapy” for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss. Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the

  12. Preventive effect of tetramethylpyrazine on intestinal mucosal injury in rats with acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jian-Xin Zhang; Sheng-Chun Dang; Jian-Guo Qu; Xue-Qing wang

    2006-01-01

    AIM: To evaluate the role of microcirculatory disorder(MCD) and the therapeutic effectivenessof tetramethylpyrazine (TMP) on intestinal mucosa injury in rats with acute necrotizing pancreatitis (ANP).METHODS: A total of 192 Sprague-Dawley rats were randomly divided into three groups: normal control group (C group), ANP group not treated with TMP (Pgroup), ANP group treated with TMP (T group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 mL/kg).C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP (10 mL/kg) via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase (MPO) expressed intracellularly in azurophilic granules of neutrophils.RESULTS: The blood flow was significantly lower in P group than in C group (P < 0.01). The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes.The intestinal MPO activities were significantly higher in P group than in C group (P < 0.01). The blood flow of intestine was significantly higher in T group than in P group after 2 h (P < 0.01). The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group (P <0.01 or P < 0.05). There was a negative correlation between intestinal blood flow and MPO activity (r = -0.981,P < 0.01) as well as between intestinal blood flow and pathologic scores (r = -0.922, P < 0.05).CONCLUSION: MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.

  13. Antibiotics increase gut metabolism and antioxidant proteins and decrease acute phase response and necrotizing enterocolitis in preterm neonates.

    Directory of Open Access Journals (Sweden)

    Pingping Jiang

    Full Text Available BACKGROUND: The appropriate use of antibiotics for preterm infants, which are highly susceptible to develop necrotizing enterocolitis (NEC, is not clear. While antibiotic therapy is commonly used in neonates with NEC symptoms and sepsis, it remains unknown how antibiotics may affect the intestine and NEC sensitivity. We hypothesized that broad-spectrum antibiotics, given immediately after preterm birth, would reduce NEC sensitivity and support intestinal protective mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: Preterm pigs were treated with antibiotics for 5 d (oral and systemic doses of gentamycin, ampicillin and metrodinazole; AB group and compared with untreated pigs. Only the untreated pigs showed evidence of NEC lesions and reduced digestive function, as indicated by lowered villus height and activity of brush border enzymes. In addition, 53 intestinal and 22 plasma proteins differed in expression between AB and untreated pigs. AB treatment increased the abundance of intestinal proteins related to carbohydrate and protein metabolism, actin filaments, iron homeostasis and antioxidants. Further, heat shock proteins and the complement system were affected suggesting that all these proteins were involved in the colonization-dependent early onset of NEC. In plasma, acute phase proteins (haptoglobin, complement proteins decreased, while albumin, cleaved C3, ficolin and transferrin increased. CONCLUSIONS/SIGNIFICANCE: Depressed bacterial colonization following AB treatment increases mucosal integrity and reduces bacteria-associated inflammatory responses in preterm neonates. The plasma proteins C3, ficolin, and transferrin are potential biomarkers of the colonization-dependent NEC progression in preterm neonates.

  14. Influence of live combined bifidobacterium, lactobacillus and enterococcus capsules inflammation factors and intestinal mucosal barrier function of severe acute pancreatitis patients

    Institute of Scientific and Technical Information of China (English)

    Ping-Ping Shi; Ling-Yun Wu; Jian-Jun Wang

    2015-01-01

    Objective:To explore the influence of inflammation factors and intestinal mucosal barrier function on severe acute pancreatitis patients treated with bifidobacterium triple viable capsules.Methods:88 cases severe acute pancreatitis patients were divided into observation group and control group according to admission order, 44 cases in each group, all patients were given conventional treatment, on this base, patients in observation group were treated by oral bifidobacterium triple viable capsules, they were treated for one week, detected the serum inflammatory factors: the tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and C-reactive protein (CRP) and intestinal mucosal barrier function index: endotoxin, diamine oxidase (DAO), D-lactic acid, urinary lactulose/mannitol (L/M) in the two groups before and after treatment.Results:The levels of TNF-α, IL-6 and CRP in two groups after treatment were significantly reduced than before treatment, and after treatment the levels of TNF-α, IL-6 and CRP in observation group was significantly lower than that of the control group, all the difference was statistically significant; The levels of endotoxin, DA, D-lactic acid, L/M in two groups after treatment were significantly reduced than before treatment, and the levels of endotoxin, DA, D-lactic acid,L/M after treatment in observation group was significantly lower than that of the control group, the difference was statistically significant.Conclusion: Based on conventional treatment combined bifidobacterium triple viable capsules can significantly reduce inflammation in patients with severe acute pancreatitis, it can protect the intestinal mucosal barrier function, and has important clinical significance.

  15. Mucosal adaptation to aspirin induced gastric damage in humans. Studies on blood flow, gastric mucosal growth, and neutrophil activation.

    Science.gov (United States)

    Konturek, J W; Dembinski, A; Stoll, R; Domschke, W; Konturek, S J

    1994-01-01

    The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess the extent of mucosal damage by aspirin and subsequent adaptation the effects of 14 days of continuous, oral administration of aspirin (2 g per day) to eight healthy male volunteers was studied. To estimate the rate of mucosal damage, gastroscopy was performed before (day 0) and at days 3, 7, 14 of aspirin treatment. Gastric microbleeding and gastric mucosal blood flow were measured using laser Doppler flowmeter and mucosal biopsy specimens were taken for the estimation of tissue DNA synthesis and RNA and DNA concentration. In addition, the activation of neutrophils in peripheral blood was assessed by measuring their ability to associate with platelets. Aspirin induced acute damage mainly in gastric corpus, reaching at day 3 about 3.5 on the endoscopic Lanza score but lessened to about 1.5 at day 14 pointing to the occurrence of gastric adaptation. Mucosal blood flow increased at day 3 by about 50% in the gastric corpus and by 88% in the antrum. The in vitro DNA synthesis and RNA concentration, an index of mucosal growth, were reduced at day 3 but then increased to reach about 150% of initial value at the end of aspirin treatment. It is concluded that the treatment with aspirin in humans induces gastric adaptation to this agent, which entails the increase in mucosal blood flow, the rise in neutrophil activation, and the enhancement in mucosal growth. PMID:7959223

  16. Long-term ethanol exposure decreases the endotoxin-induced hepatic acute phase response in rats

    DEFF Research Database (Denmark)

    Glavind, Emilie; Vilstrup, Hendrik; Grønbaek, Henning

    2017-01-01

    -fed rats showed either no liver histopathological changes or varying degrees of steatosis. Ethanol feeding decreased the spontaneous liver mRNA expression of the prevailing acute phase protein alpha-2-macroglobulin by 30% (Ptumor necrosis factor...... an induced acute phase response is impaired in long-term ethanol-fed rats. METHODS: For six weeks, rats were either fed a Lieber-DeCarli ethanol-containing (36% as calories) liquid diet ad libitum or calorically pair-fed. Then, the rats were injected intraperitoneally with a low-dose of lipopolysaccharide...... (LPS) (0.5 mg/kg) to induce an acute phase response. Two hours after LPS, we measured the plasma concentrations of an array of inflammatory cytokines. Twenty-four hours after LPS, we measured the hepatic mRNA expression and serum concentrations of prominent rat acute phase proteins. RESULTS: Ethanol...

  17. Acute decrease in serum testosterone after a mixed glucose and protein beverage in obese peripubertal boys.

    Science.gov (United States)

    Schwartz, Alexander; Patel, Barkha P; Vien, Shirley; McCrindle, Brian W; Anderson, G Harvey; Hamilton, Jill

    2015-09-01

    Delayed puberty and lower levels of testosterone (T) have been observed in adult obese males and some adolescent males. In adult men, enteral glucose ingestion results in acute lowering of serum testosterone levels; however, this has not been studied in adolescents. We aimed to examine the acute effect of a glucose/protein beverage on serum T concentration changes in obese peripubertal males. A second objective was to determine whether change in T concentration was related to appetite hormone levels. Twenty-three overweight and obese males aged 8-17 in pre-early (Tanner stage 1-2) and mid-late (Tanner stage 3-5) puberty were included in this cross-sectional study at the Clinical investigative unit at the Hospital for Sick Children. Participants consumed a beverage containing glucose and protein, and blood samples measuring pubertal hormones, ghrelin and glucagon-like peptide-1 (GLP-1) were taken over 60 min. Across pubertal stages, there was a significant decrease in T levels in adolescent boys (-18·6 ± 3·1%, P Decrease in T was associated with a decrease in LH (r = 0·52, P = 0·02), and fasting T was inversely correlated with fasting ghrelin (r = -0·51, P = 0·03) with no correlation with GLP-1. Intake of a mixed glucose/protein beverage acutely decreases T levels in overweight and obese peripubertal boys. A potential mechanism for this decrease may be secondary to an acute decrease in LH, but this requires further evaluation. © 2014 John Wiley & Sons Ltd.

  18. Acute Exercise Decreases Tribbles Homolog 3 Protein Levels in the Hypothalamus of Obese Rats.

    Science.gov (United States)

    Rodrigues, Barbara De Almeira; Pauli, Luciana Santos Souza; DE Souza, Claudio Teodoro; DA Silva, Adelino Sanchez Ramos; Cintra, Dennys Esper Correa; Marinho, Rodolfo; DE Moura, Leandro Pereira; Ropelle, Eloize Cristina Chiarreotto; Botezelli, José Diego; Ropelle, Eduardo Rochete; Pauli, José Rodrigo

    2015-08-01

    This study aims to evaluate the effects of acute exercise on tribbles homolog 3 (TRB3) protein levels and on the interaction between TRB3 and Akt proteins in the hypothalamus of obese rats. In addition, we evaluated the relationship between TRB3 and endoplasmic reticulum (ER) stress and verified whether an acute exercise session influences them. In the first part of the study, the rats were divided into three groups: control (lean), fed standard rodent chow; DIO, fed a high-fat diet; and DIO-EXE, fed a high-fat diet and submitted to a swimming acute exercise protocol. In the second part of the study, we used three other groups: control (lean) group receiving an intracerebroventricular (i.c.v.) infusion of vehicle, lean group receiving an i.c.v. infusion of thapsigargin, and lean group receiving an i.c.v. infusion of thapsigargin and performing an acute exercise session. Four hours after the exercise session, food intake was measured, and the hypothalamus was dissected and separated for subsequent protein analysis by immunoblotting and real-time polymerase chain reaction. The acute exercise session reduced TRB3 protein levels, disrupted the interaction between TRB3 and Akt proteins, increased the phosphorylation of Foxo1, and restored the anorexigenic effects of insulin on the hypothalamus of DIO rats. Interestingly, the suppressive effects of acute exercise on TRB3 protein levels may be related, at least in part, to decreased ER stress (evaluated though pancreatic ER kinase phosphorylation and C/EBP homologous protein levels) in the hypothalamus. Exercise-mediated reduction of hypothalamic TRB3 protein levels may be associated with reduction of ER stress. These data provide a new mechanism by which an acute exercise session improves insulin sensitivity in the hypothalamus and restores food intake control in obesity.

  19. Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in type 2 diabetes and obesity

    DEFF Research Database (Denmark)

    Jørgensen, Gitte Maria; Vind, Birgitte; Nybo, Mads;

    2009-01-01

    the acute effects of insulin on plasma OPG concentrations in individuals with type 2 diabetes and obese individuals compared with lean controls. DESIGN: The study population consisted of ten type 2 diabetic, ten obese subjects, and ten lean subjects with no family history of diabetes. METHODS: All subjects...... infusion decreased plasma OPG concentrations in all groups (Pobese and type 2 diabetic individuals (P=0.007). Baseline OPG correlated with fasting insulin, baseline lactate, and low density lipoprotein cholesterol in the diabetic group, and with baseline FFA...... in the lean group. The relative change of OPG in response to insulin correlated inversely with HbA1c and baseline FFA in the lean group. CONCLUSIONS: Acute hyperinsulinemia decreases plasma OPG, but with diminished effect in individuals with type 2 diabetes and obesity. Increased levels of OPG in arteries...

  20. Decreased neuroautonomic complexity in men during an acute major depressive episode: analysis of heart rate dynamics

    OpenAIRE

    Leistedt, S J-J; Linkowski, P.; Lanquart, J-P; Mietus, J E; Davis, Roger B.; Goldberger, Ary Louis; Costa, Madalena Damasio

    2011-01-01

    Major depression affects multiple physiologic systems. Therefore, analysis of signals that reflect integrated function may be useful in probing dynamical changes in this syndrome. Increasing evidence supports the conceptual framework that complex variability is a marker of healthy, adaptive control mechanisms and that dynamical complexity decreases with aging and disease. We tested the hypothesis that heart rate (HR) dynamics in non-medicated, young to middle-aged males during an acute major ...

  1. Effects of acute chemotherapy-induced mucositis on spontaneous behaviour and the grimace scale in laboratory rats.

    Science.gov (United States)

    Whittaker, A L; Leach, M C; Preston, F L; Lymn, K A; Howarth, G S

    2016-04-01

    Intestinal mucositis is a frequent side-effect of chemotherapy treatment. Many oncological research programs aim to identify novel treatments for this distressing condition, and these programs frequently use rat models. Little is known about the presence and progression of pain in these models and how this can best be treated by analgesic therapy. We used a number of behaviour-based methods of pain assessment to determine which tools were best suited for pain identification. Baseline measures for behavioural assessment, rat grimace score and sociability were determined through analysis of continuously recorded video data and an applied social interaction test (n = 16). Mucositis was then induced by intraperitoneal injection of 5-fluorouracil (150 mg/kg) and further behavioural analyses undertaken. An assessment of enrichment interaction was also made by determining the mass of a plastic chew toy gnawed both pre- and post-chemotherapy injection. Behavioural scoring was performed 1, 6, 12, 24 and 48 h after injection, with facial expression being scored at the 12, 24 and 48 h time-points. Sociability testing was performed once during the post-injection period. No significant differences were found in grimace scores between baseline and later daily measures. Behaviours similar to those previously reported post-laparotomy were observed. Writhing, twitching and back-arching behaviours were most evident in rats affected by mucositis and were increased in frequency (respective P values: 0.002, 0.004 and 0.008) 48 h after chemotherapy injection compared with baseline, implying that pain onset occurred around this time-point. Social investigatory behaviour was also increased (P = 0.002) following disease onset. Each day, rats post-5FU injection gnawed a greater percentage of their Nylabone enrichment by weight than the saline-injected control rats (P = 0.046). These data suggest that, of the tools tested, behavioural assessment scoring may find greatest

  2. Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats

    Institute of Scientific and Technical Information of China (English)

    Mehmet Kanter; Halit Demir; Cengiz Karakaya; Hanefi Ozbek

    2005-01-01

    AIM: To evaluate the role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effect of Nigella sativa L oil (NS) and its constituent thymoquinone (TQ) in an experimental model.METHODS: Male Wistar albino rats were assigned into 4groups. Control group was given physiologic saline orally (10 mL/kg body weight) as the vehicle (gavage); ethanol group was administrated 1 mL (per rat) absolute alcohol by gavage; the third and fourth groups were given NS (10 mL/kg body weight) and TQ (10 mg/kg body weight p.o) respectively 1 h prior to alcohol intake. One hour after ethanol administration, stomach tissues were excised for macroscopic examination and biochemical analysis.RESULTS: NS and TQ could protect gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index (UI) values. NS prevented alcohol-induced increase in thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation. NS also increased gastric glutathione content (GSH), enzymatic activities of gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST). Likewise, TQ protected against the ulcerating effect of alcohol and mitigated most of the biochemical adverse effects induced by alcohol in gastric mucosa, but to a lesser extent than NS. Neither NS nor TQ affected catalase activity in gastric tissue.CONCLUSION: Both NS and TQ, particularly NS can partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects might be induced, at least partly by their radical scavenging activity.

  3. Acute inflammation decreases the expression of connexin 40 in mouse lung.

    Science.gov (United States)

    Rignault, Stéphanie; Haefliger, Jacques-Antoine; Waeber, Bernard; Liaudet, Lucas; Feihl, François

    2007-07-01

    Transmigration of neutrophil polymorphonuclear leukocytes through the microvascular endothelium is a cardinal event of acute inflammation. In vitro, this process can be restricted by gap junctional intercellular communication, but whether it also occurs in vivo is unknown. Connexin 40 (Cx40) is a gap junctional protein abundantly present in the lung, notably in vascular endothelium. We hypothesized that acute lung inflammation would be aggravated in knockout mice genetically deficient in Cx40. This hypothesis was tested in two different models: 1) intranasal instillation of LPS at either supramaximal (50 microg/mouse) or inframaximal dose (0.01 microg/mouse) and 2) pulmonary inflammation as a distant consequence of an abdominal infection caused by cecal ligation and perforation. Pulmonary transmigration of neutrophils was assessed by counting these cells in bronchoalveolar lavage fluid (LPS model) or with the myeloperoxidase assay in homogenates of blood-free tissue (cecal ligation and perforation model). Pulmonary content in Cx40 and Cx43 was evaluated with immunoblots. In wild-type mice, there was a time-dependent decrease of Cx40 expression in both models. The time points for studies with the knockout mice were chosen in such a manner that inflammation was clearly present and Cx40 still largely expressed in wild-type animals. In either model, the development of lung inflammation did not differ between wild-type and Cx40-deficient mice. In conclusion, the pulmonary expression of the Cx40 protein is progressively and markedly decreased in two different murine models of acute lung inflammation, but there is no causal relationship between this process and the pulmonary transmigration of neutrophils.

  4. Acute Escherichia coli endotoxaemia decreases the plasma l-arginine/asymmetrical dimethylarginine ratio in humans.

    Science.gov (United States)

    Mittermayer, Friedrich; Namiranian, Khodadad; Pleiner, Johannes; Schaller, Georg; Wolzt, Michael

    2004-06-01

    Acute inflammation impairs vascular function. Based on the association between endothelial dysfunction and plasma concentrations of L-arginine and the endogenous nitric oxide synthase inhibitor ADMA (asymmetrical dimethylarginine), we hypothesized that the ratio between L-arginine and ADMA could be affected by experimental inflammation. Plasma concentrations of L-arginine, ADMA and SDMA (symmetrical dimethylarginine) were studied at baseline and 3.5 h after intravenous administration of Escherichia coli endotoxin [LPS (lipopolysaccharide), 20 units/kg of body mass; n =8] or placebo ( n =9) in healthy males. L-Arginine and dimethylarginines were quantified after solid-phase extraction by reversed-phase HPLC. Body temperature, heart rate and leucocyte count increased after LPS administration ( P <0.01 for all). LPS administration decreased plasma concentrations of L-arginine from 66 micromol/l [95% CI (confidence interval): 56, 88] at baseline to 48 micromol/l (CI: 40, 60) after 3.5 h ( P <0.02), but did not affect ADMA and SDMA concentrations. Consequently, the L-arginine/ADMA ratio declined significantly from a median of 159 (CI: 137, 193) to 135 (CI: 103, 146); a decrease of 25 (CI: -68, -13; P <0.02). L-Arginine, ADMA, SDMA and the L-arginine/ADMA ratio remained constant over time in controls. Acute inflammation reduces the L-arginine/ADMA ratio which could contribute to impaired vascular function.

  5. A rare aggravation of severe mucositis post chemotherapy in a child with acute lymphoblastic leukemia [v1; ref status: indexed, http://f1000r.es/1tf

    Directory of Open Access Journals (Sweden)

    Adlette Inati

    2013-09-01

    Full Text Available Oral mucositis is a debilitating manifestation in children undergoing chemotherapy and radiotherapy. Children with mucositis should be properly managed in order to prevent further exacerbation and adverse complications. We hereby present the first report of a severe chemotherapy-induced mucositis, plausibly aggravated by improper dental hygiene leading to shedding of the ventral part of the tongue in a child with pre-B acute lymphoblastic leukemia (ALL. The patient steadily and gradually recovered her oral maneuvers and ability to speak several months later. Her tongue underwent hypertrophy as a compensatory mechanism. We recommend that critical and regular assessment of the oral mucosa and proper dental care and oral hygiene be emphasized in all pediatric patients receiving chemotherapy. Families of affected children need to be educated about the benefits and modes of optimal oral hygiene for their children and the need to seek immediate care for mouth pain and or lesions. Optimal treatment for mucositis needs to be instituted without delay in this high risk pediatric population. Such a preventive and therapeutic approach may prevent associated life threatening oral and systemic complications, promote rapid and complete mucosal healing, alleviate pain and improve quality of life in children with cancer.

  6. Pneumococcal conjugate vaccination does not induce a persisting mucosal IgA response in children with recurrent acute otitis media.

    NARCIS (Netherlands)

    Bogaert, D.; Veenhoven, R.H.; Ramdin, R.; Luijendijk, I.H.; Rijkers, G.T.; Sanders, E.A.M.; Groot, R. de; Hermans, P.W.M.

    2005-01-01

    AIM: In a prospective controlled study in young children with a history of recurrent acute otitis media, we analyzed the salivary IgA and IgG antibody titers upon vaccination with a 7-valent pneumococcal conjugate vaccine (PCV) given once or twice, followed by a 23-valent polysaccharide booster vacc

  7. Hospice Enrollment in Patients With Advanced Heart Failure Decreases Acute Medical Service Utilization.

    Science.gov (United States)

    Yim, Cindi K; Barrón, Yolanda; Moore, Stanley; Murtaugh, Chris; Lala, Anuradha; Aldridge, Melissa; Goldstein, Nathan; Gelfman, Laura P

    2017-03-01

    Patients with advanced heart failure (HF) enroll in hospice at low rates, and data on their acute medical service utilization after hospice enrollment is limited. We performed a descriptive analysis of Medicare fee-for-service beneficiaries, with at least one home health claim between July 1, 2009, and June 30, 2010, and at least 2 HF hospitalizations between July 1, 2009, and December 31, 2009, who subsequently enrolled in hospice between July 1, 2009, and December 31, 2009. We estimated panel-negative binomial models on a subset of beneficiaries to compare their acute medical service utilization before and after enrollment. Our sample size included 5073 beneficiaries: 55% were female, 45% were ≥85 years of age, 13% were non-white, and the mean comorbidity count was 2.38 (standard deviation 1.22). The median number of days between the second HF hospital discharge and hospice enrollment was 45. The median number of days enrolled in hospice was 15, and 39% of the beneficiaries died within 7 days of enrollment. During the study period, 11% of the beneficiaries disenrolled from hospice at least once. The adjusted mean number of hospital, intensive care unit, and emergency room admissions decreased from 2.56, 0.87, and 1.17 before hospice enrollment to 0.53, 0.19, and 0.76 after hospice enrollment. Home health care Medicare beneficiaries with advanced HF who enrolled in hospice had lower acute medical service utilization after their enrollment. Their pattern of hospice use suggests that earlier referral and improved retention may benefit this population. Further research is necessary to understand hospice referral and palliative care needs of advanced HF patients. © 2017 American Heart Association, Inc.

  8. Acute eccentric resistance exercise decreases matrix metalloproteinase activity in obese elderly women.

    Science.gov (United States)

    Nascimento, Dahan da Cunha; Navalta, James Wilfred; Durigan, João Luiz Quagliotti; Marqueti, Rita de Cassia; Tibana, Ramires Alsamir; Luiz Franco, Octavio; de Almeida, Jesser Alves; Camarço, Nathalia Ferreira; Neto, Ivo Vieira de Sousa; Prestes, Jonato

    2016-03-01

    The association of ageing with obesity commits elderly women and has been correlated with multiple degenerative processes, which could be occasioned by an enhancing in levels of matrix metalloproteinase-2 and metalloproteinase-9 (MMPs) as well by an cytokine unbalance that included an enhancing on interleukin-6 (IL-6). Furthermore, other factors could be also related to degenerative process, as they could be reduced by eccentric resistance exercise (ERE), which seems particularly important to initiate resistance training in obese older adults. In this view, this study aims to determinate the effects of an acute ERE session on serum MMP-2, MMP-9 and IL-6 in elderly obese women. Ten elderly obese women participated in this study and completed a 10 repetitions maximum test (10 RM) utilizing leg extension exercise. Subjects then completed an acute ERE session consisting of seven sets of 10 repetitions at 110% of 10 RM with a rest of 3 min between sets. Blood samples were collected before, immediately after, 3, 24 and 48 h following the ERE session. Zymograms were utilized to measure the MMP-2 and MMP-9 enzymes from all individuals. Moreover, IL-6 concentration was also determinated. After ERE session, MMP-2 and MMP-9 decreased, remaining significantly below baseline values after 48 h (Pelderly obese women, possibly indicating a transient protection against the low grade inflammation present in this specific population.

  9. Efficacy of cryotherapy associated with laser therapy for decreasing severity of melphalan-induced oral mucositis during hematological stem-cell transplantation: a prospective clinical study.

    Science.gov (United States)

    de Paula Eduardo, Fernanda; Bezinelli, Leticia Mello; da Graça Lopes, Roberta Marques; Nascimento Sobrinho, Jairo Jose; Hamerschlak, Nelson; Correa, Luciana

    2015-09-01

    Melphalan followed by hematopoietic stem-cell transplantation (HSCT) is the standard treatment for multiple myeloma and other hematopoietic neoplasms. However, high doses of melphalan cause severe oral mucositis (OM). The objective was to verify the efficacy of cryotherapy plus laser therapy on reduction of OM severity. HSCT patients undergoing melphalan chemotherapy (n = 71) were randomly divided into two groups according to OM treatment: oral cryotherapy performed with ice chips for 1 h 35 min followed by low-level laser therapy (InGaAIP, 660 nm, 40 mW, 6 J/cm(2) ) (n = 54) and laser therapy alone with the same protocol (n = 17). A control group (n = 33) was composed of HSCT patients treated with melphalan who received no specific treatment for OM. OM scores and clinical information were collected from D0 to D + 11. The cryotherapy/laser therapy group showed the lowest OM scores (maximum Grade I) and the lowest mean number of days (8 days) with OM in comparison with the other groups (p cryotherapy with laser therapy was effective in reducing OM severity in HSCT patients who underwent melphalan conditioning.

  10. Acute decrease in the stiffness of resting muscle belly due to static stretching.

    Science.gov (United States)

    Taniguchi, K; Shinohara, M; Nozaki, S; Katayose, M

    2015-02-01

    The purpose of the study was to examine the acute effect of static stretching exercise on the resting stiffness of gastrocnemius muscle belly. Ten healthy young adults performed standing wall stretching in dorsiflexion for 1 min at a time and repeated five times. Before and after stretching, the shear modulus was measured in medial and lateral heads of the resting gastrocnemius muscle with ultrasound shear-wave elastography. After the stretching, dorsiflexion range of motion (ROM) of the ankle joint increased (P stretching, shear modulus decreased (P stretching across muscle heads. The decrease in shear modulus returned in 20 min after stretching. In the comparison group of 10 additional subjects, the standing intervention without stretching had no influence on these measures. There was a negative correlation between dorsiflexion ROM and shear modulus in either head before and after stretching. The results demonstrate the transient decreases in the stiffness of the resting gastrocnemius muscle belly and indicate that joint flexibility is greater in individuals with lower resting stiffness of the muscle belly.

  11. Efficacy of a Solution Composed by Verbascoside, Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate in the Treatment of Chemotherapy-induced Oral Mucositis in Children With Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Bardellini, Elena; Amadori, Francesca; Schumacher, Richard Fabian; D'Ippolito, Carmelita; Porta, Fulvio; Majorana, Alessandra

    2016-10-01

    The aim of this study was to assess the efficacy of a solution composed by verbascoside, polyvinylpyrrolidone, and sodium hyaluronate (Mucosyte) in the treatment of chemotherapy-induced oral mucositi (OM). Patients between 5 and 18 years receiving chemotherapy for acute lymphoblastic leukemia and with OM grade 1 or 2 were randomized in group A (treated with Mucosyte, 3 mouthwashes/d per 8 d) and group B (treated with placebo, ie, an inert water-based solution, 3 mouthwashes/d per 8 d). The OM scoring was performed at day 1 (diagnosis of OM-T0), after 3 days of treatment (T1), and at day 8 (T2). Pain was evaluated through the visual analog scale with the same timing of OM measurement. A total of 56 patients were included (28 patients per group). Group A experienced a statistically significant decline of OM at T2 (P=0.0038); a statistically significant difference in pain reduction between 2 groups both at T1 and at T2 (P<0.005) was observed. The use of Mucosyte mouthwashes in children with chemotherapy-induced OM may be recommended as supportive therapy.

  12. The Effects of Combined Adiponectin-Metformin on Glucose and Lipids Levels in Mice and Acute Toxicity and Anti-Ulcerogenic Activity of Adiponectin Against Ethanol-Induced Gastric Mucosal Injuries in Rat

    Directory of Open Access Journals (Sweden)

    Mohammed A. Alshawsh

    2011-11-01

    Full Text Available Adiponectin is a protein hormone secreted entirely by abdominal fat tissue. It exhibits various biological activities. The present study was performed to evaluate the effects of metformin alone or in combination with adiponectin on blood glucose, TG (triglyceride, CHOL (Total cholesterol, LDL (Low density lipoprotein and HDL (High density lipoprotein levels in mice and also to evaluate the anti-ulcerogenic activity of adiponectin against ethanol induced gastric mucosal injury in rats. Three groups of mice were gavaged with 1% volume/body weight high fat-sucrose. Metformin at a dosage of 250 mg/kg was added to the feed and a dosage of 2.5 mg/kg adiponectin was injected intraperitoneally (i.p. Blood glucose was measured at one hour intervals for five hours. Blood concentrations of TG, CHOL, LDL and HDL were also measured at the end of the fifth hour of the experiment. On the other hand, four groups of adult healthy rats were i.p. injected with distilled water, omeprazole 20 mg/kg, 2.5 mg/kg and 5 mg/kg adiponectin one hour before oral administration of absolute ethanol to generate gastric mucosal injury. After an additional hour the rats were sacrificed and the ulcer areas of the gastric walls were determined. Furthermore, an acute toxicity study has indicated no mortality with 5 mg/kg dose of adiponectin injected i.p in rats and no major clinical signs of toxicity were observed. The results indicate that the effect of a combination of metformin and adiponectin on blood glucose and HDL is quite effective. Histology of the gastric wall of negative control rats revealed severe damage of gastric mucosa, along with edema and leucocyte infiltration of the submucosal layer compared to rats pre-treated with either omeprazole or adiponectin extract where there was marked gastric protection along with reduction or inhibition of edema and leucocytes infiltration. The results suggest that combination of metfomin and adiponectin give a promising antidiabetic

  13. Regulatory T cells reduce acute lung injury fibroproliferation by decreasing fibrocyte recruitment.

    Science.gov (United States)

    Garibaldi, Brian T; D'Alessio, Franco R; Mock, Jason R; Files, D Clark; Chau, Eric; Eto, Yoshiki; Drummond, M Bradley; Aggarwal, Neil R; Sidhaye, Venkataramana; King, Landon S

    2013-01-01

    Acute lung injury (ALI) causes significant morbidity and mortality. Fibroproliferation in ALI results in worse outcomes, but the mechanisms governing fibroproliferation remain poorly understood. Regulatory T cells (Tregs) are important in lung injury resolution. Their role in fibroproliferation is unknown. We sought to identify the role of Tregs in ALI fibroproliferation, using a murine model of lung injury. Wild-type (WT) and lymphocyte-deficient Rag-1(-/-) mice received intratracheal LPS. Fibroproliferation was characterized by histology and the measurement of lung collagen. Lung fibrocytes were measured by flow cytometry. To dissect the role of Tregs in fibroproliferation, Rag-1(-/-) mice received CD4(+)CD25(+) (Tregs) or CD4(+)CD25(-) Tcells (non-Tregs) at the time of LPS injury. To define the role of the chemokine (C-X-C motif) ligand 12 (CXCL12)-CXCR4 pathway in ALI fibroproliferation, Rag-1(-/-) mice were treated with the CXCR4 antagonist AMD3100 to block fibrocyte recruitment. WT and Rag-1(-/-) mice demonstrated significant collagen deposition on Day 3 after LPS. WT mice exhibited the clearance of collagen, but Rag-1(-/-) mice developed persistent fibrosis. This fibrosis was mediated by the sustained epithelial expression of CXCL12 (or stromal cell-derived factor 1 [SDF-1]) that led to increased fibrocyte recruitment. The adoptive transfer of Tregs resolved fibroproliferation by decreasing CXCL12 expression and subsequent fibrocyte recruitment. Blockade of the CXCL12-CXCR4 axis with AMD3100 also decreased lung fibrocytes and fibroproliferation. These results indicate a central role for Tregs in the resolution of ALI fibroproliferation by reducing fibrocyte recruitment along the CXCL12-CXCR4 axis. A dissection of the role of Tregs in ALI fibroproliferation may inform the design of new therapeutic tools for patients with ALI.

  14. Acute and chronic estrogen supplementation decreases uterine sympathetic innervation in ovariectomized adult virgin rats.

    Science.gov (United States)

    Zoubina, E V; Mize, A L; Alper, R H; Smith, P G

    2001-10-01

    Uterine innervation undergoes substantial reorganization associated with changes in reproductive status. Nerves innervating the uterus are decreased in pregnancy and puberty, and even the normal rodent estrous cycle is characterized by fluctuations in numbers of myometrial nerve fibers. During the follicular (proestrus/estrous) phase of the estrous cycle, intact nerves are rapidly depleted and then return over the next 2-3 days in the luteal (metestrus/diestrus) phase. We hypothesize that uterine nerve depletion is initiated by increased circulating estrogen in the follicular phase. However, studies have not shown whether estrogen can reduce uterine innervation and, if so, whether the time course is compatible with the rapid changes observed in the estrous cycle. These questions were addressed in the present study. Mature ovariectomized virgin rats received 17-beta-estradiol as a single injection (10 microg/kg s.c.) or chronically from timed-release pellets (0.1 microg/pellet for 3 weeks sustained release). Total (protein gene-product 9.5-immunoreactive) and sympathetic (dopamine beta-hydroxylase-immunoreactive) uterine innervation was assessed quantitatively. Both total and sympathetic innervation was abundant in uterine longitudinal smooth muscle of ovariectomized rats. However, following acute or chronic estrogen administration, total and sympathetic fiber numbers were markedly decreased. This was not due to altered uterine size, as reductions persisted after correcting for size differences. Our results indicate that sympathetic nerves are lost from uterine smooth muscle after estradiol treatment in a manner similar to that seen in the intact animal during estrus and pregnancy. This suggests that the rise in estradiol prior to estrus is sufficient to deplete uterine sympathetic innervation.

  15. Epidural anaesthesia restores pancreatic microcirculation and decreases the severity of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Alp Demirag; Leo H Bühler; Catherine M Pastor; Philippe Morel; Copin Jean-Christophe; Andreas W Sielenk(a)mper; Nilgun Güvener; Gang Mai; Thierry Berney; Jean-Louis Frossard

    2006-01-01

    AIM: To investigate the effect of epidural anaesthesia (EA) on pancreatic microcirculation during acute pancreatitis (AP).METHODS: AP was induced by injection of sodium taurocholate into the pancreatic duct of Sprague-Dawley rats. To realize EA, a catheter was introduced into the epidural space between T7 and T9 and bupivacaine was injected. Microcirculatory flow was measured by laser Doppler flowmetry. Arterial blood gas analyses were performed. At the end of the experiment (≤ 5 h), pancreas was removed for histology. The animals were divided into three groups: Group 1 (n = 9), AP without EA; Group 2 (n = 4), EA without AP; and Group 3 (n = 6), AP treated by EA.RESULTS: In Group 1, pancreatic microcirculatory flow prior to AP was 141± 39 perfusion units (PU). After AP,microcirculatory flow obviously decreased to 9±6 PU (P<0.05). Metabolic acidosis developed with base excess (BE) of - 14±3 mmol/L. Histology revealed extensive edema and tissue necrosis. In Group 2, EA did not significantly modify microcirculatory flow. BE remained unchanged and histological analysis showed normal pancreatic tissue. In Group 3, AP initially caused a significant decrease in microcirculatory flow from 155±25 to 11±7PU (P< 0.05). After initiation of EA, microcirculatory flow obviously increased again to 81±31 PU (P<0.05).BE was -6 ±4 mmol/L, which was significantly different compared to Group 1 (P<0.05). Furthermore, histology revealed less extensive edema and necrosis in pancreatic tissue in Group 3 than that in Group 1.CONCLUSION: AP caused dramatic microcirculatory changes within the pancreas, with development of metabolic acidosis and tissue necrosis. EA allowed partial restoration of microcirculatory flow and prevented development of tissue necrosis and systemic complications.Therefore, EA should be considered as therapeutic op-.tion to prevent evolution from edematous to necrotic AP.

  16. Stronger cortisol response to acute psychosocial stress is correlated with larger decrease in temporal sensitivity

    Directory of Open Access Journals (Sweden)

    Zhuxi Yao

    2016-05-01

    Full Text Available As a fundamental dimension of cognition and behavior, time perception has been found to be sensitive to stress. However, how one’s time perception changes with responses to stress is still unclear. The present study aimed to investigate the relationship between stress-induced cortisol response and time perception. A group of 40 healthy young male adults performed a temporal bisection task before and after the Trier Social Stress Test for a stress condition. A control group of 27 male participants completed the same time perception task without stress induction. In the temporal bisection task, participants were first presented with short (400 ms and long (1,600 ms visual signals serving as anchor durations and then required to judge whether the intermediate probe durations were more similar to the short or the long anchor. The bisection point and Weber ratio were calculated and indicated the subjective duration and the temporal sensitivity, respectively. Data showed that participants in the stress group had significantly increased salivary cortisol levels, heart rates, and negative affects compared with those in the control group. The results did not show significant group differences for the subjective duration or the temporal sensitivity. However, the results showed a significant positive correlation between stress-induced cortisol responses and decreases in temporal sensitivity indexed by increases in the Weber ratio. This correlation was not observed for the control group. Changes in subjective duration indexed by temporal bisection points were not correlated with cortisol reactivity in both the groups. In conclusion, the present study found that although no significant change was observed in time perception after an acute stressor on the group-level comparison (i.e., stress vs. nonstress group, individuals with stronger cortisol responses to stress showed a larger decrease in temporal sensitivity. This finding may provide insight into the

  17. 鱼油对重症急性胰腺炎大鼠肠黏膜屏障的影响%Fish oil protects the intestinal mucosal barrier in rats with severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    张波; 刘燕燕; 刘丛丛; 武华

    2011-01-01

    目的:探讨 -3鱼油脂肪乳剂对重症急性胰腺炎(SAP)大鼠早期肠黏膜功能屏障的影响.方法:♂Wistar大鼠30只随机分为:假手术组(So组,n=10),鱼油治疗组(F组,n=10)和生理盐水治疗组(N组,n=10).通过胰管逆行注射法建成SAP模型,并分别尾静脉注射 -3鱼油脂肪乳剂和生理盐水治疗.检测大鼠血浆D-乳酸和肠脂肪酸结合蛋白(I-FABP)的水平,观察小肠黏膜组织和胰腺组织并进行病理学评分.0.23,均P<0.05或0.01).结论:ω-3鱼油脂肪乳剂能降低D-乳酸和I-FABP的浓度,从而降低肠黏膜的通透性,减轻全身炎症反应,保护大鼠的肠黏膜屏障.%AIM: To evaluate the protective effect of omega-3 fish oil on the intestinal mucosal barrier in serious acute pancreatitis (SAP) rats.METHODS: Thirty male Wistar rats were randomly divided into three groups: sham-operated group (n = 10), fish oil group (n = 10), and normal saline group (n = 10).SAP was induced in rats of the fish oil group and normal saline group by retrograde injection of 5% sodium cholate (1 mL/kg) into the pancreatic duct.These two groups were then intravenously given fish oil supplement (2 mL/kg) and normal saline (2mL/kg), respectively.The sham-operated group was subjected to sham operation.After treatment, plasma D-lactate and serum intestinal fatty acid binding protein (I-FABP) were measured, and the severity of pancreatitis and intestinal changes was evaluated by histopathological scoring.RESULTS: Plasma D-lactate (mmol/L), serum I-FABP (μg/L), and histopathological scores of intestinal changes and pancreatitis in the normal saline group were markedly lower than those in the sham-operated group and fish oil group (0.43 ± 0.12 vs 0.07 ±0.02, 0.26 ± 0.05; 1 510.00 ± 72.72 vs 80.50 ± 5.60, 904.00 + 61.50; 2.60 ± 0.32 vs 0.20 ± 0.10, 1.85 ± 0.34; 8.60 ± 0.31 vs 0.30 ± 0.12, 7.30 ± 0.23; all P < 0.05 or 0.01).CONCLUSION: Omega-3 fish oil supplementation reduces plasma D-lactate and

  18. Mucosal acid causes gastric mucosal microcirculatory disturbance in nonsteroidal anti-inflammatory drug-treated rats.

    Science.gov (United States)

    Funatsu, Toshiyuki; Chono, Koji; Hirata, Takuya; Keto, Yoshihiro; Kimoto, Aishi; Sasamata, Masao

    2007-01-01

    The mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) suppress gastric mucosal blood flow is not fully understood, although the depletion of mucosal prostaglandin E2 has been proposed as one possible explanation. We investigated the role of gastric acid on gastric mucosal blood flow in NSAID-treated rats. A rat stomach was mounted in an ex vivo chamber, and gastric mucosal blood flow was measured sequentially in a 5-mm2 area of the gastric corpus using a scanning laser Doppler perfusion image system. Results showed that diclofenac (5 mg/kg s.c.) and indomethacin (10 mg/kg s.c.) did not affect gastric mucosal blood flow, although both strongly decreased mucosal prostaglandin E2 when saline was instilled into the gastric chamber. On replacement of the saline in the chamber with 100 mM hydrochloric acid, these drugs caused a decrease in gastric mucosal blood flow levels within 30 min. The specific cyclooxygenase (COX)-2 inhibitors celecoxib (50 mg/kg s.c.) and rofecoxib (25 mg/kg s.c.) did not affect mucosal prostaglandin E2 level, nor did they decrease gastric mucosal blood flow, even when hydrochloric acid was added to the chamber. Furthermore, measurement of vasoconstrictive factors present in the mucosa showed that endothelin-1 levels increased after administration of diclofenac s.c. in the presence of intragastric hydrochloric acid. This indicates that the presence of mucosal hydrochloric acid plays an important role in the NSAID-induced decrease in gastric mucosal blood flow, while the COX-1-derived basal prostaglandin E2, which is unlikely to control gastric mucosal blood flow itself, protects microcirculatory systems from mucosal hydrochloric acid.

  19. 小鼠急性乙醇性胃黏膜损伤模型的制备%Establishment of animal model of ethanol-induced acute gastric mucosal lesions in mice

    Institute of Scientific and Technical Information of China (English)

    叶惠惠; 刘河霞; 张咏梅; 吴克俭

    2011-01-01

    Objective To investigate the optimal ethanol concentration and capacity contributing to ethanol -induced acute gastric mucosal injury and to establish the stable model of ethanol - induced acute gastric mucosal injury in mice. Methods Eighty Kunming mice were randomly divided into control group, normal saline gavage group, 75% ethanol gavage group, and 99.5% ethanol gavage group, followed by sacrifice of animals at 1 h and 4 h for removal of their stomachs and observation of the gastric mucosal lesions. Results The gastric mucosal lesions were evident following gavage of ethanol at the time point of 1 h in mice and 99.5% ethanol at 0.2 ml/10 g gavage induced much sever damage. The gastric mucosal lesions at 1 h were attenuated as compared to 4 h following 99.5% ethanol at 0.2 ml/10 g gavage. There wasn't significant change of survival rates with the concentration and duration of ethanol gavage in mice. Conclusion Ethanol gavage can induce acute gastric mucosal injury in mice, with 99.5% ethanol at 0.2 ml/10 g as the optimal choice to establish the model of acute gastric mucosal injury.%目的 研究引起小鼠急性乙醇性胃黏膜损伤的最佳乙醇浓度与容量,以建立稳定的小鼠急性乙醇性胃黏膜损伤模型.方法 80只昆明小鼠随机分成正常对照组、生理盐水灌胃组、75%乙醇灌胃组、99.5%乙醇灌胃组,然后分别在1 h、4 h处死小鼠取胃,观察小鼠胃黏膜损伤情况.结果 乙醇灌胃1 h后,胃黏膜出现不同程度的损伤,其中99.5%乙醇0.2 ml/10 g对小鼠胃黏膜的损伤较重.99.5%乙醇0.2 ml/10 g灌胃4 h与1 h相比,胃黏膜损伤指数有所下降.随着乙醇浓度的增加与乙醇灌胃时间的延长小鼠的生存率并无显著变化.结论 乙醇灌胃可致小鼠急性胃黏膜损伤,且以99.5%乙醇0.2 ml/10 g灌胃用来制备小鼠急性乙醇性胃黏膜损伤模型最佳.

  20. Oral mucositis - self-care

    Science.gov (United States)

    Cancer treatment - mucositis; Cancer treatment - mouth pain; Cancer treatment - mouth sores; Chemotherapy - mucositis; Chemotherapy - mouth pain; Chemotherapy - mouth sores; Radiation therapy - mucositis; Radiation therapy - mouth pain; Radiation ...

  1. [Preventive effects of troxipide on a newly developed model of acute gastric mucosal lesion (AGML) induced by ischemia/reperfusion plus ammonia in the rat].

    Science.gov (United States)

    Momo, K; Hoshina, K; Ishibashi, Y; Saito, T

    1994-10-01

    We have developed a unique rat AGML model produced by ischemia/reperfusion plus 0.2% ammonia (I/R.NH3), either treatment which would not induce mucosal injury when used alone. The effects of troxipide and other gastric mucosal defensive drugs were investigated with this I/R.NH3-induced AGML model and other AGML models in rats. The following results were obtained: 1) Like allopurinol, troxipide at 50-200 mg/kg, p.o. dose-dependently prevented I/R.NH3-induced development of AGML and also the ischemia/reperfusion-induced increase of gastric mucosal thiobarbituric acid (TBA)-reactive substances; 2) Troxipide at 10(-6)-10(-4) M, like allopurinol, inhibited concentration-dependently in vitro xanthine oxidase activity in gastric mucosal homogenates; 3) Troxipide at 50-200 mg/kg, p.o. inhibited AGMLs induced by bleeding plus 0.2% ammonia and by 1.0% ammonia alone; and 4) Troxipide and sofalcone were similar in preventing all AGMLs tested and also the increase of mucosal TBA-reactive substances, but somewhat differed from teprenone, cetraxate hydrochloride, azulene plus L-glutamine and sucralfate. These findings suggest that troxipide may inhibit I/R.NH3-induced AGML development by preventing generation of oxygen free radicals and by protecting against mucosal fragility due to reduced energy metabolism from poor blood flow and also against ammonia-induced disruption of the gastric mucosal barrier. Therefore, troxipide may be highly effective for various AGMLs with multifactor involvement.

  2. Acute lymphoblastic leukemia and obesity : increased energy intake or decreased physical activity?

    NARCIS (Netherlands)

    Jansen, H.; Postma, A.; Stolk, R. P.; Kamps, W. A.

    2009-01-01

    Background Obesity is a well-known problem in children with acute lymphoblastic leukemia ( ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with inter

  3. Acute acetaminophen intoxication leads to hepatic iron loading by decreased hepcidin synthesis.

    NARCIS (Netherlands)

    Swelm, R.P.L. van; Laarakkers, J.M.M.; Blous, L.; Peters, J.G.P.; Blaney Davidson, E.N.; Kraan, P.M. van der; Swinkels, D.W.; Masereeuw, R.; Russel, F.G.M.

    2012-01-01

    Acetaminophen (APAP), a major cause of acute liver injury in the Western world, is mediated by metabolism and oxidative stress. Recent studies have suggested a role for iron in potentiating APAP-induced liver injury although its regulatory mechanism is not completely understood. The current study wa

  4. Neutrophil depletion-but not prevention of Kupffer cell activation-decreases the severity of cerulein-induced acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Catherine M Pastor; Alain Vonlaufen; Fabianna Georgi; Antoine Hadengue; Philippe Morel; Jean-Louis Frossard

    2006-01-01

    AIM: To determine whether neutrophil depletion and Kupffer cell inhibition might combine their protective effects to decrease the severity of acute pancreatitis.METHODS: Mice had cerulein administration to induce acute pancreatitis and were pretreated with either anti-mouse neutrophil serum or gadolinium chloride (GdCl3) to prevent Kupffer cell activation, or both treatments. Injury was assessed in pancreas and lungs.Myeloperoxidases (MPO) assessed neutrophil infiltration.Interleukin-6 (IL-6) and IL-10 were measured in serum,pancreas, lungs and liver.RESULTS: In mice with acute pancreatitis, neutrophil depletion reduced the severity of pancreatitis and pancreatitis-associated lung injury. Kupffer cell inactivation by GdCl3 had less protective effect, although IL-6 and IL-10 concentrations were significantly decreased. The protective treatment brought by neutrophil depletion was not enhanced by Kupffer cell inactivation and both treatments did not combine their protective effects.CONCLUSION: Our results confirm the role of activated neutrophils in aggravating organ injury in acute pancreatitis while the role of Kupffer cell activation is less obvious.

  5. Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

    DEFF Research Database (Denmark)

    Castellano, J M; Bentsen, A H; Romero, M;

    2010-01-01

    of hypothalamic kisspeptin immunoreactivity (IR) and hormonal responses to kisspeptin during the acute inflammatory phase. LPS injections induced a dramatic but transient drop of serum LH and testosterone levels. Suppression of gonadotropic function was associated with a significant decrease in kisspeptin......-IR in the arcuate nucleus (ARC) that was not observed under conditions of metabolic stress induced by 48-h fasting. In addition, absolute responses to kisspeptin-10 (Kp-10), in terms of LH and testosterone secretion, were significantly attenuated in LPS-treated males that also displayed a decrease in food intake...... and body weight. Yet pair-fed males did not show similar alterations in LH and testosterone secretory responses to Kp-10, whose magnitude was preserved, if not augmented, during food restriction. In summary, our data document the impact of acute inflammation on kisspeptin content at the ARC as key center...

  6. Hyperuricemia in acute gastroenteritis is caused by decreased urate excretion via ABCG2

    Science.gov (United States)

    Matsuo, Hirotaka; Tsunoda, Tomoyuki; Ooyama, Keiko; Sakiyama, Masayuki; Sogo, Tsuyoshi; Takada, Tappei; Nakashima, Akio; Nakayama, Akiyoshi; Kawaguchi, Makoto; Higashino, Toshihide; Wakai, Kenji; Ooyama, Hiroshi; Hokari, Ryota; Suzuki, Hiroshi; Ichida, Kimiyoshi; Inui, Ayano; Fujimori, Shin; Shinomiya, Nariyoshi

    2016-01-01

    To clarify the physiological and pathophysiological roles of intestinal urate excretion via ABCG2 in humans, we genotyped ABCG2 dysfunctional common variants, Q126X (rs72552713) and Q141K (rs2231142), in end-stage renal disease (hemodialysis) and acute gastroenteritis patients, respectively. ABCG2 dysfunction markedly increased serum uric acid (SUA) levels in 106 hemodialysis patients (P = 1.1 × 10−4), which demonstrated the physiological role of ABCG2 for intestinal urate excretion because their urate excretion almost depends on intestinal excretion via ABCG2. Also, ABCG2 dysfunction significantly elevated SUA in 67 acute gastroenteritis patients (P = 6.3 × 10−3) regardless of the degree of dehydration, which demonstrated the pathophysiological role of ABCG2 in acute gastroenteritis. These findings for the first time show ABCG2-mediated intestinal urate excretion in humans, and indicates the physiological and pathophysiological importance of intestinal epithelium as an excretion pathway besides an absorption pathway. Furthermore, increased SUA could be a useful marker not only for dehydration but also epithelial impairment of intestine. PMID:27571712

  7. The onset of the progression of acute phase response mechanisms induced by extreme impacts can be followed by the decrease in blood levels of positive acute phase proteins.

    Science.gov (United States)

    Larina, Olga; Bekker, Anna

    Studies performed at space flights and earth-based simulation models detected the plasma indices of acute phase reaction (APR), i.e. the increase of APR cytokine mediators and alterations in the production of blood acute phase proteins (APP) at the initial stages of adaptation to altered gravity conditions. Acute phase response is the principal constituent of the functional activity of innate immunity system. Changes in plasma APPs contents are considered to serve the restoration of homeostasis state. According to trends of their concentration shifts at the evolving of acute phase reaction APPs are denoted as positive, neutral, or negative. Plasma concentrations of positive acute phase proteins α1-acid glycoprotein (α1-AGP), α1-antitrypsin (α1-AT), and neutral α2-macroglobulin (α2-M) were measured in human study at 12-hour antiorthostatic position (AOP) with 15° head down tilt and hypoxia experiments at 14% oxygen in pressure chamber. Both of these impacts were shown to produce alterations in the APP levels indicative for acute phase response. Nevertheless, in AOP experiment noticeable decrease in α1-AGP concentration occurred by hour 12, and even more pronounced decline of α1-AGP and α1-AT were found on hypoxia hours 12 and 36. Acute phase proteins α1-AGP and α2-M possess the features of proteinase inhibitors. This function is implemented by the formation of complexes with the molecules of proteolytic enzymes which subsequently are removed from the blood flow. Transient decrease in plasma concentrations of protease inhibitors on early phases of APR development was reported to result from the growth of plasma protease activity due to cathepsin release from activated leukocytes, which had not yet been compensated by enhanced APP synthesis. Being a carrier protein for positively charged and neutral substances, α1-AGP shows pronounced elevation in its blood content during APR development. As assumed, it is required for the transportation of the increased

  8. Enhanced gastric mucosal haemostasis after upper gastrointestinal haemorrhage.

    OpenAIRE

    Allison, M C; Fullarton, G M; Brown, I.L.; Crean, G P; McColl, K E

    1991-01-01

    An endoscopic technique for the measurement of gastric mucosal bleeding time has been developed to study gastric haemostasis in patients with acute upper gastrointestinal haemorrhage. The relation of gastric mucosal bleeding time to skin bleeding time and nonsterodial anti-inflammatory drug usage was examined in 61 control patients and in 47 patients presenting with bleeding peptic ulcers or erosions. Gastric mucosal bleeding time was shorter in patients with haemorrhage (median 2 minutes, ra...

  9. Fluconzole in treatment of acute radiation-induced oral mucositis with fungal infection%氟康唑治疗急性放射性口腔粘膜炎继发的真菌感染

    Institute of Scientific and Technical Information of China (English)

    姚原; 吴国华; 蒋马伟; 林清; 陆冬青; 翁霞

    2001-01-01

    目的:研究头颈部肿瘤放射治疗中急性放射性口腔粘膜反应与真菌感染的关系及氟康唑治疗的有效性。方法:71例口腔粘膜受到大面积照射的肿瘤病人:男性42例,女性29例;年龄52 a± s 41 a(11~76 a),在病人的口腔粘膜反应最严重的时候,做口腔粘膜真菌学检查,32例有真菌感染的病人,用氟康唑胶囊100 mg,po, qd×5 d或氟康唑注射液150 mg,iv,gtt×3 d治疗。结果:真菌的检出率为45%,以白念珠菌感染为主。有真菌感染和无真菌感染的2组病人,在急性放射性粘膜反应上差异有显著意义(P<0.05);有真菌感染的病人用氟康唑治疗,治疗前后的粘膜反应差异有显著意义(P<0.05)。结论:严重的急性放射性粘膜反应与真菌感染有密切的关系;有真菌感染的放射性口腔粘膜反应用氟康唑治疗可以明显减轻放射性粘膜反应。%AIM: To study the relation of acute radiation-induced oral mucositis to fungal infection and evaluate the effect of fluconazole in the treatment of patients with fungal infection. METHODS: Seventy-one patients (M 42, F 29; 52 a± s 41 a,11-76 a) with large area of oral mucosas irradiated were into this study. When most serious mucositis, the patients' oral mucosas were checked, 32 patients with fungal infection were treated with fluconazole (fluconazole 100 mg, po, qd×5 d or 150 mg,iv,gtt×3 d). RESULTS: The rate of fungal infection was 45%, the most of patients were infected by candida albicans. Degrees of mucositis between the patients with fungal infection to the patients without fungal infection were significantly different (P<0.05). The patients with fungal infection were treated with fluconazole. Degree of mucositis between the pretreated patients and post-treated patients were significantly different (P<0.05). CONCLUSION: The serious acute radiation-induced oral mucositis has significantly related with fungal infection. The patients

  10. Stroke awareness decreases prehospital delay after acute ischemic stroke in korea

    Directory of Open Access Journals (Sweden)

    Lee Su-Ho

    2011-01-01

    Full Text Available Abstract Background Delayed arrival at hospital is one of the major obstacles in enhancing the rate of thrombolysis therapy in patients with acute ischemic stroke. Our study aimed to investigate factors associated with prehospital delay after acute ischemic stroke in Korea. Methods A prospective, multicenter study was conducted at 14 tertiary hospitals in Korea from March 2009 to July 2009. We interviewed 500 consecutive patients with acute ischemic stroke who arrived within 48 hours. Univariate and multivariate analyses were performed to evaluate factors influencing prehospital delay. Results Among the 500 patients (median 67 years, 62% men, the median time interval from symptom onset to arrival was 474 minutes (interquartile range, 170-1313. Early arrival within 3 hours of symptom onset was significantly associated with the following factors: high National Institutes of Health Stroke Scale (NIHSS score, previous stroke, atrial fibrillation, use of ambulance, knowledge about thrombolysis and awareness of the patient/bystander that the initial symptom was a stroke. Multivariable logistic regression analysis indicated that awareness of the patient/bystander that the initial symptom was a stroke (OR 4.438, 95% CI 2.669-7.381, knowledge about thrombolysis (OR 2.002, 95% CI 1.104-3.633 and use of ambulance (OR 1.961, 95% CI 1.176-3.270 were significantly associated with early arrival. Conclusions In Korea, stroke awareness not only on the part of patients, but also of bystanders, had a great impact on early arrival at hospital. To increase the rate of thrombolysis therapy and the incidence of favorable outcomes, extensive general public education including how to recognize stroke symptoms would be important.

  11. Mucosal healing and fibrosis after acute or chronic inflammation in wild type FVB-N mice and C57BL6 procollagen α1(I-promoter-GFP reporter mice.

    Directory of Open Access Journals (Sweden)

    Shengli Ding

    Full Text Available BACKGROUND: Injury and intestinal inflammation trigger wound healing responses that can restore mucosal architecture but if chronic, can promote intestinal fibrosis. Intestinal fibrosis is a major complication of Crohn's disease. The cellular and molecular basis of mucosal healing and intestinal fibrosis are not well defined and better understanding requires well characterized mouse models. METHODS: FVB-N wild type mice and C57BL6 procollagen α1(I-GFP reporter mice were given one (DSS1 or two (DSS2 cycles of 3% DSS (5 days/cycle followed by 7 days recovery. Histological scoring of inflammation and fibrosis were performed at DSS1, DSS1+3, DSS1+7, DSS2, DSS2+3, and DSS2+7. Procollagen α1(I-GFP activation was assessed in DSS and also TNBS models by whole colon GFP imaging and fluorescence microscopy. Colocalization of GFP with α-smooth muscle actin (α-SMA or vimentin was examined. GFP mRNA levels were tested for correlation with endogenous collagen α1(I mRNA. RESULTS: Males were more susceptible to DSS-induced disease and mortality than females. In FVB-N mice one DSS cycle induced transient mucosal inflammation and fibrosis that resolved by 7 days of recovery. Two DSS cycles induced transmural inflammation and fibrosis in a subset of FVB-N mice but overall, did not yield more consistent, severe or sustained fibrosis. In C57BL6 mice, procollagen α1(I-GFP reporter was activated at the end of DSS1 and through DSS+7 with more dramatic and transmural activation at DSS2 through DSS2+7, and in TNBS treated mice. In DSS and TNBS models GFP reporter expression localized to vimentin(+ cells and much fewer α-SMA(+ cells. GFP mRNA strongly correlated with collagen α1(I mRNA. CONCLUSIONS: One DSS cycle in FVB-N mice provides a model to study mucosal injury and subsequent mucosal healing. The procollagen α1(I-GFP transgenic provides a useful model to study activation of a gene encoding a major extracellular matrix protein during acute or chronic

  12. Allergic airway inflammation decreases lung bacterial burden following acute Klebsiella pneumoniae infection in a neutrophil- and CCL8-dependent manner.

    Science.gov (United States)

    Dulek, Daniel E; Newcomb, Dawn C; Goleniewska, Kasia; Cephus, Jaqueline; Zhou, Weisong; Reiss, Sara; Toki, Shinji; Ye, Fei; Zaynagetdinov, Rinat; Sherrill, Taylor P; Blackwell, Timothy S; Moore, Martin L; Boyd, Kelli L; Kolls, Jay K; Peebles, R Stokes

    2014-09-01

    The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity.

  13. Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner

    Science.gov (United States)

    Dulek, Daniel E.; Newcomb, Dawn C.; Goleniewska, Kasia; Cephus, Jaqueline; Zhou, Weisong; Reiss, Sara; Toki, Shinji; Ye, Fei; Zaynagetdinov, Rinat; Sherrill, Taylor P.; Blackwell, Timothy S.; Moore, Martin L.; Boyd, Kelli L.; Kolls, Jay K.

    2014-01-01

    The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity. PMID:24958709

  14. Transgenic Killer Commensal Bacteria as Mucosal Protectants

    Directory of Open Access Journals (Sweden)

    Luciano Polonelli

    2001-01-01

    Full Text Available As first line of defense against the majority of infections and primary site for their transmission, mucosal surfaces of the oral cavity and genitourinary, gastrointestinal, and respiratory tracts represent the most suitable sites to deliver protective agents for the prevention of infectious diseases. Mucosal protection is important not only for life threatening diseases but also for opportunistic infections which currently represent a serious burden in terms of morbidity, mortality, and cost of cures. Candida albicans is among the most prevalent causes of mucosal infections not only in immuno- compromised patients, such as HIV-infected subjects who are frequently affected by oral and esophageal candidiasis, but also in otherwise healthy individuals, as in the case of acute vaginitis. Unfortunately, current strategies for mucosal protection against candidiasis are severely limited by the lack of effective vaccines and the relative paucity and toxicity of commercially available antifungal drugs. An additional option has been reported in a recent

  15. The antioxidant tempol decreases acute pulmonary thromboembolism-induced hemolysis and nitric oxide consumption.

    Science.gov (United States)

    Sousa-Santos, Ozelia; Neto-Neves, Evandro M; Ferraz, Karina C; Sertório, Jonas T; Portella, Rafael L; Tanus-Santos, Jose E

    2013-11-01

    Acute pulmonary thromboembolism (APT) is a critical condition associated with acute pulmonary hypertension. Recent studies suggest that oxidative stress and hemolysis contribute to APT-induced pulmonary hypertension, possibly as a result of increased nitric oxide (NO) consumption. We hypothesized that the antioxidant tempol could attenuate APT-induced hemolysis, and therefore attenuate APT-induced increases in plasma NO consumption. APT was induced in anesthetized sheep with autologous blood clots. The hemodynamic effects of tempol infused at 1.0mg/kg/min 30 min after APT were determined. Hemodynamic measurements were carried out every 15 min. To assess oxidative stress, serum 8-isoprostanes levels were measured by ELISA. Plasma cell-free hemoglobin concentrations and NO consumption by plasma samples were determined. An in vitro oxidative AAPH-induced hemolysis assay was used to further validate the in vivo effects of tempol. APT caused pulmonary hypertension, and increased pulmonary vascular resistance in proportion with the increases in 8-isoprostanes, plasma cell-free hemoglobin concentrations, and NO consumption by plasma (all Phemolysis (Phemolysis and nitric oxide consumption, thus attenuating APT-induced pulmonary hypertension. © 2013.

  16. Acute one-cigarette smoking decreases ghrelin hormone in saliva: a pilot study.

    Science.gov (United States)

    Kaabi, Yahia A; Khalifa, Mohiealdeen A

    2014-01-01

    Cigarette smoking is commonly associated with weight loss and mechanisms for these weight changes are still elusive. Ghrelin is a peptide hormone that works in a neuroendocrine fashion to stimulate hunger and the desire for food intake. Ghrelin is also secreted in saliva, probably to enhance food taste. In the current study, we tested the direct impact of acute cigarette smoking on total ghrelin found in saliva. Methods. Blood and saliva samples were collected from 30 healthy nonsmoker male volunteers before and after one-cigarette smoke. Total ghrelin in serum and saliva was measured by ELISA based method. Results. Data showed a statistically significant reduction in salivary ghrelin after smoking (P < 0.0001). In serum, total ghrelin levels were not affected before and after smoking (P = 0.1362). Additionally, positive correlation was observed between serum and salivary ghrelin before smoking (r = 0.4143 and P = 0.0158); however, this correlation was lost after smoking (r = 0.1147 and P = 0.5461). Conclusion. Acute one-cigarette smoking can negatively affect ghrelin levels in saliva that might contribute to the dull food taste in smokers.

  17. Acute One-Cigarette Smoking Decreases Ghrelin Hormone in Saliva: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Yahia A. Kaabi

    2014-01-01

    Full Text Available Cigarette smoking is commonly associated with weight loss and mechanisms for these weight changes are still elusive. Ghrelin is a peptide hormone that works in a neuroendocrine fashion to stimulate hunger and the desire for food intake. Ghrelin is also secreted in saliva, probably to enhance food taste. In the current study, we tested the direct impact of acute cigarette smoking on total ghrelin found in saliva. Methods. Blood and saliva samples were collected from 30 healthy nonsmoker male volunteers before and after one-cigarette smoke. Total ghrelin in serum and saliva was measured by ELISA based method. Results. Data showed a statistically significant reduction in salivary ghrelin after smoking (P<0.0001. In serum, total ghrelin levels were not affected before and after smoking (P=0.1362. Additionally, positive correlation was observed between serum and salivary ghrelin before smoking (r=0.4143 and P=0.0158; however, this correlation was lost after smoking (r=0.1147 and P=0.5461. Conclusion. Acute one-cigarette smoking can negatively affect ghrelin levels in saliva that might contribute to the dull food taste in smokers.

  18. Acute Respiratory Distress Syndrome Incidence, But Not Mortality, Has Decreased Nationwide: A National Trauma Data Bank Study.

    Science.gov (United States)

    Fahr, Michael; Jones, Glenn; O'Neal, Hollis; Duchesne, Juan; Tatum, Danielle

    2017-04-01

    Acute respiratory distress syndrome (ARDS) incidence is reported to have decreased in recent years. However, no large-scale study to date has exclusively examined ARDS in the critically injured. We sought to examine the national incidence of ARDS and its associated outcomes exclusively in adult trauma patients. The National Trauma Data Bank (NTDB) was queried to evaluate the incidence of ARDS and associated outcomes over a 6-year study period (2007-2012). Included patients were ≥18 years old, with at least one ventilator day, and complications recorded. ARDS-associated outcomes and complications were also analyzed. Mean age increased over the study period (48.1-51.4 years, P < 0.003). ARDS incidence decreased from 21.5 to 8.5 per cent (P < 0.001). Length of stay (LOS), intensive care unit LOS (ICU LOS), and ventilator days decreased over time. Mortality increased from 21.3 to 24.9 per cent (P < 0.002). Incidence of pneumonia and acute kidney injury increased marginally (39.5-40.9% and 11.4-12.3%, respectively). Sepsis trended down from 2007 to 2010, after which comparable NTDB data were not available. ARDS incidence in mechanically ventilated adult trauma patients has decreased significantly in recent years. We theorize this is likely attributable to improved critical care strategies. Unlike ARDS incidence, mortality in this patient population has not improved despite these advancements.

  19. Decreased incidence of acute graft-versus-host disease by continuous infusion of cyclosporine with a higher target blood level.

    Science.gov (United States)

    Oshima, Kumi; Kanda, Yoshinobu; Nakasone, Hideki; Arai, Shunya; Nishimoto, Nahoko; Sato, Hiroyuki; Watanabe, Takuro; Hosoya, Noriko; Izutsu, Koji; Asai, Takashi; Hangaishi, Akira; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2008-03-01

    Cyclosporine A (CsA) is the mainstay of pharmacologic prevention of acute graft-versus-host disease (GVHD). We previously reported that continuous infusion of CsA with a target blood level between 250 and 400 ng/ml significantly increased the incidence of acute GVHD compared to twice-daily infusion with a target trough level between 150 and 300 ng/ml. Thus, we raised the target level of CsA continuous infusion to 450-550 ng/ml. We treated 33 patients with the higher target level (CsA500) and compared the efficacy and toxicity with those in the 33 historical control patients (CsA300 group). Other transplantation procedures were not changed. The patients' characteristics were equivalent. The average CsA concentration was adjusted around 500 ng/ml and the actual daily dose was maintained at the initial dose (CsA 3mg/kg/day). Toxicities were equivalently observed among the two groups. The incidence of grades II-IV acute GVHD was significantly lower in the CsA500 group (27 vs. 52%, P = 0.033). The target level of CsA was identified as an independent significant risk factor for grades II-IV acute GVHD (P = 0.039), adjusted for the presence of HLA mismatch. The incidence of chronic GVHD was also decreased in the CsA500 group (47 vs. 73%, P = 0.016). We conclude that the toxicity of the continuous CsA infusion with a target level of 450-550 ng/ml is acceptable and the efficacy to prevent acute GVHD is significant. A larger comparative study is warranted to confirm these findings.

  20. Phase 3 Trial of Domiciliary Humidification to Mitigate Acute Mucosal Toxicity During Radiation Therapy for Head-and-Neck Cancer: First Report of Trans Tasman Radiation Oncology Group (TROG) 07.03 RadioHUM Study

    Energy Technology Data Exchange (ETDEWEB)

    Macann, Andrew, E-mail: amacann@adhb.govt.nz [Department of Radiation Oncology, Auckland City Hospital, Auckland (New Zealand); Fua, Tsien [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Milross, Chris G. [Department of Radiation Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales (Australia); Porceddu, Sandro V. [Oncology Services, Princess Alexandra Hospital, Woolloongabba, Queensland (Australia); Penniment, Michael [Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia (Australia); Wratten, Chris [Radiation Oncology, Calvary Mater Newcastle, Waratah, New South Wales (Australia); Krawitz, Hedley [Department of Radiation Oncology, Auckland City Hospital, Auckland (New Zealand); Poulsen, Michael [Department of Radiation Oncology, Radiation Oncology Mater Centre, South Brisbane, Queensland (Australia); Tang, Colin I. [Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia (Australia); Morton, Randall P. [Department of Otorhinolaryngology, Middlemore Hospital, Otahuhu, Auckland (New Zealand); Hay, K. David [Department of Oral Health, Auckland City Hospital, Auckland (New Zealand); Thomson, Vicki [Department of Otorhinolaryngology, Auckland City Hospital, Auckland (New Zealand); Bell, Melanie L.; King, Madeleine T. [Psycho-oncology Cooperative Research Group, Univerity of Sydney, Sydney, New South Wales (Australia); Fraser-Browne, Carol L. [Adult Oncology Research Centre, Auckland City Hospital, Auckland (New Zealand); Hockey, Hans-Ulrich P. [Biometrics Matters Ltd, Hamilton (New Zealand)

    2014-03-01

    Purpose: To assess the impact of domicile-based humidification on symptom burden during radiation therapy (RT) for head-and-neck (H and N) cancer. Methods and Materials: From June 2007 through June 2011, 210 patients with H and N cancer receiving RT were randomized to either a control arm or to receive humidification using the Fisher and Paykel Healthcare MR880 humidifier. Humidification commenced on day 1 of RT and continued until Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, clinical mucositis (CMuc) grade ≤1 occurred. Forty-three patients (42%) met a defined benchmark for humidification compliance and contributed to per protocol (PP) analysis. Acute toxicities, hospitalizations, and feeding tube events were recorded prospectively. The McMaster University Head and Neck Radiotherapy Questionnaire (HNRQ) was used for patient-reported outcomes. The primary endpoint was area under the curve (AUC) for CMuc grade ≥2. Results: There were no significant differences in AUC for CMuc ≥2 between the 2 arms. Humidification patients had significantly fewer days in hospital (P=.017). In compliant PP patients, the AUC for CTCAE functional mucositis score (FMuc) ≥2 was significantly reduced (P=.009), and the proportion who never required a feeding tube was significantly greater (P=.04). HNRQ PP analysis estimates also in the direction favoring humidification with less symptom severity, although differences at most time points did not reach significance. Conclusions: TROG 07.03 has provided efficacy signals consistent with a role for humidification in reducing symptom burden from mucositis, but the influence of humidification compliance on the results moderates recommendations regarding its practical utility.

  1. Rice-based oral rehydration solution decreases the stool volume in acute diarrhoea.

    Science.gov (United States)

    Molla, A M; Ahmed, S M; Greenough, W B

    1985-01-01

    A ramdomized trial using oral rehydration solutions (ORS) with rice or glucose was carried out in 342 patients with acute watery diarrhea in the outpatient ward of the International Centre for Diarrheal Disease Research, Bangladesh, during an epidemic of cholera between December 1982-March 1983. On admission, 75% of these patients had severe dehydration and 70% were positive for Vibrio cholerae. There were 185 children aged under 10 years and 157 adults; 169 patients were treated with rice-ORS and 173 with glucose-ORS. Patients in both groups were comparable in age and body weight as well as the duration and severity of illness. Patients with severe dehydration were first rehydrated intravenously, and then treated with ORS. Those with moderate dehydration received ORS from the start. The mean stool output in the first 24 hours in children treated with rice-ORS was less than that in those treated with glucose-ORS (155 vs 204 ml/kg 24h; P0.01). The same was the case for the adult patients, the corresponding values for stool output being 115 versus 159 ml/kg24h (P0.05); the corresponding intakes in adult patients were, respectively, 180.5 and 247 ml/kg24 hours. A gain of about 10% of the body weight on admission was observed in all the groups. 6 cases (4 children and 2 adults) who failed to respond to oral rehydration after intravenous therapy all belonged to the glucose-ORS group. The study shows that, even under epidemic conditions of severe cholera or in cholera-like diarrhea, the glucose or sucrose solutions can be replaced by rice powder with improved results. Glucose and sucrose are manufactured products which are expensive and not always available in countries where diarrheal diseases are a problem. Rice, a staple food in many of these countries, reduces the fluid requirements when used in ORS and also provides increased nutrition even in the acute stage of illness.

  2. Acute electromyostimulation decreases muscle sympathetic nerve activity in patients with advanced chronic heart failure (EMSICA Study.

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    Marc Labrunée

    Full Text Available BACKGROUND: Muscle passive contraction of lower limb by neuromuscular electrostimulation (NMES is frequently used in chronic heart failure (CHF patients but no data are available concerning its action on sympathetic activity. However, Transcutaneous Electrical Nerve Stimulation (TENS is able to improve baroreflex in CHF. The primary aim of the present study was to investigate the acute effect of TENS and NMES compared to Sham stimulation on sympathetic overactivity as assessed by Muscle Sympathetic Nerve Activity (MSNA. METHODS: We performed a serie of two parallel, randomized, double blinded and sham controlled protocols in twenty-two CHF patients in New York Heart Association (NYHA Class III. Half of them performed stimulation by TENS, and the others tested NMES. RESULTS: Compare to Sham stimulation, both TENS and NMES are able to reduce MSNA (63.5 ± 3.5 vs 69.7 ± 3.1 bursts / min, p < 0.01 after TENS and 51.6 ± 3.3 vs 56.7 ± 3.3 bursts / min, p < 0, 01 after NMES. No variation of blood pressure, heart rate or respiratory parameters was observed after stimulation. CONCLUSION: The results suggest that sensory stimulation of lower limbs by electrical device, either TENS or NMES, could inhibit sympathetic outflow directed to legs in CHF patients. These properties could benefits CHF patients and pave the way for a new non-pharmacological approach of CHF.

  3. Increased Interleukin-17 and decreased BAFF serum levels in drug-free acute schizophrenia.

    Science.gov (United States)

    El Kissi, Yousri; Samoud, Samar; Mtiraoui, Ahlem; Letaief, Leila; Hannachi, Neila; Ayachi, Mouna; Ali, Bechir Ben Hadj; Boukadida, Jalel

    2015-01-30

    Hypotheses regarding an immune-cytokine basis of schizophrenia have been postulated with controversial findings and a lack of data related to many cytokines. The aim of this study was to assess serum levels of Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Transforming Growth Factor-β (TGF-β), Interleukin-17 (IL-17) and B-cell Activating Factor (BAFF) in schizophrenic patients and to determine correlations between cytokine levels and clinical parameters. Serum cytokine levels were measured with ELISA techniques in 60 neuroleptic-free patients on acute phase of the disease (BPRS≥40) and 28 healthy controls matched for age and sex. Current symptoms were assessed with Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). No significant difference was found between patients and controls regarding IFN-γ serum levels. IL-4 was not detected in both groups. Patients exhibited significantly higher IL-17 and lower BAFF serum levels. IL-17 and BAFF levels were negatively correlated in schizophrenic patients. SANS global score was negatively correlated with IL-17 and positively correlated with IFN-γ serum levels. These results argue against the involvement of Th1 or Th2 population cells in schizophrenia. IL-17 and BAFF could be valuable markers for schizophrenia.

  4. Simvastatin reduces endotoxin-induced acute lung injury by decreasing neutrophil recruitment and radical formation.

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    Jochen Grommes

    Full Text Available INTRODUCTION: Treatment of acute lung injury (ALI remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions. METHODS: C57Bl/6 mice were exposed to aerosolized LPS (500 µg/ml for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor effects of simvastatin on bacterial clearance we performed phagocytosis and bacterial killing studies in vitro as well as sepsis experiments in mice. RESULTS: Simvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. Moreover, simvastatin reduces the formation of ROS species and adhesion of neutrophils without affecting apoptosis, bacterial phagocytosis and bacterial clearance. CONCLUSION: Simvastatin reduces recruitment and activation of neutrophils hereby protecting from LPS-induced ALI. Our results imply a potential role for statins in the management of ALI.

  5. Adherence to vector preventive measures decrease cases of acute Dengue among Abuja residents, Nigeria

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    Idris Abdullahi Nasir

    2017-07-01

    Full Text Available Background: Nigeria is one of the dengue hyper-endemic nations. This study investigated the level of knowledge about dengue and vector preventive practices and their impacts on acute dengue among febrile patients at Abuja, Nigeria. Materials and methods: This cross-sectional survey was conducted on febrile patients attending University of Abuja Teaching Hospital, Abuja, Nigeria. Blood samples were individually collected from 171 febrile patients residing at Gwagwalada suburb. Interviewer administered questionnaires were used to assess subjects’ knowledge about preventive measures against vector breeding and bites. Blood samples were tested for dengue virus Nonstructural glycoprotein-1antigen using enzyme linked Immunosorbent assay (ELISA. Results: Fifteen out of 171 febrile persons (8.8% were Dengue NS1 positive. Sixty percent of the subjects do not know about dengue, while 33% knew about dengue virus infection through television/ radio programs, 5% through healthcare professionals and 2% from friends/families. Those who persistently use indoor residual spraying and long sleeves/trousers during daytime had less cases of DENV NS1 than those who do not. There was statistical association between DENV NS1 and residence in proximity to waste dumpsites (P<0.0001 and frequent use of long sleeve clothing and trousers (P=0.005. However, there was no statistical association between DENV NS1 antigenemia and persistent use of indoor residual spraying and presence of in-door water containers (P>0.05. Conclusions: Findings from this study imply that proper education and adherence to preventive measures minimize people from being susceptible to Dengue virus infections.

  6. Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults.

    Science.gov (United States)

    Moore, M C; Cherrington, A D; Mann, S L; Davis, S N

    2000-12-01

    In animal models, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to the glucose load. Therefore, we examined the effect of fructose on glucose tolerance in 11 healthy human volunteers (5 men and 6 women). Each subject underwent an oral glucose tolerance test (OGTT) on 2 separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without 7.5 g fructose (OGTT+F or OGTT-F), in random order. Arterialized blood samples were obtained from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 2 h afterward. The area under the curve (AUC) of the change in plasma glucose was 19% less in OGTT+F vs. OGTT-F (P: Glucose tolerance was improved by fructose in 9 subjects and worsened in 2. All 6 subjects with the largest glucose AUC during OGTT-F had a decreased response during OGTT+F (31 +/- 5% decrease). The insulin AUC did not differ between the 2 studies. Of the 9 subjects with improved glucose tolerance during the OGTT+F, 5 had smaller insulin AUC during the OGTT+F than the OGTT-F. Plasma glucagon concentrations declined similarly during OGTT-F and OGTT+F. The blood lactate response was about 50% greater during the OGTT+F (P: fructose improves the glycemic response to an oral glucose load in normal adults without significantly enhancing the insulin or triglyceride response. Fructose appears most effective in those normal individuals who have the poorest glucose tolerance.

  7. Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model.

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    Laure B Bindels

    Full Text Available The gut microbiota has recently been proposed as a novel component in the regulation of host homeostasis and immunity. We have assessed for the first time the role of the gut microbiota in a mouse model of leukemia (transplantation of BaF3 cells containing ectopic expression of Bcr-Abl, characterized at the final stage by a loss of fat mass, muscle atrophy, anorexia and inflammation. The gut microbial 16S rDNA analysis, using PCR-Denaturating Gradient Gel Electrophoresis and quantitative PCR, reveals a dysbiosis and a selective modulation of Lactobacillus spp. (decrease of L. reuteri and L. johnsonii/gasseri in favor of L. murinus/animalis in the BaF3 mice compared to the controls. The restoration of Lactobacillus species by oral supplementation with L. reuteri 100-23 and L. gasseri 311476 reduced the expression of atrophy markers (Atrogin-1, MuRF1, LC3, Cathepsin L in the gastrocnemius and in the tibialis, a phenomenon correlated with a decrease of inflammatory cytokines (interleukin-6, monocyte chemoattractant protein-1, interleukin-4, granulocyte colony-stimulating factor, quantified by multiplex immuno-assay. These positive effects are strain- and/or species-specific since L. acidophilus NCFM supplementation does not impact on muscle atrophy markers and systemic inflammation. Altogether, these results suggest that the gut microbiota could constitute a novel therapeutic target in the management of leukemia-associated inflammation and related disorders in the muscle.

  8. Epidural anesthesia improves pancreatic perfusion and decreases the severity of acute pancreatitis.

    Science.gov (United States)

    Sadowski, Samira M; Andres, Axel; Morel, Philippe; Schiffer, Eduardo; Frossard, Jean-Louis; Platon, Alexandra; Poletti, Pierre-Alexandre; Bühler, Leo

    2015-11-21

    To study the safety of epidural anesthesia (EA), its effect on pancreatic perfusion and the outcome of patients with acute pancreatitis (AP). From 2005 to August 2010, patients with predicted severe AP [Ranson score ≥ 2, C-reactive protein > 100 or necrosis on computed tomography (CT)] were prospectively randomized to either a group receiving EA or a control group treated by patient controlled intravenous analgesia. Pain management was evaluated in the two groups every eight hours using the visual analog pain scale (VAS). Parameters for clinical severity such as length of hospital stay, use of antibiotics, admission to the intensive care unit, radiological/clinical complications and the need for surgical necrosectomy including biochemical data were recorded. A CT scan using a perfusion protocol was performed on admission and at 72 h to evaluate pancreatic blood flow. A significant variation in blood flow was defined as a 20% difference in pancreatic perfusion between admission and 72 h and was measured in the head, body and tail of the pancreas. We enrolled 35 patients. Thirteen were randomized to the EA group and 22 to the control group. There were no differences in demographic characteristics between the two groups. The Balthazar radiological severity score on admission was higher in the EA group than in the control group (mean score 4.15 ± 2.54 vs 3.38 ± 1.75, respectively, P = 0.347) and the median Ranson scores were 3.4 and 2.7 respectively (P = NS). The median duration of EA was 5.7 d, and no complications of the epidural procedure were reported. An improvement in perfusion of the pancreas was observed in 13/30 (43%) of measurements in the EA group vs 2/27 (7%) in the control group (P = 0.0025). Necrosectomy was performed in 1/13 patients in the EA group vs 4/22 patients in the control group (P = 0.63). The VAS improved during the first ten days in the EA group compared to the control group (0.2 vs 2.33, P = 0.034 at 10 d). Length of stay and mortality

  9. Cancer therapy-related oral mucositis.

    Science.gov (United States)

    Redding, Spencer W

    2005-08-01

    Oral mucositis is a common side effect of cancer therapies, particularly radiation therapy for head and neck cancer and various forms of chemotherapy. It commonly results in severe oral pain that can compromise the duration and success of cancer management. Hospitalizations are common because patients lose the ability to take anything by mouth due to severe pain and must have alimentation supported during this period. Pain management usually requires potent narcotic analgesia. Cancer therapy-related oral mucositis is commonly described as the most significant and debilitating acute complication associated with radiation therapy and chemotherapy. Until recently, cancer therapy-induced oral mucositis was thought to be a process involving the epithelium only. Evidence is building that the process of oral mucositis involves far more than just the epithelium, but includes multiple cellular processes of the submucosa as well. Many strategies have been evaluated to prevent oral mucositis, but the data is confusing since it is often conflicting. Therapy with the growth factor, KGF1, appears promising, as it is the only medication currently approved by the FDA. A multifaceted approach that targets the entire mucositis process will probably be needed to optimize overall prevention.

  10. Decrease in serum adiponectin levels in response to treatment predicts good prognosis in acute decompensated heart failure.

    Science.gov (United States)

    Matsumoto, Mika; Lee-Kawabata, Masaaki; Tsujino, Takeshi; Naito, Yoshiro; Ezumi, Akira; Sakoda, Tsuyoshi; Ohyanagi, Mitsumasa; Shimomura, Iichiro; Masuyama, Tohru

    2010-11-01

    Adiponectin is a cardioprotective adipocytokine. Serum adiponectin concentration decreases in patients who are obese but increases in patients with chronic heart failure (CHF). The aim of this study was to explore the temporal changes in serum adiponectin concentration following treatment for acute decompensated heart failure (ADHF). Serum adiponectin was measured on admission and at discharge in 95 patients who were admitted to our hospital with ADHF. Ten patients without heart failure (HF) served as controls. Serum adiponectin concentration was higher on admission in HF patients than in the controls (22.6±13.3 μg/mL vs 9.3±3.9 μg/mL, P<.01). Serum adiponectin concentration decreased after treatment in HF patients (18.0±11.7 μg/mL vs 22.6±13.3 μg/mL, P<.01). The larger temporal decrease in adiponectin level in ADHF was associated with the lower incidence of cardiac death or HF hospitalizations (log-rank, P<.05). Serum adiponectin concentration was elevated in ADHF and decreased following the treatment. How much serum adiponectin decreases in response to treatment in ADHF is an important determinant of the prognosis. © 2010 Wiley Periodicals, Inc.

  11. Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

    DEFF Research Database (Denmark)

    Castellano, J M; Bentsen, A H; Romero, M;

    2010-01-01

    Severe inflammatory challenges are frequently coupled to decreased food intake and disruption of reproductive function, the latter via deregulation of different signaling pathways that impinge onto GnRH neurons. Recently, the hypothalamic Kiss1 system, a major gatekeeper of GnRH function...... of hypothalamic kisspeptin immunoreactivity (IR) and hormonal responses to kisspeptin during the acute inflammatory phase. LPS injections induced a dramatic but transient drop of serum LH and testosterone levels. Suppression of gonadotropic function was associated with a significant decrease in kisspeptin...... for the neuroendocrine control of reproduction. Our results also suggest that suppressed gonadotropic function following inflammatory challenges might involve a reduction in absolute responsiveness to kisspeptin that is independent of the anorectic effects of inflammation....

  12. Establishment of a Single Dose Radiation Model of Oral Mucositis in Mice

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    Ryu, Seung Hee; Moon, Soo Young; Choi, Eun Kyung; Kim, Jong Hoon; Ahn, Seung Do; Song, Si Yeol; Park, Jin Hong; Noh, Young Ju; Lee, Sang Wook [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2008-12-15

    Oral mucositis induced by radiotherapy to the head and neck area, is a common acute complication and is considered as the most severe symptom for cancer patients in the early stages of treatment. This study was proposed to establish the oral mucositis mouse model induced by a single dose of radiation for the facility of testing therapeutic candidates which can be used for the oral mucositis treatments. Materials and Methods: Fifty-five BALB/c mice were divided into four groups: control, 16 Gy, 18 Gy, and 20 Gy. Oral mucositis was induced by a single dose of radiation to the head and neck using 6 MV x-Ray from linear accelerator. After irradiation, body weight and physical abnormalities were checked daily. Tongue tissues from all groups were taken on days 1, 2, 3, 5, 7, 9, and 14, respectively and H and E staining was conducted to examine morphological changes. Results: Body weight dramatically decreased after day 5 in all irradiated mice. In the 16 Gy treatment group, body weight was recovered on day 14. The histology data showed that the thickness of the epithelial cell layer was decreased by the accumulated time after radiation treatment, up to day 9. Severe ulceration was revealed on day 9. Conclusion: A single dose of 16 Gy is sufficient dose to induce oral mucositis in Balb/C mice. Significant changes were observed in the Balb/C mice on days 7 and 9 after radiation. It is suggested that this mouse model might be a useful standard tool for studying oral mucositis induced by radiation.

  13. Radiation induced oral mucositis

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    P S Satheesh Kumar

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  14. Impact of decreased serum albumin levels on acute kidney injury in patients with acute decompensated heart failure: a potential association of atrial natriuretic peptide.

    Science.gov (United States)

    Takaya, Yoichi; Yoshihara, Fumiki; Yokoyama, Hiroyuki; Kanzaki, Hideaki; Kitakaze, Masafumi; Goto, Yoichi; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kawano, Yuhei; Kangawa, Kenji

    2017-02-07

    Although hypoalbuminemia at admission is a risk for acute kidney injury (AKI) and mortality in patients with acute decompensated heart failure (ADHF), the clinical significance of decreased serum albumin levels (DAL) during ADHF therapy has not been elucidated. This study aimed to evaluate whether DAL was associated with AKI, and whether intravenous atrial natriuretic peptide (ANP) administration, which provides an effective treatment for ADHF but promotes albumin extravasation, was associated with DAL and AKI. A total of 231 consecutive patients with ADHF were enrolled. AKI was defined as ≥0.3 mg/dl absolute or 1.5-fold increase in serum creatinine levels within 48 h. AKI occurred in 73 (32%) of the 231 patients during ADHF therapy. The median value of decreases in serum albumin levels was 0.3 g/dl at 7 days after admission. When DAL was defined as ≥0.3 g/dl decrease in serum albumin levels, DAL occurred in 113 patients, and was independently associated with AKI. Of the 231 patients, 73 (32%) were treated with intravenous ANP. DAL occurred more frequently in patients receiving ANP than in those not receiving ANP (77 vs. 36%, p < 0.001), and ANP was independently associated with DAL. The incidence of AKI was higher in patients receiving ANP than in those not receiving ANP (48 vs. 24%, p < 0.001). ANP was independently associated with AKI. In conclusion, DAL is associated with AKI. Intravenous ANP administration may be one of the promoting factors of DAL, which leads to AKI, indicating a possible novel mechanism of AKI.

  15. Mortality after acute trauma:progressive decreasing rather than a trimodal distribution

    Institute of Scientific and Technical Information of China (English)

    Ionut Negoi; Sorin Paun; Sorin Hostiuc; Bogdan Stoica; Ioan Tanase; Ruxandra Irina Negoi; Gabriel Constantinescu; Mircea Beuran

    2015-01-01

    actual for developing trauma care systems. In conclusion, the pattern of mortality due to major trauma seems decreasing continuously with time rather than presenting high peaks of frequency at some moments.

  16. Decreased Incentive Motivation Following Knockout or Acute Blockade of the Serotonin Transporter: Role of the 5-HT2C Receptor.

    Science.gov (United States)

    Browne, Caleb J; Fletcher, Paul J

    2016-09-01

    Acute pharmacological elevation of serotonin (5-hydroxytryptamine; 5-HT) activity decreases operant responding for primary reinforcers, suggesting that 5-HT reduces incentive motivation. The mechanism by which 5-HT alters incentive motivation is unknown, but parallel evidence that 5-HT2C receptor agonists also reduce responding for primary reinforcers implicates this receptor as a potential candidate. These experiments examined whether chronic and acute disruptions of serotonin transporter (SERT) activity altered incentive motivation, and whether the 5-HT2C receptor mediated the effects of elevated 5-HT on behavior. To assess incentive motivation, we measured responding for three different reinforcers: a primary reinforcer (saccharin), a conditioned reinforcer (CRf), and an unconditioned sensory reinforcer (USRf). In the chronic condition, responding was compared between SERT knockout (SERT-KO) mice and their wild-type littermates. In the acute condition, responding was examined in wild-type mice following treatment with 10 or 20 mg/kg citalopram, or its vehicle. The ability of the selective 5-HT2C antagonist SB 242084 to prevent the effects of SERT-KO and citalopram on responding was subsequently examined. Both SERT-KO and citalopram reduced responding for saccharin, a CRf, and a USRf. Treatment with SB 242084 enhanced responding for a CRf and a USRf in SERT-KO mice and blocked the effects of citalopram on CRf and USRf responding. However, SB 242084 was unable to prevent the effects of SERT-KO or citalopram on responding for saccharin. These results support a powerful inhibitory function for 5-HT in the control of incentive motivation, and indicate that the 5-HT2C receptor mediates these effects of 5-HT in a reinforcer-dependent manner.

  17. Decreased humoral antibody episodes of acute renal allograft rejection in recipients expressing the HLA-DQβ1*0202 allele.

    Science.gov (United States)

    Mannam, Venkat K R; Santos, Mark; Lewis, Robert E; Cruse, Julius M

    2012-10-01

    The present investigation was designed to show the effect of human leukocyte antigen (HLA) class II molecular allelic specificities in the recipient on the induction of humoral antibody rejection, identified by C4d peritubular capillary staining, as well as specific antibody identified by Luminex technology. Major histocompatibility complex (MHC) class II molecules are expressed on dendritic cells, macrophages, and B lymphocytes and they present antigenic peptides to CD4 positive T lymphocytes. Human renal peritubular and glomerular capillaries express class II MHC molecules upon activation. Expression of class II molecules on renal microvascular endothelial cells exposes them to possible interaction with specific circulating antibodies. We hypothesize that HLA-DQβ1*0202 expression in recipients decreases the likelihood of antibody-mediated renal allograft rejection. We found that 80% (=25) of DQ2 positive haplotype recipients failed to induce humoral antibody renal allograft rejection and 20% (n=25) of DQ2 positive haplotype recipients induced humoral antibody renal allograft rejection (p=0.008). By contrast, 48% (n=46) of DQ2 negative haplotype recipients failed to induce a humoral antibody component of renal allograft rejection and 52% (n=46) of DQ2 negative haplotype recipients induced humoral antibody-mediated renal allograft rejection. Our results suggest that recipients who express the DQβ1*0202 allele are less likely to induce a humoral antibody component of acute renal allograft rejection than are those expressing DQ1, DQ3, or DQ4 alleles. DQβ1*0202 allele expression in recipients could possibly be protective against acute humoral allograft rejection and might serve as a future criterion in recipient selection and in appropriate therapy for acute renal rejection episodes.

  18. Non-dirt house floor and the stimulant of environmental health decreased the risk Acute Respiratory Infection (ARI

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    Putu Suriyasa

    2006-03-01

    Full Text Available The risk factors related to acute respiratory infection (ARI, among others, is house floor. The aim of this research was to identify the influence of the Family Health and Nutrition program (FHN and other risk factors related to ARI. Data was obtained from a survey conducted in 5 provinces in Indonesia, which received the project of Family Health and Nutrition (FHN in 2003. The number of subjects was 1,500 families, selected by stratified random sampling method. The questionnaire completion and the observation were done on the spot in the subject’s house by special trained interviewers. The use of non-dirt house floor built prior to the project of FHN decreased the risk of ARI cases of 51% than the use of dirt house floor [Odds Ratio (OR = 0.49; 95% Confidence Interval (CI = 0.25-0.96]. The risk of ARI decreased of 52% among those who received than those which never received the stimulant of environmental health Family Health and Nutrition program (OR = 0.48; 95% CI =0.33-0.70. To decrease the risks of ARI cases, the program of environmental health is necessarily continued. (Med J Indones 2006; 15:60-5Keywords: ARI, non-dirt house floor, and stimulant of environmental health

  19. Train-the-trainer intervention to increase nursing teamwork and decrease missed nursing care in acute care patient units.

    Science.gov (United States)

    Kalisch, Beatrice J; Xie, Boqin; Ronis, David L

    2013-01-01

    Teamwork is essential for patient safety and results in less missed nursing care. The aim of this study was to test the impact of a train-the-trainer intervention on the level of satisfaction with nursing teamwork and the amount of missed nursing care. This study used a quasiexperimental design with repeated measures taken at pretest, posttest, and 2 months after completion of the intervention. The sample for this study was the nursing staff on three medical-surgical units in three separate acute care hospitals (one unit in each hospital). Three nurses from each unit underwent a training program and then taught the skills and knowledge they acquired to the staff members on their units in three-hour-long sessions. The training involved staff role-playing scenarios based on teamwork problems that occur regularly on inpatient units in acute care hospitals followed by debriefing, which focused on teamwork behaviors (e.g., leadership, team orientation, backup, performance monitoring) and missed nursing care. Four measures were used to test the efficacy of this intervention: The Nursing Teamwork Survey, the MISSCARE Survey, and questions about the knowledge of and satisfaction with teamwork. Return rates for the surveys ranged from 73% to 84%. Follow-up tests individually comparing pretest, posttest, and delayed posttest were conducted within the mixed model and used the Bonferroni correction for multiple comparisons. Teamwork increased (F = 6.91, df = 259.01, p = .001) and missed care decreased (F = 3.59, df = 251.29, p = .03) over time. Nursing staff also reported a higher level of satisfaction with teamwork and an increase of teamwork knowledge after the intervention. The intervention tested in this study shows promise of being an effective and efficient approach to increase nursing teamwork and decrease missed nursing care.

  20. Emu Oil Combined with Lyprinol™ Reduces Small Intestinal Damage in a Rat Model of Chemotherapy-Induced Mucositis.

    Science.gov (United States)

    Mashtoub, Suzanne; Lampton, Lorrinne S; Eden, Georgina L; Cheah, Ker Y; Lymn, Kerry A; Bajic, Juliana E; Howarth, Gordon S

    2016-10-01

    Chemotherapy-induced mucositis is characterized by inflammation and ulcerating lesions lining the alimentary tract. Emu Oil and Lyprinol™ have independently demonstrated their therapeutic potential in intestinal inflammatory disorders, including mucositis. We investigated Emu Oil and Lyprinol™ in combination for their further potential to alleviate chemotherapy-induced mucositis in rats. Rats were gavaged with (1 ml) water, Olive Oil, Emu Oil + Olive Oil, Lyprinol™ + Olive Oil or Emu Oil + Lyprinol™ from Days 0 to 7, injected with saline (control) or 5-Fluorouracil (5-FU) on Day 5 and euthanized on Day 8. Myeloperoxidase (MPO) activity (indicative of acute inflammation), histological severity scores, and intestinal architecture were quantified. Myeloperoxidase activity was significantly increased in the jejunum and ileum following 5-FU, compared to saline controls. Both Olive Oil and Emu Oil + Lyprinol™ significantly reduced jejunal MPO levels (1.8-fold and 1.7-fold, respectively), whereas only Emu Oil + Lyprinol™ significantly decreased ileal MPO levels, relative to 5-FU controls. All oil treatments decreased histological severity scores in the jejunum and ileum, and normalized crypt depth in the mid small intestine, relative to 5-FU controls. Emu Oil combined with Lyprinol™ partially reduced acute small intestinal inflammation. Isolating bioactive constituents of these naturally sourced oils could provide a more targeted strategy to protect against intestinal mucositis.

  1. Nasal mucosal biopsy

    Science.gov (United States)

    Biopsy - nasal mucosa; Nose biopsy ... to fast for a few hours before the biopsy. ... Nasal mucosal biopsy is usually done when abnormal tissue is seen during examination of the nose. It may also be done ...

  2. Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats

    Directory of Open Access Journals (Sweden)

    Peng Wang

    2015-08-01

    Full Text Available Carbon monoxide (CO has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI has not been reported as of yet. The purpose of the present study was to explore the effects of exogenous CO on sepsis-induced AKI and nucleotide-binding domain-like receptor protein 3 (NLRP3 inflammasome activation in rats. Male rats were subjected to cecal ligation and puncture (CLP to induce sepsis and AKI. Exogenous CO delivered from CO-releasing molecule 2 (CORM-2 was used intraperitoneally as intervention after CLP surgery. Therapeutic effects of CORM-2 on sepsis-induced AKI were assessed by measuring serum creatinine (Scr and blood urea nitrogen (BUN, kidney histology scores, apoptotic cell scores, oxidative stress, levels of cytokines TNF-α and IL-1β, and NLRP3 inflammasome expression. CORM-2 treatment protected against the sepsis-induced AKI as evidenced by reducing serum Scr/BUN levels, apoptotic cells scores, increasing survival rates, and decreasing renal histology scores. Furthermore, treatment with CORM-2 significantly reduced TNF-α and IL-1β levels and oxidative stress. Moreover, CORM-2 treatment significantly decreased NLRP3 inflammasome protein expressions. Our study provided evidence that CORM-2 treatment protected against sepsis-induced AKI and inhibited NLRP3 inflammasome activation, and suggested that CORM-2 could be a potential therapeutic candidate for treating sepsis-induced AKI.

  3. Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats.

    Science.gov (United States)

    Wang, Peng; Huang, Jian; Li, Yi; Chang, Ruiming; Wu, Haidong; Lin, Jiali; Huang, Zitong

    2015-08-31

    Carbon monoxide (CO) has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI) has not been reported as of yet. The purpose of the present study was to explore the effects of exogenous CO on sepsis-induced AKI and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in rats. Male rats were subjected to cecal ligation and puncture (CLP) to induce sepsis and AKI. Exogenous CO delivered from CO-releasing molecule 2 (CORM-2) was used intraperitoneally as intervention after CLP surgery. Therapeutic effects of CORM-2 on sepsis-induced AKI were assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN), kidney histology scores, apoptotic cell scores, oxidative stress, levels of cytokines TNF-α and IL-1β, and NLRP3 inflammasome expression. CORM-2 treatment protected against the sepsis-induced AKI as evidenced by reducing serum Scr/BUN levels, apoptotic cells scores, increasing survival rates, and decreasing renal histology scores. Furthermore, treatment with CORM-2 significantly reduced TNF-α and IL-1β levels and oxidative stress. Moreover, CORM-2 treatment significantly decreased NLRP3 inflammasome protein expressions. Our study provided evidence that CORM-2 treatment protected against sepsis-induced AKI and inhibited NLRP3 inflammasome activation, and suggested that CORM-2 could be a potential therapeutic candidate for treating sepsis-induced AKI.

  4. Large decrease in acute aquatic toxicity of linear alkylbenzene sulfonate in hard water and seawater by adding adsorbent.

    Science.gov (United States)

    Oya, Masaru; Takemoto, Yuka; Ishikawa, Yusuke

    2008-01-01

    LAS (Linear Alkylbenzene Sulphonate) shows relatively high aquatic toxicity in hard freshwater or seawater. In this paper, we studied the effect of adsorbent on the aquatic toxicity of LAS in hard freshwater and seawater. Daphnia magna and Artemia salina were used for acute aquatic toxicity test in freshwater and seawater, respectively. Kaolin was used as a model adsorbent and toxic surface tension (gamma(tox)) was used as an indicator of toxic condition. Results showed that the values of gamma(tox) of LAS to D. magna and A. salina were about 45-55 mN/m and 35-40 mN/m, respectively. Surface tension of LAS solution decreased and its aquatic toxicity increased with increasing the water hardness or the salinity. By adding adsorbent into the solutions, the surface activity and the aquatic toxicity were decreased greatly, and the effect of water hardness or salinity on surface tension and aquatic toxicity were removed. That is to say, the surface tension curve of soft freshwater corresponds with that of hard freshwater containing adsorbent and the surface tension curve at low salinity corresponds with that obtained for high salinity solutions containing the adsorbent. Therefore, our experimental data leads to the conclusion that the relatively high aquatic toxicity of LAS in concentrated solution of inorganic salts disappears in the presence of adsorbents. This is an important viewpoint in conducting environmental risk assessment of surfactants.

  5. Aspiration Thrombectomy and Drug-Eluting Stent Implantation Decrease the Occurrence of Angina Pectoris One Year After Acute Myocardial Infarction.

    Science.gov (United States)

    Lee, Wei-Chieh; Fang, Chih-Yuan; Chen, Huang-Chung; Hsueh, Shu-Kai; Chen, Chien-Jen; Yang, Cheng-Hsu; Yip, Hon-Kan; Hang, Chi-Ling; Wu, Chiung-Jen; Fang, Hsiu-Yu

    2016-04-01

    Angina pectoris is a treatable symptom that is associated with mortality and decreased quality of life. Angina eradication is a primary care goal of care after an acute myocardial infarction (AMI). Our aim was to evaluate factors influencing angina pectoris 1 year after an AMI.From January 2005 to December 2013, 1547 patient received primary percutaneous intervention in our hospital for an acute ST-segment elevation myocardial infarction (MI). Of these patients, 1336 patients did not experience post-MI angina during a 1-year follow-up, and 211 patients did. Univariate and multivariate logistic regression analyses were performed to identify the factors influencing angina pectoris 1 year after an AMI. Propensity score matched analyses were performed for subgroups analyses.The average age of the patients was 61.08 ± 12.77 years, with a range of 25 to 97 years, and 82.9% of the patients were male. During 1-year follow-up, 13.6% of the patients experienced post-MI angina. There was a longer chest pain-to-reperfusion time in the post-MI angina group (P = 0.01), as well as a higher fasting sugar level, glycohemoglobin (HbA1C), serum creatinine, troponin-I and creatine kinase MB (CK-MB). The post-MI angina group also had a higher prevalence of multiple-vessel disease. Manual thrombectomy, and distal protective device and intracoronary glycoprotein IIb/IIIa inhibitor injection were used frequently in the no post-MI angina group. Antiplatelet agents and post-MI medication usage were similar between the 2 groups. Multivariate logistic regression analyses demonstrated that prior MI was a positive independent predictor of occurrence of post-MI angina. Manual thrombectomy use and drug-eluting stent implantation were negative independent predictors of post-MI angina. Higher troponin-I and longer chest pain-to-reperfusion time exhibited a trend toward predicting post-MI angina.Prior MIs were strong, independent predictors of post-MI angina. Manual thrombectomy and drug

  6. 急性出血坏死性胰腺炎大鼠肠道免疫功能的改变%Intestinal mucosal immune barrier injury of rats with acute hemorrhagic necrotic pancreatiti

    Institute of Scientific and Technical Information of China (English)

    金英朝; 王海宽; 张弘超; 李小东; 刘大伟

    2015-01-01

    ObjectiveTo observe intestinal mucosal immune barrier relative factors TNF-α in serum, sIgA levels of intestinal juice, and CD3+ and CD4+ cell change of intestinal tissue in rats with acute hemorrhagic necrotic pancreatitis. To investigate the change of intestinal mucosal immune barrier injury in this model.Methods36 wistar rats were randomly divided into three groups: SAP model group(A group), the sham operation control group (B group) (N = 18). Abdominal aortic and Portal vein blood were collected, and stored in refrigerator for next assays. Intestinal juice were collected and stored in refrigerator for next assays. The intestinal tissue were ifxed in 4% neutral formaldehyde buffer. TNF-α concentration of blood and sIgA levels of intestinal juice were evaluated by ELISA method. Immunohistochemistry was adopted to detect intestinal tissue CD3+ and CD4+ expression. Endotoxin levels of portal vein blood was detected following the kit instruction.ResultsTesting the indicators after model building of each group,we have the following ifndings: In group A, Blood TNF-a and sIgA levels of intestinal juice are signiifcantly lower than that in the group B, while endotoxin levels of portal vein blood signiifcantly higher. The expression of CD3+ and CD4+ T immune cell are signiifcantly lower in group A.ConclusionThis study conifrmed the participation of the intestinal mucosal immune barrier function injury are important inlfammatory disorders in acute pancreatitis in rats with acute hemorrhagic necrotic pancreatitis.%目的:探讨分析急性出血坏死性胰腺炎(AHNP)大鼠肠道黏膜免疫功能的变化情况。方法选取成年的Wistar雄性大鼠,随机分成AHNP组、假手术组。分别于造模后24 h取标本检测(主要包括内毒素的含量、CD3、CD4及CD8的阳性T淋巴细胞的比例、盲肠内容物sIgA的浓度,血清肿瘤坏死因子-α(TNF-α)的水平等。结果 AHNP组各时间段的门静脉血内毒素含量均有显著

  7. 肥大细胞在急性应激性肠黏膜屏障损伤中的作用机制%Mechanism of Mast Cells in Acute Stress Induced Intestinal Mucosal Barrier Injury

    Institute of Scientific and Technical Information of China (English)

    唐宇; 马洪升

    2013-01-01

    背景:应激所致肠黏膜屏障损伤的机制以及肥大细胞(MC)在其中的作用尚未明确.目的:探讨肠黏膜MC(IMMC)在急性应激性肠黏膜屏障损伤中的作用机制.方法:Sprague-Dawley(SD)大鼠随机分为正常对照组(N组)、应激组(S组),S组给予急性冷束缚应激建立模型,按照应激结束后处死时间进一步分为S2h、S4h、S8h、S16h、S24h组.取回肠末端观察组织病理学改变,以Chiu's评分评估肠黏膜组织损伤程度,以甲苯胺蓝染色计数IMMC,以透射电镜观察肠黏膜组织和IMMC超微结构,以ELISA法检测肠黏膜组织组胺含量.结果:S组的Chiu's评分均显著高于N组(P0.05).IMMC计数与Chiu's评分无相关性(P>0.05).S组肠黏膜超微结构破坏明显,IMMC胞质大量脱颗粒.S2h、S4h、S8h 组的肠黏膜组织组胺含量较N组显著降低(P0.05).肠黏膜组织组胺含量与Chiu's评分呈负相关(P=0.03).结论:急性应激状态下,IMMC脱颗粒释放炎性介质是导致肠黏膜屏障损伤的重要机制.%Background: The mechanism of stress induced intestinal barrier injury and the mechanistic role of mast cells ( MC ) have not yet been clarified. Aims: To investigate the mechanistic role of intestinal mucosal MC ( IMMC ) in acute stress induced intestinal mucosal barrier injury. Methods: Sprague-Dawley ( SD ) rats were randomly divided into normal control group ( N group ) and stress group ( S group ). Rats in S group were given acute cold/restraint stress and were further divided into S2h, S4h, S8h, S16h and S24h subgroups according to the time point of sacrificing after stress. Histological change of terminal ileum tissue was observed and the degree of damage was evaluated by Chiu s scoring system. IMMC number was counted by toluidine blue staining. The ultrastructure of intestinal tissue and IMMC was observed by transmission electron microscopy. The content of histamine in intestinal tissue was determined by ELISA. Results: Chiu s score in S

  8. Effects of dexmedetomidine on sufentanil pretreatment rats with acute gastric mucosal lessions induced by water-immersion-restraint stress%右美托咪定或(和)舒芬太尼预处理对浸水束缚应激大鼠急性胃黏膜损害的影响

    Institute of Scientific and Technical Information of China (English)

    曹明; 屠伟峰; 刘晓燕; 郄文斌

    2012-01-01

    = 6, intraperitoneal infusion of sufentanil at 10 μg/kg 2 min before WIRS); DEX and SF pretreatment group (Group DSP, n = 6, intraperitoneal infusion of dexmedetomidine at 7.5 μg/kg 10 min and intraperitoneal infusion of sufentanil at 10 μg/ kg 2 min before WIRS). All rats were anesthetized by intraperitioneal injection of 10% chloral hydrate 6h after WIRS.Then the whole stomach was removed and the gastric pH, SOD, MDA, MPO and NOS levels were measured. The gastric mucosal lesion index (GI) was assessed and gastric mucosal tissues underwent pathological examination. Results The increased range of MDA and MPO, the decreased range of pH and SOD, GI and pathological changes of gastric mucosal damage in the DP group were significantly lower than those in the WC group (P 〈 0.05), but the change of NOS was not statistically significance (P〉0.05). Compared with the SP group, the various of SOD, MDA, UI, pH, MPO, NOS in DSP group have no significant change (P 〉 0.05). Conclusions Dexmedetomidine pretreatment can effectively reduce the stress-induced acute gastric mucosal injury, and the mechanism may be related to control harmful stress response,reduce oxidative stress, reduce gastric acid and inhibit the inflammatory response, but it did not enhance the protective effect of sufentanil on acute gastric mucosal injury.

  9. DECREASING PREVALENCE OF THE ACUTE/SUBACUTE CLINICAL FORM OF PARACOCCIDIOIDOMYCOSIS IN MATO GROSSO DO SUL STATE, BRAZIL

    Directory of Open Access Journals (Sweden)

    Larissa Rodrigues Fabris

    2014-04-01

    Full Text Available With the objective to evaluate the behavior of paracoccidioidomycosis in the last three decades, clinical and epidemiological data of 595 patients admitted to clinical services of the Federal University of Mato Grosso do Sul from 1980 to 2009 were investigated. Gender, age distribution, clinical form, comorbidity with tuberculosis or AIDS, and mortality were compared by decades of clinical admission. It was shown that during the three decades there was a decrease in women percentage, and the same manner occurred a reduction in participants in the age group of 20 to 39 years. Moreover, the acute/subacute forms have been diminished in the period. These fluctuations are closely related and can be simultaneously analyzed. Increased AIDS co-infection prevalence from the first to the second decade was also revealed, coinciding with the appearance of the retroviral epidemic and stabilizing during the third decade. No change in the tuberculosis co-infection rate was observed (overall = 6.9%. It reinforces the importance of this co-morbidity. The overall mortality rate remained steady at 6.7%, not varying significantly from one decade to another. The persistent mortality rate calls attention to the importance of this neglected disease.

  10. The effect of cocaine on gastric mucosal PGE2, LTC4 and ulcerations

    Directory of Open Access Journals (Sweden)

    L. D. G. Angus

    1993-01-01

    Full Text Available The association between cocaine use and acute gastroduodenal perforation is known. The effect of cocaine and stress on gastric mucosal ulceration and the levels of prostaglandin E2 (PGE2 and leukotriene C4 (LTC4 was studied in 40 Sprague–Dawley rats. Controls received intraperitoneal (i.p. saline, ten received i.p. cocaine (35 mg/kg, ten were stressed by the cold restraint method, and ten had i.p. cocaine and stress. Cocaine alone did not induce ulceration, but decreased PGE2 levels. Stress alone caused ulceration, but was not associated with a change in either PGE2 or LTC4 levels. When combined with stress, however, cocaine caused a three-fold increase in ulceration and a significant increase in PGE2 and LTC4 levels. Stress may predispose the cocaine addict to loss of gastroduodenal mucosal integrity, which is related to an imbalance of PGE2 and LTC4 synthesis.

  11. Efficacy of Enteral Supplementation Enriched with Glutamine, Fiber, and Oligosaccharide on Mucosal Injury following Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Satoshi Iyama

    2014-10-01

    Full Text Available The combination of glutamine, fiber and oligosaccharides (GFO is thought to be beneficial for alleviating gastrointestinal mucosal damage caused by chemotherapy. A commercial enteral supplementation product (GFO enriched with these 3 components is available in Japan. We performed a retrospective study to test whether oral GFO decreased the severity of mucosal injury following hematopoietic stem cell transplantation (HSCT. Of 44 HSCT patients, 22 received GFO and 22 did not. Severity of diarrhea/mucositis, overall survival, weight loss, febrile illness/documented infection, intravenous hyperalimentation days/hospital days, engraftment, acute and chronic GVHD, and cumulative incidence of relapse were studied. Sex, age, performance status, diagnosis, disease status, and treatment variables were similar in both groups. There were fewer days of diarrhea grade 3-4 in patients receiving GFO than in those who did not (0.86 vs. 3.27 days; the same was true for days of mucositis grade 3-4 (3.86 vs. 6.00 days. Survival at day 100 was 100% in the GFO group, but only 77.3% for the patients not receiving GFO (p = 0.0091, log-rank test. Weight loss and the number of days of intravenous hyperalimentation were better in the GFO group (p Enterococcus species developed in the GFO group (p = 0.0728 than in the non-GFO group. Other outcomes were not affected. To the best of our knowledge, this is the first comparative clinical study of GFO supplementation to alleviate mucosal injury after allo-HSCT. We conclude that glutamine, fiber and oligosaccharide supplementation is an effective supportive therapy to decrease the severity of mucosal damage in HSCT.

  12. Mucosal vaccination of fish

    NARCIS (Netherlands)

    Rombout, J.H.W.M.; Kiron, V.

    2014-01-01

    Among the novel vaccination methods, mucosal vaccination seems to possess all the desired criteria. The chapter reviews the state-of-the-art knowledge regarding this type of vaccination with a focus on their uptake, immune stimulation, and where possible, discusses their potential as future vaccines

  13. A novel cardioprotective agent in cardiac transplantation: metformin activation of AMP-activated protein kinase decreases acute ischemia-reperfusion injury and chronic rejection.

    Science.gov (United States)

    Chin, Jocelyn T; Troke, Joshua J; Kimura, Naoyuki; Itoh, Satoshi; Wang, Xi; Palmer, Owen P; Robbins, Robert C; Fischbein, Michael P

    2011-12-01

    The main cause of mortality after the first year from cardiac transplantation is cardiac allograft vasculopathy (CAV), which leads to chronic rejection of the heart. To improve long-term outcomes in cardiac transplantation, treatments to prevent or diminish CAV are actively being researched. Ischemia-reperfusion (I-R) injury has been shown to be the strongest alloantigen-independent factor in the development of CAV. Here, we investigate the use of metformin in murine cardiac transplantation models as a novel cardioprotective agent to limit acute I-R injury and subsequent chronic rejection. We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo. In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8. In the chronic transplantation model, metformin pretreatment of allografts led to significantly improved graft function and significantly decreased CAV, as measured on POD 52. Taken together, our results in the acute and chronic rejection studies suggest a potential cardioprotective mechanism for metformin; we demonstrate a correlation between metformin-induced decrease in acute I-R injury and metformin-related decrease in chronic rejection. Thus, one of the ways by which metformin and AMPK activation may protect the transplanted heart from chronic rejection is by decreasing initial I-R injury inherent in donor organ preservation and implantation. Our findings suggest novel therapeutic strategies for minimizing chronic cardiac rejection via the use of metformin- and AMPK-mediated pathways to suppress acute I-R injury.

  14. Small molecule ErbB inhibitors decrease proliferative signaling and promote apoptosis in philadelphia chromosome-positive acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Mary E Irwin

    Full Text Available The presence of the Philadelphia chromosome in patients with acute lymphoblastic leukemia (Ph(+ALL is a negative prognostic indicator. Tyrosine kinase inhibitors (TKI that target BCR/ABL, such as imatinib, have improved treatment of Ph(+ALL and are generally incorporated into induction regimens. This approach has improved clinical responses, but molecular remissions are seen in less than 50% of patients leaving few treatment options in the event of relapse. Thus, identification of additional targets for therapeutic intervention has potential to improve outcomes for Ph+ALL. The human epidermal growth factor receptor 2 (ErbB2 is expressed in ~30% of B-ALLs, and numerous small molecule inhibitors are available to prevent its activation. We analyzed a cohort of 129 ALL patient samples using reverse phase protein array (RPPA with ErbB2 and phospho-ErbB2 antibodies and found that activity of ErbB2 was elevated in 56% of Ph(+ALL as compared to just 4.8% of Ph(-ALL. In two human Ph+ALL cell lines, inhibition of ErbB kinase activity with canertinib resulted in a dose-dependent decrease in the phosphorylation of an ErbB kinase signaling target p70S6-kinase T389 (by 60% in Z119 and 39% in Z181 cells at 3 µM. Downstream, phosphorylation of S6-kinase was also diminished in both cell lines in a dose-dependent manner (by 91% in both cell lines at 3 µM. Canertinib treatment increased expression of the pro-apoptotic protein Bim by as much as 144% in Z119 cells and 49% in Z181 cells, and further produced caspase-3 activation and consequent apoptotic cell death. Both canertinib and the FDA-approved ErbB1/2-directed TKI lapatinib abrogated proliferation and increased sensitivity to BCR/ABL-directed TKIs at clinically relevant doses. Our results suggest that ErbB signaling is an additional molecular target in Ph(+ALL and encourage the development of clinical strategies combining ErbB and BCR/ABL kinase inhibitors for this subset of ALL patients.

  15. Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Holleman, Amy; den Boer, Monique L; Kazemier, Karin M; Beverloo, H Berna; von Bergh, Anne R M; Janka-Schaub, Gritta E; Pieters, Rob

    2005-09-01

    Drug resistance in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with impaired ability to induce apoptosis. To elucidate causes of apoptotic defects, we studied the protein expression of Apaf-1, procaspases-2, -3, -6, -7, -8, -10, and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) in cells from children with acute lymphoblastic leukemia (ALL; n = 43) and acute myeloid leukemia (AML; n = 10). PARP expression was present in all B-lineage samples, but absent in 4 of 15 T-lineage ALL samples and 3 of 10 AML cases, which was not caused by genomic deletions. PARP expression was a median 7-fold lower in T-lineage ALL (P < .001) and 10-fold lower in AML (P < .001) compared with B-lineage ALL. PARP expression was 4-fold lower in prednisolone, vincristine and L-asparaginase (PVA)-resistant compared with PVA-sensitive ALL patients (P < .001). Procaspase-2 expression was 3-fold lower in T-lineage ALL (P = .022) and AML (P = .014) compared with B-lineage ALL. In addition, procaspase-2 expression was 2-fold lower in PVA-resistant compared to PVA-sensitive ALL patients (P = .042). No relation between apoptotic protease-activating factor 1 (Apaf-1), procaspases-3, -6, -7, -8, -10, and drug resistance was found. In conclusion, low baseline expression of PARP and procaspase-2 is related to cellular drug resistance in childhood acute lymphoblastic leukemia.

  16. 大黄素对急性放射性肠炎肠黏膜屏障的保护作用%Protective effects of emodin on intestinal mucosal barrier in acute radiation enteritis

    Institute of Scientific and Technical Information of China (English)

    王玉; 周冬枝; 夏欣欣; 韩萍萍; 曹丽君

    2013-01-01

    Objective To investigate the effects and mechanisms of emodin on acute radiation enteritis models and intestinal mucosal barrier. Methods Totally 50 healthy male SD rats were randomly divided into normal group, model group, emodin prevention group, emodin treatment group and SiMiDa group. Emodin prevention group had been given emodin for 3 consecutive days in advance. Except normal group, the others were given a single dose of 10 Gy 6 MV of higher-energy X-rays on the abdominal region to establish acute radiation enteritis models. After 6 h, emodin prevention group, emodin treatment group and SiMiDa group were given intragastric administration for 4 days. The morphologic indexes were measured by light microscopy and the image analysis system. Intestinal diamine oxidase (DAO) activities as well as bacteria translocation rates of liver, spleen and mesenteric lymph node were measured. Intestinal tumor necrosis factor alpha (TNF-α) was measured by ELISA and nitric oxide (NO) level was measured by spectrophotometer. Results Emodin prevention group, emodin treatment group and SiMiDa group had significantly higher levels of villus height, crypt depth, thickness of mucosa and entire wall as well as DAO activities than model group (P0.05). Conclusion Emodin could significantly increase villus height of the small intestine, crypt depth and mucosal layer thickness, enhance intestinal tissue DAO activities, protect the intestinal mucosa, reduce bacterial translocation rate, and reduce TNF-α expression in the intestinal tissue and NO generation. There are no significant differences between prophylaxis and treatment administration of emodin.%目的 探讨大黄素对急性放射性肠炎疗效及对肠黏膜屏障保护的疗效机制.方法 SD大鼠50只,随机分为正常组、模型组、大黄素预防组、大黄素治疗组、思密达组.大黄素预防组提前灌胃给药3d,除正常组外的各组采用X射线照射建立急性放射性肠炎模型,照射后6h

  17. [Mucositis in head and neck cancer patients undergoing radiochemotherapy].

    Science.gov (United States)

    Santos, Renata Cristina Schmidt; Dias, Rodrigo Souza; Giordani, Adelmo José; Segreto, Roberto Araújo; Segreto, Helena Regina Comodo

    2011-12-01

    The objective of present study was to classify oral mucositis according to the Common Toxicity Criterion (CTC) international parameters in head and neck tumor patients simultaneously treated with radio and chemotherapy, and characterize a patient profile in our area, observing the individuals' habits, tumor characteristics, treatment protocol and acute reaction intensity. Fifty patients undergoing simultaneous 66 to 70 Gy megavoltage radiotherapy and cisplatin/carboplatin chemotherapy were evaluated in this study. Weekly evaluations of the degree of mucositis were perfoemed according to CTC, a four-degree ordinal scale; 36% of all patients and 100% of those with diabetes discontinued treatment due to mucositis, showing that this pathology contributes to the severity of mucositis.

  18. Black esophagus: Acute esophageal necrosis syndrome

    Institute of Scientific and Technical Information of China (English)

    Grigoriy; E; Gurvits

    2010-01-01

    Acute esophageal necrosis (AEN), commonly referred to as "black esophagus", is a rare clinical entity arising from a combination of ischemic insult seen in hemodynamic compromise and low-flow states, corrosive injury from gastric contents in the setting of esophago-gastroparesis and gastric outlet obstruction, and decreased function of mucosal barrier systems and reparative mechanisms present in malnourished and debilitated physical states. AEN may arise in the setting of multiorgan dysfunction, hypoperfusi...

  19. MUCOSAL DRUG DELIVERY SYSTEM

    OpenAIRE

    Madan Jyotsana; Banode Sagar; Dangi Mahesh

    2010-01-01

    The process of mucoadhesion involving a polymeric drug delivery system is a complex one that includes processes such as wetting, adsorption and interpenetration of polymer chains. The success and degree of mucoadhesion bonding is influenced by various polymer-based properties such as the degree of cross-linking, chain length and the presence of various functional groupings. The attractiveness of mucosal-targeted controlled drug delivery of active pharmaceutical ingredients, has led formulatio...

  20. Decreased uric acid levels correlate with poor outcomes in acute ischemic stroke patients, but not in cerebral hemorrhage patients.

    Science.gov (United States)

    Wu, Hongliang; Jia, Qian; Liu, Gaifen; Liu, Liping; Pu, Yuehua; Zhao, Xingquan; Wang, Chunxue; Wang, Yilong; Wang, Yongjun

    2014-03-01

    The relationship between uric acid and stroke prognosis is ambiguous. Some studies have explored this relationship in acute stroke but have different results. In this study, we explored the relationship between uric acid levels and 1-year outcomes and vascular events of acute ischemic stroke patients and cerebral hemorrhage patients. In all, 1452 continued first, acute ischemic stroke patients and 380 continued cerebral hemorrhage patients were admitted to our hospitals. Serum uric acid concentrations were measured in 1351 ischemic stroke patients and 380 cerebral hemorrhage patients at admission. We evaluated the relationship between uric acid levels and outcomes (modified Rankin scale [mRS] > 2, all-cause death, vascular events, stroke recurrent) at 14 days, 90 days, and 1 year after stroke onset. The median uric acid concentration was 303.0 μmol/L in ischemic stroke patients and 269 μmol/L in cerebral hemorrhage patients. In univariate analysis, uric acid levels were not correlated with outcomes in cerebral hemorrhage patients. We used multiple logistic regression analysis to show that lower serum uric acid levels independently predicted poor functional outcomes (mRS >2) at 1 year after ischemic stroke onset (odds ratio [OR] = .335, 95% confidence interval [CI]: .164-.684, P = .003). Also, lower serum uric acid levels were independently correlated with vascular events in the first year in ischemic stroke patients. By multiple cox proportional hazards analysis, we obtained data which reveal that serum uric acid levels were not correlated with all-cause death (OR = .992, 95% CI: .683-1.443, P = .969) in ischemic stroke patients. Serum uric acid may be neuroprotective in acute ischemic stroke patients. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Rest energy expenditure is decreased during the acute as compared to the recovery phase of sepsis in newborns

    Directory of Open Access Journals (Sweden)

    de Carvalho Tatiana

    2010-07-01

    Full Text Available Abstract Background Little is known with respect to the metabolic response and the requirements of infected newborns. Moreover, the nutritional needs and particularly the energy metabolism of newborns with sepsis are controversial matter. In this investigation we aimed to evaluate the rest energy expenditure (REE of newborns with bacterial sepsis during the acute and the recovery phases. Methods We studied nineteen neonates (27.3 ± 17.2 days old with bacterial sepsis during the acute phase and recovery of their illness. REE was determined by indirect calorimetry and VO2 and VCO2 measured by gas chromatography. Results REE significantly increased from 49.4 ± 13.1 kcal/kg/day during the acute to 68.3 ± 10.9 kcal/kg/day during recovery phase of sepsis (P 2 (7.4 ± 1.9 vs 10 ± 1.5 ml/kg/min and VCO2 (5.1 ± 1.7 vs 7.4 ± 1.5 ml/kg/min were also increased during the course of the disease (P Conclusion REE was increased during recovery compared to the sepsis phase. REE of septic newborns should be calculated on individualized basis, bearing in mind their metabolic capabilities.

  2. Contrastive study of Dahuanggancao Decoction on intestinal mucosal barrier function in severe acute pancreatitis%大黄甘草汤对重症急性胰腺炎肠黏膜屏障功能的对照研究

    Institute of Scientific and Technical Information of China (English)

    陈小鹏; 樊勇; 王跃斌; 陈罗飞; 王琛

    2016-01-01

    目的:探讨大黄甘草汤对重症急性胰腺炎(SAP)肠黏膜屏障功能的影响。方法将45只清洁级健康雄性SD大鼠采用随机数字表法随机分为大黄甘草汤治疗组(D组)、SAP模型组(P组)和假手术组(S组),每组15只。采用逆行注射5%牛黄胆酸钠(0.5 mL/100 g)制备大鼠SAP模型。D组给予大黄甘草汤(2.0 mL/100 g),P、S组给予0.9%氯化钠溶液(2.0 mL/100 g)。分别于建模后12、24、36 h经腹主动脉采集血标本检测血淀粉酶、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、IL-10、D-乳酸水平等。结果 D组大鼠血淀粉酶、TNF-α、IL-6、D-乳酸水平明显低于P组,IL-10水平明显高于P组,差异均有统计学意义(P<0.05)。结论大黄甘草汤对SAP大鼠肠黏膜屏障功能具有保护作用,治疗SAP疗效较好。%Objective To explore the effect of Dahuanggancao Decoction on the intestinal mucosal barrier function of se-vere acute pancreatitis(SAP). Methods Forty-five clean class SD healthy male rats were randomly divided into the Dahuanggancao Decoction group(D,n=15),SAP model group(P,n=15)and sham operation group(S,n=15). The SAP rat model was induced by the retrograde injection of 5%sodium taurocholate(0.5 mL/100 g). The group D was given Dahuanggancao Decoction(2.0 m/100 g), while the group P and S was given 0.9%sodium chloride solution(2.0 mL/100 g). The blood samples were collected from inferior vena cava at 12,24,36 h after model construction and serum amylase,TNF-α,IL-6,IL-10 and D-lactic acid levels were detected. Results The serum amylase,TNF-α,IL-6 and D-lactic acid levels in the group D were significantly lower than those in the group P,while the IL-10 level was significantly higher than that in the group P,the difference was statistically significant(P<0.05). Conclusion Dahuanggancao Decoction has a protective effect on the intestinal mucosal barrier function of SAP rats and has good effect in

  3. Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

    Science.gov (United States)

    Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N

    2016-11-02

    Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.Mucosal Immunology advance online publication 2 November 2016. doi:10.1038/mi.2016.95.

  4. Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis.

    Science.gov (United States)

    Choi, Yoon Seok; Lee, Jeewon; Lee, Hyun Woong; Chang, Dong-Yeop; Sung, Pil Soo; Jung, Min Kyung; Park, Jun Yong; Kim, Ja Kyung; Lee, Jung Il; Park, Hana; Cheong, Jae Youn; Suh, Kyung-Suk; Kim, Hyung Joon; Lee, June Sung; Kim, Kyung-Ah; Shin, Eui-Cheol

    2015-08-01

    Foxp3(+)CD4(+)CD25(+) regulatory T cells (Tregs) control immune responses, but their role in acute viral hepatitis remains elusive. Herein, we investigated alteration in the peripheral blood Treg population during acute hepatitis A (AHA) and its implication in the immune-mediated liver injury. The study included 71 patients with AHA, and peripheral blood mononuclear cells (PBMCs) were isolated. The suppressive activity of Treg population was determined by assessing anti-CD3/CD28-stimulated proliferation of Treg-depleted and reconstituted PBMCs. Treg cell frequency, phenotype and apoptosis in PBMCs were analysed by flow cytometry. The frequency of circulating Tregs was reduced during AHA. Moreover, the suppressive activity of the total Treg pool in the peripheral blood was attenuated during AHA. Treg frequency and suppressive activity of the Treg population inversely correlated with the serum alanine aminotransferase level. Fas was overexpressed on Tregs during AHA, suggesting their susceptibility to Fas-induced apoptosis. Indeed, increased apoptotic death was observed in Tregs of patients with AHA compared with healthy controls. In addition, agonistic anti-Fas treatment further increased apoptotic death of Tregs from patients with AHA. The decreased Treg frequency and Fas overexpression on Tregs were not observed in other acute liver diseases such as acute hepatitis B, acute hepatitis C and toxic/drug-induced hepatitis. The size of the Treg pool was contracted during AHA, resulting from apoptosis of Tregs induced by a Fas-mediated mechanism. Decrease in Treg numbers led to reduced suppressive activity of the Treg pool and consequently resulted in severe liver injury during AHA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor.

    Science.gov (United States)

    Ribeiro, Alison; Ferraz-de-Paula, Viviane; Pinheiro, Milena L; Vitoretti, Luana B; Mariano-Souza, Domenica P; Quinteiro-Filho, Wanderley M; Akamine, Adriana T; Almeida, Vinícius I; Quevedo, João; Dal-Pizzol, Felipe; Hallak, Jaime E; Zuardi, Antônio W; Crippa, José A; Palermo-Neto, João

    2012-03-05

    Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4days after the induction of LPS-induced acute lung injury. Additionally, adenosine A(2A) receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (a highly selective antagonist of adenosine A(2A) receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A(2A) receptor.

  6. Sacral nerve stimulation enhances early intestinal mucosal repair following mucosal injury in a pig model.

    Science.gov (United States)

    Brégeon, Jérémy; Coron, Emmanuel; Da Silva, Anna Christina Cordeiro; Jaulin, Julie; Aubert, Philippe; Chevalier, Julien; Vergnolle, Nathalie; Meurette, Guillaume; Neunlist, Michel

    2016-08-01

    Reducing intestinal epithelial barrier (IEB) dysfunctions is recognized as being of major therapeutic interest for various intestinal disorders. Sacral nerve stimulation (SNS) is known to reduce IEB permeability. Here, we report in a pig model that SNS enhances morphological and functional recovery of IEB following mucosal injury induced via 2,4,6-trinitrobenzenesulfonic acid. These effects are associated with an increased expression of tight junction proteins such as ZO-1 and FAK. These results establish that SNS enhances intestinal barrier repair in acute mucosal injury. They further set the scientific basis for future use of SNS as a complementary or alternative therapeutic option for the treatment of gut disorders with IEB dysfunctions such as inflammatory bowel diseases or irritable bowel syndrome. Intestinal epithelial barrier (IEB) dysfunctions, such as increased permeability or altered healing, are central to intestinal disorders. Sacral nerve stimulation (SNS) is known to reduce IEB permeability, but its ability to modulate IEB repair remains unknown. This study aimed to characterize the impact of SNS on mucosal repair following 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced lesions. Six pigs were stimulated by SNS 3 h prior to and 3 h after TNBS enema, while sham animals (n = 8) were not stimulated. The impact of SNS on mucosal changes was evaluated by combining in vivo imaging, histological and functional methods. Biochemical and transcriptomic approaches were used to analyse the IEB and mucosal inflammatory response. We observed that SNS enhanced the recovery from TNBS-induced increase in transcellular permeability. At 24 h, TNBS-induced alterations of mucosal morphology were significantly less in SNS compared with sham animals. SNS reduced TNBS-induced changes in ZO-1 expression and its epithelial pericellular distribution, and also increased pFAK/FAK expression compared with sham. Interestingly, SNS increased the mucosal density of neutrophils

  7. Endocan, a putative endothelial cell marker, is elevated in preeclampsia, decreased in acute pyelonephritis, and unchanged in other obstetrical syndromes

    Science.gov (United States)

    Adekola, Henry; Romero, Roberto; Chaemsaithong, Piya; Korzeniewski, Steven J.; Dong, Zhong; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn

    2015-01-01

    Abstract Objective: Endocan, a dermatan sulphate proteoglycan produced by endothelial cells, is considered a biomarker for endothelial cell activation/dysfunction. Preeclampsia is characterized by systemic vascular inflammation, and endothelial cell activation/dysfunction. Therefore, the objectives of this study were to determine whether: (1) plasma endocan concentrations in preeclampsia differ from those in uncomplicated pregnancies; (2) changes in plasma endocan concentration relate to the severity of preeclampsia, and whether these changes are specific or observed in other obstetrical syndromes such as small-for-gestational age (SGA), fetal death (FD), preterm labor (PTL) or preterm prelabor rupture of membranes (PROM); (3) a correlation exists between plasma concentration of endocan and angiogenic (placental growth factor or PlGF)/anti-angiogenic factors (soluble vascular endothelial growth factor receptor or sVEGFR-1, and soluble endoglin or sEng) among pregnancies complicated by preeclampsia; and (4) plasma endocan concentrations in patients with preeclampsia and acute pyelonephritis (both conditions in which there is endothelial cell activation) differ. Method: This cross-sectional study included the following groups: (1) uncomplicated pregnancy (n = 130); (2) preeclampsia (n = 102); (3) pregnant women without preeclampsia who delivered an SGA neonate (n = 51); (4) FD (n = 49); (5) acute pyelonephritis (AP; n = 35); (6) spontaneous PTL (n = 75); and (7) preterm PROM (n = 64). Plasma endocan concentrations were determined in all groups, and PIGF, sEng and VEGFR-1 plasma concentrations were measured by ELISA in the preeclampsia group. Results: (1) Women with preeclampsia had a significantly higher median plasma endocan concentration than those with uncomplicated pregnancies (p = 0.004); (2) among women with preeclampsia, the median plasma endocan concentration did not differ significantly according to disease severity (p = 0

  8. Endocan, a putative endothelial cell marker, is elevated in preeclampsia, decreased in acute pyelonephritis, and unchanged in other obstetrical syndromes.

    Science.gov (United States)

    Adekola, Henry; Romero, Roberto; Chaemsaithong, Piya; Korzeniewski, Steven J; Dong, Zhong; Yeo, Lami; Hassan, Sonia S; Chaiworapongsa, Tinnakorn

    2015-01-01

    Endocan, a dermatan sulphate proteoglycan produced by endothelial cells, is considered a biomarker for endothelial cell activation/dysfunction. Preeclampsia is characterized by systemic vascular inflammation, and endothelial cell activation/dysfunction. Therefore, the objectives of this study were to determine whether: (1) plasma endocan concentrations in preeclampsia differ from those in uncomplicated pregnancies; (2) changes in plasma endocan concentration relate to the severity of preeclampsia, and whether these changes are specific or observed in other obstetrical syndromes such as small-for-gestational age (SGA), fetal death (FD), preterm labor (PTL) or preterm prelabor rupture of membranes (PROM); (3) a correlation exists between plasma concentration of endocan and angiogenic (placental growth factor or PlGF)/anti-angiogenic factors (soluble vascular endothelial growth factor receptor or sVEGFR-1, and soluble endoglin or sEng) among pregnancies complicated by preeclampsia; and (4) plasma endocan concentrations in patients with preeclampsia and acute pyelonephritis (both conditions in which there is endothelial cell activation) differ. This cross-sectional study included the following groups: (1) uncomplicated pregnancy (n = 130); (2) preeclampsia (n = 102); (3) pregnant women without preeclampsia who delivered an SGA neonate (n = 51); (4) FD (n = 49); (5) acute pyelonephritis (AP; n = 35); (6) spontaneous PTL (n = 75); and (7) preterm PROM (n = 64). Plasma endocan concentrations were determined in all groups, and PIGF, sEng and VEGFR-1 plasma concentrations were measured by ELISA in the preeclampsia group. (1) Women with preeclampsia had a significantly higher median plasma endocan concentration than those with uncomplicated pregnancies (p = 0.004); (2) among women with preeclampsia, the median plasma endocan concentration did not differ significantly according to disease severity (p = 0.1), abnormal uterine artery Doppler

  9. Sabiporide improves cardiovascular function, decreases the inflammatory response and reduces mortality in acute metabolic acidosis in pigs.

    Directory of Open Access Journals (Sweden)

    Dongmei Wu

    Full Text Available INTRODUCTION: Acute metabolic acidosis impairs cardiovascular function and increases the mortality of critically ill patients. However, the precise mechanism(s underlying these effects remain unclear. We hypothesized that targeting pH-regulatory protein, Na(+/H(+ exchanger (NHE1 could be a novel approach for the treatment of acute metabolic acidosis. The aim of the present study was to examine the impact of a novel NHE1 inhibitor, sabiporide, on cardiovascular function, blood oxygen transportation, and inflammatory response in an experimental model of metabolic acidosis produced by hemorrhage-induced hypovolemia followed by an infusion of lactic acid. METHODS AND RESULTS: Anesthetized pigs were subjected to hypovolemia for 30 minutes. The animals then received a bolus infusion of sabiporide (3 mg/kg or vehicle, followed by an infusion of lactic acid for 2 hours. The animals were continuously monitored for additional 3 hours. Hypovolemia followed by a lactic acid infusion resulted in a severe metabolic acidosis with blood pH falling to 6.8. In association with production of the acidemia, there was an excessive increase in pulmonary artery pressure (PAP and pulmonary vascular resistance (PVR. Treatment with sabiporide significantly attenuated the increase in PAP by 38% and PVR by 67%, as well as significantly improved cardiac output by 51%. Sabiporide treatment also improved mixed venous blood oxygen saturation (55% in sabiporide group vs. 28% in control group, and improved systemic blood oxygen delivery by 36%. In addition, sabiporide treatment reduced plasma levels of TNF-α (by 33%, IL-6 (by 63%, troponin-I (by 54%, ALT (by 34%, AST (by 35%, and urea (by 40%. CONCLUSION: These findings support the possible beneficial effects of sabiporide in the treatment of acute metabolic acidosis and could have implications for the treatment of metabolic acidosis in man.

  10. Buccal Mucosal Graft Urethroplasty

    Directory of Open Access Journals (Sweden)

    Angela M. Arlen

    2010-01-01

    Full Text Available At our institution, the majority of buccal mucosal graft urethroplasties are performed using a two-team approach with an otolaryngologic surgeon. We report our two-surgeon experience with buccal mucosal grafting for reconstruction of all anterior urethral strictures. Twenty-four men underwent autologous buccal mucosal graft urethroplasty between October 2001 and September 2008 for recurrent urethral stricture disease. Twenty-two underwent a single-stage repair and two underwent a two-stage repair. Medical charts were retrospectively reviewed for demographics, comorbidities, etiology, location and length of stricture, and prior interventions in order to identify predictors of buccal urethroplasty success, defined as no evidence of stricture recurrence. All patients underwent retrograde urethrogram and cystoscopy. Operative and anesthesia times were evaluated. We determined an overall success rate of 83.3% (20 of 24 cases. Mean anesthesia time for single-stage urethroplasty was 155 min and mean operative time was 123 min. One of the two two-stage urethroplasties experienced stricture recurrence (50%. The single-stage buccal graft success rate was 86.4% (19 of 22 cases. Two of the four who developed recurrent stricture disease that required intervention had undergone a previous mesh urethroplasty. Complications developed in four of 24 patients (16.6%, including superficial wound infection (one, superficial wound dehiscence (two, and abscess/fistula formation requiring reoperation (one. The buccal mucosa is an ideal tissue for both single- and two-stage substitution urethroplasty for patients with recurrent stricture disease. Our two-surgeon technique minimizes anesthesia and operative times, and contributes to the overall high success rate and relatively low complication rate.

  11. Mucositis and non-invasive markers of small intestinal function.

    Science.gov (United States)

    Tooley, Katie L; Howarth, Gordon S; Butler, Ross N

    2009-05-01

    Mucositis is a common and debilitating side effect of chemotherapy that manifests due to the inability of chemotherapy agents to discriminate between normal and neoplastic cells. This results in ulcerating lesions lining the gastrointestinal tract. Moreover, the development of efficacious treatments for small intestinal mucositis has been hindered as the pathobiology of mucositis is still not fully understood. The small intestine is an extensive organ which is largely inaccessible by conventional means. Non-invasive biomarkers such as small intestinal permeability, H(2) breath tests, serum citrulline tests and the (13)C-sucrose breath test (SBT) have emerged as potential markers of small intestinal function. The SBT is emerging as the more appropriate biomarker to assess chemotherapy-induced mucositis in cancer patients and animal models, where it measures the decrease in sucrase activity associated with villus blunting and crypt disruption. The SBT has been successfully applied to detect mucositis induced by different classes of chemotherapy agents and has been used successfully to monitor small intestinal function with a range of candidate anti-mucositis treatments. We propose the SBT a superior biomarker of small intestinal function that could be successfully applied in clinical practice for monitoring the development of mucositis in cancer patients undergoing chemotherapy.

  12. Testing a two step Nursing intervention focused on decreasing rehospitalizations and nursing home sdmission post discharge from acute care

    DEFF Research Database (Denmark)

    Rosted, Elizabeth Emilie; Poulsen, Ingrid; Hendriksen, Carsten

    2013-01-01

    Older adults are at high risk of readmission on discharge from the Acute Medical and Emergency Department (ED). This study examines the effect of a two-stage nursing assessment and intervention to address older adults' uncompensated problems and thus intend to prevent readmission and functional...... decline. A randomized controlled study was conducted. Included were 271 patients aged 70 and over admitted to an ED. A brief standardized nursing assessment and intervention was carried out after discharge and at follow-up. No effect was found on readmission to hospital, admission to nursing home......, or death but the intervention group was less likely to be at risk of depression after 180 days. Whether this method can be recommended needs further study as well as knowledge is needed as to the organization and to reveal older adults' experiences on follow-up after ED stay....

  13. Loss of CD28 on Peripheral T Cells Decreases the Risk for Early Acute Rejection after Kidney Transplantation.

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    Burç Dedeoglu

    Full Text Available End-stage renal disease patients have a dysfunctional, prematurely aged peripheral T-cell system. Here we hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR.222 living donor kidney transplant recipients were prospectively analyzed. EAR was defined as biopsy proven acute allograft rejection within 3 months after kidney transplantation. The differentiation status of circulating T cells, the relative telomere length and the number of CD31+ naive T cells were determined as T-cell ageing parameters.Of the 222 patients analyzed, 30 (14% developed an EAR. The donor age and the historical panel reactive antibody score were significantly higher (p = 0.024 and p = 0.039 respectively and the number of related donor kidney transplantation was significantly lower (p = 0.018 in the EAR group. EAR-patients showed lower CD4+CD28null T-cell numbers (p<0.01 and the same trend was observed for CD8+CD28null T-cell numbers (p = 0.08. No differences regarding the other ageing parameters were found. A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p = 0.028. In vitro, a significant lower percentage of alloreactive T cells was observed within CD28null T cells (p<0.001.Immunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR.

  14. The impaired intestinal mucosal immune system by valine deficiency for young grass carp (Ctenopharyngodon idella) is associated with decreasing immune status and regulating tight junction proteins transcript abundance in the intestine.

    Science.gov (United States)

    Luo, Jian-Bo; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Wu, Pei; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu

    2014-09-01

    This study investigated the effects of dietary valine on the growth, intestinal immune response, tight junction proteins transcript abundance and gene expression of immune-related signaling molecules in the intestine of young grass carp (Ctenopharyngodon idella). Six iso-nitrogenous diets containing graded levels of valine (4.3-19.1 g kg(-)(1) diet) were fed to the fish for 8 weeks. The results showed that percentage weight gain (PWG), feed intake and feed efficiency of fish were the lowest in fish fed the valine-deficient diet (P valine deficiency decreased lysozyme, acid phosphatase activities and complement 3 content in the intestine (P valine deficiency significantly decreased transcript of Occludin, Claudin b, Claudin c, Claudin 3, and ZO-1 (P valine did not have a significant effect on expression of Claudin 12 in the intestine of grass carp (P > 0.05). In conclusion, valine deficiency decreased fish growth and intestinal immune status, as well as regulated gene expression of tight junction proteins, NF-κB P65, IκBα and TOR in the fish intestine. Based on the quadratic regression analysis of lysozyme activity or PWG, the dietary valine requirement of young grass carp (268-679 g) were established to be 14.47 g kg(-1) diet (4.82 g 100 g(-1) CP) or 14.00 g kg(-1) diet (4.77 g 100 g(-1) CP), respectively.

  15. The concentration of apolipoprotein A-I decreases during experimentally induced acute-phase processes in pigs

    DEFF Research Database (Denmark)

    Carpintero, R.; Pineiro, M.; Andres, M.

    2005-01-01

    In this work, apolipoprotein A-I (ApoA-I) was purified from pig sera. The responses of this protein after sterile inflammation and in animals infected with Actinobacillus pleuropneumoniae or Streptococcus suis were investigated. Decreases in the concentrations of ApoA-I, two to five times lower...

  16. Dental prophylaxis decreases the risk of acute myocardial infarction: a nationwide population-based study in Taiwan

    Directory of Open Access Journals (Sweden)

    Lee YL

    2015-01-01

    Full Text Available Ya-Ling Lee,1,2 Hsiao-Yun Hu,2,3 Pesus Chou,2 Dachen Chu2,4,5 1Department of Dentistry, Taipei City Hospital, 2Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, 3Department of Education and Research, Taipei City Hospital, 4Department of Health Care Management, National Taipei University of Nursing and Health Sciences, 5Department of Neurosurgery, Taipei City Hospital, Taipei, Taiwan Purpose: To investigate the association between periodontal disease (PD and acute ­myocardial infarction (AMI, and evaluate the effect of dental prophylaxis on the incidence rate (IR of AMI.Methods: The Longitudinal Health Insurance Database 2000 from the National Health Insurance program was used to identify 511,630 patients with PD and 208,713 without PD during 2000–2010. Subjects with PD were grouped according to treatment (dental prophylaxis, intensive treatment, and PD without treatment. The IRs of AMI during the 10-year follow-up period were compared among groups. Cox regression analysis adjusted for age, sex, socioeconomic status, residential urbanicity, and comorbidities was used to evaluate the effect of PD treatment on the incidence of AMI.Results: The IR of AMI among subjects without PD was 0.19%/year. Among those with PD, the IR of AMI was lowest in the dental prophylaxis group (0.11%/year, followed by the intensive treatment (0.28%/year and PD without treatment (0.31%/year; P<0.001 groups. Cox regression showed that the hazard ratio (HR for AMI was significantly lower in the dental prophylaxis group (HR =0.90, 95% confidence interval =0.86–0.95 and higher in the intensive treatment (HR =1.09, 95% confidence interval =1.03–1.15 and PD without treatment (HR =1.23, 95% confidence interval =1.13–1.35 groups than in subjects without PD.Conclusion: PD is associated with a higher risk of AMI, which can be reduced by dental prophylaxis to maintain periodontal health. Keywords: periodontal disease

  17. Chamomile Mouth Rinse Effects on Mucositis Reduction After Radiotherapy

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    Talaipour AR

    2000-05-01

    Full Text Available In recent years many patients have been received radiotherapy for head and neck tumors and"na large number of them have been survived for some years."nThe side effects of radiotherapy in oral region are mucositis, ulcers, fungal and viral infections and"nsalivary glands dysfunction. Among these, mucositis is the most important one."nA randomized double blind clinical trial was performed in radiotherapy department of Tehran Imam"nKhomeini Hospital to determine chamomile mouth rinse effects on mucositis after radiotherapy."nThe patients are selected randomly from those with oral oropharyngeal or nasopharyngeal cancers."nData showed that chamomile administration could decrease mucositis rate significantly,

  18. Mucoadhesive formulation of Bidens pilosa L. (Asteraceae reduces intestinal injury from 5-fluorouracil-induced mucositis in mice

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    Paulo Henrique Marcelino de Ávila

    2015-01-01

    Full Text Available Gastrointestinal mucositis induced during cancer treatment is considered a serious dose-limiting side effect of chemotherapy and/or radiotherapy. Frequently, interruption of the cancer treatment due to this pathology leads to a reduction in cure rates, increase of treatment costs and decrease life quality of the patient. Natural products such as Bidens pilosa L. (Asteraceae, represent a potential alternative for the treatment of mucositis given its anti-inflammatory properties. In this study, B. pilosa glycolic extract was formulated (BPF with poloxamer, a mucoadhesive copolymer, was used for treatment of 5-fluorouracil (5-FU-induced mucositis in mice. As expected, animals only treated with 5-FU (200 mg/kg presented marked weight loss, reduction of intestinal villi, crypts and muscular layer, which was associated with severe disruption of crypts, edema, inflammatory infiltrate and vacuolization in the intestinal tissue, as compared to the control group and healthy animals only treated with BPF. On the other hand, the treatment of intestinal mucositis-bearing mice with BPF (75, 100 or 125 mg/kg managed to mitigate clinical and pathologic changes, noticeably at 100 mg/kg. This dose led to the restoration of intestinal proliferative activity through increasing Ki-67 levels; modulated the expression of Bax, Bcl2 and p53 apoptotic markers protecting intestinal cells from cell death. Moreover, this treatment regulated lipid peroxidation and inflammatory infiltration. No acute toxic effects were observed with this formulation. This work demonstrated that BPF was safe and effective against 5-FU-induced intestinal mucositis in mice. Additional studies are already in progress to further characterize the mechanisms involved in the protective effects of this technological formulation toward the development of a new medicine for the prevention and treatment of intestinal injury in patients undergoing chemotherapy/radiotherapy.

  19. Acute administration of nicotine into the higher order auditory Te2 cortex specifically decreases the fear-related charge of remote emotional memories.

    Science.gov (United States)

    Cambiaghi, Marco; Grosso, Anna; Renna, Annamaria; Concina, Giulia; Sacchetti, Benedetto

    2015-12-01

    Nicotine elicits several behavioural effects on mood as well as on stress and anxiety processes. Recently, it was found that the higher order components of the sensory cortex, such as the secondary auditory cortex Te2, are essential for the long-term storage of remote fear memories. Therefore, in the present study, we examined the effects of acute nicotine injection into the higher order auditory cortex Te2, on the remote emotional memories of either threat or incentive experiences in rats. We found that intra-Te2 nicotine injection decreased the fear-evoked responses to a tone previously paired with footshock. This effect was cue- and dose-specific and was not due to any interference with auditory stimuli processing, innate anxiety and fear processes, or with motor responses. Nicotine acts acutely in the presence of threat stimuli but it did not determine the permanent degradation of the fear-memory trace, since memories tested one week after nicotine injection were unaffected. Remarkably, nicotine did not affect the memory of a similar tone that was paired to incentive stimuli. We conclude from our results that nicotine, when acting acutely in the auditory cortex, relieves the fear charge embedded by learned stimuli.

  20. Neuromuscular training with injury prevention counselling to decrease the risk of acute musculoskeletal injury in young men during military service: a population-based, randomised study

    Directory of Open Access Journals (Sweden)

    Suni Jaana

    2011-04-01

    Full Text Available Abstract Background The rapidly increasing number of activity-induced musculoskeletal injuries among adolescents and young adults is currently a true public health burden. The objective of this study was to investigate whether a neuromuscular training programme with injury prevention counselling is effective in preventing acute musculoskeletal injuries in young men during military service. Methods The trial design was a population-based, randomised study. Two successive cohorts of male conscripts in four companies of one brigade in the Finnish Defence Forces were first followed prospectively for one 6-month term to determine the baseline incidence of injury. After this period, two new successive cohorts in the same four companies were randomised into two groups and followed prospectively for 6 months. Military service is compulsory for about 90% of 19-year-old Finnish men annually, who comprised the cohort in this study. This randomised, controlled trial included 968 conscripts comprising 501 conscripts in the intervention group and 467 conscripts in the control group. A neuromuscular training programme was used to enhance conscripts' motor skills and body control, and an educational injury prevention programme was used to increase knowledge and awareness of acute musculoskeletal injuries. The main outcome measures were acute injuries of the lower and upper limbs. Results In the intervention groups, the risk for acute ankle injury decreased significantly compared to control groups (adjusted hazards ratio (HR = 0.34, 95% confidence interval (95% CI = 0.15 to 0.78, P = 0.011. This risk decline was observed in conscripts with low as well as moderate to high baseline fitness levels. In the latter group of conscripts, the risk of upper-extremity injuries also decreased significantly (adjusted HR = 0.37, 95% CI 0.14 to 0.99, P = 0.047. In addition, the intervention groups tended to have less time loss due to injuries (adjusted HR = 0.55, 95% CI 0

  1. The Influence of Different Periods Aerosol Inhalation Treatment on Acute Oral Mucositis Caused by Radiotherapy%不同雾化吸入时机对放射性急性口腔黏膜炎治疗效果的影响

    Institute of Scientific and Technical Information of China (English)

    刘琼

    2015-01-01

    Objective To observe the influence of different periods aerosal inhalation treatment on acute o-ral mucositis caused by radiotherapy.Methods Totally 60 patients hospitalized with head and neck cancer and undergoing radiotherapy were randomly divided into observation group and control group,with 30 ca-ses in each group.The observation group received aerosol inhalation while the radiotherapy started,while the control group only received aerosol inhalation while the acute oral mucositis appeared.The incidence rate of acute oral mucositis caused by radiotherapy,inj ury of oral mucosa and pain degree were compared between two groups.Results During the radiotherapy,the incidence rate of acute oral mucositis caused by radiotherapy,inj ury of oral mucosa and pain degree in observation group were less or lower than which in control group (P<0.05 or P<0.01).Conclusion Giving inhalation treatment at the beginning of radio-therapy can reduces the incidence rate of acute oral mucositis caused by radiotherapy,and the inj ury level of oral mucosa,and also ease the pain,which guarantees the success of radiotherapy,and thus to improve pa-tient’s quality of life.%目的:了解不同雾化吸入开始时间对放射性急性口腔黏膜炎治疗效果的影响.方法便利抽样法选择2012年10月至2013年7月,上海交通大学附属第六人民医院肿瘤放疗科收治的头颈部恶性肿瘤行根治性放射治疗的患者60例,按入院先后将其分为观察组和对照组各30例,观察组患者放疗开始即给予雾化吸入,对照组患者放疗过程中出现放射性急性口腔黏膜炎后再给予雾化吸入,评价并比较两组患者放射性急性口腔黏膜炎的发生情况、口腔黏膜损伤及疼痛程度.结果放疗期间,观察组患者放射性急性口腔黏膜炎的发生率、口腔黏膜损伤及疼痛程度均低于或轻于对照组患者,差异均有统计学意义(P<0.05或P<0.01).结论放疗开始即给予雾化

  2. Rates of cortisol increase and decrease in channel catfish and sunshine bass exposed to an acute confinement stressor.

    Science.gov (United States)

    Davis, Kenneth B; Small, Brian C

    2006-05-01

    Channel catfish and sunshine bass were exposed to a low-water stress event and allowed to recover in fresh water or a solution of metomidate (dl-1-(1-phenylethyl)-5-(metoxycarbonyl) imidazole hydrochloride), which inhibits the synthesis of cortisol. Change in time of plasma cortisol was used as an index of cortisol secretion and clearance. Plasma cortisol and glucose increased during the exposure to low-water stress in both fish, but the changes of both plasma components were more dramatic in sunshine bass. Exposure to metomidate during recovery resulted in a short-term increase in plasma glucose but differences between controls and metomidate-exposed fish were relatively minor thereafter. Cortisol began to decrease in catfish immediately after the removal of the stress but continued to increase for 15 min in sunshine bass recovering in fresh water and for 5 min in bass recovering in metomidate. Catfish recovering in fresh water had a cortisol elimination rate of -1.28 ng/mL/min compared with -2.45 ng/mL/min for fish recovering in metomidate (P>0.05) while sunshine bass recovering in fresh water had an elimination rate of -6.96 ng/mL/min compared with -4.50 ng/mL/min for fish recovering in metomidate (P>0.05). These data indicate that the rapid decrease of plasma cortisol after removal of the stressor is due to an almost immediate decrease of secretion, tissue uptake and a rapid renal loss due to the absence of a plasma binding protein.

  3. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context

    Directory of Open Access Journals (Sweden)

    Joan F. Alonso

    2016-04-01

    Full Text Available Sleep deprivation (SD has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE. Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

  4. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context

    Science.gov (United States)

    Alonso, Joan F.; Romero, Sergio; Mañanas, Miguel A.; Alcalá, Marta; Antonijoan, Rosa M.; Giménez, Sandra

    2016-01-01

    Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships. PMID:27089346

  5. Dose-dependent increase and decrease in active glucose uptake in jejunal epithelium of broilers after acute exposure to ethanol.

    Science.gov (United States)

    Yunus, Agha Waqar; Awad, Wageha A; Kröger, Susan; Zentek, Jürgen; Böhm, Josef

    2011-06-01

    Little is known about the effects of ethanol on gastrointestinal tract of chicken. In this study, we investigated the effects of low levels of ethanol on electrophysiological variables of jejunal epithelium of commercial broilers. Jejunal tissues from 35- to 39-day-old broilers were exposed to either 0 or 0.1% ethanol in Ussing chambers, and electrophysiological variables were monitored for 40 min. After 40 and 60 min of incubation, glucose (20 mM) and carbamoylcholine (200 μM), respectively, were introduced into the chambers. The absolute and percent increase in short-circuit current (Isc) and potential difference (Vt) induced by glucose were increased significantly with 0.1% ethanol. There was no significant effect of 0.1% ethanol on carbamoylcholine-induced electrophysiological variables. To investigate if higher levels of ethanol have similar effects, we tested the effects of 0, 0.33, and 0.66% ethanol under similar experimental conditions until the glucose-addition step. Contrary to 0.1% ethanol, both the 0.33 and 0.66% ethanol levels significantly decreased the basal and glucose-induced Isc and Vt. Tissue conductivity remained unaffected in all cases. These results indicate that intestinal epithelia of chicken may be more sensitive to the effects of ethanol as compared with other species. This is the first report indicating dose-dependent increase and decrease in active glucose absorption in intestinal epithelia in the presence of ethanol.

  6. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context.

    Science.gov (United States)

    Alonso, Joan F; Romero, Sergio; Mañanas, Miguel A; Alcalá, Marta; Antonijoan, Rosa M; Giménez, Sandra

    2016-04-14

    Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

  7. Decrease in circulating tryptophan availability to the brain after acute ethanol consumption by normal volunteers: implications for alcohol-induced aggressive behaviour and depression.

    Science.gov (United States)

    Badawy, A A; Morgan, C J; Lovett, J W; Bradley, D M; Thomas, R

    1995-10-01

    Acute ethanol consumption by fasting male volunteers decreases circulating trytophan (Trp) concentration and availability to the brain as determined by the ratio of (Trp) to the sum of its five competitors ([Trp]/[CAA]ratio). These effects of alcohol are specific to Trp, because levels of the 5 competitors are not increased. The decrease in circulating (Trp) is not associated with altered binding to albumin and may therefore be due to enhancement of hepatic Trp pyrrolase activity. It is suggested that, under these conditions brain serotonin synthesis is likely to be impaired and that, as a consequence, a possible strong depletion of brain serotonin in susceptible individuals may induce aggressive behaviour after alcohol consumption. The possible implications of these findings in the relationship between alcohol and depression are also briefly discussed.

  8. A high-protein diet during hospitalization is associated with an accelerated decrease in soluble urokinase plasminogen activator receptor levels in acutely ill elderly medical patients with SIRS.

    Science.gov (United States)

    Tavenier, Juliette; Haupt, Thomas H; Andersen, Aino L; Buhl, Sussi F; Langkilde, Anne; Andersen, Jens R; Jensen, Jens-Erik B; Pedersen, Mette M; Petersen, Janne; Andersen, Ove

    2017-05-01

    Acute illness and hospitalization in elderly individuals are often accompanied by the systemic inflammatory response syndrome (SIRS) and malnutrition, both associated with wasting and mortality. Nutritional support and resistance training were shown to increase muscle anabolism and reduce inflammation in healthy elderly. We hypothesized that nutritional support and resistance training would accelerate the resolution of inflammation in hospitalized elderly patients with SIRS. Acutely admitted patients aged >65 years with SIRS were randomized to an intervention consisting of a high-protein diet (1.7 g/kg per day) during hospitalization, and daily protein supplement (18.8 g) and 3 weekly resistance training sessions for 12 weeks after discharge (Intervention, n=14), or to standard-care (Control, n=15). Plasma levels of the inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR), interleukin-6, C-reactive protein (CRP), and albumin were measured at admission, discharge, and 4 and 13 weeks after discharge. The Intervention group had an earlier decrease in suPAR levels than the Control group: -15.4% vs. +14.5%, P=.007 during hospitalization, and -2.4% vs. -28.6%, P=.007 between discharge and 4 weeks. There were no significant effects of the intervention on the other biomarkers. All biomarkers improved significantly between admission and 13 weeks, although with different kinetics (suPAR: -22%, interleukin-6: -86%, CRP: -89%, albumin: +11%). Nutritional support during hospitalization was associated with an accelerated decrease in suPAR levels, whereas the combined nutrition and resistance training intervention after discharge did not appear to affect the inflammatory state. Our results indicate that improved nutritional care during hospitalization may accelerate recovery in acutely ill elderly medical patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Decreased saliva/serum irisin concentrations in the acute myocardial infarction promising for being a new candidate biomarker for diagnosis of this pathology.

    Science.gov (United States)

    Aydin, Suna; Aydin, Suleyman; Kobat, Mehmet Ali; Kalayci, Mehmet; Eren, Mehmet Nesimi; Yilmaz, Musa; Kuloglu, Tuncay; Gul, Evrim; Secen, Ozlem; Alatas, Omer Dogan; Baydas, Adil

    2014-06-01

    Irisin is a muscle-secreted protein. Cardiac muscle produces more irisin than skeletal muscle in response to acute exercise, and is associated with myocardial infarction (MI) in an experimental model induced by isoproterenol in rats. The timing and significance of its release in patients with acute myocardial infarction (AMI) needs further investigation. We have studied the relationship between serum/saliva irisin concentration and AMI in humans. Serum and saliva samples were taken within 3 days of admission in 11 patients with AMI and in 14 matched controls. Salivary gland irisin was detected immunohistochemically, and serum and saliva levels were measured by ELISA. The three major paired salivary glands (submandibular, sublingual and parotid) produce and release irisin into saliva. Troponin-I, CK, CK-MB concentrations in the AMI group gradually increased from up to 12h, while saliva and serum irisin gradually decreased from up to 48 h, compared with the control group (Psaliva and serum irisin started to increase at 72 h. Serum irisin levels correlated with age, while troponin I, CK-MB, and CK were correlated and with saliva irisin in AMI patients. Besides cardiac troponin and CK-MB, irisin adds new diagnostic information in AMI patients, and the gradual decrease of saliva/serum irisin over 48 h could be a useful biomarker.

  10. Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

    Science.gov (United States)

    Bajic, Juliana E; Eden, Georgina L; Lampton, Lorrinne S; Cheah, Ker Y; Lymn, Kerry A; Pei, Jinxin V; Yool, Andrea J; Howarth, Gordon S

    2016-01-01

    AIM To investigate the effects of orally gavaged aqueous rhubarb extract (RE) on 5-fluorouracil (5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats (n = 8/group) were gavaged daily (1 mL) with water, high-dose RE (HDR; 200 mg/kg) or low-dose RE (LDR; 20mg/kg) for eight days. Intestinal mucositis was induced (day 5) with 5-FU (150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase (MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA. RESULTS Bodyweight was significantly reduced in rats administered 5-FU compared to healthy controls (P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels (≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity (by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness (by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats (19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis. CONCLUSION In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal

  11. Berberine Reduces Uremia-Associated Intestinal Mucosal Barrier Damage.

    Science.gov (United States)

    Yu, Chao; Tan, Shanjun; Zhou, Chunyu; Zhu, Cuilin; Kang, Xin; Liu, Shuai; Zhao, Shuang; Fan, Shulin; Yu, Zhen; Peng, Ai; Wang, Zhen

    2016-11-01

    Berberine is one of the main active constituents of Rhizoma coptidis, a traditional Chinese medicine, and has long been used for the treatment of gastrointestinal disorders. The present study was designed to investigate the effects of berberine on the intestinal mucosal barrier damage in a rat uremia model induced by the 5/6 kidney resection. Beginning at postoperative week 4, the uremia rats were treated with daily 150 mg/kg berberine by oral gavage for 6 weeks. To assess the intestinal mucosal barrier changes, blood samples were collected for measuring the serum D-lactate level, and terminal ileum tissue samples were used for analyses of intestinal permeability, myeloperoxidase activity, histopathology, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity. Berberine treatment resulted in significant decreases in the serum D-lactate level, intestinal permeability, intestinal myeloperoxidase activity, and intestinal mucosal and submucosal edema and inflammation, and the Chiu's scores assessed for intestinal mucosal injury. The intestinal MDA level was reduced and the intestinal SOD activity was increased following berberine treatment. In conclusion, berberine reduces intestinal mucosal barrier damage induced by uremia, which is most likely due to its anti-oxidative activity. It may be developed as a potential treatment for preserving intestinal mucosal barrier function in patients with uremia.

  12. Sodium alginate inhibits methotrexate-induced gastrointestinal mucositis in rats.

    Science.gov (United States)

    Yamamoto, Atsuki; Itoh, Tomokazu; Nasu, Reishi; Kajiwara, Eiji; Nishida, Ryuichi

    2013-01-01

    Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin-eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis.

  13. Transient decrease in serum potassium level during ischemic attack of acute coronary syndrome: Paradoxical contribution of plasma glucose level and glycohemoglobin

    Directory of Open Access Journals (Sweden)

    Sekiyama Hiroshi

    2013-01-01

    Full Text Available Abstract Background Although a decrease in serum potassium level has been suggested to be a fairly common observation in acute coronary syndrome (ACS, there have so far been no definitive reports directly demonstrating the transient potassium decrease (the potassium dip during ischemic attack of ACS compared to stable phase in individual patients. To understand the pathophysiological significance of the potassium dip, we examined the changes in serum potassium level throughout ischemic attack and evaluated the clinical factors affecting it. Methods The degree of the potassium dip during ischemic attack (as indicated by ΔK, ΔK = K at discharge − K on admission was examined in 311 consecutive patients with ACS who required urgent hospitalization in our institution. Results Serum potassium level during ischemic attack was significantly decreased compared to that during stable phase (P  Conclusions We have clearly demonstrated that there is a transient decrease in serum potassium level during ischemic attack of ACS compared to stable phase. The degree of the potassium dip was tightly correlated with glucose level, which overwhelmed the diabetic condition, and it also indicates the disease severity. The present study therefore promotes awareness of the significance of monitoring potassium level in parallel with glucose level in patients with ACS.

  14. Cutaneous and mucosal pain syndromes

    Directory of Open Access Journals (Sweden)

    Siddappa K

    2002-01-01

    Full Text Available The cutaneous and mucosal pain syndromes are characterized by pain, burning sensation, numbness or paraesthesia of a particular part of the skin or mucosal surface without any visible signs. They are usually sensory disorders, sometimes with a great deal of psychologic overlay. In this article various conditions have been listed and are described. The possible causative mechanisms are discussed when they are applicable and the outline of their management is described.

  15. Survey on acute oral and/or oropharyngeal reactions induced by radiotherapy for head and neck malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Karasawa, Kumiko; Kokubo, Nahoko; Takemoto, Mitsuhiro; Kaneyasu, Yuko; Fukuhara, Noboru; Okawa, Tomohiko [Tokyo Women`s Medical Coll. (Japan)

    1998-02-01

    Recently, the relationship between radiation induced salivary gland dysfunction and acute radiation mucositis in head and neck malignancies has been discussed. We evaluated this relationship in 8 patients treated with radiotherapy in our institute between June and July 1997. Patients were evaluated for symptom, oral condition, foods intake, body weight and 5 minutes flow of saliva. There was a strong relationship among feeling of oral dryness and oral pain and mucositis. The decrease of saliva flow appeared in the first week of radiation therapy. By the analysis of saliva contents, decrease of amylase was the most important prognostic factor. (author)

  16. Decreased respiratory system compliance on the sixth day of mechanical ventilation is a predictor of death in patients with established acute lung injury

    Directory of Open Access Journals (Sweden)

    Matthay Michael A

    2011-04-01

    Full Text Available Abstract Background Multiple studies have identified single variables or composite scores that help risk stratify patients at the time of acute lung injury (ALI diagnosis. However, few studies have addressed the important question of how changes in pulmonary physiologic variables might predict mortality in patients during the subacute or chronic phases of ALI. We studied pulmonary physiologic variables, including respiratory system compliance, P/F ratio and oxygenation index, in a cohort of patients with ALI who survived more than 6 days of mechanical ventilation to see if changes in these variables were predictive of death and whether they are informative about the pathophysiology of subacute ALI. Methods Ninety-three patients with ALI who were mechanically ventilated for more than 6 days were enrolled in this prospective cohort study. Patients were enrolled at two medical centers in the US, a county hospital and a large academic center. Bivariate analyses were used to identify pulmonary physiologic predictors of death during the first 6 days of mechanical ventilation. Predictors on day 1, day 6 and the changes between day 1 and day 6 were compared in a multivariate logistic regression model. Results The overall mortality was 35%. In multivariate analysis, the PaO2/FiO2 (OR 2.09, p th day of acute lung injury. In addition, a decrease in respiratory system compliance between days 1 and days 6 (OR 2.14, p Conclusions A low respiratory system compliance on day 6 or a decrease in the respiratory system compliance between the 1st and 6th day of mechanical ventilation were associated with increased mortality in multivariate analysis of this cohort of patients with ALI. We suggest that decreased respiratory system compliance may identify a subset of patients who have persistent pulmonary edema, atelectasis or the fibroproliferative sequelae of ALI and thus are less likely to survive their hospitalization.

  17. Indomethacin decreases gastroduodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K

    1995-01-01

    healthy volunteers. Bicarbonate and PGE2 were measured in the gastroduodenal effluents by back-titration and radioimmunoassay, respectively. RESULTS: Vagal stimulation and duodenal luminal acidification (0.1 M HCl; 20 ml; 5 min) increased gastroduodenal bicarbonate secretion (p

  18. New insights into impairment of mucosal defense in portal hypertensive gastric mucosa.

    Science.gov (United States)

    Tomikawa, M; Akiba, Y; Kaunitz, J D; Kawanaka, H; Sugimachi, K; Sarfeh, I J; Tarnawski, A S

    2000-01-01

    Portal hypertension (PHT) increases susceptibility of the gastric mucosa to injury. The aim of this study was to investigate whether PHT affects rat gastric mucosal defense mechanisms in vivo at the pre-epithelial, epithelial, and/or post-epithelial levels. PHT was produced in rats by staged portal vein ligation and sham-operated (SO) rats served as controls. The gastric mucosa was exposed, chambered, and continuously superfused with buffers under in vivo microscopy. We measured gastric mucosal gel layer thickness, surface epithelial cell intracellular pH (pHi), mucosal blood flow, and mucosal/serosal oxygenation. In PHT rats, gastric mucosal gel layer thickness was significantly reduced (88 +/- 16 microm in PHT rats vs. 135 +/- 25 microm in SO rats; P oxygenation of the gastric mucosal surface was decreased by 42% (P portal hypertensive gastric mucosa to injury.

  19. Fish oil, but not soy bean or olive oil enriched infusion decreases histopathological severity of acute pancreatitis in rats without affecting eicosanoid synthesis.

    Science.gov (United States)

    Kilian, Maik; Heukamp, Ina; Gregor, Ja Ilja; Schimke, Ingolf; Kristiansen, Glen; Wenger, Frank Axel

    2011-12-01

    Different dietary fatty acids affect eicosanoid metabolism in different ways, thus influencing the pro- and anti-inflammatory balance of prostaglandins and leukotrienes. Therefore, we analyzed the impact of [n-3], [n-6], and [n-9] fatty acids on eicosanoid metabolism and histopathology in acute pancreatitis in rats. Seventy-five male Sprague-Dawley rats were randomized into five groups (n = 15). Group 1 underwent only laparotomy, while in groups, 2-5 pancreatitis was induced. Groups 1 and 2 were then given saline infusion, groups 3-5 received fat emulsion (group 3: rich in [n-6], group 4: rich in [n-9], group 5: rich in [n-3] fatty acids) for another 18 h. Infusion rich in [n-3] fatty acids significantly decreased histopathological severity of pancreatitis, compared to all other groups. There was no difference concerning the concentrations of prostaglandins and leukotrienes between all groups. Parenteral infusion rich in [n-3] fatty acids reduced histopathological severity of acute pancreatitis in rats without changing eicosanoid metabolism at the endpoint.

  20. Acute starvation in C57BL/6J mice increases myocardial UCP2 and UCP3 protein expression levels and decreases mitochondrial bio-energetic function.

    Science.gov (United States)

    Wang, Chun-Ming; Almsherqi, Zakaria A; McLachlan, Craig S; Matthews, Slade; Ramachandran, Malarmathy; Tay, Stacey Kh; Deng, Yuru

    2011-01-01

    Associations between uncoupling protein (UCP) expression and functional changes in myocardial mitochondrial bio-energetics have not been well studied during periods of starvation stress. Our aim was to study the effects of acute starvation, for 24 or 48 h, on combined cardiac mitochondrial function and UCP expression in mice. Isolated heart mitochondria from female mice starved for 48 h compared to that from mice fed revealed a significantly (p bio-energetic functional changes were associated with increases in mitochondrial UCP2 and UCP3 protein expression. In conclusion, our findings suggest that increased UCP2 and UCP3 levels may contribute to decreased myocardial mitochondrial bio-energetic function due to starvation.

  1. Acute renal failure induced by markedly decreased appetite secondary to a depressive episode after discontinuation of long-term lithium therapy in an elderly patient with bipolar disorder.

    Science.gov (United States)

    Okada, Akira

    2014-05-16

    Some elderly patients on chronic lithium therapy for bipolar disorder and their doctors may be faced with a therapeutic dilemma over whether or not to continue prescribing/taking lithium given their increased risk of reduced renal function. We present the case of a 78-year-old woman with bipolar disorder who discontinued lithium therapy due to increased risk factors for renal injury. After discontinuation, she experienced markedly decreased appetite secondary to a depressive episode, and developed acute renal failure, which subsequently progressed to a more advanced stage of chronic kidney disease. This case suggests that extreme care must be taken to prevent the recurrence of depression in elderly patients with bipolar disorder who discontinue lithium therapy, even when they had been emotionally stable for a long time while receiving lithium. Medications other than lithium for bipolar disorder may be needed at the time lithium therapy is discontinued. 2014 BMJ Publishing Group Ltd.

  2. Aberrant mucosal lymphocyte number and subsets in the colon of post-infectious irritable bowel syndrome patients.

    Science.gov (United States)

    Sundin, Johanna; Rangel, Ignacio; Kumawat, Ashok K; Hultgren-Hörnquist, Elisabeth; Brummer, Robert J

    2014-09-01

    Irritable bowel syndrome (IBS) is characterized by chronic abdominal symptoms such as pain, discomfort, and altered bowel habits. A subset of IBS patients, denoted as post-infectious IBS (PI-IBS) patients, develop symptoms after an enteric infection. Distinct abnormalities in the gut mucosa, including mucosal inflammation, have been proposed to contribute to or be the cause of PI-IBS. This study investigated lymphocyte subsets in PI-IBS patients compared to healthy controls. Ten PI-IBS patients and nine healthy controls participated. All PI-IBS patients met the Rome III diagnostic criteria for IBS and reported sustained symptoms at least 1 year after an episode of acute gastroenteritis. Intraepithelial lymphocytes and lamina propria lymphocytes (LPLs), isolated from mucosal tissue samples, were stained and analyzed for a comprehensive set of cell markers using flow cytometry. The number of LPLs in PI-IBS was significantly increased compared to those in healthy controls (p < 0.05). PI-IBS patients showed significantly increased proportions of CD45RO(+) CD4(+) activated/memory T cells (p < 0.05) and double-positive CD4(+) CD8(+) cells (p < 0.05), respectively, in the lamina propria. The number of CD19(+) LPLs was decreased in PI-IBS patients compared to healthy controls (p < 0.001). This study presents new evidence that PI-IBS is associated with a sustained aberrant mucosal immune response and support future studies of anti-inflammatory or immune-modulating treatments in these patients.

  3. Gastric mucosal damage in water immersion stress:Mechanism and prevention with GHRP-6

    Institute of Scientific and Technical Information of China (English)

    Shu Guo; Qian Gao; Qing Jiao; Wei Hao; Xue Gao; Ji-Min Cao

    2012-01-01

    AIM:To investigate the mechanism of gastric mucosal demage induced by water immersion restraint stress (WRS) and its prevention by growth hormone releasing peptide-6 (GHRP-6).METHODS:Male Wistar rats were subjected to conscious or unconscious (anesthetized) WRS,simple restraint (SR),free swimming (FS),non-water fluid immersion,immersion without water contact,or rats were placed in a cage surrounded by sand.To explore the sensitivity structures that influence the stress reaction besides skin stimuli,a group the rats had their eyes occluded.Cervical bilateral trunk vagotomy or atropine injection was performed in some rats to assess the parasympathetic role in mucosal damage.Gastric mucosal lesions,acid output and heart rate variability were measured.Plasma renin,endothelin-1 and thromboxane B2 and gastric heat shock protein 70 were also assayed.GHRP-6 was injected [intraperitoneal (IP) or intracerebroventricular (ICV)]2 h before the onset of stress to observe its potential prevention of the mucosal lesion.RESULTS:WRS for 6 h induced serious gastric mucosal lesion [lesion area,WRS 81.8 ± 6.4 mm2 vs normal control 0.0 ± 0.0 mm2,P < 0.01],decreased the heart rate,and increased the heart rate variability and gastric acid secretion,suggesting an increase in vagal nervecarrying stimuli.The mucosal injury was inversely correlated with water temperature (lesion area,WRS at 35 ℃ 56.4 ± 5.2 mm2 vs WRS at 23 ℃ 81.8 ± 6.4 mm2,P < 0.01) and was consciousness-dependent.The injury could not be prevented by eye occlusion,but could be prevented by avoiding contact of the rat body with the water by dressing it in an impermeable plastic suit.When water was replaced by vegetable oil or liquid paraffin,there were gastric lesions in the same grade of water immersion.When rat were placed in a cage surrounded by sand,there were no gastric lesions.All these data point to a remarkable importance of cutenuous information transmitted to the high neural center that by vagal nerves

  4. Adrenergic influence on gastric mucosal blood flow in gastric fistula dogs

    DEFF Research Database (Denmark)

    Hovendal, C P; Bech, K; Gottrup, F;

    1984-01-01

    by an initial increase in mucosal blood flow and in the last two periods a decrease in blood flow. alpha-Blockade (phentolamine) reduced the pentagastrin stimulated gastric acid secretion and gastric mucosal blood flow but the ratio between blood flow and acid secretion was increased, indicating a relatively...

  5. 高迁移率族蛋白B1与急性胰腺炎肠黏膜屏障损伤关系的研究%Study on the Relationship between High Mobility Group Box 1 and Intestinal Mucosal Barrier Injury in Acute Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    张伟杰; 徐桂芳; 田志强; 吴国忠; 邹晓平

    2012-01-01

    背景:急性胰腺炎(AP)是临床常见的急腹症,肠黏膜屏障损伤引起继发感染是AP患者死亡的主要原因之一.近年动物模型研究发现高迁移率族蛋白B1(HMGB1)在AP肠黏膜屏障损伤中发挥重要作用.目的:研究HMGB1与AP患者肠黏膜屏障损伤的关系.方法:纳入2007年12月~2009年3月南京大学医学院附属鼓楼医院和中国人民解放军第101医院收治、确诊的AP患者80例,其中重症急性胰腺炎(SAP) 38例,轻症急性胰腺炎(MAP) 42例,选取30名同期健康体检者作为正常对照组.检测患者血清HMGB1含量,分析其与AP病情严重程度、血清内毒素含量、二胺氧化酶(DAO)含量、尿液乳果糖/甘露醇(L/M)比值的关系.结果:SAP组和MAP组血清HMGB1含量、内毒素含量、DAO含量和尿液L/M比值与对照组相比显著升高(P<0.05).患者血清HMGB1含量与血清内毒素含量、DAO含量、尿液L/M比值以及Ranson评分、24 h APACHEⅡ评分、Balthazar CT评分均呈正相关(P<0.001).结论:血清HMGB1含量可反映AP病情严重程度,并可作为判断AP患者肠黏膜屏障损伤的参考指标.%Background: Acute pancreatitis (AP) is a common acute abdomen of digestive system, secondary infection induced by intestinal mucosal barrier injury is one of the main causes of death in AP. Recent experimental studies have shown that high mobility group box 1 ( HMGB1) plays an important role in the intestinal mucosal barrier injury of AP. Aims: To define the relationship between HMGB1 and intestinal mucosal barrier injury of AP patients. Methods: A total of 80 AP patients from Dec. 2007 to Mar. 2009 at Drum Tower Hospital of Nanjing University Medical School and 101th Hospital of People's Liberation Army were enrolled, 38 cases were severe acute pancreatitis (SAP) and 42 were mild acute pancreatitis (MAP). Thirty healthy subjects were served as controls. Serum levels of HMGB1, endotoxin, diamine oxidase (DAO) and urine lactose/mannitol ( L

  6. Ethanol Extract of Fructus Schisandrae Decreases Hepatic Triglyceride Level in Mice Fed with a High Fat/Cholesterol Diet, with Attention to Acute Toxicity

    Directory of Open Access Journals (Sweden)

    Si-Yuan Pan

    2011-01-01

    Full Text Available Effects of the ethanol extract of Fructus Schisandrae (EtFSC on serum and liver lipid contents were investigated in mice fed with high fat/cholesterol (HFC diet for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC levels (up to 62% and 165%, resp. and hepatic triglyceride (TG levels (up to 528% in mice. EtFSC treatment (1 or 5 g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14, i.g. significantly decreased the hepatic TG level (down to 35% and slightly increased the hepatic index (by 8% in hypercholesterolemic mice. Whereas fenofibrate treatment (0.1 g/kg/day for 7 days, i.g. significantly lowered the hepatic TG level (by 61%, it elevated the hepatic index (by 77% in hypercholesterolemic mice. Acute toxicity test showed that EtFSC was relatively non-toxic, with an LD50 value of 35.63 ± 6.46 g/kg in mice. The results indicate that EtFSC treatment can invariably decrease hepatic TG in hypercholesterolemic mice, as assessed by both preventive and therapeutic protocols, suggesting its potential use for fatty liver treatment.

  7. An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase

    Science.gov (United States)

    Olmo, Francisco; Urbanová, Kristína; Rosales, Maria Jose; Martín-Escolano, Ruben; Sánchez-Moreno, Manuel; Marín, Clotilde

    2015-01-01

    In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by 1H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent. PMID:26236582

  8. Acute electroconvulsive therapy followed by maintenance electroconvulsive therapy decreases hospital re-admission rates of older patients with severe mental illness.

    Science.gov (United States)

    Shelef, Assaf; Mazeh, Doron; Berger, Uri; Baruch, Yehuda; Barak, Yoram

    2015-06-01

    Electroconvulsive therapy (ECT) is a highly effective treatment for patients with severe mental illness (SMI). Maintenance ECT (M-ECT) is required for many elderly patients experiencing severe recurrent forms of mood disorders, whereas M-ECT for schizophrenia patients is a poorly studied treatment. We report on the outcomes in aged patients with SMI: schizophrenia and severe affective disorders treated by M-ECT of varying duration to prevent relapse after a successful course of acute ECT. The study measured the effectiveness of M-ECT in preventing hospital readmissions and reducing admission days. A retrospective chart review of 42 consecutive patients comparing the number and length of psychiatric admissions before and after the start of M-ECT was used. We analyzed diagnoses, previous ECT treatments, number of ECT treatments, and number and length of psychiatric admissions before and after M-ECT. Mean age in our sample was 71.5 (6.9) years. Twenty-two (52%) patients experienced severe affective disorders and 20 (48%) experienced schizophrenia. Patients were administered 92.8 (85.9) M-ECT treatments. Average duration of the M-ECT course was 34 (29.8) months. There were on average 1.88 admissions before M-ECT and only 0.38 admissions in the M-ECT period (P < 0.001). Duration of mean hospitalization stay decreased from 215.9 to 12.4 days during the M-ECT (P < 0.01). Our findings suggest that acute ECT followed by M-ECT is highly effective in selected elderly patients with SMIs.

  9. NOD样受体通路在急性腹腔感染早期对大鼠肠屏障的作用机制初探%Effect mechanism of NOD like receptor signaling pathway on intestinal mucosal barrier of rat during early phase of acute intra-abdominal infection

    Institute of Scientific and Technical Information of China (English)

    肖元廷; 李国逊; 王西墨

    2013-01-01

    Objective To initially investigate the expressing regularity and effect of enterocyte NOD like receptors on gut mucosal barrier during early phase of acute intra-abdominal infection.Methods Sprague-Dawley (SD) rats were randomly allocated into control group (n=6) and experimental group (n=24).Acute intra-abdominal infection model was induced by cecal ligation and puncture (CLP).The level of NOD2 and NOD like receptor 3 (NLRP3) mRNA expression in gut mucosa was determined using fluorescent polymerase chain reaction (PCR) ; the expression of caspase-1 and tight junction protein was determined by Western blotting; the activity of nuclear factor-κB (NF-κB) was determined by electrophoretic mobility shift assay (EMSA) ; the level of serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was determined by enzyme linked immunosorbent assay (ELISA).The dead cell percentage of enterocyte was observed by terminaldeoxynucleoitidyl transferase mediated nick end labeling,and the gut mucosal permeability using an in situ loop preparation of gut with fluorescence isothiocyanate-conjugated dextran was determined.Results NOD2 mRNA expression was quickly increased to a very high apex at 2 hours after operation,compared with the control group,the difference was statistically significant (75.50 ± 13.03 vs.1.00 ± 0.00,P<0.01),and quickly descended at 6 hours,and then slowing descended.The expression of NLRP3 mRNA was decreased at 2 hours after the operation,then increased gradually,and peaked at 12 hours,which was significantly higher than that in control group (4.03 ± 0.71 vs.1.00 ± 0.00,P<0.05).The level of caspase-1 was significantly higher than that in control group at 2 hours (3.56 ± 0.14 vs.2.10 ± 0.11,P<0.01) and then gradually increased.The levels of Occludin,ZO-1 and Claudin-4 were obviously lowered than that in control group at 2-6 hours (2 hours Occludin:7.24 ± 1.13 vs.12.72 ± 1.34,6 hours ZO-1:0.47 ± 0.09 vs.1.57 ± 0.17,2 hours Claudin-4:1.63

  10. Intestinal colonization with Candida albicans and mucosal immunity

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Bai; Xian-Hua Liu; Qing-Ying Tong

    2004-01-01

    AIM: To observe the relationship between intestinal lumen colonization with Candida albicans and mucosal secretory IgA (sIgA).METHODS: A total of 82 specific-pathogen-free mice were divided randomly into control and colonization groups. After Candida albicans were inoculated into specific-pathogenfree mice, the number of Candida albicans adhering to cecum and mucosal membrane was counted. The lymphocyte proliferation in Peyer's patch and in lamina propria was shown by BrdU incorporation, while mucosal sIgA (surface membrane) isotype switch in Peyer's patch was investigated. IgA plasma cells in lamina propria were observed by immunohistochemical staining. Specific IgA antibodies to Candida albicans were measured with ELISA.RESULTS: From d 3 to d 14 after Candida albicans gavaging to mice, the number of Candida albicans colonizing in lumen and adhering to mucosal membrane was sharply reduced.Candida albicans translocation to mesenteric lymph nodes occurred at early time points following gavage administration and disappeared at later time points. Meanwhile, the content of specific IgA was increased obviously. Proliferation and differentiation of lymphocytes in lamina propria were also increased.CONCLUSION: Lymphocytes in lamina propria play an important role in intestinal mucosal immunity of specificpathogen-free mice when they are first inoculated with Candida albicans. The decreasing number of Candida albicans in intestine is related to the increased level of specific IgA antibodies in the intestinal mucus.

  11. The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis.

    Directory of Open Access Journals (Sweden)

    Michel J van Vliet

    2010-05-01

    Full Text Available Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of radiotherapy and chemotherapy treatment. Clinically, mucositis is associated with pain, bacteremia, and malnutrition. Furthermore, mucositis is a frequent reason to postpone chemotherapy treatment, ultimately leading towards a higher mortality in cancer patients. According to the model introduced by Sonis, both inflammation and apoptosis of the mucosal barrier result in its discontinuity, thereby promoting bacterial translocation. According to this five-phase model, the intestinal microbiota plays no role in the pathophysiology of mucositis. However, research has implicated a prominent role for the commensal intestinal microbiota in the development of several inflammatory diseases like inflammatory bowel disease, pouchitis, and radiotherapy-induced diarrhea. Furthermore, chemotherapeutics have a detrimental effect on the intestinal microbial composition (strongly decreasing the numbers of anaerobic bacteria, coinciding in time with the development of chemotherapy-induced mucositis. We hypothesize that the commensal intestinal microbiota might play a pivotal role in chemotherapy-induced mucositis. In this review, we propose and discuss five pathways in the development of mucositis that are potentially influenced by the commensal intestinal microbiota: 1 the inflammatory process and oxidative stress, 2 intestinal permeability, 3 the composition of the mucus layer, 4 the resistance to harmful stimuli and epithelial repair mechanisms, and 5 the activation and release of immune effector molecules. Via these pathways, the commensal intestinal microbiota might influence all phases in the Sonis model of the pathogenesis of mucositis. Further research is needed to show the clinical relevance of restoring dysbiosis, thereby possibly decreasing the degree of intestinal mucositis.

  12. Immunology of Gut Mucosal Vaccines

    Science.gov (United States)

    Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

    2011-01-01

    Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

  13. Mucosal immunity and the microbiome.

    Science.gov (United States)

    Neish, Andrew S

    2014-01-01

    By definition, the mucosal immune system is responsible for interfacing with the outside world, specifically responding to external threats, of which pathogenic microbes represent a primary challenge. However, it has become apparent that the human host possesses a numerically vast and taxonomically diverse resident microbiota, predominantly in the gut, and also in the airway, genitourinary tract, and skin. The microbiota is generally considered symbiotic, and has been implicated in the regulation of cellular growth, restitution after injury, maintenance of barrier function, and importantly, in the induction, development, and modulation of immune responses. The mucosal immune system uses diverse mechanisms that protect the host from overt pathogens, but necessarily has coevolved to monitor, nurture, and exploit the normal microbiota. As a whole, mucosal immunity encompasses adaptive immune regulation that can involve systemic processes, local tissue-based innate and inflammatory events, intrinsic defenses, and highly conserved cell autonomous cytoprotective responses. Interestingly, specific taxa within the normal microbiota have been implicated in roles shaping specific adaptive, innate, and cell autonomous responses. Taken together, the normal microbiota exerts profound effects on the mucosal immune system, and likely plays key roles in human physiology and disease.

  14. The optimal use of granulocyte macrophage colony stimulating factor in radiation induced mucositis in head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Patni Nidhi

    2005-01-01

    Full Text Available Objective: Evaluation of response of granulocyte macrophage colony stimulating factor (GM-CSF on acute radiation toxicity profile in head and neck squamous cell carcinoma. Methods and Materials: Thirty three patients with proven stage I or II head & neck carcinoma received conventional external beam radiation therapy. Out of these, six patients received postoperative adjuvant therapy while remaining 27 received definitive RT. Patients were given 100 mcg GM-CSF subcutaneously per day along with radiation after they developed grade 2 mucositis and /or grade 2 dysphagia and / or complained of moderate pain. GM-CSF was administered till there was a subjective relief or objective response. Patients were evaluated for oral ulceration, swallowing status, pain and weight loss. Response to the treatment and patient outcome was assessed. Results: There was a decreased severity of mucositis and dysphagia in the evaluated patients. None of the patients suffered severe pain or required opioids. The mean weight loss was only 1.94%. Minimal side effects were experienced with GM-CSF. Conclusions: GM-CSF reduces the severity of acute side effects of radiation therapy thereby allowing completion of the treatment without interruption. Its remarkable response needs to be evaluated further in large randomized trials. The time of initiation and cessation of GM-CSF during radiation therapy and the required dose needs to be established.

  15. Hydrophobicity of mucosal surface and its relationship to gut barrier function.

    Science.gov (United States)

    Qin, Xiaofa; Caputo, Francis J; Xu, Da-Zhong; Deitch, Edwin A

    2008-03-01

    Loss of the gut barrier has been implicated in the pathogenesis of the multiple organ dysfunction syndrome, and, thus, understanding the intestinal barrier is of potential clinical importance. An important, but relatively neglected, component of the gut barrier is the unstirred mucus layer, which through its hydrophobic and other properties serves as an important barrier to bacterial and other factors within the gut lumen. Thus, the goal of this study was to establish a reproducible method of measuring mucosal hydrophobicity and test the hypothesis that conditions that decrease mucosal hydrophobicity are associated with increased gut permeability. Hydrophobicity was measured in various segments of normal gut by measuring the contact angle of an aqueous droplet placed on the mucosal surface using a commercial goniometer. Second, the effect of the mucolytic agent N-acetyl cysteine on mucosal hydrophobicity and gut permeability was measured, as was the effects of increasing periods of in vivo gut ischemia on these parameters. Gut ischemia was induced by superior mesenteric artery occlusion, and gut permeability was measured by the mucosal-to-serosal passage of fluoresceine isothiocyanate-dextran (4.3 kDa) (FD4) across the everted sacs of ileum. Intestinal mucosal hydrophobicity showed a gradual increase from the duodenum to the end of the ileum and remained at high level in the cecum, colon, and rectum. Both N-acetyl cysteine treatment and ischemia caused a dose-dependent decrease in mucosal hydrophobicity, which significantly correlated increased gut permeability. Mucosal hydrophobicity of the intestine can be reproducibly measured, and decreases in mucosal hydrophobicity closely correlate with increased gut permeability. These results suggest that mucosal hydrophobicity can be a reliable method of measuring the barrier function of the unstirred mucus layer and a useful parameter in evaluating the pathogenesis of gut barrier dysfunction.

  16. The Mucosal Immune System of Teleost Fish

    Directory of Open Access Journals (Sweden)

    Irene Salinas

    2015-08-01

    Full Text Available Teleost fish possess an adaptive immune system associated with each of their mucosal body surfaces. Evidence obtained from mucosal vaccination and mucosal infection studies reveal that adaptive immune responses take place at the different mucosal surfaces of teleost. The main mucosa-associated lymphoid tissues (MALT of teleosts are the gut-associated lymphoid tissue (GALT, skin-associated lymphoid tissue (SALT, the gill-associated lymphoid tissue (GIALT and the recently discovered nasopharynx-associated lymphoid tissue (NALT. Teleost MALT includes diffuse B cells and T cells with specific phenotypes different from their systemic counterparts that have co-evolved to defend the microbe-rich mucosal environment. Both B and T cells respond to mucosal infection or vaccination. Specific antibody responses can be measured in the gills, gut and skin mucosal secretions of teleost fish following mucosal infection or vaccination. Rainbow trout studies have shown that IgT antibodies and IgT+ B cells are the predominant B cell subset in all MALT and respond in a compartmentalized manner to mucosal infection. Our current knowledge on adaptive immunity in teleosts is limited compared to the mammalian literature. New research tools and in vivo models are currently being developed in order to help reveal the great intricacy of teleost mucosal adaptive immunity and help improve mucosal vaccination protocols for use in aquaculture.

  17. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Watkins, E.B.; Findlay, P.; Gelmann, E.; Lane, H.C.; Zabell, A.

    1987-09-01

    The oropharynx and hypopharynx are common sites of involvement in AIDS patients with mucocutaneous Kaposi's sarcoma. The radiotherapist is often asked to intervene with these patients due to problems with pain, difficulty in swallowing, or impending airway obstruction. We have noted an unexpected decrease in normal tissue tolerance of the oropharyngeal mucosa to irradiation in AIDS patients treated in our department. Data on 12 patients with AIDS and Kaposi's sarcoma receiving oropharyngeal irradiation are presented here. Doses ranged from 1000 cGy to 1800 cGy delivered in 150-300 cGy fractions. Seven of eight patients receiving doses of 1200 cGy or more developed some degree of mucositis, four of these developed mucositis severe enough to require termination of treatment. All patients in this study received some form of systemic therapy during the course of their disease, but no influence on mucosal response to irradiation was noted. Four patients received total body skin electron treatments, but no effect on degree of mucositis was seen. Presence or absence of oral candidiasis was not an obvious factor in the radiation response of the oral mucosa in these patients. T4 counts were done on 9 of the 12 patients. Although the timing of the T4 counts was quite variable, no correlation with immune status and degree of mucositis was found. The degree of mucositis seen in these patients occurred at doses much lower than expected based on normal tissue tolerances seen in other patient populations receiving head and neck irradiations. We believe that the ability of the oral mucosa to repair radiation damage is somehow altered in patients with AIDS.

  18. Jun N-Terminal Protein Kinase Enhances Middle Ear Mucosal Proliferation during Bacterial Otitis Media▿

    Science.gov (United States)

    Furukawa, Masayuki; Ebmeyer, Jörg; Pak, Kwang; Austin, Darrell A.; Melhus, Åsa; Webster, Nicholas J. G.; Ryan, Allen F.

    2007-01-01

    Mucosal hyperplasia is a characteristic component of otitis media. The present study investigated the participation of signaling via the Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase in middle ear mucosal hyperplasia in animal models of bacterial otitis media. Otitis media was induced by the inoculation of nontypeable Haemophilus influenzae into the middle ear cavity. Western blotting revealed that phosphorylation of JNK isoforms in the middle ear mucosa preceded but paralleled mucosal hyperplasia in this in vivo rat model. Nuclear JNK phosphorylation was observed in many cells of both the mucosal epithelium and stroma by immunohistochemistry. In an in vitro model of primary rat middle ear mucosal explants, bacterially induced mucosal growth was blocked by the Rac/Cdc42 inhibitor Clostridium difficile toxin B, the mixed-lineage kinase inhibitor CEP11004, and the JNK inhibitor SP600125. Finally, the JNK inhibitor SP600125 significantly inhibited mucosal hyperplasia during in vivo bacterial otitis media in guinea pigs. Inhibition of JNK in vivo resulted in a diminished proliferative response, as shown by a local decrease in proliferating cell nuclear antigen protein expression by immunohistochemistry. We conclude that activation of JNK is a critical pathway for bacterially induced mucosal hyperplasia during otitis media, influencing tissue proliferation. PMID:17325051

  19. Protective role of Rheum tanguticum polysaccharide 1 on the radiation-induced acute intestinal mucosal injury%唐古特大黄多糖组分1对大鼠急性放射性肠损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    刘琳娜; 张甜; 石磊; 张志培; 李诗草; 关波; 张文娟

    2015-01-01

    Objective To investigate the protective role of Rheum tanguticum polysaccharides 1 ( RTP1 ) on the ra-diation-induced acute intestinal mucosal injury in rats .Methods Rats in RTP1 group were treated with 200 , 400 or 800 mg/kg RTP1 by intragastric administration for 7 days.At the 7th day, rats in IC group and RTP1 groups received a single dose of 10 .0 Gy for the abdomianl regions .At the 4 th day of radiation , the small intestinal samples were collected for pathology analysis and levels of SOD , MDA, GSH were also detected .The levels of DAO , D-lactate and endotoxin in blood plasma were measured .Results Compared with the IC group , the mucosa structure of small intestine in the RTP1 group was greatly improved .RTP1 pretreatment decreased the levels of MDA , the plasma levels of DAO D-lactate and endotoxin (P<0.05);enhanced the activity of SOD and the level of GSH (P<0.05).Conclusion RTP1 can promote the recovery of intestinal mucosa damage , which may be related to its inhibition of intestinal epithelial injury and intracellular reactive oxygen species production caused by radiation .%目的:探讨唐古特大黄多糖组分1( Rheum tanguticum polysaccharides , RTP1)对辐射所致大鼠急性肠黏膜损伤的保护作用。方法 RTP1灌胃给药(剂量200、400、800 mg/kg)7 d后,除正常组大鼠外,其余各组均接受10.0 Gy/只一次性全腹均匀X射线照射1次,3d后处死动物,观察小肠黏膜病理形态改变,测定肠黏膜屏障功能、小肠组织氧化还原酶活性及血浆内毒素水平。结果RTP1预处理后可以改善肠黏膜损伤,升高SOD活性及GSH含量,降低MDA水平,抑制血浆中DAO、D-乳酸及内毒素水平,与IC组比较,差异具有统计学意义(P<0.05)。结论 RTP1通过减轻肠黏膜屏障功能损害,增强抗氧化能力保护辐射所致肠黏膜损伤。

  20. Vestibuloplasty: allograft versus mucosal graft.

    Science.gov (United States)

    Hashemi, H M; Parhiz, A; Ghafari, S

    2012-04-01

    The aim of the present study was to compare the application of alloderm and mucosal graft for vestibuloplasty. This randomized controlled trial with split mouth design was carried out on 20 edentulous patients. Patients underwent vestibuloplasty surgery with the Clark technique. Half of the prepared bed in each patient was covered with alloderm and the other half with mucosal graft. Vestibule depth (width of fixed tissue) and relapse in the two sides immediately after surgery, and 1, 3 and 6 months after surgery were measured and compared. Statistical analysis was carried out using the Kolmogorov-Smirnov, Student's paired t and Friedman tests. The width of the fixed tissue in the alloderm graft at 1, 3 and 6 month intervals was significantly lower than that in the autograft (Pvestibuloplasty. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. All rights reserved.

  1. S_3神经根电刺激改善急性完全性脊髓损伤后肠黏膜屏障功能%Role of electrical stimulation of S_3 nerve root in improvement of intestinal mucosal barrier function after acute complete spinal cord injury in rabbits

    Institute of Scientific and Technical Information of China (English)

    白春宏; 安洪; 王莎莉; 蒋电明; 范伟; 聂海

    2010-01-01

    目的 探讨S_3神经根电刺激对急性完全性脊髓损伤后肠黏膜屏障功能障碍的作用. 方法 建立兔脊髓损伤性截瘫模型,以截瘫后行S_3神经根电刺激为实验组,不做刺激截瘫兔为对照组,正常白兔为正常组.无菌条件下,采集门静脉血进行内毒素定量测定和细菌培养,采集肝、脾、肠系膜淋巴结作细菌培养并进行菌种鉴定.取实验组和对照组各动物的肝、脾、肠系膜淋巴结、小肠进行病理切片HE染色检查,取小肠进行电镜检查. 结果 对照组肠黏膜屏障及其他器官破坏严重,血清内毒素水平较实验组和正常组明显增高,肠道菌群移位发生率较高;实验组电刺激S_3神经根使失神经肠道蠕动增强,排出的肠内容物明显增加,同时肠黏膜破坏较轻,其他脏器损伤也较对照组轻,血清内毒素水平较对照组明显减轻并且与正常组差异无统计学意义,细菌移位率明显下降. 结论 急性脊髓损伤后电刺激S_3神经根能较好地促进肠道蠕动,促进肠内容物的排出,良好地改善肠黏膜屏障功能,进而减轻内毒素血症和肠道细菌移位;有利于减少SIRS和MODS的产生.%Objective To investigate the effect of electrical stimulation of S_3 nerve root on improvement of intestinal mucosal barrier function in rabbits with acute complete spinal cord injury. Methods Model of paraplegia was built by injuring spinal cord in rabbits. Then, the rabbits with electrical stimulation of S_3 nerve root were set as experimental group and those without set as control group. Normal rabbits were set as normal group. Under aseptic condition, portal vein blood was collected for quantitative determination of endotoxin and bacterial culture ; and liver, spleen and mesenteric lymph nodes were collected for bacterial culture and strain identification. Liver, spleen, mesenteric lymph nodes and small intestines were collected from experimental group and control group for

  2. A high-protein diet during hospitalization is associated with an accelerated decrease in soluble urokinase plasminogen activator receptor levels in acutely ill elderly medical patients with SIRS

    DEFF Research Database (Denmark)

    Tavenier, Juliette; Haupt, Thomas Huneck; Andersen, Aino L

    2017-01-01

    Acute illness and hospitalization in elderly individuals are often accompanied by the systemic inflammatory response syndrome (SIRS) and malnutrition, both associated with wasting and mortality. Nutritional support and resistance training were shown to increase muscle anabolism and reduce...... inflammation in healthy elderly. We hypothesized that nutritional support and resistance training would accelerate the resolution of inflammation in hospitalized elderly patients with SIRS. Acutely admitted patients aged >65 years with SIRS were randomized to an intervention consisting of a high-protein diet...... accelerate recovery in acutely ill elderly medical patients....

  3. Cryotherapy effect on oral mucositis severity among recipients of bone marrow transplantation: a literature review.

    Science.gov (United States)

    Tayyem, Abdel-Qader Mahmoud

    2014-08-01

    Oral mucositis is a distressing toxic effect of cancer therapy and one of the major side effects of the myeloablative conditioning used to prepare patients for bone marrow transplantation (BMT). Oral cryotherapy is one of the recent modalities used to prevent and manage oral mucositis. The purpose of this review is to clarify the cryotherapy effect on oral mucositis severity among patients receiving myeloablative conditioning followed by BMT. A literature search was performed using six different electronic databases: CINAHL®, MEDLINE®, Nursing Ovid, PubMed, Springer, and Science Direct. Six articles were deemed relevant and included in this review. Oral mucositis increases mortality rate, length of hospital stay, opioid use, and the need for parenteral nutrition usage. It also decreases patient's quality of life and his or her desire to complete treatment. However, oral cryotherapy significantly minimizes the incidence and severity of oral mucositis and decreases secondary oral mucositis complications. Using oral cryotherapy concurrently with a regular oral care protocol can improve its efficacy for preventing and managing oral mucositis. Additional studies should be conducted to create standard oral cryotherapy protocols.

  4. Protective and therapeutic effects of electroacupuncture on gastric motor disorders and acute gastric mucosal lesions under psychological stress in rats%心理性应激状态下针刺对大鼠DMV放电、胃电和胃粘膜损伤的影响

    Institute of Scientific and Technical Information of China (English)

    王景杰; 黄裕新; 郭庆东; 秦明; 高巍; 王庆莉

    2001-01-01

    AIM To test the protective and therapeutic effects of electroacupuncture on gastric motor disorders and acute gastric mucosal lesions under psychological stress in rats. METHODS Ninety-six male Sprague-Dauley rats were randomly divided into three groups: control group (CG, n=32), psychological stress group (PSG, n=32) and electroacupuncture group (EAG, n=32). Every group was randomly divided into four subgroups (CG, n=32, n=8; PSG, n=32, n=8; EAG, n=32, n=8). Animal model was constructed with impulsive stimulator of high voltage and stable currency stimulating the Chusanli with electroacupuncture. Then spontaneous electroactivity of dorsal motor nucleus of the vagus nerve (DMV) was recorded extracellularly and EGG with the serosa method, and the gastric mucosa injury index was calculated. RESULTS The spontaneous electroactivity from DMV was rarely observed in normal rats. EGG was regular with frequency 3 per minute and amplitude 360~370 μV. Gastric mucosa was normal. Under psychological stress, spontaneous electroactivity from DMV was irregular which did not significantly correlate with time and degree of psychological stress. But we observed that increasing frequency of spontaneous electroactivity from DMV was predominant. EGG was disorderly and irregular. There was no difference in frequency and amplitude of EGG between C group and A group on the 2nd day, the 4th day, the 6th day, the 8th day after psychological stress with stimulating chusanli by electroacupuncture under psychological stress. Gastric mucosal lesion appeared, even did ulcer. The degree of gastric mucosal lesion became more and more serious, and lesion index increased gradually with the continues psychological stress. But gastric mucosal lesion alleviated significantly under psychological stress with electroacupuncture stimulation. And the effect was more significant with the continues electroacupuncture stimulation. There was significant difference in lesion index between C group and B

  5. Protein energy malnutrition alters mucosal IgA responses and reduces mucosal vaccine efficacy in mice.

    Science.gov (United States)

    Rho, Semi; Kim, Heejoo; Shim, Seung Hyun; Lee, Seung Young; Kim, Min Jung; Yang, Bo-Gie; Jang, Myoung Ho; Han, Byung Woo; Song, Man Ki; Czerkinsky, Cecil; Kim, Jae-Ouk

    2017-08-30

    Oral vaccine responsiveness is often lower in children from less developed countries. Childhood malnutrition may be associated with poor immune response to oral vaccines. The present study was designed to investigate whether protein energy malnutrition (PEM) impairs B cell immunity and ultimately reduces oral vaccine efficacy in a mouse model. Purified isocaloric diets containing low protein (1/10 the protein of the control diet) were used to determine the effect of PEM. PEM increased both nonspecific total IgA and oral antigen-specific IgA in serum without alteration of gut permeability. However, PEM decreased oral antigen-specific IgA in feces, which is consistent with decreased expression of polymeric Immunoglobulin receptor (pIgR) in the small intestine. Of note, polymeric IgA was predominant in serum under PEM. In addition, PEM altered B cell development status in the bone marrow and increased the frequency of IgA-secreting B cells, as well as IgA secretion by long-lived plasma cells in the small intestinal lamina propria. Moreover, PEM reduced the protective efficacy of the mucosally administered cholera vaccine and recombinant attenuated Salmonella enterica serovar Typhimurium vaccine in a mouse model. Our results suggest that PEM can impair mucosal immunity where IgA plays an important role in host protection and may partly explain the reduced efficacy of oral vaccines in malnourished subjects. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  6. Mucosal vaccination by adenoviruses displaying reovirus sigma 1

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, Eric A. [Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902 (United States); Camacho, Zenaido T. [Department of Cell Biology, Department of Natural Sciences, Western New Mexico University, Silver City, NM 88062 (United States); Hillestad, Matthew L. [Nephrology Training Program, Mayo Clinic, Rochester, MN 55902 (United States); Crosby, Catherine M.; Turner, Mallory A.; Guenzel, Adam J.; Fadel, Hind J. [Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902 (United States); Mercier, George T. [Department of Physics, University of Houston, Houston, TX 77004 (United States); Barry, Michael A., E-mail: mab@mayo.edu [Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902 (United States); Department of Immunology and Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902 (United States)

    2015-08-15

    We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. When wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5.

  7. Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation

    OpenAIRE

    Campbell, Eric L.; Bruyninckx, Walter J.; Kelly, Caleb J; Louise E. Glover; McNamee, Eóin N.; Bowers, Brittelle E.; Bayless, Amanda J.; Scully, Melanie; Saeedi, Bejan J.; Golden-Mason, Lucy; Ehrentraut, Stefan F.; Curtis, Valerie F; Burgess, Adrianne; Garvey, John F; Sorensen, Amber

    2014-01-01

    Acute intestinal inflammation involves early accumulation of neutrophils (PMN) followed by either resolution or progression to chronic inflammation. Based on recent evidence mucosal metabolism influences disease outcomes, we hypothesized that transmigrating PMN influence the transcriptional profile of the surrounding mucosa. Microarray studies revealed a cohort of hypoxia-responsive genes regulated by PMN-epithelial crosstalk. Transmigrating PMN rapidly depleted microenvironmental O2 sufficie...

  8. Citrulline as a Marker for Chemotherapy Induced Mucosal Barrier Injury in Pediatric Patients

    NARCIS (Netherlands)

    van Vilet, Michel J.; Tissing, Wim J. E.; Rings, Edmond H. H. M.; Koetse, Harma A.; Stellaard, Frans; Kamps, Willem A.; de Bont, Eveline S. J. M.

    2009-01-01

    Background. The Currently used National Cancer Institute (NCI) adverse events criteria for mucosal barrier injury (MBI) are insufficient for use in children. We searched for objective, easily measurable indicators for MBI in children with cancer. Purpose. In children with acute myeloid leukemia, var

  9. The Development of an AIDS Mucosal Vaccine

    Directory of Open Access Journals (Sweden)

    Xian Tang

    2010-01-01

    Full Text Available It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1, a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies.

  10. Voice disorders in mucosal leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Ana Cristina Nunes Ruas

    Full Text Available INTRODUCTION: Leishmaniasis is considered as one of the six most important infectious diseases because of its high detection coefficient and ability to produce deformities. In most cases, mucosal leishmaniasis (ML occurs as a consequence of cutaneous leishmaniasis. If left untreated, mucosal lesions can leave sequelae, interfering in the swallowing, breathing, voice and speech processes and requiring rehabilitation. OBJECTIVE: To describe the anatomical characteristics and voice quality of ML patients. MATERIALS AND METHODS: A descriptive transversal study was conducted in a cohort of ML patients treated at the Laboratory for Leishmaniasis Surveillance of the Evandro Chagas National Institute of Infectious Diseases-Fiocruz, between 2010 and 2013. The patients were submitted to otorhinolaryngologic clinical examination by endoscopy of the upper airways and digestive tract and to speech-language assessment through directed anamnesis, auditory perception, phonation times and vocal acoustic analysis. The variables of interest were epidemiologic (sex and age and clinic (lesion location, associated symptoms and voice quality. RESULTS: 26 patients under ML treatment and monitored by speech therapists were studied. 21 (81% were male and five (19% female, with ages ranging from 15 to 78 years (54.5+15.0 years. The lesions were distributed in the following structures 88.5% nasal, 38.5% oral, 34.6% pharyngeal and 19.2% laryngeal, with some patients presenting lesions in more than one anatomic site. The main complaint was nasal obstruction (73.1%, followed by dysphonia (38.5%, odynophagia (30.8% and dysphagia (26.9%. 23 patients (84.6% presented voice quality perturbations. Dysphonia was significantly associated to lesions in the larynx, pharynx and oral cavity. CONCLUSION: We observed that vocal quality perturbations are frequent in patients with mucosal leishmaniasis, even without laryngeal lesions; they are probably associated to disorders of some

  11. Effect of Hymenolepis nana on the mouse ileal mucosal cells: histochemical studies.

    Science.gov (United States)

    Sanad, M M; Salem, S A; el-Gamal, R L; Darwish, R A; el-Ridi, A M

    1990-12-01

    Histochemical studies of the ileal mucosal cells of mice experimentally infected with H. nana revealed definite increase in mucous secretions indicating increased activity of the goblet cells in response to mucosal irritation. The activity of acid phosphatase was also increased representing a sort of defence mechanism against the attached worms. The activities of ATP-ase and NADH diaphorase enzymes were decreased indicating disturbance in the metabolic and transport processes and in the absorptive function of the intestinal epithelial cells.

  12. Partial liquid ventilation decreases tissue and serum tumor necrosis factor-α concentrations in acute lung injury model of immature piglet induced by oleic acid

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; FAN Xiang-ming; LI Xiao-feng; LI Zhi-qiang; WANG Qiang; SUN Li-zhong; LIU Ying-long

    2012-01-01

    Background Pediatric patients are susceptible to lung injury.Acute lung injury in children often results in high mortality.Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models.This study was designed to examine the hypothesis that PLV would attenuate the production of local and systemic tumor necrosis factor (TNF)-α in an immature piglet model of acute lung injury induced by oleic acid (OA).Methods Twelve Chinese immature piglets were induced acute lung injury by OA.The animals were randomly assigned to two groups of six animals,(1) conventional mechanical ventilation (MV) group and (2) PLV with 10 ml/kg FC-77 group.Results Compared with MV group,the PLV group had better cardiopulmonary variables (P <0.05).These variables included heart rate,mean blood pressure,blood pH,partial pressure of arterial oxygen (PaO2),PaO2/inspired O2 fraction (FiO2) and partial pressure of arterial carbon dioxide (PaCO2).PLV reduced TNF-α levels both in plasma and tissue compared with MV group (P <0.05).Conclusion PLV provides protective effects against TNF-a response in OA-induced acute lung injury in immature piglets.

  13. Mucosal immunity and probiotics in fish.

    Science.gov (United States)

    Lazado, Carlo C; Caipang, Christopher Marlowe A

    2014-07-01

    Teleost mucosal immunity has become the subject of unprecedented research studies in recent years because of its diversity and defining characteristics. Its immune repertoire is governed by the mucosa-associated lymphoid tissues (MALT) which are divided into gut-associated lymphoid tissues (GALT), skin-associated lymphoid tissues (SALT), and gill-associated lymphoid tissues (GIALT). The direct contact with its immediate environment makes the mucosal surfaces of fish susceptible to a wide variety of pathogens. The inherent immunocompetent cells and factors in the mucosal surfaces together with the commensal microbiota have pivotal role against pathogens. Immunomodulation is a popular prophylactic strategy in teleost and probiotics possess this beneficial feature. Most of the studies on the immunomodulatory properties of probiotics in fish mainly discussed their impacts on systemic immunity. In contrast, few of these studies discussed the immunomodulatory features of probiotics in mucosal surfaces and are concentrated on the influences in the gut. Significant attention should be devoted in understanding the relationship of mucosal immunity and probiotics as the present knowledge is limited and are mostly based on extrapolations of studies in humans and terrestrial vertebrates. In the course of the advancement of mucosal immunity and probiotics, new perspectives in probiotics research, e.g., probiogenomics have emerged. This review affirms the relevance of probiotics in the mucosal immunity of fish by revisiting and bridging the current knowledge on teleost mucosal immunity, mucosal microbiota and immunomodulation of mucosal surfaces by probiotics. Expanding the knowledge of immunomodulatory properties of probiotics especially on mucosal immunity is essential in advancing the use of probiotics as a sustainable and viable strategy for successful fish husbandry.

  14. Oral health as a predictive factor for oral mucositis

    Directory of Open Access Journals (Sweden)

    Fabio Luiz Coracin

    2013-06-01

    Full Text Available OBJECTIVES: Oral mucositis is a complication frequently associated with hematopoietic stem cell transplantation, decreasing a patient's quality of life and increasing the occurrence of opportunistic infections. The purpose of this study was to determine the incidence and severity of oral mucositis and to assess the correlation of this disease with the oral health of an individual at the time of hematopoietic stem cell transplantation. METHODS: Before transplantation, patients' oral health and inflammatory conditions were determined using the gingival index and the plaque index, which are based on gingival bleeding and the presence of dental plaque, respectively. Additionally, the dental health status was determined using the decayed, missing, and filled teeth index. The monitoring of oral mucositis was based on the World Health Organization grading system and was performed for five periods: from Day 0 to D+5, from D+6 to D+10, from D+11 to D+15, from D+16 to D+20, and from D+21 to D+30. RESULTS: A total of 97 patients (56% male and 44% female who underwent hematopoietic stem cell transplantation at the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo between January 2008 and July 2009 were prospectively examined. The incidence of ulcerative mucositis was highest from days +6 to +10 and from days +11 to +15 in the patients who underwent autologous and allogeneic hematopoietic stem cell transplantation, respectively. CONCLUSION: The data, including the dental plaque and periodontal status data, showed that these oral health factors were predictive of the incidence and severity of oral mucositis in a cohort of patients with similar conditioning regimens before hematopoietic stem cell transplantation.

  15. Modulation of gut mucosal biofilms.

    Science.gov (United States)

    Kleessen, Brigitta; Blaut, Michael

    2005-04-01

    Non-digestible inulin-type fructans, such as oligofructose and high-molecular-weight inulin, have been shown to have the ability to alter the intestinal microbiota composition in such a way that members of the microbial community, generally considered as health-promoting, are stimulated. Bifidobacteria and lactobacilli are the most frequently targeted organisms. Less information exists on effects of inulin-type fructans on the composition, metabolism and health-related significance of bacteria at or near the mucosa surface or in the mucus layer forming mucosa-associated biofilms. Using rats inoculated with a human faecal flora as an experimental model we have found that inulin-type fructans in the diet modulated the gut microbiota by stimulation of mucosa-associated bifidobacteria as well as by partial reduction of pathogenic Salmonella enterica subsp. enterica serovar Typhimurium and thereby benefit health. In addition to changes in mucosal biofilms, inulin-type fructans also induced changes in the colonic mucosa stimulating proliferation in the crypts, increasing the release of mucins, and altering the profile of mucin components in the goblet cells and epithelial mucus layer. These results indicate that inulin-type fructans may stabilise the gut mucosal barrier. Dietary supplementation with these prebiotics could offer a new approach to supporting the barrier function of the mucosa.

  16. Emerging evidence on the pathobiology of mucositis.

    NARCIS (Netherlands)

    Al-Dasooqi, N.; Sonis, S.T.; Bowen, J.M.; Bateman, E.; Blijlevens, N.M.; Gibson, R.J.; Logan, R.M.; Nair, R.G.; Stringer, A.M.; Yazbeck, R.; Elad, S.; Lalla, R.V.

    2013-01-01

    BACKGROUND: Considerable progress has been made in our understanding of the biological basis for cancer therapy-induced mucosal barrier injury (mucositis). The last formal review of the subject by MASCC/ISOO was published in 2007; consequently, an update is timely. METHODS: Panel members reviewed th

  17. Biology and mucosal immunity to myxozoans.

    Science.gov (United States)

    Gómez, Daniela; Bartholomew, Jerri; Sunyer, J Oriol

    2014-04-01

    Myxozoans are among the most abundant parasites in nature. Their life cycles involve two hosts: an invertebrate, usually an annelid, and a vertebrate, usually a fish. They affect fish species in their natural habitats but also constitute a menace for fish aquaculture. Using different strategies they are able to parasitize and cause damage in multiple organs, including mucosal tissues, which they use also as portals of entry. In fish, the main mucosal sites include the intestine, skin and gills. Recently the finding of a specific mucosal immunoglobulin in teleost (IgT), analogous to mammalian IgA, and the capacity of fish to develop a specific mucosal immune response against different pathogens, has highlighted the importance of studying immune responses at mucosal sites. In this review, we describe the major biological characteristics of myxozoan parasites and present the data available regarding immune responses for species that infect mucosal sites. As models for mucosal immunity we review the responses to Enteromyxum spp. and Ceratomyxa shasta, both of which parasitize the intestine. The immune response at the skin and gills is also described, as these mucosal tissues are used by myxozoans as attaching surfaces and portal of entry, and some species also parasitize these sites. Finally, the development of immunoprophylactic strategies is discussed.

  18. Nutrition and Gut Mucositis in Pediatric Oncology

    DEFF Research Database (Denmark)

    Pontoppidan, Peter Erik Lotko

    . Unfortunately, effective treatment strategies against mucositis are not in general available. The overall aim of the present PhD was to study interactions between mucositis, inflammation and nutrition. We hypothesized that toxic reactions in the alimentary tract, induced by chemotherapy, followed by release...

  19. Effect of electroacupunture on gastric mucosal intestinal trefoil factor gene expression of stress-induced gastric mucosal injury in rats

    Institute of Scientific and Technical Information of China (English)

    Xi-Ping Li; Jie Yan; Shou-Xiang Yi; Xiao-Rong Chang; Ya-Ping Lin; Zong-Bao Yang; Ai Huang; Rong Hu

    2006-01-01

    AIM: To investigate electroacupunture(EA) at the acupoints of Stomach Meridian of Foot-Yangming(SMFY),Gallbladder Meridian of Foot-Yangming(SMFY) on gastric mucosal intestinal trefoil factor (ITF) gene expression detection in stress-induced rats with gastric mucosal lesion, and to explore the regulatory mechanism and significance of EA-related gastric mucosal protective effect.METHODS: Forty rats were randomly divided into 4 groups: Blank group, Model group, Model group+EA at acupoints of SMFY group("SMFY group"), and Model group+EA at acupoints of GMFY group(GMFY group).All rats (except blank group) were made model by water immersion and restraint stress (WRS). Then the gastric mucosa tissue in each rat was taken off after assessment of gastric mucosal lesion index(GUI), and the expression of ITF mRNA of the tissues was detected by reverse transcription-polymerase chain reaction(RT-PCR) method.RESULTS: Compared with Model group(54.3 ± 1.34),the GUI value in SMFY group (31±2.21) decreased significantly(P 0.05), in SMFY group(0.76± 0.01)with an extremely obvious difference (P<0.01), furthermore the expression in SMFY group was significantly higher than in GMFY group (P< 0.01).CONCLUSION: The gastric mucosal protective effect by EA at the acupoints of SMFY and GMFY was related to the expression variance of ITF, indicating certain meridian specificity exists. It could be one proof for the TCM theory "Relative particularity between SMFY and stomach".

  20. Antibiotics Suppress Activation of Intestinal Mucosal Mast Cells and Reduce Dietary Lipid Absorption in Sprague-Dawley Rats.

    Science.gov (United States)

    Sato, Hirokazu; Zhang, Linda S; Martinez, Kristina; Chang, Eugene B; Yang, Qing; Wang, Fei; Howles, Philip N; Hokari, Ryota; Miura, Soichiro; Tso, Patrick

    2016-11-01

    The gut microbiota affects intestinal permeability and mucosal mast cells (MMCs) responses. Activation of MMCs has been associated with absorption of dietary fat. We investigated whether the gut microbiota contributes to the fat-induced activation of MMCs in rats, and how antibiotics might affect this process. Adult male Sprague-Dawley rats were given streptomycin and penicillin for 4 days (n = 6-8) to reduce the abundance of their gut flora, or normal drinking water (controls, n = 6-8). They underwent lymph fistula surgery and after an overnight recovery were given an intraduodenal bolus of intralipid. We collected intestinal tissues and lymph fluid and assessed activation of MMCs, intestinal permeability, and fat transport parameters. Compared with controls, intestinal lymph from rats given antibiotics had reduced levels of mucosal mast cell protease II (produced by MMCs) and decreased activity of diamine oxidase (produced by enterocytes) (P antibiotics had reduced intestinal permeability in response to dietary lipid compared with controls (P antibiotics also reduced lymphatic transport of triacylglycerol and phospholipid (P antibiotics and controls. These effects were not seen with an acute dose of antibiotics or 4 weeks after the antibiotic regimen ended. The intestinal microbiota appears to activate MMCs after the ingestion of fat in rats; this contributes to fat-induced intestinal permeability. We found that the gut microbiome promotes absorption of lipid, probably by intestinal production of apolipoproteins and secretion of chylomicrons. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles.

    Science.gov (United States)

    Srivastava, Atul; Gowda, Devegowda Vishakante; Madhunapantula, SubbaRao V; Shinde, Chetan G; Iyer, Meenakshi

    2015-04-01

    Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  2. Mucosal vaccines: novel strategies and applications for the control of pathogens and tumors at mucosal sites.

    Science.gov (United States)

    Nizard, Mevyn; Diniz, Mariana O; Roussel, Helene; Tran, Thi; Ferreira, Luis Cs; Badoual, Cecile; Tartour, Eric

    2014-01-01

    The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites.

  3. ٍEvaluating Baremoom Mouthwash Efficacy in Treatment of Chemotherapy-Induced Mucositis

    Directory of Open Access Journals (Sweden)

    MH Akhavan Karbasi

    2016-03-01

    Full Text Available Introduction: Chemotherapy-induced oral mucositis is regarded as a painful and discomforting chemotherapy complication , affecting patient’s quality of life and endurance to continue the treatment. Hence, treatment of mucositis is of great significance. The present study was conducted to evaluate the effect of Baremoom mouthwash in treatment of chemotherapy-induced mucositis . Methods: This interventional double-blinded randomized clinical trial study was performed on 40 adult patients under chemotherapy in blood and oncology department of Shahid Sadouqhi hospital. The total of 40 patients were randomly divided into two groups: an experimental baremoom group and a control placebo group each containing 20 subjects. Baremoom mouthwash (30% extract, Soren Tektoos, Mashhad and placebo mouthwash ( Sterile water with allowable additives ,Soren Tektoos, Mashhad with same apparent properties were given to the patients (3 times a day for 7 days after mucositis detection. The patients were evaluated in regard with mucositis grade (0-4 WHO and wounds extension on 1th , 3th and 7th days after the study begining. In order to statistically analyze the collected data, Freidman, Mann–Whitney, and wilcoxon W tests were applied utilizing SPSS software (ver, 17. Results: On 3rd  and 7th  days, mean degree of wound extension and mucositis were demonstrated to be significantly different between the two groups. According to Friedman test, both experimental and control groups revealed a significant difference in regard with wound extension and mucositis grade within the three time periods. Conclusion: The study findings indicated that Baremoom mouthwash was more effective in chemotherapy- induced mucositis than placebo. Hence, this agent can be recommended as an appropriate medicine in order to eliminate mucositis symtoms and decrease oral ulcers.

  4. Contributions of Neutrophils to Resolution of Mucosal Inflammation

    Science.gov (United States)

    Colgan, Sean P.; Ehrentraut, Stefan F.; Glover, Louise E.; Kominsky, Douglas J.; Campbell, Eric L.

    2014-01-01

    Neutrophil (PMN) recruitment from the blood stream into surrounding tissues involves a regulated series of events central to acute responses in host defense. Accumulation of PMN within mucosal tissues have historically been considered pathognomonic features of both acute and chronic inflammatory conditions. Historically PMNs have been deemed necessary but detrimental when recruited, given the potential for tissue damage that results from a variety of mechanisms. Recent work, however, has altered our preconcieved notions of PMN contributions to inflammatory processes. In particular, significant evidence implicates a central role for the PMN in triggering inflammatory resolution. Such mechanisms involve both metabolic and biochemical crosstalk pathways during the intimate interactions of PMN with other cell types at inflammatory sites. Here, we highlight several recent examples of how PMN coordinate the resolution of ongoing inflammation, with a particular focus on the gastrointestinal mucosa. PMID:22968707

  5. Intestinal mucosal atrophy and adaptation

    Institute of Scientific and Technical Information of China (English)

    Darcy Shaw; Kartik Gohil; Marc D Basson

    2012-01-01

    Mucosal adaptation is an essential process in gut homeostasis.The intestinal mucosa adapts to a range of pathological conditions including starvation,short-gut syndrome,obesity,and bariatric surgery.Broadly,these adaptive functions can be grouped into proliferation and differentiation.These are influenced by diverse interactions with hormonal,immune,dietary,nervous,and mechanical stimuli.It seems likely that clinical outcomes can be improved by manipulating the physiology of adaptation.This review will summarize current understanding of the basic science surrounding adaptation,delineate the wide range of potential targets for therapeutic intervention,and discuss how these might be incorporated into an overall treatment plan.Deeper insight into the physiologic basis of adaptation will identify further targets for intervention to improve clinical outcomes.

  6. Topical retinoic acid changes the epidermal cell surface glycosylation pattern towards that of a mucosal epithelium

    DEFF Research Database (Denmark)

    Griffiths, C E; Dabelsteen, Erik; Voorhees, J J

    1996-01-01

    in the epidermis and in oral mucosal epithelium. Although type 1 chain structures were not demonstrated in any of the samples, the distribution of type 2 and 3 chain structures in RA-treated epidermis was altered towards that seen in a mucosal epithelium. T antigen, a mucin-type cell surface carbohydrate structure...... normally expressed throughout the epidermis, was only observed in the granular layer of RA-treated epidermis--a feature of mucosal epithelia. Ley, normally only seen in non-keratinized buccal epithelium, was strongly expressed in RA-treated epidermis. In contrast, the glycosylation pattern of the SLS......-treated epidermis was not significantly different from that observed after vehicle treatment. Thus, RA treatment converts normal stratified epithelium towards the phenotype of mucosal epithelium with a decrease in T antigen and a concomitant increase in Ley. These changes are not observed following treatment...

  7. Protective effect of 3,4-methylenedioxyphenol (sesamol) on stress-related mucosal disease in rats.

    Science.gov (United States)

    Hsu, Dur-Zong; Chen, Yi-Wei; Chu, Pei-Yi; Periasamy, Srinivasan; Liu, Ming-Yie

    2013-01-01

    Stress-related mucosal disease (SRMD) causes considerable morbidity and mortality in critically ill patients. 3,4-Methylenedioxyphenol (sesamol) has been reported to have potent antioxidative and anti-inflammatory properties. The aim of this study was to investigate the effect of sesamol on water immersion restraint- (WIR-) induced SRMD in rats. Rat gastric ulcer and hemorrhage were induced by WIR. Rats were pretreated orally with various doses of sesamol (0.1, 0.3, and 1 mg/kg, resp.) 30 min before WIR. Gastric mucosal ulceration, hemoglobin, lipid peroxidation, mucus secretion, proinflammatory cytokines, and nuclear factor (NF)-κB levels were determined 4 h after WIR. In addition, the infiltration of neutrophil and macrophage into gastric mucosa was also determined after WIR. Water immersion restraint increased gastric mucosal ulcer and hemorrhage, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels but failed to affect mucosal lipid peroxidation and mucus secretion compared with non-WIR. Sesamol significantly decreased gastric ulceration and hemorrhage and inhibited mucosal TNF-α, IL-1β, and IL-6 production and NF-κB activity in WIR-treated rats. In addition, increased myeloperoxidase and CD68 levels in gastric mucosa were found in WIR-treated rats compared to non-WIR rats. Sesamol did not affect myeloperoxidase but decreased CD68 levels in mucosa in WIR-treated rats. Sesamol may protect against SRMD by inhibiting gastric mucosal proinflammatory cytokines in rats.

  8. Mucosal and salivary microbiota associated with recurrent aphthous stomatitis.

    Science.gov (United States)

    Kim, Yun-Ji; Choi, Yun Sik; Baek, Keum Jin; Yoon, Seok-Hwan; Park, Hee Kyung; Choi, Youngnim

    2016-04-01

    Recurrent aphthous stomatitis (RAS) is a common oral mucosal disorder of unclear etiopathogenesis. Although recent studies of the oral microbiota by high-throughput sequencing of 16S rRNA genes have suggested that imbalances in the oral microbiota may contribute to the etiopathogenesis of RAS, no specific bacterial species associated with RAS have been identified. The present study aimed to characterize the microbiota in the oral mucosa and saliva of RAS patients in comparison with control subjects at the species level. The bacterial communities of the oral mucosa and saliva from RAS patients with active lesions (RAS, n = 18 for mucosa and n = 8 for saliva) and control subjects (n = 18 for mucosa and n = 7 for saliva) were analyzed by pyrosequencing of the 16S rRNA genes. There were no significant differences in the alpha diversity between the controls and the RAS, but the mucosal microbiota of the RAS patients showed increased inter-subject variability. A comparison of the relative abundance of each taxon revealed decreases in the members of healthy core microbiota but increases of rare species in the mucosal and salivary microbiota of RAS patients. Particularly, decreased Streptococcus salivarius and increased Acinetobacter johnsonii in the mucosa were associated with RAS risk. A dysbiosis index, which was developed using the relative abundance of A. johnsonii and S. salivarius and the regression coefficients, correctly predicted 83 % of the total cases for the absence or presence of RAS. Interestingly, A. johnsonii substantially inhibited the proliferation of gingival epithelial cells and showed greater cytotoxicity against the gingival epithelial cells than S. salivarius. RAS is associated with dysbiosis of the mucosal and salivary microbiota, and two species associated with RAS have been identified. This knowledge may provide a diagnostic tool and new targets for therapeutics for RAS.

  9. [Changes of rat gastric mucosal barrier under stress conditions].

    Science.gov (United States)

    Zhan, Xianbao; Li, Zhaoshen; Cui, Zhongmin; Duan, Yimin; Nie, Shinan; Liu, Jing; Xu, Guoming

    2002-06-01

    OBJECTIVE To explore the changes of rat gastric mucosal barrier under conditions of water immersion restraint stress. METHODS Eighty rats were randomly divided into Group A (20 rats), B (40 rats) and C (20 rats) after being fasted for 24 hours. And then Group A was divided into two subgroups with ten rats in each. The two subgroups in Group A were given normal saline or omeprazole respectively while under the stress condition. The changes of gastric acid or bicarbonate secretion were determined. Group B (40 rats) were randomly divided into four subgroups,which were subgroup control, 1h, 2h and 4h after beginning of the stress. The quantity of glandular mucosal adherent mucus, the thickness of mucus gel layer and ulcer index were measured after stress in Group B. The glandular mucosal samples were labeled by Lanthanum and observed by transmission electromicroscopy. Group C was randomly divided into two subgroups in the same way with Group A. And each subgroup received normal saline or omeprazole respectively H(+) loss in gastric lumen was calculated by determining the difference of acidity between lavage and drainage fluid H(+) concentration. RESULTS It was found that gastric alkaline secretion decreased progressively (P omeprazole subgroup, the amount of H(+) loss (micromol) was 7.46 +/- 1.22, 4.56 +/- 0.35, 3.11 +/- 0.81, 2.32 +/- 1.42 and 2.13 +/- 1.60, which decreased progressively, however still higher than those in normal saline subgroup (P "bicarbonate secretion is inhibited; gastric barrier is damaged; and hydrogen permeability through gastric mucosal barrier increases under stress conditions.

  10. An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function

    DEFF Research Database (Denmark)

    Holtkamp, Frank A; de Zeeuw, Dick; Thomas, Merlin C

    2011-01-01

    Intervention in the renin-angiotensin-aldosterone-system (RAAS) is associated with slowing the progressive loss of renal function. During initiation of therapy, however, there may be an acute fall in glomerular filtration rate (GFR). We tested whether this initial fall in GFR reflects a renal hem......GFR, during losartan treatment, the slower the rate of long-term eGFR decline. Hence, interpretation of trial results relying on slope-based GFR outcomes should separate the initial drug-induced GFR change from the subsequent long-term effect on GFR....

  11. Sex differences and effects of oestrogen in rat gastric mucosal defence

    Science.gov (United States)

    Shore, Richard; Björne, Håkan; Omoto, Yoko; Siemiatkowska, Anna; Gustafsson, Jan-Åke; Lindblad, Mats; Holm, Lena

    2017-01-01

    AIM To evaluate sex differences and the effects of oestrogen administration in rat gastric mucosal defence. METHODS Sex differences in gastric mucus thickness and accumulation rate, absolute gastric mucosal blood flow using microspheres, the integrity of the gastric mucosal epithelium in response to a chemical irritant and the effects of oestrogen administration on relative gastric mucosal blood flow in an acute setting was assessed in an in vivo rat experimental model. Subsequently, sex differences in the distribution of oestrogen receptors and calcitonin gene related peptide in the gastric mucosa of animals exposed to oestrogen in the above experiments was evaluated using immunohistochemistry. RESULTS The absolute blood flow in the GI-tract was generally higher in males, but only significantly different in the corpus part of the stomach (1.12 ± 0.12 mL/min•g in males and 0.51 ± 0.03 mL/min•g in females) (P = 0.002). After removal of the loosely adherent mucus layer the thickness of the firmly adherent mucus layer in males and females was 79 ± 1 µm and 80 ± 3 µm respectively. After 60 min the mucus thickness increased to 113 ± 3 µm in males and 121 ± 3 µm in females with no statistically significant difference seen between the sexes. Following oestrogen administration (0.1 followed by 1 µg/kg•min), mean blood flow in the gastric mucosa decreased by 31% [68 ± 13 perfusion units (PFU)] in males which was significantly different compared to baseline (P = 0.02). In females however, mean blood flow remained largely unchanged with a 4% (5 ± 33 PFU) reduction. The permeability of the gastric mucosa increased to a higher level in females than in males (P = 0.01) after taurocholate challenge. However, the calculated mean clearance increase did not significantly differ between the sexes [0.1 ± 0.04 to 1.1 ± 0.1 mL/min•100 g in males and 0.4 ± 0.3 to 2.1 ± 0.3 mL/min•100 g in females (P = 0.065)]. There were no significant differences between 17

  12. [Therapeutic effect of rebamipide for oral mucositis associated with FEC therapy for breast cancer].

    Science.gov (United States)

    Enami, Akiko; Masuda, Norikazu; Yamamura, Jun; Mizutani, Makiko; Yasojima, Hiroyuki; Shikata, Ayako; Masaoka, Miyuki; Takada, Seiko; Bamba, Nao; Yamamoto, Mie; Abe, Megumi; Makihara, Katsuya

    2014-11-01

    No guidelines for supportive drug therapy have been established for oral mucositis occurring during cancer chemotherapy. We retrospectively examined the progression of oral mucositis in 91 patients with breast cancer who received the 5-fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 regimen between September 2007 and August 2008. Daily rebamipide was administered to patients with oral mucositis as per hospital protocol to evaluate the hypothesized preventive and mucosal protective effects of rebamipide(Mucosta®). Oral mucositis was observed in 43 patients (47%)during 4 courses of FEC. The median age of the patients was 55 years(range, 32-76 years). Of the 91 patients, 49 patients who did not receive rebamipide during the 4 FEC courses were classified as group A, 14 patients who received rebamipide before the start of FEC were classified as group B, and 28 patients who received rebamipide after developing oral mucositis were classified as group C. The incidence of oral mucositis at the start of FEC with or without rebamipide administration was observed in 5 patients in group B (36%) and 38 patients in groups A and C (49%) (p=0.3472). The mucositis grade was G1 in 4 patients and G2 in 1 patient in group B, and G1 in 20 patients and G2 plus G3 in 18 patients in groups A and C (p=0.2467). In group C, the grade decreased in 25 patients (89%) and did not occur (G0) in 17 patients (61%) during the next course, and 15 patients (54%) continued to the final course without any occurrence of mucositis. These results suggest that rebamipide is effective for the treatment of oral mucositis. Although significant differences were not observed in the groups, rebamipide has the potential to prevent development of oral mucositis and alleviate its symptoms, and seems promising as a new supportive drug therapy. We hope to verify the preventive and protective effects of rebamipide by conducting a prospective, randomized trial while treating oral mucositis with basic oral care

  13. An acute bout of self-myofascial release increases range of motion without a subsequent decrease in muscle activation or force.

    Science.gov (United States)

    MacDonald, Graham Z; Penney, Michael D H; Mullaley, Michelle E; Cuconato, Amanda L; Drake, Corey D J; Behm, David G; Button, Duane C

    2013-03-01

    Foam rolling is thought to improve muscular function, performance, overuse, and joint range of motion (ROM); however, there is no empirical evidence demonstrating this. Thus, the objective of the study was to determine the effect of self-myofascial release (SMR) via foam roller application on knee extensor force and activation and knee joint ROM. Eleven healthy male (height 178.9 ± 3.5 cm, mass 86.3 ± 7.4 kg, age 22.3 ± 3.8 years) subjects who were physically active participated. Subjects' quadriceps maximum voluntary contraction force, evoked force and activation, and knee joint ROM were measured before, 2 minutes, and 10 minutes after 2 conditions: (a) 2, 1-minute trials of SMR of the quadriceps via a foam roller and (b) no SMR (Control). A 2-way analysis of variance (condition × time) with repeated measures was performed on all dependent variables recorded in the precondition and postcondition tests. There were no significant differences between conditions for any of the neuromuscular dependent variables. However, after foam rolling, subjects' ROM significantly (p foam rolling, which no longer existed after foam rolling. In conclusion, an acute bout of SMR of the quadriceps was an effective treatment to acutely enhance knee joint ROM without a concomitant deficit in muscle performance.

  14. Circumferential mucosal dissection and esophageal perforation in a patient with eosinophilic esophagitis

    Institute of Scientific and Technical Information of China (English)

    Gennaro Liguori; Maurizio Cortale; Fabrizio Cimino; Michele Sozzi

    2008-01-01

    A young man with a previous history of episodes of mild solid food dysphagia was admitted with a total dysphagia.The esophagogastroduodenoscopy (EGDS) showed an extensive disruption of mucosal layer with a cul-de-sac in the lower part of the esophagus.Soon after the procedure,the patient suffered from an acute chest pain and subsequent CT scan demonstrated an intramural circumferential dissection of thoracic esophagus,and a mediastinal emphysema.An emergency right thoracotomy was performed,followed by a total esophagectomy with esophagogastroplasty and jejunostomy.The histopathology confirmed that mucosal and submucosal layers were circumferentially detached from muscular wall and showed an eosinophilic infiltration of the whole organ with necrosis and erosions of mucosal,submucosal and muscular layers.The diagnosis was esophageal perforation in eosinophilic esophagitis.

  15. Brain neuropeptides in gastric mucosal protection.

    Science.gov (United States)

    Gyires, Klára; Zádori, Zoltán S

    2014-12-01

    The centrally induced gastroprotective effect of neuropeptides has been intensively studied. Besides many similarities, however, differences can also be observed in their gastroprotective actions. The gastroprotective dose-response curve proved to be either sigmoid, or bell-shaped. Additional gastrointestinal effects of neuropeptides can contribute to their mucosal protective effect. Part of the neuropeptides induces gastroprotection by peripheral administration as well. Besides vagal nerve the sympathetic nervous system may also be involved in conveying the central effect to the periphery. Better understanding of the complex mechanism of the maintenance of gastric mucosal integrity may result in the development of new strategy to enhance gastric mucosal resistance against injury.

  16. An NK Cell Perforin Response Elicited via IL-18 Controls Mucosal Inflammation Kinetics during Salmonella Gut Infection.

    Directory of Open Access Journals (Sweden)

    Anna A Müller

    2016-06-01

    Full Text Available Salmonella Typhimurium (S.Tm is a common cause of self-limiting diarrhea. The mucosal inflammation is thought to arise from a standoff between the pathogen's virulence factors and the host's mucosal innate immune defenses, particularly the mucosal NAIP/NLRC4 inflammasome. However, it had remained unclear how this switches the gut from homeostasis to inflammation. This was studied using the streptomycin mouse model. S.Tm infections in knockout mice, cytokine inhibition and -injection experiments revealed that caspase-1 (not -11 dependent IL-18 is pivotal for inducing acute inflammation. IL-18 boosted NK cell chemoattractants and enhanced the NK cells' migratory capacity, thus promoting mucosal accumulation of mature, activated NK cells. NK cell depletion and Prf-/- ablation (but not granulocyte-depletion or T-cell deficiency delayed tissue inflammation. Our data suggest an NK cell perforin response as one limiting factor in mounting gut mucosal inflammation. Thus, IL-18-elicited NK cell perforin responses seem to be critical for coordinating mucosal inflammation during early infection, when S.Tm strongly relies on virulence factors detectable by the inflammasome. This may have broad relevance for mucosal defense against microbial pathogens.

  17. An NK Cell Perforin Response Elicited via IL-18 Controls Mucosal Inflammation Kinetics during Salmonella Gut Infection.

    Science.gov (United States)

    Müller, Anna A; Dolowschiak, Tamas; Sellin, Mikael E; Felmy, Boas; Verbree, Carolin; Gadient, Sandra; Westermann, Alexander J; Vogel, Jörg; LeibundGut-Landmann, Salome; Hardt, Wolf-Dietrich

    2016-06-01

    Salmonella Typhimurium (S.Tm) is a common cause of self-limiting diarrhea. The mucosal inflammation is thought to arise from a standoff between the pathogen's virulence factors and the host's mucosal innate immune defenses, particularly the mucosal NAIP/NLRC4 inflammasome. However, it had remained unclear how this switches the gut from homeostasis to inflammation. This was studied using the streptomycin mouse model. S.Tm infections in knockout mice, cytokine inhibition and -injection experiments revealed that caspase-1 (not -11) dependent IL-18 is pivotal for inducing acute inflammation. IL-18 boosted NK cell chemoattractants and enhanced the NK cells' migratory capacity, thus promoting mucosal accumulation of mature, activated NK cells. NK cell depletion and Prf-/- ablation (but not granulocyte-depletion or T-cell deficiency) delayed tissue inflammation. Our data suggest an NK cell perforin response as one limiting factor in mounting gut mucosal inflammation. Thus, IL-18-elicited NK cell perforin responses seem to be critical for coordinating mucosal inflammation during early infection, when S.Tm strongly relies on virulence factors detectable by the inflammasome. This may have broad relevance for mucosal defense against microbial pathogens.

  18. Alteration of the redox state with reactive oxygen species for 5-fluorouracil-induced oral mucositis in hamsters.

    Directory of Open Access Journals (Sweden)

    Fumihiko Yoshino

    Full Text Available Oral mucositis is often induced in patients receiving cancer chemotherapy treatment. It has been reported that oral mucositis can reduce quality of life, as well as increasing the incidence of mortality. The participation of reactive oxygen species (ROS in the pathogenesis of oral mucositis is well known, but no report has actually demonstrated the presence of ROS. Thus, the purpose of this study was thus to demonstrate the involvement of ROS and the alteration of the redox state in oral mucositis using an in vivo L-band electron spin resonance (ESR technique. An oral mucositis animal model induced by treatment of 5-fluorouracil with 10% acetic acid in hamster cheek pouch was used. Lipid peroxidation was measured as the level of malondialdehyde determined by the thiobarbituric acid reaction. The rate constants of the signal decay of nitroxyl compounds using in vivo L-band ESR were calculated from the signal decay curves. Firstly, we established the oral mucositis animal model induced by treatment of 5-fluorouracil with acetic acid in hamster cheek pouch. An increased level of lipid peroxidation in oral mucositis was found by measuring malondialdehyde using isolated hamster cheek pouch ulcer. In addition, as a result of in vivo L-band ESR measurements using our model animals, the decay rate constants of carbamoyl-PROXYL, which is a reagent for detecting the redox balance in tissue, were decreased. These results suggest that a redox imbalance might occur by excessive generation of ROS at an early stage of oral mucositis and the consumption of large quantities of antioxidants including glutathione in the locality of oral mucositis. These findings support the presence of ROS involved in the pathogenesis of oral mucositis with anti-cancer therapy, and is useful for the development of novel therapies drugs for oral mucositis.

  19. Prevention and management of radiation-induced dermatitis, mucositis, and xerostomia.

    Science.gov (United States)

    Radvansky, Lauren J; Pace, Makala B; Siddiqui, Asif

    2013-06-15

    Current strategies for preventing and managing radiation-induced dermatitis, mucositis, and xerostomia are reviewed, with an emphasis on pharmacologic interventions. Nearly two thirds of all patients with cancer receive radiation therapy during the course of treatment, frequently resulting in acute skin and mucosal toxicities. The severity of radiotherapy-associated toxicities varies according to multiple treatment- and patient-related factors (e.g., total radiation dose and dose fractionation schedule, volume of organ or tissue irradiated, use of concurrent versus sequential chemotherapy, comorbid conditions, functional performance status). Three major radiation toxicities encountered in clinical practice are (1) radiation dermatitis, typically managed with a variety of topical agents such as water-based moisturizing creams or lotions, topical steroids, antiinflammatory emulsions, and wound dressings, (2) radiation-induced oral mucositis, which can be managed through proper basic oral care practices, appropriate pain management, and the use of medicated mouthwashes and oral rinses and gels, and (3) radiation-induced xerostomia, which can be alleviated with saliva substitutes, moistening agents, and sialagogues. Pharmacists involved in the care of patients receiving radiotherapy can play an important role in optimizing symptom control, educating patients on self-care strategies, and adverse effect monitoring and reporting. Radiation-induced dermatitis, mucositis, and xerostomia can cause significant morbidity and diminished quality of life. Pharmacologic interventions for the prevention and treatment of these toxicities include topical agents for dermatitis; oral products, analgesics, and palifermin for mucositis; and amifostine, saliva substitutes, and pilocarpine for xerostomia.

  20. Development of oral mucositis model induced by radiation in hamsters: prevention and treatment with low power laser

    Energy Technology Data Exchange (ETDEWEB)

    Galletta, Vivian C.; Folgosi-Correa, Melissa S.; Zezell, Denise M., E-mail: vivian.galletta@gmail.com, E-mail: melfolgosi@gmail.com, E-mail: zezell@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Gouw-Soares, Sheila, E-mail: sheilagouw@hotmail.com [Universidade Cruzeiro do Sul (UNICSUL), Sao Paulo, SP (Brazil). Fac. de Odontologia; Correa, Luciana, E-mail: lcorrea@usp.br [Universidade de Sao Paulo (FO/USP), SP (Brazil). Fac. de Odontologia

    2013-07-01

    Despite the benefits for the prognosis of patients treated with radiotherapy for oral cancer treatment, it might cause local side effects such as oral mucositis. The oral mucositis is a pathological condition that may appear in affected oral mucosa by ionizing radiation, and the pain related can alter and even stop the antineoplastic treatment, decreasing tumor control rates. Oral mucositis has several treatment modalities, although it remains as a problem since therapies available are not enough to treat efficiently this inflammatory process. Many pharmacological solutions (anti-inflammatory, antibiotics, antiseptic, lubricant agents) are used to alleviate oral mucositis symptoms. Laser treatment has been used as an option, but there is lack of studies to verify the process of laser therapy in oral mucositis caused by ionizing radiation. This work accomplishes follow-up of oral mucositis evolution, comparing laser and benzydamine therapies in an animal model. Forty-two animals were irradiated at head and neck in a single dose of 30 Grays, by means of a Co{sup 60} source. After irradiation, treatments were applied daily, once a day, for 20 days, in which severity of lesions were clinically classified by two calibrated examiners. Histological evaluation was performed to search for mucosal alterations at treated tissues. Statistical analysis of data showed that laser treatment was more efficient than benzydamine treatment, diminishing severity and duration of oral mucosal lesions caused by ionizing irradiation. (author)

  1. Oral Candida as an aggravating factor of mucositis Induced by radiotherapy; Candida Oral como fator agravante da mucosite radioinduzida

    Energy Technology Data Exchange (ETDEWEB)

    Simoes, Cristiane Araujo; Castro, Jurema Freire Lisboa de; Cazal, Claudia [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de odontologia

    2011-07-01

    Antineoplastic treatment induces some undesirable consequences in head and neck cancer patients. Often, the emergence of major clinical manifestations, such as oral mucositis, results in temporary interruption of the treatment, decreasing the patients' quality of life, and increasing hospital costs. Radio-induced or chemo-induced oral mucositis is possibly aggravated by opportunist fungal infections, which turn the mucositis more resistant to the conventional treatments. Objective: this study aims to identify the presence of Candida sp. as a possible aggravating factor of oral mucositis in patients with head and neck cancer under antineoplastic treatment. Method: all patients with radio- or chemo-induced oral mucositis from the Cancer Hospital of Pernambuco, treated between October 2008 and April 2009, were selected for the study. The prevalence of Candida sp was measured through the cytological analysis of oral mucosa in patients with oral mucositis. The fungal presence was correlated with the mucositis severity. Results: the results showed a positive association between fungal colonization and more several lesions (degrees III and IV of mucositis). Conclusion: The outcomes shown may contribute to a solution for unconventional mucosites, which do not respond to the usual treatment. (author)

  2. Exploiting Mucosal Immunity for Antiviral Vaccines.

    Science.gov (United States)

    Iwasaki, Akiko

    2016-05-20

    Mucosal surfaces provide a remarkably effective barrier against potentially dangerous pathogens. Therefore, enhancing mucosal immunity through vaccines-strengthening that first line of defense-holds significant promise for reducing the burden of viral diseases. The large and varied class of viral pathogens, however, continues to present thorny challenges to vaccine development. Two primary difficulties exist: Viruses exhibit a stunning diversity of strategies for evading the host immune response, and even when we understand the nature of effective immune protection against a given virus, eliciting that protection is technically challenging. Only a few mucosal vaccines have surmounted these obstacles thus far. Recent developments, however, could greatly improve vaccine design. In this review, we first sketch out our understanding of mucosal immunity and then compare the herpes simplex virus, human immunodeficiency virus, and influenza virus to illustrate the distinct challenges of developing successful vaccines and to outline potential solutions.

  3. Microbiota and mucosal immunity in amphibians.

    Science.gov (United States)

    Colombo, Bruno M; Scalvenzi, Thibault; Benlamara, Sarah; Pollet, Nicolas

    2015-01-01

    We know that animals live in a world dominated by bacteria. In the last 20 years, we have learned that microbes are essential regulators of mucosal immunity. Bacteria, archeas, and viruses influence different aspects of mucosal development and function. Yet, the literature mainly covers findings obtained in mammals. In this review, we focus on two major themes that emerge from the comparative analysis of mammals and amphibians. These themes concern: (i) the structure and functions of lymphoid organs and immune cells in amphibians, with a focus on the gut mucosal immune system; and (ii) the characteristics of the amphibian microbiota and its influence on mucosal immunity. Lastly, we propose to use Xenopus tadpoles as an alternative small-animal model to improve the fundamental knowledge on immunological functions of gut microbiota.

  4. Microbiota and mucosal immunity in amphibians

    Directory of Open Access Journals (Sweden)

    Bruno M Colombo

    2015-03-01

    Full Text Available We know that animals live in a world dominated by bacteria. In the last twenty years we have learned that microbes are essential regulators of mucosal immunity. Bacterias, archeas and viruses influence different aspects of mucosal development and function. Yet the literature mainly covers findings obtained in mammals. In this review, we focus on two major themes that emerge from the comparative analysis of mammals and amphibians. These themes concern: i the structure and functions of lymphoid organs and immune cells in amphibians, with a focus on the gut mucosal immune system; and ii the characteristics of the amphibian microbiota and its influence on mucosal immunity. Lastly, we propose to use Xenopus tadpoles as an alternative small animal model to improve the fundamental knowledge on immunological functions of gut microbiota.

  5. Effect of ageing on colonic mucosal regeneration

    Institute of Scientific and Technical Information of China (English)

    Ferenc Sipos; Katalin Leiszter; Zsolt Tulassay

    2011-01-01

    The physiologic and pathologic cellular and molecular changes occurring with age in the human colon affect both the inflammatory process leading to mucosal injury and the regenerative capacity of the epithelium. On the one hand, age-related telomere shortening and inflamm-ageing may lead to the development of colonic inflammation, which results in epithelial damage. On the other hand, the altered migration and function of regenerative stem cells, the age-related methylation of mucosal healing-associated genes, together with the alterations of growth factor signaling with age, may be involved in delayed mucosal regeneration. The connections of these alterations to the process of ageing are not fully known. The understanding and customtailored modification of these mechanisms are of great clinical importance with regard to disease prevention and modern therapeutic strategies. Here, we aim to summarize the age-related microscopic and molecular changes of the human colon, as well as their role in altered mucosal healing.

  6. A regenerative approach towards mucosal fenestration closure.

    Science.gov (United States)

    Gandi, Padma; Anumala, Naveen; Reddy, Amarender; Chandra, Rampalli Viswa

    2013-06-06

    Mucosal fenestration is an opening or an interstice through the oral mucosa. A lesion which occurs with greater frequency than generally realised, its occurrence is attributed to a myriad of causes. Mucogingival procedures including connective tissue grafts, free gingival grafts and lateral pedicle grafts are generally considered to be the treatment of choice in the closure of a mucosal fenestration. More often, these procedures are performed in conjunction with other procedures such as periradicular surgery and with bone grafts. However, the concomitant use of gingival grafts and bone grafts in mucosal fenestrations secondary to infections in sites exhibiting severe bone loss is highly debatable. In this article, we report two cases of mucosal fenestrations secondary to trauma and their management by regenerative periodontal surgery with the placement of guided tissue regeneration membrane and bone graft. The final outcome was a complete closure of the fenestration in both the cases.

  7. Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function.

    Science.gov (United States)

    Taché, Y; Perdue, M H

    2004-04-01

    Central corticotrophin releasing-factor (CRF) signalling pathways are involved in the endocrine, behavioural and visceral responses to stress. Recent studies indicate that peripheral CRF-related mechanisms also contribute to stress-induced changes in gut motility and intestinal mucosal function. Peripheral injection of CRF or urocortin inhibits gastric emptying and motility through interaction with CRF2 receptors and stimulates colonic transit, motility, Fos expression in myenteric neurones and defecation through activation of CRF1 receptors. With regard to intestinal epithelial cell function, intraperitoneal CRF increases ion secretion and mucosal permeability to macromolecules. The motility and mucosal changes induced by peripheral CRF mimic those induced by acute stress. In addition, CRF receptor antagonists given peripherally prevent acute restraint and water avoidance stress-induced delayed gastric emptying, stimulation of colonic motor function and mucosal permeability. Similarly, early trauma enhanced intestinal mucosal dysfunction to an acute stressor in adult rats and the response is prevented by peripheral injection of CRF antagonist. Chronic psychological stress results in reduced host defence and initiates intestinal inflammation through mast cell-dependent mechanisms. These findings provide convergent evidence that activation of peripheral CRF receptors and mast cells are important mechanisms involved in stress-related alterations of gut physiology.

  8. Changes in intestinal mucosal immune barrier in rats with endotoxemia

    Institute of Scientific and Technical Information of China (English)

    Chong Liu; Ang Li; Yi-Bing Weng; Mei-Li Duan; Bao-En Wang; Shu-Wen Zhang

    2009-01-01

    AIM: To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS: Male Wistar rats were randomly distributed into two groups: control group and lipopolysaccharide (LPS) group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold (M)-cells, dendritic cells (DCs), CD4~+ T cells, CD8~+ T cells, regulatory T (Tr) cells and IgA~+ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin (IL)-4, interferon (IFN)-γ and forkhead box P3 (Foxp3) in mucosal homogenates were measured by ELISA. The secretory IgA (sIgA) content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay. RESULTS: This research demonstrated that LPS LPSinduced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~+ T cells, and IgA~+ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4~+ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-γ increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased. CONCLUSION: Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.

  9. The development of an AIDS mucosal vaccine

    OpenAIRE

    Xian Tang; Zhiwei Chen

    2010-01-01

    It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, ...

  10. Use of {sup 60}Co panoramic source in the induction of oral mucositis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Maira F.; Benetti, Carolina; Zezell, Denise M., E-mail: mairandrade@yahoo.com, E-mail: zezell@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Correa, Luciana, E-mail: lcorrea@usp.br [Universidade de Sao Paulo (FO/USP), Sao Paulo, SP (Brazil). Fac. de Odontologia

    2013-07-01

    Oral Mucositis is a well-known side effect of chemo-radiotherapy in cancer patients or transplant recipients that could induce hospitalization or impairs therapy in different levels of severity. This study is devoted to define the first steps in the research of low level laser treatments in oral mucositis, proposing a {sup 60}Co radiation to experimentally induce oral mucositis in rats using Panoramic gamma irradiator, simulating usual radiotherapy of head and neck cancer. Fifteen male Wistar rats, above 250g, were irradiated at Centro de Tecnologia das Radiacoes (IPEN - CNEN/SP) and divided in three experimental groups, with different single doses of radiation (30 Gy, 25 Gy and 20 Gy). The animals were observed for a 20 days period. Animals that received 30 Gy and 25 Gy developed greater severity of mucositis and premature euthanasia was performed in these groups on the 7th and 11th day after the irradiation, respectively. The 20 Gy group developed oral mucositis grading from moderated to severe between the days 7 and 11 after irradiation, with progressive body mass loss and decrease in the intake of food and water. These animals recovered from oral mucositis around the 18th day and clinical remission at the 20th day. The single dose of 20 Gy Gamma radiation proved to be efficient way for inducing oral mucositis in rats, allowing the establishment of an experimental model for oral mucositis in rats for future use on interventions of this serious aspect of radiation therapy, such as laser therapy using different wave lengths and power densities. (author)

  11. Effect of Oral Zinc Sulphate in Preventionof Radiation Induced OropharyngealMucositis During and After Radiotherapyin Patients with Head and Neck Cancers

    Directory of Open Access Journals (Sweden)

    Mohammad Mohammadianpanah

    2010-04-01

    Full Text Available Introduction:Mucositis is a disturbing side effect of radiotherapy treatment forhead and neck cancer. To date, no effective modality for its prophylaxis and treatmenthas been found. We performed this study to evaluate the efficacy of oral zincsulphate in delaying the onset of oral and pharyngeal mucositis and decreasing theirseverity.Materials and Methods: Atotal of 58 patients who were treated for head andneck squamous cell carcinoma with radiotherapy or chemoradiotherapy wererandomly assigned to receive oral zinc sulphate (220 mg or an oral placebo 3 timesa day during their radiotherapy course. Total radiation dose was 6000 cGy to 7000cGy by conventional radiotherapy. Seventy nine percent of the patients also receivedconcurrent chemotherapy. Oral and pharyngeal mucositis were scored according toan RTOG protocol. Results:Time to onset of mucositis did not vary between the two groups.However, oral mucositis scores were less severe in the zinc group in weeks 4 to 6.The difference was statistically significant and the Pvalues for weeks 4, 5 and 6 were0.02, 0.007, and 0.012, respectively. Treatment interruptions in both groups were thesame (four cases each and all were due to dysphagia (pharyngeal mucositis.Conclusion:Our results suggest that zinc is effective in reducing the severity oforal mucositis but not pharyngeal mucositis. Treatment interruptions were morefrequently caused by pharyngeal mucositis which presented as dysphagia, rather thanoral pain that was a manifestation of oral mucositis.

  12. A single acute dose of pinitol from a naturally-occurring food ingredient decreases hyperglycaemia and circulating insulin levels in healthy subjects.

    Science.gov (United States)

    Hernández-Mijares, Antonio; Bañuls, Celia; Peris, Jose E; Monzó, Nuria; Jover, Ana; Bellod, Lorena; Victor, Victor M; Rocha, Milagros

    2013-11-15

    A limited amount of research suggests that oral ingestion of pinitol (3-O-methyl-d-chiro-inositol) positively influences glucose tolerance in humans. This study assessed the effects of different doses of pinitol supplementation on glucose tolerance, insulin sensitivity and plasma pinitol concentrations. Thirty healthy subjects underwent two one-day trials in which they consumed a nutritive beverage (Fruit Up®) containing 2.5, 4.0 or 6.0g of pinitol and a corresponding placebo equivalent in both energy and carbohydrates. Blood samples were collected frequently over the 240-min test period. The pinitol-enriched beverage reduced serum glucose and insulin at 45 and 60min, but only at a dose of 6.0g. Plasma pinitol concentrations, maximum concentration and AUC increased according to the dose administered. The results show that a single dose of pinitol from a naturally-occurring food ingredient at the highest dose administered acutely influences indices of whole-body glucose tolerance and insulin sensitivity in healthy subjects.

  13. ‘Mother-in-child’ thrombectomy technique: a novel and effective approach to decrease intracoronary thrombus burden in acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Dauvergne, Christian; Araya, Mario [Department of Cardiology, Clinica Alemana, Santiago (Chile); Uriarte, Polentzi [Department of Cardiology, Instituto Nacional del Torax, Santiago (Chile); Novoa, Oscar; Novoa, Lilian [Department of Cardiology, Clinica Alemana, Santiago (Chile); Maluenda, Gabriel, E-mail: gabrielmaluenda@gmail.com [Department of Cardiology, Clinica Alemana, Santiago (Chile)

    2013-01-15

    Background: The presence of large thrombus burden in patients presenting with acute myocardial infarction (AMI) is common and associated with poor prognosis. This study aimed to describe the feasibility and safety of the novel ‘mother-in-child’ thrombectomy (MCT) technique in patients presenting with AMI and large thrombus burden undergoing percutaneous coronary intervention (PCI). Methods: We studied 13 patients presenting with AMI who underwent PCI with persistent large intracoronary thrombus after standard thrombectomy. The procedure was performed using a 5 F ‘Heartrail II-ST01’ catheter (Terumo Medical) into a 6 F guiding system. Angiographic assessment of thrombus burden and coronary flow was obtained at baseline, immediately after thrombectomy and at the end of the procedure. Results: The mean age was 55.9 ± 13.0 years and involved mostly males (76.9%). All patients underwent PCI via radial approach. Following MCT Thrombolysis In Myocardial Infarction (TIMI) flow improved by 2 or more degrees in 11 patients (84.5%), while visible angiographic thrombus was reduced in 11 patients (84.5%). In the final angiogram, normal TIMI flow was restored in 11 patients (84.5%), with normal myocardial ‘blush’ in 7 patients (53.8%) and total clearance of a visible thrombus in 7 patients (53.8%). Overall, 6 patients received thrombectomy as ‘stand-alone’ procedure. All patients were discharged alive after a mean of 5.6 ± 2 days. Conclusion: This initial report suggests that significant reduction in thrombus burden and improvement of the coronary flow can be safely achieved in patients presenting with AMI and large thrombus burden by using the novel MCT technique.

  14. Osthole ameliorates acute myocardial infarction in rats by decreasing the expression of inflammatory-related cytokines, diminishing MMP-2 expression and activating p-ERK.

    Science.gov (United States)

    Duan, Juan; Yang, Yu; Liu, Hong; Dou, Peng-Cheng; Tan, Sheng-Yu

    2016-01-01

    Osthole, the active constituent of Cnidium monnieri extracts, has been shown to have a diverse range of pharmacological properties. In the present study, we aimed to evaluate the cardioprotective effects of osthole in a rat model of acute myocardial infarction (AMI). The rats with AMI were treated with 1, 3 and 10 mg/kg of osthole or the vehicle for 4 weeks. The infarct size of the rats with AMI was measured, and casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) activities in the rats with AMI were analyzed using commercially available kits. The nuclear factor-κB (NF-κB), tumor necrosis factor‑α (TNF-α), interleukin (IL)-1β and IL-6 levels in whole blood from rats with AMI were also detected using commercially available kits. The levels of Toll-like receptors 2/4 (TLR2/4) and nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2) were also detected by RT-qPCR. Moreover, the protein expression levels of endothelial nitric oxide synthase (eNOS) and mitogen-activated protein kinase (MAPK) cascades, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38, cyclooxygenase-2 (COX-2), as well as matrix metalloproteinase-2 (MMP-2) were all assayed by western blot analysis. Our results revealed that osthole markedly reduced the infarct size, and the levels of CK, CK-MB, LDH and cTnT in the rats with AMI, and that these cardioprotective effects may be associated with the inhibition of inflammatory reactions, the reduction in MMP-2 activity and the activation of MAPK cascades.

  15. Inside the mucosal immune system.

    Directory of Open Access Journals (Sweden)

    Jerry R McGhee

    Full Text Available An intricate network of innate and immune cells and their derived mediators function in unison to protect us from toxic elements and infectious microbial diseases that are encountered in our environment. This vast network operates efficiently by use of a single cell epithelium in, for example, the gastrointestinal (GI and upper respiratory (UR tracts, fortified by adjoining cells and lymphoid tissues that protect its integrity. Perturbations certainly occur, sometimes resulting in inflammatory diseases or infections that can be debilitating and life threatening. For example, allergies in the eyes, skin, nose, and the UR or digestive tracts are common. Likewise, genetic background and environmental microbial encounters can lead to inflammatory bowel diseases (IBDs. This mucosal immune system (MIS in both health and disease is currently under intense investigation worldwide by scientists with diverse expertise and interests. Despite this activity, there are numerous questions remaining that will require detailed answers in order to use the MIS to our advantage. In this issue of PLOS Biology, a research article describes a multi-scale in vivo systems approach to determine precisely how the gut epithelium responds to an inflammatory cytokine, tumor necrosis factor-alpha (TNF-α, given by the intravenous route. This article reveals a previously unknown pathway in which several cell types and their secreted mediators work in unison to prevent epithelial cell death in the mouse small intestine. The results of this interesting study illustrate how in vivo systems biology approaches can be used to unravel the complex mechanisms used to protect the host from its environment.

  16. Adenosine mediates decreased cerebral metabolic rate and increased cerebral blood flow during acute moderate hypoxia in the near-term fetal sheep.

    Science.gov (United States)

    Blood, Arlin B; Hunter, Christian J; Power, Gordon G

    2003-12-15

    Exposure of the fetal sheep to moderate to severe hypoxic stress results in both increased cortical blood flow and decreased metabolic rate. Using intravenous infusion of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist that is permeable to the blood brain barrier, we examine the role of adenosine A1 receptors in mediating cortical blood flow and metabolic responses to moderate hypoxia. The effects of DPCPX blockade are compared to controls as well as animals receiving intravenous 8-(p-sulfophenyl)-theophylline) (8-SPT), a non-selective adenosine receptor antagonist which has been found to be blood brain barrier impermeable. Laser Doppler flow probes, tissue PO2, and thermocouples were implanted in the cerebral cortices of near-term fetal sheep. Catheters were placed in the brachial artery and sagittal sinus vein for collection of samples for blood gas analysis. Three to seven days later responses to a 30-min period of fetal hypoxemia (arterial PO2 10-12 mmHg) were studied with administration of 8-SPT, DPCPX, or vehicle. Cerebral metabolic rate was determined by calculation of both brain heat production and oxygen consumption. In response to hypoxia, control experiments demonstrated a 42 +/- 7 % decrease in cortical heat production and a 35 +/- 10 % reduction in oxygen consumption. In contrast, DPCPX infusion during hypoxia resulted in no significant change in brain heat production or oxygen consumption, suggesting the adenosine A1 receptor is involved in lowering metabolic rate during hypoxia. The decrease in cerebral metabolic rate was not altered by 8-SPT infusion, suggesting that the response is not mediated by adenosine receptors located outside the blood brain barrier. In response to hypoxia, control experiments demonstrated a 35 +/- 7 % increase in cortical blood flow. DPCPX infusion did not change this increase in cortical blood flow, however 8-SPT infusion attenuated increases in flow, indicating that hypoxic

  17. Mucosal Immunity and the Onset of Allergic Disease

    Directory of Open Access Journals (Sweden)

    Yusei Ohshima

    2013-01-01

    Full Text Available Mucosal barriers encounter an environment that is rich in pathogens that possess mechanisms for invading mucosal tissues. These barriers also encounter innocuous antigens, such as foods, airborne antigens, and microbiota. The mucosa has developed a sophisticated immune system that can mount robust immune responses against pathogenic antigens, while maintaining mucosal tolerance against non-pathogenic antigens. Accumulating evidence indicates that the mucosal epithelium, dendritic cells, and a subtype of T cells with regulatory properties play important roles in the development and maintenance of mucosal tolerance. Moreover, the micribiota also contribute to regulating the mucosal immune system. A failure to develop or the breakdown of mucosal tolerance can result in allergic diseases, such as food allergy and asthma. By taking advantage of the unique characteristics of the mucosal immune system, strategies that induce regulatory cells in vivo and, thereby, reconstitute mucosal tolerance may be used to develop novel therapies that are suitable for treating or preventing of allergic diseases.

  18. Clonal repertoires of virus-specific CD8+ T lymphocytes are shared in mucosal and systemic compartments during chronic simian immunodeficiency virus infection in rhesus monkeys.

    Science.gov (United States)

    Sircar, Piya; Furr, Kathryn L; Dorosh, Lauren A; Letvin, Norman L

    2010-08-15

    Because it is thought that mucosal tissues play a fundamental role in early HIV/SIV infection, it is crucial to understand the virus-specific responses in mucosal tissues to facilitate devising strategies to prevent and control these infections. We have employed TCR repertoire analyses to define the clonal composition of a dominant SIV epitope-specific CD8(+) T cell population in mucosal and systemic compartments of SIV-infected rhesus monkeys during both acute and chronic infection. We show that the CD8(+) T cell repertoire in mucosal tissues of uninfected rhesus monkeys is oligoclonal, whereas the CD8(+) T cell repertoire in blood is polyclonal. Early postinfection, the SIV-specific CD8(+) T cell clonal repertoire is distinct in mucosal compartments and peripheral blood. However, we observed a narrowing of the virus-specific CD8(+) T cell clonal repertoire in all sampled anatomic compartments as infection progressed from acute to chronic, and there was comparable clonal diversity in all anatomic compartments. We showed during chronic infection that the same clonal populations of virus-specific CD8(+) T cells are present in all compartments. These data indicate that the SIV-specific CD8(+) T cells in systemic and mucosal sites have a shared clonal origin and are, therefore, capable of both responding to infection in the systemic circulation and trafficking to mucosal tissues.

  19. Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis.

    Science.gov (United States)

    Cheah, Ker Y; Howarth, Gordon S; Yazbeck, Roger; Wright, Tessa H; Whitford, Eleanor J; Payne, Caroline; Butler, Ross N; Bastian, Susan E P

    2009-02-01

    Mucositis is a common side-effect of high-dose chemotherapy regimens. Grape seed extract (GSE) represents a rich source of proanthocyanidins with the potential to decrease oxidative damage and inflammation within the gastrointestinal tract. We evaluated GSE for its capacity to decrease the severity of chemotherapy-induced mucositis in vitro and in vivo. In vitro: GSE was administered to IEC-6 intestinal epithelial cells prior to damage induced by 5-Fluorouracil (5-FU). Cell viability was determined by neutral red assay. In vivo: Female Dark Agouti rats (130-180 g) were gavaged with 1 ml GSE (400 mg/kg) daily (day 3-11) and received 5-FU (150 mg/kg) by intraperitoneal (i.p.) injection on day nine to induce mucositis. Rats were sacrificed at day 12 and intestinal tissues collected for myeloperoxidase and sucrase activity assays and histological analyses. Statistical analysis was performed by one-way ANOVA. GSE prevented the decrease in IEC-6 cell viability induced by 5-FU (p < 0.01). Compared with 5-FU controls, GSE significantly reduced myeloperoxidase activity by 86% and 27% in the proximal jejunum (p < 0.001) and distal ileum (p < 0.05) respectively; decreased qualitative histological scores of damage (p < 0.05) in the proximal jejunum; increased villus height in the proximal jejunum (17%; p < 0.05) and distal ileum (50%; p < 0.01), and attenuated the 5-FU-induced reduction of mucosal thickness by 16% in the jejunum (p < 0.05) and 45% in the ileum (p < 0.01). GSE partially protected IEC-6 cells from 5-FU-induced cytotoxicity and ameliorated intestinal damage induced by 5-FU in rats. GSE may represent a promising prophylactic adjunct to conventional chemotherapy for preventing intestinal mucositis.

  20. Honey and a mixture of honey, beeswax, and olive oil-propolis extract in treatment of chemotherapy-induced oral mucositis: a randomized controlled pilot study.

    Science.gov (United States)

    Abdulrhman, Mamdouh; Elbarbary, Nancy Samir; Ahmed Amin, Dina; Saeid Ebrahim, Rania

    2012-04-01

    In spite of being one of the most investigated subjects among supportive care in cancer, no therapy has been found effective in treatment of chemotherapy-induced oral mucositis. Based on the observations that honey bees products have anti-inflammatory and wound healing effects, the present study tried to evaluate the effect of topical application of honey and a mixture of honey, olive oil-propolis extract, and beeswax (HOPE) in treatment of oral mucositis. This was a randomized controlled clinical trial conducted on 90 patients with acute lymphoblastic leukemia and oral mucositis grades 2 and 3. The mean age of enrolled patients was 6.9 years. The patients were assigned into 3 equal treatment groups: Honey, HOPE, and control groups. Topical treatment for each patient consists of honey, HOPE, and benzocaine gel for honey, HOPE, and control groups, respectively. Recovery time in grade 2 mucositis was significantly reduced in the honey group as compared with either HOPE or controls (P < .05). In grade 3 mucositis, recovery time did not differ significantly between honey and HOPE (P = 0.61) but compared with controls, healing was faster with either honey or HOPE (P < .01). Generally, in both grades of mucositis, honey produced faster healing than either HOPE or controls (P < .05). Based on our results that showed that honey produced faster healing in patients with grade 2/3 chemotherapy-induced mucositis, we recommend using honey and possibly other bee products and olive oil in future therapeutic trials targeting chemotherapy-induced mucositis.

  1. 大鼠口腔黏膜急性排斥反应外周血CD68水平与巨噬细胞浸润的相关性研究%Correlation between the CD68 proportion of peripheral blood mononuclear cell and macrophage infiltration during acute rejection of rat oral mucosal xenotransplantation

    Institute of Scientific and Technical Information of China (English)

    左雯鑫; 王红; 李晓宇; 陶小安; 程斌

    2011-01-01

    Objective To investigate the role of the dynamic process of peripheral blood CD68 mononuclear cells proportion and macrophages inflitration and possible correlation between them during acute rejection of rat oral mucosal xenotransplantation. Methods Thirty-six female wistar rats were divided into three groups randomly, including xenotransplantation group( n = 15 ), trauma control group( n = 12) and normal control group ( n = 9). The rat oral mucosa xenotransplantation model was established. The flow cytometry was used to evaluate the peripheral blood CD68 mononuclear cell and immunohistochemical assay performed to detect the macrophages infiltration one week (W1), two weeks (W2)and four weeks (W4) after xenotransplantation. Results The peripheral blood CD68 mononuclear cells percentage of each xenotransplantation group presented a rise and fall tendency at the three time points, and the peak value appeared at W4(43. 1% ), and the nadir at W2( 10.4% ). The macrophage counts achieved peak value in xenotransplantation group at W1 [ 580.0 (195.5) cell/high power field ], and then reduced with time. Conclusions The mononuclear cells and macrophage were capable of recognizing the xenograft and directly participated the acute rejection of rat oral mucosal xenotransplantation. The peripheral blood mononuclear cells percentage could reflect macrophage infiltrating condition at the early stage of the acute rejection.%目的 探讨大鼠外周血CD68单核细胞比例和颊黏膜巨噬细胞浸润变化及二者相关性在口腔黏膜急性排斥反应中的作用和意义.方法 36只雌性Wistar大鼠按随机数字表随机分为移植组(15只)、创伤对照组(12只)及正常对照组(9只),建立口腔黏膜异种移植模型,分别于术后1、2、4周采用流式细胞术检测各组大鼠外周血CD68单核细胞百分数,免疫组化SP法检测颊黏膜巨噬细胞CD68的表达.结果 移植组3个时点外周血CD68单核细胞百分数呈高低起伏的变

  2. Fas-deficient mice have impaired alveolar neutrophil recruitment and decreased expression of anti-KC autoantibody:KC complexes in a model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Gil Sucheol

    2012-10-01

    Full Text Available Abstract Background Exposure to mechanical ventilation enhances lung injury in response to various stimuli, such as bacterial endotoxin (LPS. The Fas/FasL system is a receptor ligand system that has dual pro-apoptotic and pro-inflammatory functions and has been implicated in the pathogenesis of lung injury. In this study we test the hypothesis that a functioning Fas/FasL system is required for the development of lung injury in mechanically ventilated mice. Methods C57BL/6 (B6 and Fas-deficient lpr mice were exposed to either intra-tracheal PBS followed by spontaneous breathing or intra-tracheal LPS followed by four hours mechanical ventilation with tidal volumes of 10 mL/kg, respiratory rate of 150 breaths per minute, inspired oxygen 0.21 and positive end expiratory pressure (PEEP of 3 cm of water. Results Compared with the B6 mice, the lpr mice showed attenuation of the neutrophilic response as measured by decreased numbers of BAL neutrophils and lung myeloperoxidase activity. Interestingly, the B6 and lpr mice had similar concentrations of pro-inflammatory cytokines, including CXCL1 (KC, and similar measurements of permeability and apoptosis. However, the B6 mice showed greater deposition of anti-KC:KC immune complexes in the lungs, as compared with the lpr mice. Conclusions We conclude that a functioning Fas/FasL system is required for full neutrophilic response to LPS in mechanically ventilated mice.

  3. Decreased level of Nurr1 in heterozygous young adult mice leads to exacerbated acute and long-term toxicity after repeated methamphetamine exposure.

    Directory of Open Access Journals (Sweden)

    Yu Luo

    Full Text Available The abuse of psychostimulants, such as methamphetamine (METH, is prevalent in young adults and could lead to long-term adaptations in the midbrain dopamine system in abstinent human METH abusers. Nurr1 is a gene that is critical for the survival and maintenance of dopaminergic neurons and has been implicated in dopaminergic neuron related disorders. In this study, we examined the synergistic effects of repeated early exposure to methamphetamine in adolescence and reduction in Nurr1 gene levels. METH binge exposure in adolescence led to greater damage in the nigrostrial dopaminergic system when mice were exposed to METH binge later in life, suggesting a long-term adverse effect on the dopaminergic system. Compared to naïve mice that received METH binge treatment for the first time, mice pretreated with METH in adolescence showed a greater loss of tyrosine hydroxylase (TH immunoreactivity in striatum, loss of THir fibers in the substantia nigra reticulata (SNr as well as decreased dopamine transporter (DAT level and compromised DA clearance in striatum. These effects were further exacerbated in Nurr1 heterozygous mice. Our data suggest that a prolonged adverse effect exists following adolescent METH binge exposure which may lead to greater damage to the dopaminergic system when exposed to repeated METH later in life. Furthermore, our data support that Nurr1 mutations or deficiency could be a potential genetic predisposition which may lead to higher vulnerability in some individuals.

  4. The effect of prebiotics on intestinal mucosal barrier protein occludin in model rats acutely exposed to high altitude%添加益生元对急进高原大鼠肠黏膜屏障紧密连接蛋白Occludin的作用研究

    Institute of Scientific and Technical Information of China (English)

    段云; 张方信; 单体栋; 邵珂; 张盼

    2011-01-01

    Objective To investigate the effect of prebioties on the expression of occludin intestinal mueosal barrier in model rats acutely exposed to high altitude.Method Forty-eight rat medels in radical plateau hypoxia environment were established(3 848 m).These rats were randomly divided into hypoxia control group (n =24) and prebiotics group ( n = 24), then further randomly divided into six groups ( n = 8) by 2 d, 4 d and 6 d time points, respectively.The expression of occludin protein in intestinal mucosa was analyzed by immunohistochemistry method, and Tumor necrosis factorα (TNF-α) and interleukin-10 (IL-10) in ileum tissue were determined with ELISA.Result At each time point, occludin protein in all hypoxia control groups were significantly lower than in prebiotica group (P < 0.01 ), while TNF-α was significantly increased and serum IL-10 was remarkably reduced(P <0.05).Conclusion Prebiotics has the effect of maintaining the integrity of epithelial cells by increasing occludin protein expression and reducing the damage of intestinal mucosal barrier caused by hypoxia.%目的 探讨通过灌胃的方式给予益生元(低聚半乳糖)对急进高原大鼠肠黏膜屏障紧密连接Occludin蛋白的表达及作用.方法 在3 848米建立高原缺氧模型大鼠共48只,随机选24只为高原缺氧对照组,另24只为添加益生元组,再按2 d,4 d和6 d时间点,分为6组,每组8只.采用免疫组织化学法检测Occludin蛋白表达,用ELISA法测定回肠组织肿瘤坏死因子-α(TNF-α)、白介素-10(IL-10).结果 和高原缺氧组各时间点比较,添加益生元组Occludin蛋白表达显著升高(P<0.01),TNF-α水平降低、IL-10水平升高(P<0.05).结论 益生元可以增加急进高原缺氧大鼠肠黏膜紧密连接蛋白Occludin的表达,改善高原缺氧对大鼠肠黏膜屏障的破坏.

  5. Connexins in respiratory and gastrointestinal mucosal immunity.

    Science.gov (United States)

    Bou Saab, Joanna; Losa, Davide; Chanson, Marc; Ruez, Richard

    2014-04-17

    The mucosal lining forms the physical and chemical barrier that protects against pathogens and hostile particles and harbors its own population of bacteria, fungi and archea, known as the microbiota. The immune system controls tolerance of this population of microorganisms that have proven to be beneficial for its host. Keeping its physical integrity and a correct balance with the microbiota, the mucosa preserves its homeostasis and its protective function and maintains host's health. However, in some conditions, pathogens may succeed in breaching mucosal homeostasis and successfully infecting the host. In this review we will discuss the role the mucosa plays in the defense against bacterial pathogens by considering the gap junction protein connexins. We will detail their implication in mucosal homeostasis and upon infection with bacteria in the respiratory and the gastrointestinal tracts. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  6. Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury.

    Science.gov (United States)

    Hu, JiangWei; Yang, ZaiLiang; Wang, Jun; Tang, YongYong; Liu, Hao; Zhang, Bin; Chen, Hu

    2013-01-01

    A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC) assay, a hydrogen peroxide (H2O2) content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline) that were exposed to 4.5 Gy (60)Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin(-)CD117(+): hucMSC-Trx-1 vs. hucMSC, Pgene and cell therapy as a multifunctional radioprotector for ARI.

  7. Novel vaccine development strategies for inducing mucosal immunity.

    Science.gov (United States)

    Fujkuyama, Yoshiko; Tokuhara, Daisuke; Kataoka, Kosuke; Gilbert, Rebekah S; McGhee, Jerry R; Yuki, Yoshikazu; Kiyono, Hiroshi; Fujihashi, Kohtaro

    2012-03-01

    To develop protective immune responses against mucosal pathogens, the delivery route and adjuvants for vaccination are important. The host, however, strives to maintain mucosal homeostasis by responding to mucosal antigens with tolerance, instead of immune activation. Thus, induction of mucosal immunity through vaccination is a rather difficult task, and potent mucosal adjuvants, vectors or other special delivery systems are often used, especially in the elderly. By taking advantage of the common mucosal immune system, the targeting of mucosal dendritic cells and microfold epithelial cells may facilitate the induction of effective mucosal immunity. Thus, novel routes of immunization and antigen delivery systems also show great potential for the development of effective and safe mucosal vaccines against various pathogens. The purpose of this review is to introduce several recent approaches to induce mucosal immunity to vaccines, with an emphasis on mucosal tissue targeting, new immunization routes and delivery systems. Defining the mechanisms of mucosal vaccines is as important as their efficacy and safety, and in this article, examples of recent approaches, which will likely accelerate progress in mucosal vaccine development, are discussed.

  8. Role of gastric blood flow, neutrophil infiltration, and mucosal cell proliferation in gastric adaptation to aspirin in the rat.

    Science.gov (United States)

    Konturek, S J; Brzozowski, T; Stachura, J; Dembinski, A; Majka, J

    1994-01-01

    Gastric mucosa exhibits the ability to adapt to ulcerogenic action of aspirin but the mechanism of this phenomenon is unknown. In this study, acute gastric lesions were produced by single or repeated doses of acidified aspirin in rats with intact or resected salivary glands and with intact or suppressed synthase of nitric oxide. A single oral dose of aspirin produced a dose dependent increase in gastric lesions accompanied by considerable blood neutrophilia and mucosal neutrophil infiltration, significant reduction in gastric blood flow, and almost complete suppression of biosynthesis of prostaglandins. After rechallenge with aspirin, the mucosal damage became smaller and progressively declined with repeated aspirin insults. Gastric adaptation to aspirin was accompanied by a significant rise in gastric blood flow, reduction in both blood neutrophilia and mucosal neutrophil infiltration, and a remarkable increase in mucosal cell regeneration and mucosal content of epidermal growth factor. Salivectomy, which reduced the mucosal content of epidermal growth factor, aggravated the initial mucosal damage induced by the first exposure to acidified aspirin but did not prevent the adaptation of this mucosa to repeated aspirin insults. Pretreatment with NG-nitro-L-arginine (L-NNA), a specific inhibitor of nitric oxide synthase, eliminated the hyperaemic response to repeated aspirin but did not abolish the development of adaptation to aspirin showing that the maintenance of the gastric blood flow plays little part in this adaptation. In conclusion, the stomach adapts readily to repeated aspirin insults and this is accompanied by a considerable reduction in blood neutrophilia and the severity of neutrophil infiltration and by an extensive proliferation of mucosal cells possibly involving epidermal growth factor. PMID:7525421

  9. Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury.

    Directory of Open Access Journals (Sweden)

    JiangWei Hu

    Full Text Available A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC assay, a hydrogen peroxide (H2O2 content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline that were exposed to 4.5 Gy (60Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin(-CD117(+: hucMSC-Trx-1 vs. hucMSC, P<0.05; hucMSC-Trx-1 vs. NS, P<0.01, promoting the formation of red blood cells and hemoglobin (hucMSC-Trx-1 vs. hucMSC or NS, P<0.05, reducing inflammation and damage in important organs (Bone marrow and lung: hucMSC-Trx-1 vs. NS, P<0.01; hucMSC-Trx-1 vs. hucMSC, P<0.05. Liver and intestine: hucMSC-Trx-1 vs. NS, P<0.05; hucMSC-Trx-1 vs. hucMSC, P<0.05, and prolonging survival (hucMSC-Trx-1 vs. hucMSC or NS, P<0

  10. Oral mucosal diseases: evaluation and management.

    Science.gov (United States)

    Stoopler, Eric T; Sollecito, Thomas P

    2014-11-01

    Oral mucosal diseases encompass several common conditions that affect the general population. Some of these disorders present with signs and symptoms that are pathognomonic for the condition, whereas others present with similar features that can make clinical diagnosis difficult to achieve. It is important for physicians to have a clear understanding of these disorders to provide appropriate care to patients. This article reviews clinical aspects of common oral mucosal disorders, including candidiasis, herpes simplex viral infections, aphthous stomatitis, lichen planus, pemphigus vulgaris, and mucous membrane pemphigoid.

  11. Endoscopic, assisted, modified turbinoplasty with mucosal flap.

    Science.gov (United States)

    Puterman, M M; Segal, N; Joshua, B-Z

    2012-05-01

    A variety of surgical methods have been developed to reduce the volume of the inferior turbinates, in order to create a more patent nasal airway. We describe a technique used in our department since February 2002 for all patients undergoing inferior turbinectomy. We resect with endoscopic assistance the lateral mucosa and bony inferior turbinate. This technique can reduce a large volume of the turbinate while preserving the mucosal continuity and the submucosa by covering the raw surface with a mucosal flap. We believe our method minimises post-operative side effects and complications such as dryness, infection, bleeding and pain.

  12. Sinusitis (acute)

    Science.gov (United States)

    2008-01-01

    Introduction Acute sinusitis is defined pathologically, by transient inflammation of the mucosal lining of the paranasal sinuses lasting less than 4 weeks. Clinically, it is characterised by nasal congestion, rhinorrhoea, facial pain, hyposmia, sneezing, and, if more severe, additional malaise and fever. It affects 1−5% of the adult population each year in Europe. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with clinically diagnosed acute sinusitis, and with radiologically or bacteriologically confirmed acute sinusitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (amoxicillin, co-amoxiclav, doxycycline, cephalosporins, macrolides, different doses [amoxicillin, co-amoxiclav, doxycycline, cephalosporins, macrolides], long-course regimens), antihistamines, cephalosporins or macrolides, decongestants (xylometazoline, phenylephrine, pseudoephedrine), doxycycline, saline nasal washes, steam inhalation, and topical corticosteroids (intra-nasal). PMID:19450327

  13. Beneficial effects of Camellia Oil (Camellia oleifera Abel.) on ketoprofen-induced gastrointestinal mucosal damage through upregulation of HO-1 and VEGF.

    Science.gov (United States)

    Cheng, Yu-Ting; Wu, Shu-Li; Ho, Cheng-Ying; Huang, Shang-Ming; Cheng, Chun-Lung; Yen, Gow-Chin

    2014-01-22

    Nonsteroidal anti-inflammatory drugs, such as ketoprofen, are generally used to treat pain and inflammation and as pyretic agents in clinical medicine. However, the usage of these drugs may lead to oxidative injury to the gastrointestinal mucosa. Camellia oil ( Camellia oleifera Abel.) is commonly used in Taiwan and China as cooking oil. Traditional remedies containing this oil exert beneficial health effects on the bowel, stomach, liver, and lungs. However, the effects of camellia oil on ketoprofen-induced oxidative gastrointestinal mucosal lesions remain unknown. The objective of this study was to evaluate the effect of camellia oil on ketoprofen-induced acute gastrointestinal ulcers. The results showed that treatment of Int-407 cells with camellia oil (50-75 μg/mL) not only increased the levels of heme oxygenase-1 (HO-1), glutathione peroxidase (GPx), and superoxide dismutase (SOD) mRNA expression but also increased vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) protein secretion, which served as a mucosal barrier against gastrointestinal oxidative injury. Moreover, Sprague-Dawley (SD) rats treated with camellia oil (2 mL/kg/day) prior to the administration of ketoprofen (50 mg/kg/day) successfully inhibited COX-2 protein expression, inhibited the production of interleukin-6 (IL-6) and nitrite oxide (NO), reversed the impairment of the antioxidant system, and decreased oxidative damage in the gastrointestinal mucosa. More importantly, pretreatment of SD rats with camellia oil strongly inhibited gastrointestinal mucosal injury induced by ketoprofen, which was proved by the histopathological staining of gastrointestinal tissues. Our data suggest that camellia oil exerts potent antiulcer effects against oxidative damage in the stomach and intestine induced by ketoprofen.

  14. 重症急性胰腺炎大鼠肠粘膜免疫屏障功能损伤及早期腹腔引流对其影响的实验研究%Research of Intestinal Mucosal Immune Barrier Injury to Rats with Severe Acute Pancreatitis and Impact on It by Early Catheter Drainage

    Institute of Scientific and Technical Information of China (English)

    郑晓博; 邹洪; 伍松; 唐均成; 文艺; 冯梨; 陈振宇; 张少华; 汤礼军

    2013-01-01

    目的:探讨早期腹腔引流对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠肠粘膜免疫屏障功能损伤的影响及作用机制。方法将72只Wistar大鼠随机分为3组:SAP组(A组)、SAP引流组(B组)、假手术对照组(C组)。观察术后12、24 h大鼠死亡率,各时相点腹水量。分别于术后的第6、12、24 h采集血液、腹水、肠液、肠组织、胰腺标本,冻存以备检测。采用全自动生化分析仪检测血清及腹水淀粉酶活性,ELISA法测定血清及腹水IL-6、TNF-a浓度,胰腺组织冰冻切片HE染色观察病理变化,ELISA法检测肠液sIgA水平,肠组织作CD4+T淋巴细胞免疫组化染色。结果分别于术后6、12、24 h,通过各项指标的检测,有以下发现:①术后同时相点A、B两组大鼠血清及腹水淀粉酶、IL-6、TNF-a水平均显著高于C组大鼠水平,且术后同时相点A、B两组大鼠胰腺组织水肿及出血坏死程度均较C组大鼠显著加重。②对肠液sIgA的检测发现,术后各时相点A、B两组大鼠均显著低于C组大鼠水平,且A、B两组大鼠肠组织中CD4+T淋巴细胞浸润程度也均显著低于C组。③术后同时相点B组大鼠血清及腹水淀粉酶、IL-6、TNF-a水平均显著低于A组大鼠水平;B组大鼠胰腺组织水肿及出血坏死程度较A组明显减轻。④术后同时相点B组肠液sIgA水平显著高于A组水平;且B组肠组织中CD4+T淋巴细胞浸润程度较A组显著增加。结论SAP发病早期,通过腹腔置管引流将富含诸如IL-6、TNF-a等炎性因子的腹水引流出体外,对肠粘膜免疫屏障功能起到显著的保护作用。%Objective To investigate the impact and mechanism of the catheter drainage on the rats with intestinal mucosal immune barrier in-jury by severe acute pancreatitis(SAP).Methods 72 wistar rats were randomly divided into three groups:SAP model group(A group),SAP drainage group (B group

  15. The Role of Intestinal Microbiota in the Development and Severity of Chemotherapy-Induced Mucositis

    NARCIS (Netherlands)

    van Vliet, Michel J.; Harmsen, Hermie J. M.; de Bont, Eveline S. J. M.; Tissing, Wim J. E.

    2010-01-01

    Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of radiotherapy and chemotherapy treatment. Clinically, mucositis is associated with pain, bacteremia, and malnutrition. Furthermore, mucositis is a frequent reason to postpone chemotherapy treatment,

  16. Changes in the Mucus Barrier during Cisplatin-Induced Intestinal Mucositis in Rats

    Directory of Open Access Journals (Sweden)

    Hajime Yamamoto

    2013-01-01

    Full Text Available Aim. Gastrointestinal mucositis is a frequent complication of antineoplastic chemotherapy, but the effects of chemotherapy on mucosal defense mechanisms remain poorly understood. We studied the effects of cisplatin on mucin, one of the principal defense factors of the gastrointestinal mucosa, and evaluated the efficacy of two different types of H2-receptor antagonists against cisplatin-induced mucositis. Methods. Cisplatin (6 mg/kg was administered intravenously to rats (day 0. The rats were sacrificed 1, 3, 7, and 11 days after treatment, and their stomach, jejunum, ileum, and colon were removed. Immunoreactivity of the mucosa was compared with the use of anti-mucin monoclonal antibody. To evaluate the efficacy of H2-receptor antagonists, either famotidine (3 mg/kg or lafutidine (30 mg/kg was given orally once daily on days 0, 1, and 2. Histological and biochemical findings were compared among the groups to assess effects on cisplatin-induced injury. Results. Cisplatin significantly altered the immunoreactivity and content of mucin in the small intestinal mucosa, especially in the ileum. Lafutidine protected against cisplatin-induced mucosal injury and attenuated decreased mucin accumulation. Conclusion. Cisplatin appears to alter the mucus barrier function in the intestinal mucosa. Lafutidine might effectively prevent chemotherapy-induced mucositis by activating intestinal mucus cells.

  17. Protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats

    Institute of Scientific and Technical Information of China (English)

    Wei Gao; Hai-Ying Li; Li-Xin Wang; Li-Jun Hao; Jian-Li Gao; Rong-Juan Zheng; Chun-Jiang Cai; Yan-Ling Si

    2014-01-01

    Objective:To observe the protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats.Methods:All rats were randomly divided into normal control group, cirrhosis and treatment group.Thioacetamide was used to establish rat model of cirrhotic portal hypertension.The necrotic tissue of gastric mucosa ulcer focus, degree of neutrophils infiltration at the ulcer margin, portal pressure, portal venous flow, abdominal aortic pressure, abdominal aortic blood flow at front end, gastric mucosal blood flow(GMBF), glycoprotein(GP) of gastric mucosa,basal acid secretion,H+ back -diffusion, gastric mucosal damage index,NO, prostaglandinE2(PGE2) and tumor necrosis factor-α(TNF-α) were determined respectively, and the pathological changes of gastric mucosa were also observed by microscope.Results:Compared with cirrhosis group and the control group, the ulcer bottom necrotic material, gastric neutrophil infiltration andUI of the treatment group were all decreased significantly(P<0.01), GMBF value,GP values, serumNO,PGE2,TNF-α were all significantly increased.Conclusions:Omeprazole has an important protective effect on gastric mucosal and it can increase gastric mucosal blood flow and related to many factors.

  18. Flagellin stimulates protective lung mucosal immunity: role of cathelicidin-related antimicrobial peptide.

    Science.gov (United States)

    Yu, Fu-shin; Cornicelli, Matthew D; Kovach, Melissa A; Newstead, Michael W; Zeng, Xianying; Kumar, Ashok; Gao, Nan; Yoon, Sang Gi; Gallo, Richard L; Standiford, Theodore J

    2010-07-15

    TLRs are required for generation of protective lung mucosal immune responses against microbial pathogens. In this study, we evaluated the effect of the TLR5 ligand flagellin on stimulation of antibacterial mucosal immunity in a lethal murine Pseudomonas aeruginosa pneumonia model. The intranasal pretreatment of mice with purified P. aeruginosa flagellin induced strong protection against intratracheal P. aeruginosa-induced lethality, which was attributable to markedly improved bacterial clearance, reduced dissemination, and decreased alveolar permeability. The protective effects of flagellin on survival required TLR5 and were observed even in the absence of neutrophils. Flagellin induced strong induction of innate genes, most notably the antimicrobial peptide cathelicidin-related antimicrobial peptide. Finally, flagellin-induced protection was partially abrogated in cathelicidin-related antimicrobial peptide-deficient mice. Our findings illustrate the profound stimulatory effect of flagellin on lung mucosal innate immunity, a response that might be exploited therapeutically to prevent the development of gram-negative bacterial infection of the respiratory tract.

  19. In Vivo and Cadaver Studies of the Canalicular/Lacrimal Sac Mucosal Folds

    Directory of Open Access Journals (Sweden)

    Yongsheng You

    2016-01-01

    Full Text Available Purpose. The study aimed to investigate canalicular/lacrimal sac mucosal folds (CLS-MFs in vivo and in cadavers in order to explore their functional roles in the lacrimal drainage system. Method. The observations of CLS-MFs in vivo were performed on 16 patients with chronic dacryocystitis after undergoing an endonasal endoscopic dacryocystorhinostomy (EE-DCR. The lacrimal sacs and common canaliculi of 19 adult cadavers were dissected. The opening/closing of an orifice and mucosal fold was recorded. All of the specimens were subjected to a histological examination. Results. The upper and lower lacrimal canaliculi in all of the samples united to form a common canaliculus that opened to the lacrimal sac. CLS-MFs were observed in 10 of the 16 patients (62.5% and 9 of the 19 cadavers (47.4%. The orifices or mucosal folds could be opened or closed when related muscles contracted or relaxed. Histological sections showed a mucosal fold at one side of an orifice. Conclusion. Common canaliculus is the most common type that the canaliculus opens to lacrimal sac. CLS-MFs exist in a certain ratio that can be opened/closed with the movement of the orifices. They may be involved in the drainage of tears or the pathogenesis of acute dacryocystitis or lacrimal sac mucocele.

  20. Mucosal microbiome in patients with recurrent aphthous stomatitis.

    Science.gov (United States)

    Hijazi, K; Lowe, T; Meharg, C; Berry, S H; Foley, J; Hold, G L

    2015-03-01

    Recurrent aphthous stomatitis (RAS) is the most common disease affecting oral mucosae. Etiology is unknown, but several factors have been implicated, all of which influence the composition of microbiota residing on oral mucosae, which in turn modulates immunity and thereby affects disease progression. Although no individual pathogens have been conclusively shown to be causative agents of RAS, imbalanced composition of the oral microbiota may play a key role. In this study, we sought to determine composition profiles of bacterial microbiota in the oral mucosa associated with RAS. Using high-throughput 16S rRNA gene sequencing, we characterized the most abundant bacterial populations residing on healthy and ulcerated mucosae in patients with RAS (recruited using highly stringent criteria) and no associated medical conditions; we also compared these to the bacterial microbiota of healthy controls (HCs). Phylum-level diversity comparisons revealed decreased Firmicutes and increased Proteobacteria in ulcerated sites, as compared with healthy sites in RAS patients, and no differences between RAS patients with healthy sites and HCs. Genus-level analysis demonstrated higher abundance of total Bacteroidales in RAS patients with healthy sites over HCs. Porphyromonadaceae comprising species associated with periodontal disease and Veillonellaceae predominated in ulcerated sites over HCs, while no quantitative differences of these families were observed between healthy sites in RAS patients and HCs. Streptococcaceae comprising species associated with oral health predominated in HCs over ulcerated sites but not in HCs over healthy sites in RAS patients. This study demonstrates that mucosal microbiome changes in patients with idiopathic RAS--namely, increased Bacteroidales species in mucosae of RAS patients not affected by active ulceration. While these changes suggest a microbial role in initiation of RAS, this study does not provide data on causality. Within this limitation

  1. Topical morphine for oral mucositis in children

    DEFF Research Database (Denmark)

    Nielsen, Bettina Nygaard; Aagaard, Gitte; Henneberg, Steen W;

    2012-01-01

    Systemic opioids for painful chemotherapy-induced oral mucositis in children often result in unsatisfactory pain relief and a high frequency of side effects. Opioids applied topically can produce analgesia by binding to opioid receptors on peripheral terminals of sensory neurons. These receptors...

  2. Nutrition and Gut Mucositis in Pediatric Oncology

    DEFF Research Database (Denmark)

    Pontoppidan, Peter Erik Lotko

    and differential regulation of miRNA-155 and -146a. This was sustained during the first three weeks after transplantation, along with increased spontaneous production of inflammatory cytokines by early trafficking of leukocytes. In conclusion, we successfully induced oral and intestinal mucositis in piglets...

  3. Management of mucositis in oral irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Feber, T. [Cookridge Hospital, Leeds (United Kingdom)

    1996-10-01

    Mucositis significantly affects quality of life and tolerance of treatment in oral irradiation. Effective management of this complication is therefore very important. However, there is a scarcity of up-to-date oral care protocols, with most centres using ritualized regimens. The literature on oral rinses in radiation mucositis is at best inconclusive and at worst confusing. In this study, patients undergoing radical radiotherapy treatment (55-60 Gy in 4 weeks) to more than 50% of the oral cavity and oropharynx were randomized to a research based oral care protocol with either saline 0.9% or hydrogen peroxide 3.5 volumes (HP) as rinses. The results of this study show that, on average, the group receiving saline rinses appeared to do better on some outcomes than the group receiving HP. This suggests that frequent mechanical cleansing of the mouth may be more important than the antiseptic properties of a mouthwash. Antiseptic mouthwashes may be contra-indicated in radiation mucositis. In order to determine best practice in mucositis management, multicentre, multidisciplinary trials should be conducted. (Author).

  4. Measuring mucosal damage induced by cytotoxic therapy.

    NARCIS (Netherlands)

    Blijlevens, N.M.A.; Land, B. van 't; Donnelly, J.P.; Rabet, L. M'; Pauw, B.E. de

    2004-01-01

    We scored oral mucositis and gut toxicity and measured sugar permeability testing among 56 recipients of a haematopoietic stem cell transplant (HSCT) given myeloablative conditioning with idarubicin, cyclophosphamide and TBI, and a group of 18 patients given cytotoxic chemotherapy for newly diagnose

  5. Mucosal melanoma of the head and neck.

    Science.gov (United States)

    Ascierto, Paolo Antonio; Accorona, Remo; Botti, Gerardo; Farina, Davide; Fossati, Piero; Gatta, Gemma; Gogas, Helen; Lombardi, Davide; Maroldi, Roberto; Nicolai, Piero; Ravanelli, Marco; Vanella, Vito

    2017-04-01

    Mucosal melanoma of the head and neck is a very rare and aggressive malignancy with a very poor prognosis. The nasal cavity, paranasal sinuses, and oral cavity are the most common locations. One-, 3- and 5-year survival rates between 2000 and 2007 were 63%, 30% and 20%, respectively. Cigarette smoking seems to be a risk factor even though the evidence for this is very low. Clinical signs and symptoms are usually nonspecific. While surgery is considered the mainstay of treatment for most mucosal melanomas of the head and neck region, radiotherapy has a role in local control of the disease after surgery. Many new treatment options in the last years, in particular targeted therapies (i.e. inhibitors of c-KIT, NRAS/MEK or BRAF) and immunotherapies (anti CTLA-4 and anti PD-1/PD-L1 antibodies), have changed the history of cutaneous melanoma. Despite the different biology, mucosal melanoma is currently treated in the same way as cutaneous melanoma; however, patients with mucosal melanoma were excluded from the majority of recent clinical trials. Recent molecular findings offer new hope for the development of more effective systemic therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Mucosal biofilm detection in chronic otitis media

    DEFF Research Database (Denmark)

    Wessman, Marcus; Bjarnsholt, Thomas; Eickhardt-Sørensen, Steffen Robert

    2015-01-01

    The objectives of this study were to examine middle ear biopsies from Greenlandic patients with chronic otitis media (COM) for the presence of mucosal biofilms and the bacteria within the biofilms. Thirty-five middle ear biopsies were obtained from 32 Greenlandic COM patients admitted to ear...

  7. Biomarkers and non-invasive tests for gastrointestinal mucositis

    NARCIS (Netherlands)

    N.S.S. Kuiken (Nicoline S. S.); E.H.H.M. Rings (Edmond); N.M. Blijlevens (Nicole ); W.J.E. Tissing (Wim)

    2017-01-01

    textabstractGastrointestinal mucositis is a complex inflammatory reaction of the mucous membranes, a side effect of both chemotherapy and radiotherapy. Currently, assessment scales are used to diagnose mucositis. However, a biomarker which would determine whether there is mucositis and thereby

  8. Can the oral microflora affect oral ulcerative mucositis?

    NARCIS (Netherlands)

    Laheij, A.M.G.A.; de Soet, J.J.

    2014-01-01

    Purpose of review: Oral mucositis is one of the most prevalent toxicities after hematopoietic stem cell transplantation. Mucositis is initiated by the chemotherapy or radiotherapy preceding the transplantation. It is commonly accepted that microorganisms play a role in the process of oral mucositis.

  9. Mucosal Vaccination and Therapy with Genetically Modified Lactic Acid Bacteria

    NARCIS (Netherlands)

    Wells, J.

    2011-01-01

    Lactic acid bacteria (LAB) have proved to be effective mucosal delivery vehicles that overcome the problem of delivering functional proteins to the mucosal tissues. By the intranasal route, both live and killed LAB vaccine strains have been shown to elicit mucosal and systemic immune responses that

  10. Biomarkers and non-invasive tests for gastrointestinal mucositis

    NARCIS (Netherlands)

    Kuiken, N. S. S.; Rings, E. H. H. M.; Blijlevens, N. M. A.; Tissing, Wim J. E.

    Gastrointestinal mucositis is a complex inflammatory reaction of the mucous membranes, a side effect of both chemotherapy and radiotherapy. Currently, assessment scales are used to diagnose mucositis. However, a biomarker which would determine whether there is mucositis and thereby establish the

  11. Concomitant early mucosal and cutaneous leishmaniasis in Brazil.

    Science.gov (United States)

    Boaventura, Viviane S; Cafe, Virginia; Costa, Jackson; Oliveira, Fabiano; Bafica, Andre; Rosato, Andrea; de Freitas, Luiz A R; Brodskyn, Claudia; Barral-Netto, Manoel; Barral, Aldina

    2006-08-01

    Mucosal leishmaniasis (ML) is often clinically silent until reaching a highly advanced state. In this prospective study, 6 of 220 patients with early cutaneous leishmaniasis were diagnosed with mucosal involvement by otorhinolaryngological examination (a rate similar to the reported rate of late ML). Detection of early ML may represent an important strategy in preventing severe mucosal destruction in human leishmaniasis.

  12. Mucosal Vaccination and Therapy with Genetically Modified Lactic Acid Bacteria

    NARCIS (Netherlands)

    Wells, J.

    2011-01-01

    Lactic acid bacteria (LAB) have proved to be effective mucosal delivery vehicles that overcome the problem of delivering functional proteins to the mucosal tissues. By the intranasal route, both live and killed LAB vaccine strains have been shown to elicit mucosal and systemic immune responses that

  13. What is the best treatment to decrease pro-inflammatory cytokine release in acute skeletal muscle injury induced by trauma in rats: low-level laser therapy, diclofenac, or cryotherapy?

    Science.gov (United States)

    de Almeida, Patrícia; Tomazoni, Shaiane Silva; Frigo, Lucio; de Carvalho, Paulo de Tarso Camillo; Vanin, Adriane Aver; Santos, Larissa Aline; Albuquerque-Pontes, Gianna Móes; De Marchi, Thiago; Tairova, Olga; Marcos, Rodrigo Labat; Lopes-Martins, Rodrigo Álvaro Brandão; Leal-Junior, Ernesto Cesar Pinto

    2014-03-01

    Currently, treatment of muscle injuries represents a challenge in clinical practice. In acute phase, the most employed therapies are cryotherapy and nonsteroidal anti-inflammatory drugs. In the last years, low-level laser therapy (LLLT) has becoming a promising therapeutic agent; however, its effects are not fully known. The aim of this study was to analyze the effects of sodium diclofenac (topical application), cryotherapy, and LLLT on pro-inflammatory cytokine levels after a controlled model of muscle injury. For such, we performed a single trauma in tibialis anterior muscle of rats. After 1 h, animals were treated with sodium diclofenac (11.6 mg/g of solution), cryotherapy (20 min), or LLLT (904 nm; superpulsed; 700 Hz; 60 mW mean output power; 1.67 W/cm(2); 1, 3, 6 or 9 J; 17, 50, 100 or 150 s). Assessment of interleukin-1β and interleukin-6 (IL-1β and IL-6) and tumor necrosis factor-alpha (TNF-α) levels was performed at 6 h after trauma employing enzyme-linked immunosorbent assay method. LLLT with 1 J dose significantly decreased (p cryotherapy groups. On the other hand, treatment with diclofenac and cryotherapy does not decrease pro-inflammatory cytokine levels compared to the non-treated injured group. Therefore, we can conclude that 904 nm LLLT with 1 J dose has better effects than topical application of diclofenac or cryotherapy in acute inflammatory phase after muscle trauma.

  14. Effects of Honey on Oral Mucositis among Pediatric Cancer Patients Undergoing Chemo/Radiotherapy Treatment at King Abdulaziz University Hospital in Jeddah, Kingdom of Saudi Arabia

    Science.gov (United States)

    Al Jaouni, Soad K.; Al Muhayawi, Mohammad S.; Hussein, Abear; Elfiki, Iman; Al-Raddadi, Rajaa; Al Muhayawi, Saad M.; Almasaudi, Saad

    2017-01-01

    One of the most common complications of cancer chemotherapy is oral mucositis. This study evaluates the therapeutic effects of honey with the focus on grade III and IV oral mucositis, reduction of bacterial and fungal infections, duration of episodes of oral mucositis, and body weight in pediatric leukemic patients undergoing chemo/radiotherapy. This is an open labeled randomized controlled study conducted at our hospital on 40 pediatric cancer patients undergoing chemo/radiotherapy. All the 40 patients included in this study experienced a sum total of 390 episodes of fever and neutropenia associated with oral mucositis. A significant reduction of oral mucositis, associated Candida, and aerobic pathogenic bacterial infections was noted in patients in the honey treatment group. Also, there is a significant decrease in the duration of hospitalization for all those in the treatment group combined with a significant increase of body weight, delayed onset, and decreased severity of pain related to oral mucositis. Complications of oral mucositis can be tremendously reduced by the topical application of local Saudi honey and honey should be used as an integrative approach in prophylaxis and treatment of chemo/radiotherapy-induced oral mucositis in pediatric cancer patients. Further research is needed to elucidate and better understand the underlying mechanism.

  15. Strategies of mucosal immunotherapy for allergic diseases

    Institute of Scientific and Technical Information of China (English)

    Yi-Ling Ye; Ya-Hui Chuang; Bor-Luen Chiang

    2011-01-01

    Incidences of allergic disease have recently increased worldwide.Allergen-specific immunotherapy (SIT) has long been a controversial treatment for allergic diseases.Although beneficial effects on clinically relevant outcomes have been demonstrated in clinical trials by subcutaneous immunotherapy (SCIT),there remains a risk of severe and sometimes fatal anaphylaxis.Mucosal immunotherapy is one advantageous choice because of its non-injection routes of administration and lower side-effect profile.This study reviews recent progress in mucosal immunotherapy for allergic diseases.Administration routes,antigen quality and quantity,and adjuvants used are major considerations in this field.Also,direct uses of unique probiotics,or specific cytokines,have been discussed.Furthermore,some researchers have reported new therapeutic ideas that combine two or more strategies.The most important strategy for development of mucosal therapies for allergic diseases is the improvement of antigen formulation,which includes continuous searching for efficient adjuvants,collecting more information about dominant T-cell epitopes of allergens,and having the proper combination of each.In clinics,when compared to other mucosal routes,sublingual immunotherapy (SLIT) is a preferred choice for therapeutic administration,although local and systemic side effects have been reported.Additionally,not every allergen has the same beneficial effect.Further studies are needed to determine the benefits of mucosal immunotherapy for different allergic diseases after comparison of the different administration routes in children and adults.Data collected from large,well-designed,double-blind,placebo-controlled,and randomized trials,with post-treatment follow-up,can provide robust substantiation of current evidence.

  16. Documentation of radiation-induced oral mucositis. Scoring Systems

    Energy Technology Data Exchange (ETDEWEB)

    Riesenbeck, D. [Klinik und Poliklinik fuer Strahlentherapie - Radioonkologie, Westfaelische Wilhelms-Universitaet Muenster (Germany); Doerr, W. [Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Technische Universitaet Dresden (Germany)

    1998-11-01

    Background: Radiation therapy of tumors in the head and neck region is frequently associated with severe side effects in the oral mucosa which often necessitate interruption of the prescribed treatment protocol. In order to compare therapeutic strategies and, more important, in order to perform multicenter studies, generally accepted scoring systems have to be applied for uniform documentation of the oral mucosal response. Methods: Different scoring protocols are found in the literature. The scoring protocols most widely accepted are the CTC classification and the RTOG/EORTC classification. These are compared with more detailed systems. Results: In the CTC classification, grading of stomatitis is included in the responses of the gastrointestinal tract and emphasizes dietary effects. For effects of radiation alone or of radiochemotherapy, the RTOG/EORTC system, focusing on therapeutic interventions, has been established. However, there are only minor differences in the grading of mucositis between these 2 protocols. Based on the RTOG/EORTC classification, Maciejewski et al. introduced a classification system with inclusion of the area affected, but also changed the sensitivity of the scores. The latter may be confusing if the source of the system used is not cited in a report. An alternative system was proposed by Dische, which in addition to objective morphologic criteria also includes the symptoms induced by the mucosal response, and hence includes some subjective aspects reported by the patient. Conclusions: For routine documentation of acute radiation side effects in the oral cavity, the German version of the RTOG/EORTC classification can be recommended. In studies with particular interest in oral mucositis, a more sensitive scoring system may be applied. In any publication concerning mucositis, a table or a detailed description of the system used should be included. (orig.) [Deutsch] Hintergrund: Die Strahlentherapie von Tumoren der Kopf-Hals-Region ist haeufig

  17. Long term immunologic consequences of experimental stroke and mucosal tolerance

    Directory of Open Access Journals (Sweden)

    Gee J Michael

    2009-10-01

    Full Text Available Abstract Background An inflammatory insult following middle cerebral artery occlusion (MCAO is associated with a predisposition to develop a deleterious autoimmune response to the brain antigen myelin basic protein (MBP. Induction of immunologic tolerance to brain antigens prior to MCAO prevents this deleterious autoimmune response and is associated with better functional outcome early after stroke. In this study, we sought to determine the long term immunologic consequences of experimental stroke and induction of mucosal tolerance. Methods Male Lewis rats were tolerized to MBP or ovalbumin (OVA by intranasal administration prior to MCAO and administration of lipopolysaccharide (LPS. Neurological outcome was assessed at set points after MCAO and animals sacrificed at 3 months; the immune response to MBP in brain and spleen was determined using ELISPOT assay and degree of cellular inflammatory brain infiltrate assessed by immunocytochemistry. Results Animals that developed a pro-inflammatory (TH1 response to MBP experienced worse outcome, while those that developed a regulatory response (TREG experienced better outcome. A TREG response in spleen was also associated with decreased inflammation and an increase in the number of FoxP3 positive cells in brain. In this study, tolerization to MBP prior to MCAO was associated with a tendency to develop a TH1 response to MBP by 3 months after MCAO. Conclusion These data show that induction of immunological tolerance to MBP is associated with improved outcome after stroke. This study, however, raises concern about the potential for inadvertent induction of detrimental autoimmunity through mucosal administration of antigen.

  18. Management of radiation therapy-induced mucositis in head and neck cancer patients. Part II: supportive treatments

    Directory of Open Access Journals (Sweden)

    Wei Cheong Ngeow

    2011-12-01

    Full Text Available Oropharyngeal mucositis is the acute inflammatory and ulcerative reaction of the oral mucosa following radiation therapy to the head and neck region. It is such a common problem that nearly all head and neck cancer patients develop some degree of mucositis. This complication is usually transient in nature but it also represents an important clinical problem as it is a painful, debilitating, dose-dependent side effect for which there is no widely acceptable prophylaxis or effective treatment. As several authoritative groups have recently either undertaken systematic reviews or issued guidelines on the management of mucositis, it is the aim of this review instead, to provide an overview of all the remedies and pharmaceutical agents available, as well as highlighting to researchers the gaps that need to be filled.

  19. A mouse model of otitis media identifies HB-EGF as a mediator of inflammation-induced mucosal proliferation.

    Directory of Open Access Journals (Sweden)

    Keigo Suzukawa

    Full Text Available Otitis media is one of the most common pediatric infections. While it is usually treated without difficulty, up to 20% of children may progress to long-term complications that include hearing loss, impaired speech and language development, academic underachievement, and irreversible disease. Hyperplasia of middle ear mucosa contributes to the sequelae of acute otitis media and is of important clinical significance. Understanding the role of growth factors in the mediation of mucosal hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae.From a whole genome gene array analysis of mRNA expression during acute otitis media, we identified growth factors with expression kinetics temporally related to hyperplasia. We then tested these factors for their ability to stimulate mucosal epithelial growth in vitro, and determined protein levels and histological distribution in vivo for active factors.From the gene array, we identified seven candidate growth factors with upregulation of mRNA expression kinetics related to mucosal hyperplasia. Of the seven, only HB-EGF (heparin-binding-epidermal growth factor induced significant mucosal epithelial hyperplasia in vitro. Subsequent quantification of HB-EGF protein expression in vivo via Western blot analysis confirmed that the protein is highly expressed from 6 hours to 24 hours after bacterial inoculation, while immunohistochemistry revealed production by middle ear epithelial cells and infiltrating lymphocytes.Our data suggest an active role for HB-EGF in the hyperplasia of the middle ear mucosal epithelium during otitis media. These results imply that therapies targeting HB-EGF could ameliorate mucosal growth during otitis media, and thereby reduce detrimental sequelae of this childhood disease.

  20. PIKA Provides an Adjuvant Effect to Induce Strong Mucosal and Systemic Humoral Immunity Against SARS-CoV

    Institute of Scientific and Technical Information of China (English)

    Wei-wei Gai; Yan Zhang; Di-han Zhou; Yao-qing Chen; Jing-yi Yang; Hui-min Yan

    2011-01-01

    Severe Acute Respiratory Syndrome(SARS)is a deadly infectious disease caused by SARS Coronavirus(SARS-CoV).Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV.However,safe and potent adjuvants,especially with more efficient and economical needle-free vaccination are always needed more urgently in a pandemic.The development of a safe and effective mucosal adjuvant and vaccine for prevention of emergent infectious diseases such as SARS will be an important advancement.PIKA,a stabilized derivative of Poly(I:C),was previously reported to be safe and potent as adjuvant in mouse models.In the present study,we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly(I:C)derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus.Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites,co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity.When intranasal immunization was used,PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response.Overall,PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.

  1. Factor XIII Transglutaminase Supports the Resolution of Mucosal Damage in Experimental Colitis.

    Directory of Open Access Journals (Sweden)

    Christina Andersson

    Full Text Available The thrombin-activated transglutaminase factor XIII (FXIII that covalently crosslinks and stablizes provisional fibrin matrices is also thought to support endothelial and epithelial barrier function and to control inflammatory processes. Here, gene-targeted mice lacking the FXIII catalytic A subunit were employed to directly test the hypothesis that FXIII limits colonic pathologies associated with experimental colitis. Wildtype (WT and FXIII-/- mice were found to be comparable in their initial development of mucosal damage following exposure to dextran sulfate sodium (DSS challenge. However, unlike FXIII-sufficient mice, FXIII-deficient cohorts failed to efficiently resolve colonic inflammatory pathologies and mucosal damage following withdrawal of DSS. Consistent with prior evidence of ongoing coagulation factor activation and consumption in individuals with active colitis, plasma FXIII levels were markedly decreased in colitis-challenged WT mice. Treatment of colitis-challenged mice with recombinant human FXIII-A zymogen significantly mitigated weight loss, intestinal bleeding, and diarrhea, regardless of whether cohorts were FXIII-sufficient or were genetically devoid of FXIII. Similarly, both qualitative and quantitative microscopic analyses of colonic tissues revealed that exogenous FXIII improved the resolution of multiple colitis disease parameters in both FXIII-/- and WT mice. The most striking differences were seen in the resolution of mucosal ulceration, the most severe histopathological manifestation of DSS-induced colitis. These findings directly demonstrate that FXIII is a significant determinant of mucosal healing and clinical outcome following inflammatory colitis induced mucosal injury and provide a proof-of-principle that clinical interventions supporting FXIII activity may be a means to limit colitis pathology and improve resolution of mucosal damage.

  2. Factor XIII Transglutaminase Supports the Resolution of Mucosal Damage in Experimental Colitis

    Science.gov (United States)

    Andersson, Christina; Kvist, Peter H.; McElhinney, Kathryn; Baylis, Richard; Gram, Luise K.; Pelzer, Hermann; Lauritzen, Brian; Holm, Thomas L.; Hogan, Simon; Wu, David; Turpin, Brian; Miller, Whitney; Palumbo, Joseph S.

    2015-01-01

    The thrombin-activated transglutaminase factor XIII (FXIII) that covalently crosslinks and stablizes provisional fibrin matrices is also thought to support endothelial and epithelial barrier function and to control inflammatory processes. Here, gene-targeted mice lacking the FXIII catalytic A subunit were employed to directly test the hypothesis that FXIII limits colonic pathologies associated with experimental colitis. Wildtype (WT) and FXIII-/- mice were found to be comparable in their initial development of mucosal damage following exposure to dextran sulfate sodium (DSS) challenge. However, unlike FXIII-sufficient mice, FXIII-deficient cohorts failed to efficiently resolve colonic inflammatory pathologies and mucosal damage following withdrawal of DSS. Consistent with prior evidence of ongoing coagulation factor activation and consumption in individuals with active colitis, plasma FXIII levels were markedly decreased in colitis-challenged WT mice. Treatment of colitis-challenged mice with recombinant human FXIII-A zymogen significantly mitigated weight loss, intestinal bleeding, and diarrhea, regardless of whether cohorts were FXIII-sufficient or were genetically devoid of FXIII. Similarly, both qualitative and quantitative microscopic analyses of colonic tissues revealed that exogenous FXIII improved the resolution of multiple colitis disease parameters in both FXIII-/- and WT mice. The most striking differences were seen in the resolution of mucosal ulceration, the most severe histopathological manifestation of DSS-induced colitis. These findings directly demonstrate that FXIII is a significant determinant of mucosal healing and clinical outcome following inflammatory colitis induced mucosal injury and provide a proof-of-principle that clinical interventions supporting FXIII activity may be a means to limit colitis pathology and improve resolution of mucosal damage. PMID:26098308

  3. Amelioration of Chemotherapy-Induced Intestinal Mucositis by Orally Administered Probiotics in a Mouse Model

    Science.gov (United States)

    Jiang, Chun-Bin; Cheng, Mei-Lien; Liu, Chia-Yuan; Chang, Szu-Wen; Chiang Chiau, Jen-Shiu; Lee, Hung-Chang

    2015-01-01

    Background and Aims Intestinal mucositis is a frequently encountered side effect in oncology patients undergoing chemotherapy. No well-established or up to date therapeutic strategies are available. To study a novel way to alleviate mucositis, we investigate the effects and safety of probiotic supplementation in ameliorating 5-FU-induced intestinal mucositis in a mouse model. Methods Seventy-two mice were injected saline or 5-Fluorouracil (5-FU) intraperitoneally daily. Mice were either orally administrated daily saline, probiotic suspension of Lactobacillus casei variety rhamnosus (Lcr35) or Lactobacillus acidophilus and Bifidobacterium bifidum (LaBi). Diarrhea score, pro-inflammatory cytokines serum levels, intestinal villus height and crypt depth and total RNA from tissue were assessed. Samples of blood, liver and spleen tissues were assessed for translocation. Results Marked diarrhea developed in the 5-FU groups but was attenuated after oral Lcr35 and LaBi administrations. Diarrhea scores decreased significantly from 2.64 to 1.45 and 0.80, respectively (Pprobiotics administration. We also found TNF-α, IL-1β and IL-6 mRNA expressions were up-regulated in intestinal mucositis tissues following 5-FU treatment (TNF-α: 4.35 vs. 1.18, IL-1β: 2.29 vs. 1.07, IL-6: 1.49 vs. 1.02) and that probiotics treatment suppressed this up-regulation (Pprobiotics Lcr35 and LaBi can ameliorate chemotherapy-induced intestinal mucositis in a mouse model. This suggests probiotics may serve as an alternative therapeutic strategy for the prevention or management of chemotherapy-induced mucositis in the future. PMID:26406888

  4. Loss of NHE8 expression impairs intestinal mucosal integrity

    Science.gov (United States)

    Wang, Aiping; Li, Jing; Zhao, Yang; Johansson, Malin E. V.; Xu, Hua

    2015-01-01

    The newest member of the Na+/H+ exchanger (NHE) family, NHE8, is abundantly expressed at the apical membrane of the intestinal epithelia. We previously reported that mucin 2 expression was significantly decreased in the colon in NHE8−/− mice, suggesting that NHE8 is involved in intestinal mucosal protection. In this study, we further evaluated the role of NHE8 in intestinal epithelial protection after dextran sodium sulfate (DSS) challenge. Compared with wild-type mice, NHE8−/− mice have increased bacterial adhesion and inflammation, especially in the distal colon. NHE8−/− mice are also susceptible to DSS treatment. Real-time PCR detected a remarkable increase in the expression of IL-1β, IL-6, TNF-α, and IL-4 in DSS-treated NHE8−/− mice compared with DSS-treated wild-type littermates. Immunohistochemistry showed a disorganized epithelial layer in the colon of NHE8−/− mice. Periodic acid-Schiff staining showed a reduction in the number of mature goblet cells and the area of the goblet cell theca in NHE8−/− mice. Phyloxine/tartrazine staining revealed a decrease in functional Paneth cell population in the NHE8−/− small intestinal crypt. The expression of enteric defensins was also decreased in NHE8−/− mice. The reduced mucin production in goblet cells and antimicrobial peptides production in Paneth cells lead to disruption of the intestinal mucosa protection. Therefore, NHE8 may be involved in the establishment of intestinal mucosal integrity by regulating the functions of goblet and Paneth cells. PMID:26505975

  5. Therapeutic management of radiation-induced oral mucositis; Therapeutische Beeinflussung der radiogenen oralen Mukositis

    Energy Technology Data Exchange (ETDEWEB)

    Doerr, W. [Klinik und Poliklinik fuer Strahlentherapie, Universitaetsklinikum Carl Gustav Carus, Technische Univ. Dresden (Germany); Doelling-Jochem, I. [Klinik und Poliklinik fuer Strahlentherapie, Universitaetsklinikum Carl Gustav Carus, Technische Univ. Dresden (Germany); Baumann, M. [Klinik und Poliklinik fuer Strahlentherapie, Universitaetsklinikum Carl Gustav Carus, Technische Univ. Dresden (Germany); Herrmann, T. [Klinik und Poliklinik fuer Strahlentherapie, Universitaetsklinikum Carl Gustav Carus, Technische Univ. Dresden (Germany)

    1997-04-01

    Background: Acute reactions of oral mucosa are a frequent side effect of radiotherapy, which often necessitates interruption of the treatment. Marked proliferation of tumor stem cells during treatment interruptions may occur in squamous cell carcinomata, which represent the majority of tumors in the head and neck area. Hence a fatal consequence of treatment breaks may be a significant decrease in tumor cure rates. Furthermore, marked acute responses frequently result in increased late sequelae (`consequential damage`). Therefore, amelioration of the mucosal response aiming at avoiding treatment breaks and at reduction of late reactions coul definitely increase the therapeutic success of radiation treatment. Results: A variety of prophylactic and therapeutic methods have been proposed for the management of acute radiation reactions of the oral mucosa. Frequently, their efficiacy has been established for chemotherapy or in combination with other immunosuppressive treatments. Hence, systemical rather than local effects have to be considered. Conclusions: In general, prophylaxis of oral mucositis is mainly based on dental restoration or edentation, in combination with frequent oral hygienic measures after the meals and with antiseptic mouthwashes. Intensive personal care is recommended. The necessity of a percutaneous endoscopic gastrostoma is dependent on the status of the patient and on size and localization of the treatment area, i.e. the impairment of food uptake which is to be expected. Therapeutic intervention is restricted to local or systemic treatment of pain and local application of antimycotics and antibiotics. (orig./VHE) [Deutsch] Die akute Reaktion der Mundschleimhaut ist eine regelmaessige Nebenwirkung der klinischen Strahlentherapie von Kopf-Hals-Tumoren, die in vielen Faellen eine Unterbrechung der Behandlung erzwingt. In den Behandlungspausen besteht gerade bei den im Kopf-Hals-Bereich haeufigen Plattenepithelkarzinomen die Gefahr der verstaerkten

  6. Level of Fecal Calprotectin Correlates With Endoscopic and Histologic Inflammation and Identifies Patients With Mucosal Healing in Ulcerative Colitis

    DEFF Research Database (Denmark)

    Theede, Klaus; Holck, Susanne; Ibsen, Per

    2015-01-01

    BACKGROUND & AIMS: In patients with ulcerative colitis (UC), mucosal healing is an important goal of treatment. However, mucosal healing is difficult to determine on the basis of clinical evaluation alone, and endoscopy is uncomfortable and can cause complications. Fecal calprotectin (FC) is a ma......BACKGROUND & AIMS: In patients with ulcerative colitis (UC), mucosal healing is an important goal of treatment. However, mucosal healing is difficult to determine on the basis of clinical evaluation alone, and endoscopy is uncomfortable and can cause complications. Fecal calprotectin (FC...... or inactive UC who underwent sigmoidoscopy at Copenhagen University Hospital Hvidovre from September 2012 through 2014. Endoscopic inflammation was evaluated by using the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and histologic inflammatory activity by a slightly...... modified Harpaz Index, which measures acute inflammation. The Partial Mayo Score was used to measure the clinical disease activity. RESULTS: A cutoff level of FC of 192 mg/kg identified patients with endoscopic evidence of mucosal healing, which was based on the MES and UCEIS, with positive predictive...

  7. Mucosal Schwann cell "Hamartoma": A new entity?

    Institute of Scientific and Technical Information of China (English)

    Paola Pasquini; Andrea Baiocchini; Laura Falasca; Dante Annibali; Guido Gimbo; Francesco Pace; Franca Del Nonno

    2009-01-01

    Schwannoma is a well-described, benign nerve sheath tumor of the soft tissue, but is rare in the gastrointestinal tract. Gastrointestinal schwannomas are often incidentally discovered as small polypoid intraluminal lesions. In this report, we describe the clinicopathologic and immunohistochemical features of a distinctive neural mucosal polyp composed of a diffuse cellular proliferation of uniform bland spindled cells in the lamina propria that entraps the colonic crypts. Immunohistochemical analysis revealed strong and diffuse positivity for the S-100 protein. To avoid confusion of these solitary colorectal polyps containing pure spindled Schwann cell proliferation in the lamina propria with neural lesions that have significant association with inherited syndromes, it is better to use the designation "mucosal Schwann hamartoma".

  8. Age, gender, dentures and oral mucosal disorders.

    Science.gov (United States)

    MacEntee, M I; Glick, N; Stolar, E

    1998-03-01

    The numbers of participants over 75 years of age in previous studies of oral health have not been sufficient to permit a full investigation of the influence of age on the mouth. In this study a disproportionate stratified random sample of 255 independent elders was selected from a list of urban voters to provide similar numbers of men and women in three age groups. The subjects were interviewed and examined, and nearly half of them had mucosal disorders. There was a significant (P angular cheilitis in particular were associated significantly with men and with the use of defective dentures. Logistic regression revealed that neither age alone nor the quality of dentures predispose to mucosal lesions, but that the odds of finding stomatitis, denture-related hyperplasia and angular cheilitis in particular increased about three-fold in denture-users, and almost doubled in men.

  9. Effect of epicatechin against radiation-induced oral mucositis: in vitro and in vivo study.

    Directory of Open Access Journals (Sweden)

    Yoo Seob Shin

    Full Text Available PURPOSE: Radiation-induced oral mucositis limits the delivery of high-dose radiation to head and neck cancer. This study investigated the effectiveness of epicatechin (EC, a component of green tea extracts, on radiation-induced oral mucositis in vitro and in vivo. EXPERIMENTAL DESIGN: The effect of EC on radiation-induced cytotoxicity was analyzed in the human keratinocyte line HaCaT. Radiation-induced apoptosis, change in mitochondrial membrane potential (MMP, reactive oxygen species (ROS generation and changes in the signaling pathway were investigated. In vivo therapeutic effects of EC for oral mucositis were explored in a rat model. Rats were monitored by daily inspections of the oral cavity, amount of oral intake, weight change and survival rate. For histopathologic evaluation, hematoxylin-eosin staining and TUNEL staining were performed. RESULTS: EC significantly inhibited radiation-induced apoptosis, change of MMP, and intracellular ROS generation in HaCaT cells. EC treatment markedly attenuated the expression of p-JNK, p-38, and cleaved caspase-3 after irradiation in the HaCaT cells. Rats with radiation-induced oral mucositis showed decreased oral intake, weight and survival rate, but oral administration of EC significantly restored all three parameters. Histopathologic changes were significantly decreased in the EC-treated irradiated rats. TUNEL staining of rat oral mucosa revealed that EC treatment significantly decreased radiation-induced apoptotic cells. CONCLUSIONS: This study suggests that EC significantly inhibited radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis.

  10. Effects of dosmalfate, a new cytoprotective agent, on acute and chronic trinitrobenzene sulphonic acid-induced colitis in rats.

    Science.gov (United States)

    Villegas, Isabel; La Casa, Carmen; Orjales, Aurelio; Alarcón de la Lastra, Catalina

    2003-01-24

    Activated neutrophils and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) are clearly involved in the pathogenesis of bowel disease. Increased expression of epidermal growth factor-receptor (EGF receptor) has been reported for the colon mucosa surrounding areas of ulceration, suggesting a pivotal role in mucosal defence and repair. In this study, we examined the effects of dosmalfate, a new flavonoid derivative compound (diosmin heptakis) with antioxidant and cytoprotective properties, on acute and chronic experimental trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. The inflammation response was assessed by neutrophil infiltration as evaluated by histology and myeloperoxidase activity. Mucosal TNF-alpha production and histological analysis of the lesions was also carried out. In addition, we studied the expression of the EGF receptor inmunohistochemically during the healing of TNBS-induced chronic colitis. A 2-day treatment with 400 or 800 mg/kg of dosmalfate ameliorated the colon damage score and the incidence of adhesions. It also significantly (P<0.05) decreased myeloperoxidase activity and colonic mucosal production of TNF-alpha. Chronic treatment (14 days) with 800 mg/kg/day of dosmalfate also had significant protective effects on TNBS-induced colitis which were reflected by significant attenuation (P<0.05) of the damage score while the inflammatory indicators were not improved. The chronic beneficial effect of dosmalfate was apparently related to the enhancement of EGF receptor expression. These findings confirm the protective effects of dosmalfate in acute and chronic experimental colitis.

  11. The microbiome and regulation of mucosal immunity.

    Science.gov (United States)

    McDermott, Andrew J; Huffnagle, Gary B

    2014-05-01

    The gastrointestinal tract is a mucosal surface constantly exposed to foreign antigens and microbes, and is protected by a vast array of immunologically active structures and cells. Epithelial cells directly participate in immunological surveillance and direction of host responses in the gut and can express numerous pattern recognition receptors, including Toll-like receptor 5 (TLR5), TLR1, TLR2, TLR3, TLR9, and nucleotide oligomerization domain 2, as well as produce chemotactic factors for both myeloid and lymphoid cells following inflammatory stimulation. Within the epithelium and in the underlying lamina propria resides a population of innate lymphoid cells that, following stimulation, can become activated and produce effector cytokines and exert both protective and pathogenic roles during inflammation. Lamina propria dendritic cells play a large role in determining whether the response to a particular antigen will be inflammatory or anti-inflammatory. It is becoming clear that the composition and metabolic activity of the intestinal microbiome, as a whole community, exerts a profound influence on mucosal immune regulation. The microbiome produces short-chain fatty acids, polysaccharide A, α-galactosylceramide and tryptophan metabolites, which can induce interleukin-22, Reg3γ, IgA and interleukin-17 responses. However, much of what is known about microbiome-host immune interactions has come from the study of single bacterial members of the gastrointestinal microbiome and their impact on intestinal mucosal immunity. Additionally, evidence continues to accumulate that alterations of the intestinal microbiome can impact not only gastrointestinal immunity but also immune regulation at distal mucosal sites.

  12. Peptic activity and gastroduodenal mucosal damage.

    OpenAIRE

    Raufman, J P

    1996-01-01

    This contribution reviews briefly the history of the discovery and characterization of peptic activity; secretory models and current concepts regarding the regulation of pepsinogen secretion; and evidence that pepsin is a necessary co-factor for gastroduodenal mucosal injury. Several animal studies indicate that peptic activity is required for acid- and nonsteroidal anti-inflammatory drug-induced gastroduodenal ulceration. A more vigorous approach to the development of anti-peptic drugs for t...

  13. Saccharomyces cerevisiae UFMG A-905 treatment reduces intestinal damage in a murine model of irinotecan-induced mucositis.

    Science.gov (United States)

    Bastos, R W; Pedroso, S H S P; Vieira, A T; Moreira, L M C; França, C S; Cartelle, C T; Arantes, R M E; Generoso, S V; Cardoso, V N; Neves, M J; Nicoli, J R; Martins, F S

    2016-09-01

    Indigenous microbiota plays a crucial role in the development of several intestinal diseases, including mucositis. Gastrointestinal mucositis is a major and serious side effect of cancer therapy, and there is no effective therapy for this clinical condition. However, some probiotics have been shown to attenuate such conditions. To evaluate the effects of Saccharomyces cerevisiae UFMG A-905 (Sc-905), a potential probiotic yeast, we investigated whether pre- or post-treatment with viable or inactivated Sc-905 could prevent weight loss and intestinal lesions, and maintain integrity of the mucosal barrier in a mucositis model induced by irinotecan in mice. Only post-treatment with viable Sc-905 was able to protect mice against the damage caused by chemotherapy, reducing the weight loss, increase of intestinal permeability and jejunal lesions (villous shortening). Besides, this treatment reduced oxidative stress, prevented the decrease of goblet cells and stimulated the replication of cells in the intestinal crypts of mice with experimental mucositis. In conclusion, Sc-905 protects animals against irinotecan-induced mucositis when administered as a post-treatment with viable cells, and this effect seems to be related with the reduction of oxidative stress and preservation of intestinal mucosa.

  14. Low energy laser in prevention of oral mucositis in patients receiving radiotherapy and/or chemotherapy in Pernambuco Cancer Hospital

    Energy Technology Data Exchange (ETDEWEB)

    Kelner, Natalie; Castro, Jurema Freire Lisboa de [Federal University of Pernambuco, Recife (Brazil). Dept. of Clinics and Preventive Dentistry. Discipline of Oral Pathology]. E-mail: jlisboa72@hotmail.com

    2007-07-01

    Oral mucositis induced by antineoplastic therapy causes wide-range pain and discomfort resulting in decreased quality of life. The present study evaluated the benefits of low intensity laser and 0.12% chlorhexidine gluconate in the prevention of oral mucositis induced by radiation, associated or not with chemotherapy, and considered degrees/severity, time of appearance of the lesions and functional loss. Eighty-four outpatients were considered and 49 were included in this study and divided into two groups: Group 1 received laser treatments in three stages, starting three days before treatment until the end of therapy. Group 2 was instructed to do daily mouth rinses with chlorhexidine gluconate. The prevalence of clinical mucositis was 49%, and of functional mucositis, 28.6%, when the two groups were considered together. This percentage was smaller in the laser group, 44% for the clinical mucositis group and 24% for the functional. The two protocols were well tolerated and showed benefits, mainly from the point of view of functionality, and delayed the onset and development of mucositis. (author)

  15. Acute kidney failure

    Science.gov (United States)

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  16. Hitting the mucosal road in tolerance induction.

    Science.gov (United States)

    Wiedermann, Ursula

    2009-01-01

    Within the last decades a dramatic increase in allergic diseases has been recognized in the Westernized societies, leading to the fact that meanwhile 25-30% of the population is afflicted by allergic disorders. Besides a hereditary disposition, other factors, including a reduced microbial contact early in life or changes in nutrition, might also have influenced this epidemiological development. So far the only causative treatment against type-I allergies is specific immunotherapy. In young and monosensitized patients this treatment is highly efficacious, while there are clear limitations in older or multisensitized patients. Allergy research therefore aims at establishing new and more efficacious treatment strategies in prophylactic as well as therapeutic settings. Our research programs focus on the development of novel allergy vaccines based on the induction of mucosal tolerance. In different mouse models of respiratory allergy mucosal treatment with genetically engineered allergen constructs proved to prevent the development of allergic mono- and multisensitivities. The additional use of mucosal adjuvants seems particularly important to improve therapeutic treatment approaches. Recent studies on the inverse relation of certain parasite infections and the development of allergy prompted us to search for selected parasitic molecules with immunosuppressive properties as potential adjuvant systems for novel allergy vaccines. An overview of our recent studies will be given.

  17. Brain-gut axis and mucosal immunity: a perspective on mucosal psychoneuroimmunology.

    LENUS (Irish Health Repository)

    Shanahan, F

    2012-02-03

    The role of the brain-gut axis has traditionally been investigated in relation to intestinal motility, secretion, and vascularity. More recently, the concept of brain-gut dialogue has extended to the relationship between the nervous system and mucosal immune function. There is compelling evidence for a reciprocal or bi-directional communication between the immune system and the neuroendocrine system. This is mediated, in part, by shared ligands (chemical messengers) and receptors that are common to the immune and nervous systems. Although the concept of psychoneuroimmunology and neuroimmune cross-talk has been studied primarily in the context of the systemic immune system, it is likely to have special significance in the gut. The mucosal immune system is anatomically, functionally, and operationally distinct from the systemic immune system and is subject to independent regulatory signals. Furthermore, the intestinal mucosal immune system operates in a local milieu that depends on a dense innervation for its integrity, with juxtaposition of neuroendocrine cells and mucosal immune cells. An overview of evidence for the biologic plausibility of a brain-gut-immune axis is presented and its potential relevance to mucosal inflammatory disorders is discussed.

  18. Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

    Directory of Open Access Journals (Sweden)

    Logan Richard M

    2010-03-01

    Full Text Available Abstract Background Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

  19. Use of noninvasive ventilation in severe acute respiratory distress syndrome due to accidental chlorine inhalation: a case report

    Science.gov (United States)

    Matos, Adriano Medina; de Oliveira, Rodrigo Ribeiro; Lippi, Mauro Martins; Takatani, Rodrigo Ryoji; de Oliveira Filho, Wilson

    2017-01-01

    Acute respiratory distress syndrome is characterized by diffuse inflammatory lung injury and is classified as mild, moderate, and severe. Clinically, hypoxemia, bilateral opacities in lung images, and decreased pulmonary compliance are observed. Sepsis is one of the most prevalent causes of this condition (30 - 50%). Among the direct causes of acute respiratory distress syndrome, chlorine inhalation is an uncommon cause, generating mucosal and airway irritation in most cases. We present a case of severe acute respiratory distress syndrome after accidental inhalation of chlorine in a swimming pool, with noninvasive ventilation used as a treatment with good response in this case. We classified severe acute respiratory distress syndrome based on an oxygen partial pressure/oxygen inspired fraction ratio <100, although the Berlin classification is limited in considering patients with severe hypoxemia managed exclusively with noninvasive ventilation. The failure rate of noninvasive ventilation in cases of acute respiratory distress syndrome is approximately 52% and is associated with higher mortality. The possible complications of using noninvasive positive-pressure mechanical ventilation in cases of acute respiratory distress syndrome include delays in orotracheal intubation, which is performed in cases of poor clinical condition and with high support pressure levels, and deep inspiratory efforts, generating high tidal volumes and excessive transpulmonary pressures, which contribute to ventilation-related lung injury. Despite these complications, some studies have shown a decrease in the rates of orotracheal intubation in patients with acute respiratory distress syndrome with low severity scores, hemodynamic stability, and the absence of other organ dysfunctions. PMID:28444079

  20. Effects of Mycotoxins on mucosal microbial infection and related pathogenesis.

    Science.gov (United States)

    Park, Seong-Hwan; Kim, Dongwook; Kim, Juil; Moon, Yuseok

    2015-10-30

    Mycotoxins are fungal secondary metabolites detected in many agricultural commodities and water-damaged indoor environments. Susceptibility to mucosal infectious diseases is closely associated with immune dysfunction caused by mycotoxin exposure in humans and other animals. Many mycotoxins suppress immune function by decreasing the proliferation of activated lymphocytes, impairing phagocytic function of macrophages, and suppressing cytokine production, but some induce hypersensitive responses in different dose regimes. The present review describes various mycotoxin responses to infectious pathogens that trigger mucosa-associated diseases in the gastrointestinal and respiratory tracts of humans and other animals. In particular, it focuses on the effects of mycotoxin exposure on invasion, pathogen clearance, the production of cytokines and immunoglobulins, and the prognostic implications of interactions between infectious pathogens and mycotoxin exposure.

  1. Moving towards a new era in the research of tonsils and mucosal barriers.

    Science.gov (United States)

    Yamanaka, Noboru

    2011-01-01

    The palatine and nasopharyngeal tonsils (adenoids) are lymphoepithelial tissues located in strategic anatomical areas of the oral pharynx and nasopharynx. These immunocompetent tissues represent the first line of defense against ingested or inhaled foreign proteins such as bacteria, viruses, or food antigens. Accompanying the advances being made in the field of medicine today, the role of the tonsils in immunocompetence is becoming extremely important. Upper respiratory tract infections such as acute otitis media, acute rhinosinusitis and acute pharyngo-tonsillitis are diseases that occur with extremely high frequency, and the antimicrobial agents used to treat these diseases account for a large proportion of health care costs. The increasingly refractory nature of upper respiratory tract infections caused by drug-resistant bacteria has become a major worldwide concern. The elucidation of the immune functions of the tonsils and mucosal membranes of the upper respiratory tract is considered to have important significance. The tonsils are also considered to play an important role as one of the causes of sleep apnea syndrome, and have been reported to be intimately involved in the manifestation of IgA nephropathy and palmoplantar pustulosis, a kind of skin disorder. Interest has continued to grow in this symposium with each session ever since it was first held in Kyoto, Japan in 1987. Since then, the symposium has been held every 3-4 years; in Pavia in 1991, in Sapporo in 1995, in Ghent in 1999, in Wakayama in 2003, and in Siena in 2006. Since the 5th symposium in Wakayama, the topics were extended to mucosal barriers of upper airways including the mucosal immune system, innate immunity, and mucosal vaccine. Recent fine technologies and information on molecular biological approaches for upper airways will continue to advance our understanding of epidemiology, etiology, pathogenesis, diagnosis and management of tonsil-related disorders and various upper respiratory

  2. Comparison of Alloderm and mucosal graft in mandibular vestibuloplasty

    Directory of Open Access Journals (Sweden)

    Mahmoodhashemi H.

    2009-12-01

    Full Text Available "nBackground and Aim: The usage of free gingival grafts for vestibuloplasty is a routine procedure. The free gingival procedure requires harvesting the graft from a donor site which increases morbidity and the risk of surgical complications. In addition, adequate amount of donor tissue may not be available. Acceptable results of Alloderm application as a substitute for autogenous soft tissue grafts are: Not exposing the patient to an additional surgery, no donor site morbidity, unlimited availability, decreasing the bleeding during the surgery, decreasing the surgical complications, and better color match. The aim of this study was to evaluate the maintenance of the vestibular depth in vestibuloplasty with mucosal graft and Alloderm."nMaterials and Methods: Both methods of anterior mandibular vestibuloplasty by Clark, utilizing Alloderm and mucosal grafts, were employed in ten clinical cases. During the surgeries, half the prepared recipient sites received Alloderm, while the remaining half received autografts in a randomized fashion. Immediately, 1, 3, and 6 months postoperatively, the variables of graft rejection, depth of vestibule and the degree of relapse were evaluated. SPSS software was used for analysis of the data and the methods used for "statistical tests" were as follows: Friedman Method, Paired sample t-test, Smirnov-kolmogrove Method. (The statistical significance level was established at P-value<0.05."nResults: The mean difference of the relapse measurements in both methods throughout the survey did not have significant predictive value (P>0.05. Similar results were achieved for the mean difference of depth of the vestibule."nConclusion: In patients undergoing Vestibuloplasty, Alloderm could be material of choice to be utilized as autogenic soft tissue grafts in pre-prosthesis procedures.

  3. Ghrelin improves intestinal mucosal atrophy during parenteral nutrition: An experimental study.

    Science.gov (United States)

    Yamada, Waka; Kaji, Tatsuru; Onishi, Shun; Nakame, Kazuhiko; Yamada, Koji; Kawano, Takafumi; Mukai, Motoi; Souda, Masakazu; Yoshioka, Takako; Tanimoto, Akihide; Ieiri, Satoshi

    2016-12-01

    Total parenteral nutrition (TPN) has been reported to be associated with mucosal atrophy of the small intestine. Ghrelin has hormonal, orexigenic, and metabolic activities. We investigated whether ghrelin improved intestinal mucosal atrophy using a TPN-supported rat model. Rats underwent jugular vein catheterization and were divided into four groups: TPN alone (TPN), TPN plus low-dose ghrelin (TPNLG), TPN plus high-dose ghrelin (TPNHG), and oral feeding with normal chow (OF). Ghrelin was administered continuously at dosages of 10 or 50 μg/kg/day. On day 6 rats were euthanized, and the small intestine was harvested and divided into the jejunum and ileum. Then the villus height (VH) and crypt depth (CD) were evaluated. The jejunal and ileal VH and CD in the TPN group were significantly decreased compared with those in the OF group. TPNHG improved only VH of the jejunum. TPNLG improved VH and CD of the jejunum and CD of the ileum. The improvement of TPNLG was significantly stronger than that in CD of the jejunum and ileum. TPN was more strongly associated with mucosal atrophy in the jejunum than in the ileum. Low-dose intravenous administration of ghrelin improved TPN-associated intestinal mucosal atrophy more effectively than high-dose administration. Copyright © 2016. Published by Elsevier Inc.

  4. Acute toxicity and gastroprotection studies of a new schiff base derived copper (II complex against ethanol-induced acute gastric lesions in rats.

    Directory of Open Access Journals (Sweden)

    Maryam Hajrezaie

    Full Text Available BACKGROUND: Copper is an essential element in various metabolisms. The investigation was carried out to evaluate acute gastroprotective effects of the Copper (II complex against ethanol-induced superficial hemorrhagic mucosal lesions in rats. METHODOLOGY/PRINCIPAL FINDINGS: Rats were divided into 7 groups. Groups 1 and 2 were orally administered with Tween 20 (10% v/v. Group 3 was orally administered with 20 mg/kg omeprazole (10% Tween 20. Groups 4-7 received 10, 20, 40, and 80 mg/kg of the complex (10% Tween 20, respectively. Tween 20 (10% v/v was given orally to group 1 and absolute ethanol was given orally to groups 2-7, respectively. Rats were sacrificed after 1 h. Group 2 exhibited severe superficial hemorrhagic mucosal lesions. Gastric wall mucus was significantly preserved by the pre-treatment complex. The results showed a significant increase in glutathione (GSH, superoxide dismutase (SOD, nitric oxide (NO, and Prostaglandin E2 (PGE(2 activities and a decrease in malondialdehyde (MDA level. Histology showed marked reduction of hemorrhagic mucosal lesions in groups 4-7. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. PAS staining of groups 4-7 showed intense stain uptake of gastric mucosa. The acute toxicity revealed the non-toxic nature of the compound. CONCLUSIONS/SIGNIFICANCE: The gastroprotective effect of the Copper (II complex may possibly be due to preservation of gastric wall mucus; increase in PGE(2 synthesis; GSH, SOD, and NO up-regulation of Hsp70 protein; decrease in MDA level; and down-regulation of Bax protein.

  5. Chitosan-Based Nanoparticles for Mucosal Delivery of RNAi Therapeutics

    DEFF Research Database (Denmark)

    Martirosyan, Alina; Olesen, Morten Jarlstad; Howard, Kenneth A.

    2014-01-01

    of the polysaccharide chitosan have been used to facilitate delivery of siRNA across mucosal surfaces following local administration. This chapter describes the mucosal barriers that need to be addressed in order to design an effective mucosal delivery strategy and the utilization of the mucoadhesive properties...... of chitosan. Focus is given to preparation methods and the preclinical application of chitosan nanoparticles for respiratory and oral delivery of siRNA....

  6. Chitosan-Based Nanoparticles for Mucosal Delivery of RNAi Therapeutics

    DEFF Research Database (Denmark)

    Martirosyan, Alina; Olesen, Morten Jarlstad; Howard, Kenneth A.

    2014-01-01

    of the polysaccharide chitosan have been used to facilitate delivery of siRNA across mucosal surfaces following local administration. This chapter describes the mucosal barriers that need to be addressed in order to design an effective mucosal delivery strategy and the utilization of the mucoadhesive properties...... of chitosan. Focus is given to preparation methods and the preclinical application of chitosan nanoparticles for respiratory and oral delivery of siRNA....

  7. Scoring irradiation mucositis in head and neck cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Spijkervet, F.K.L.; Panders, A.K. (Departments of Oral and Maxillofacial Surgery, University Hospital Groningen (Netherlands)); Saene, H.K.F. van (Medical Microbiology, University of Liverpool (UK)); Vermey, A. (Department of Surgery Oncology Division, University Hospital Groningen (Netherlands)); Mehta, D.M. (Department of Radiotherapy, University Hospital Groningen (Netherlands))

    1989-01-01

    Irradiation mucositis is defined as an inflammatory-like process of the oropharyngeal mucosa following therapeutic irradiation of patients who have head and neck cancer. Clinically, it is a serious side effect because severe mucositis can cause generalized problems (weight loss, nasogastic tube feedings) and interferes with the well-being of the patient seriously. Grading mucositis is important for the evaluation of preventive and therapeutic measures. The object of this study was to develop a scoring method based on local mucositis signs only. Four clinical local signs of mucositis were used in this score: white discoloration, erythema, pseudomembranes and ulceration. Mucositis of the oral cavity was calcualted during conventional irradiation protocol for 8 distinguishable areas using the 4 signs and their extent. A prospective evaluation of this method in 15 irradiated head and neck cancer patients displayed an S-curve reflecting a symptomless first irradiation week, followed by a rapid and steady increase of white discoloration, erythema and pseudomembranes during the second and third week. Oral candidiasis, generalized symptoms such as weight loss and the highest mucositis scores were seen after 3 weeks irradiation. The novel mucositis scoring method may be of value in studying the effect of hygiene programs, topical application of disinfectans or antibiotics on oral mucositis. (author).

  8. Mucosal and systemic adjuvant activity of alphavirus replicon particles

    Science.gov (United States)

    Thompson, Joseph M.; Whitmore, Alan C.; Konopka, Jennifer L.; Collier, Martha L.; Richmond, Erin M. B.; Davis, Nancy L.; Staats, Herman F.; Johnston, Robert E.

    2006-03-01

    Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucosal surfaces is the natural route by which mucosal immunity is generated, as peripheral antigen delivery typically fails to induce mucosal immune responses. However, we demonstrate in this article that mucosal immune responses are evident at multiple mucosal surfaces after parenteral delivery of Venezuelan equine encephalitis virus replicon particles (VRP). Moreover, coinoculation of null VRP (not expressing any transgene) with inactivated influenza virions, or ovalbumin, resulted in a significant increase in antigen-specific systemic IgG and fecal IgA antibodies, compared with antigen alone. Pretreatment of VRP with UV light largely abrogated this adjuvant effect. These results demonstrate that alphavirus replicon particles possess intrinsic systemic and mucosal adjuvant activity and suggest that VRP RNA replication is the trigger for this activity. We feel that these observations and the continued experimentation they stimulate will ultimately define the specific components of an alternative pathway for the induction of mucosal immunity, and if the activity is evident in humans, will enable new possibilities for safe and inexpensive subunit and inactivated vaccines. vaccine vector | Venezuelan equine encephalitis virus | viral immunology | RNA virus

  9. Oral mucosal immunization using glucomannosylated bilosomes.

    Science.gov (United States)

    Jain, Sanyog; Indulkar, Anura; Harde, Harshad; Agrawal, Ashish K

    2014-06-01

    The present study embarks on the feasibility of GM-bilosomes as a rationally designed vehicle for oral mucosal immunization. Bilosomes containing BSA as a model antigen were found to have vesicle size of 157 +/- 3 nm, PDI of 0.287 +/- 0.045, zeta potential of -21.8 +/- 2.01 mV and entrapment efficiency of 71.3 +/- 4.3%. Bilosomal formulations were freeze dried and entrapped BSA in freeze dried formulations was found to retain its structural and conformational stability as evident by SDS-PAGE and CD analysis. The GM-bilosomes were also found stable in different simulated biological fluids and bile salt solutions of different concentrations. In-vitro drug release revealed that GM-bilosomes were able to sustain drug release up to 24 h. In-vitro cell uptake in RAW 264.7 macrophage cells demonstrated significantly higher uptake of GM-bilosomes in comparison with bilosomes and free antigen. Intestinal uptake studies on excised rat intestinal sections further demonstrated higher uptake of vesicular systems throughout the intestinal region in comparison with free antigen. Significantly higher (p alum adsorbed BSA (BSA-AL) following oral administration. The immune response observed in case of GM-bilosomes was comparable to BSA-AL administered through im route without any significant difference (p > 0.05). More importantly, GM-bilosomes were found capable of inducing mucosal immune response as well as cell mediated immune response which was not induced by im BSA-AL. In conclusion, GM-bilosomes could be considered as promising carrier and adjuvant system for oral mucosal immunization and productively exploited for oral delivery of other candidate antigens.

  10. Oral lichen planus and lichenoid mucositis.

    Science.gov (United States)

    De Rossi, Scott S; Ciarrocca, Katharine

    2014-04-01

    Oral lichen planus (OLP) is commonly found in middle-aged women. Although the cause is unknown, research points to several complex immunologic events and cells that are responsible for the inflammatory destruction and chronicity of these lesions. Biopsy for histologic diagnosis is recommended. The mainstay of treatment remains topical corticosteroids; however, newer therapies such as immunomodulating agents are available for recalcitrant lesions. In cases of lichenoid mucositis or reactions, treatment should be directed at identifying and removing the presumed cause. Given the apparent risk of squamous cell carcinoma in these patients, frequent follow-up and repeat biopsy are vital.

  11. Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat.

    Science.gov (United States)

    Kang, J Y; Teng, C H; Wee, A; Chen, F C

    1995-05-01

    Capsaicin, the pungent ingredient of chilli, is gastroprotective against experimental gastric injury when given intragastrically. Epidemiological and clinical data suggest that chilli ingestion may have a beneficial effect on human peptic ulcer disease. This study showed a gastroprotective effect of intragastric capsaicin, in doses of 2 and 5 mg, on ethanol induced gastric mucosal injury using macroscopic, histological, scanning electron microscopic, and biochemical indices. Subcutaneous administration of 2 mg of capsaicin had the same gastroprotective effect as intragastric administration. Acute intragastric administration and chronic ingestion of chilli powder in doses comparable with that consumed in humans (up to 200 mg in single doses or 200 mg daily for four weeks) likewise protected the gastric mucosa. Both the mucosa and gastric juice had higher mucus contents when capsaicin or chilli rather than saline or solvent was used before ethanol challenge. In control animals capsaicin also increased gastric juice mucus content although the mucosal content was unaffected. Increased gastric mucus production may therefore be one mechanism by which capsaicin and chilli exert their gastroprotective effect although an alternative explanation is that the reduction in mucosal mucus depletion is secondary to the protective effect of capsaicin and chilli.

  12. Classification of pulmonary airway disease based on mucosal color analysis

    Science.gov (United States)

    Suter, Melissa; Reinhardt, Joseph M.; Riker, David; Ferguson, John Scott; McLennan, Geoffrey

    2005-04-01

    Airway mucosal color changes occur in response to the development of bronchial diseases including lung cancer, cystic fibrosis, chronic bronchitis, emphysema and asthma. These associated changes are often visualized using standard macro-optical bronchoscopy techniques. A limitation to this form of assessment is that the subtle changes that indicate early stages in disease development may often be missed as a result of this highly subjective assessment, especially in inexperienced bronchoscopists. Tri-chromatic CCD chip bronchoscopes allow for digital color analysis of the pulmonary airway mucosa. This form of analysis may facilitate a greater understanding of airway disease response. A 2-step image classification approach is employed: the first step is to distinguish between healthy and diseased bronchoscope images and the second is to classify the detected abnormal images into 1 of 4 possible disease categories. A database of airway mucosal color constructed from healthy human volunteers is used as a standard against which statistical comparisons are made from mucosa with known apparent airway abnormalities. This approach demonstrates great promise as an effective detection and diagnosis tool to highlight potentially abnormal airway mucosa identifying a region possibly suited to further analysis via airway forceps biopsy, or newly developed micro-optical biopsy strategies. Following the identification of abnormal airway images a neural network is used to distinguish between the different disease classes. We have shown that classification of potentially diseased airway mucosa is possible through comparative color analysis of digital bronchoscope images. The combination of the two strategies appears to increase the classification accuracy in addition to greatly decreasing the computational time.

  13. Serological assessment of gastric mucosal atrophy in gastric cancer

    Directory of Open Access Journals (Sweden)

    Bornschein Jan

    2012-01-01

    Full Text Available Abstract Background Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1 (PG1, pepsinogen 2 (PG2 and gastrin 17 (G17 offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia. Methods Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Laurén type, localisation, degree of mucosal abnormalities (intestinal metaplasia, atrophy and serological parameters (PG1, PG2, PG1/2-ratio, G17, H. pylori IgG, CagA status. Association of the general factors to the different serological values have been statistically analyzed. Results Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (p = 0.003. The serum levels of PG2 itself and G17 were not significantly altered. H. pylori infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (p = 0.058. The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p Conclusions Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer.

  14. Cholecystokinin but not ghrelin stimulates mucosal bicarbonate secretion in rat duodenum: independence of feeding status and cholinergic stimuli.

    Science.gov (United States)

    Sjöblom, Markus; Lindqvist, Ramin; Bengtsson, Magnus W; Jedstedt, Gunilla; Flemström, Gunnar

    2013-05-10

    Cholecystokinin (CCK) is an important regulator of food digestion but its influence on small intestinal secretion has received little attention. We characterized effects of CCK-8, ghrelin and some related peptides on duodenal HCO3(-) secretion in vivo and demonstrated CCK-induced calcium signaling in acutely isolated enterocytes. A segment of proximal duodenum with intact blood supply was cannulated in situ in anaesthetized rats. Mucosal HCO3(-) secretion was continuously recorded (pH-stat). Peptides were administrated to the duodenum by close intra-arterial infusion. Clusters of duodenal enterocytes were attached to the bottom of a perfusion chamber. The intracellular calcium concentration ([Ca(2+)]i) was examined by dual-wavelength imaging. CCK-8 (3.0, 15 and 60 pmol/kg,h) caused dose-dependent increases (psecretion in both overnight fasted and continuously fed animals. The CCK1R-antagonist devazepide but neither the CCK2R-antagonist YMM022 nor the melatonin MT2-selective antagonist luzindole inhibited the rise in secretion. Atropine decreased sensitivity to CCK-8. The appetite-related peptide ghrelin was without effect on the duodenal secretion in fasted as well as fed animals. Superfusion with CCK-8 (1.0-50 nM) induced [Ca(2+)]i signaling in acutely isolated duodenal enterocytes. After an initial peak response, [Ca(2+)]i returned to near basal values within 3-5min. Devazepide but not YMM022 inhibited this [Ca(2+)]i response. Low doses of CCK-8 stimulate duodenal alkaline secretion and induce enterocyte [Ca(2+)]i signaling by an action at CCK1 receptors. The results point to importance of CCK in the rapid postprandial rise in mucosa-protective duodenal secretion.

  15. The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats.

    Science.gov (United States)

    Ibrahim, Ibrahim Abdel Aziz; Abdulla, Mahmood Ameen; Hajrezaie, Maryam; Bader, Ammar; Shahzad, Naiyer; Al-Ghamdi, Saeed S; Gushash, Ahmad S; Hasanpourghadi, Mohadeseh

    2016-01-01

    Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE) was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg) to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg) orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid-Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the experimental rats pretreated with MHAE compared to the ulcer control group. Immunohistochemistry staining revealed an upregulation of the Hsp70 protein and a downregulation of the Bax protein in rats pretreated with MHAE compared with the control rats. Gastric homogenate showed significantly increased catalase and superoxide dismutase, and the level of malondialdehyde (MDA) was reduced in the rats pretreated with MHAE compared to the control group. In conclusion, MHAE exhibited a gastroprotective effect against ethanol-induced gastric mucosal injury in rats. The mechanism of this gastroprotection included an increase in pH and gastric wall mucus, an increase in endogenous enzymes, and a decrease in the level of MDA

  16. Protective effect of Cratoxylum formosum extract against acid/alcohol-induced gastric mucosal damage in rats.

    Science.gov (United States)

    Sripanidkulchai, Kittisak; Teepsawang, Somsuda; Sripanidkulchai, Bungorn

    2010-10-01

    Cratoxylum formosum is an edible plant that is commonly consumed among the people in Northeast Thailand. This study aimed to investigate the gastroprotective effect of the ethanolic extract of C. formosum leaves (C. formosum ethanolic extract [CFE]). Gastric ulceration was induced in Wistar male rats by oral administration of acid/alcohol. Oral dosing with CFE at 250 and 500 mg/kg of body weight after the acid/alcohol induction significantly decreased the number of bleeding spots, area of bleeding, ulcer score, and ulcer index. Pretreatment with 500 mg/kg CFE significantly prevented the gastric damage. Histological studies of the acid/alcohol-induced animals indicated the gastric inflammation with lesion depth through the mucosal layer. Whereas the gastric lesion of the CFE-treated animals at both 250 and 500 mg/kg doses was decreased to be one-fourth of the mucosal layers, pretreatment with 500 mg/kg CFE prior to acid/alcohol induction completely protected against the mucosal damage. Biochemical analysis of gastric mucosa revealed a significant decrease of malondialdehyde in the CFE-treated group in a dose-response manner. These findings suggest that the gastroprotective activity of CFE could be mediated possibly through its antioxidant effect.

  17. Preliminary study on radio-chemo-induced oral mucositis and low level laser therapy

    Science.gov (United States)

    Merigo, Elisabetta; Fontana, Matteo; Fornaini, Carlo; Clini, Fabio; Cella, Luigi; Vescovi, Paolo; Oppici, Aldo

    2012-09-01

    Background: Oral mucositis remains one of the most common and troubling side effects of antineoplastic radiation and drug therapy: its incidence in onco-hematological radio-chemotreated patients is variable between 50 and 100% and its impact on this populations is directly linked with the experience of intense pain causing reduction and modification of therapy regimens, decreased survival rates and increased cost of care. Purpose: Aim of this study is the preliminary evaluation of a Low Level Laser therapy (LLLT) protocol on healing process of oral mucositis and on pain and quality of life of patients experiencing this dramatic side-effect. Materials and methods: Patients were evaluated and treated at the Unita` Operativa Semplice Dipartimentale di Odontostomatologia e Chirurgia Maxillo-Facciale of the Hospital of Piacenza were they were treated for primary disease with protocols of chemotherapy and/or radiotherapy. LLLT protocol was performed with a diode laser (808 nm -XD Smile - Fotona -Slovenia) on a two weeks-6 treatments schedule with power of 0.5 W and application of 30 seconds. Mucositis grading was scored on the basis of WHO classification by two blind operators at each treatment and at 1 and 2 weeks after treatment. Pain and capability of deglutition were described by patients by means questionnaires based on Visual Analogue Scale, Numerical Rating Scale and Quality of Life. Results: A relevant improvement of healing of oral mucositis, in terms of reduction of grading score, and of pain, swallowing discomfort and quality of life was recorded. Discussion and conclusion: Results of this preliminary study are encouraging for the realization of larger studies focused on the application of LLLT protocols in management of radio-chemotreated patients with oral mucositis.

  18. Oats do not induce systemic or mucosal autoantibody response in children with coeliac disease.

    Science.gov (United States)

    Koskinen, Outi; Villanen, Mikko; Korponay-Szabo, Ilma; Lindfors, Katri; Mäki, Markku; Kaukinen, Katri

    2009-05-01

    A gluten-free diet omitting wheat, rye, and barley is the only effective treatment for coeliac disease. The necessity of excluding oats from the diet has remained controversial. We studied the toxicity of oats in children with coeliac disease during a 2-year follow-up by investigating jejunal transglutaminase 2 (TG2)-targeted IgA-class autoantibody deposits, a potentially more sensitive disease marker than serum antibodies or conventional histology. Twenty-three coeliac children in remission were randomized to undergo oat or gluten challenge with wheat, rye, barley, and oats. When jejunal histological relapse was evident after gluten challenge, patients excluded wheat, rye, and barley but continued with oats. Mucosal morphology and TG2-targeted autoantibody deposits were studied in jejunal biopsies taken at baseline and after 6 and 24 months. Furthermore, serum IgA-class TG2 antibodies were measured. At baseline, serum TG2 antibodies were negative in all 23 patients, but 7 of them had minor mucosal deposits. In the oats group, there was no significant change in the intensity of the deposits within 2 years. In contrast, during the gluten challenge, the intensity of the deposits clearly increased and decreased again when wheat, rye, and barley were excluded but consumption of oats was continued; this was in line with serum autoantibodies. The intensity of the mucosal deposits correlated well with both villous morphology and serum autoantibody levels. Consumption of oats does not induce TG2 autoantibody production at mucosal level in children with coeliac disease. Measurement of small-intestinal mucosal autoantibody deposits is suitable for monitoring treatment in coeliac patients.

  19. S-Nitrosoglutathione Accelerates Recovery from 5-Fluorouracil-Induced Oral Mucositis

    Science.gov (United States)

    Skeff, Maria Adriana; Brito, Gerly A. C.; de Oliveira, Marcelo G.; Braga, Cintia M.; Cavalcante, Matheus M.; Baldim, Victor; Holanda-Afonso, Rosenilde C.; Silva-Boghossian, Carina M.; Colombo, Ana Paula; Ribeiro, Ronaldo A.; Moura-Neto, Vivaldo; Leitão, Renata F. C.

    2014-01-01

    Introduction Mucositis induced by anti-neoplastic drugs is an important, dose-limiting and costly side-effect of cancer therapy. Aim To evaluate the effect of the topical application of S-nitrosoglutathione (GSNO), a nitric oxide donor, on 5-fluorouracil (5-FU)-induced oral mucositis in hamsters. Materials and Methods Oral mucositis was induced in male hamsters by two intraperitoneal administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) followed by mechanical trauma on the fourth day. Animals received saline, HPMC or HPMC/GSNO (0.1, 0.5 or 2.0 mM) 1 h prior to the 5-FU injection and twice a day for 10 or 14 days. Samples of cheek pouches were harvested for: histopathological analysis, TNF-α and IL-1β levels, immunohistochemical staining for iNOS, TNF-α, IL-1β, Ki67 and TGF-β RII and a TUNEL assay. The presence and levels of 39 bacterial taxa were analyzed using the Checkerboard DNA-DNA hybridization method. The profiles of NO released from the HPMC/GSNO formulations were characterized using chemiluminescence. Results The HPMC/GSNO formulations were found to provide sustained release of NO for more than 4 h at concentration-dependent rates of 14 to 80 nmol/mL/h. Treatment with HPMC/GSNO (0.5 mM) significantly reduced mucosal damage, inflammatory alterations and cell death associated with 5-FU-induced oral mucositis on day 14 but not on day 10. HPMC/GSNO administration also reversed the inhibitory effect of 5-FU on cell proliferation on day 14. In addition, we observed that the chemotherapy significantly increased the levels and/or prevalence of several bacterial species. Conclusion Topical HPMC/GSNO accelerates mucosal recovery, reduces inflammatory parameters, speeds up re-epithelization and decreases levels of periodontopathic species in mucosal ulcers. PMID:25478918

  20. Probiotics as Antifungals in Mucosal Candidiasis.

    Science.gov (United States)

    Matsubara, Victor H; Bandara, H M H N; Mayer, Marcia P A; Samaranayake, Lakshman P

    2016-05-01

    Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  1. IL-36R signalling activates intestinal epithelial cells and fibroblasts and promotes mucosal healing in vivo.

    Science.gov (United States)

    Scheibe, Kristina; Backert, Ingo; Wirtz, Stefan; Hueber, Axel; Schett, Georg; Vieth, Michael; Probst, Hans Christian; Bopp, Tobias; Neurath, Markus F; Neufert, Clemens

    2017-05-01

    Interleukin (IL)-36R signalling plays a proinflammatory role in different organs including the skin, but the expression of IL-36R ligands and their molecular function in intestinal inflammation are largely unknown. We studied the characteristics of IL-36R ligand expression in IBDs and experimental colitis. The functional role of IL-36R signalling in the intestine was addressed in experimental colitis and wound healing models in vivo by using mice with defective IL-36R signalling (IL-36R-/-) or Myd88, neutralising anti-IL-36R antibodies, recombinant IL-36R ligands and RNA-seq genome expression analysis. Expression of IL-36α and IL-36γ was significantly elevated in active human IBD and experimental colitis. While IL-36γ was predominantly detected in nuclei of the intestinal epithelium, IL-36α was mainly found in the cytoplasm of CD14(+) inflammatory macrophages. Functional studies showed that defective IL-36R signalling causes high susceptibility to acute dextran sodium sulfate colitis and impairs wound healing. Mechanistically, IL-36R ligands released upon mucosal damage activated IL-36R(+) colonic fibroblasts via Myd88 thereby inducing expression of chemokines, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-6. Moreover, they induced proliferation of intestinal epithelial cells (IECs) and expression of the antimicrobial protein lipocalin 2. Finally, treatment of experimental intestinal wounds with IL-36R ligands significantly accelerated mucosal healing in vivo. IL-36R signalling is activated upon intestinal damage, stimulates IECs and fibroblasts and drives mucosal healing. Modulation of the IL-36R pathway emerges as a potential therapeutic strategy for induction of mucosal healing in IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. Importance of the CCR5-CCL5 axis for mucosal Trypanosoma cruzi protection and B cell activation.

    Science.gov (United States)

    Sullivan, Nicole L; Eickhoff, Christopher S; Zhang, Xiuli; Giddings, Olivia K; Lane, Thomas E; Hoft, Daniel F

    2011-08-01

    Trypanosoma cruzi is an intracellular parasite and the causative agent of Chagas disease. Previous work has shown that the chemokine receptor CCR5 plays a role in systemic T. cruzi protection. We evaluated the importance of CCR5 and CCL5 for mucosal protection against natural oral and conjunctival T. cruzi challenges. T. cruzi-immune CCR5(-/-) and wild-type C57BL/6 mice were generated by repeated infectious challenges with T. cruzi. CCR5(-/-) and wild-type mice developed equivalent levels of cellular, humoral, and protective mucosal responses. However, CCR5(-/-)-immune mice produced increased levels of CCL5 in protected gastric tissues, suggesting compensatory signaling through additional receptors. Neutralization of CCL5 in CCR5(-/-)-immune mice resulted in decreased mucosal inflammatory responses, reduced T. cruzi-specific Ab-secreting cells, and significantly less mucosal T. cruzi protection, confirming an important role for CCL5 in optimal immune control of T. cruzi replication at the point of initial mucosal invasion. To investigate further the mechanism responsible for mucosal protection mediated by CCL5-CCR5 signaling, we evaluated the effects of CCL5 on B cells. CCL5 enhanced proliferation and IgM secretion in highly purified B cells triggered by suboptimal doses of LPS. In addition, neutralization of endogenous CCL5 inhibited B cell proliferation and IgM secretion during stimulation of highly purified B cells, indicating that B cell production of CCL5 has important autocrine effects. These findings demonstrate direct effects of CCL5 on B cells, with significant implications for the development of mucosal adjuvants, and further suggest that CCL5 may be important as a general B cell coactivator.

  3. Role of sulfhydryls in mucosal injury caused by ethanol: relation to microvascular permeability, gastric motility and cytoprotection

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, K.; Okada, M.; Niida, H.; Okabe, S.

    1989-02-01

    The relationship between gastric mucosal glutathione (GSH) levels, vascular permeability, gastric motility and mucosal injury caused by ethanol was investigated in rats. Oral administration of 50% ethanol (1 ml) produced elongated reddish bands of lesions in the mucosa with a significant reduction of GSH levels and increase of microvascular permeability. These lesions were significantly inhibited by pretreatment with s.c. administered diethylmaleate (DEM: 1 ml/kg), cysteamine (100 mg/kg) and 16, 16-dimethyl prostaglandin E2 (dmPGE2, 10 micrograms/kg) but worsened markedly by N-ethylmaleimide (NEM: 10 mg/kg). Irrespective of whether the animals were treated with 50% ethanol or not, the mucosal GSH levels were significantly decreased or increased, respectively, by DEM or cysteamine, and were not affected by both NEM and dmPGE2. NEM significantly enhanced the vascular permeability in the absence or presence of ethanol (greater than 10%), whereas other agents significantly inhibited only the increased vascular permeability caused by ethanol. On the other hand, gastric motility was potently and persistently inhibited by either DEM, cysteamine or dmPGE2 at the doses which prevented ethanol-induced mucosal injury, whereas NEM had no effect on the motility. These results suggest that 1) the mucosal GSH levels do not relate directly to either development or prevention of ethanol-induced gastric injury, 2) potentiation by NEM of the mucosal injury may be accounted for by its enhancement of the vascular permeability and 3) inhibition of gastric motility may be associated with prevention of mucosal lesions.

  4. Rebamipide protects small intestinal mucosal injuries caused by indomethacin by modulating intestinal microbiota and the gene expression in intestinal mucosa in a rat model.

    Science.gov (United States)

    Kurata, Satoshi; Nakashima, Takako; Osaki, Takako; Uematsu, Naoya; Shibamori, Masafumi; Sakurai, Kazushi; Kamiya, Shigeru

    2015-01-01

    The effect of rebamipide, a mucosal protective drug, on small intestinal mucosal injury caused by indomethacin was examined using a rat model. Indomethacin administration (10 mg/kg, p.o.) induced intestinal mucosal injury was accompanied by an increase in the numbers of intestinal bacteria particularly Enterobacteriaceae in the jejunum and ileum. Rebamipide (30 and 100 mg/kg, p.o., given 5 times) was shown to inhibit the indomethacin-induced small intestinal mucosal injury and decreased the number of Enterococcaceae and Enterobacteriaceae in the jejunal mucosa to normal levels. It was also shown that the detection rate of segmented filamentous bacteria was increased by rebamipide. PCR array analysis of genes related to inflammation, oxidative stress and wound healing showed that indomethacin induced upregulation and downregulation of 14 and 3 genes, respectively in the rat jejunal mucosa by more than 5-fold compared to that of normal rats. Rebamipide suppressed the upregulated gene expression of TNFα and Duox2 in a dose-dependent manner. In conclusion, our study confirmed that disturbance of intestinal microbiota plays a crucial role in indomethacin-induced small intestinal mucosal injury, and suggests that rebamipide could be used as prophylaxis against non-steroidal anti-inflammatory drugs -induced gastrointestinal mucosal injury, by modulating microbiota and suppressing mucosal inflammation in the small intestine.

  5. Induction of mucosal immunity through systemic immunization: Phantom or reality?

    Science.gov (United States)

    Su, Fei; Patel, Girishchandra B; Hu, Songhua; Chen, Wangxue

    2016-04-02

    Generation of protective immunity at mucosal surfaces can greatly assist the host defense against pathogens which either cause disease at the mucosal epithelial barriers or enter the host through these surfaces. Although mucosal routes of immunization, such as intranasal and oral, are being intensely explored and appear promising for eliciting protective mucosal immunity in mammals, their application in clinical practice has been limited due to technical and safety related challenges. Most of the currently approved human vaccines are administered via systemic (such as intramuscular and subcutaneous) routes. Whereas these routes are acknowledged as being capable to elicit antigen-specific systemic humoral and cell-mediated immune responses, they are generally perceived as incapable of generating IgA responses or protective mucosal immunity. Nevertheless, currently licensed systemic vaccines do provide effective protection against mucosal pathogens such as influenza viruses and Streptococcus pneumoniae. However, whether systemic immunization induces protective mucosal immunity remains a controversial topic. Here we reviewed the current literature and discussed the potential of systemic routes of immunization for the induction of mucosal immunity.

  6. Chemotherapy induced intestinal mucositis; from bench to bed

    NARCIS (Netherlands)

    B.A.E. Koning, de (Barbara)

    2008-01-01

    textabstractPart 1 focuses primarily on the pathophysiology of mucositis, in order to gain more insight different experimental mouse models were used. Chapter 2 describes mucositis induced by high dose doxorubicin (DOX)- treatment. DOX is a frequently used cytostatic drug in childhood cancer,

  7. Minimally invasive treatment of oral ranula with a mucosal tunnel.

    Science.gov (United States)

    Jia, T; Xing, L; Zhu, F; Jin, X; Liu, L; Tao, J; Chen, Y; Gao, Z; Zhang, H

    2015-02-01

    We have developed a new method for minimally-invasive treatment of uncomplicated oral ranulas using a mucosal tunnel, and we report the clinical outcome. We constructed a mucosal tunnel for each of 35 patients who presented with an oral ranula, by making 2 parallel incisions across the top of the protruding ranula 2-3mm apart, and dissected the soft tissue along the incisions to its wall. The fluid was removed and the cavity irrigated with normal saline. The wall of the ranula was not treated. The first mucosal tunnel was made by suturing the base of the mucosal strip to the deepest part of the wall of the ranula. The mucosal base of the tunnel and the deepest part of the base of the ranula were fixed with absorbable sutures. The two external edges of the incisions were sutured together to form the second mucosal tunnel, and apposing sutures were inserted between the two parallel incisions to form two natural mucosal tunnels. The duration of follow-up ranged from 1 to 5 years. One patient was lost to follow-up and 34 patients were cured. Outcomes were satisfactory without relapse during the follow-up period and the patients were satisfied with the outcome. The mucosal tunnel is a safe, effective, simple, and minimally-invasive treatment for oral ranula.

  8. Chemotherapy induced intestinal mucositis; from bench to bed

    NARCIS (Netherlands)

    B.A.E. Koning, de (Barbara)

    2008-01-01

    textabstractPart 1 focuses primarily on the pathophysiology of mucositis, in order to gain more insight different experimental mouse models were used. Chapter 2 describes mucositis induced by high dose doxorubicin (DOX)- treatment. DOX is a frequently used cytostatic drug in childhood cancer,

  9. Decreased mucosal oxygen tension in the maxillary sinuses in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Aanæs, Kasper; Rickelt, Lars Fledelius; Johansen, Helle Krogh;

    2011-01-01

    Pseudomonas aeruginosa in the sinuses plays a role in the lungs in cystic fibrosis (CF) patients, but little is known about the sinus environment where the bacteria adapt. Anoxic areas are found in the lower respiratory airways but it is unknown if the same conditions exist in the sinuses....

  10. HIV and mucosal barrier interactions: consequences for transmission and pathogenesis.

    Science.gov (United States)

    Burgener, Adam; McGowan, Ian; Klatt, Nichole R

    2015-10-01

    The mucosal barrier plays an integral function in human health as it is the primary defense against pathogens, and provides a critical transition between the external environment and the human internal body. In the context of HIV infection, the most relevant mucosal surfaces include those of the gastrointestinal (GI) and genital tract compartments. Several components help maintain the effectiveness of this mucosal surface, including the physical anatomy of the barrier, cellular immunity, soluble factors, and interactions between the epithelial barrier and the local microenvironment, including mucus and host microbiota. Any defects in barrier integrity or function can rapidly lead to an increase in acquisition risk, or with established infection may result in increased pathogenesis, morbidities, or mortality. Indeed, a key feature to all aspects of HIV infection from transmission to pathogenesis is disruption and/or dysfunction of mucosal barriers. Herein, we will detail the host-pathogen relationship of HIV and mucosal barriers in both of these scenarios.

  11. Erythropoietin-induced proliferation of gastric mucosal cells

    Institute of Scientific and Technical Information of China (English)

    Kazuro Itoh; Masato Higuchi; Fumio Ishihata; Yushi Sudoh; Soichiro Miura; Yoshio Sawasaki; Kyoko Takeuchi; Shingo Kato; Nobuhiro Imai; Yoichiro Kato; Noriyuki Shibata; Makio Kobayashi; Yoshiyuki Moriguchi

    2006-01-01

    AIM: To analyze the localization of erythropoietin receptor on gastric specimens and characterize the effects of erythropoietin on the normal gastric epithelial proliferation using a porcine gastric epithelial cell culture model.METHODS: Erythropoietin receptor was detected by RT-PCR, Western blotting and immunohistochermistry.Growth stimulation effects of erythropoietin on cultured gastric mucosal cells were determined by ELISA using bromodeoxyuridine (BrdU).RESULTS: Erythropoietin receptor was detected on cultured porcine gastric mucosal epithelial cells.Erythropoietin receptor was also detected histochemically at the base of gastric mucosal epithelium. BrdU assay demonstrated a dose-dependent increase in growth potential of cultured porcine gastric mucosal epithelial cells by administration of erythropoietin, as well as these effects were inhibited by administration of antierythropoietin antibody (P< 0.01).CONCLUSION: These findings indicate that erythropoietin has a potential to proliferate gastric mucosal epithelium via erythropoietin receptor.

  12. Frank hematuria as the presentation feature of acute leukemia

    Directory of Open Access Journals (Sweden)

    Suriya Owais

    2010-01-01

    Full Text Available Muco-cutaneous bleeding is a common presenting feature of acute leukemias. Mucosal bleeding usually manifests as gum bleeding and/or epistaxis but may occur in any mucosal surface of the body. Hematuria as an isolated or main presenting feature of acute leukemia is rare. We describe two cases of acute leukemia, a 19 year old male with acute lymphoblastic leukemia and a 52 year old male with acute myeloid leukemia, both presenting with gross hematuria. There was no demonstrable leukemic infiltration of the urinary tract on imaging studies. Hematuria in these patients was likely to be due to occult leukemic infiltration of the urinary system, aggravated by thrombocytopenia, as it subsided after starting chemotherapy. Our cases highlight that hematuria should be remembered as a rare presenting feature of acute leukemia.

  13. Dietary cysteine is used more efficiently by children with severe acute malnutrition with edema compared with those without edema

    Science.gov (United States)

    Children with edematous severe acute malnutrition (SAM) produce less cysteine than do their nonedematous counterparts. They also have marked glutathione (GSH) depletion, hair loss, skin erosion, gut mucosal atrophy, and depletion of mucins. Because GSH, skin, hair, mucosal, and mucin proteins are ri...

  14. Preventive Effect of Rebamipide Gargle on Chemoradiotherpy-Induced Oral Mucositis in Patients with Oral Cancer: a Pilot Study

    Directory of Open Access Journals (Sweden)

    Takashi Yasuda

    2011-11-01

    Full Text Available Objectives: To assess the efficacy and safety of rebamipide in preventing chemoradiotherapy-induced oral mucositis in patients with oral cancer.Material and Methods: Patients with oral cancer treated with chemoradiotherapy (daily radiotherapy plus docetaxel hydrate once a week were enrolled for this study. They were assigned in a double-blind fashion to receive either rebamipide gargle or placebo on the days of chemoradiotherapy. Oral mucositis was assessed using the WHO grading system. The primary endpoint of this study was the incidence of grade 3 - 4 mucositis after exposure to 40 Gy radiation (4 weeks. The secondary endpoint was the effect of rebamipide gargle on tumour response to chemoradiotherapy.Results: Twenty-four patients were randomly assigned to receive rebamipide gargle (n = 12 or placebo-gargle (n = 12 during chemoradiotherapy. The number of patients with severe mucositis (WHO ≥ 3 was higher in the placebo group than in the rebamipide group (83.3% vs. 33.3%, P = 0.036. In addition, no effect of rebamipide gargle on tumour response to chemoradiotherapy was recognized compared with the placebo group.Conclusions: For patients with oral cancer undergoing chemoradiotherapy, rebamipide gargle may contribute to decrease the severity of oral mucositis.

  15. Preventive effect of rebamipide gargle on chemoradiotherpy-induced oral mucositis in patients with oral cancer: a pilot study.

    Science.gov (United States)

    Yasuda, Takashi; Chiba, Hiroshige; Satomi, Takafumi; Matsuo, Akira; Kaneko, Tadayoshi; Chikazu, Daichi; Miyamatsu, Hironobu

    2012-01-01

    To assess the efficacy and safety of rebamipide in preventing chemoradiotherapy-induced oral mucositis in patients with oral cancer. Patients with oral cancer treated with chemoradiotherapy (daily radiotherapy plus docetaxel hydrate once a week) were enrolled for this study. They were assigned in a double-blind fashion to receive either rebamipide gargle or placebo on the days of chemoradiotherapy. Oral mucositis was assessed using the WHO grading system. The primary endpoint of this study was the incidence of grade 3 - 4 mucositis after exposure to 40 Gy radiation (4 weeks). The secondary endpoint was the effect of rebamipide gargle on tumour response to chemoradiotherapy. Twenty-four patients were randomly assigned to receive rebamipide gargle (n = 12) or placebo-gargle (n = 12) during chemoradiotherapy. The number of patients with severe mucositis (WHO ≥ 3) was higher in the placebo group than in the rebamipide group (83.3% vs. 33.3%, P = 0.036). In addition, no effect of rebamipide gargle on tumour response to chemoradiotherapy was recognized compared with the placebo group. For patients with oral cancer undergoing chemoradiotherapy, rebamipide gargle may contribute to decrease the severity of oral mucositis.

  16. Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage.

    Science.gov (United States)

    Sun, Zhaorui; Liu, Hongmei; Yang, Zhizhou; Shao, Danbing; Zhang, Wei; Ren, Yi; Sun, Baodi; Lin, Jinfeng; Xu, Min; Nie, Shinan

    2014-09-01

    Intestinal trefoil factor (ITF, also named as trefoil factor 3, TFF3) is a member of the TFF-domain peptide family, which plays an essential role in the regulation of cell survival, cell migration and maintains mucosal epithelial integrity in the gastrointestinal tract. However, the underlying mechanisms and associated molecules remain unclear. The aim of this study was to explore the protective effects of ITF on gastric mucosal epithelium injury and its possible molecular mechanisms of action. In the present study, we show that ITF was able to promote the proliferation and migration of GES-1 cells via a mechanism that involves the PI3K/Akt signaling pathway. Western blot results indicated that ITF induced a dose- and time-dependent increase in the Akt signaling pathway. ITF also plays an essential role in the restitution of GES-1 cell damage induced by lipopolysaccharide (LPS). LPS induced the apoptosis of GES-1 cells, decreased cell viability significantly (Pinhibition of the PI3K/Akt pathway. Taken together, our results demonstrate that ITF promotes the proliferation and migration of gastric mucosal epithelial cells and preserves gastric mucosal epithelial integrity after damage is mediated by activation of the PI3K/Akt signaling pathway. This study suggested that the PI3K/Akt pathway could act as a key intracellular pathway in the gastric mucosal epithelium that may serve as a therapeutic target to preserve epithelial integrity during injury.

  17. A comparison between zinc sulfate and chlorhexidine gluconate mouthwashes in the prevention of chemotherapy-induced oral mucositis

    Directory of Open Access Journals (Sweden)

    M Mehdipour

    2011-03-01

    Full Text Available "n Background and the Purpose of the Study: Patients undergoing high-dose chemotherapy for hematological malignancies are susceptible to development of oral mucositis, and no effective modality has been reported for its prophylaxis and treatment. The aim of this study was to evaluate the effectiveness of zinc mouthwash on chemotherapy-induced oral mucositis lesions. "nMethods: In this double-blind randomized trial, patients under chemotherapy for acute leukemia were divided into two test and control groups of 15 patients each. The groups were homogeneous with respect to medical history, tumor characteristics, and therapeutic details. The test group received 10ml 0.2% zinc sulfate mouthwash, and the control group received 10ml 0.2% chlorhexidine gluconate mouthwash, twice a day for a period of two weeks. Spijkervet scale was used to grade the severity of mucositis at every other week during eight weeks. The severity scores were analyzed with repeated measure ANOVA using SPSS 13.0 computer software. "nResults: Mean severity scores were generally lower in the test group compared to the controls at all four time intervals evaluated; but only, the differences in weeks of 2 and 3 were statistically significant (P=0.025. Conclusion: Zinc mouthwash used in conjunction with chemotherapy may reduce the severity of oral mucositis lesions in patients with leukaemia.

  18. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients.

    NARCIS (Netherlands)

    Saunders, D.P.; Epstein, J.B.; Elad, S.; Allemano, J.; Bossi, P.; Wetering, M.D. van de; Rao, N.G.; Potting, C.M.J.; Cheng, K.K.; Freidank, A.; Brennan, M.T.; Bowen, J.; Dennis, K.; Lalla, R.V.

    2013-01-01

    PURPOSE: The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients. METHODS: A systematic review of the available literature was

  19. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients.

    NARCIS (Netherlands)

    Saunders, D.P.; Epstein, J.B.; Elad, S.; Allemano, J.; Bossi, P.; Wetering, M.D. van de; Rao, N.G.; Potting, C.M.J.; Cheng, K.K.; Freidank, A.; Brennan, M.T.; Bowen, J.; Dennis, K.; Lalla, R.V.

    2013-01-01

    PURPOSE: The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients. METHODS: A systematic review of the available literature was con

  20. Efficacy and toxicity of Samen-ista emulsion on treatment of cutaneous and mucosal bleeding.

    Science.gov (United States)

    Hosseini, Mousalreza; Pourakbar, Ali; Forouzanfar, Fatemeh; Arian, Amirali; Ghaffarzadegan, Kamran; Salehi, Maryam; Esfandiari, Samaneh; Rakhshandeh, Hassan

    2016-10-01

    Despite new treatment methods, upper gastrointestinal bleeding remains challenging. Samen-ista emulsion is a new agent based on traditional medicine with coagulant properties. The efficacy and safety of Samen-ista were assessed in cutaneous and mucosal bleeding animal models. Coagulant properties of Samen-ista were evaluated using mice tail bleeding assay, marginal ear vein and upper gastrointestinal mucosal bleeding times in rabbits. After 7 days, clinical signs, mortality and end-organ (kidney, liver, lung, brain and gastric mucosa) histopathological changes were also examined. Samen-ista dose-dependently decreased mean cutaneous tail (128 vs. 14 s) and marginal ear vein (396 vs. 84 s) bleeding times. Rabbit's upper gastrointestinal bleeding time was also significantly decreased (214 vs. 15.8 s) upon Samen-ista local endoscopic application. Treatment with Samen-ista for 7 days did not cause any mortality, abnormal signs of bleeding, changes in appetite or significant histopathologicl changes. Samen-ista emulsion is well tolerated and highly effective in achieving hemostasis in cutaneous and mucosal bleeding animal models.

  1. Possible mechanism of gastric mucosal protection by epidermal growth factor in rats

    Energy Technology Data Exchange (ETDEWEB)

    Amagase, Harunobu (Hiroshima Univ. School of Medicine (Japan) Wakunaga Pharmaceutical Co., Ltd., Hiroshima (Japan)); Murakami, Teruo; Misaki, Masafumi; Higashi, Yutaka; Yata, Noboru (Hiroshima Univ. School of Medicine (Japan)); Hashimoto, Ken; Fuwa, Tohru (Wakunaga Pharmaceutical Co., Ltd., Hiroshima (Japan))

    1990-01-01

    At different times following the subcutaneous administration of hEGF, intragastric acidified ethanol was administered to induce an experimental gastric mucosal lesion. Mean length of the lesion in the gastric mucosa was used as a lesion index. Extravasation of intraveneously injected Evans blue into the gastric wall and gastric contents was used as an indicator of vascular permeability. Pretreatment with hEGF decreased both the gastric mucosal lesions and the increase of vascular permeability caused by acidified ethanol with similar time profiles relative to pretreatment with hEGF. Maximal protective actions of hEGF occurred about 10 to 30 min after the observed peak plasma concentration of hEGF. Indomethacine and {und N}-ethylmaleimide, but not iodoacetamide, blocked the protective action of hEGF, indicating that endogeneous prostaglandins and/or sulfhydryls may participate in the protective action of hEGF. The content of endogeneous nonprotein sulfhydryls in the gastric mucosa decreased markedly after acidified ethanol. However, pretreated hEGF did not restore the sulfhydryl contents. Thus, it seemed that endogenous prostaglandins, but not sulfhydryls, are the probable mediators for protection against gastric mucosal injury caused by acidified ethanol.

  2. Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring

    Science.gov (United States)

    Ahadome, Sarah D.; Abraham, David J.; Rayapureddi, Suryanarayana; Saw, Valerie P.; Saban, Daniel R.; Calder, Virginia L.; Norman, Jill T.; Ponticos, Markella; Daniels, Julie T.; Dart, John K.

    2016-01-01

    Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. Aldehyde dehydrogenase family 1 (ALDH1) is upregulated in both ocular MMP (OMMP) conjunctiva and cultured fibroblasts. Application of the ALDH metabolite, retinoic acid (RA), to normal human conjunctival fibroblasts in vitro induced a diseased phenotype. Conversely, application of ALDH inhibitors, including disulfiram, to OMMP fibroblasts in vitro restored their functionality to that of normal controls. ALDH1 is also upregulated in the mucosa of the mouse model of scarring allergic eye disease (AED), used here as a surrogate for OMMP, in which topical application of disulfiram decreased fibrosis in vivo. These data suggest that progressive scarring in OMMP results from ALDH/RA fibroblast autoregulation, that the ALDH1 subfamily has a central role in immune-mediated ocular mucosal scarring, and that ALDH inhibition with disulfiram is a potential and readily translatable antifibrotic therapy. PMID:27699226

  3. Mucosal immunity to pathogenic intestinal bacteria.

    Science.gov (United States)

    Perez-Lopez, Araceli; Behnsen, Judith; Nuccio, Sean-Paul; Raffatellu, Manuela

    2016-03-01

    The intestinal mucosa is a particularly dynamic environment in which the host constantly interacts with trillions of commensal microorganisms, known as the microbiota, and periodically interacts with pathogens of diverse nature. In this Review, we discuss how mucosal immunity is controlled in response to enteric bacterial pathogens, with a focus on the species that cause morbidity and mortality in humans. We explain how the microbiota can shape the immune response to pathogenic bacteria, and we detail innate and adaptive immune mechanisms that drive protective immunity against these pathogens. The vast diversity of the microbiota, pathogens and immune responses encountered in the intestines precludes discussion of all of the relevant players in this Review. Instead, we aim to provide a representative overview of how the intestinal immune system responds to pathogenic bacteria.

  4. Oral mucosal involvement in visceral leishmaniasis

    Institute of Scientific and Technical Information of China (English)

    Sunny Garg; Richik Tripathi; Kamlakar Tripathi

    2013-01-01

    Leishmaniasis affects both the visceral and cutaneous tissues in body.OralMucosal involvement in leishmaniasis is rare and is often overlooked.We present a case17 year old boy from the north east region ofBihar who has a history of visceral leishmaniasis one year back, came to the department of oral surgery for treatment of persistent oral ulcers.Oral examination did not give any diagnostic information while systemic examination revealed enlarged spleen and low grade fever.Patient was screened for leishmaniasis by rK39 based immunochromatographic strip test which came to be positive.Biopsy of the ulcer as well as splenic and bone marrow aspirate confirmed the presence of leishmaniasis.Patient was administeredAmphotericinB for20 days following which significant clinical and haematological improvement followed.

  5. Role of polyamines in gastrointestinal mucosal growth

    Institute of Scientific and Technical Information of China (English)

    Zhao Xiang Bian; Jian Hua Wang

    2000-01-01

    The polyamines [putrescine (PU), spermidine (SPD) and spermine (SPM)] are ubiquitous polycationiccompounds found in all prokaryotic and eukaryotic cells, are essentially involved in a variety of regulatorysteps during normal, adaptive, and malignant cell proliferation. Nearly four decades investigation about thepolyamines contributed to the synthesis and decomposition of polyamines and the active and passive enzymeswhich regulate them at different levels. This review focuses on the sources and homeostasis of intracellularpolyamines, the transport and role of the polyamines in the growth of the gastrointestinal mucosa and theirpossible mechanism. We tried to point out the gaps remaining in the story and give a working hypothesis forthe role of polyamines in gastrointestinal mucosal growth. We propose in the hypothesis that polyamine is a“key”to unlock the “door”of cell proliferation. How many “doors” between the “polyamine key” and the“real start” of proliferation? The polyamine might be the only key for cell proliferation. Another possibilityis that polyamine is the first key and its “unlocking-effect” resulting in getting another key for the next doorin the proliferation chain, for example, proto-oncogenes. To decide whether polyamine is an intermediatestep or just only one step of cell proliferation, the possible way is to keep polyamine to be a stimulus and finda way to deprive the function of proto-oncogene protein (or other possible gene expression product) to checkthe effect on the cell proliferation. Another important question is how polyamine can trigger the synthesis ofDNA in virtual. Arabinose operon model may give us some ideas to investigate about that. And furthermore,it is necessary to pay attention to the relationship between polyamine and other cell proliferation regulator,like growth factor, chalone, cAMP, cGMP, etc. Further studies are needed to investigate the mechanism ofpolyamine acted on the gastrointestinal mucosal

  6. Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis.

    Science.gov (United States)

    van der Velden, Walter J F M; Herbers, Alexandra H E; Netea, Mihai G; Blijlevens, Nicole M A

    2014-11-01

    Infection remains one of the most prominent complications after cytotoxic treatment for cancer. The connection between neutropenia and both infections and fever has long been designated as 'febrile neutropenia', but treatment with antimicrobial agents and haematopoietic growth factors has failed to significantly reduce its incidence. Moreover, emerging antimicrobial resistance is becoming a concern that necessitates the judicious use of available antimicrobial agents. In addition to neutropenia, patients who receive cytotoxic therapy experience mucosal barrier injury (MBI) or 'mucositis'. MBI creates a port-de-entrée for resident micro-organisms to cause blood stream infections and contributes directly to the occurrence of fever by disrupting the highly regulated host-microbe interactions, which, even in the absence of an infection, can result in strong inflammatory reactions. Indeed, MBI has been shown to be a pivotal factor in the occurrence of inflammatory complications after cytotoxic therapy. Hence, the concept 'febrile neutropenia' alone may no longer suffice and a new concept 'febrile mucositis' should be recognized as the two are at least complementary. This review we summarizes the existing evidence for both paradigms and proposes new therapeutic approaches to tackle the perturbed host-microbe interactions arising from cytotoxic therapy-induced tissue damage in order to reduce fever in neutropenic patients with cancer.

  7. Stimulation of colonic mucosal growth associated with oxidized redox status in rats.

    Science.gov (United States)

    Tian, Junqiang; Washizawa, Naohiro; Gu, Li H; Levin, Marc S; Wang, Lihua; Rubin, Deborah C; Mwangi, Simon; Srinivasan, Shanthi; Gao, Yuhao; Jones, Dean P; Ziegler, Thomas R

    2007-03-01

    Limited data in animal models suggest that colonic mucosa undergoes adaptive growth following massive small bowel resection (SBR). In vitro data suggest that intestinal cell growth is regulated by reactive oxygen species and redox couples [e.g., glutathione (GSH)/glutathione disulfide (GSSG) and cysteine (Cys)/cystine (CySS) redox]. We investigated the effects of SBR and alterations in redox on colonic growth indexes in rats after either small bowel transection (TX) or 80% midjejunoileal resection (RX). Rats were pair fed +/- blockade of endogenous GSH synthesis with buthionine sulfoximine (BSO). Indexes of colonic growth, proliferation, and apoptosis and GSH/GSSG and Cys/CySS redox potentials (E(h)) were determined. RX significantly increased colonic crypt depth, number of cells per crypt, and epithelial cell proliferation [crypt cell bromodeoxyuridine (BrdU) incorporation]. Administration of BSO markedly decreased colonic mucosal GSH, GSSG, and Cys concentrations in both TX and RX groups, with a resultant oxidation of GSH/GSSG and Cys/CySS E(h). BSO did not alter colonic crypt cell apoptosis but significantly increased all colonic mucosal growth indexes (crypt depth, cells/crypt, and BrdU incorporation) in both TX and RX groups in a time- and dose-dependent manner. BSO significantly decreased plasma GSH and GSSG, oxidized GSH/GSSG E(h), and increased plasma Cys and CySS concentrations. Collectively, these data provide in vivo evidence indicating that oxidized colonic mucosal redox status stimulates colonic mucosal growth in rats. The data also suggest that GSH is required to maintain normal colonic and plasma Cys/CySS homeostasis in these animal models.

  8. Regulation of intestinal mucosal growth by amino acids.

    Science.gov (United States)

    Ray, Ramesh M; Johnson, Leonard R

    2014-03-01

    Amino acids, especially glutamine (GLN) have been known for many years to stimulate the growth of small intestinal mucosa. Polyamines are also required for optimal mucosal growth, and the inhibition of ornithine decarboxylase (ODC), the first rate-limiting enzyme in polyamine synthesis, blocks growth. Certain amino acids, primarily asparagine (ASN) and GLN stimulate ODC activity in a solution of physiological salts. More importantly, their presence is also required before growth factors and hormones such as epidermal growth factor and insulin are able to increase ODC activity. ODC activity is inhibited by antizyme-1 (AZ) whose synthesis is stimulated by polyamines, thus, providing a negative feedback regulation of the enzyme. In the absence of amino acids mammalian target of rapamycin complex 1 (mTORC1) is inhibited, whereas, mTORC2 is stimulated leading to the inhibition of global protein synthesis but increasing the synthesis of AZ via a cap-independent mechanism. These data, therefore, explain why ASN or GLN is essential for the activation of ODC. Interestingly, in a number of papers, AZ has been shown to inhibit cell proliferation, stimulate apoptosis, or increase autophagy. Each of these activities results in decreased cellular growth. AZ binds to and accelerates the degradation of ODC and other proteins shown to regulate proliferation and cell death, such as Aurora-A, Cyclin D1, and Smad1. The correlation between the stimulation of ODC activity and the absence of AZ as influenced by amino acids is high. Not only do amino acids such as ASN and GLN stimulate ODC while inhibiting AZ synthesis, but also amino acids such as lysine, valine, and ornithine, which inhibit ODC activity, increase the synthesis of AZ. The question remaining to be answered is whether AZ inhibits growth directly or whether it acts by decreasing the availability of polyamines to the dividing cells. In either case, evidence strongly suggests that the regulation of AZ synthesis is the

  9. Modeling mucosal candidiasis in larval zebrafish by swimbladder injection.

    Science.gov (United States)

    Gratacap, Remi L; Bergeron, Audrey C; Wheeler, Robert T

    2014-01-01

    Early defense against mucosal pathogens consists of both an epithelial barrier and innate immune cells. The immunocompetency of both, and their intercommunication, are paramount for the protection against infections. The interactions of epithelial and innate immune cells with a pathogen are best investigated in vivo, where complex behavior unfolds over time and space. However, existing models do not allow for easy spatio-temporal imaging of the battle with pathogens at the mucosal level. The model developed here creates a mucosal infection by direct injection of the fungal pathogen, Candida albicans, into the swimbladder of juvenile zebrafish. The resulting infection enables high-resolution imaging of epithelial and innate immune cell behavior throughout the development of mucosal disease. The versatility of this method allows for interrogation of the host to probe the detailed sequence of immune events leading to phagocyte recruitment and to examine the roles of particular cell types and molecular pathways in protection. In addition, the behavior of the pathogen as a function of immune attack can be imaged simultaneously by using fluorescent protein-expressing C. albicans. Increased spatial resolution of the host-pathogen interaction is also possible using the described rapid swimbladder dissection technique. The mucosal infection model described here is straightforward and highly reproducible, making it a valuable tool for the study of mucosal candidiasis. This system may also be broadly translatable to other mucosal pathogens such as mycobacterial, bacterial or viral microbes that normally infect through epithelial surfaces.

  10. Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection.

    Science.gov (United States)

    Li, Wu; Deng, Guangcun; Li, Min; Liu, Xiaoming; Wang, Yujiong

    2012-01-01

    Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is one of the world's leading infectious causes of morbidity and mortality. As a mucosal-transmitted pathogen, Mtb infects humans and animals mainly through the mucosal tissue of the respiratory tract. Apart from providing a physical barrier against the invasion of pathogen, the major function of the respiratory mucosa may be to serve as the inductive sites to initiate mucosal immune responses and sequentially provide the first line of defense for the host to defend against this pathogen. A large body of studies in the animals and humans have demonstrated that the mucosal immune system, rather than the systemic immune system, plays fundamental roles in the host's defense against Mtb infection. Therefore, the development of new vaccines and novel delivery routes capable of directly inducing respiratory mucosal immunity is emphasized for achieving enhanced protection from Mtb infection. In this paper, we outline the current state of knowledge regarding the mucosal immunity against Mtb infection, including the development of TB vaccines, and respiratory delivery routes to enhance mucosal immunity are discussed.

  11. Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Wu Li

    2012-01-01

    Full Text Available Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis (TB, is one of the world's leading infectious causes of morbidity and mortality. As a mucosal-transmitted pathogen, Mtb infects humans and animals mainly through the mucosal tissue of the respiratory tract. Apart from providing a physical barrier against the invasion of pathogen, the major function of the respiratory mucosa may be to serve as the inductive sites to initiate mucosal immune responses and sequentially provide the first line of defense for the host to defend against this pathogen. A large body of studies in the animals and humans have demonstrated that the mucosal immune system, rather than the systemic immune system, plays fundamental roles in the host’s defense against Mtb infection. Therefore, the development of new vaccines and novel delivery routes capable of directly inducing respiratory mucosal immunity is emphasized for achieving enhanced protection from Mtb infection. In this paper, we outline the current state of knowledge regarding the mucosal immunity against Mtb infection, including the development of TB vaccines, and respiratory delivery routes to enhance mucosal immunity are discussed.

  12. Dental students' ability to detect and diagnose oral mucosal lesions.

    Science.gov (United States)

    Ali, Mohammad A; Joseph, Bobby K; Sundaram, Devipriya B

    2015-02-01

    The aim of this study was to assess the ability of dental students in the screening clinic of the Kuwait University Dental Center to detect and diagnose oral mucosal lesions. Clinical examinations performed by dental students between January 2009 and February 2011 were included. All their findings regarding the oral mucosal lesions and dental carious lesions detected were recorded, after which the patients were re-examined by faculty examiners. The students rated their own ability to detect mucosal and carious lesions before each examination. Among the 341 patients screened, 375 oral mucosal lesions were found by the faculty examiners. Of those, the students detected 178 (47.5%). Out of the 375 lesions, including the ones they failed to detect, the students diagnosed 272 (72.5%) correctly. The students were more likely (p≤0.01) to correctly diagnose a mucosal lesion when they themselves had detected it (n=169/178) than when they failed to detect it and had it subsequently pointed out by the faculty examiners (n=103/197). The students were more competent in detecting carious lesions (p≤0.001) than in detecting mucosal lesions. A significantly higher proportion of students who felt confident in detecting mucosal lesions were actually more competent in detecting the lesions than those who were not confident (p≤0.001). Further educational strategies are needed to motivate Kuwait University dental students to develop the knowledge, skills, and judgment necessary to integrate a complete intraoral examination into their routine practice.

  13. Oral mucosal status and major salivary gland function

    Energy Technology Data Exchange (ETDEWEB)

    Wolff, A.; Fox, P.C.; Ship, J.A.; Atkinson, J.C.; Macynski, A.A.; Baum, B.J. (National Institute of Dental Research, Bethesda, MD (USA))

    1990-07-01

    Normal salivary function is considered to be critical for the maintenance of healthy oral mucosa. However, few studies have examined mucosal changes in patients with objectively documented salivary gland performance. In the present report, the mucosal status of 298 subjects being evaluated in a dry mouth clinic was assessed. A complete oral examination was performed and unstimulated and stimulated salivary samples were collected separately from the parotid and submandibular/sublingual glands. Data were analyzed according to diagnosis and salivary output after the assignment of an oral mucosal rating to each subject. In general, the mucosal surfaces were well preserved and infections were not seen. Patients evaluated for Sjoegren's syndrome and radiation-induced xerostomia had the lowest salivary gland performance but displayed a mucosal status similar to denture-wearing healthy subjects or patients with normal salivary flow who had idiopathic xerostomia. However, those patients with a total lack of salivary flow rarely had normal-appearing oral mucosa. These results confirm a role for saliva in oral mucosal preservation and also suggest that other factors may act to maintain oral mucosal integrity.

  14. Impact of colonic mucosal lipoxin A4 synthesis capacity on healing in rats with dextran sodium sulfate-induced colitis.

    Science.gov (United States)

    Ağış, Erol R; Savaş, Berna; Melli, Mehmet

    2015-09-01

    Ulcerative colitis is a chronic inflammatory disease of the colon. This study evaluates the role of colonic mucosal lipoxin A4 (LXA4) synthesis in an experimental rat model of dextran sodium sulfate (DSS)-induced colitis. Wistar rats were randomly assigned to four groups: healthy controls, DSS-induced colitis with no or vehicle therapy, misoprostol or 5-aminosalicylic acid (5-ASA) therapy groups. Disease severity and colonic mucosal LXA4 synthesis was assessed specifically during the acute phase (day 5), chronic phase (day 15) and healing phases (day 19). Both misoprostol and 5-ASA reduced histopathologic score during the acute phase and reduced disease activity score at the healing phase. In addition, misoprostol reduced histopathologic score and colon weight/length ratio during the healing phase. Only misoprostol therapy increased colonic mucosal LXA4 synthesis. Furthermore, LXA4 levels correlated negatively with disease progression (R=-0.953). Collectively, our findings suggest that misoprostol-induced LXA4 synthesis may be favorable for the healing of ulcerative colitis.

  15. The impact of antioxidant and splanchnic-directed therapy on persistent uncorrected gastric mucosal pH in the critically injured trauma patient.

    Science.gov (United States)

    Barquist, E; Kirton, O; Windsor, J; Hudson-Civetta, J; Lynn, M; Herman, M; Civetta, J

    1998-02-01

    Critically ill trauma patients with gastric intramucosal acidosis, as measured by gastric tonometry, have an increased incidence of multiple organ dysfunction syndrome despite supranormal O2 delivery. We altered our resuscitation protocol to maximize splanchnic blood flow and decrease oxygen-derived free radical damage. Prospective clinical trial with historical controls. The protocol differed from control by including administration of folate, mannitol, and low-dose isoproterenol. All patients had gastric tonometers and pulmonary artery catheters. If the intramucosal pH (pHi) was less than 7.25, splanchnic-sparing inotropic and vasodilatory agents were used to optimize systemic cardiac output. Two groups of trauma patients with persistent intramucosal acidosis at 24 hours (pHi < 7.25) were compared: a control group (n = 7), and patients who received the splanchnic/antioxidant protocol (n = 13). The two groups were similar based on Acute Physiology and Chronic Health Evaluation II score, Injury Severity Score, age, cardiac index, oxygen delivery, and oxygen consumption. The "splanchnic therapy" group had fewer organ system failures as well as shortened length of intensive care unit and hospital stay. Three of 7 patients in the control group and 2 of 13 patients in the splanchnic therapy group had a final pHi < 7.25. Gastric tonometry-guided resuscitation and antioxidant/splanchnic therapy in critically ill trauma patients with persistent gastric mucosal acidosis may decrease multiple organ dysfunction syndrome.

  16. HIV infection and specific mucosal immunity: workshop 4B.

    Science.gov (United States)

    Challacombe, S J; Fidel, P L; Tugizov, S; Tao, L; Wahl, S M

    2011-04-01

    Most HIV infections are transmitted across mucosal epithelium. An area of fundamental importance is understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, which leads to increased susceptibility to bacterial, fungal, and viral infections of oral and other mucosae. This workshop attempted to address 5 basic issues-namely, HIV acquisition across mucosal surfaces, innate and adaptive immunity in HIV resistance, antiviral activity of breast milk as a model mucosal fluid, neutralizing immunoglobulin A antibodies against HIV, and progress toward a mucosal vaccine against HIV. The workshop attendants agreed that progress had been made in each area covered, with much recent information. However, these advances revealed how little work had been performed on stratified squamous epithelium compared with columnar epithelium, and the attendants identified several important biological questions that had not been addressed. It is increasingly clear that innate immunity has an important biological role, although basic understanding of the mechanisms of normal homeostasis is still being investigated. Application of the emerging knowledge was lacking with regard to homeostatic mucosal immunity to HIV and its role in changing this homeostasis. With regard to breast milk, a series of studies have demonstrated the differences between transmitters and nontransmitters, although whether these findings could be generalized to other secretions such as saliva was less clear. Important progress toward an oral mucosal HIV vaccine has been made, demonstrating proof of principle for administering vaccine candidates into oral lymphoid tissues to trigger anti-HIV local and systemic immune responses. Similarly, experimental data emphasized the central role of neutralizing antibodies to prevent HIV infection via mucosal routes.

  17. Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.

    Science.gov (United States)

    Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

    2012-11-01

    The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

  18. Prickly Pear Cactus (Opuntia ficus indica var. saboten) Protects Against Stress-Induced Acute Gastric Lesions in Rats

    Science.gov (United States)

    Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha

    2012-01-01

    Abstract The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague–Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800–1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production. PMID:23062184

  19. Neuropeptides control the dynamic behavior of airway mucosal dendritic cells.

    Science.gov (United States)

    Voedisch, Sabrina; Rochlitzer, Sabine; Veres, Tibor Z; Spies, Emma; Braun, Armin

    2012-01-01

    The airway mucosal epithelium is permanently exposed to airborne particles. A network of immune cells patrols at this interface to the environment. The interplay of immune cells is orchestrated by different mediators. In the current study we investigated the impact of neuronal signals on key functions of dendritic cells (DC). Using two-photon microscopic time-lapse analysis of living lung sections from CD11c-EYFP transgenic mice we studied the influence of neuropeptides on airway DC motility. Additionally, using a confocal microscopic approach, the phagocytotic capacity of CD11c(+) cells after neuropeptide stimulation was determined. Electrical field stimulation (EFS) leads to an unspecific release of neuropeptides from nerves. After EFS and treatment with the neuropeptides vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP), airway DC in living lung slices showed an altered motility. Furthermore, the EFS-mediated effect could partially be blocked by pre-treatment with the receptor antagonist CGRP(8-37). Additionally, the phagocytotic capacity of bone marrow-derived and whole lung CD11c(+) cells could be inhibited by neuropeptides CGRP, VIP, and Substance P. We then cross-linked these data with the in vivo situation by analyzing DC motility in two different OVA asthma models. Both in the acute and prolonged OVA asthma model altered neuropeptide amounts and DC motility in the airways could be measured. In summary, our data suggest that neuropeptides modulate key features motility and phagocytosis of mouse airway DC. Therefore altered neuropeptide levels in airways during allergic inflammation have impact on regulation of airway immune mechanisms and therefore might contribute to the pathophysiology of asthma.

  20. Comparison of atorvastatin 80 mg/day versus simvastatin 20 to 40 mg/day on frequency of cardiovascular events late (five years) after acute myocardial infarction (from the Incremental Decrease in End Points through Aggressive Lipid Lowering [IDEAL] trial)

    DEFF Research Database (Denmark)

    Pedersen, TR; Cater, Nilo B; Faergeman, Ole;

    2010-01-01

    Previous studies have demonstrated that benefits of intensive statin therapy compared to standard statin therapy begin shortly after an acute event and are continued up to 2 years of follow-up. However, whether efficacy and safety of intensive statin therapy in patients with a recent cardiac even...

  1. Suppressive effect of astaxanthin isolated from the Xanthophyllomyces dendrorhous mutant on ethanol-induced gastric mucosal injury in rats.

    Science.gov (United States)

    Kim, Jeong-Hwan; Choi, Seok-Keun; Choi, Sang-Yun; Kim, Han-Kyeom; Chang, Hyo-Ihl

    2005-07-01

    Ethanol has been found to induce ulcerative gastric lesion in humans. The present study investigated the in vivo protective effect of astaxanthin isolated from the Xanthophyllomyces dendrorhous mutant against ethanol-induced gastric mucosal injury in rats. The rats were treated with 80% ethanol for 3 d after pretreatment with two doses of astaxanthin (5 and 25 mg/kg of body weight respectively) for 3 d, while the control rats received only 80% ethanol for 3 d. The oral administration of astaxanthin (5 and 25 mg/kg of body weight) showed significant protection against ethanol-induced gastric lesion and inhibited elevation of the lipid peroxide level in gastric mucosa. In addition, pretreatment with astaxanthin resulted in a significant increase in the activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. A histologic examination clearly indicated that the acute gastric mucosal lesion induced by ethanol nearly disappeared after pretreatment with astaxanthin.

  2. 5-Fluorouracil induced intestinal mucositis via nuclear factor-κB activation by transcriptomic analysis and in vivo bioluminescence imaging.

    Directory of Open Access Journals (Sweden)

    Chung-Ta Chang

    Full Text Available 5-Fluorouracil (5-FU is a commonly used drug for the treatment of malignant cancers. However, approximately 80% of patients undergoing 5-FU treatment suffer from gastrointestinal mucositis. The aim of this report was to identify the drug target for the 5-FU-induced intestinal mucositis. 5-FU-induced intestinal mucositis was established by intraperitoneally administering mice with 100 mg/kg 5-FU. Network analysis of gene expression profile and bioluminescent imaging were applied to identify the critical molecule associated with 5-FU-induced mucositis. Our data showed that 5-FU induced inflammation in the small intestine, characterized by the increased intestinal wall thickness and crypt length, the decreased villus height, and the increased myeloperoxidase activity in tissues and proinflammatory cytokine production in sera. Network analysis of 5-FU-affected genes by transcriptomic tool showed that the expression of genes was regulated by nuclear factor-κB (NF-κB, and NF-κB was the central molecule in the 5-FU-regulated biological network. NF-κB activity was activated by 5-FU in the intestine, which was judged by in vivo bioluminescence imaging and immunohistochemical staining. However, 5-aminosalicylic acid (5-ASA inhibited 5-FU-induced NF-κB activation and proinflammatory cytokine production. Moreover, 5-FU-induced histological changes were improved by 5-ASA. In conclusion, our findings suggested that NF-κB was the critical molecule associated with the pathogenesis of 5-FU-induced mucositis, and inhibition of NF-κB activity ameliorated the mucosal damage caused by 5-FU.

  3. Grain-rich diets altered the colonic fermentation and mucosa-associated bacterial communities and induced mucosal injuries in goats.

    Science.gov (United States)

    Ye, Huimin; Liu, Junhua; Feng, Panfei; Zhu, Weiyun; Mao, Shengyong

    2016-02-04

    Remarkably little information is available about the impact of high-grain (HG) feeding on colonic mucosa-associated bacteria and mucosal morphology. In the present study, 12 male goats were randomly assigned to either a hay diet (n = 6) or an HG diet (65% grain; n = 6) to characterise the changes in the composition of the bacterial community in colonic mucosa and the mucosal morphology of the colon. The results showed that HG feeding decreased the colonic pH and increased the concentrations of total short chain fatty acids and lipopolysaccharides in colonic digesta. The principal coordinate analysis results showed that the HG diet altered the colonic mucosal bacterial communities, with an increase in the abundance of genus Blautia and a decrease in the abundance of genera Bacillus, Enterococcus, and Lactococcus. The HG-fed goats showed sloughing of the surface layer epithelium, intercellular tight junction erosion, cell mitochondrial damage, and upregulation of the relative mRNA expression of IL-2 and IFN-γ in colonic mucosa. Collectively, our data indicate that HG feeding induced changes in colonic mucosal morphology and cytokines expression that might be caused by excessive fermentation and dramatic shifts in the bacterial populations in the colon.

  4. Risk analysis, diagnosis and management of gastrointestinal mucositis in pediatric cancer patients

    NARCIS (Netherlands)

    Kuiken, Nicoline S. S.; Rings, Edmond H. H. M.; Tissing, Wim J. E.

    2015-01-01

    Mucositis is a complex inflammatory reaction of the mucous membranes of the alimentary tract upon chemotherapy and radiotherapy treatment in oncology patients. Mucositis can be subdivided in oral and gastrointestinal mucositis (GI mucositis). The damage to the gastrointestinal tract compromises the

  5. Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats

    Science.gov (United States)

    Gong, Jing; Hu, Meilin; Huang, Zhaoyi; Fang, Ke; Wang, Dingkun; Chen, Qingjie; Li, Jingbin; Yang, Desen; Zou, Xin; Xu, Lijun; Wang, Kaifu; Dong, Hui; Lu, Fuer

    2017-01-01

    Background: Intestinal mucosal barrier dysfunction plays an important role in the development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline alkaloid, is widely known to be effective for both DM and diarrhea. Here, we explored whether the anti-diabetic effect of BBR was related to the intestine mucosal barrier. Methods and Results: The rat model of T2DM was established by high glucose and fat diet feeding and intravenous injection of streptozocin. Then, those diabetic rats were treated with BBR at different concentrations for 9 weeks. The results showed, in addition to hyperglycemia and hyperlipidemia, diabetic rats were also characterized by proinflammatory intestinal changes, altered gut-derived hormones, and 2.77-fold increase in intestinal permeability. However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage. BBR treatment at a high concentration also decreased the intestinal permeability by 27.5% in diabetic rats. Furthermore, BBR regulated the expressions of the molecules involved in TLR4/MyD88/NF-κB signaling pathways in intestinal tissue of diabetic rats. Conclusion: The hypoglycemic effects of BBR might be related to the improvement in gut-derived hormones and the attenuation of intestinal mucosal mechanic and immune barrier damages. PMID:28217099

  6. Prognostic factors and epidemiological characteristics of cutaneous and mucosal head and neck melanoma.

    Science.gov (United States)

    Berzina, Anna; Azarjana, Kristine; Cema, Ingrida; Pjanova, Dace; Rivosh, Alexander

    2011-01-01

    OBJECTIVE. To describe the prognostic factors and epidemiological characteristics of cutaneous and mucosal head and neck melanoma and to identify the variables associated with mortality from this disease. MATERIAL AND METHODS. Patients treated for head and neck melanoma in the Oncology Centre of Latvia, Riga during a 10-year period were identified. Records from 124 cases were analyzed in a descriptive, retrospective study. For each patient, information regarding age, sex, tumor anatomic site, as well as ulceration, histological tumor subtypes, Breslow thickness and Clark invasion level was viewed. Disease specific survival rates were calculated. The frequencies of all study variables and their 95% confidence intervals were determined. Kaplan-Meier survival curves were produced to illustrate the survival differences for each variable. RESULTS. The patients' mean age was 67.36 years. The study included 81 females (65.32%) and 43 males (34.67%). The prevalent anatomical site for cutaneous head and neck melanoma was the cheek - 49% (n=55) and the intraocular site for mucosal melanoma (61.5%). A high percentage of thick cutaneous melanoma was detected. In 53 cases (47.3%) out of 112 cutaneous melanoma the tumor ulceration was found. Nodular melanoma subtype was predominating (38%). The incidence of cutaneous melanoma has increased unequally whereas mucosal melanoma of the head and neck is an uncommon cancer and the incidence rates in Latvia during a ten year period are decreasing. CONCLUSION. Female sex, advanced age, facial skin, tumor thickness, nodular subtype and ulceration carried a relevant risk of poor prognosis.

  7. HVEM signalling at mucosal barriers provides host defence against pathogenic bacteria.

    Science.gov (United States)

    Shui, Jr-Wen; Larange, Alexandre; Kim, Gisen; Vela, Jose Luis; Zahner, Sonja; Cheroutre, Hilde; Kronenberg, Mitchell

    2012-08-09

    The herpes virus entry mediator (HVEM), a member of the tumour-necrosis factor receptor family, has diverse functions, augmenting or inhibiting the immune response. HVEM was recently reported as a colitis risk locus in patients, and in a mouse model of colitis we demonstrated an anti-inflammatory role for HVEM, but its mechanism of action in the mucosal immune system was unknown. Here we report an important role for epithelial HVEM in innate mucosal defence against pathogenic bacteria. HVEM enhances immune responses by NF-κB-inducing kinase-dependent Stat3 activation, which promotes the epithelial expression of genes important for immunity. During intestinal Citrobacter rodentium infection, a mouse model for enteropathogenic Escherichia coli infection, Hvem−/− mice showed decreased Stat3 activation, impaired responses in the colon, higher bacterial burdens and increased mortality. We identified the immunoglobulin superfamily molecule CD160 (refs 7 and 8), expressed predominantly by innate-like intraepithelial lymphocytes, as the ligand engaging epithelial HVEM for host protection. Likewise, in pulmonary Streptococcus pneumoniae infection, HVEM is also required for host defence. Our results pinpoint HVEM as an important orchestrator of mucosal immunity, integrating signals from innate lymphocytes to induce optimal epithelial Stat3 activation, which indicates that targeting HVEM with agonists could improve host defence.

  8. Folate levels in mucosal tissue but not methylenetetrahydrofolate reductase polymorphisms are associated with gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Yu-Rong Weng; Dan-Feng Sun; Jing-Yuan Fang; Wei-Qi Gu; Hong-Yin Zhu

    2006-01-01

    AIM: To evaluate whether folate levels in mucosal tissue and some common methylenetetrahydrofolate reductase (MTHFR) variants are associated with the risk of gastric cancer through DNA methylation.METHODS: Real-time PCR was used to study the expression of tumor related genes in 76 mucosal tissue samples from 38 patients with gastric cancer. Samples from the gastroscopic biopsy tissues of 34 patients with chronic superficial gastritis (CSG) were used as controls.Folate concentrations in these tissues were detected by the FOL ACS: 180 automated chemiluminescence system.MTHFR polymorphisms were analyzed by PCR-RFLP, and the promoter methylation of tumor-related genes was determined by methylation-specific PCR (MSP).RESULTS: Folate concentrations were significantly higher in CSG than in cancerous tissues. Decreased expression and methylation of c-myc accompanied higher folate concentrations. Promoter hypermethylation and loss of p16INK4A in samples with MTHFR 677CC were more frequent than in samples with the 677TT or 677CT genotype. And the promoter hypermethylation and loss of p21WAF1 in samples with MTHFR 677CT were more frequent than when 677CC or 677TT was present. The 677CT genotype showed a non-significant higher risk for gastric cancer as compared with the 677CC genotype.CONCLUSION: Lower folate levels in gastric mucosal tissue may confer a higher risk of gastric carcinogenesis through hypomethylation and overexpression of c-myc.

  9. Buccal mucosal ulcer healing effect of rhEGF/Eudispert hv hydrogel.

    Science.gov (United States)

    Park, Jeong Sook; Yoon, Joon Il; Li, Hong; Moon, Dong Cheul; Han, Kun

    2003-08-01

    We have studied the effect of rhEGF on the buccal mucosal ulcer healing. rhEGF was rapidly degraded upon incubation with the hamster buccal mucosal homogenates; The degradation of rhEGF was significantly inhibited by sodium lauryl sulfate (SLS). Eudispert hv hydrogel and Polycarbophil 974P hydrogel were prepared for rhEGF delivery and their mucoadhesiveness was measured by the Instron method. The mucoadhesive force of Eudispert hv was significantly greater than that of Polycarbophil 974P. Moreover, rhEGF in Eudispert hv hydrogel remained stable for about 2 months. To evaluate the ulcer healing effect of rhEGF, the buccal mucosal ulcer was induced in golden hamsters using acetic acid. At 24 h after administration of rhEGF/Eudispert hv hydrogel, the ulcerous area was decreased compared with rhEGF solution and, as a result, the curative ratio was 36.8 +/- 5.68%. By the addition of SLS (0.5%) to Eudispert hv hydrogel, the curative ratio increased 1.5 times. The mechanism of the action was probably due to a combination of protection of the drug against proteases present in mucosa and prolongation of the release of rhEGF from the formulation at the site of action.

  10. IGF-I augments resection-induced mucosal hyperplasia by altering enterocyte kinetics.

    Science.gov (United States)

    Dahly, Elizabeth M; Guo, Ziwen; Ney, Denise M

    2003-10-01

    Our objective was to determine if exogenous insulin-like growth factor-I (IGF-I) augments the adaptive growth response to mid small bowel resection in association with changes in enterocyte kinetics. We determined structural adaptation and concomitant changes in enterocyte proliferation, apoptosis, and migration of the jejunum in growing, parenterally fed rats after mid small bowel resection or small bowel transection, and treatment with IGF-I or vehicle. IGF-I treatment in resected rats significantly increased jejunal mucosal mass by 20% and mucosal concentrations of protein and DNA by 36 and 33%, respectively, above the response to resection alone. The enhancement of resection-induced adaptive growth and cellularity by IGF-I reflected an increase in enterocyte proliferation, an expansion of the proliferative compartment in the crypt, and no further decrease in enterocyte apoptosis or increase in enterocyte migration beyond the effects of resection. The ability of IGF-I to augment the mucosal hyperplasia stimulated by the endogenous response to resection substantiates the role of IGF-I as an intestinal mitogen that promotes tissue regeneration.

  11. How can probiotics and prebiotics impact mucosal immunity?

    National Research Council Canada - National Science Library

    O'Flaherty, Sarah; Saulnier, Delphine; Pot, Bruno; Versalovic, James

    2010-01-01

    ...? These questions were part of a discussion entitled "How Can Probiotics and Prebiotics Impact Mucosal Immunity" at the 2009 annual meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP...

  12. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey

    DEFF Research Database (Denmark)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian

    2016-01-01

    melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins......Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral...... cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma...

  13. Mucosal environmental sensors in the pathogenesis of dry eye.

    Science.gov (United States)

    Pflugfelder, Stephen C; Stern, Michael E

    2014-09-01

    The 4th Cullen Symposium, held April 17 and 18, 2014, included expert researchers in mucosal immunity of the eye and other mucosal surfaces, particularly the gut. The theme of the meeting was environmental sensing mechanisms in mucosal tissues and their relevance for initiating ocular surface inflammation in dry eye. There are a number of shared features between the ocular surface and other mucosal surfaces, but distinct differences may exist in the type and distribution of mucins and microbiota. Mechanisms to regulate DC maturation and prevent tissue-damaging inflammation are shared among these sites. Epithelial and dendritic cells are key environmental sensors participating in initiation of innate and adaptive immune responses in response to a variety of environmental stresses.

  14. A DETAILED REVIEW ON ORAL MUCOSAL DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Radha Bhati

    2012-03-01

    Full Text Available Oral mucosal drug delivery system is widely applicable as novel site for administration of drug for immediate and controlled release action by preventing first pass metabolism and enzymatic degradation due to GI microbial flora. Oral mucosal drug delivery system provides local and systemic action. In this review, attention is focused to give regarding physiology of oral mucosal including tissue permeability, barriers to permeation and route of permeation, biopharmaceutics of buccal and sublingual absorption, factors affecting drug absorption, detailed information of penetration enhancers, design of oral mucosal drug delivery system and role of mucoadhesion and various theories of bioadhesion. Evaluation techniques and selection of animal model for in-vivo studies are also discussed.

  15. (CGRP) on gastric mucosal barrier in stress induced rats

    African Journals Online (AJOL)

    STORAGESEVER

    2009-04-20

    Apr 20, 2009 ... phospholipids (Kao et al., 1987), mucosal blood flow. (Stein, 1989 .... in blood vessels of tunica mucosa. A diffuse ... improve and there were signs of regeneration in lamina epitelialis ... The dilatation and edema of the vessels.

  16. Protective effect of histamine microinjected into cerebellar fastigial nucleus on stress gastric mucosal damage in rats.

    Science.gov (United States)

    Qiao, Xiao; Yang, Jun; Fei, Su-Juan; Zhu, Jin-Zhou; Zhu, Sheng-Ping; Liu, Zhang-Bo; Li, Ting-Ting; Zhang, Jian-Fu

    2015-12-10

    In the study, we investigated the effect of histamine microinjected into cerebellar fastigial nucleus (FN) on stress gastric mucosal damage (SGMD), and its mechanisms in rats. The model of SGMD was established by restraining and water (21±1°C)-immersion for 3h. The gastric mucosal damage index (GMDI) indicated the severity of gastric mucosal damage. Histamine or receptor antagonist was microinjected into the FN. The decussation of superior cerebellar peduncle (DSCP) and the lateral hypothalamic area (LHA) were destroyed, respectively. The pathological changes of gastric mucosa were evaluated using biological signal acquisition system, Laser-Doppler flowmeter, and western blotting. We found that the microinjection of histamine (0.05, 0.5, and 5μg) into FN significantly attenuated the SGMD, in a dose-dependent manner, whereas, the microinjection of histamine H2 receptor antagonist, ranitidine, and glutamic acid decarboxylase antagonist, 3-mercaptopropionic acid (3-MPA) exacerbated the SGMD. The protective effect of histamine on SGMD was abolished by electrical lesion of DSCP or chemical ablation of LHA. The microinjection of histamine decreased the discharge frequency of the greater splanchnic nerve, and the gastric mucosal blood flow was increased. In addition, the cellular proliferation was enhanced, but the cellular apoptosis was reduced in the gastric mucosa. Also the pro-apoptosis protein, Bax, and caspase-3 were down-regulated, and the anti-apoptosis protein, Bcl-2 was up-regulated following microinjection of histamine. In conclusion, the FN participated in the regulation of SGMD after histamine microinjected into FN, and cerebellar-hypothalamic circuits (include: DSCP, LHA) contribute to the process, which may provide a new therapeutic strategy for SGMD.

  17. Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection.

    Science.gov (United States)

    Leber, Andrew; Viladomiu, Monica; Hontecillas, Raquel; Abedi, Vida; Philipson, Casandra; Hoops, Stefan; Howard, Brad; Bassaganya-Riera, Josep

    2015-01-01

    Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17) effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg) cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions.

  18. Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes.

    Science.gov (United States)

    Wang, Xiaoting; Ota, Naruhisa; Manzanillo, Paolo; Kates, Lance; Zavala-Solorio, Jose; Eidenschenk, Celine; Zhang, Juan; Lesch, Justin; Lee, Wyne P; Ross, Jed; Diehl, Lauri; van Bruggen, Nicholas; Kolumam, Ganesh; Ouyang, Wenjun

    2014-10-09

    The connection between an altered gut microbiota and metabolic disorders such as obesity, diabetes, and cardiovascular disease is well established. Defects in preserving the integrity of the mucosal barriers can result in systemic endotoxaemia that contributes to chronic low-grade inflammation, which further promotes the development of metabolic syndrome. Interleukin (IL)-22 exerts essential roles in eliciting antimicrobial immunity and maintaining mucosal barrier integrity within the intestine. Here we investigate the connection between IL-22 and metabolic disorders. We find that the induction of IL-22 from innate lymphoid cells and CD4(+) T cells is impaired in obese mice under various immune challenges, especially in the colon during infection with Citrobacter rodentium. While innate lymphoid cell populations are largely intact in obese mice, the upregulation of IL-23, a cytokine upstream of IL-22, is compromised during the infection. Consequently, these mice are susceptible to C. rodentium infection, and both exogenous IL-22 and IL-23 are able to restore the mucosal host defence. Importantly, we further unveil unexpected functions of IL-22 in regulating metabolism. Mice deficient in IL-22 receptor and fed with high-fat diet are prone to developing metabolic disorders. Strikingly, administration of exogenous IL-22 in genetically obese leptin-receptor-deficient (db/db) mice and mice fed with high-fat diet reverses many of the metabolic symptoms, including hyperglycaemia and insulin resistance. IL-22 shows diverse metabolic benefits, as it improves insulin sensitivity, preserves gut mucosal barrier and endocrine functions, decreases endotoxaemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. In summary, we identify the IL-22 pathway as a novel target for therapeutic intervention in metabolic diseases.

  19. Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection.

    Directory of Open Access Journals (Sweden)

    Andrew Leber

    Full Text Available Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17 effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions.

  20. Shuidouchi (Fermented Soybean) Fermented in Different Vessels Attenuates HCl/Ethanol-Induced Gastric Mucosal Injury.

    Science.gov (United States)

    Suo, Huayi; Feng, Xia; Zhu, Kai; Wang, Cun; Zhao, Xin; Kan, Jianquan

    2015-11-02

    Shuidouchi (Natto) is a fermented soy product showing in vivo gastric injury preventive effects. The treatment effects of Shuidouchi fermented in different vessels on HCl/ethanol-induced gastric mucosal injury mice through their antioxidant effect was determined. Shuidouchi contained isoflavones (daidzein and genistein), and GVFS (glass vessel fermented Shuidouchi) had the highest isoflavone levels among Shuidouchi samples fermented in different vessels. After treatment with GVFS, the gastric mucosal injury was reduced as compared to the control mice. The gastric secretion volume (0.47 mL) and pH of gastric juice (3.1) of GVFS treated gastric mucosal injury mice were close to those of ranitidine-treated mice and normal mice. Shuidouchi could decrease serum motilin (MTL), gastrin (Gas) level and increase somatostatin (SS), vasoactive intestinal peptide (VIP) level, and GVFS showed the strongest effects. GVFS showed lower IL-6, IL-12, TNF-α and IFN-γ cytokine levels than other vessel fermented Shuidouchi samples, and these levels were higher than those of ranitidine-treated mice and normal mice. GVFS also had higher superoxide dismutase (SOD), nitric oxide (NO) and malonaldehyde (MDA) contents in gastric tissues than other Shuidouchi samples. Shuidouchi could raise IκB-α, EGF, EGFR, nNOS, eNOS, Mn-SOD, Gu/Zn-SOD, CAT mRNA expressions and reduce NF-κB, COX-2, iNOS expressions as compared to the control mice. GVFS showed the best treatment effects for gastric mucosal injuries, suggesting that glass vessels could be used for Shuidouchi fermentation in functional food manufacturing.

  1. Gut Dendritic Cell Activation Links an Altered Colonic Microbiome to Mucosal and Systemic T Cell Activation in Untreated HIV-1 infection

    Science.gov (United States)

    Dillon, SM; Lee, EJ; Kotter, CV; Austin, GL; Gianella, S; Siewe, B; Smith, DM; Landay, AL; McManus, MC; Robertson, CE; Frank, DN; McCarter, MD; Wilson, CC

    2015-01-01

    HIV-1-associated disruption of intestinal homeostasis is a major factor contributing to chronic immune activation and inflammation. Dendritic cells (DCs) are crucial in maintaining intestinal homeostasis, but the impact of HIV-1 infection on intestinal DC number and function has not been extensively studied. We compared the frequency and activation/maturation status of colonic myeloid DC (mDC) subsets (CD1c+ and CD1cneg) and plasmacytoid DCs in untreated HIV-1-infected subjects with uninfected controls. Colonic mDCs in HIV-1-infected subjects had increased CD40 but decreased CD83 expression, and CD40 expression on CD1c+ mDCs positively correlated with mucosal HIV-1 viral load, with mucosal and systemic cytokine production, and with frequencies of activated colon and blood T cells. Percent of CD83+CD1c+ mDCs negatively correlated with frequencies of IFN-γ-producing colon CD4+ and CD8+ T cells. CD40 expression on CD1c+ mDCs positively associated with abundance of high prevalence mucosal Prevotella copri and P. stercorea, but negatively associated with a number of low prevalence mucosal species including Rumminococcus bromii. CD1c+ mDC cytokine production was greater in response to in vitro stimulation with Prevotella species relative to R. bromii. These findings suggest that during HIV infection, colonic mDCs become activated upon exposure to mucosal pathobiont bacteria leading to mucosal and systemic immune activation. PMID:25921339

  2. Role of mucus in ischemia/reperfusion-induced gastric mucosal injury in rats.

    Science.gov (United States)

    Mojzis, J; Hegedüsová, R; Mirossay, L

    2000-01-01

    Gastric mucus plays an important role in gastric mucosal protection. Apart from its "barrier" function, it has been demonstrated that mucus protects gastric epithelial cells against toxic oxygen metabolites derived from the xanthine/ xanthine oxidase system. In this study, we investigated the effect of malotilate and sucralfate (mucus production stimulators) and N-acetylcysteine (mucolytic agent) on ischemia/reperfusion-induced gastric mucosal injury. Gastric ischemia was induced by 30 min clamping of the coeliac artery followed by 30 min of reperfusion. The mucus content was determined by the Alcian blue method. Sucralfate (100 mg/kg), malotilate (100 mg/kg), and N-acetylcysteine (100 mg/kg) were given orally 30 min before surgery. Both sucralfate and malotilate increased the mucus production in control rats. On the other hand, N-acetyloysteine significantly decreased mucus content in control (sham) group. A significant decrease of mucus content was found in the control and the N-acetylcysteine pretreated group during the period of ischemia. On the other hand, sucralfate and malotilate prevented the decrease the content of mucus during ischemia. A similar result can be seen after ischemia/reperfusion. In the control group and N-acetylcysteine pretreated group a significant decrease of adherent mucus content was found. However, sucralfate and malotilate increased mucus production (sucralfate significantly). Sucralfate and malotilate also significantly protected the gastric mucosa against ischemia/reperfusion-induced injury. However, N-acetylcysteine significantly increased gastric mucosal injury after ischemia/reperfusion. These results suggest that gastric mucus may be involved in the protection of gastric mucosa after ischemia/reperfusion.

  3. MUCOSAL MALIGNANT MELANOMA OF NASOPHARYNX: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Chandrasekhar

    2015-06-01

    Full Text Available Primary mucosal malignant melanomas of sinonasal tract are uncommon tumors comprising 0.3-2% of all malignant melanomas and 4% of all head and Neck melanomas. We are reporting a rare case of mucosal malignant melanoma in a 45 year old female arising from nasopharynx which was excised completely by trans palatal approach followed by irradiation. This case is being reported because of its isolated involvement of nasopharynx, and early age of presentation.

  4. Limitations in assessment of mucosal healing in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2010-01-01

    An emerging parameter to define the effectiveness of new therapeutic agents in clinical trials,and by extension,for use in day-to-day clinical practice has been labeled mucosal healing.It has been hypothesized that complete healing of the intestinal mucosa in inflammatory bowel diseases should result in reduced disease complications,reduced hospitalization and reduced surgical treatment.By implication,the natural history of inflammatory bowel disease might then be altered. Measurement of mucosal healing,how...

  5. Mucosal Inflammatory Response to Salmonella Typhimurium Infection

    Directory of Open Access Journals (Sweden)

    Samir ePatel

    2014-07-01

    Full Text Available The human intestinal epithelium consists of a single layer of epithelial cells that forms a barrier against food antigens and the resident microbiota within the lumen. This delicately balanced organ functions in a highly sophisticated manner to uphold the fidelity of the intestinal epithelium and to eliminate disease-causing microorganisms. On the luminal side, this barrier is fortified by a thick mucus layer, and on the serosal side exists the lamina propria containing a resident population of immune cells. Pathogens that are able to breach this barrier disrupt the healthy epithelial lining by interfering with the regulatory mechanisms that govern the normal balance of intestinal architecture and function. This disruption results in a coordinated innate immune response deployed to eliminate the intruder that includes the release of antimicrobial peptides, activation of pattern recognition receptors, and recruitment of a variety of immune cells. In the case of Salmonella enterica serovar Typhimurium (S. Typhimurium infection, induction of an inflammatory response has been linked to its virulence mechanism, the type III secretion system (T3SS. The T3SS secretes protein effectors that exploit the host’s cell biology to facilitate bacterial entry and intracellular survival, and to modulate the host immune response. As the role of the intestinal epithelium in initiating an immune response has been increasingly realized, this review will highlight recent research that details progress made in understanding mechanisms underlying the mucosal inflammatory response to Salmonella infection, and how such inflammatory responses impact pathogenic fitness of this organism.

  6. [New routes of administration: epidermal, transcutaneous mucosal ways of vaccination].

    Science.gov (United States)

    Denis, François; Alain, Sophie; Ploy, Marie-Cécile

    2007-04-01

    A successful vaccine triggers the interaction of various cells of the immune system as does a regular immune response. It is thus necessary to introduce the vaccine antigens into an anatomic site where they will contact immune cells. The route of administration is thus critical for the outcome of vaccination. Intramuscular or subcutaneous injections are the most popular. Antigens injected intramuscularly can form persistent precipitates that are dissolved and re-absorbed relatively slowly. If injecting antigens is a quick, easy and reproducible way to vaccination, it requires trained personnel. Alternatives exist, through non-invasive formulations which allow administration by the patient or a third party with no particular expertise. The skin, especially its epidermal layer, is an accessible and competent immune environment and an attractive target for vaccine delivery, through transcutaneous delivery or immunostimulant patches. Mucosal immunization is another strategy: its major rationale is that organisms invade the body via mucosal surfaces. Therefore, local protection at mucosal surface as well as systemic defense is beneficial. Various formulations of mucosal vaccines have been developed, such as the Sabin oral polio vaccine (OPV), rotavirus vaccines, cold-adapted influenza vaccines or vaccine against typhoid fever. Thus we are entering in an era where mucosal and transcutaneous immunisation will play an important role in disease management. However, it has not been so easy to obtain regulatory approval for mucosal or transcutaneous formulations and needle-based vaccines continue to dominate the market.

  7. Differential Apoptosis in Mucosal and Dermal Wound Healing

    Science.gov (United States)

    Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann

    2014-01-01

    Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; pwound healing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing. PMID:25493209

  8. Using Light to Treat Mucositis and Help Wounds Heal

    Science.gov (United States)

    Ignatius, Robert W.; Martin, Todd S.; Kirk, Charles

    2008-01-01

    A continuing program of research and development is focusing on the use of controlled illumination by light-emitting diodes (LEDs) to treat mucositis and to accelerate healing of wounds. The basic idea is to illuminate the affected area of a patient with light of an intensity, duration, and wavelength (or combination of wavelengths) chosen to produce a therapeutic effect while generating only a minimal amount of heat. This method of treatment was originally intended for treating the mucositis that is a common complication of chemotherapy and radiation therapy for cancer. It is now also under consideration as a means to accelerate the healing of wounds and possibly also to treat exposure to chemical and radioactive warfare agents. Radiation therapy and many chemotherapeutic drugs often damage the mucosal linings of the mouth and gastrointestinal tract, leading to mouth ulcers (oral mucositis), nausea, and diarrhea. Hyperbaric-oxygen therapy is currently the standard of care for ischemic, hypoxic, infected, and otherwise slowlyhealing problem wounds, including those of oral mucositis. Hyperbaric-oxygen therapy increases such cellular activities as collagen production and angiogenesis, leading to an increased rate of healing. Biostimulation by use of laser light has also been found to be effective in treating mucositis. For hyperbaricoxygen treatment, a patient must remain inside a hyperbaric chamber for an extended time. Laser treatment is limited by laser-wavelength capabilities and by narrowness of laser beams, and usually entails the generation of significant amounts of heat.

  9. Alterations of intestinal immune function and regulatory effects of L-arginine in experimental severe acute pancreatitis rats

    Institute of Scientific and Technical Information of China (English)

    Shi-Feng Qiao; Tian-Jing Lü; Jia-Bang Sun; Fei Li

    2005-01-01

    AIM: To discuss the changes of intestinal mucosal immune function in rats with experimental severe acute pancreatitis(SAP) and the regulatory effect of L-arginine.METHODS: Male adult Wistar rats were randomly divided into pancreatitis group, sham-operation group, and L-arginine treatment group. Animals were killed at 24, 48, and 72 h after SAP models were developed and specimens were harvested. Endotoxin concentration in portal vein was determined by limulus endotoxin analysis kit. CD3+, CD4+,CD8+ T lymphocytes in intestinal mucosal lamina propria were examined by immunohistochemistry. Secretory immunoglobulin A (SIgA) in cecum feces was examined by radioimmunoassay.RESULTS: Compared to the control group, plasma endotoxin concentration in the portal vein increased, percentage of CD3+ and CD4+ T lymphocyte subsets in the end of intestinal mucosal lamina propria reduced significantly,CD4+/CD8+ ratio decreased, and SIgA concentrations in cecum feces reduced at 24, 48, and 72 h after SAP developed. Compared to SAP group, the L-arginine treatment group had a lower level of plasma endotoxin concentration in the portal vein, a higher CD3+ and CD4+ T lymphocyte percentage in the end of intestinal mucosal lamina propria,an increased ratio of CD4+/CD8+ and a higher SIgA concentration in cecum feces.CONCLUSION: Intestinal immune suppression occurs in the early stage of SAP rats, which may be the main reason for bacterial and endotoxin translocation. L-arginine can improve the intestinal immunity and reduce bacterial and endotoxin translocation in SAP rats.

  10. Comparison of systemic and mucosal immunization with helper-dependent adenoviruses for vaccination against mucosal challenge with SHIV.

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    Eric A Weaver

    Full Text Available Most HIV-1 infections are thought to occur at mucosal surfaces during sexual contact. It has been hypothesized that vaccines delivered at mucosal surfaces may mediate better protection against HIV-1 than vaccines that are delivered systemically. To test this, rhesus macaques were vaccinated by intramuscular (i.m. or intravaginal (ivag. routes with helper-dependent adenoviral (HD-Ad vectors expressing HIV-1 envelope. Macaques were first immunized intranasally with species C Ad serotype 5 (Ad5 prior to serotype-switching with species C HD-Ad6, Ad1, Ad5, and Ad2 vectors expressing env followed by rectal challenge with CCR5-tropic SHIV-SF162P3. Vaccination by the systemic route generated stronger systemic CD8 T cell responses in PBMC, but weaker mucosal responses. Conversely, mucosal immunization generated stronger CD4 T cell central memory (Tcm responses in the colon. Intramuscular immunization generated higher levels of env-binding antibodies, but neither produced neutralizing or cytotoxic antibodies. After mucosal SHIV challenge, both groups controlled SHIV better than control animals. However, more animals in the ivag. group had lower viral set points than in in the i.m. group. These data suggest mucosal vaccination may have improve protection against sexually-transmitted HIV. These data also demonstrate that helper-dependent Ad vaccines can mediate robust vaccine responses in the face of prior immunity to Ad5 and during four rounds of adenovirus vaccination.

  11. Clotrimazole nanoparticle gel for mucosal administration

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Elisabetta, E-mail: ese@unife.it [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Ravani, Laura [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Contado, Catia [Department of Chemistry, University of Ferrara, Ferrara (Italy); Costenaro, Andrea [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Drechsler, Markus [Macromolecular Chemistry II, University of Bayreuth (Germany); Rossi, Damiano [Department of Biology and Evolution, LT Terra and Acqua Tech UR7, University of Ferrara, Ferrara (Italy); Menegatti, Enea [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Grandini, Alessandro [Department of Biology and Evolution, LT Terra and Acqua Tech UR7, University of Ferrara, Ferrara (Italy); Cortesi, Rita [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy)

    2013-01-01

    In this study a formulation suitable to be applied on oral and/or vaginal mucosa has been developed for the treatment of fungal infections. The aim of the research is a comparison between clotrimazole (CLO) containing semisolid formulations based on monoolein aqueous dispersion (MAD) or nanostructured lipid carrier (NLC). MAD and NLC have been characterized in terms of morphology and dimensional distribution by cryogenic Transmission Electron Microscopy (cryo-TEM) and Photon Correlation Spectroscopy (PCS). CLO was encapsulated with high entrapment efficiency both in MAD and in NLC, according to Sedimentation Field Flow Fractionation (SdFFF) combined with HPLC. CLO recovery in MAD and NLC has been investigated by time. In order to obtain formulations with suitable viscosity for mucosal application, MAD was diluted with a carbomer gel, while NLC was directly viscosized by the addition of poloxamer 407 in the dispersion. The rheological properties of MAD and NLC after viscosizing have been investigated. Franz cell has been employed to study CLO diffusion from the different vehicles, evidencing diffusion rates from MAD and NLC superimposable to that obtained using Canesten{sup Registered-Sign }. An anticandidal activity study demonstrated that both CLO-MAD and CLO-NLC were more active against Candida albicans with respect to the pure drug. Highlights: Black-Right-Pointing-Pointer Comparison between monoolein aqueous dispersion (MAD) and nanostructured lipid carrier (NLC). Black-Right-Pointing-Pointer Clotrimazole (CLO) encapsulated with high entrapment efficiency both in MAD and in NLC. Black-Right-Pointing-Pointer The solid matrix of NLC controls CLO degradation better than MAD. Black-Right-Pointing-Pointer CLO containing MAD and NLC exhibits a higher anticandidal activity than the free drug. Black-Right-Pointing-Pointer Simple production of CLO-NLC based poloxamer gel, suitable for industry scaling up.

  12. Effects of omeprazole and eradication of Helicobacter pylori on gastric and duodenal mucosal enzyme activities and DNA in duodenal ulcer patients.

    Science.gov (United States)

    Vetvik, K; Schrumpf, E; Mowinckel, P; Aase, S; Andersen, K J

    1994-11-01

    Duodenal and gastric content of mucosal enzymes in duodenal ulcer (DU) patients differs from that of controls. The purpose of this study has been to examine the effect of omeprazole and eradication of Helicobacter pylori on mucosal enzymes in DU patients. The enzyme activities of seven gastric and duodenal mucosal marker enzymes from the brush border, lysosomes, and mitochondria have been studied. In study I the measurements were made in 29 patients with an active DU before and after 14 days of omeprazole treatment. In study II 22 duodenal ulcer patients were given bismuth subnitrate, oxytetracycline, and metronidazole (triple therapy) for 2 weeks to eradicate H. pylori. Biopsy specimens were taken from the duodenum and the stomach for enzyme measurements and histologic assessment. In study II additional specimens were obtained from the prepyloric region for urease tests and culture of H. pylori. The ulcer healing rates were more than 90% after both omeprazole and triple therapy. H. pylori was eradicated in 86% after triple therapy. The activities of the brush-border enzymes lactase, neutral-alpha-glucosidase, alkaline phosphatase, leucyl-beta-naphthylamidase, and gamma-glutamyltransferase (gamma-GT) increased significantly in the duodenal bulb and the descending duodenum during treatment with omeprazole. No changes in duodenal enzyme activity were detected after triple therapy, whereas a significant fall in gamma-GT and acid phosphatase activities was seen in the stomach. The mucosal DNA in the gastric antrum decreased both after treatment with omeprazole and after triple therapy. A similar decrease in mucosal DNA of the gastric antrum was demonstrated after both omeprazole and triple therapy with bismuth subnitrate, oxytetracycline, and metronidazole. Omeprazole also affects the content of duodenal mucosal enzymes, whereas triple therapy particularly affects the gastric mucosal enzyme activity.

  13. Protein profiles in mucosal and systemic compartments in response to Vibrio cholerae in a mouse pulmonary infection model.

    Science.gov (United States)

    Kang, Seok-Seong; Baik, Jung Eun; Yang, Jae Seung; Cho, Kun; Yun, Cheol-Heui; Han, Seung Hyun

    2015-09-01

    We have recently shown that a mouse lung infection model resulting in acute pneumonia could be used for evaluating the protective immunity induced by mucosal vaccines against Vibrio cholerae. In order to gain insight and better understanding of the pathogenicity of V. cholerae infection, we identified and compared proteins induced by V. cholerae in nasal washes, bronchoalveolar lavages (BAL), and sera. Intranasal administration of V. cholerae increased the concentration of total proteins in nasal washes and BAL fluids, but not in sera. LTQ-Orbitrap hybrid Fourier transform mass spectrometry showed that cytoskeletal proteins, protease inhibitors and anti-inflammatory mediators were present in nasal washes from uninfected mice. The distinctly expressed proteins in nasal washes in response to V. cholerae mainly consisted of protease inhibitors, anti-inflammatory proteins, and anti-microbial proteins. A number of protease inhibitors and anti-inflammatory proteins were selectively expressed in BAL fluids from V. cholerae-infected mice, while cytoskeletal proteins and heat shock proteins were mainly observed in BAL fluids from uninfected mice. A large number of serum complements, protease inhibitors, and acute phase proteins were expressed in V. cholerae-infected mice. Collectively, these results suggest that intranasal administration of V. cholerae leading to acute pneumonia elicited alterations of protein profiles associated with immune homeostasis and host protection in both the mucosal and systemic compartments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Acute duodenal Crohn's disease successfully managed with low-speed elemental diet infusion via nasogastric tube: A case report

    Institute of Scientific and Technical Information of China (English)

    Takayuki Yamamoto; Maki Nakahigashi; Satoru Umegae; Tatsushi Kitagawa; Koichi Matsumoto

    2006-01-01

    Duodenal Crohn's disease is rare, and patients without obstruction are treated medically. We herein report one case whose duodenal Crohn's disease was successfully managed with low-speed elemental diet infusion through a nasogastric tube. A 28-year-old female developed acute duodenal Crohn's disease. Upper GI radiologic and endoscopic examinations showed a stricture in the duodenal bulb. Using the duodenal biopsy specimens,mucosal cytokine levels were measured; interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α levels were remarkably elevated. For initial 2 wk, powdered mesalazine was orally given but it was not effective. For the next 2 wk, she was treated with low-speed elemental diet therapy using a commercially available ElentalTM,which was infused continuously through a nasogastric tube using an infusion pump. The tip of the nasogastric tube was placed at an immediate oral side of the pylorus.The infusion speed was 10 mL/h (usual speed, 100 mL/h).After the 2-wk treatment, her symptoms were very much improved, and endoscopically, the duodenal stricture and inflammation improved. The duodenal mucosal cytokine levels remarkably decreased compared with those before the treatment. Although our experience was limited, lowspeed elemental diet infusion through a nasogastric tube may be a useful treatment for acute duodenal Crohn's disease.

  15. Sphingosine Kinase-1-Dependent and -Independent Inhibitory Effects of Zanthoxyli Fructus to Attenuate the Activation of Mucosal Mast Cells and Ameliorate Food Allergies in Mice

    Directory of Open Access Journals (Sweden)

    Xiaoyu Wang

    2012-01-01

    Full Text Available Food allergy (FA is relatively a common disease in infants, but effective drug therapies are not yet available. Notably, mucosal mast cells, but not connective-tissue mast cells, play important roles in food allergic reactions via the release of inflammatory mediators. Therefore, we screened medicinal herb extracts for in vitro and in vivo antiallergic activity through inhibiting mucosal mast cell activation. As a result, both antigen-induced and calcium ionophore-induced degranulation was significantly inhibited by Zanthoxyli Fructus water extract (ZF in mucosal-type murine bone marrow-derived mast cells (mBMMCs. ZF suppressed the antigen-induced [Ca2+] elevation and the antigen-enhanced mRNA expression of TNF-α, IL-4, and IL-13. The transcriptome and real-time PCR analyses revealed that ZF greatly decreased the antigen-enhanced expression level of sphingosine kinase 1 (Sphk1, which plays a key role in the FcεRI-mediated immune responses in mast cells. Furthermore, ZF inhibited allergic symptoms in an ovalbumin-caused murine FA model and decreased the number of infiltrating mucosal mast cells and the enhanced mRNA expression levels of IL-4 and Sphk1 in the FA mice colons. These results indicate that ZF suppresses mucosal mast cell activities mainly through Sphk1-dependent mechanism, and ZF is utilized for the development of a novel, potent anti-FA agent.

  16. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies

    Science.gov (United States)

    Cheeseman, Hannah M.; Olejniczak, Natalia J.; Rogers, Paul M.; Evans, Abbey B.; King, Deborah F. L.; Ziprin, Paul; Liao, Hua-Xin; Haynes, Barton F.

    2016-01-01

    tissue have not been defined. While bnAbs are highly effective against cell-free virus, they are not induced by current vaccine candidates. However, nnAbs, readily induced by vaccines, can trigger antibody-dependent cellular effector functions, through engagement of their Fc-gamma receptors. Fc-mediated antiviral activity has been implicated as a secondary correlate of decreased HIV-1 risk in the RV144 vaccine efficacy trial, suggesting that protection might be mediated in the absence of classical neutralization. To aid vaccine design and selection of antibodies for use in passive protection strategies, we assessed a range of bnAbs and nnAbs for their potential to block ex vivo challenge of mucosal tissues. Our data clearly indicate the superior efficacy of neutralizing antibodies in preventing mucosal acquisition of infection. These results underscore the importance of maintaining the central focus of HIV-1 vaccine research on the induction of potently neutralizing antibodies. PMID:27795431

  17. Intrauterine Growth Restriction Impairs Small Intestinal Mucosal Immunity in Neonatal Piglets.

    Science.gov (United States)

    Dong, Li; Zhong, Xiang; Ahmad, Hussain; Li, Wei; Wang, Yuanxiao; Zhang, Lili; Wang, Tian

    2014-07-01

    Intrauterine growth restriction (IUGR) is a very common problem in both piglet and human neonate populations. We hypothesized that IUGR neonates have impaired intestinal mucosal immunity from birth. Using neonatal piglets as IUGR models, immune organ weights, the weight and length of the small intestine (SI), intestinal morphology, intraepithelial immune cell numbers, levels of cytokines and immunoglobulins, and the relative gene expression of cytokines in the SI were investigated. IUGR neonatal piglets were observed to have lower absolute immune organ weight and SI length, decreased relative weights of the thymus, spleen, mesenteric lymph node, and thinner but longer SIs. Damaged and jagged villi, shorter microvilli, presence of autophagosomes, swelled mitochondria, and decreased villus surface areas were also found in the SIs of IUGR neonatal piglets. We also found a smaller number of epithelial goblet cells and lymphocytes in the SIs of IUGR neonates. In addition, we detected reduced levels of the cytokines TNF-α and IFN-γ and decreased gene expression of cytokines in IUGR neonates. In conclusion, IUGR was shown to impair the mucosal immunity of the SI in neonatal piglets, and the ileum was the major site of impairment.

  18. Prospective small bowel mucosal assessment immediately after chemoradiotherapy of unresectable locally advanced pancreatic cancer using capsule endoscopy: a case series.

    Science.gov (United States)

    Yamashina, Takeshi; Takada, Ryoji; Uedo, Noriya; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Ioka, Tatsuya; Ishihara, Ryu; Teshima, Teruki; Nishiyama, Kinji; Iishi, Hiroyasu

    2016-01-01

    In this case series, three consecutive patients with unresectable locally advanced pancreatic cancer (ULAPC) underwent capsule endoscopy (CE) before and after chemoradiotherapy (CRT) to evaluate duodenal and jejunal mucosa, and to examine the relationship between CE findings and dose distribution. CE after CRT showed duodenitis and proximal jejunitis in all three patients. The most inflamed region was the third part of the duodenum, and in dose distribution, this was the closest region to the center of irradiation. This case series shows that CE can safely diagnose acute duodenitis and proximal jejunitis caused by CRT for ULAPC, and that dose distribution is possible to predict the degree of duodenal and jejunal mucosal injuries.

  19. Homeostatic regulation of Salmonella-induced mucosal inflammation and injury by IL-23.

    Directory of Open Access Journals (Sweden)

    Muyiwa Awoniyi

    Full Text Available IL-12 and IL-23 regulate innate and adaptive immunity to microbial pathogens through influencing the expression of IFN-γ, IL-17, and IL-22. Herein we define the roles of IL-12 and IL-23 in regulating host resistance and intestinal inflammation during acute Salmonella infection. We find that IL-23 alone is dispensable for protection against systemic spread of bacteria, but synergizes with IL-12 for optimal protection. IL-12 promotes the production of IFN-γ by NK cells, which is required for resistance against Salmonella and also for induction of intestinal inflammation and epithelial injury. In contrast, IL-23 controls the severity of inflammation by inhibiting IL-12A expression, reducing IFN-γ and preventing excessive mucosal injury. Our studies demonstrate that IL-23 is a homeostatic regulator of IL-12-dependent, IFN-γ-mediated intestinal inflammation.

  20. Therapeutic effect of ghrelin in the course of cerulein-induced acute pancreatitis in rats.

    Science.gov (United States)

    Warzecha, Z; Ceranowicz, P; Dembinski, A; Cieszkowski, J; Kusnierz-Cabala, B; Tomaszewska, R; Kuwahara, A; Kato, I

    2010-08-01

    Recent studies have shown that pretreatment with ghrelin exhibits protective effect in the gut. Administration of ghrelin reduces gastric mucosal damage, as well as inhibits the development of experimental pancreatitis. However, this protective effect requires administration of ghrelin before gastric or pancreatic damage and thus has a limited clinical value. The aim of present study was to assess the influence of ghrelin administered after development of acute pancreatitis on the course of this disease. Acute pancreatitis was induced by cerulein. Ghrelin was administered twice a day for 1, 2, 4, 6 or 9 days at the dose of 4, 8 or 16 nmol/kg/dose. The first dose of ghrelin was given 24 hours after last injection of cerulein. The severity of acute pancreatitis was assessed between 0 h and 10 days after cessation of cerulein administration. Administration of caerulein led to the development of acute edematous pancreatitis and maximal severity of this disease was observed 24 hours after induction of pancreatitis. Treatment with ghrelin reduced morphological signs of pancreatic damage such as pancreatic edema, leukocyte infiltration and vacuolization of acinar cells, and led to earlier regeneration of the pancreas. Also biochemical indexes of the severity of acute pancreatitis, serum activity of lipase and amylase were significantly reduced in animals treated with ghrelin. These effects were accompanied by an increase in the pancreatic DNA synthesis and a decrease in serum level of pro-inflammatory interleukin-1b. Administration of ghrelin improved pancreatic blood flow in rats with acute pancreatitis. We conclude that: (1) treatment with ghrelin exhibits therapeutic effect in caerulein-induced experimental acute pancreatitis; (2) this effect is related, at least in part, to the improvement of pancreatic blood flow, reduction in proinflammatory interleukin-1beta and stimulation of pancreatic cell proliferation.

  1. Cannabinoid HU210 protects isolated rat stomach against impairment caused by serum of rats with experimental acute pancreatitis.

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    Ming-hua Cao

    Full Text Available Acute pancreatitis (AP, especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alterations in the pathogenesis of AGML. In addition, we explored the intervention effects of cannabinoid receptor agonist HU210 and antagonist AM251 on isolated and serum-perfused rat stomach. Our results showed that the AGML occurred after 5 h of AP replication, and the body homeostasis was disturbed in AP rat, with increased levels of pancreatic enzymes, lipopolysaccharide (LPS, proinflammtory cytokines and chemokines in the blood, and an imbalance of the gastric secretion function. Perfusing the isolated rat stomach with the AP rat serum caused morphological changes in the stomach, accompanied with a significant increment of pepsin and [H+] release, and increased gastrin and decreased somatostatin secretion. HU210 reversed the AP-serum-induced rat pathological alterations, including the reversal of transformation of the gastric morphology to certain degree. The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis.

  2. Cannabinoid HU210 Protects Isolated Rat Stomach against Impairment Caused by Serum of Rats with Experimental Acute Pancreatitis

    Science.gov (United States)

    Cao, Ming-hua; Li, Yong-yu; Xu, Jing; Feng, Ya-jing; Lin, Xu-hong; Li, Kun; Han, Tong; Chen, Chang-Jie

    2012-01-01

    Acute pancreatitis (AP), especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML) which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alterations in the pathogenesis of AGML. In addition, we explored the intervention effects of cannabinoid receptor agonist HU210 and antagonist AM251 on isolated and serum-perfused rat stomach. Our results showed that the AGML occurred after 5 h of AP replication, and the body homeostasis was disturbed in AP rat, with increased levels of pancreatic enzymes, lipopolysaccharide (LPS), proinflammtory cytokines and chemokines in the blood, and an imbalance of the gastric secretion function. Perfusing the isolated rat stomach with the AP rat serum caused morphological changes in the stomach, accompanied with a significant increment of pepsin and [H+] release, and increased gastrin and decreased somatostatin secretion. HU210 reversed the AP-serum-induced rat pathological alterations, including the reversal of transformation of the gastric morphology to certain degree. The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis. PMID:23285225

  3. IFN-γ Hinders Recovery from Mucosal Inflammation during Antibiotic Therapy for Salmonella Gut Infection.

    Science.gov (United States)

    Dolowschiak, Tamas; Mueller, Anna Angelika; Pisan, Lynn Joanna; Feigelman, Rounak; Felmy, Boas; Sellin, Mikael Erik; Namineni, Sukumar; Nguyen, Bidong Dinh; Wotzka, Sandra Yvonne; Heikenwalder, Mathias; von Mering, Christian; Mueller, Christoph; Hardt, Wolf-Dietrich

    2016-08-10

    Salmonella Typhimurium (S.Tm) causes acute enteropathy resolving after 4-7 days. Strikingly, antibiotic therapy does not accelerate disease resolution. We screened for factors blocking remission using a S.Tm enterocolitis model. The antibiotic ciprofloxacin clears pathogen stool loads within 3-24 hr, while gut pathology resolves more slowly (ψ50: ∼48 hr, remission: 6-9 days). This delayed resolution is mediated by an interferon-γ (IFN-γ)-dependent response that is triggered during acute infection and continues throughout therapy. Specifically, IFN-γ production by mucosal T and NK cells retards disease resolution by maintaining signaling through the transcriptional regulator STAT1 and boosting expression of inflammatory mediators like IL-1β, TNF, and iNOS. Additionally, sustained IFN-γ fosters phagocyte accumulation and hampers antimicrobial defense mediated by IL-22 and the lectin REGIIIβ. These findings reveal a role for IFN-γ in delaying resolution of intestinal inflammation and may inform therapies for acute Salmonella enteropathy, chronic inflammatory bowel diseases, or disease resolution during antibiotic treatment.

  4. The association between cytokines and intestinal mucosal immunity among broilers fed on diets supplemented with fluorine.

    Science.gov (United States)

    Luo, Qin; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Liu, Juan; Wu, Bangyuan; Deng, Yubing

    2013-05-01

    Fluorine (F) bioaccumulation has been reported in the organs and tissues of organisms, including intestine. The intestinal mucosa is very important to the immune development. Meanwhile, cytokines are present in the normal intestinal mucosal and play an important role in the immune function. Thus, changes of the cytokine contents are related to the state of intestinal mucosal immunity. In this study, we investigated the changes in contents of cytokines such as interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interferon gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) induced by dietary high F in the mucosa of different parts of intestines (duodenum, jejunum, and ileum) by enzyme-linked immunosorbent assay. A total of 280 one-day-old healthy avian broilers were randomly divided into four groups and fed on a corn-soybean basal diet as control diet (F 22.6 mg/kg) or the same basal diet supplemented with 400, 800, and 1,200 mg F/kg (high F groups I, II, and III) in the form of sodium fluoride for 42 days. The experimental data showed that the contents of IL-2, IL-4, IL-6, IFN-γ, and TNF-α in the intestinal mucosa were significantly decreased in the high F groups II and III when compared with those of the control group from 14 to 42 days of age. It was concluded that dietary F in the range of 800-1,200 mg/kg significantly reduced the contents of aforementioned cytokines in the intestinal mucosa of broilers, which could impact the function of intestinal mucosal immunity through the pathways that decreased the lymphocyte population and/or lymphocyte activation.

  5. Effects of aging on apoptosis gene expression in oral mucosal tissues.

    Science.gov (United States)

    Gonzalez, Octavio A; Novak, M John; Kirakodu, Sreenatha; Stromberg, Arnold J; Shen, Shu; Orraca, Luis; Gonzalez-Martinez, Janis; Ebersole, Jeffrey L

    2013-03-01

    Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti-inflammatory effects that benefits the mucosa. The oral cavity presents a model of host-bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues. This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model. Macaca mulatta primates from 2 to 23 years of age (n = 23) were used in a cross-sectional study to obtain clinical healthy gingival tissues specimens. Further, mRNA was prepared and evaluated using the Affymetrix Rhesus GeneChip and 88 apoptotic pathway genes were evaluated. The results identified significant positive correlations with age in 12 genes and negative correlations with an additional five genes. The gene effects were predicted to alter apoptosis receptor levels, extrinsic apoptotic pathways through caspases, cytokine effects on apoptotic events, Ca(+2)-induced death signaling, cell cycle checkpoints, and potential effects of survival factors. Both the positively and negatively correlated genes within the apoptotic pathways provided evidence that healthy tissues in aging animals exhibit decreased apoptotic potential compared to younger animals. The results suggested that decreased physiologic apoptotic process in the dynamic septic environment of the oral mucosal tissues could increase the risk of aging tissues to undergo destructive disease processes through dysregulated inflammatory responses to the oral microbial burden.

  6. Effects of feminine hygiene products on the vaginal mucosal biome

    Directory of Open Access Journals (Sweden)

    Raina N. Fichorova

    2013-02-01

    Full Text Available Background: Over-the-counter (OTC feminine hygiene products come with little warning about possible side effects. This study evaluates in-vitro their effects on Lactobacillus crispatus, which is dominant in the normal vaginal microbiota and helps maintain a healthy mucosal barrier essential for normal reproductive function and prevention of sexually transmitted infections and gynecologic cancer. Methods: A feminine moisturizer (Vagisil, personal lubricant, and douche were purchased OTC. A topical spermicide (nonoxynol-9 known to alter the vaginal immune barrier was used as a control. L. crispatus was incubated with each product for 2 and 24h and then seeded on agar for colony forming units (CFU. Human vaginal epithelial cells were exposed to products in the presence or absence of L. crispatus for 24h, followed by epithelium-associated CFU enumeration. Interleukin-8 was immunoassayed and ANOVA was used for statistical evaluation. Results: Nonoxynol-9 and Vagisil suppressed Lactobacillus growth at 2h and killed all bacteria at 24h. The lubricant decreased bacterial growth insignificantly at 2h but killed all at 24h. The douche did not have a significant effect. At full strength, all products suppressed epithelial viability and all, except the douche, suppressed epithelial-associated CFU. When applied at non-toxic dose in the absence of bacteria, the douche and moisturizer induced an increase of IL-8, suggesting a potential to initiate inflammatory reaction. In the presence of L. crispatus, the proinflammatory effects of the douche and moisturizer were countered, and IL-8 production was inhibited in the presence of the other products. Conclusion: Some OTC vaginal products may be harmful to L. crispatus and alter the vaginal immune environment. Illustrated through these results, L. crispatus is essential in the preservation of the function of vaginal epithelial cells in the presence of some feminine hygiene products. More research should be invested

  7. Oral ingestion of Streptococcus thermophilus does not affect mucositis severity or tumor progression in the tumor-bearing rat.

    Science.gov (United States)

    Tooley, Katie L; Howarth, Gordon S; Lymn, Kerry A; Lawrence, Andrew; Butler, Ross N

    2011-07-15

    Preventative or adjunctive agents for the amelioration of small intestinal chemotherapy-induced mucositis are not currently available for clinical use. We have previously demonstrated that oral ingestion of Streptococcus thermophilus (TH-4) partially attenuated chemotherapy-induced mucositis in the rat. Here we assess the effects of TH-4 on small intestinal damage and tumor progression in tumor-bearing rats with experimentally-induced mucositis. Female Dark Agouti tumor-bearing (mammary adenocarcinoma) rats (n = 36; 139 ± 1 g) had small intestinal damage induced via the administration of methotrexate (MTX). Rats were administered MTX; (1.5 mg/kg intramuscular) or saline at 0 and 24 h; with daily gavage administration of TH-4 (109 cfu/mL) or skim milk from -48 to +96 h post-MTX. Rats were allocated to groups (n=9): saline control, TH-4 control, MTX control or TH-4+MTX. The non-invasive ( 13) C-sucrose breath test (SBT) was conducted prior to tumor inoculation, pre-MTX (-24 h) and prior to sacrifice (96 h) to monitor gut function. At sacrifice small intestinal segments were excised and assessed for sucrase and myeloperoxidase activity as well as histological damage. Irrespective of TH-4 treatment, MTX-treated rats had a significant decrease in bodyweight, SBT levels, sucrase and myeloperoxidase activity, and histological damage score (p 0.05) but failed to alleviate mucositis indices. Although TH-4, at a dose of 109 cfu/mL, yielded neither protection nor amelioration of chemotherapy-induced mucositis, progression of mammary adenocarcinoma was unaffected.

  8. Local glutathione redox status does not regulate ileal mucosal growth after massive small bowel resection in rats.

    Science.gov (United States)

    Tian, Junqiang; Washizawa, Naohiro; Gu, Li H; Levin, Marc S; Wang, Lihua; Rubin, Deborah C; Mwangi, Simon; Srinivasan, Shanthi; Jones, Dean P; Ziegler, Thomas R

    2007-02-01

    Glutathione (GSH) concentration affects cell proliferation and apoptosis in intestinal and other cell lines in vitro. However, in vivo data on gut mucosal GSH redox status and cell turnover are limited. We investigated the effect of altered GSH redox status on the ileal mucosa in a rat model of short bowel syndrome following massive small bowel resection (SBR). Rats underwent 80% mid-jejunoileal resection (RX) or small bowel transection (TX; as operative controls), with administration of either saline or D, L-buthionine-sulfoximine (BSO), a specific inhibitor of cellular GSH synthesis. Ileal mucosal redox, morphology, and indices of cell proliferation and apoptosis were determined at different days after surgery. Ileal GSH redox status was assessed by GSH and GSH disulfide (GSSG) concentrations and the redox potential of GSH/GSSG (Eh). Ileal lipid peroxidation [free malondialdehyde (MDA)] was measured as an index of lipid peroxidation. BSO markedly decreased ileal mucosal GSH, oxidized GSH/GSSG Eh, and increased MDA content without inducing morphological damage as assessed by light or electron microscopy. As expected, SBR stimulated adaptive growth of ileal villus height and total mucosal height at 7 d after surgery, but this response was unaffected by BSO treatment despite a modest increase in crypt cell apoptosis. Ileal cell proliferation (crypt cell bromodeoxyuridine incorporation) increased at 2 d after SBR but was unaffected by BSO. Collectively, our in vivo data show that marked depletion of ileal GSH and oxidation of the GSH redox pool does not alter indices of ileal epithelial proliferation or SBR-induced ileal mucosal adaptive growth.

  9. Oral mucosal alterations among the institutionalized elderly in Brazil

    Directory of Open Access Journals (Sweden)

    Raquel Conceição Ferreira

    2010-09-01

    Full Text Available This study determined the prevalence of oral mucosal alterations and associated factors among the institutionalized elderly in Brazil. Data were collected through a structured questionnaire, a review of their medical records and an intra-oral examination. A sample of 335 individuals over 60 years of age was randomly selected. In total, 646 alterations were diagnosed; 59.1% were variations of the normal oral mucosa. The most frequent variation consisted of sublingual varicosities (51.6%. Denture stomatitis (15.2% and denture hyperplasia (12.8% were the most frequent lesions. Elderly patients who wore dentures had a significantly higher prevalence of oral mucosal lesions (p = 0.00 than those that didn't wear dentures. There was a high prevalence of variations of the normal oral mucosa and of mucosal lesions, especially denture-induced lesions, among the institutionalized elderly.

  10. Mucosal immunity in the gut: the non-vertebrate perspective.

    Science.gov (United States)

    Garcia-Garcia, Erick; Galindo-Villegas, Jorge; Mulero, Victor

    2013-01-01

    Much is now known about the vertebrate mechanisms involved in mucosal immunity, and the requirement of commensal microbiota at mucosal surfaces for the proper functioning of the immune system. In comparison, very little is known about the mechanisms of immunity at the barrier epithelia of non-vertebrate organisms. The purpose of this review is to summarize key experimental evidence illustrating how non-vertebrate immune mechanisms at barrier epithelia compare to those of higher vertebrates, using the gut as a model organ. Not only effector mechanisms of gut immunity are similar between vertebrates and non-vertebrates, but it also seems that the proper functioning of non-vertebrate gut defense mechanisms requires the presence of a resident microbiota. As more information becomes available, it will be possible to obtain a more accurate picture of how mucosal immunity has evolved, and how it adapts to the organisms' life styles.

  11. Potential Benefits of Oral Cryotherapy for Chemotherapy-Induced Mucositis.

    Science.gov (United States)

    Wodzinski, Amelia

    2016-10-01

    Mucositis is a common side effect of cancer therapies that causes painful, erythematous lesions to develop in the gastrointestinal tract. These lesions can lead to malnutrition, increased risk for serious infection, prolonged hospital stays, and reduced quality of life. Oral cryotherapy, or the use of ice chips to cool the mucous membranes during bolus chemotherapy infusions (e.g., 5-fluorouracil [Adrucil®] and melphalan [Alkeran®]), is the most readily accessible and cost-effective intervention available. Although many factors may contribute to the development of mucositis during cancer treatment, studies have found a reduction in the incidence and the severity of mucositis with the use of oral cryotherapy.


  12. Peptic ulcer pathophysiology: acid, bicarbonate, and mucosal function

    DEFF Research Database (Denmark)

    Højgaard, L; Mertz Nielsen, A; Rune, S J

    1996-01-01

    The previously accepted role of gastric acid hypersecretion in peptic ulcer disease has been modified by studies showing no correlation between acid output and clinical outcome of ulcer disease, or between ulcer recurrence rate after vagotomy and preoperative acid secretion. At the same time......, studies have been unable to demonstrate increased acidity in the duodenal bulb in patients with duodenal ulcer, and consequently more emphasis has been given to the mucosal protecting mechanisms. The existence of an active gastric and duodenal mucosal bicarbonate secretion creates a pH gradient from...... cell removal and repair regulated by epidermal growth factor. Sufficient mucosal blood flow, including a normal acid/base balance, is important for subepithelial protection. In today's model of ulcer pathogenesis, gastric acid and H. pylori work in concert as aggressive factors, with the open question...

  13. DNA damage, apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Ling-Fei He; Jian-Gang Chen

    2006-01-01

    AIM: To study the effect of fluoride on oxidativestress,DNA damage and apoptosis as well as cell cycle of rat oral mucosal cells and hepatocytes.METHODS: Ten male SD rats weighing 80~120 g were randomly divided into control group and fluoride group,5 animals each group. The animals in fluoride group had free access to deionized water containing 150 mg/L sodium fluoride (NaF). The animals in control group were given distilled water. Four weeks later, the animals were killed. Reactive oxygen species (ROS) in oral mucosa and liver were measured by Fenton reaction, lipid peroxidation product, malondialdehyde (MDA), was detected by thiobarbituric acid (TBA) reaction, reduced glutathione (GSH) was assayed by dithionitrobenzoic acid (DTNB)reaction. DNA damage in oral mucosal cells and hepatocytes was determined by single cell gel (SCG) electrophoresis or comet assay. Apoptosis and cell cycle in oral mucosal cells and hepatocytes were detected by flow cytometry.RESULTS: The contents of ROS and MDA in oral mucosa and liver tissue of fluoride group were significantly higher than those of control group (P<0.01), but the level of GSH was markedly decreased (P<0.01). The contents of ROS, MDA and GSH were (134.73±12.63) U/mg protein,(1.48±0.13) mmol/mg protein and (76.38±6.71) mmol/mg protein in oral mucosa respectively, and (143.45±11.76) U/mg protein, (1.44±0.12) mmol/mg protein and (78.83±7.72) mmol/mg protein in liver tissue respectively. The DNA damage rate in fluoride group was 50.20%in oral mucosal cells and 44.80% in hepatocytes, higher than those in the control group (P<0.01). The apoptosis rate in oral mucosal cells was (13.63±1.81) % in fluoride group, and (12.76±1.67) % in hepatocytes,higher than those in control group. Excess fluoride could differently lower the number of oral mucosal cells and hepatocytes at G0/G1 and S G2/M phases (P<0.05).CONCLUSION: Excess fluoride can induce oxidative stress and DNA damage and lead to apoptosis and cell cycle

  14. Oral cryotherapy reduced oral mucositis in patients having cancer treatments.

    Science.gov (United States)

    Spivakovsky, Sylvia

    2016-09-01

    Data sourcesCochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CANCERLIT, CINAHL, the US National Institutes of Health Trials Registry and the WHO Clinical Trials Registry Platform.Study selectionRandomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment compared to usual care, no treatment or other interventions to prevent mucositis. The primary outcome was incidence of mucositis and its severity.Data extraction and synthesisTwo reviewers carried out study assessment and data extraction independently. Treatment effect for continuous data was calculated using mean values and standard deviations and expressed as mean difference (MD) and 95% confidence interval. Risk ratio (RR) was calculated for dichotomous data. Meta-analysis was performed.ResultsFourteen studies with 1280 participants were included. Subgroup analysis was undertaken according to the main cancer treatment type. Cryotherapy reduced the risk of developing mucositis by 39% (RR = 0.61; 95%CI, 0.52 to 0.72) on patients treated with fluorouracil (5FU). For melphalan-based treatment the risk of developing mucositis was reduced by 41% (RR =0.59; 95%CI, 0.35 to 1.01). Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, numbness/taste disturbance and tooth pain. This appears to contribute to the high rates of compliance seen in the included studies.ConclusionsThere is confidence that oral cryotherapy leads to a large reduction in oral mucositis in adults treated with 5FU. Although there is less certainty on the size of the reduction on patients treated with melphalan, it is certain there is reduction of severe mucositis.

  15. Mucosal biofilm communities in the human intestinal tract.

    Science.gov (United States)

    Macfarlane, Sandra; Bahrami, Bahram; Macfarlane, George T

    2011-01-01

    Complex and highly variable site-dependent bacterial ecosystems exist throughout the length of the human gastrointestinal tract. Until relatively recently, the majority of our information on intestinal microbiotas has come from studies on feces, or from aspirates taken from the upper gut. However, there is evidence showing that mucosal bacteria growing in biofilms on surfaces lining the gut differ from luminal populations, and that due to their proximity to the epithelial surface, these organisms may be important in modulating the host's immune system and contributing to some chronic inflammatory diseases. Over the past decade, increasing interest in mucosal bacteria, coupled with advances in molecular approaches for assessing microbial diversity, has begun to provide some insight into the complexity of these mucosa-associated communities. In gastrointestinal conditions such as inflammatory bowel diseases (ulcerative colitis, Crohn's disease), it has been shown that a dysbiosis exists in microbial community structure, and that there is a reduction in putatively protective mucosal organisms such as bifidobacteria. Therefore, manipulation of mucosal communities may be beneficial in restoring normal functionality in the gut, thereby improving the immune status and general health of the host. Biofilm structure and function has been studied intensively in the oral cavity, and as a consequence, mucosal communities in the mouth will not be covered in this chapter. This review addresses our current knowledge of mucosal populations in the gastrointestinal tract, changes that can occur in community structure in disease, and therapeutic modulation of biofilm composition by antibiotics, prebiotics, and probiotics. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100-Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

    NARCIS (Netherlands)

    Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

    2013-01-01

    Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery

  17. Low lactase activity in a small-bowel biopsy specimen : Should dietary lactose intake be restricted in children with small intestinal mucosal damage?

    NARCIS (Netherlands)

    Koetse, HA; Vonk, RJ; Gonera-de Jong, GBC; Priebe, MG; Antoine, JM; Stellaard, F; Sauer, PJJ

    2006-01-01

    Objective. Small intestinal mucosal damage can result in decreased lactase activity (LA). When LA is low in a small-bowel biopsy (SBB) specimen, a reduction of dietary lactose intake is usually advised. This is often done by reducing dietary dairy products, which also reduces the intake of calcium,

  18. Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice

    Science.gov (United States)

    Onuma, Wakana; Tomono, Susumu; Miyamoto, Shinngo; Fujii, Gen; Hamoya, Takahiro; Fujimoto, Kyoko; Miyoshi, Noriyuki; Fukai, Fumio; Wakabayashi, Keiji; Mutoh, Michihiro

    2016-01-01

    This study aimed to identify gastric mucosal protectants that suppress intestinal tumorigenesis in a mouse model. We chose six gastric mucosal protectants (ecabet sodium hydrate, irsogladine maleate, rebamipide, sofalcone, teprenone and troxipide) and examined their effects on the activity of oxidative stress-related transcriptional factors, including AP-1, NF-jB, NRF2, p53 and STAT3, in Caco-2 cells using a luciferase reporter gene assay. Among the six protectants, irsogladine maleate clearly inhibited NF-jB and AP-1 transcriptional activity. Furthermore, the chemopreventive property of irsogladine maleate was examined in a Min mouse model of familial adenomatous polyposis. Treatment with irsogladine maleate at doses of 5 and 50 ppm significantly reduced the number of intestinal polyps to 69% and 66% of the untreated control value, respectively. In these polyps, mRNA levels of the downstream targets of NF-jB, such as IL-1β and IL-6, were decreased by irsogladine maleate treatment. Moreover, the levels of oxidative stress-related markers, reactive carbonyl species, in the livers of Min mice were clearly decreased following the administration of irsogladine maleate. This study demonstrated that irsogladine maleate suppresses intestinal polyp formation in Min mice partly through the NF-jB signaling pathway, thus reducing oxidative stress. PMID:26840084

  19. Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice.

    Science.gov (United States)

    Onuma, Wakana; Tomono, Susumu; Miyamoto, Shinngo; Fujii, Gen; Hamoya, Takahiro; Fujimoto, Kyoko; Miyoshi, Noriyuki; Fukai, Fumio; Wakabayashi, Keiji; Mutoh, Michihiro

    2016-02-23

    This study aimed to identify gastric mucosal protectants that suppress intestinal tumorigenesis in a mouse model. We chose six gastric mucosal protectants (ecabet sodium hydrate, irsogladine maleate, rebamipide, sofalcone, teprenone and troxipide) and examined their effects on the activity of oxidative stress-related transcriptional factors, including AP-1, NF-jB, NRF2, p53 and STAT3, in Caco-2 cells using a luciferase reporter gene assay. Among the six protectants, irsogladine maleate clearly inhibited NF-jB and AP-1 transcriptional activity. Furthermore, the chemopreventive property of irsogladine maleate was examined in a Min mouse model of familial adenomatous polyposis. Treatment with irsogladine maleate at doses of 5 and 50 ppm significantly reduced the number of intestinal polyps to 69% and 66% of the untreated control value, respectively. In these polyps, mRNA levels of the downstream targets of NF-jB, such as IL-1β and IL-6, were decreased by irsogladine maleate treatment. Moreover, the levels of oxidative stress-related markers, reactive carbonyl species, in the livers of Min mice were clearly decreased following the administration of irsogladine maleate. This study demonstrated that irsogladine maleate suppresses intestinal polyp formation in Min mice partly through the NF-jB signaling pathway, thus reducing oxidative stress.

  20. The pleiotropic role of vitamin A in regulating mucosal immunity.

    Science.gov (United States)

    Sirisinha, Stitaya

    2015-06-01

    The effect of vitamin A on mucosal immunity has never been subjected to extensive studies until recently. We started to work in this area in the early 1970s when we observed that children with protein-calorie malnutrition (PCM) often had defective mucosal immunity, judging from the incidence of respiratory tract infections and diarrhea. We reported that these children had depressed secretory IgA (sIgA) levels in their nasal wash fluids. The IgA level in specimens collected from those superimposed with some degrees of vitamin A deficiency state appeared to be more severely affected. In order to better understand the underlying mechanism associated with this condition, we started to study more detail the deficiency state using experimental vitamin A-deficient rats. From a series of experiments using this animal model, we proposed that vitamin A was needed for transport and/or secretion of sIgA across the mucosa. This conclusion was based on the observation that the secretory component of sIgA synthesized by the epithelial cells of these vitamin A deficient animals was adversely affected as compared to the control animals. From that time onward, much progress has been made by several other groups showing that other mechanisms could also influence the integrity and immune function of the mucosa. For instance, recent studies demonstrated that retinoic acid which is a biologically active form of vitamin A has an essential role in mucosal homeostasis, controlling tolerance and immunity in these non-lymphoid tissues. Such a conclusion was made possible by the availability of sophisticated new molecular biology and genetic engineering techniques together with advances in the field of immunoregulation, e.g., the discovery of dendritic cells (DCs) and T helper cell subsets in 1980s, and the role of Toll-like receptors (TLRs) together with other innate immune regulators in controlling adaptive immune response in the early 1990s. These advances provided considerable new

  1. Polymer nanomicelles for efficient mucus delivery and antigen-specific high mucosal immunity.

    Science.gov (United States)

    Noh, Young-Woock; Hong, Ji Hyun; Shim, Sang-Mu; Park, Hye Sun; Bae, Hee Ho; Ryu, Eun Kyoung; Hwang, Jung Hwan; Lee, Chul-Ho; Cho, Seong Hun; Sung, Moon-Hee; Poo, Haryoung; Lim, Yong Taik

    2013-07-22

    Micelles for mucosal immunity: A mucosal vaccine system based on γ-PGA nanomicelles and viral antigens was synthesized. The intranasal administration of the vaccine system induces a high immune response both in the humoral and cellular immunity (see picture).

  2. Mucosal delivery routes for optimal immunization: targeting immunity to the right tissues.

    Science.gov (United States)

    Czerkinsky, C; Holmgren, J

    2012-01-01

    The mucosal immune system exhibits a high degree of anatomic compartmentalization related to the migratory patterns of lymphocytes activated at different mucosal sites. The selective localization of mucosal lymphocytes to specific tissues is governed by cellular "homing" and chemokine receptors in conjunction with tissue-specific addressins and epithelial cell-derived chemokines that are differentially expressed in "effector" tissues. The compartmentalization of mucosal immune responses imposes constraints on the selection of vaccine administration route. Traditional routes of mucosal immunization include oral and nasal routes. Other routes for inducing mucosal immunity include the rectal, vaginal, sublingual, and transcutaneous routes. Sublingual administration is a new approach that results in induction of mucosal and systemic T cell and antibody responses with an exceptionally broad dissemination to different mucosae, including the gastrointestinal and respiratory tracts, and the genital mucosa. Here, we discuss how sublingual and different routes of immunization can be used to generate immune responses in the desired mucosal tissue(s).

  3. The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Ibrahim IAA

    2015-12-01

    Full Text Available Ibrahim Abdel Aziz Ibrahim,1 Mahmood Ameen Abdulla,2 Maryam Hajrezaie,2 Ammar Bader,3 Naiyer Shahzad,1 Saeed S Al-Ghamdi,1 Ahmad S Gushash,4 Mohadeseh Hasanpourghadi5 1Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 4College of Arts and Science in Baljurashi, Albaha University, Baljurashi, Saudi Arabia; 5Cell Biology and Drug Discovery Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Abstract: Monolluma quadrangula (Forssk. Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid–Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the

  4. Preventing and Therapeutic Effect of Propolis in Radiotherapy Induced Mucositis of Head and Neck Cancers: A Triple-Blind, Randomized, Placebo-Controlled Trial

    Science.gov (United States)

    Javadzadeh Bolouri, Abbas; Pakfetrat, Atessa; Tonkaboni, Arghavan; Aledavood, Seyed Amir; Fathi Najafi, Mohsen; Delavarian, Zahra; Shakeri, Mohammad Taghi; Mohtashami, Azade

    2015-01-01

    Background: Mucositis is one of the acute complications of radiotherapy which can ulcerate oral mucosa and cause severe pain and discomfort which can affect oral normal function. Propolis is a natural source of flavenoid which has antiulcer, antibacterial, antifungal, healing and anti-inflammatory effects. Using such an affordable compound without any bad smell or taste that has reasonable price can help the radiotherapy undergoing patients. Objectives: Our goal is assessing the preventing and therapeutic effect of propolis in radiotherapy induced mucositis in patients with head and neck cancer. Patients and Methods: In a randomized triple blind clinical trial, 20 patient were selected randomly to swish and swallow 15 ml of water based extract of propolis mouth wash 3 times a day in the case group (n = 10) and 15 ml placebo mouth wash in control group (n = 10). we use NIC-CTC scale for determining mucositis grading. Results: We use T-test, Man-Whitney, Chi-square, and Friedman as analyzing tests. Case group had significantly (P 0.05). Conclusions: This is a pilot study which shows water based extract of propolis efficiently prevents and heals radiotherapy induced mucositis. PMID:26634113

  5. Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain

    Directory of Open Access Journals (Sweden)

    Shim Byoung-Shik

    2012-09-01

    Full Text Available Abstract Background Sublingual (s.l. administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle. In this study we examined whether s.l. immunization with rADV encoding spike protein (S (rADV-S of severe acute respiratory syndrome-associated coronavirus (SARS-CoV induces protective immunity against SARS-CoV and could serve as a safe mucosal route for delivery of rADV. Results Here, we show that s.l. administration of rADV-S induced serum SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses are comparable to those induced by intranasal (i.n. administration. In addition, s.l. immunization induced antigen-specific CD8+ T cell responses in the lungs that are superior to those induced by intramuscular immunization. Importantly, unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV vector to the olfactory bulb. Conclusion Our study indicates that s.l. immunization with rADV-S is safe and effective in induction of a broad spectrum of immune responses and presumably protection against infection with SARS-CoV.

  6. Regeneration of Vocal Fold Mucosa Using Tissue-Engineered Structures with Oral Mucosal Cells.

    Directory of Open Access Journals (Sweden)

    Mioko Fukahori

    Full Text Available Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells.Animal experiment using eight beagles (including three controls.A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed.A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site.The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds.

  7. Acute pancreatitis

    Science.gov (United States)

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... pancreatitis; Pancreas - inflammation Images Digestive system Endocrine glands Pancreatitis, acute - CT scan Pancreatitis - series References Forsmark CE. Pancreatitis. ...

  8. Cystitis - acute

    Science.gov (United States)

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  9. The Mucosal Immune System and Its Regulation by Autophagy.

    Science.gov (United States)

    Kabat, Agnieszka M; Pott, Johanna; Maloy, Kevin J

    2016-01-01

    The gastrointestinal tract presents a unique challenge to the mucosal immune system, which has to constantly monitor the vast surface for the presence of pathogens, while at the same time maintaining tolerance to beneficial or innocuous antigens. In the intestinal mucosa, specialized innate and adaptive immune components participate in directing appropriate immune responses toward these diverse challenges. Recent studies provide compelling evidence that the process of autophagy influences several aspects of mucosal immune responses. Initially described as a "self-eating" survival pathway that enables nutrient recycling during starvation, autophagy has now been connected to multiple cellular responses, including several aspects of immunity. Initial links between autophagy and host immunity came from the observations that autophagy can target intracellular bacteria for degradation. However, subsequent studies indicated that autophagy plays a much broader role in immune responses, as it can impact antigen processing, thymic selection, lymphocyte homeostasis, and the regulation of immunoglobulin and cytokine secretion. In this review, we provide a comprehensive overview of mucosal immune cells and discuss how autophagy influences many aspects of their physiology and function. We focus on cell type-specific roles of autophagy in the gut, with a particular emphasis on the effects of autophagy on the intestinal T cell compartment. We also provide a perspective on how manipulation of autophagy may potentially be used to treat mucosal inflammatory disorders.

  10. Live bacterial delivery systems for development of mucosal vaccines

    NARCIS (Netherlands)

    Thole, J.E.R.; Dalen, P.J. van; Havenith, C.E.G.; Pouwels, P.H.; Seegers, J.F.M.L.; Tielen, F.D.; Zee, M.D. van der; Zegers, N.D.; Shaw, M.

    2000-01-01

    By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed

  11. Mucosal damage and neutropenia are required for Candida albicans dissemination.

    Directory of Open Access Journals (Sweden)

    Andrew Y Koh

    2008-02-01

    Full Text Available Candida albicans fungemia in cancer patients is thought to develop from initial gastrointestinal (GI colonization with subsequent translocation into the bloodstream after administration of chemotherapy. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but we have hypothesized that both neutropenia and GI mucosal damage are critical for allowing widespread invasive C. albicans disease. We investigated these parameters in a mouse model of C. albicans GI colonization that led to systemic spread after administration of immunosuppression and mucosal damage. After depleting resident GI intestinal flora with antibiotic treatment and achieving stable GI colonization levels of C. albicans, it was determined that systemic chemotherapy with cyclophosphamide led to 100% mortality, whereas selective neutrophil depletion, macrophage depletion, lymphopenia or GI mucosal disruption alone resulted in no mortality. Selective neutrophil depletion combined with GI mucosal disruption led to disseminated fungal infection and 100% mortality ensued. GI translocation and dissemination by C. albicans was also dependent on the organism's ability to transform from the yeast to the hyphal form. This mouse model of GI colonization and fungemia is useful for studying factors of innate host immunity needed to prevent invasive C. albicans disease as well as identifying virulence factors that are necessary for fungal GI colonization and dissemination. The model may also prove valuable for evaluating therapies to control C. albicans infections.

  12. Live bacterial delivery systems for development of mucosal vaccines

    NARCIS (Netherlands)

    Thole, J.E.R.; Dalen, P.J. van; Havenith, C.E.G.; Pouwels, P.H.; Seegers, J.F.M.L.; Tielen, F.D.; Zee, M.D. van der; Zegers, N.D.; Shaw, M.

    2000-01-01

    By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed

  13. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey.

    Science.gov (United States)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian; Drzewiecki, Krzysztof T; Prause, Jan U; Heegaard, Steffen

    2016-06-01

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma).

  14. Management of oral mucositis in patients with cancer.

    NARCIS (Netherlands)

    Stone, R.; Fliedner, M.C.; Smiet, A.C.M.

    2005-01-01

    Oral mucositis (OM) is a distressing toxic effect of chemotherapy and radiotherapy. It can