HIV enteropathy and aging: gastrointestinal immunity, mucosal epithelial barrier, and microbial translocation.

Science.gov (United States)

Wang, Hongyin; Kotler, Donald P

2014-07-01

Despite decreases in morbidity and mortality as a result of antiretroviral therapy, gastrointestinal dysfunction remains common in HIV infection. Treated patients are at risk for complications of 'premature' aging, such as cardiovascular disease, osteopenia, neurocognitive decline, malignancies, and frailty. This review summarizes recent observations in this field. Mucosal CD4 lymphocytes, especially Th17 cells, are depleted in acute HIV and simian immune deficiency virus (SIV) infections, although other cell types also are affected. Reconstitution during therapy often is incomplete, especially in mucosa. Mucosal barrier function is affected by both HIV infection and aging and includes paracellular transport via tight junctions and uptake through areas of apoptosis; other factors may affect systemic antigen exposure. The resultant microbial translocation is associated with systemic immune activation in HIV and SIV infections. There is evidence of immune activation and microbial translocation in the elderly. The immune phenotypes of immunosenescence in HIV infection and aging appear similar. There are several targets for intervention; blockage of residual mucosal virus replication, preventing antigen uptake, modulating the microbiome, improving T cell recovery, combining therapies aimed at mucosal integrity, augmenting mucosal immunity, and managing traditional risk factors for premature aging in the general population. Aging may interact with HIV enteropathy to enhance microbial translocation and immune activation.

Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

Science.gov (United States)

Leung, Felix W

2008-07-04

This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral

Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy

International Nuclear Information System (INIS)

Dean, Jamie A.; Wong, Kee H.; Gay, Hiram; Welsh, Liam C.; Jones, Ann-Britt; Schick, Ulrike; Oh, Jung Hun; Apte, Aditya; Newbold, Kate L.; Bhide, Shreerang A.; Harrington, Kevin J.; Deasy, Joseph O.; Nutting, Christopher M.; Gulliford, Sarah L.

2016-01-01

Purpose: Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue–sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. Methods and Materials: FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares–logistic regression [FPLS-LR] and functional principal component–logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate–response associations, assessed using bootstrapping. Results: The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/−0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/−0.96, 0.79/−0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe

Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Dean, Jamie A., E-mail: jamie.dean@icr.ac.uk [Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London (United Kingdom); Wong, Kee H. [Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Gay, Hiram [Department of Radiation Oncology, School of Medicine, Washington University in St Louis, St Louis, Missouri (United States); Welsh, Liam C.; Jones, Ann-Britt; Schick, Ulrike [Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Oh, Jung Hun; Apte, Aditya [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Newbold, Kate L.; Bhide, Shreerang A.; Harrington, Kevin J. [Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Division of Radiotherapy and Imaging, The Institute of Cancer Research, London (United Kingdom); Deasy, Joseph O. [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Nutting, Christopher M. [Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Division of Radiotherapy and Imaging, The Institute of Cancer Research, London (United Kingdom); Gulliford, Sarah L. [Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London (United Kingdom)

2016-11-15

Purpose: Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue–sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. Methods and Materials: FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares–logistic regression [FPLS-LR] and functional principal component–logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate–response associations, assessed using bootstrapping. Results: The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/−0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/−0.96, 0.79/−0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe

Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy.

Science.gov (United States)

Dean, Jamie A; Wong, Kee H; Gay, Hiram; Welsh, Liam C; Jones, Ann-Britt; Schick, Ulrike; Oh, Jung Hun; Apte, Aditya; Newbold, Kate L; Bhide, Shreerang A; Harrington, Kevin J; Deasy, Joseph O; Nutting, Christopher M; Gulliford, Sarah L

2016-11-15

Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue-sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares-logistic regression [FPLS-LR] and functional principal component-logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate-response associations, assessed using bootstrapping. The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/-0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/-0.96, 0.79/-0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than

How robotic-assisted surgery can decrease the risk of mucosal tear during Heller myotomy procedure?

Science.gov (United States)

Ballouhey, Quentin; Dib, Nabil; Binet, Aurélien; Carcauzon-Couvrat, Véronique; Clermidi, Pauline; Longis, Bernard; Lardy, Hubert; Languepin, Jane; Cros, Jérôme; Fourcade, Laurent

2017-06-01

We report the first description of robotic-assisted Heller myotomy in children. The purpose of this study was to improve the safety of Heller myotomy by demonstrating, in two adolescent patients, the contribution of the robot to the different steps of this procedure. Due to the robot's freedom of movement and three-dimensional vision, there was an improvement in the accuracy, a gain in the safety regarding different key-points, decreasing the risk of mucosal perforation associated with this procedure.

A randomised clinical trial of misoprostol for radiation mucositis

International Nuclear Information System (INIS)

Faroudi, F.; Timms, I.; Sathiyuaseelan, Y.; Cakir, B.; Tiver, K.W.; Gebski, V.; Veness, M.

2003-01-01

Radiation mucositis is a major acute toxicity of radiation therapy for head and neck malignancies. We tested whether Misoprostol, a synthetic prostaglandin E 1 analogue given prophylactically decreased intensity of radiation mucositis. A double blind randomized trial was conducted. The intervention consisted of swishing dissolved drug or placebo as a mouthwash, and then swallowing two hours prior to radiation treatment. Patients were stratified based on concurrent chemotherapy, altered fractionation, smoking, extent of oral mucosa in radiation field, and institution. The main end point was the extent of RTOG grade III mucositis, taking into account both time and duration of mucositis. 42 patients were randomized to active drug, and 41 patients to placebo. The trial was designed to have 70 patients in each arm. The trial closed due to poor accrual. In the Misoprostol group 18/42 (43%) had grade III/IV mucositis, and in the placebo group 17/40 (42%). The mean difference between the areas under the curve was 0.38 (p-value: 0.38). For grade II mucositis the corresponding figures were 18 (42%) and 19 (47%). The time from commencement of radiation therapy to the development of peak mucositis was 49 days in the misoprostol patients and 51 days in the placebo group. The duration of grade III mucositis 12.5 days in the Misoprostol patients and 7 days in the placebo patients. In the Misoprostol arm 4 patients had an interruption to their Radiation Therapy, in the Placebo arm 5 had interruptions. Patients average weight loss was 8.1 and 8.2kg. Average self-assessment was via a 10cm LASA scale for soreness of throat and overall well-being. Misoprostol showed a worse QoL on soreness of mouth (mean difference: 0.84 units (p-value .03), but overall well-being was similar on both treatment arms 1 patient withdrew in the Misoprostol arm and 2 in the placebo arm. Misoprostol given prophylactically does not reduce the incidence of Grade III/IV mucositis, is associated with a shorter

Gastric Mucosal Erosions - Radiologic evaluation -

International Nuclear Information System (INIS)

Kim, Seung Hyup

1985-01-01

70 cases of gastric mucosal erosions were diagnosed by double contrast upper gastrointestinal examinations and endoscopic findings. Analyzing the radiologic findings of these 70 cases of gastric mucosal erosions, the following results were obtained. 1. Among the total 70 cases, 65 cases were typical varioliform erosions showing central depressions and surrounding mucosal elevations. Remaining 5 cases were erosions of acute phase having multiple irregular depressions without surrounding elevations. 2. The gastric antrum was involved alone or in part in all cases. Duodenal bulb was involved with gastric antrum in 4 cases. 3. The majority of the cases had multiple erosions. There were only 2 cases of single erosion. 4. In 65 cases of varioliform erosions; 1) The diameter of the surrounding elevations varied from 3 to 20 mm with the majority (47 cases) between 6 and 10 mm. 2) In general, the surrounding elevations with sharp margin on double contrast films were also clearly demonstrated on compression films but those with faint margin were not. 3) The size of the central barium collections varied from pinpoint to 10 mm with the majority under 5 mm. The shape of the central barium collections in majority of the cases were round with a few cases of linear, triangular or star-shape. 5. In 5 cases of acute phase erosions; 1) All the 5 cases were females. 2) On double contrast radiography, all the cases showed multiple irregular depressed lesions without surrounding elevations. 3) 1 case had the history of hematemesis. 4) In 1 case, there was marked radiological improvement on follow-up study of 2 months interval. 6. In 23 cases, there were coexistent diseases with gastric mucosal erosions. These were 13 cases of duodenal bulb ulcers,7 cases of benign gastric ulcers and 3 others

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

Mucosal healing in ulcerative colitis

DEFF Research Database (Denmark)

Seidelin, Jakob Benedict; Coskun, Mehmet; Nielsen, Ole Haagen

2013-01-01

. With the introduction of the tumor necrosis factor-alpha inhibitors for the treatment of UC, it has become increasingly evident that the disease course is influenced by whether or not the patient achieves mucosal healing. Thus, patients with mucosal healing have fewer flare-ups, a decreased risk of colectomy......, and a lower probability of developing colorectal cancer. Understanding the mechanisms of mucosal wound formation and wound healing in UC, and how they are affected therapeutically is therefore of importance for obtaining efficient treatment strategies holding the potential of changing the disease course of UC....... This review is focused on the pathophysiological mechanism of mucosal wound formation in UC as well as the known mechanisms of intestinal wound healing. Regarding the latter topic, pathways of both wound healing intrinsic to epithelial cells and the wound-healing mechanisms involving interaction between...

Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice

Science.gov (United States)

Pineton de Chambrun, G; Body-Malapel, M; Frey-Wagner, I; Djouina, M; Deknuydt, F; Atrott, K; Esquerre, N; Altare, F; Neut, C; Arrieta, M C; Kanneganti, T-D; Rogler, G; Colombel, J-F; Cortot, A; Desreumaux, P; Vignal, C

2014-01-01

The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10−/−) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor. PMID:24129165

Prior mucosal exposure to heterologous cells alters the pathogenesis of cell-associated mucosal feline immunodeficiency virus challenge

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Leavell Sarah

2010-05-01

Full Text Available Abstract Background Several lines of research suggest that exposure to cellular material can alter the susceptibility to infection by HIV-1. Because sexual contact often includes exposure to cellular material, we hypothesized that repeated mucosal exposure to heterologous cells would induce an immune response that would alter the susceptibility to mucosal infection. Using the feline immunodeficiency virus (FIV model of HIV-1 mucosal transmission, the cervicovaginal mucosa was exposed once weekly for 12 weeks to 5,000 heterologous cells or media (control and then cats were vaginally challenged with cell-associated or cell-free FIV. Results Exposure to heterologous cells decreased the percentage of lymphocytes in the mucosal and systemic lymph nodes (LN expressing L-selectin as well as the percentage of CD4+ CD25+ T cells. These shifts were associated with enhanced ex-vivo proliferative responses to heterologous cells. Following mucosal challenge with cell-associated, but not cell-free, FIV, proviral burden was reduced by 64% in cats previously exposed to heterologous cells as compared to media exposed controls. Conclusions The pathogenesis and/or the threshold for mucosal infection by infected cells (but not cell-free virus can be modulated by mucosal exposure to uninfected heterologous cells.

Acute decrease in renal microvascular PO2 during acute normovolemic hemodilution

NARCIS (Netherlands)

Johannes, Tanja; Mik, Egbert G.; Nohé, Boris; Unertl, Klaus E.; Ince, Can

2007-01-01

Large differences in the tolerance of organ systems to conditions of decreased O(2) delivery such as hemodilution exist. The kidney receives approximately 25% of the cardiac output and O(2) delivery is in excess of the oxygen demand under normal circumstances. In a rat model of acute normovolemic

Effects of sucralfate, cimetidine and rabeprazole on mucosal hydroxyproline content in healing of ethanol-hcl-induced gastric lesions.

Science.gov (United States)

Arisawa, Tomiyasu; Shibata, Tomoyuki; Kamiya, Yoshio; Nagasaka, Mitsuo; Nakamura, Masakatsu; Fujita, Hiroshi; Hasegawa, Shin; Harata, Masao; Nakamura, Masahiko; Mizuno, Tamaki; Tahara, Tomomitsu; Ohta, Yoshiji; Nakano, Hiroshi

2006-07-01

1. No general consensus has been reached on the treatment of acute gastric lesions. The aims of the present study were to clarify the effects of sucralfate, cimetidine and rabeprazole monotherapies and combination therapies on acute gastric lesions from the viewpoint of connective tissue regeneration. 2. Gastric lesions were experimentally created by the oral administration of 50% ethanol-0.15 mol/L HCl to rats. After 30 min, the anti-ulcer agents sucralfate (100 mg/kg), cimetidine (20 mg/kg) and rabeprazole (2 mg/kg) were administered separately or in combination and the stomach was excised at different times to measure the level of hydroxyproline in the gastric mucosa and determine lesion index. Immunostaining against prolylhydroxylase was performed on some specimens. 3. In the control group, lesion index decreased linearly from 30 min after ethanol-HCl administration and the level of mucosal hydroxyproline peaked between 2 and 4 h later. Although sucralfate significantly promoted lesion healing, it had no effect on mucosal hydroxyproline level. Cimetidine suppressed increases in mucosal hydroxyproline and prolonged lesion healing, but these findings were reversed by combining cimetidine and sucralfate. Rabeprazole had no significant effect on lesion healing, but promoted lesion healing in combination with sucralfate. Immunohistochemical analysis showed that prolylhydroxylase was expressed in spindle cells that lined the glandular cells in a boundary area between normal and injured tissues. 4. Under conditions in which the effects of intragastric pH are minimal, sucralfate is superior to antisecretory agents in promoting the healing of acute gastric lesions.

Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

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Ohta, Y; Chiba, S; Imai, Y; Kamiya, Y; Arisawa, T; Kitagawa, A

2006-12-01

We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

Sled Towing Acutely Decreases Acceleration Sprint Time.

Science.gov (United States)

Wong, Megan A; Dobbs, Ian J; Watkins, Casey M; Barillas, Saldiam R; Lin, Anne; Archer, David C; Lockie, Robert G; Coburn, Jared W; Brown, Lee E

2017-11-01

Wong, MA, Dobbs, IJ, Watkins, C, Barillas, SR, Lin, A, Archer, DC, Lockie, RG, Coburn, JW, and Brown, LE. Sled towing acutely decreases acceleration sprint time. J Strength Cond Res 31(11): 3046-3051, 2017-Sled towing is a common form of overload training in sports to develop muscular strength for sprinting. This type of training leads to acute and chronic outcomes. Acute training potentially leads to postactivation potentiation (PAP), which is when subsequent muscle performance is enhanced after a preload stimulus. The purpose of this study was to determine differences between rest intervals after sled towing on acute sprint speed. Twenty healthy recreationally trained men (age = 22.3 ± 2.4 years, height = 176.95 ± 5.46 cm, mass = 83.19 ± 11.31 kg) who were currently active in a field sport twice a week for the last 6 months volunteered to participate. A maximal 30-meter (m) baseline (BL) body mass (BM) sprint was performed (with splits at 5, 10, 20, and 30 m) followed by 5 visits where participants sprinted 30 m towing a sled at 30% BM then rested for 2, 4, 6, 8, or 12 minutes. They were instructed to stand still during rest times. After the rest interval, they performed a maximal 30-m post-test BM sprint. Analysis of variance (ANOVA) revealed that post sled tow BM sprint times (4.47 ± 0.21 seconds) were less than BL times (4.55 ± 0.18 seconds) on an individualized rest interval basis. A follow-up 2 × 4 ANOVA showed that this decrease occurred only in the acceleration phase over the first 5 m (BL = 1.13 ± 0.08 seconds vs. Best = 1.08 ± 0.08 seconds), which may be the result of PAP and the complex relationship between fatigue and potentiation relative to the intensity of the sled tow and the rest interval. Therefore, coaches should test their athletes on an individual basis to determine optimal rest time after a 30-m 30% BM sled tow to enhance acute sprint speed.

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

Double-blind randomized phase III study comparing a mixture of natural agents versus placebo in the prevention of acute mucositis during chemoradiotherapy for head and neck cancer.

Science.gov (United States)

Marucci, Laura; Farneti, Alessia; Di Ridolfi, Paolo; Pinnaro, Paola; Pellini, Raul; Giannarelli, Diana; Vici, Patrizia; Conte, Mario; Landoni, Valeria; Sanguineti, Giuseppe

2017-09-01

There is no widely accepted intervention in the prevention of acute mucositis during chemoradiotherapy for head and neck carcinoma. In the present double-blind study, we tested 4 natural agents, propolis, aloe vera, calendula, and chamomile versus placebo. Patients undergoing concomitant chemo-intensity-modulated radiotherapy (IMRT) were given natural agent or matched placebo; grade 3 mucositis on physical examination according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was the primary endpoint. Various covariates were tested at logistic regression, including the individual amount of mucosa receiving at least 9.5 Gy per week (V9.5w). One hundred seven patients were randomized from January 2011 to July 2014, and 104 were assessable (51%-49% were assigned to the placebo group and 53%-51% were assigned to the natural agent). Overall, 61 patients developed peak grade 3 mucositis with no difference between arms (P = .65). Conversely, V9.5w (P = .007) and primary site (P = .037) were independent predictors. The selected natural agents do not prevent mucositis, whereas the role of V9.5w is confirmed. © 2017 Wiley Periodicals, Inc.

Dose–response analysis of acute oral mucositis and pharyngeal dysphagia in patients receiving induction chemotherapy followed by concomitant chemo-IMRT for head and neck cancer

International Nuclear Information System (INIS)

Bhide, Shreerang A.; Gulliford, Sarah; Schick, Ulrike; Miah, Aisha; Zaidi, Shane; Newbold, Katie; Nutting, Christopher M.; Harrington, Kevin J.

2012-01-01

Dose–response curves (DRCs) and the quantitative parameters describing these curves were generated for grade 3 oral mucositis and dysphagia in 144 patients using individual patient DVHs. Curve fits to the oral mucositis clinical data yielded parameter values of mean dose in 2 Gy equivalent, MD 50 = 51 Gy (95% CI 40–61), slope of the curve, k = 1(95% CI 0.6–1.5). R 2 value for the goodness of fit was 0.80. Fits to the grade 3 dysphagia clinical data yielded parameter values of MD 50 = 44.5 Gy (95% CI 36–53), k = 2.6 (95% CI 0.8–4.5). R 2 value for the goodness of fit was 0.65. This is the first study to derive DRCs in patients receiving induction chemotherapy followed by chemo-radiation (IC-C-IMRT) for head and neck cancer. The dose–response model described in this study could be useful for comparing acute mucositis rates for different dose–fractionation schedules when using IMRT for head and neck cancer.

Bile acid receptor TGR5 overexpression is associated with decreased intestinal mucosal injury and epithelial cell proliferation in obstructive jaundice.

Science.gov (United States)

Ji, Chen-Guang; Xie, Xiao-Li; Yin, Jie; Qi, Wei; Chen, Lei; Bai, Yun; Wang, Na; Zhao, Dong-Qiang; Jiang, Xiao-Yu; Jiang, Hui-Qing

2017-04-01

Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS). Internal biliary drainage was superior to external biliary drainage in recovering intestinal permeability and mucosal histology in patients with obstructive jaundice. In BDL rats, feeding of chenodeoxycholic acid (CDCA) decreased intestinal mucosa injury. The levels of PCNA, a marker of proliferation, increased in response to CDCA feeding and were paralleled by elevated TGR5 expression. CDCA upregulated TGR5 expression and promoted proliferation in Caco-2 and FHs 74 Int cells pretreated with LPS. Overexpression of TGR5 resulted in increased PCNA, cell viability, EdU incorporation, and the proportion of cells in S phase, whereas knockdown of TGR5 had the opposite effect. Our data indicate that bile acids promote intestinal epithelial cell proliferation and decrease mucosal injury by upregulating TGR5 expression in obstructive jaundice. Copyright © 2016 Elsevier Inc. All rights reserved.

Endoscopic mucosal resection for early gastric cancer. A case report.

Science.gov (United States)

Gheorghe, Cristian; Sporea, Ioan; Becheanu, Gabriel; Gheorghe, Liana

2002-03-01

European experience in endoscopic mucosal resection (EMR) for early gastric cancer is still relatively low, since early stomach cancer is diagnosed at a much lower rate in Europe than in Japan and generally operable patients are referred to surgery for radical resection. Endoscopic mucosal resection or mucosectomy was developed as a promising technology to diagnose and treat mucosal lesions in the esophagus, stomach and colon. In contrast to surgical resection, EMR allows "early cancers" to be removed with a minimal cost, morbidity and mortality. We present the case of a patient with hepatic cirrhosis incidentally diagnosed with an elevated-type IIa early gastric cancer. Echoendoscopy was performed in order to assess the depth of invasion into the gastric wall confirming the only mucosal involvement. We performed an EMR using "cup and suction" method. After the procedure, the patient experienced an acute upper gastrointestinal bleeding from the ulcer bed requiring argon plasma coagulation. The histopathological examination confirmed an early cancer, without involvement of muscularis mucosae. The patient has had an uneventful evolution being well at six months after the procedure

Peak heart rate decreases with increasing severity of acute hypoxia

DEFF Research Database (Denmark)

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

2001-01-01

, 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......-202) (mean and range) at sea level to 189 (179-200), 182 (172-189), 175 (166-183), and 165 (162-169) in the acute hypoxic conditions. Peak HR did not decrease further after 4 and 8 h at 4300 m compared to the acute exposure at this altitude. Between barometric pressures of 518 and 355 mmHg (approximately...... 3300 and 6300 m), peak HR decreased linearly: peak HR(hypobaria) = peak HR(sea level) - 0.135 x [hypobaria(3100) - hypobaria (mmHg)]; or peak HR(altitude) = peak HR(sea level) - 0.15 x (altitude - 3100 m). This corresponds to approximately 1-beat x min(-1) reduction in peak HR for every 7-mmHg decrease...

Pelvis dilatation and mucosal thickening of transplanted kidney: comparative study of resistive index and ultrasonographic finding

International Nuclear Information System (INIS)

Kim, Myung Joon; Yoo, Hyung Sik; Lee, Jong Tae; Kim, Yu Seun; Park, Ki Il

1992-01-01

Diagnostic ability of duplex Doppler ultrasonography relying on resistive index is limited when clinical symptoms and signs of rejection are subtle or renal dysfunction is caused by other conditions such as urinary tract infection. To investigate the significance in the changes of renal pelvis, a combined analysis of resistive index and ultrasonographic findings in cases of renal pelvis dilatation and mucosal thickening was undertaken. A mean resistive index was calculated from Doppler measurements of the main, segmental and interlobar arteries. The cause of mucosal thickening was retrospectively analysed using the clinical and laboratory findings. Twenty three cases of renal pelvis dilatation and 17 cases of mucosal thickening were found in a total of 159 renal transplantation cases. In 14 of the 23 cases with renal pelvis dilatation, renal function was normal and their mean resistive index was 0.64 ± 0.04. Pelvis and ureter dilatation caused by ureteral stenosis or compression was demonstrated in 6 cases and their mean resistive index (0.72 ± 0.05) was increased. Mucosal thickening of renal pelvis was found in 7 of 32 cases with acute injection and in 2 of 13 cases with chronic rejection, but their mean resistive index was not different from that of the cases without pelvic mucosal changes. Three cases of acute rejection associated with urinary tract infection and 2 cases of chronic rejection in whom resistive indices were indeterminate, but mucosal thickening of the renal pelvis was prominent at ultrasonography. In renal transplant patients having indeterminate resistive index and mucosal thickening of the renal pelvis, ultrasonographic features must be correlated with the clinical and laboratory findings for an accurate diagnosis and treatment of renal dysfunction

Pretreatment with Saccharomyces boulardii does not prevent the experimental mucositis in Swiss mice.

Science.gov (United States)

Maioli, Tatiani Uceli; de Melo Silva, Brenda; Dias, Michelle Nobre; Paiva, Nivea Carolina; Cardoso, Valbert Nascimento; Fernandes, Simone Odilia; Carneiro, Cláudia Martins; Dos Santos Martins, Flaviano; de Vasconcelos Generoso, Simone

2014-04-11

The antimetabolite chemotherapy 5-Fluorouracil is one of the most commonly prescribed drugs in clinical cancer treatment. Although this drug is not specific for cancer cells and also acts on healthy cells, it can cause mucositis, a common collateral effect. Dysbiosis has also been described in 5-fluorouracil-induced mucositis and is likely to contribute to the overall development of mucositis. In light of this theory, the use of probiotics could be a helpful strategy to alleviate mucositis. So the aim of this study was evaluate the impact of the probiotic Saccharomyces boulardii in a model of mucositis. After induced of mucositis, mice from the Mucositis groups showed a decrease in food consumption (p Saccharomyces boulardii did not reverse this effect (p > 0.05). Mucositis induced an increase in intestinal permeability and intestinal inflammation (p  0.05) in mice pretreated with S. boulardii. S. boulardii was not able to prevent the effects of experimental mucositis induced by 5- Fluorouracil.

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.

Oral Candida as an aggravating factor of mucositis Induced by radiotherapy

International Nuclear Information System (INIS)

Simoes, Cristiane Araujo; Castro, Jurema Freire Lisboa de; Cazal, Claudia

2011-01-01

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)

Study of reduction methods for irradiation on oral mucositis. The examination of reduction methods for mucosal failure

International Nuclear Information System (INIS)

Tonogi, Morio; Yamane, Genyuki; Aoyagi, Yutaka; Hasegawa, Azusa; Mizoe, Junetsu; Tsujii, Hirohiko

2004-01-01

Reduction methods for irradiation on oral mucosa examined concerning in acute phase of the carbon ion radiotherapy for head and neck malignancies. We enforced a mechanical teeth and gingival cleaning as an Oral hearth care and gargled a polaprezinc with sodium alginate, and azulene- lidocaine with glycerin sodium as a oral linces before radiation. The response of the mucosal failure was reduced compare with no care group. In this Result, we considered that oral hearth care for prevention of infection, and mucosa protection by the drug was important factor. (author)

A diet containing whey protein, glutamine, and TGFbeta modulates gut protein metabolism during chemotherapy-induced mucositis in rats.

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Boukhettala, Nabile; Ibrahim, Ayman; Claeyssens, Sophie; Faure, Magali; Le Pessot, Florence; Vuichoud, Jacques; Lavoinne, Alain; Breuillé, Denis; Déchelotte, Pierre; Coëffier, Moïse

2010-08-01

Mucositis, a common side effect of chemotherapy, is characterized by compromised digestive function, barrier integrity and immune competence. Our aim was to evaluate the impact of a specifically designed diet Clinutren Protect (CP), which contains whey proteins, TGFbeta-rich casein, and free glutamine, on mucositis in rats. Mucositis was induced by three consecutive injections (day 0, day 1, day 2) of methotrexate (2.5 mg/kg). Rats had free access to CP or placebo diets from days -7 to 9. In the placebo diet, whey proteins and TGFbeta-rich casein were replaced by TGFbeta-free casein and glutamine by alanine. Intestinal parameters were assessed at day 3 and 9. Values, expressed as mean +/- SEM, were compared using two-way ANOVA. At day 3, villus height was markedly decreased in the placebo (296 +/- 11 microm) and CP groups (360 +/- 10 microm) compared with controls (464 +/- 27 microm), but more markedly in the placebo as compared to CP group. The intestinal damage score was also reduced in the CP compared with the placebo group. Glutathione content increased in the CP compared with the placebo group (2.2 +/- 0.2 vs. 1.7 +/- 0.2 micromol/g tissue). Gut protein metabolism was more affected in the placebo than in the CP group. The fractional synthesis rate was decreased in the placebo group (93.8 +/- 4.9%/day) compared with controls (121.5 +/- 12.1, P < 0.05), but not in the CP group (106.0 +/- 13.1). In addition, at day 9, rats exhibited improved body weight and food intake recovery in the CP compared to the placebo group. Clinutren Protect feeding reduces intestinal injury in the acute phase of methotrexate-induced mucositis in rats and improves recovery.

Frank hematuria as the presentation feature of acute leukemia

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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.

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

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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.

Oral mucositis and selective elimination of oral flora in head and neck cancer patients receiving radiotherapy : a double-blind randomised clinical trial

NARCIS (Netherlands)

Stokman, MA; Spijkervet, FKL; Burlage, FR; Dijkstra, PU; Manson, WL; de Vries, EGE; Roodenburg, JLN

2003-01-01

Mucositis is an acute inflammation of the oral mucosa because of radiotherapy and/or chemotherapy. All patients receiving radiotherapy in the head and neck region develop oral mucositis. The aim of this study was to analyse the effects of selective oral flora elimination on radiotherapy-induced oral

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.

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.

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

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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.

Evaluation of Oral Mucositis Occurrence in Oncologic Patients under Antineoplastic Therapy Submitted to the Low-Level Laser Coadjuvant Therapy.

Science.gov (United States)

Leite Cavalcanti, Alessandro; José de Macêdo, Dário; Suely Barros Dantas, Fernanda; Dos Santos Menezes, Karla; Filipe Bezerra Silva, Diego; Alves de Melo Junior, William; Fabia Cabral Cavalcanti, Alidianne

2018-04-24

Low-level laser therapy has been widely used in treating many conditions, including oral mucositis. The purpose of this study was to evaluate the occurrence of oral mucositis in patients undergoing antineoplastic therapy submitted to preventive and therapeutic treatment with low-level laser therapy. This cross-sectional study was carried out with 51 children and adolescents of both sexes with malignant neoplasias who developed oral mucositis and underwent low-level laser therapy. Data were collected on sex, age, type and degree of neoplasia, region affected, and remission time. 64.7% of the patients were male and were between 3 and 6 years of age (39.2%). Acute lymphoid leukemia was the most frequent neoplasm (37.3%). Regarding the maximum oral mucositis, grade 2 (41.2%) was predominant, with jugal mucosa (29.9%) and tongue (17.7%) being the most affected regions. The majority of cases presented lesion remission time between 4 and 7 days (44.0%). Most patients were young, male, and diagnosed with acute lymphoid leukemia. Predominance of grade 2 oral mucositis was observed, with jugal mucosa and tongue being the most affected regions, with the majority of cases presenting lesion remission time between 4 and 7 days. Low-level laser therapy has been shown to be an essential therapy in the prevention and treatment of these lesions, since it is a non-invasive and low-cost method.

[The usage of inferior turbinate mucosal flap for repairing cleft lip].

Science.gov (United States)

Gao, Pu; Zhao, Min; Qi, Ke-ming; Zhao, Zhen-min; Xiong, Bin

2004-05-01

To evaluate a technique for decreasing the tension of the nasal floor during the procedures of repairing complete clef lip. With the designation of an inferior turbinate mucosal flap combined with an oral mucosal flap in the splitting side, the tension was effectively decreased and the nasal floor was closed easily. Eighteen patients was selected for the treatment with this technique since 2000. The follow-ups were 10 to 24 months. All of the patients showed wound healing well with the significant improvement in the donor site. The above mentioned technique may effectively decrease the tension and be used to close the nasal floor safely. It could also reduce the incidence of the complications.

Glucagon-like peptide-1 as a treatment for chemotherapy-induced mucositis

DEFF Research Database (Denmark)

Kissow, Hannelouise; Hartmann, Bolette; Holst, Jens Juul

2012-01-01

: To determine whether endogenous GLP-1 contributes to the healing processes and if exogenous GLP-1 has a potential role in treating mucositis. METHODS: Mice were injected with 5-fluorouracil (5-FU) or saline to induce mucositis and were then treated with GLP-1, GLP-2, GLP-2 (3-33), exendin (9-39) or vehicle....... The mice were sacrificed 48 or 96 h after the 5-FU injections. The end points were intestinal weight, villus height, proliferation and histological scoring of mucositis severity. Rats were injected with 5-FU or saline, and after 48 h, blood was drawn and analysed for GLP-1 and GLP-2 concentration. RESULTS......: GLP-1 and GLP-2 significantly prevented the loss of mucosal mass and villus height and significantly decreased the mucositis severity score in the duodenum and jejunum 48 h after chemotherapy. The effect was equivalent. Exendin (9-39) reduced the intestinal weight 96 h after chemotherapy. The GLP-1...

Customized mouthpieces designed to reduce tongue mucositis in carbon-ion radiotherapy for tumors of the nasal and paranasal sinuses

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Atsushi Musha

2017-07-01

Full Text Available Mouthpieces are used to fix the positions of the lower jaw and teeth during carbon-ion radiotherapy for head and neck tumors. We used a customized mouthpiece to reduce radiation mucositis by displacing the tongue. Acute radiation mucositis gradually increased for the palate and tongue after approximately six irradiation fractions (maximal mean grade: palate, 2.5 during radiation fractions 15; tongue, 0.8 during radiation fractions 12 and 13. The mean grade of mucositis was significantly lower for the tongue than for the palate from irradiation fraction six until two weeks after irradiation.

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.

Mucosal vaccination by adenoviruses displaying reovirus sigma 1

International Nuclear Information System (INIS)

Weaver, Eric A.; Camacho, Zenaido T.; Hillestad, Matthew L.; Crosby, Catherine M.; Turner, Mallory A.; Guenzel, Adam J.; Fadel, Hind J.; Mercier, George T.; Barry, Michael A.

2015-01-01

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

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

OpenAIRE

Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

2016-01-01

Cardiovascular disease is the largest cause of mortality worldwide, and stress is a significant contributor to the development of cardiovascular disease. The relationship between acute and chronic stress and cardiovascular disease is well-evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury. Conversely, chronic stress is arrythmogenic and incr...

Evaluation of Oral Mucositis Occurrence in Oncologic Patients under Antineoplastic Therapy Submitted to the Low-Level Laser Coadjuvant Therapy

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Alessandro Leite Cavalcanti

2018-04-01

Full Text Available Low-level laser therapy has been widely used in treating many conditions, including oral mucositis. The purpose of this study was to evaluate the occurrence of oral mucositis in patients undergoing antineoplastic therapy submitted to preventive and therapeutic treatment with low-level laser therapy. This cross-sectional study was carried out with 51 children and adolescents of both sexes with malignant neoplasias who developed oral mucositis and underwent low-level laser therapy. Data were collected on sex, age, type and degree of neoplasia, region affected, and remission time. 64.7% of the patients were male and were between 3 and 6 years of age (39.2%. Acute lymphoid leukemia was the most frequent neoplasm (37.3%. Regarding the maximum oral mucositis, grade 2 (41.2% was predominant, with jugal mucosa (29.9% and tongue (17.7% being the most affected regions. The majority of cases presented lesion remission time between 4 and 7 days (44.0%. Most patients were young, male, and diagnosed with acute lymphoid leukemia. Predominance of grade 2 oral mucositis was observed, with jugal mucosa and tongue being the most affected regions, with the majority of cases presenting lesion remission time between 4 and 7 days. Low-level laser therapy has been shown to be an essential therapy in the prevention and treatment of these lesions, since it is a non-invasive and low-cost method.

New Pathways for Alimentary Mucositis

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Joanne M. Bowen

2008-01-01

Full Text Available Alimentary mucositis is a major dose-limiting toxicity associated with anticancer treatment. It is responsible for reducing patient quality of life and represents a significant economic burden in oncology. The pathobiology of alimentary mucositis is extremely complex, and an increased understanding of mechanisms and pathway interactions is required to rationally design improved therapies. This review describes the latest advances in defining mechanisms of alimentary mucositis pathobiology in the context of pathway activation. It focuses particularly on the recent genome-wide analyses of regimen-related mucosal injury and the identification of specific regulatory pathways implicated in mucositis development. This review also discusses the currently known alimentary mucositis risk factors and the development of novel treatments. Suggestions for future research directions have been raised.

Effectiveness of Tai-Chi for decreasing acute pain in fibromyalgia patients.

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Segura-Jiménez, V; Romero-Zurita, A; Carbonell-Baeza, A; Aparicio, V A; Ruiz, J R; Delgado-Fernández, M

2014-05-01

Tai-Chi has shown benefits in physical and psychological outcomes in diverse populations. We aimed to determine the changes elicited by a Tai-Chi program (12 and 24 weeks) in acute pain (before vs. after session) in fibromyalgia patients. We also assessed the cumulative changes in pain brought about by a Tai-Chi program. Thirty-six patients (29 women) with fibromyalgia participated in a low-moderate intensity Tai-Chi program for 12 weeks (3 sessions/week). Twenty-eight patients (27 women) continued the program for an additional 12 weeks (i. e., 24 weeks). We assessed pain by means of a Visual Analogue Scale (VAS) before and after each single session (i. e., 72 sessions). We observed significant immediate changes (P-values from 0.037 to 0.0001) with an approximately 12% mean decrease of acute pain in the comparison of VAS-values before and after each session (72 sessions in total), with the exception of 4 sessions. We observed significant changes in cumulative pain pre-session (95% CI=-0.019; -0.014; PTai-Chi program for 12 weeks (3 times/week) decreased levels of acute pain in fibromyalgia patients. A longer period is necessary (e. g. 24 weeks) for observing cumulative changes in pain. © Georg Thieme Verlag KG Stuttgart · New York.

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

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

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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.

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.

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.

Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer

International Nuclear Information System (INIS)

Antonadou, Dosia; Pepelassi, Marizenia; Synodinou, Maria; Puglisi, Maria; Throuvalas, Nicolas

2002-01-01

Purpose: To determine the prophylactic properties of amifostine against acute and late toxicities from radiochemotherapy in patients with head-and-neck cancer. Methods and Materials: Fifty patients were randomized to receive conventional radiotherapy (RT) (2-Gy fractions, 5 days weekly, to a total of 60-74 Gy, depending on the tumor localization and TNM classification) and carboplatin (90 mg/m 2 infusion once per week before RT). Amifostine (300 mg/m 2 ) was administered in the study group only 15-30 min before RT for 6-7.5 weeks. The primary study end point was the grading of acute and late nonhematologic toxicities (mucositis, dysphagia, xerostomia) induced by radiochemotherapy. Secondary end points included treatment duration, hematologic toxicity, and clinical outcome. Results: The treatment duration was significantly shorter in the amifostine-treated group (p=0.013), because treatment interruptions were more frequent in the control group. Acute toxicities (mucositis and dysphagia) were less severe in the amifostine-treated group. By Week 3, all in the control group experienced Grade 2 mucositis compared with only 9% in the amifostine-treated group (p<0.0001). By Week 5, 52.2% of the patients in the control group experienced Grade 4 mucositis compared with 4.5% in the amifostine-treated group (p=0.0006). Similar results were obtained for dysphagia. At 3 months of follow-up, only 27% of patients in the study group experienced Grade 2 xerostomia compared with 73.9% in the control group (p=0.0001). Eighteen months after cessation of therapy, the proportion of patients with Grade 2 xerostomia was 4.5% vs. 30.4% for each respective treatment group (p=0.047). Cytoprotection with amifostine did not affect treatment outcome, with 90.9% complete responses in the amifostine-treated group compared with 78.3% in the control group (p=0.414). Conclusion: Amifostine was effective in reducing mucositis and dysphagia resulting from radiochemotherapy in patients with head

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

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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.

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. © Society for Leukocyte Biology.

Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

Science.gov (United States)

Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

1989-07-01

1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reaction. 4. Aspirin increased bleeding from a rate on placebo of 1.2 microliters 10 min-1 geometric mean (95% confidence limits) (0.7-1.8) microliters 10 min-1 to 20.0 (11.6-34.2) microliters 10 min-1, (P less than 0.01). The rate of bleeding after aspirin preceded by ethamsylate [14.1 (8.5-23.4) microliters 10 min-1] was not significantly different from that after aspirin alone. 5. We conclude that ethamsylate does not reduce acute aspirin-induced gastric mucosal bleeding in healthy humans.

Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure

NARCIS (Netherlands)

Lisman, T.; Bakhtiari, K.; Adelmeijer, J.; Meijers, J. C. M.; Porte, R. J.; Stravitz, R. T.

2012-01-01

. Background: It has been well established that hemostatic potential in patients with chronic liver disease is in a rebalanced status due to a concomitant decrease in pro- and antihemostatic drivers. The hemostatic changes in patients with acute liver injury/failure (ALI/ALF) are similar but not

Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure

NARCIS (Netherlands)

Lisman, T.; Bakhtiari, K.; Adelmeijer, J.; Meijers, J. C. M.; Porte, R. J.; Stravitz, R. T.

. Background: It has been well established that hemostatic potential in patients with chronic liver disease is in a rebalanced status due to a concomitant decrease in pro- and antihemostatic drivers. The hemostatic changes in patients with acute liver injury/failure (ALI/ALF) are similar but not

[Protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats].

Science.gov (United States)

Mu, F H; Hu, F L; Wei, H; Zhang, Y Y; Yang, G B; Lei, X Y; Yang, Y P; Sun, W N; Cui, M H

2016-02-01

To investigate the protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats and its possible mechanism. Acute gastric mucosal injury model was developed with intraperitoneal injection of aspirin in Wistar rats. The rats were divided into normal control group, injury group, sucralfate protection group, compound bismuth and magnesium granules protection group and its herbal components protection group(each group 12 rats). In the protection groups, drugs as mentioned above were administered by gavage before treated with intraperitoneal injection of aspirin. To evaluate the extent of gastric mucosal injury and the protective effect of drugs, gastric mucosal lesion index, gastric mucosal blood flow, content of gastric mucosal hexosamine, prostaglandins (PG), nitric oxide(NO), tumor necrosis factor (TNF), and interleukin (IL) -1, 2, 8 were measured in each group, and histological changes were observed by gross as well as under microscope and electron microscope. Contents of hexosamine, NO, and PG in all the protection groups were significantly higher than those in the injury group (all Pcompound bismuth and magnesium granules group was significantly higher than that in the sucralfate group ((11.29±0.51) vs(10.80±0.36)nmol/ml, Pcompound bismuth and magnesium granules group were significantly lower than those in the sucralfate group ((328.17±6.56) vs(340.23±8.05)pg/ml, PCompound bismuth and magnesium granules and its herbal components may have significant protective effect on aspirin-induced gastric mucosal injury.

A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis

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Bryan Oronsky

2018-06-01

Full Text Available The first tenet of medicine, “primum non nocere” or “first, do no harm”, is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonly result in significant toxicities. One of the more frequent and serious treatment-induced toxicities is mucositis and particularly oral mucositis (OM described as inflammation, atrophy and breakdown of the mucosa or lining of the oral cavity. The sequelae of oral mucositis (OM, which include pain, odynodysphagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions and discontinuations that not only negatively impact quality of life but also tumor control and survivorship. One potential strategy to reduce or prevent the development of mucositis, for which no effective therapies exist only best supportive empirical care measures, is the administration of agents referred to as radioprotectors and/or chemoprotectors, which are intended to differentially protect normal but not malignant tissue from cytotoxicity. This limited-scope review briefly summarizes the incidence, pathogenesis, symptoms and impact on patients of OM as well as the background and mechanisms of four clinical stage radioprotectors/chemoprotectors, amifostine, palifermin, GC4419 and RRx-001, with the proven or theoretical potential to minimize the development of mucositis particularly in the treatment of head and neck cancers.

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

2017-07-01

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.

ٍEvaluating Baremoom Mouthwash Efficacy in Treatment of Chemotherapy-Induced Mucositis

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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.

Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury.

Science.gov (United States)

Husain, Kareem D; Stromberg, Paul E; Woolsey, Cheryl A; Turnbull, Isaiah R; Dunne, W Michael; Javadi, Pardis; Buchman, Timothy G; Karl, Irene E; Hotchkiss, Richard S; Coopersmith, Craig M

2005-10-01

The aim of this study was to determine the effects of acute lung injury on the gut epithelium and examine mechanisms underlying changes in crypt proliferation and apoptosis. The relationship between severity and timing of lung injury to intestinal pathology was also examined. Randomized, controlled study. University research laboratory. Genetically inbred mice. Following induction of acute lung injury, gut epithelial proliferation and apoptosis were assessed in a) C3H/HeN wild-type and C3H/HeJ mice, which lack functional Toll-like receptor 4 (n = 17); b) C57Bl/6 mice that received monoclonal anti-tumor necrosis factor-alpha or control antibody (n = 22); and c) C57Bl/6 wild-type and transgenic mice that overexpress Bcl-2 in their gut epithelium (n = 21). Intestinal epithelial proliferation and death were also examined in animals with differing degrees of lung inflammation (n = 24) as well as in a time course analysis following a fixed injury (n = 18). Acute lung injury caused decreased proliferation and increased apoptosis in crypt epithelial cells in all animals studied. C3H/HeJ mice had higher levels of proliferation than C3H/HeN animals without additional changes in apoptosis. Anti-tumor necrosis factor-alpha antibody had no effect on gut epithelial proliferation or death. Overexpression of Bcl-2 did not change proliferation despite decreasing gut apoptosis. Proliferation and apoptosis were not correlated to severity of lung injury, as gut alterations were lost in mice with more severe acute lung injury. Changes in both gut epithelial proliferation and death were apparent within 12 hrs, but proliferation was decreased 36 hrs following acute lung injury while apoptosis returned to normal. Acute lung injury causes disparate effects on crypt proliferation and apoptosis, which occur, at least in part, through differing mechanisms involving Toll-like receptor 4 and Bcl-2. Severity of lung injury does not correlate with perturbations in proliferation or death in the

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

DEFF Research Database (Denmark)

Schmiegelow, Kjeld; Müller, Klaus Gottlob; Mogensen, Signe Sloth

2017-01-01

During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal...... useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall...... obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically...

New frontiers in mucositis.

Science.gov (United States)

Peterson, Douglas E; Keefe, Dorothy M; Sonis, Stephen T

2012-01-01

Mucositis is among the most debilitating side effects of radiotherapy, chemotherapy, and targeted anticancer therapy. Research continues to escalate regarding key issues such as etiopathology, incidence and severity across different mucosae, relationships between mucosal and nonmucosal toxicities, and risk factors. This approach is being translated into enhanced management strategies. Recent technology advances provide an important foundation for this continuum. For example, evolution of applied genomics is fostering development of new algorithms to rapidly screen genomewide single-nucleotide polymorphisms (SNPs) for patient-associated risk prediction. This modeling will permit individual tailoring of the most effective, least toxic treatment in the future. The evolution of novel cancer therapeutics is changing the mucositis toxicity profile. These agents can be associated with unique mechanisms of mucosal damage. Additional research is needed to optimally manage toxicity caused by agents such as mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors, without reducing antitumor effect. There has similarly been heightened attention across the health professions regarding clinical practice guidelines for mucositis management in the years following the first published guidelines in 2004. New opportunities exist to more effectively interface this collective guideline portfolio by capitalizing upon novel technologies such as an Internet-based Wiki platform. Substantive progress thus continues across many domains associated with mucosal injury in oncology patients. In addition to enhancing oncology patient care, these advances are being integrated into high-impact educational and scientific venues including the National Cancer Institute Physician Data Query (PDQ) portfolio as well as a new Gordon Research Conference on mucosal health and disease scheduled for June 2013.

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.

Mucosal melanosis associated with chemoembolization

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Ali Alkan

2015-06-01

Full Text Available Mucosal lesions due to underlying disease or drug toxicity, are important part of oncology practice. Patient with a diagnosis of hepatocellular carcinoma was treated with chemoembolisation. She presented with new onset of mucosal hyperpigmented lesion all through her oral cavity. Biopsy was consistent with mucosal melanosis, which was associated with the chemotherapeutics used in the chemoembolisation procedure. Lesion progressively improved without any treatment. Here we present an mucosal melanosis experience after chemoembolisation. J Clin Exp Invest 2015; 6 (2: 189-191

Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

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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.

Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

International Nuclear Information System (INIS)

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

1987-01-01

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

Activation of IGF-1/IGFBP-3 signaling by berberine improves intestinal mucosal barrier of rats with acute endotoxemia.

Science.gov (United States)

He, Yan; Yuan, Xiaoming; Zhou, Guangrong; Feng, Aiwen

2018-01-01

Insulin-like growth factor I (IGF-I) and binding protein 3 (IGFBP-3) play a role in the maintenance of gut mucosal barrier function. Nevertheless, IGF-I/IGFBP-3 and tight junction protein (TJP) expression in small intestinal mucosa are often impaired during endotoxemia. In this model of acute endotoxemia, the regulatory effect of berberine on IGF-I/IGFBP-3 and TJP expression in ileal mucosa was evaluated. The findings revealed systemic injection of lipopolysaccharide (LPS) suppressed mRNA and protein expression of IGF-I and IGFBP-3, but berberine ameliorated their production. LPS injection inhibited occludin and claudin-1 protein generation, and this inhibitory effect of LPS was abolished by berberine. Inhibition of IGF-I/IGFBP-3 signaling by AG1024 or siRNAs reduced berberine-induced occludin and claudin-1 production. Additionally, GW9662 was found to repress berberine-induced IGF-I/IGFBP-3 expression, indicating of a cross-link between PPARγ and IGF-I/IGFBP-3 axis. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute Whole Body Vibration Decreases the Glucose Levels in Elderly Diabetic Women

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Maíra Florentino Pessoa

2018-01-01

Full Text Available Type II diabetes (TIIDM is characterized by high levels of blood glucose followed by excessive insulin release so that the target cells become less sensitive, developing insulin resistance and maintaining hyperglycemic levels. Physical activity is the strongest element to prevent and to manage the TIIDM, and the majority of patients do not remain in regularly active levels, because the premature fatigue in these patients decreases the adherence to the training. Contrastingly, the whole body vibration (WBV training may improve the glucose metabolism in diabetic patients, reducing the peripheral blood sugar, decreasing the physical discomfort and perceived exertion. Therefore, the purpose of the study was to determine the effect of an acute WBV session as therapy to promote fasting decreases in insulin levels in peripheral blood in TIIDM when compared to healthy elderly. For this, fifteen healthy elderly women and fourteen diabetic elderly women, all sedentary, were allocated in diabetic or control groups, and we made an acute whole body session composed of 10 bouts lasting 2 minutes each one, separated by a 30-second rest period. The WBV was executed in a triaxial platform MY3 Power Plate® at 35 hertz and has been chosen a peak-to-peak displacement of 4 millimeters. After the protocol, both groups decreased the glycemic levels and increased lactate production in relation to the basal levels and when compared diabetic and control, where the most important results have been shown in diabetic women. This study revealed that WBV training in TIIDM has had significant beneficial effects on the control of glucose levels, still in an acute session. So that, the complete training probably will show better results about glycemic control and this finding could be especially important when prescribing exercise for elderly who are unable or unwilling to use traditional loads or who show poor exercise compliance.

Acute bouts of wheel running decrease cocaine self-administration: Influence of exercise output.

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Smith, Mark A; Fronk, Gaylen E; Zhang, Huailin; Magee, Charlotte P; Robinson, Andrea M

Exercise is associated with lower rates of drug use in human populations and decreases drug self-administration in laboratory animals. Most of the existing literature examining the link between exercise and drug use has focused on chronic, long-term exercise, and very few studies have examined the link between exercise output (i.e., amount of exercise) and drug self-administration. The purpose of this study was to examine the effects of acute bouts of exercise on cocaine self-administration, and to determine whether these effects were dependent on exercise output and the time interval between exercise and drug self-administration. Female rats were trained to run in automated running wheels, implanted with intravenous catheters, and allowed to self-administer cocaine on a fixed ratio (FR1) schedule of reinforcement. Immediately prior to each test session, subjects engaged in acute bouts of exercise in which they ran for 0, 30, or 60min at 12m/min. Acute bouts of exercise before test sessions decreased cocaine self-administration in an output-dependent manner, with the greatest reduction in cocaine intake observed in the 60-min exercise condition. Exercise did not reduce cocaine self-administration when wheel running and test sessions were separated by 12h, and exercise did not reduce responding maintained by food or responding during a saline substitution test. These data indicate that acute bouts of exercise decrease cocaine self-administration in a time- and output-dependent manner. These results also add to a growing body of literature suggesting that physical activity may be an effective component of drug abuse treatment programs. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional, histological structure and mastocytes alterations in rat urinary bladders following acute and [corrected] chronic cyclophosphamide treatment.

Science.gov (United States)

Juszczak, K; Gil, K; Wyczolkowski, M; Thor, P J

2010-08-01

Neurogenic inflammation is linked to urinary bladder overactivity development. Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and induces cystitis with overactivity. The aim of this study was to estimate the effect of CYP on rat urinary bladder function, histological structure and mastocytes numbers following acute and chronic CYP treatment. Fourty two female rats were divided into four groups: I (control), II (acute cystitis), III (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively. In group I-III the cystometric evaluation was performed. Sections of the bladder were stained with HE and toluidine blue for the detection of mastocytes. The severity of inflammation was examined according to mucosal abrasion, haemorrhage, leukocyte infiltration and oedema. Acute and chronic CYP treatment caused inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage, oedema) and increased infiltration of inflammatory cells in urinary bladder. Acute treatment induced the infiltration of mastocytes within bladder wall contrary to chronic one decrement. Acute treatment caused more severe mucosal abrasion, whereas chronic one revealed more developed haemorrhage changes. Additionally, cystometric evaluation revealed urinary bladder overactivity development in both types of cystitis. Basal pressure and detrusor overactivity index after acute treatment increased considerably in comparison with the increase obtained after chronic one. Our results proved that acute model of CYP-induced cystitis in rats is more credible for further evaluation of neurogenic inflammation response in pathogenesis of overactive bladder as compared to chronic one.

The Mucosal Immune System of Teleost Fish

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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.

Inner ocular blood flow responses to an acute decrease in blood pressure in resting humans

International Nuclear Information System (INIS)

Ikemura, Tsukasa; Kashima, Hideaki; Yamaguchi, Yuji; Miyaji, Akane; Hayashi, Naoyuki

2015-01-01

Whether inner ocular vessels have an autoregulatory response to acute fluctuations in blood pressure is unclear. We tried to examine the validity of acute hypotension elicited by thigh-cuff release as to assess the dynamic autoregulation in the ocular circulation. Blood flow velocity in the superior nasal and inferior temporal retinal arterioles, and in the retinal and choroidal vasculature were measured with the aid of laser speckle flowgraphy before and immediately after an acute decrease in blood pressure in 20 healthy subjects. Acute hypotension was induced by a rapid release of bilateral thigh occlusion cuffs that had been inflated to 220 mmHg for 2 min. The ratio of the relative change in retinal and choroidal blood flow velocity to the relative change in mean arterial blood pressure (MAP) was calculated. Immediately after cuff release, the MAP and blood flows in the all ocular target vessels decreased significantly from the baseline values obtained before thigh-cuff release. The ratio of the relative change in inner ocular blood flow velocity to that in the MAP exceeded 1% / %mmHg. An explicit dynamic autoregulation in inner ocular vessels cannot be demonstrated in response to an acute hypotension induced by the thigh-cuff release technique. (paper)

Close association between oral Candida species and oral mucosal disorders in patients with xerostomia.

Science.gov (United States)

Shinozaki, S; Moriyama, M; Hayashida, J-N; Tanaka, A; Maehara, T; Ieda, S; Nakamura, S

2012-10-01

Heightened interest in oral health has lead to an increase in patients complaining of xerostomia, which is associated with various oral mucosal disorders. In this study, we investigated the relationship between Candida species and oral mucosal disorders in patients with xerostomia. We evaluated whole salivary flow rate and presence of oral mucosal disorders in 48 patients with xerostomia and 15 healthy controls. The number of Candida species was measured as colony-forming units after propagation on selective medium. Identification of Candida at the species level was carried out by polymerase chain reaction and restriction fragment length polymorphism analysis. We then examined the relationship between Candida species and oral mucosal symptoms. Compared with controls, patients with xerostomia exhibited significantly decreased whole salivary flow rate, increased rate of oral mucosal symptoms, and higher numbers of Candida. Salivary flow rate negatively correlated with the number Candida. Among patients with oral candidiasis, Candida albicans was isolated from the tongue mucosa and Candida glabrata was isolated from the angle of the mouth. These results suggest that particular Candida species are involved in the pathogenesis of oral mucosal disorders in patients with xerostomia. © 2012 John Wiley & Sons A/S.

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

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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

2017-10-01

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.

Gastroduodenal mucosal defence mechanisms and the action of non-steroidal anti-inflammatory agents.

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Garner, A; Allen, A; Rowe, P H

1987-01-01

This review summarises gastroduodenal protective mechanisms, the actions of non-steroidal anti-inflammatory (NSAI) agents on mucus and HCO3 secretions, and the basis of gastric mucosal injury induced by acetylsalicylic and salicylic acids (ASA and SA). Resistance to autodigestion by acid and pepsin present in gastric juice is multifactorial involving pre-epithelial (mucus-bicarbonate barrier) and post-epithelial (blood flow, acid-base balance) factors in addition to properties of the surface cell layer per se. The latter includes mucosal re-epithelialisation, a property which appears particularly important with respect to recovery from acute injury. A range of NSAI agents (ASA, fenclofenac, ibuprofen and indomethacin) inhibit gastric HCO3 transport in isolated mucosal preparations. Inhibition of duodenal HCO3 transport has been demonstrated in response to indomethacin in vitro and in vivo. These effects on secretion can be antagonised by exogenous prostaglandins of the E series. The layer of secreted mucus gel overlying the epithelial surface is not affected by NSAI drugs in the short term. However a number of these agents have been shown to inhibit glycoprotein biosynthesis by the epithelial cells. Thus loss of this protective coat could be anticipated during chronic drug exposure since erosion of adherent mucus by luminal shear and proteolysis would not be compensated by continued secretion. Detailed analysis of the gastric mucosal injury induced by salicylates both in vitro and in vivo reveals that much of the damage previously attributed to ASA is in fact due to the metabolic product SA. In this respect it is concluded that mucosal injury caused by ASA is due to a combination of two factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis

International Nuclear Information System (INIS)

Miller, M.J.; Adams, J.; Gu, X.A.; Zhang, X.J.; Clark, D.A.

1990-01-01

We examined the local hemodynamic response of intestinal loops during acute necrotizing enterocolitis (NEC) in anesthetized rabbits. NEC was induced in ileal loops by transmural injection of a solution containing casein (10 mg/ml) and calcium gluconate (50 mg/ml) acidified to pH 4.0 with propionic or acetic acid. Control loops received casein only (pH 5.0). Mucosal damage was quantified by the blood-to-lumen movement of [51Cr]EDTA, fluid shifts into the lumen, and histology. Mean arterial pressure and loop blood flow were steady over the 3-hr period, loop fluid volume decreased, and there was no evidence of necrosis or epithelial damage. In loops receiving acidified casein and calcium gluconate, there was an immediate dramatic increase in loop blood flow that returned to baseline by 50 min. In addition, loop fluid volume was dramatically increased, necrosis was noted in the form of blunting and loss of villi, and sevenfold increase in [51Cr]EDTA permeability was evident. Administration of CV 1808 (30 mg/kg/hr), a selective adenosine2 agonist, which maintained and elevated loop blood flow throughout the 3 hr protocol, failed to alter the changes in loop fluid volume or prevent necrosis. Histamine levels in loop fluid levels were significantly elevated 20-30 min after NEC induction when compared to saline controls, indicating an early activation of mucosal defenses with this luminal insult. Thus, this model of NEC is characterized by a transient, acute hyperemia, increased intestinal permeability, and histamine release. As mucosal damage was independent of ischemia and could not be prevented by vasodilatory therapy, this model supports the clinical findings that NEC is correlated with luminal factors related to feeding and independent of cardiovascular stress

Immediate effect of benzalkonium chloride in decongestant nasal spray on the human nasal mucosal temperature.

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Lindemann, J; Leiacker, R; Wiesmiller, K; Rettinger, G; Keck, T

2004-08-01

Benzalkonium chloride is a preservative commonly used in nasal decongestant sprays. It has been suggested that benzalkonium chloride may be harmful to the nasal mucosa. Decongestion with the vasoconstrictor xylometazoline containing benzalkonium chloride has been shown to cause a significant reduction of the nasal mucosal temperature. The purpose of the present study was to determine the short-term influence of xylometazoline nasal spray with and without benzalkonium chloride on the nasal mucosal temperature. Healthy volunteers (30) were included in the study. Fifteen volunteers received xylometazoline nasal spray (1.0 mg/mL) containing benzalkonium chloride (0.1 mg/mL) and 15 age-matched subjects, received xylometazoline nasal spray without benzalkonium chloride. Using a miniaturized thermocouple the septal mucosal temperature was continuously measured at defined intranasal detection sites before and after application of the nasal spray. The mucosal temperature values did not significantly differ between the group receiving xylometazoline containing benzalkonium chloride and the group receiving xylometazoline spray without benzalkonium chloride before and after decongestion (P > 0.05). In both study groups septal mucosal temperatures significantly decreased after decongestion (P reduction of the nasal mucosal blood flow following vasoconstriction. This study indicates that benzalkonium chloride itself does not seem to influence nasal blood flow and nasal mucosal temperature in topical nasal decongestants.

Gastric mucosal defence mechanism during stress of pyloric obstruction in albino rats.

Science.gov (United States)

Somasundaram, K; Ganguly, A K

1987-04-01

1. The integrity of the gastric mucosa and its ability to secrete mucus are believed to be essential for protection of gastric mucosa against ulceration induced by aggressive factors active in any stress situation. This study involves a three-compartmental analysis of gastric mucosal barrier in pylorus-ligated albino rats. 2. Quantitative analyses of histologically identifiable gastric mucosal epithelial neutral glycoproteins and gastric adherent mucus from oxyntic and pyloric gland areas, and components of non-dialysable mucosubstances in gastric secretion were made under stress of pyloric obstruction for 4, 8, and 16 h durations. Epithelial mucin was identified by periodic acid-Schiff (PAS) staining technique and assessed from the ratio of gastric mucosal thickness to the depth of PAS positive materials in it. The remaining visible mucus adhered to the gastric mucosa was estimated by Alcian blue binding technique. The results were compared with that of identical control groups. 3. A significant reduction in mucosal epithelial PAS positive materials after 8 or 16 h of pylorus ligation was observed. 4. The Alcian blue binding capacity of the pyloric gland area was increased significantly after 4 h of pylorus ligation, while after 8 or 16 h it was reduced in both oxyntic and pyloric gland areas. 5. Significant reductions in the rate of gastric secretion and volume, as well as concentration of the components of non-dialysable mucosubstances, were observed, indicating decreased synthesis of mucus glycoproteins. 6. Disruption of the mucosal barrier may have occurred due to decreased mucus synthesis and acid-pepsin accumulation; both could be due to stress associated with gastric distension. 7. The present findings confirm the role of mucus in protecting the underlying gastric epithelium during stress. The adherent mucus offers a first line of defence and epithelial mucus a second line of defence.

Prophylaxis of mucosal toxicity by oral propantheline and cryotherapy in children with malignancies undergoing myeloablative chemo-radiotherapy

International Nuclear Information System (INIS)

Sato, Atsushi; Imaizumi, Masue; Saisho-Hattori, Takako; Koizumi, Yoshitsugu; Iinuma, Kazuie; Minegishi, Masayoshi

2006-01-01

Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders, and is physically and psychologically distressful. It is therefore important to minimize mucosal toxicity in those patients. In this report, the effects of the combined prophylaxis of oral cooling (cryotherapy) and administration of propantheline, an anticholinergic drug, were studied in patients (aged 2-16 year) with acute leukemias or solid tumors, who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997. Patients were pretreated with the combined prophylaxis (n=12) or single prophylaxis (n=5), or left untreated (n=7). The combined prophylaxis significantly reduced the severe mucositis (combined, 8.3%; single, 20.0%; and untreated, 42.9%) and severe diarrhea (combined, 16.7%; single, 60.0%; and untreated, 57.1%). Moreover, the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature >38 deg C (combined, 3.8 days; single, 4.6 days; and untreated, 5.6 days). Therefore, the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy. (author)

Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake

NARCIS (Netherlands)

Mars, M.; Graaf, de C.; Groot, de C.P.G.M.; Kok, F.J.

2005-01-01

The decrease in leptin after energy restriction is a starvation signal to the brain. Several studies have found an association between this decrease and subjective appetite; however, no solid data are available on the acute decrease in fasting leptin concentration and subsequent caloric

Use of 60Co panoramic source in the induction of oral mucositis in rats

International Nuclear Information System (INIS)

Andrade, Maira F.; Benetti, Carolina; Zezell, Denise M.; Correa, Luciana

2013-01-01

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 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)

Radio and chemioinduced oral mucositis treatment: comparison between conventional drug protocol and treatments with low intensity lasers

International Nuclear Information System (INIS)

Alencar, Anelise Ribeiro Peixoto

2011-01-01

In this clinical study verified the effects of low intensity laser in the prevention and treatment of oral mucositis radio and/or chemical induced. Thirty one patients with head and neck cancer were selected before being submitted to cancer exclusive radiotherapy or radio and associated chemotherapy. The patients were distributed into three randomly groups as follows: group 1- (control) conventional medicine treatment; group 2 - conventional medicine treatment and daily laser therapy as soon as grade two oral mucositis appeared; group 3 - conventional medicine treatment and daily laser therapy to be initiated immediately before radiotherapy sessions.The irradiation parameters were: wavelength of 660nm, potency of 100mW, continuous mode, punctual application, 2J energy on thirty pre-determined 30 points, with 20s of exposure per point. The control group received medical treatment which consisted in using a set of preventive and therapeutic approach for acute radiation-induced adverse effects. Results were evaluated observing occurrence and grade of oral mucositis, score of pain, loss of body mass, use of nasogastric sound line, internment and interruption of oncologic treatment due to oral mucositis. The results showed that the preventive protocol as used was the most effective in prevention and treatment of oral mucositis and that its daily application contributed in relieving the painful symptomatology so collaborating to maintain and/or bettering the life quality of oncologic patients. (author)

Acute radiation proctitis. A clinical, histopathological and histochemical study

International Nuclear Information System (INIS)

Hovdenak, Nils

2004-01-01

The aim of the study is: 1) A sequential description of the clinical course of acute radiation proctitis during pelvic RT. 2) A sequential description of the rectal mucosal histopathology during pelvic RT as a possible substrate for clinical toxicity. 3) To assess the mucosal protease activity during RT as a possible explanation of the observed tissue changes. 4) To assess the efficacy of prophylactic sucralfate in acute radiation proctitis a randomised study was initiated and carried out together with a meta-analysis of previously available data. 5) Most studies on clinical acute toxicity in pelvic RT use either the RTOG/EORTC score system or focus on diarrhoea/stool frequency. A more differentiated and sensitive recording was developed and tested to pick up symptoms escaping the commonly used scores. 6) Study the relation between histopathological findings and the clinical picture. 4 papers presenting various studies are included. The titles are: 1) Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy. 2) Clinical significance of increased gelatinolytic activity in the rectal mucosa during external beam radiation therapy of prostate cancer. 3) Profiles and time course of acute radiation toxicity symptoms during conformal radiotherapy for cancer of the prostate. 4) Sucralfate does not ameliorate acute radiation proctitis. Some future prospects are discussed

Acute radiation proctitis. A clinical, histopathological and histochemical study

Energy Technology Data Exchange (ETDEWEB)

Hovdenak, Nils

2004-07-01

The aim of the study is: 1) A sequential description of the clinical course of acute radiation proctitis during pelvic RT. 2) A sequential description of the rectal mucosal histopathology during pelvic RT as a possible substrate for clinical toxicity. 3) To assess the mucosal protease activity during RT as a possible explanation of the observed tissue changes. 4) To assess the efficacy of prophylactic sucralfate in acute radiation proctitis a randomised study was initiated and carried out together with a meta-analysis of previously available data. 5) Most studies on clinical acute toxicity in pelvic RT use either the RTOG/EORTC score system or focus on diarrhoea/stool frequency. A more differentiated and sensitive recording was developed and tested to pick up symptoms escaping the commonly used scores. 6) Study the relation between histopathological findings and the clinical picture. 4 papers presenting various studies are included. The titles are: 1) Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy. 2) Clinical significance of increased gelatinolytic activity in the rectal mucosa during external beam radiation therapy of prostate cancer. 3) Profiles and time course of acute radiation toxicity symptoms during conformal radiotherapy for cancer of the prostate. 4) Sucralfate does not ameliorate acute radiation proctitis. Some future prospects are discussed.

Effects of synbiotics on intestinal mucosal barrier in rat model

Directory of Open Access Journals (Sweden)

Zhigang Xue

2017-06-01

Conclusions: Probiotics can improve the concentration of colonic probiotics, while synbiotics can improve probiotics concentration and mucosa thickness in colon, decrease L/M ratio and bacterial translocation. Synbiotics shows more protective effects on intestinal mucosal barrier in rats after cecectomy and gastrostomy and the intervention of specific antibiotics.

Prospective Evaluation to Establish a Dose Response for Clinical Oral Mucositis in Patients Undergoing Head-and-Neck Conformal Radiotherapy

International Nuclear Information System (INIS)

Narayan, Samir; Lehmann, Joerg; Coleman, Matthew A.; Vaughan, Andrew; Yang, Claus Chunli; Enepekides, Danny; Farwell, Gregory; Purdy, James A.; Laredo, Grace; Nolan, Kerry A.S.; Pearson, Francesca S.; Vijayakumar, Srinivasan

2008-01-01

Purpose: We conducted a clinical study to correlate oral cavity dose with clinical mucositis, perform in vivo dosimetry, and determine the feasibility of obtaining buccal mucosal cell samples in patients undergoing head-and-neck radiation therapy. The main objective is to establish a quantitative dose response for clinical oral mucositis. Methods and Materials: Twelve patients undergoing radiation therapy for head-and-neck cancer were prospectively studied. Four points were chosen in separate quadrants of the oral cavity. Calculated dose distributions were generated by using AcQPlan and Eclipse treatment planning systems. MOSFET dosimeters were used to measure dose at each sampled point. Each patient underwent buccal sampling for future RNA analysis before and after the first radiation treatment at the four selected points. Clinical and functional mucositis were assessed weekly according to National Cancer Institute Common Toxicity Criteria, Version 3. Results: Maximum and average doses for sampled sites ranged from 7.4-62.3 and 3.0-54.3 Gy, respectively. A cumulative point dose of 39.1 Gy resulted in mucositis for 3 weeks or longer. Mild severity (Grade ≤ 1) and short duration (≤1 week) of mucositis were found at cumulative point doses less than 32 Gy. Polymerase chain reaction consistently was able to detect basal levels of two known radiation responsive genes. Conclusions: In our sample, cumulative doses to the oral cavity of less than 32 Gy were associated with minimal acute mucositis. A dose greater than 39 Gy was associated with longer duration of mucositis. Our technique for sampling buccal mucosa yielded sufficient cells for RNA analysis using polymerase chain reaction

Mucosal immunization using proteoliposome and cochleate structures from Neisseria meningitidis serogroup B induce mucosal and systemic responses.

Science.gov (United States)

Campo, Judith Del; Zayas, Caridad; Romeu, Belkis; Acevedo, Reinaldo; González, Elizabeth; Bracho, Gustavo; Cuello, Maribel; Cabrera, Osmir; Balboa, Julio; Lastre, Miriam

2009-12-01

Most pathogens either invade the body or establish infection in mucosal tissues and represent an enormous challenge for vaccine development by the absence of good mucosal adjuvants. A proteoliposome-derived adjuvant from Neisseria meningitidis serogroup B (AFPL1, Adjuvant Finlay Proteoliposome 1) and its derived cochleate form (Co, AFCo1) contain multiple pathogen-associated molecular patterns as immunopotentiators, and can also serve as delivery systems to elicit a Th1-type immune response. The present studies demonstrate the ability of AFPL1and AFCo1 to induce mucosal and systemic immune responses by different mucosal immunizations routes and significant adjuvant activity for antibody responses of both structures: a microparticle and a nanoparticle with a heterologous antigen. Therefore, we used female mice immunized by intragastric, intravaginal, intranasal or intramuscular routes with both structures alone or incorporated with ovalbumin (OVA). High levels of specific IgG antibody were detected in all sera and in vaginal washes, but specific IgA antibody in external secretions was only detected in mucosally immunized mice. Furthermore, antigen specific IgG1 and IgG2a isotypes were all induced. AFPL1 and AFCo1 are capable of inducing IFN-gamma responses, and chemokine secretions, like MIP-1alpha and MIP-1beta. However, AFCo1 is a better alternative to induce immune responses at mucosal level. Even when we use a heterologous antigen, the AFCo1 response was better than with AFPL1 in inducing mucosal and systemic immune responses. These results support the use of AFCo1 as a potent Th1 inducing adjuvant particularly suitable for mucosal immunization.

Proton Beam Therapy as a Nonsurgical Approach to Mucosal Melanoma of the Head and Neck: A Pilot Study

International Nuclear Information System (INIS)

Zenda, Sadamoto; Kawashima, Mitsuhiko; Nishio, Teiji; Kohno, Ryosuke; Nihei, Keiji; Onozawa, Masakatsu; Arahira, Satoko; Ogino, Takashi

2011-01-01

Purpose: The aim of this pilot study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the head and neck. Methods and Materials: Patients with mucosal melanoma of the head and neck with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. Results: Fourteen consecutive patients were enrolled from January 2004 through February 2008. Patient characteristics were as follows: median age 73 years old (range, 56 to 79 years); male/female ratio, 7/7; and T stage 1/2/3/4, 3/2/0/9. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 21%) and mild dermatitis (grade 3, 0%). As for late toxicity, 2 patients had a unilateral decrease in visual acuity, although blindness did not occur. No treatment-related deaths occurred throughout the study. Initial local control rate was 85.7%, and, with a median follow-up period of 36.7 months, median progression-free survival was 25.1 months, and 3-year overall survival rates were 58.0%. The most frequent site of first failure was cervical lymph nodes (6 patients), followed by local failure in 1 patient and lung metastases in 1 patient. On follow-up, 5 patients died of disease, 4 died due to cachexia caused by distant metastases, and 1 patient by carotid artery perforation cause by lymph nodes metastases. Conclusions: Proton beam radiotherapy showed promising local control benefits and would benefit from ongoing clinical study.

Proton Beam Therapy as a Nonsurgical Approach to Mucosal Melanoma of the Head and Neck: A Pilot Study

Energy Technology Data Exchange (ETDEWEB)

Zenda, Sadamoto [Division of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Chiba (Japan); Kawashima, Mitsuhiko; Nishio, Teiji; Kohno, Ryosuke; Nihei, Keiji; Onozawa, Masakatsu; Arahira, Satoko; Ogino, Takashi [Division of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Chiba (Japan)

2011-09-01

Purpose: The aim of this pilot study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the head and neck. Methods and Materials: Patients with mucosal melanoma of the head and neck with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. Results: Fourteen consecutive patients were enrolled from January 2004 through February 2008. Patient characteristics were as follows: median age 73 years old (range, 56 to 79 years); male/female ratio, 7/7; and T stage 1/2/3/4, 3/2/0/9. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 21%) and mild dermatitis (grade 3, 0%). As for late toxicity, 2 patients had a unilateral decrease in visual acuity, although blindness did not occur. No treatment-related deaths occurred throughout the study. Initial local control rate was 85.7%, and, with a median follow-up period of 36.7 months, median progression-free survival was 25.1 months, and 3-year overall survival rates were 58.0%. The most frequent site of first failure was cervical lymph nodes (6 patients), followed by local failure in 1 patient and lung metastases in 1 patient. On follow-up, 5 patients died of disease, 4 died due to cachexia caused by distant metastases, and 1 patient by carotid artery perforation cause by lymph nodes metastases. Conclusions: Proton beam radiotherapy showed promising local control benefits and would benefit from ongoing clinical study.

Pharmacokinetics of flomoxef in mucosal tissue of the middle ear and mastoid following intravenous administration in humans.

Science.gov (United States)

Saito, H; Kimura, T; Takeda, T; Kishimoto, S; Oguma, T; Shimamura, K

1990-01-01

The pharmacokinetics of flomoxef in serum and in the mucosal tissue of the middle ear and mastoid were studied in 9 patients undergoing tympanoplasties. All patients received 1 g of flomoxef intravenously. Flomoxef levels in serum and in mucosal tissue were determined by a bioassay method. The peak value of mean concentrations of flomoxef in the mucosal tissue was 30.3 +/- 11.7 micrograms/ml at 10 min after the administrations. Pharmacokinetic analyses showed that the concentration of flomoxef in the mucosal tissue was over 1.56 micrograms/ml (which is the MIC90 for the common pathogens of otitis media) for more than 2 h and decreased parallel with serum concentration with a half-life of about 40 min.

Irradiation mucositis and oral flora

International Nuclear Information System (INIS)

Spijkervet, F.K.L.

1989-01-01

This study, which is motivated by the substantial morbidity of local signs of mucositis and generalized symptoms that result from mucositis induced by therapeutic irradiation, has the following objectives: To investigate if it is possible to prevent irradiation mucositis via oral flora elimination, and, if it is true that flora plays a role in irradiation mucositis, what fraction of the oral flora may be involved; to evaluate oral Gram-negative bacillary carriage; to investigate the possibility to eradicate Gram-negative bacilli from the oral cavity; to evaluate oral yeast carriage; to investigate the possibility to eradicate yeasts stomatitis and the 'selectivity' of elimination of flora. Two methods are described for monitoring alterations of mucositis of the oral cavity and changes in oral flora. Chlorhexidine has been tested as the commonly used prophylaxis. The effect of chlorhexidine 0.1% rinses on oral flora and mucositis has been studied in a prospective placebo controlled double blind randomized programme. The results of the influence of saliva on the antimicrobial activity of chlorhexidine and the results of selective elimination of oral flora in irradiated patients who have head and neck cancer are reported. Salivary inactivation of the topical antimicrobials used for selective elimination of oral flora has been studied and the results are reported. Finally, the objectives that have been achieved (or not) are delineated. The significance of the results of the study are discussed in terms of published information and further lines of research are suggested. (author). 559 refs.; 29 figs.; 20 tabs

Chemotherapy: the effect of oral cryotherapy on the development of mucositis.

Science.gov (United States)

Karagözoğlu, Serife; Filiz Ulusoy, Mehlika

2005-07-01

The aim of this study is to investigate the effect of oral cryotherapy on the development of chemotherapy-induced mucositis in patients administered combined chemotherapy. Mucositis has been of interest to scientists for more than 20 years. Unfortunately, this has not resulted in the development of standard procedures for prevention and management. To cope with this side-effect and to prevent opportunistic infections that may emerge during treatment, attempts are taken to provide preventative and comfort measures. In this context, cryotherapy (oral cooling) has become popular as a cheap and readily applicable method in preventing the developing due the rapid infusion of chemotherapy agents, or decreasing its severity. Study involved 60 patients, 30 of whom were in the study group and 30 in the control group. Ice cubes at a size that can be moved easily in the mouth and whose corners have been smoothed in order that they will not cause irritation in the mouth has been used in oral cryotherapy in the study group. Oral chemotherapy was initiated five minutes before chemotherapy and maintained during venous infusions of etoposide (Vepesid), platinol (Cisplatin), mitomycin (Mitomycin-C) and vinblastin (Velbe) depending on the chemotherapy course. According to Patient-Judged Mucositis Grading, the rate of mucositis is 36.7% in study group and 90.0% in control group, the difference between two groups being statistically significant (P cryotherapy makes an important contribution to the protection of oral health by reducing the mucositis score according to patient- and physician-judged mucositis score and by increasing oral pH values. Aggressive cancer therapy places patients at greater risk for oral complications and treatment-related consequences. Unfortunately, prevention and/or treatment of such oral sequelae have often become overlooked as priorities of the treatment team. Effective approaches for the prevention or treatment of oral mucositis have not been standardized

The Multidisciplinary Swallowing Team Approach Decreases Pneumonia Onset in Acute Stroke Patients.

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Shiro Aoki

Full Text Available Dysphagia occurs in acute stroke patients at high rates, and many of them develop aspiration pneumonia. Team approaches with the cooperation of various professionals have the power to improve the quality of medical care, utilizing the specialized knowledge and skills of each professional. In our hospital, a multidisciplinary participatory swallowing team was organized. The aim of this study was to clarify the influence of a team approach on dysphagia by comparing the rates of pneumonia in acute stroke patients prior to and post team organization. All consecutive acute stroke patients who were admitted to our hospital between April 2009 and March 2014 were registered. We analyzed the difference in the rate of pneumonia onset between the periods before team organization (prior period and after team organization (post period. Univariate and multivariate analyses were performed using a Cox proportional hazards model to determine the predictors of pneumonia. We recruited 132 acute stroke patients from the prior period and 173 patients from the post period. Pneumonia onset was less frequent in the post period compared with the prior period (6.9% vs. 15.9%, respectively; p = 0.01. Based on a multivariate analysis using a Cox proportional hazards model, it was determined that a swallowing team approach was related to pneumonia onset independent from the National Institutes of Health Stroke Scale score on admission (adjusted hazard ratio 0.41, 95% confidence interval 0.19-0.84, p = 0.02. The multidisciplinary participatory swallowing team effectively decreased the pneumonia onset in acute stroke patients.

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

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Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

2017-01-01

During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

Preventive Effect of Glycyrrhiza Glabra Extract on Oral Mucositis in Patients under Head and Neck Radiotherapy: A Randomized Clinical Trial

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Shamsolmolok Najafi

2017-12-01

Full Text Available Objectives: About two-thirds of cancer patients undergo radiotherapy. Oral mucositis represents a major complication of radiotherapy, causing morbidity and mortality and decreasing the quality of life of patients. This study aimed to assess the preventive effect of Glycyrrhiza aqueous extract on oral mucositis in cancer patients under head and neck radiotherapy.Materials and Methods: In this double-blind clinical trial, 37 head and neck cancer patients were divided into intervention (n=19 group receiving Glycyrrhiza aqueous extract and control (n=18 group receiving placebo. Patients in the test group used Glycyrrhiza aqueous extract topically twice a day from the first day of starting radiotherapy until the end of the second week. Patients were examined in the first day of radiotherapy for any type of wound before treatment and those with oral ulcers before radiotherapy were excluded from the study. The grade of mucositis was determined using the classification by the World Health Organization. ANCOVA was performed to assess any difference between the two groups with regard to oral mucosal irritation and wound size after the intervention while controlling for the covariates such as sex and age.Results: Significant differences were found in the maximum grade of mucositis and oral mucosal irritation between the intervention and control groups (P<0.001.Conclusions: This study showed that aqueous extract of Glycyrrhiza can be effective for decreasing the severity of oral mucositis in head and neck cancer patients undergoing radiotherapy.

Mucosal vaccines: recent progress in understanding the natural barriers.

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Borges, Olga; Lebre, Filipa; Bento, Dulce; Borchard, Gerrit; Junginger, Hans E

2010-02-01

It has long been known that protection against pathogens invading the organism via mucosal surfaces correlates better with the presence of specific antibodies in local secretions than with serum antibodies. The most effective way to induce mucosal immunity is to administer antigens directly to the mucosal surface. The development of vaccines for mucosal application requires antigen delivery systems and immunopotentiators that efficiently facilitate the presentation of the antigen to the mucosal immune system. This review provides an overview of the events within mucosal tissues that lead to protective mucosal immune responses. The understanding of those biological mechanisms, together with knowledge of the technology of vaccines and adjuvants, provides guidance on important technical aspects of mucosal vaccine design. Not being exhaustive, this review also provides information related to modern adjuvants, including polymeric delivery systems and immunopotentiators.

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

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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)

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

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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)

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

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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)

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

International Nuclear Information System (INIS)

Galletta, Vivian C.; Folgosi-Correa, Melissa S.; Zezell, Denise M.; Gouw-Soares, Sheila; Correa, Luciana

2013-01-01

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 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)

Radiation-induced mucositis pain in laryngeal cancer

International Nuclear Information System (INIS)

Takahashi, Atsuhito; Shoji, Kazuhiko; Iki, Takehiro; Mizuta, Masanobu; Matsubara, Mami

2009-01-01

Radiation therapy in those with head and neck malignancies often triggers painful mucositis poorly controlled by nonsteroidal antiinflammatory drugs (NSAIDs). To better understand how radiation-induced pain develops over time, we studied the numerical rating scale (NRS 0-5) pain scores from 32 persons undergoing radiation therapy of 60-72 Gy for newly diagnosed laryngeal cancer. The degree of mucositis was evaluated using Common Terminology Criteria for Adverse Events version3.0 (CTCAE v3.0). We divided the 32 into a conventional fractionation (CF) group of 14 and a hyperfractionation (HF) group of 18, and further divided laryngeal cancer into a small-field group of 23 and a large-field group of 9. The mucositis pain course was similar in CF and HF, but mucositis pain was severer in the HF group, which also required more NSAIDs. Those in the large-field group had severer pain and mucositis and required more NSAIDs than those in the small-field group. We therefore concluded that small/large-field radiation therapy, rather fractionation type, was related to the incidence of radiation-induced mucositis pain. (author)

Use of Bidens pilosa L. (Asteraceae and Curcuma longa L. (Zingiberaceae to treat intestinal mucositis in mice: Toxico-pharmacological evaluations

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Carla Caroline Cunha Bastos

Full Text Available Introduction: Several studies towards the development of an effective treatment for intestinal mucositis have been reported, since this condition represents a major problem in clinical oncology practice due to cytotoxic effects of chemotherapy. However standardized protocols and universally accepted treatment options are yet to be established. Objectives: Given above, this study evaluated the protective effects of a mucoadhesive formulation containing both Bidens pilosa L. (Asteraceae (BP and curcuminoids from Curcuma longa L. (Zingiberaceae (CL on intestinal mucositis induced by 5-fluoruoacil (5-FU in mice. Results: As expected, animals only treated with 5-FU (200 mg/kg showed a significant reduction of 60.3 and 42.4% in villi and crypts size, respectively, when compared to control. On the other hand, the proposed therapeutic/prophylactic treatment with mucoadhesive formulations managed to reduce histopathologic changes in mice bearing mucositis, especially at 125 mg/kg BP + 15 mg/kg CL dose. The formulation promoted an increase of 275.5% and 148.7% for villi and crypts size, respectively. Moreover, chemotherapy-related weight loss was reduced by 7.4% following the treatment. In addition, an increase of 10 and 30.5% in red and white blood cells was observed when compared to 5-FU group. Furthermore, treatments with the mucoadhesive formulation containing BP/CL up modulated Ki-67 and Bcl-2 expression while reduced pro-apoptotic regulator Bax. The formulation also modulated inflammatory response triggered by 5-FU through reduction of 68% of myeloperoxidase activity and a 4-fold increase in anti-inflammatory IL-10 levels. In parallel, the oxidative stress via lipid peroxidation was reduced as indicated by decrease of 63% of malondialdehyde concentrations. Additionally, the new formulation presented low acute oral systemic toxicity, being classified in the category 5 (2000 mg/kg < LD50 < 5000 mg/kg of the Globally Harmonized

Dietary cysteine is used more efficiently by children with severe acute malnutrition with edema compared with those without edema

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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...

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents.

Science.gov (United States)

Eisenmann, Eric D; Rorabaugh, Boyd R; Zoladz, Phillip R

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions.

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

Science.gov (United States)

Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

Intrauterine Growth Restriction Impairs Small Intestinal Mucosal Immunity in Neonatal Piglets

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Dong, Li; Zhong, Xiang; Ahmad, Hussain; Li, Wei; Wang, Yuanxiao; Zhang, Lili

2014-01-01

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. PMID:24710659

Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection

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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.

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

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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.

Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced mucositis.

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Wang, Hanru; Brook, Caitlin L; Whittaker, Alexandra L; Lawrence, Andrew; Yazbeck, Roger; Howarth, Gordon S

2013-08-01

Mucositis is a debilitating intestinal side effect of chemotherapeutic regimens. Probiotics have been considered a possible preventative treatment for mucositis. Streptococcus thermophilus TH-4 (TH-4), a newly identified probiotic, has been shown to partially alleviate mucositis induced by administration of the antimetabolite chemotherapy drug, methotrexate in rats; likely mediated through a mechanism of folate production. However, its effects against other classes of chemotherapy drug have yet to be determined. The authors investigated the effects of TH-4 in a rat model of mucositis induced by the anthracycline chemotherapy drug, doxorubicin. Gastrointestinal damage was induced in female Dark Agouti rats (148.3 ± 1.5 g) by intraperitoneal injection of doxorubicin (20 mg/kg). Animals recieved a daily oral gavage of TH-4 at 10(9) cfu/ml or skim milk (vehicle) from days 0 to 8. At day 6, rats were injected with either saline or doxorubicin. At kill, small intestinal tissues were collected for determination of sucrase and myeloperoxidase (MPO) activities and histological assessment. Body weight was significantly decreased by doxorubicin compared with normal controls (p TH-4 partially prevented the loss of body weight induced by doxorubicin (2.3% compared with 4%), but provided no further therapeutic benefit. The minimal amelioration of doxorubicin-induced mucositis by TH-4 further supports folate production as a likely mechanism of TH-4 action against methotrexate-induced mucositis. Further studies into TH-4 are required to confirm its applicability to other conventional chemotherapy regimens.

Self-reported pain perception of patients after mucosal graft harvesting in the palatal area.

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Burkhardt, Rino; Hämmerle, Christoph H F; Lang, Niklaus P

2015-03-01

To evaluate the patient-reported pain perception after palatal graft harvesting during a 4 weeks healing period Ninety patients, scheduled for different periodontal and peri-implant plastic surgeries requiring palatal mucosal graft harvesting, were consecutively recruited. Mucosal thickness was measured at the donor sites with an ultrasonic device prior to the surgeries. Graft thickness, length, and width were assessed after harvesting, and the wound areas were calculated. Based on a Visual Analogue Scale (VAS), the patients were asked to report their perceived pain after the intervention and 1, 3, 7, 14, 21 and 28 days thereafter. Pain was most pronounced on the first postoperative day and decreased within the course of time. Graft thickness directly correlated with the amount of pain perceived while increased palatal mucosal thickness before and after graft harvesting decreased pain levels. The denuded wound surface area, however, did not influence the perceived pain level. The wound depth at the donor site (graft thickness) was positively correlated with the patient's perception for pain. The wound surface area, however, did not influence the perceived pain level. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2–4 Laryngeal Cancer: Results of a Phase III Randomized Trial

International Nuclear Information System (INIS)

Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; Ende, Piet van den; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

2012-01-01

Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2–4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2–4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2–4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

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.

A New Model for Predicting Acute Mucosal Toxicity in Head-and-Neck Cancer Patients Undergoing Radiotherapy With Altered Schedules

International Nuclear Information System (INIS)

Strigari, Lidia; Pedicini, Piernicola; D’Andrea, Marco; Pinnarò, Paola; Marucci, Laura; Giordano, Carolina; Benassi, Marcello

2012-01-01

Purpose: One of the worst radiation-induced acute effects in treating head-and-neck (HN) cancer is grade 3 or higher acute (oral and pharyngeal) mucosal toxicity (AMT), caused by the killing/depletion of mucosa cells. Here we aim to testing a predictive model of the AMT in HN cancer patients receiving different radiotherapy schedules. Methods and Materials: Various radiotherapeutic schedules have been reviewed and classified as tolerable or intolerable based on AMT severity. A modified normal tissue complication probability (NTCP) model has been investigated to describe AMT data in radiotherapy regimens, both conventional and altered in dose and overall treatment time (OTT). We tested the hypothesis that such a model could also be applied to identify intolerable treatment and to predict AMT. This AMT NTCP model has been compared with other published predictive models to identify schedules that are either tolerable or intolerable. The area under the curve (AUC) was calculated for all models, assuming treatment tolerance as the gold standard. The correlation between AMT and the predicted toxicity rate was assessed by a Pearson correlation test. Results: The AMT NTCP model was able to distinguish between acceptable and intolerable schedules among the data available for the study (AUC = 0.84, 95% confidence interval = 0.75-0.92). In the equivalent dose at 2 Gy/fraction (EQD2) vs OTT space, the proposed model shows a trend similar to that of models proposed by other authors, but was superior in detecting some intolerable schedules. Moreover, it was able to predict the incidence of ≥G3 AMT. Conclusion: The proposed model is able to predict ≥G3 AMT after HN cancer radiotherapy, and could be useful for designing altered/hypofractionated schedules to reduce the incidence of AMT.

The analysis of bacterial culture in radiation mucositis

International Nuclear Information System (INIS)

Wen Zunbei; Su Deqing; Liang Yuxue

2006-01-01

Objective: To investigate pathogen dose existing or not in patients with radiation mucositis. Methods: From Juanary 2004 to August 2005, from 46 patients with radiation mucositis some pharynx secretion were taken for culture. Then they were treated with antibiotics selected by the cultured results and gargle. Results: 5 patients with grade 0 of radiation mucositis were with no cultured pathogen, and the results of some other patients with radiation mucositis include 8 cases of epiphyte, 1 cases of p. vulgaris and 3 cases of Staphylococcus. the positive rate is 29.2% (12/41); Conclusion: Some patients with radiation mucositis do exist pathogen, and we must slect antibiotics by the bacterial cultured results. (authors)

Acute stress decreases but chronic stress increases myocardial sensitivity to ischemic injury in rodents

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Eric D Eisenmann

2016-04-01

Full Text Available Cardiovascular disease is the largest cause of mortality worldwide, and stress is a significant contributor to the development of cardiovascular disease. The relationship between acute and chronic stress and cardiovascular disease is well-evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury. Conversely, chronic stress is arrythmogenic and increases sensitivity to myocardial ischemia-reperfusion injury. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions.

Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

Science.gov (United States)

Kutsuna, Nobuo; Yamashita, Akiko; Eriguchi, Takashi; Oshima, Hideki; Suma, Takeshi; Sakatani, Kaoru; Yamamoto, Takamitsu; Yoshino, Atsuo; Katayama, Yoichi

2014-01-01

Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Scoring irradiation mucositis in head and neck cancer patients

International Nuclear Information System (INIS)

Spijkervet, F.K.L.; Panders, A.K.; Saene, H.K.F. van; Vermey, A.; Mehta, D.M.

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)

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).

BISPHOSPHONATE - RELATED MUCOSITIS (BRM: A CASE REPORT

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Pavel Stanimirov

2017-03-01

Full Text Available Bisphosphonates (BPs are the most widely used and effective antiresorptive agents for the treatment of diseases in which there is an increase in osteoclastic resorption, including post-menopausal osteoporosis, Paget’s disease, and tumor-associated osteolysis. Oral and maxillofacial surgeons are well aware of the side effects of bisphosphonates and mainly with bisphosphonate-related osteonecrosis of the jaws (BRONJ. Less known are the mucosal lesions associated with the use of these agents. In the scientific literature, there are only few reports of mucosal lesions due to the direct contact of the oral form of BPs with the mucosa (bisphosphonate-related mucositis. They are mostly related to improper use of bisphosphonate tablets that are chewed, sucked or allowed to melt in the mouth before swallowing. Lesions are atypical and need to be differentiated from other mucosal erosions. We present a case of bisphosphonate-related mucositis due to the improper use of alendronate.

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

International Nuclear Information System (INIS)

Kelner, Natalie; Castro, Jurema Freire Lisboa de

2007-01-01

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)

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)

Treatment modalities of oral mucositis after radiation of head and neck cancers

International Nuclear Information System (INIS)

Lapeyre, M.; Charra-Brunaud, C.; Kaminsky, M.C.; Geoffrois, L.; Dolivet, G.; Pourel, N.; Marchal, C.; Bey, P.; Maire, F.; Simon, M.; Toussaint, B.

2001-01-01

Acute mucositis is common after radiotherapy for head and neck cancers. During the past 3 decades, there was a gradual evolution in the treatment modalities for locally advanced carcinomas (concomitant radio-chemotherapy, accelerated radiotherapy). These new strategies are accompanied by an increase in early mucosal reactions. At the present time, there is no widely accepted prophylaxis or effective treatment. Many traditional remedies or new agents seem ineffective (Sucralfate, Chlorhexidine, GM-CSF, Silver nitrate, Prostaglandin, anti-oxidants, Benzydamine hydrochloride), while others seem promising (Povidone-iodine, nonabsorbable antibiotic lozenges and anti-fungal, local GM-CSF, Glutamide, Low-energy laser, corticosteroids). Radioprotectors are controversial and should be only used in experimental protocols and not in routine practice. However, some recommendations can be proposed: general prevention and global care before cancer therapy should be systematic (oral hygiene, dental and periodontal treatment, advice to avoid the use of tobacco and alcohol); frequent oral rinsing with a bland mouthwash (Povidone-iodine or others) should be used at the start of treatment because there are significant modifications of the oral microflora increased by a disturbed salivary flow; these mouthwashes could be associated with nonabsorbable antibiotic lozenges or anti-fungal topical (bicarbonates, Amphotericine B); Systematic percutaneous fluoroscopic gastrostomy should be decided before any aggressive treatments (concomitant radio-chemotherapy, accelerated radiotherapy); pain should be controlled; finally, the radiation technique should be optimized (mucosal sparing block, conformal radiotherapy and intensity modulated radiation therapy). (authors)

The role of Wnt/β-catenin signaling in enterocyte turnover during methotrexate-induced intestinal mucositis in a rat.

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Igor Sukhotnik

Full Text Available BACKGROUND/AIMS: Intestinal mucositis is a common side-effect in patients who receive aggressive chemotherapy. The Wnt signaling pathway is critical for establishing and maintaining the proliferative compartment of the intestine. In the present study, we tested whether Wnt/β-catenin signaling is involved in methotrexate (MTX-induced intestinal damage in a rat model. METHODS: Non-pretreated and pretreated with MTX Caco-2 cells were evaluated for cell proliferation and apoptosis using FACS analysis. Adult rats were divided into three experimental groups: Control rats; MTX-2 animals were treated with a single dose of MTX given IP and were sacrificed on day 2, and MTX-4 rats were treated with MTX similar to group B and were sacrificed on day 4. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation, and enterocyte apoptosis were measured at sacrifice. Real Time PCR and Western blot was used to determine the level of Wnt/β-catenin related genes and protein expression. RESULTS: In the vitro experiment, treatment with MTX resulted in marked decrease in early cell proliferation rates following by a 17-fold increase in late cell proliferation rates compared to early proliferation. Treatment with MTX resulted in a significant increase in early and late apoptosis compared to Caco-2 untreated cells. In the vivo experiment, MTX-2 and MTX-4 rats demonstrated intestinal mucosal hypoplasia. MTX-2 rats demonstrated a significant decrease in FRZ-2, Wnt 3A Wnt 5A, β-catenin, c-myc mRNA expression and a significant decrease in β-catenin and Akt protein levels compared to control animals. Four days following MTX administration, rats demonstrated a trend toward a restoration of Wnt/β-catenin signaling especially in ileum. CONCLUSIONS: Wnt/β-catenin signaling is involved in enterocyte turnover during MTX-induced intestinal mucositis in a rat.

Acute lymphoid and gastrointestinal toxicity induced by selective p38alpha map kinase and map kinase-activated protein kinase-2 (MK2) inhibitors in the dog.

Science.gov (United States)

Morris, Dale L; O'Neil, Shawn P; Devraj, Rajesh V; Portanova, Joseph P; Gilles, Richard W; Gross, Cindy J; Curtiss, Sandra W; Komocsar, Wendy J; Garner, Debra S; Happa, Fernando A; Kraus, Lori J; Nikula, Kristen J; Monahan, Joseph B; Selness, Shaun R; Galluppi, Gerald R; Shevlin, Kimberly M; Kramer, Jeffrey A; Walker, John K; Messing, Dean M; Anderson, David R; Mourey, Robert J; Whiteley, Laurence O; Daniels, John S; Yang, Jerry Z; Rowlands, Philip C; Alden, Carl L; Davis, John W; Sagartz, John E

2010-06-01

Exposure to moderately selective p38alpha mitogen-activated protein kinase (MAPK) inhibitors in the Beagle dog results in an acute toxicity consisting of mild clinical signs (decreased activity, diarrhea, and fever), lymphoid necrosis and depletion in the gut-associated lymphoid tissue (GALT), mesenteric lymph nodes and spleen, and linear colonic and cecal mucosal hemorrhages. Lymphocyte apoptosis and necrosis in the GALT is the earliest and most prominent histopathologic change observed, followed temporally by neutrophilic infiltration and acute inflammation of the lymph nodes and spleen and multifocal mucosal epithelial necrosis and linear hemorrhages in the colon and cecum. These effects are not observed in the mouse, rat, or cynomolgus monkey. To further characterize the acute toxicity in the dog, a series of in vivo, in vitro, and immunohistochemical studies were conducted to determine the relationship between the lymphoid and gastrointestinal (GI) toxicity and p38 MAPK inhibition. Results of these studies demonstrate a direct correlation between p38alpha MAPK inhibition and the acute lymphoid and gastrointestinal toxicity in the dog. Similar effects were observed following exposure to inhibitors of MAPK-activated protein kinase-2 (MK2), further implicating the role of p38alpha MAPK signaling pathway inhibition in these effects. Based on these findings, the authors conclude that p38alpha MAPK inhibition results in acute lymphoid and GI toxicity in the dog and is unique among the species evaluated in these studies.

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...

The postnatal development of the mucosal immune system and mucosal tolerance in domestic animals

OpenAIRE

Bailey , Mick; Haverson , Karin

2006-01-01

International audience; The mucosal immune system is exposed to a range of antigens associated with pathogens, to which it must mount active immune responses. However, it is also exposed to a large number of harmless antigens associated with food and with commensal microbial flora, to which expression of active, inflammatory immune responses to these antigens is undesirable. The mucosal immune system must contain machinery capable of evaluating the antigens to which it is exposed and mounting...

Mucosal immunogenicity of plant lectins in mice

Science.gov (United States)

Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O’Hagan, D T

2000-01-01

The mucosal immunogenicity of a number of plant lectins with different sugar specificities was investigated in mice. Following intranasal (i.n.) or oral administration, the systemic and mucosal antibody responses elicited were compared with those induced by a potent mucosal immunogen (cholera toxin; CT) and a poorly immunogenic protein (ovalbumin; OVA). After three oral or i.n. doses of CT, high levels of specific serum antibodies were measured and specific IgA was detected in the serum, saliva, vaginal wash, nasal wash and gut wash of mice. Immunization with OVA elicited low titres of serum IgG but specific IgA was not detected in mucosal secretions. Both oral and i.n. delivery of all five plant lectins investigated [Viscum album (mistletoe lectin 1; ML‐1), Lycospersicum esculentum (tomato lectin; LEA), Phaseolus vulgaris (PHA), Triticum vulgaris (wheat germ agglutinin (WGA), Ulex europaeus I (UEA‐1)] stimulated the production of specific serum IgG and IgA antibody after three i.n. or oral doses. Immunization with ML‐1 induced high titres of serum IgG and IgA in addition to specific IgA in mucosal secretions. The response to orally delivered ML‐1 was comparable to that induced by CT, although a 10‐fold higher dose was administered. Immunization with LEA also induced high titres of serum IgG, particularly after i.n. delivery. Low specific IgA titres were also detected to LEA in mucosal secretions. Responses to PHA, WGA and UEA‐1 were measured at a relatively low level in the serum, and little or no specific mucosal IgA was detected. PMID:10651938

Evidence for a common mucosal immune system in the pig.

Science.gov (United States)

Wilson, Heather L; Obradovic, Milan R

2015-07-01

The majority of lymphocytes activated at mucosal sites receive instructions to home back to the local mucosa, but a portion also seed distal mucosa sites. By seeding distal sites with antigen-specific effector or memory lymphocytes, the foundation is laid for the animal's mucosal immune system to respond with a secondary response should to this antigen be encountered at this site in the future. The common mucosal immune system has been studied quite extensively in rodent models but less so in large animal models such as the pig. Reasons for this paucity of reported induction of the common mucosal immune system in this species may be that distal mucosal sites were examined but no induction was observed and therefore it was not reported. However, we suspect that the majority of investigators simply did not sample distal mucosal sites and therefore there is little evidence of immune response induction in the literature. It is our hope that more pig immunologists and infectious disease experts who perform mucosal immunizations or inoculations on pigs will sample distal mucosal sites and report their findings, whether results are positive or negative. In this review, we highlight papers that show that immunization/inoculation using one route triggers mucosal immune system induction locally, systemically, and within at least one distal mucosal site. Only by understanding whether immunizations at one site triggers immunity throughout the common mucosal immune system can we rationally develop vaccines for the pig, and through these works we can gather evidence about the mucosal immune system that may be extrapolated to other livestock species or humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neonatal mucosal immunology.

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Torow, N; Marsland, B J; Hornef, M W; Gollwitzer, E S

2017-01-01

Although largely deprived from exogenous stimuli in utero, the mucosal barriers of the neonate after birth are bombarded by environmental, nutritional, and microbial exposures. The microbiome is established concurrently with the developing immune system. The nature and timing of discrete interactions between these two factors underpins the long-term immune characteristics of these organs, and can set an individual on a trajectory towards or away from disease. Microbial exposures in the gastrointestinal and respiratory tracts are some of the key determinants of the overall immune tone at these mucosal barriers and represent a leading target for future intervention strategies. In this review, we discuss immune maturation in the gut and lung and how microbes have a central role in this process.

Worse Neurological State During Acute Ischemic Stroke is Associated with a Decrease in Serum Albumin Levels.

Science.gov (United States)

Bielewicz, Joanna; Kurzepa, Jacek; Czekajska-Chehab, Elżbieta; Kamieniak, Piotr; Daniluk, Beata; Bartosik-Psujek, Halina; Rejdak, Konrad

2016-04-01

High serum albumin levels during ischemic stroke (IS) decrease the risk of a poor outcome. This study aimed to determine whether serum albumin levels within the first days after IS correlate with radiological and biochemical markers of brain tissue damage. Fifty-six IS patients were enrolled into the study. Neurological examinations were based on the National Institute of Health Stroke Scale. Serum albumin levels and S100BB were evaluated using commercially available ELISA kits. The albumin decrease index (ADI) was calculated as the difference between serum albumin levels measured on days 1 and 10 of IS. All parameters were estimated on the 1st, 3rd, 5th, and 10th days of IS, and the volume of ischemic focus was measured on the 10th day. Mean serum albumin levels were decreased during acute IS. There were correlations between the ADI and mean S100BB serum levels (r = 0.36, p albumin levels during the acute phase of IS corresponds to a worse neurological state as a result of a large ischemic focus with intense catabolic processes.

Sucralfate for the treatment of radiation induced mucositis

International Nuclear Information System (INIS)

Belka, C.; Hoffmann, W.; Paulsen, F.; Bamberg, M.

1997-01-01

Purpose: Radiotherapy, a cornerstone in the management of head and neck cancer, pelvic cancer, and esophageal cancer is associated with a marked mucosal toxicity. Pain, malnutrition and diarrhea are the most prevalent clinical symptoms of radiation induced mucosal damage. Because there is no known way to obviate radiation mucositis all efforts to prevent aggravation and accelerate healing of mucosal changes are of great importance. Numerous agents including antimicrobials, local and systemic analgesics, antiinflammatory drugs, antidiarrheal drugs, in combination with intensive dietetic care are used to relieve symptoms. Recently coating agents like the polyaluminum-sucrose complex sucralfate were suggested for the prevention and treatment of mucosal reactions. Since sucralfate protects ulcerated epithelium by coating, liberates protective prostaglandins and increases the local availability of protective factors this drug might directly interact with the pathogenesis of mucositis. Patients and Method: The results of available studies are analysed and discussed. Results: The results of several studies indicate that sucralfate treatment especially during radiotherapy for pelvic cancer leads to a significant amelioration of clinical symptoms and morphological changes. An application of sucralfate during radiotherapy of head and neck cancer reveals only limited benefits in most studies performed. Conclusion: Nevertheless sucralfate is a save, cheap and active drug for the prevention and treatment of radiation mucositis especially in patients with pelvic irradiation. (orig.) [de

Humidification mitigates acute mucosal toxicity during radiotherapy when factoring volumetric parameters. Trans Tasman Radiation Oncology Group (TROG) RadioHUM 07.03 substudy.

Science.gov (United States)

Macann, A; Fauzi, F; Simpson, J; Sasso, G; Krawitz, H; Fraser-Browne, C; Manitz, J; Raith, A

2017-12-01

To model in a subset of patients from TROG 07.03 managed at a single site the association between domiciliary based humidification use and mucositis symptom burden during radiotherapy (RT) for head and neck cancer (HNC) when factoring in volumetric radiotherapy parameters derived from tumour and normal tissue regions of interest. From June 2008 through June 2011, 210 patients with HNC receiving RT were randomised to either a control arm or humidification using the Fisher & Paykel Healthcare MR880 humidifier. This subset analysis involves patients recruited from Auckland City Hospital treated with a prescribed dose of ≥70 Gy. Regression models included control variables for Planning Target Volume 70 GY (PTV70Gy); Equivalent Uniform Dose (EUD) MOIST and TSV (surrogates of total mucosal and total swallowing volumes respectively). The analysis included 39 patients (humidification 20, control 19). There was a significant odds reduction in CTCAE v3.0 functional mucositis score of 0.29 associated with the use of humidification (pfactor of 11.11 for humidification patients (p=.013). The results support the hypothesis that humidification can help mitigate mucositis symptom burden. Radiotherapy dosimetric parameters assist in the evaluation of toxicity interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cutaneous and mucosal pain syndromes

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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.

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

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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.

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).

Management of mucositis in oral irradiation

International Nuclear Information System (INIS)

Feber, T.

1996-01-01

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)

Use of atropine to reduce mucosal eversion during intestinal resection and anastomosis in the dog.

Science.gov (United States)

Agrodnia, Marta; Hauptman, Joe; Walshaw, Richard

2003-01-01

To determine whether atropine altered the degree of mucosal eversion during jejunal resection and anastomosis in the dog. Part I: Prospective, blinded, randomized, controlled study using a therapeutic dose (0.04 mg/kg systemic) of atropine. Part II: Prospective, unblinded, assigned, controlled study using a pharmacologic (0.04 mg/kg local arterial) dose of atropine. Part I: Twenty-two young adult female Beagle dogs used during a nonsurvival third-year veterinary student surgical laboratory (small intestinal resection and anastomosis). Part II: Ten young adult female Beagle dogs used immediately after completion of a nonsurvival third-year veterinary student orthopedic surgical laboratory. Part I: Dogs were randomly assigned to receive either atropine (0.04 mg/kg), or an equal volume of saline, given intramuscularly (premedication) and again intravenously prior to intestinal resection. Part II: In each dog, atropine (0.04 mg/kg)/saline was alternately given in the proximal/distal jejunum. Part I: There was no clinically or statistically significant difference between systemic atropine and saline solution on the degree of jejunal mucosal eversion after resection. Part II: There was a statistically significant decrease in jejunal mucosal eversion with atropine compared with saline solution when injected into a local jejunal artery. Systemic atropine (0.04 mg/kg) does not alter the degree of jejunal mucosal eversion during resection and anastomosis. Jejunal intraarterial atropine (0.04 mg/kg) reduced jejunal mucosal eversion during resection and anastomosis. The clinical usefulness and consequences of jejunal arterial atropine administration to reduce mucosal eversion remain to be determined. Copyright 2003 by The American College of Veterinary Surgeons

Biochanin a gastroprotective effects in ethanol-induced gastric mucosal ulceration in rats.

Science.gov (United States)

Hajrezaie, Maryam; Salehen, NurAin; Karimian, Hamed; Zahedifard, Maryam; Shams, Keivan; Al Batran, Rami; Majid, Nazia Abdul; Khalifa, Shaden A M; Ali, Hapipah Mohd; El-Seedi, Hesham; Abdulla, Mahmood Ameen

2015-01-01

Biochanin A notable bioactive compound which is found in so many traditional medicinal plant. In vivo study was conducted to assess the protective effect of biochanin A on the gastric wall of Spraguedawley rats` stomachs. The experimental set included different animal groups. Specifically, four groups with gastric mucosal lesions were receiving either a) Ulcer control group treated with absolute ethanol (5 ml/kg), b) 20 mg/kg of omeprazole as reference group, c) 25 of biochanin A, d) 50 mg/kg of biochanin A. Histopathological sectioning followed by immunohistochemistry staining were undertaken to evaluate the influence of the different treatments on gastric wall mucosal layer. The gastric secretions were collected in the form of homogenate and exposed to superoxide dismutase (SOD) and nitric oxide enzyme (NO) and the level of malondialdehyde (MDA) and protein content were measured. Ulceration and patchy haemorrhage were clearly observed by light microscopy. The morphology of the gastric wall as confirmed by immunohistochemistry and fluorescent microscopic observations, exhibited sever deformity with notable thickness, oedematous and complete loss of the mucosal coverage however the biochanin-pretreated animals, similar to the omeprazole-pretreated animals, showed less damage compared to the ulcer control group. Moreover, up-regulation of Hsp70 protein and down-regulation of Bax protein were detected in the biochanin A pre-treated groups and the gastric glandular mucosa was positively stained with Periodic Acid Schiff (PAS) staining and the Leucocytes infiltration was commonly seen. Biochanin A displayed a great increase in SOD and NO levels and decreased the release of MDA. This gastroprotective effect of biochanin A could be attributed to the enhancement of cellular metabolic cycles perceived as an increase in the SOD, NO activity, and decrease in the level of MDA, and also decrease in level of Bax expression and increase the Hsp70 expression level.

The Effect of Topical Application of Royal Jelly on Chemoradiotherapy-Induced Mucositis in Head and Neck Cancer: A Preliminary Study

Directory of Open Access Journals (Sweden)

Kohichi Yamauchi

2014-01-01

Full Text Available Purpose. One of the common side effects experienced by head and neck cancer patients on chemoradiotherapy is mucositis. Severe mucositis may be controllable by limiting cancer therapy, but it has resulted in decreasing the completion rate of chemoradiotherapy. The efficacy of royal jelly (RJ as prophylaxis against chemoradiotherapy-induced mucositis was evaluated through clinical scoring of oral and pharyngeal mucositis. Methods. In this randomized, single-blind (physician-blind, clinical trial, 13 patients with head and neck cancer requiring chemoradiation were randomly assigned to two groups. Seven patients assigned to the study group received RJ, and 6 patients were assigned to the control group. RJ group patients took RJ three times per day during treatment. The patients in both groups were evaluated twice a week for the development of mucositis using Common Terminology Criteria for Adverse Events version 3.0. Results. A significant reduction in mucositis was seen among RJ-treated patients compared with controls (P<0.001. Conclusion. This study demonstrated that prophylactic use of RJ was effective in reducing mucositis induced by chemoradiotherapy in head and neck cancer patients. However, further studies are needed because of the small sample size and the absence of double blinding.

Probiotic supplements and debridement of peri-implant mucositis

DEFF Research Database (Denmark)

Hallström, Hadar; Lindgren, Susann; Widén, Cecilia

2016-01-01

OBJECTIVE: The aim of this double-blind randomized placebo-controlled trial was to evaluate the effects of probiotic supplements in adjunct to conventional management of peri-implant mucositis. MATERIALS AND METHODS: Forty-nine adult patients with peri-implant mucositis were consecutively recruited...... debridement and oral hygiene reinforcement resulted in clinical improvement of peri-implant mucositis and a reduction in cytokine levels. Probiotic supplements did not provide added benefit to placebo....

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

Gastrointestinal mucosal abnormalities using videocapsule endoscopy in systemic sclerosis.

Science.gov (United States)

Marie, I; Antonietti, M; Houivet, E; Hachulla, E; Maunoury, V; Bienvenu, B; Viennot, S; Smail, A; Duhaut, P; Dupas, J-L; Dominique, S; Hatron, P-Y; Levesque, H; Benichou, J; Ducrotté, P

2014-07-01

To date, there are no large studies on videocapsule endoscopy in systemic sclerosis (SSc). Consequently, the prevalence and features of gastrointestinal mucosal abnormalities in SSc have not been determined. To determine both prevalence and characteristics of gastrointestinal mucosal abnormalities in unselected patients with SSc, using videocapsule endoscopy. To predict which SSc patients are at risk of developing potentially bleeding gastrointestinal vascular mucosal abnormalities. Videocapsule endoscopy was performed on 50 patients with SSc. Prevalence of gastrointestinal mucosal abnormalities was 52%. Potentially bleeding vascular mucosal lesions were predominant, including: watermelon stomach (34.6%), gastric and/or small intestinal telangiectasia (26.9%) and gastric and/or small intestinal angiodysplasia (38.5%). SSc patients with gastrointestinal vascular mucosal lesions more often exhibited: limited cutaneous SSc (P = 0.06), digital ulcers (P = 0.05), higher score of nailfold videocapillaroscopy (P = 0.0009), anaemia (P = 0.02), lower levels of ferritin (P correlation between gastrointestinal vascular mucosal lesions and presence of severe extra-digestive vasculopathy (digital ulcers and higher nailfold videocapillaroscopy scores). This latter supports the theory that SSc-related diffuse vasculopathy is responsible for both cutaneous and digestive vascular lesions. Therefore, we suggest that nailfold videocapillaroscopy may be a helpful test for managing SSc patients. In fact, nailfold videocapillaroscopy score should be calculated routinely, as it may result in identification of SSc patients at higher risk of developing potentially bleeding gastrointestinal vascular mucosal lesions. © 2014 John Wiley & Sons Ltd.

A regenerative approach towards mucosal fenestration closure

Science.gov (United States)

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

2013-01-01

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. PMID:23749826

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy [version 1; referees: 3 approved

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Kjeld Schmiegelow

2017-04-01

Full Text Available During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both, bone toxicities (including osteonecrosis, thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia, high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

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Blandizzi, Corrado; Fornai, Matteo; Colucci, Rocchina; Natale, Gianfranco; Lubrano, Valter; Vassalle, Cristina; Antonioli, Luca; Lazzeri, Gloria; Tacca, Mario Del

2005-01-01

AIM: This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal anti-inflammatory drugs (NSAIDs) in rats. METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 µmol/kg), diclofenac (60 µmol/kg), piroxicam (150 µmol/kg) or ketoprofen (150 µmol/kg). Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 µmol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 µmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate. RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 µmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 µmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 µmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro. CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID

Predictive single nucleotide polymorphism markers for acute oral mucositis in patients with nasopharyngeal carcinoma treated with radiotherapy

Science.gov (United States)

Le, Ziyu; Niu, Xiaoshuang; Chen, Ying; Ou, Xiaomin; Zhao, Guoqi; Liu, Qi; Tu, Wenzhi; Hu, Chaosu; Kong, Lin; Liu, Yong

2017-01-01

The aim of this study was to investigate the association between the susceptibility of severe oral mucositis (OM) in Chinese nasopharyngeal carcinoma (NPC) patients treated with radiotherapy and single nucleotide polymorphisms (SNPs) across the whole genome. SNPs were screened in a total of 24 patients with NPC and an additional 6 were subjected to mRNA expression analysis. Patients were subdivided into CTC 0-2 (CTC toxicity grade 0, 1, and 2) and CTC 3+ (CTC toxicity grade 3 and above) groups according to their CTC (common toxicity criteria) scores. The GTEx dataset was used to performed eQTL analyses and in-vitro functional assays were performed for eQTL-associated genes. Our data identified 7 functional SNPs associated with the development of OM. We observed that rs11081899-A, located in the 5′-UTR of the ZNF24 gene, was significantly correlated with a higher risk of severe mucositis (OR = 14.631, 95% CI = 2.61-105.46, p = 1.2 × 10−4), and positively associated with ZNF24 mRNA expression (p = 4.1 × 10−6) from GTEx dataset. In addition, high ZNF24 mRNA expression was associated with severe OM in patients with NPC (p = 0.02). Further functional assays revealed that ZNF24 knockdown reduced p65 expression and suppressed TNF-α-induced NF-κB activation and pro-inflammatory cytokines release. These findings suggested that rs11081899-A may be a genetic susceptibility factor for radiation-induced OM in patients with NPC, although its value in clinical application needs to be further verified in a large cohort. Also, we suggested that downregulation of ZNF24 may attenuate the development of mucositis by suppressing NF-κB activation. PMID:28968968

Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil 1.

Science.gov (United States)

Silva, Viviane Carvalho da; Leitão, Renata Ferreira de Carvalho; Brito, Gerly Anne de Castro; Martins, Conceição da Silva; Freire, Gildenio Estevam; Aragão, Karoline Saboia; Wanderley, Carlos Wagner de Souza; Freitas, Marcos Rabelo de

2017-09-01

To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.

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.

Feeding an elemental diet vs a milk-based formula does not decrease intestinal mucosal growth in infant pigs

DEFF Research Database (Denmark)

Stoll, Barbara; Price, Pamela T; Reeds, Peter J

2006-01-01

BACKGROUND: We previously showed that the level of enteral nutrient intake determines the rate of intestinal growth in piglets. Our objective was to determine whether providing enteral nutrition in the form of elemental nutrients (glucose, amino acids, lipid [ED]) rather than cow's milk formula...... conclude that intestinal mucosal growth and villus morphology are similar in pigs fed ED and FORM, despite higher cell proliferation and protein synthesis rates and lower lactase activity with ED. This implies that elemental diets may be as trophic as polymeric formulas to simultaneously provide nutrition...

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.

Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients

NARCIS (Netherlands)

Saunders, Deborah P.; Epstein, Joel B.; Elad, Sharon; Allemano, Justin; Bossi, Paolo; van de Wetering, Marianne D.; Rao, Nikhil G.; Potting, Carin; Cheng, Karis K.; Freidank, Annette; Brennan, Michael T.; Bowen, Joanne; Dennis, Kristopher; Lalla, Rajesh V.

2013-01-01

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. A systematic review of the available literature was conducted. The body

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

Microneedle and mucosal delivery of influenza vaccines

Science.gov (United States)

Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun

2017-01-01

In recent years with the threat of pandemic influenza and other public health needs, alternative vaccination methods other than intramuscular immunization have received great attention. The skin and mucosal surfaces are attractive sites probably because of both non-invasive access to the vaccine delivery and unique immunological responses. Intradermal vaccines using a microinjection system (BD Soluvia) and intranasal vaccines (FluMist) are licensed. As a new vaccination method, solid microneedles have been developed using a simple device that may be suitable for self-administration. Because coated micorneedle influenza vaccines are administered in the solid state, developing formulations maintaining the stability of influenza vaccines is an important issue to be considered. Marketable microneedle devices and clinical trials remain to be developed. Other alternative mucosal routes such as oral and intranasal delivery systems are also attractive for inducing cross protective mucosal immunity but effective non-live mucosal vaccines remain to be developed. PMID:22697052

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

International Nuclear Information System (INIS)

Macann, Andrew; Fua, Tsien; Milross, Chris G.; Porceddu, Sandro V.; Penniment, Michael; Wratten, Chris; Krawitz, Hedley; Poulsen, Michael; Tang, Colin I.; Morton, Randall P.; Hay, K. David; Thomson, Vicki; Bell, Melanie L.; King, Madeleine T.; Fraser-Browne, Carol L.; Hockey, Hans-Ulrich P.

2014-01-01

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

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.

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.

Science.gov (United States)

Macann, Andrew; Fua, Tsien; Milross, Chris G; Porceddu, Sandro V; Penniment, Michael; Wratten, Chris; Krawitz, Hedley; Poulsen, Michael; Tang, Colin I; Morton, Randall P; Hay, K David; Thomson, Vicki; Bell, Melanie L; King, Madeleine T; Fraser-Browne, Carol L; Hockey, Hans-Ulrich P

2014-03-01

To assess the impact of domicile-based humidification on symptom burden during radiation therapy (RT) for head-and-neck (H&N) cancer. From June 2007 through June 2011, 210 patients with H&N cancer receiving RT were randomized to either a control arm or to receive humidification using the Fisher & 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. 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. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake.

Science.gov (United States)

Mars, Monica; de Graaf, Cees; de Groot, Lisette C P G M; Kok, Frans J

2005-03-01

The decrease in leptin after energy restriction is a starvation signal to the brain. Several studies have found an association between this decrease and subjective appetite; however, no solid data are available on the acute decrease in fasting leptin concentration and subsequent caloric compensation. The objective was to assess the effect of acute decreases in fasting leptin concentrations, induced by energy restriction, on subsequent energy intake compensation. We hypothesized that men with a large decrease in fasting leptin concentrations would have larger ad libitum energy intakes than would men with a small decrease in leptin. Thirty-four male unrestrained eaters [age: 23 +/- 3 y; body mass index (in kg/m(2)): 22.3 +/- 1.6] participated in a semicontrolled intervention study. Fasting serum leptin and insulin concentrations were measured before and 2 d after 62% energy restriction. Energy intake was measured on the 2 following days on which food was provided ad libitum. During energy restriction, fasting leptin and insulin concentrations decreased by 27.2% (95% CI: -34.4%, -19.9%) and 30.7% (95% CI: -41.0%, -20.4%), respectively. Subjects consumed 143 +/- 27% of their estimated energy requirements (18.3 +/- 2.9 MJ) on the first day and 124 +/- 20% (16.0 +/- 2.6 MJ) on the second day of ad libitum intake. No significant correlations were observed between decreases in fasting leptin or insulin concentrations and subsequent ad libitum energy intake; however, decreases in insulin were correlated with an increase in carbohydrate intake (r=-0.49, P < 0.01). Although fasting leptin concentrations decreased significantly during energy restriction and subjects showed compensatory behavior during subsequent ad libitum food intake, no association was observed between the decrease in fasting leptin concentrations and caloric compensation.

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; phealing 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

Streptococcus agalactiae Inhibits Candida albicans Hyphal Development and Diminishes Host Vaginal Mucosal TH17 Response.

Science.gov (United States)

Yu, Xiao-Yu; Fu, Fei; Kong, Wen-Na; Xuan, Qian-Kun; Wen, Dong-Hua; Chen, Xiao-Qing; He, Yong-Ming; He, Li-Hua; Guo, Jian; Zhou, Ai-Ping; Xi, Yang-Hong; Ni, Li-Jun; Yao, Yu-Feng; Wu, Wen-Juan

2018-01-01

Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans , and that EFG1 -Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC), the fungal burden and the levels of pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α showed a increase on co-infection with S. agalactiae , while the level of TH17 T cells and IL-17 in the cervicovaginal lavage fluid were significantly decreased. Our results indicate that S. agalactiae inhibits C. albicans hyphal development by downregulating the expression of EFG1 -Hwp1. The interaction between S. agalactiae and C. albicans may attenuate host vaginal mucosal TH17 immunity and contribute to mucosal colonization by C. albicans .

Clinical impact of predictive assays for acute and late radiation morbidity

International Nuclear Information System (INIS)

Budach, W.; Classen, J.; Belka, C.; Bamberg, M.

1998-01-01

Background: Clinically reliable predictive assays for normal tissue radiation sensitivity would help to avoid severe radiation induced morbidity and result in individualized dose prescriptions. Profound differences of individual fibroblast and lymphocyte radiation sensitivity in vitro have been documented in patients with certain genetic syndromes but also in patients without known genetic disorders. The following review evaluates whether fibroblast or lymphocyte radiation sensitivity measured in vitro correlates with the degree of acute and late radiation induced morbidity. Results: Acute radiation side effects and lymphocyte sensitivity has been investigated in 2 studies. One of them reported an insecure correlation, the other no correlation at all. Fibroblast radiation sensitivity and the extent of acute radiation induced side effects on skin and mucosal sites has been compared in a total of 5 studies. None of these studies found a consistent significant correlation. Lymphocyte radiation sensitivity and late effects have been studied by 2 institutions. Late radiation induced skin and mucosal changes did not correlate with lymphocyte sensitivity in head and neck cancer patients, whereas in breast cancer patients a weak (R 2 =0.06) correlation between the degree of late skin reactions and lymphocyte sensitivity was observed. Late skin or mucosal radiation reactions and fibroblast sensitivity were examined by 5 research groups. Data analysis revealed significant correlations or at least a trend towards a significant correlation in all studies. The quality of the reported correlations expressed as R 2 ranged from 0.13 to 0.60, indicating a low predictive value. Conclusions: Lymphocyte radiation sensitivity as measured by currently available assays does not or only poorly correlate with acute and late effects of radiation in patients, precluding predictive tests based on lymphocyte sensitivity. Fibroblast radiation sensitivity does not correlate with acute but

Oral mucositis in head and neck cancer: risk, biology, and management.

Science.gov (United States)

Sonis, Stephen T

2013-01-01

Of the toxicities associated with conventional forms of treatment for head and neck cancers, probably none has such a consistent legacy as oral mucositis.1 Despite the fact that mucosal injury was noted as far back as Marie Curie's first forays into therapeutic radiation, an effective intervention has yet to be developed. In addition to its historic link to radiation, new therapeutic strategies including induction chemotherapy often produce mucositis, and targeted therapies appear to alter mucositis risk and its severity and course.2 The symptomatic effect of oral mucositis is profound. Disabling oral and oropharyngeal pain prevents patients from eating normally, requires opiate analgesics, and in some cases results in alteration or discontinuation of anticancer therapy.3 Furthermore, the health and economic consequences of oral mucositis are far from trivial. The incremental cost of oral mucositis in patients with head and neck cancer exceeds $17,000 (USD).4.

Oral Mucositis Prevention By Low-Level Laser Therapy in Head-and-Neck Cancer Patients Undergoing Concurrent Chemoradiotherapy: A Phase III Randomized Study

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Gouvea de Lima, Aline [Departamento de Radiologia, Disciplina de Oncologia, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP (Brazil); Villar, Rosangela Correa [Instituto de Radiologia, Servico de Radioterapia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP (Brazil); Castro, Gilberto de, E-mail: gilberto.castro@usp.br [Department of Clinical Oncology, Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, SP (Brazil); Antequera, Reynaldo [Divisao de Odontologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP (Brazil); Gil, Erlon; Rosalmeida, Mauro Cabral [Instituto de Radiologia, Servico de Radioterapia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP (Brazil); Federico, Miriam Hatsue Honda; Snitcovsky, Igor Moises Longo [Departamento de Radiologia, Disciplina de Oncologia, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP (Brazil)

2012-01-01

Purpose: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. Methods and Materials: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm{sup 2} or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. Results: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. Conclusions: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might

Assessment of intestinal permeability and bacterial translocation employing nuclear methods in murine mucositis

International Nuclear Information System (INIS)

Pessoa, Rafaela M.; Takenaka, Isabella K.T.M.; Barros, Patricia A.V.; Moura, Livia P.; Contarini, Sara M.L.; Amorim, Juliana M.; Castilho, Raquel O.; Leite, Camila M.A.; Cardoso, Valbert N.; Diniz, Simone Odilia F.

2017-01-01

. The individual amount of food ingested was evaluated every three days and the weight of the mice was measured with a semi analytical balance also every three days. Results: Mice from the MUC group had higher weight loss compared with the control group and reduced food consumption (p<0.05). However, mice that received oral administration of A. chica extract and underwent mucositis (MUC + AC) had reduced weight loss and higher food consumption (p<0.05). Intestinal permeability and bacterial translocation were higher in the MUC group compared to the CTL group (p<0.05), whereas, the animals that received A. chica extract and underwent mucositis, had decreased intestinal permeability and bacterial translocation compared to the MUC group mice (p<0.05). Histology analyses were used to assess alterations in the ileum mucosa. Mice from the MUC group showed lesions in the small intestine with cell infiltration in the lamina propria, as well as inflammation in the submucosa and muscular layers. Mice that received A. chica extracts and underwent mucositis showed more preserved ileum mucosa that the MUC group mice and showed a similar histology compared to the mice from the control group. Conclusion: A. chica extract treatment reduced the weight loss, the intestinal permeability, bacterial translocation and the inflammation, indicating that the extract can be effective in the management of the inflammatory process in the intestinal mucosal after the chemotherapy treatment. (author)

Assessment of intestinal permeability and bacterial translocation employing nuclear methods in murine mucositis

Energy Technology Data Exchange (ETDEWEB)

Pessoa, Rafaela M.; Takenaka, Isabella K.T.M.; Barros, Patricia A.V.; Moura, Livia P.; Contarini, Sara M.L.; Amorim, Juliana M.; Castilho, Raquel O.; Leite, Camila M.A.; Cardoso, Valbert N.; Diniz, Simone Odilia F. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Mg (Brazil)

2017-07-01

intestinal histology. The individual amount of food ingested was evaluated every three days and the weight of the mice was measured with a semi analytical balance also every three days. Results: Mice from the MUC group had higher weight loss compared with the control group and reduced food consumption (p<0.05). However, mice that received oral administration of A. chica extract and underwent mucositis (MUC + AC) had reduced weight loss and higher food consumption (p<0.05). Intestinal permeability and bacterial translocation were higher in the MUC group compared to the CTL group (p<0.05), whereas, the animals that received A. chica extract and underwent mucositis, had decreased intestinal permeability and bacterial translocation compared to the MUC group mice (p<0.05). Histology analyses were used to assess alterations in the ileum mucosa. Mice from the MUC group showed lesions in the small intestine with cell infiltration in the lamina propria, as well as inflammation in the submucosa and muscular layers. Mice that received A. chica extracts and underwent mucositis showed more preserved ileum mucosa that the MUC group mice and showed a similar histology compared to the mice from the control group. Conclusion: A. chica extract treatment reduced the weight loss, the intestinal permeability, bacterial translocation and the inflammation, indicating that the extract can be effective in the management of the inflammatory process in the intestinal mucosal after the chemotherapy treatment. (author)

Effect of epidermal growth factor against radiotherapy-induced oral mucositis in rats

International Nuclear Information System (INIS)

Lee, Sang-wook; Jung, Kwon Il; Kim, Yeun Wha B.S.; Jung, Heun Don; Kim, Hyun Sook; Hong, Joon Pio

2007-01-01

Purpose: We tested the efficacy of oral recombinant human epidermal growth factor (rhEGF) against radiation-induced oral mucositis in a rat model. Methods and Materials: Each of 35 Sprague-Dawley rats, 7 to 8 weeks of age and weighing 178 ± 5 grams, was irradiated once in the head region with 25 Gy, using a 4-MV therapeutic linear accelerator at a rate of 2 Gy/min. The irradiated rats were randomly divided into four groups: those receiving no treatment (Group 1), those treated with vehicle only three times per day (Group 2), and those treated with 50 μg/mL (Group 3), or 100 μg/mL (Group 4) rhEGF three times per day. Results: Rats were monitored for survival rate and daily activity, including hair loss, sensitivity, and anorexia. We found that survival rate and oral intake were significantly increased and histologic changes were significantly decreased in the rhEGF-treated rats. There was no difference, however, between rats treated with 50 μg/mL or 100 μg/mL rhEGF. Conclusion: These findings suggest that orally administered rhEGF decreased radiation-induced oral mucositis in rats

Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infections (MBI-LCBI): Descriptive Analysis of Data Reported to National Healthcare Safety Network (NHSN), 2013.

Science.gov (United States)

Epstein, Lauren; See, Isaac; Edwards, Jonathan R; Magill, Shelley S; Thompson, Nicola D

2016-01-01

OBJECTIVES To determine the impact of mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBIs) on central-line-associated bloodstream infection (CLABSI) rates during the first year of MBI-LCBI reporting to the National Healthcare Safety Network (NHSN) DESIGN Descriptive analysis of 2013 NHSN data SETTING Selected inpatient locations in acute care hospitals METHODS A descriptive analysis of MBI-LCBI cases was performed. CLABSI rates per 1,000 central-line days were calculated with and without the inclusion of MBI-LCBIs in the subset of locations reporting ≥1 MBI-LCBI, and in all locations (regardless of MBI-LCBI reporting) to determine rate differences overall and by location type. RESULTS From 418 locations in 252 acute care hospitals reporting ≥1 MBI-LCBIs, 3,162 CLABSIs were reported; 1,415 (44.7%) met the MBI-LCBI definition. Among these locations, removing MBI-LCBI from the CLABSI rate determination produced the greatest CLABSI rate decreases in oncology (49%) and ward locations (45%). Among all locations reporting CLABSI data, including those reporting no MBI-LCBIs, removing MBI-LCBI reduced rates by 8%. Here, the greatest decrease was in oncology locations (38% decrease); decreases in other locations ranged from 1.2% to 4.2%. CONCLUSIONS An understanding of the potential impact of removing MBI-LCBIs from CLABSI data is needed to accurately interpret CLABSI trends over time and to inform changes to state and federal reporting programs. Whereas the MBI-LCBI definition may have a large impact on CLABSI rates in locations where patients with certain clinical conditions are cared for, the impact of MBI-LCBIs on overall CLABSI rates across inpatient locations appears to be more modest. Infect. Control Hosp. Epidemiol. 2015;37(1):2-7.

Nasal mucosal blood flow after intranasal allergen challenge

International Nuclear Information System (INIS)

Holmberg, K.; Bake, B.; Pipkorn, U.

1988-01-01

The nasal mucosal blood flow in patients with allergic rhinitis was determined at nasal allergen challenges with the 133 Xenon washout method. Determinations were made in 12 subjects before and 15 minutes after challenge with diluent and increasing doses of allergen. The time course was followed in eight subjects by means of repeated measurements during 1 hour after a single allergen dose. Finally, the blood flow was measured after unilateral allergen challenge in the contralateral nasal cavity. A dose-dependent decrease in blood flow was found after nasal challenge with increasing doses of allergens, whereas challenge with diluent alone did not induce any changes. The highest allergen dose, which also induced pronounced nasal symptoms, resulted in a decrease in blood flow of 25% (p less than 0.001). The time-course study demonstrated a maximum decrease in blood flow 10 to 20 minutes after challenge and then a gradual return to baseline. Unilateral allergen challenge resulted in a decrease in blood flow in the contralateral, unchallenged nasal cavity, suggesting that part of the allergen-induced changes in blood flow were reflex mediated

Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity.

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Sya N Ukena

2007-12-01

Full Text Available Probiotics are proposed to positively modulate the intestinal epithelial barrier formed by intestinal epithelial cells (IECs and intercellular junctions. Disruption of this border alters paracellular permeability and is a key mechanism for the development of enteric infections and inflammatory bowel diseases (IBDs.To study the in vivo effect of probiotic Escherichia coli Nissle 1917 (EcN on the stabilization of the intestinal barrier under healthy conditions, germfree mice were colonized with EcN or K12 E. coli strain MG1655. IECs were isolated and analyzed for gene and protein expression of the tight junction molecules ZO-1 and ZO-2. Then, in order to analyze beneficial effects of EcN under inflammatory conditions, the probiotic was orally administered to BALB/c mice with acute dextran sodium sulfate (DSS induced colitis. Colonization of gnotobiotic mice with EcN resulted in an up-regulation of ZO-1 in IECs at both mRNA and protein levels. EcN administration to DSS-treated mice reduced the loss of body weight and colon shortening. In addition, infiltration of the colon with leukocytes was ameliorated in EcN inoculated mice. Acute DSS colitis did not result in an anion secretory defect, but abrogated the sodium absorptive function of the mucosa. Additionally, intestinal barrier function was severely affected as evidenced by a strong increase in the mucosal uptake of Evans blue in vivo. Concomitant administration of EcN to DSS treated animals resulted in a significant protection against intestinal barrier dysfunction and IECs isolated from these mice exhibited a more pronounced expression of ZO-1.This study convincingly demonstrates that probiotic EcN is able to mediate up-regulation of ZO-1 expression in murine IECs and confer protection from the DSS colitis-associated increase in mucosal permeability to luminal substances.

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....

Efficacy and safety of granulocyte macrophage-colony stimulating factor (GM-CSF) on the frequency and severity of radiation mucositis in patients with head and neck carcinoma

International Nuclear Information System (INIS)

Kannan, V.; Bapsy, Poonamallee P.; Anantha, Naranappa; Doval, Dinesh Chandra; Vaithianathan, Hema; Banumathy, G.; Reddy, Krishnamurthy B.; Kumaraswamy, Saklaspur Veerappaiah; Shenoy, Ashok Mohan

1997-01-01

Purpose: Based on the clinical evidence of mucosal protection by GM-CSF during cytotoxic chemotherapy, a pilot study was undertaken to determine the safety and mucosal reaction of patients receiving GM-CSF while undergoing definitive conventional fractionated radiotherapy in head and neck carcinoma. Methods and Materials: Patients were considered eligible if buccal mucosa and oropharynx were included in the teleradiation field. Ten adult patients with squamous cell carcinoma of head and neck (buccal mucosa--8 and posterior (1(3)) tongue--2) were entered into the trial. Radiation therapy was delivered with telecobalt machine at conventional 2 Gy fraction and 5 fractions/week. The radiation portals consisted of two parallel opposing lateral fields. GM-CSF was given subcutaneously at a dose of 1 μg/kg body weight, daily, after 20 Gy until the completion of radiation therapy. Patients were evaluated daily for mucosal reaction, pain, and functional impairment. Results: The median radiation dose was 66 Gy. Eight patients received ≥60 Gy. The tolerance to GM-CSF was good. All 10 patients completed the planned daily dose of GM-CSF without interruption. Mucosal toxicity was Grade I in four patients till the completion of radiotherapy (dose range 50-66 Gy). Six patients developed Grade II reaction, fibrinous mucosal lesions of maximum size 1.0-1.5 cm, during radiotherapy. None developed Grade III mucositis. The maximum mucosal pain was Grade I during GM-CSF therapy. In two patients after starting GM-CSF the pain reduced in intensity. Functional impairment was mild to moderate. All patients were able to maintain adequate oral intake during the treatment period. Total regression of mucosal reaction occurred within 8 days following completion of radiotherapy. Conclusions: GM-CSF administration concurrently with conventional fractionated radiotherapy was feasible without significant toxicity. The acute side effects of radiotherapy namely mucositis, pain, and functional

Increased melatonin in oral mucosal tissue of oral lichen planus (OLP) patients: A possible link between melatonin and its role in oral mucosal inflammation.

Science.gov (United States)

Luengtrakoon, Kirawut; Wannakasemsuk, Worraned; Vichitrananda, Vilasinee; Klanrit, Poramaporn; Hormdee, Doosadee; Noisombut, Rajda; Chaiyarit, Ponlatham

2017-06-01

The existence of extra-pineal melatonin has been observed in various tissues. No prior studies of melatonin in human oral mucosal tissue under the condition of chronic inflammation have been reported. The aim of this study was to investigate the presence of melatonin in oral mucosal tissue of patients with oral lichen planus (OLP) which was considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations. Sections from formalin-fixed and paraffin-embedded oral mucosal tissue of OLP patients (n=30), and control subjects (n=30) were used in this study. Immunohistochemical staining was performed and the semiquantitative scoring system was used to assess the levels of arylalkylamine-N-acetyltransferase (AANAT: a rate-limiting enzyme in the biosynthesis pathway of melatonin), melatonin, and melatonin receptor 1 (MT1) in oral mucosa of OLP patients and normal oral mucosa of control subjects. AANAT, melatonin, and MT1were detected in oral mucosal tissue of OLP patients and control subjects. Immunostaining scores of AANAT, melatonin, and MT1 in oral mucosal tissue of OLP patients were significantly higher than those in control subjects (p=0.002, poral mucosal tissue of OLP patients imply that chronic inflammation may induce the local biosynthesis of melatonin via AANAT, and may enhance the action of melatonin via MT1. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy of Sucralfate Mouth Wash in Prevention of 5-fluorouracil Induced Oral Mucositis: A Prospective, Randomized, Double-Blind, Controlled Trial.

Science.gov (United States)

Ala, Shahram; Saeedi, Majid; Janbabai, Ghasem; Ganji, Reza; Azhdari, Elham; Shiva, Afshin

2016-01-01

Sucralfate has been used for the prevention and treatment of radiotherapy- and chemotherapy-induced stomatitis and mucositis in a number of studies, but the results are contradictory. To answer such discrepancies, the present study was designed to evaluate the efficacy of sucralfate mouthwash in prevention of 5-fluorouracil (5-FU)-induced oral mucositis in patients with gastrointestinal malignancies. Patients with gastrointestinal cancers receiving 5-FU-based chemotherapy regimens were included in this randomized, blinded, controlled trial and were randomly allocated to either sucralfate mouthwash (every 6 h) or placebo. The patients were visited at fifth and tenth day of trial; the presence and severity of oral mucositis and the intensity of pain were assessed. The patients receiving sucralfate experienced lower frequency and severity of mucositis (76% vs. 38.5%, P = 0.005 and 84 vs. 38.5%, P < 0.001, respectively) and less intense pain (2.5 ± 2.2 vs. 5.08 ± 3.82, P = 0.004 and 1.33 ± 0.86 vs. 4.12 ± 3.5, P = 0.001, respectively) compared with the placebo group both at day 5 and day 10. Within the sucralfate group, a decrease in frequency and severity of mucositis was observed throughout the trial period, while in the placebo group no such effect was observed. Sucralfate mouthwash reduced the frequency and severity of 5-FU-induced oral mucositis in patients with gastrointestinal malignancies compared with placebo, indicating its efficacy in the prevention of chemotherapy-induced mucositis.

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,

Kinesio Taping does not decrease swelling in acute, lateral ankle sprain of athletes: a randomised trial

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Guilherme S Nunes

2015-01-01

Full Text Available Question: Does Kinesio Taping reduce swelling in athletes who have suffered an acute, lateral ankle sprain? Design: Randomised controlled trial with concealed allocation, intention-to-treat analysis and blinded assessment. Participants: Thirty-six athletes who participated regularly in one of seven different sports modalities and suffered an acute ankle sprain. Intervention: The experimental group received Kinesio Taping application for 3 days, which was designed to treat swelling. The control group received an inert Kinesio Taping application. Outcome measures: For the comparison between groups, the swelling was measured via volumetry, perimetry, relative volumetry and two analyses of the difference in volume and perimetry between ankles of each participant. Data were collected immediately after the 3 days of intervention and at follow-up, which was 15 days post intervention. Results: At 3 days after intervention, there were no differences between groups for swelling in volumetry (MD –2 ml, 95% CI –28 to 32; perimetry (MD 0.2 cm, 95% CI –0.6 to 1.0; relative volumetry (MD 0.0 cm, 95% CI –0.1 to 0.1; and the other analyses. At day 15 follow-up, there were no significant between-group differences in outcomes. Conclusion: The application of Kinesio Taping, with the aim of stimulating the lymphatic system, is ineffective in decreasing acute swelling after an ankle sprain in athletes. Trial registration: Brazilian Registry of Clinical Trials, RBR-32sctf. [Nunes GS, Vargas VZ, Wageck B, dos Santos Hauphental DP, da Luz CM, de Noronha M (2015 Kinesio Taping does not decrease swelling in acute, lateral ankle sprain of athletes: a randomised trial. Journal of Physiotherapy 61: 28–33

Hypercytotoxicity and rapid loss of NKp44+ innate lymphoid cells during acute SIV infection.

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Haiying Li

2014-12-01

Full Text Available HIV/SIV infections break down the integrity of the gastrointestinal mucosa and lead to chronic immune activation and associated disease progression. Innate lymphoid cells (ILCs, distinguishable by high expression of NKp44 and RORγt, play key roles in mucosal defense and homeostasis, but are depleted from gastrointestinal (GI tract large bowel during chronic SIV infection. However, less is known about the kinetics of ILC loss, or if it occurs systemically. In acute SIV infection, we found a massive, up to 8-fold, loss of NKp44+ILCs in all mucosae as early as day 6 post-infection, which was sustained through chronic disease. Interestingly, no loss of ILCs was observed in mucosa-draining lymph nodes. In contrast, classical NK cells were not depleted either from gut or draining lymph nodes. Both ILCs and NK cells exhibited significantly increased levels of apoptosis as measured by increased Annexin-V expression, but while classical NK cells also showed increased proliferation, ILCs did not. Interestingly, ILCs, which are normally noncytolytic, dramatically upregulated cytotoxic functions in acute and chronic infection and acquired a polyfunctional phenotype secreting IFN-γ, MIP1-β, and TNF-α, but decreased production of the prototypical cytokine, IL-17. Classical NK cells had less dramatic functional change, but upregulated perforin expression and increased cytotoxic potential. Finally, we show that numerical and functional loss of ILCs was due to increased apoptosis and ROR γt suppression induced by inflammatory cytokines in the gut milieu. Herein we demonstrate the first evidence for acute, systemic, and permanent loss of mucosal ILCs during SIV infection associated with reduction of IL-17. The massive reduction of ILCs involves apoptosis without compensatory de novo development/proliferation, but the full mechanism of depletion and the impact of functional change so early in infection remain unclear.

Mucosal vaccination with formalin-inactivated avian metapneumovirus subtype C does not protect turkeys following intranasal challenge.

Science.gov (United States)

Kapczynski, Darrell R; Perkins, Laura L; Sellers, Holly S

2008-03-01

Studies were performed to determine if mucosal vaccination with inactivated avian metapneumovirus (aMPV) subtype C protected turkey poults from clinical disease and virus replication following mucosal challenge. Decreases in clinical disease were not observed in vaccinated groups, and the vaccine failed to inhibit virus replication in the tracheas of 96% of vaccinated birds. Histopathologically, enhancement of pulmonary lesions following virus challenge was associated with birds receiving the inactivated aMPV vaccine compared to unvaccinated birds. As determined by an enzyme-linked immunosorbent assay (ELISA), all virus-challenged groups increased serum immunoglobulin (Ig) G and IgA antibody production against the virus following challenge; however, the unvaccinated aMPV-challenged group displayed the highest increases in virus-neutralizing antibody. On the basis of these results it is concluded that intranasal vaccination with inactivated aMPV does not induce protective immunity, reduce virus shedding, or result in decreased histopathologic lesions.

The Secretion of IL-22 from Mucosal NKp44+ NK Cells Is Associated with Microbial Translocation and Virus Infection in SIV/SHIV-Infected Chinese Macaques

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Wei Wang

2014-01-01

Full Text Available Microbial translocation (MT causes systemic immune activation in chronic human immunodeficiency virus (HIV infection. The role of a novel subtype of innate lymphoid cells, the NKp44+ NK cells, in HIV/simian immunodeficiency virus- (SIV- induced MT remains unknown. In this study, 12 simian-human immunodeficiency virus- (SHIV- infected macaques were chosen and split into two groups based on the MT level. Blood and Peripheral lymphoid tissue were sampled for flow cytometric analysis, viral load detection, and interleukin testing. Then, six naive Chinese macaques were used to determine the dynamics of cytokine secretion from mucosal NKp44+ NK cells in different phases of SIV infection. As a result, the degranulation capacity and IL-22 production of mucosal NKp44+ NK cells were associated with the MT level in the SHIV-infected macaques. And the number of mucosal NKp44+ NK cells and IL-22 secretion by these cells were lower in the chronic phase than in the early acute phase of SIV infection. The number of mucosal NKp44+ NK cells and interleukin-22 (IL-22 secretion by these cells increased before MT occurred. Therefore, we conclude that a decline in IL-22 production from mucosal NKp44+ NK cells induced by virus infection may be one of the causes of microbial translocation in HIV/SIV infection.

The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs.

Science.gov (United States)

Adriaens, E; Dierckens, K; Bauters, T G; Nelis, H J; van Goethem, F; Vanparys, P; Remon, J P

2001-07-01

The objective of this study was to evaluate the mucosal toxicity of different benzalkonium chloride (BAC) analogues using slugs as the alternative test organism. The effect of different BAC analogues on the mucosal tissue of slugs was determined from the protein, lactate dehydrogenase, and alkaline phosphatase released from the foot mucosa after treatment. Additionally, mucus production and reduction in body weight of the slugs were measured. The eye irritation potency of the molecules was evaluated with the Bovine Corneal Opacity and Permeability (BCOP) assay. The antimicrobial activity of the different BAC analogues was also assessed. All BAC analogues induced severe damage to the mucosal epithelium of the slugs, and the irritation increased with decreasing alkyl chain length: BAC-C16 or = BAC-C16 > BAC-C12. The BAC-C14 exhibited higher activity than the BAC-mix. The toxicity and activity of BAC analogues depend on the alkyl chain length. The use of BAC-C14 as a conservative agent in pharmaceutical preparations instead of the BAC-mix should be considered.

Streptococcus agalactiae Inhibits Candida albicans Hyphal Development and Diminishes Host Vaginal Mucosal TH17 Response

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Xiao-Yu Yu

2018-02-01

Full Text Available Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans, and that EFG1-Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC, the fungal burden and the levels of pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α showed a increase on co-infection with S. agalactiae, while the level of TH17 T cells and IL-17 in the cervicovaginal lavage fluid were significantly decreased. Our results indicate that S. agalactiae inhibits C. albicans hyphal development by downregulating the expression of EFG1-Hwp1. The interaction between S. agalactiae and C. albicans may attenuate host vaginal mucosal TH17 immunity and contribute to mucosal colonization by C. albicans.

Effectiveness of Cepharanthin in decreasing interruptions during radiation therapy for oral cancer

International Nuclear Information System (INIS)

Uchiyama, Yuka; Murakami, Shumei; Kamimoto, Naoya; Nakatani, Atsutoshi; Furukawa, Souhei

2005-01-01

The objectives of this study was to examine the effectiveness of Cepharanthin (Kakensyoyaku, Tokyo, Japan) at decreasing side effects during radiation therapy for oral cancer and thereby allowing the completion of radiation therapy without interruption. Two hundred fifteen patients diagnosed with oral cancers were assigned to either Cepharanthin or control groups and underwent external beam irradiation. The completion of the course of radiation therapy and the occurrence of side effects such as mucositis, dysgeusia, and xerostomia during the radiation therapy were evaluated and compared. The completion rate was 87.4% for the Cepharanthin group versus 67.0% for the control group, and the difference was statistically significant (P<0.01). Mucositis did not appear in 58 of 127 cases (45.7%) in the Cepharanthin group or in 21 of 88 cases (23.9%) in the control group. Mucositis developed in 24.6% of the Cepharanthin group and 53.7% of the control group within 2 weeks of irradiation. There were significant relationships between the use of Cepharanthin and the development and timing of mucositis (both P<0.01). Cepharanthin improved the completion of radiation therapy without interruption and reduced or delayed the development of mucositis during radiation therapy for oral cancer. (author)

Sidestream smoke inhalation decreases respiratory clearance of 99mTc-DTPA acutely

International Nuclear Information System (INIS)

Yates, D.H.; Havill, K.; Thompson, M.M.; Rittano, A.B.; Chu, J.; Glanville, A.R.

1996-01-01

The permeability of the alveolar-capillary barrier to an inhaled aerosol of technetium 99m labelled diethylenetriamine penta-acetate ( 99m Tc-DTPA is used as an index of alveolar epithelial injury. Permeability is greatly increased in active smokers. The aim of this study was to determine the effect of sidestream smoke inhalation on permeability as this has not been described previously. Lung clearance of inhaled 99m Tc-DTPA aerosol was measured in 20 normal non-smoking subjects before and after exposure to one hours sidestream smoke inhalation. Measured carbon monoxide (CO) levels rose to a maximum of 23.5 ±6.2 ppm from baseline values of 0.6±1.3 (p 99m Tc-DTPA clearance rose from baseline 69.1± 15.6 (mean ± to 77.4 ±17.8) after smoke exposure. No effect of 99m Tc-DTPA scanning of sidestream smoke was demonstrated on lung function. It was concluded that low level sidestream smoke inhalation decreases 99m Tc-DTPA clearance acutely in humans. The mechanism of this unexpected result is not established but may include differences in constituents between sidestream and mainstream smoke, alterations in pulmonary microvascular blood flow, or changes in surfactant due to an acute phase irritant response. 34 refs., 2 figs

Novel mucosal DNA-MVA HIV vaccination in which DNA-IL-12 plus Cholera Toxin B subunit (CTB) cooperates to enhance cellular systemic and mucosal genital tract immunity

OpenAIRE

Maeto, Cynthia Alejandra; Rodríguez, Ana María; Holgado, María Pía; Falivene, Juliana; Gherardi, Maria Magdalena

2017-01-01

Induction of local antiviral immune responses at the mucosal portal surfaces where HIV-1 and other viral pathogens are usually first encountered remains a primary goal for most vaccines against mucosally acquired viral infections. Exploring mucosal immunization regimes in order to find optimal vector combinations and also appropriate mucosal adjuvants in the HIV vaccine development is decisive. In this study we analyzed the interaction of DNA-IL-12 and cholera toxin B subunit (CTB) after thei...

T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination

Directory of Open Access Journals (Sweden)

Masahisa Hemmi

2017-11-01

Full Text Available Few current vaccines can establish antigen (Ag-specific immune responses in both mucosal and systemic compartments. Therefore, development of vaccines providing defense against diverse infectious agents in both compartments is of high priority in global health. Intramuscular vaccination of an adenovirus vector (Adv has been shown to induce Ag-specific cytotoxic T lymphocytes (CTLs in both systemic and gut-mucosal compartments. We previously found that type I interferon (IFN signaling is required for induction of gut-mucosal, but not systemic, CTLs following vaccination; however, the molecular mechanism involving type I IFN signaling remains unknown. Here, we found that T helper 17 (Th17-polarizing cytokine expression was down-regulated in the inguinal lymph nodes (iLNs of Ifnar2−/− mice, resulting in the reduction of Ag-specific Th17 cells in the iLNs and gut mucosa of the mice. We also found that prior transfer of Th17 cells reversed the decrease in the number of Ag-specific gut-mucosal CTLs in Ifnar2−/− mice following Adv vaccination. Additionally, prior transfer of Th17 cells into wild-type mice enhanced the induction of Ag-specific CTLs in the gut mucosa, but not in systemic compartments, suggesting a gut mucosa-specific mechanism where Th17 cells regulate the magnitude of vaccine-elicited Ag-specific CTL responses. These data suggest that Th17 cells translate systemic type I IFN signaling into a gut-mucosal CTL response following vaccination, which could promote the development of promising Adv vaccines capable of establishing both systemic and gut-mucosal protective immunity.

Tolerance doses of cutaneous and mucosal tissues in ring-necked parakeets (Psittacula krameri) for external beam megavoltage radiation.

Science.gov (United States)

Barron, Heather W; Roberts, Royce E; Latimer, Kenneth S; Hernandez-Divers, Stephen; Northrup, Nicole C

2009-03-01

Currently used dosages for external-beam megavoltage radiation therapy in birds have been extrapolated from mammalian patients and often appear to provide inadequate doses of radiation for effective tumor control. To determine the tolerance doses of cutaneous and mucosal tissues of normal birds in order to provide more effective radiation treatment for tumors that have been shown to be radiation responsive in other species, ingluvial mucosa and the skin over the ingluvies of 9 ring-necked parakeets (Psittacula krameri) were irradiated in 4-Gy fractions to a total dose of either 48, 60, or 72 Gy using an isocentric cobalt-60 teletherapy unit. Minimal radiation-induced epidermal changes were present in the high-dose group histologically. Neither dose-related acute nor chronic radiation effects could be detected in any group grossly in cutaneous or mucosal tissue over a 9-month period. Radiation doses of 72 Gy in 4-Gy fractions were well tolerated in the small number of ring-necked parakeets in this initial tolerance dose study.

Oral Mucositis Prevention By Low-Level Laser Therapy in Head-and-Neck Cancer Patients Undergoing Concurrent Chemoradiotherapy: A Phase III Randomized Study

International Nuclear Information System (INIS)

Gouvêa de Lima, Aline; Villar, Rosângela Correa; Castro, Gilberto de; Antequera, Reynaldo; Gil, Erlon; Rosalmeida, Mauro Cabral; Federico, Miriam Hatsue Honda; Snitcovsky, Igor Moisés Longo

2012-01-01

Purpose: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. Methods and Materials: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm 2 or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60–70 Gy (range, 1.8–2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. Results: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. Conclusions: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might

Cytokines levels, Severity of acute mucositis and the need of PEG tube installation during chemo-radiation for head and neck cancer - a prospective pilot study

International Nuclear Information System (INIS)

Meirovitz, Amichay; Kuten, Michal; Billan, Salem; Abdah-Bortnyak, Roxolyana; Sharon, Anat; Peretz, Tamar; Sela, Mordechai; Schaffer, Moshe; Barak, Vivian

2010-01-01

The purpose of this pilot study was to detect a correlation between serum cytokine levels and severity of mucositis, necessitating installation of a percutaneous endoscopic gastrostomy tube (PEG) in head and neck (H&N) cancer patients receiving combined chemo-radiation therapy. Fifteen patients with H&N epithelial cancer were recruited to this study. All patients received radiotherapy to the H&N region, with doses ranging from 50-70 Gy. Chemotherapy with cisplatin, carboplatin, 5-fluorouracil and taxanes was given to high-risk patients, using standard chemotherapy protocols. Patients were evaluated for mucositis according to WHO common toxicity criteria, and blood samples were drawn for inflammatory (IL-1, IL-6, IL-8, TNF-α) and anti-inflammatory (IL-10) cytokine levels before and during treatment. A positive correlation was found between IL-6 serum levels and severity of mucositis and dysphagia; specifically, high IL-6 levels at week 2 were correlated with a need for PEG tube installation. A seemingly contradictory correlation was found between low IL-8 serum levels and a need for a PEG tube. These preliminary results, indicating a correlation between IL-6 and IL-8 serum levels and severity of mucositis and a need for a PEG tube installation, justify a large scale study

Improved capacity to evaluate changes in intestinal mucosal surface area using mathematical modeling.

Science.gov (United States)

Greig, Chasen J; Cowles, Robert A

2017-07-01

Quantification of intestinal mucosal growth typically relies on morphometric parameters, commonly villus height, as a surrogate for presumed changes in mucosal surface area (MSA). We hypothesized that using mathematical modeling based on multiple unique measurements would improve discrimination of the effects of interventions on MSA compared to standard measures. To determine the ability of mathematical modeling to resolve differences in MSA, a mouse model with enhanced serotonin (5HT) signaling known to stimulate mucosal growth was used. 5-HT signaling is potentiated by targeting the serotonin reuptake transporter (SERT) molecule. Selective serotonin reuptake inhibitor-treated wild-type (WT-SSRI), SERT-knockout (SERTKO), and wild-type C57Bl/6 (WT) mice were used. Distal ileal sections were H&E-stained. Villus height (VH), width (VW), crypt width (CW), and bowel diameter were used to calculate surface area enlargement factor (SEF) and MSA. VH alone for SERTKO and SSRI was significantly increased compared to WT, without a difference between SERTKO and WT-SSRI. VW and CW were significantly decreased for both SERTKO and WT-SSRI compared to WT, and VW for WT-SSRI was also decreased compared to SERTKO. These changes increased SEF and MSA for SERTKO and WT-SSRI compared to WT. Additionally, SEF and MSA were significantly increased for WT-SSRI compared to SERTKO. Mathematical modeling provides a valuable tool for differentiating changes in intestinal MSA. This more comprehensive assessment of surface area does not appear to correlate linearly with standard morphometric measures and represents a more comprehensive method for discriminating between therapies aimed at increasing functional intestinal mucosa. © 2017 Wiley Periodicals, Inc.

Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers.

Science.gov (United States)

Nishino, Masafumi; Sugimoto, Mitsushige; Kodaira, Chise; Yamade, Mihoko; Uotani, Takahiro; Shirai, Naohito; Ikuma, Mutsuhiro; Tanaka, Tatsuo; Sugimura, Haruhiko; Hishida, Akira; Furuta, Takahisa

2011-07-01

The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen. Aspirin induced gastric mucosal injury (median MLS = 3). Lansoprazole significantly decreased MLS to 0, which was significantly lower than that by famotidine (MLS = 1) (P lansoprazole regimen were significantly higher than those with famotidine (P lansoprazole appeared to be more protective than famotidine against low-dose aspirin-induced mucosal injury but a larger well-controlled study is necessary to establish a definitive clinical benefit.

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

Modulation of radiation-induced oral mucositis by pentoxifylline: Preclinical studies

International Nuclear Information System (INIS)

Gruber, Sylvia; Bozsaky, Eva; Schmidt, Margret; Doerr, Wolfgang

2015-01-01

Oral mucositis is a frequent early side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is accompanied by inflammatory reactions; their interaction with epithelial processes remains unclear. The aim of the present study was to investigate the effect of pentoxifylline (PTX) on the oral mucosal radiation response in the mouse tongue model. Irradiation comprised fractionation (5 fractions of 3 Gy/week) over 1 (days 0-4) or 2 weeks (days 0-4, 7-11), followed by graded local top-up doses (day 7/14), in order to generate complete dose-effect curves. PTX (15 mg/kg subcutaneously) was applied once daily over varying time intervals. Ulceration of mouse tongue epithelium, corresponding to confluent mucositis, was analyzed as the clinically relevant endpoint. With fractionated irradiation over 1 week, PTX administration significantly reduced the incidence of mucosal reactions when initiated before (day - 5) the onset of fractionation; a trend was observed for start of PTX treatment on day 0. Similarly, PTX treatment combined with 2 weeks of fractionation had a significant effect on ulcer incidence in all but one experiment. This clearly illustrates the potential of PTX to ameliorate oral mucositis during daily fractionated irradiation. PTX resulted in a significant reduction of oral mucositis during fractionated irradiation, which may be attributed to stimulation of mucosal repopulation processes. The biological basis of this effect, however, needs to be clarified in further, detailed mechanistic studies. (orig.) [de

Effect of plantain banana on gastric ulceration in NIDDM rats: role of gastric mucosal glycoproteins, cell proliferation, antioxidants and free radicals.

Science.gov (United States)

Mohan Kumar, M; Joshi, M C; Prabha, T; Dorababu, M; Goel, R K

2006-04-01

Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect

Mucosal immunity and B cells in teleosts: effect of vaccination and stress.

Directory of Open Access Journals (Sweden)

David eParra

2015-07-01

Full Text Available Fish are subjected to several insults from the environment, which may endanger animal survival. Mucosal surfaces are the first line of defense against those threats and they act as a physical barrier to protect the animal but also function as immunologically active tissues. Thus, four mucosal-associated lymphoid tissues have been described in fish, which lead the immune responses in gut, skin, gills and nose. Humoral and cellular immunity, as well as its regulation and the factors that influence the response in these mucosal lymphoid tissues is still not well known in most of fish species. Mucosal B-lymphocytes and immunoglobulins (Igs are one of the key players in the immune response after vaccination. Recent findings about IgT in trout have delimited the compartmentalization of immune response in systemic and mucosal. The existence of IgT as a specialized mucosa Ig gives us the opportunity of measuring mucosal specific responses after vaccination, a fact that was not possible until recently in most of the fish species. Vaccination process is influenced by several factors, being stress one of the main stimuli determining the success of the vaccine. Thus, one of the major goals in a vaccination process is to avoid possible situations of stress, which might interfere with fish immune performance. However, the interaction between immune and neuroendocrine systems at mucosal tissues is still unknown. In this review we will summarized the latest findings about B-lymphocytes and immunoglobulins in mucosal immunity and the effect of stress and vaccines on B cell response at mucosal sites. It is important to point out that a small number of studies have been published regarding mucosal stress and very few about the influence of stress over mucosal B-lymphocytes.

Perspectives toward oral mucositis prevention from parents and health care professionals in pediatric cancer.

Science.gov (United States)

Ethier, Marie-Chantal; Regier, Dean A; Tomlinson, Deborah; Judd, Peter; Doyle, John; Gassas, Adam; Naqvi, Ahmed; Sung, Lillian

2012-08-01

The objectives of this study were: (1) to describe parents and health care professionals (HCPs) perceived importance of oral mucositis prevention in children with cancer; (2) To describe utilities and willingness-to-pay (WTP) to prevent mucositis. Respondents included parents of children receiving intensive chemotherapy for leukemia/lymphoma or undergoing stem cell transplantation and HCPs caring for children with cancer. Importance of mild and severe oral mucositis was estimated using a visual analogue scale (VAS). Mucositis-associated utilities were elicited using the time trade-off technique (TTO). WTP to avoid mucositis was obtained using contingent valuation. These techniques quantify how much time or money the participant is willing to relinquish in order to prevent mucositis. Eighty-two parents and 60 HCPs were included. Parents and HCPs believed mild mucositis to be of similar importance (median VAS 2.5 versus 3.6; P = 0.357) while parents considered severe mucositis less important than HCPs (median VAS 8.3 versus 9.0; P parent versus HCP responses were seen with TTO (mild or severe mucositis) and most parents were not willing to trade any survival time to prevent severe mucositis. Parents were willing to pay significantly more than HCPs to prevent mild mucositis (average median WTP $1,371 CAN vs. $684 CAN, P = 0.031). No differences were seen in WTP to prevent severe mucositis. Parents and HCP believe severe mucositis to be important, although it is more important to HCPs. Parents would not be willing to reduce life expectancy to eliminate mucositis.

Physiopathology, prevention and treatment of the oral mucositis induced by chemotherapy and radiotherapy

International Nuclear Information System (INIS)

Avila G, Andres; Cardona Z, Andres Felipe; Perea B, Ana Helena

2000-01-01

The oral mucositis is a frequent and potentially severe complication of the antineoplasic therapy; it is considered that approximately 400.000 new patients per year in United States will develop acute or chronic complications in oral cavity after the beginning of its treatment. Some of the basic manifestations that are inside the clinical descriptions understand the erythema, the desquamation, formation of ulcers, the bled, and exudation. The epithelial oropharynge surface has a quick replication rate, and for this reason it is highly exposed to the direct insult due to the cytotoxic effects of the chemotherapy, the radiotherapy, and indirectly the infectious agents. The paper includes topics like physiopathology, risk factors, chemotherapy, radiotherapy, the patient's evaluation and conclusions

C-kit expression in canine mucosal melanomas.

Science.gov (United States)

Newman, S J; Jankovsky, J M; Rohrbach, B W; LeBlanc, A K

2012-09-01

The c-kit receptor is responsible for transmission of promigration signals to melanocytes; its downregulation may be involved in malignant progression of human melanocytic neoplasms. Expression of this receptor has not been examined in normal or neoplastic melanocytes from dogs. In this study, 14 benign dermal and 61 malignant mucosal melanocytic tumors were examined for c-kit (KIT) expression. Sites of the mucosal melanomas were gingiva (not further specified; n = 30), buccal gingiva (n = 6), soft palate (n = 4), hard palate (n = 5), tongue (n = 7), lip (n = 6), and conjunctiva (n = 3). Melan A was expressed in all 14 dermal melanocytomas and in 59 of 61 (96.7%) tumors from oral or conjunctival mucosa, confirming melanocytic origin. C-kit receptor expression was strong and diffuse throughout the cytoplasm in all 14 dermal melanocytomas and was identified in basilar mucosal melanocytes over submucosal neoplasms (27 of 61, 44.3%), junctional (neoplastic) melanocytes (17 of 61, 27.9%), and, less commonly, neoplastic melanocytes of the subepithelial tumors (6 of 61, 9.8%). KIT expression anywhere within the resected melanomas correlated with significantly longer survival. These results suggest that c-kit receptor expression may be altered in canine melanomas and may have potential as a prognostic indicator for mucosal melanomas.

Prevention of ethanol-induced vascular injury and gastric mucosal lesions by sucralfate and its components: possible role of endogenous sulfhydryls

Energy Technology Data Exchange (ETDEWEB)

Szabo, S.; Brown, A.

1987-09-01

The authors tested the hypothesis that sucralfate, which contains eight sulfate and aluminum molecules on a sucrose and its other components might decrease ethanol-induced vascular injury and hemorrhagic mucosal lesions through a sulfhydryl (SH)-sensitive process. Experiments performed in rats revealed that the entire sucralfate molecule is not a prerequisite for protection against ethanol-induced mucosal vascular injury and erosions. It appears that sulfate and sucrose octasulfate are potent components of sucralfate, although an equimolar amount of sucralfate is at least twice as effective in gastroprotection than its components. The SH alkylator N-ethylmaleimide abolished the gastroprotection by sucralfate, suggesting SH-sensitive process in the mucosal protection which seems to be associated with the prevention of rapidly developing vascular injury in the stomach of rats given ethanol.

Citrullus colocynthis as the Cause of Acute Rectorrhagia

Directory of Open Access Journals (Sweden)

Hamid Reza Javadzadeh

2013-01-01

Full Text Available Introduction. Citrullus colocynthis Schrad. is a commonly used medicinal plant especially as a hypoglycemic agent. Case Presentation. Four patients with colocynth intoxication are presented. The main clinical feature was acute rectorrhagia preceeded by mucosal diarrhea with tenesmus, which gradually progressed to bloody diarrhea and overt rectorrhagia within 3 to 4 hours. The only colonoscopic observation was mucosal erosion which was completely resolved in follow-up colonoscopy after 14 days. Conclusion. The membranolytic activity of some C. colocynthis ingredients is responsible for the intestinal damage. Patients and herbalists should be acquainted with the proper use and side effects of the herb. Clinicians should also be aware of C. colocynthis as a probable cause of lower GI bleeding in patients with no other suggestive history, especially diabetics.

Human colorectal mucosal microbiota correlates with its host niche physiology revealed by endomicroscopy.

Science.gov (United States)

Wang, Ai-Hua; Li, Ming; Li, Chang-Qing; Kou, Guan-Jun; Zuo, Xiu-Li; Li, Yan-Qing

2016-02-26

The human gut microbiota plays a pivotal role in the maintenance of health, but how the microbiota interacts with the host at the colorectal mucosa is poorly understood. We proposed that confocal laser endomicroscopy (CLE) might help to untangle this relationship by providing in vivo physiological information of the mucosa. We used CLE to evaluate the in vivo physiology of human colorectal mucosa, and the mucosal microbiota was quantified using 16 s rDNA pyrosequencing. The human mucosal microbiota agglomerated to three major clusters dominated by Prevotella, Bacteroides and Lactococcus. The mucosal microbiota clusters did not significantly correlate with the disease status or biopsy sites but closely correlated with the mucosal niche physiology, which was non-invasively revealed by CLE. Inflammation tilted two subnetworks within the mucosal microbiota. Infiltration of inflammatory cells significantly correlated with multiple components in the predicted metagenome, such as the VirD2 component of the type IV secretory pathway. Our data suggest that a close correlation exists between the mucosal microbiota and the colorectal mucosal physiology, and CLE is a clinically available tool that can be used to facilitate the study of the in vivo correlation between colorectal mucosal physiology and the mucosal microbiota.

Decreased reaction time variability is associated with greater cardiovascular responses to acute stress.

Science.gov (United States)

Wawrzyniak, Andrew J; Hamer, Mark; Steptoe, Andrew; Endrighi, Romano

2016-05-01

Cardiovascular (CV) responses to mental stress are prospectively associated with poor CV outcomes. The association between CV responses to mental stress and reaction times (RTs) in aging individuals may be important but warrants further investigation. The present study assessed RTs to examine associations with CV responses to mental stress in healthy, older individuals using robust regression techniques. Participants were 262 men and women (mean age = 63.3 ± 5.5 years) from the Whitehall II cohort who completed a RT task (Stroop) and underwent acute mental stress (mirror tracing) to elicit CV responses. Blood pressure, heart rate, and heart rate variability were measured at baseline, during acute stress, and through a 75-min recovery. RT measures were generated from an ex-Gaussian distribution that yielded three predictors: mu-RT, sigma-RT, and tau-RT, the mean, standard deviation, and mean of the exponential component of the normal distribution, respectively. Decreased intraindividual RT variability was marginally associated with greater systolic (B = -.009, SE = .005, p = .09) and diastolic (B = -.004, SE = .002, p = .08) blood pressure reactivity. Decreased intraindividual RT variability was associated with impaired systolic blood pressure recovery (B = -.007, SE = .003, p = .03) and impaired vagal tone (B = -.0047, SE = .0024, p = .045). Study findings offer tentative support for an association between RTs and CV responses. Despite small effect sizes and associations not consistent across predictors, these data may point to a link between intrinsic neuronal plasticity and CV responses. © 2016 The Authors. Psychophysiology published by Wiley Periodicals, Inc. on behalf of Society for Psychophysiological Research.

Oral Cryotherapy for Preventing Oral Mucositis in Patients Receiving Cancer Treatment.

Science.gov (United States)

Riley, Philip; McCabe, Martin G; Glenny, Anne-Marie

2016-10-01

In patients receiving treatment for cancer, does oral cryotherapy prevent oral mucositis? Oral cryotherapy is effective for the prevention of oral mucositis in adults receiving fluorouracil-based chemotherapy for solid cancers, and for the prevention of severe oral mucositis in adults receiving high-dose melphalan-based chemotherapy before hematopoietic stem cell transplantation (HSCT).

Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Rathe, Mathias; Sorensen, Grith L; Skov Wehner, Peder

2017-01-01

with acute lymphoblastic leukemia (ALL). PROCEDURE: In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C......BACKGROUND: Surfactant protein D (SP-D) is a host defense molecule of the innate immune system that enhances pathogen clearance and modulates inflammatory responses. We hypothesized that circulating SP-D levels are associated with chemotherapy-induced mucositis and infectious morbidity in children...

Pilot study of ice-ball cryotherapy for radiation-induced oral mucositis

International Nuclear Information System (INIS)

Ohyama, Waichiro; Ebihara, Satoshi

1996-01-01

Oral mucositis caused by radiotherapy is intractable and may worsen the patient's nutritional condition and interrupt treatment. To reduce the incidence and severity of oral mucositis induced by cancer therapy and promote early improvement of its symptoms, we devised cryotherapy by ice balls using Elase (fibrinolysin and deoxyribonuclease, combined). The therapeutic effect of ice-ball cryotherapy was evaluated in 10 patients with carcinoma of the oral cavity and pharynx who were undergoing radiotherapy. Cryotherapy was continued from the development of oral mucositis until its disappearance. The severity of various symptoms of mucositis were reduced by cryotherapy. Healing required 3 to 16 days (median, 7 days) after the end of radiotherapy. Radiotherapy was not interrupted in any cases. This preliminary report suggests that ice-ball cryotherapy is an effective treatment for radiation-induced oral mucositis. (author)

The Mucosal Adjuvant Cholera Toxin B Instructs Non-Mucosal Dendritic Cells to Promote IgA Production Via Retinoic Acid and TGF-β

NARCIS (Netherlands)

A.K. Gloudemans (Anouk); M. Plantinga (Maud); M. Guilliams (Martin); M.A. Willart (Monique); A. Ozir-Fazalalikhan (Arifa); A. van der Ham (Alwin); L. Boon (Louis); N.L. Harris (Nicola); H. Hammad (Hamida); H.C. Hoogsteden (Henk); M. Yazdanbakhsh (Maria); R.W. Hendriks (Rudi); B.N.M. Lambrecht (Bart); H.H. Smits (Hermelijn)

2013-01-01

textabstractIt is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing

Biocompatibility effects of indirect exposure of base-metal dental casting alloys to a human-derived three-dimensional oral mucosal model.

Science.gov (United States)

McGinley, Emma Louise; Moran, Gary P; Fleming, Garry J P

2013-11-01

The study employed a three-dimensional (3D) human-derived oral mucosal model to assess the biocompatibility of base-metal dental casting alloys ubiquitous in fixed prosthodontic and orthodontic dentistry. Oral mucosal models were generated using primary human oral keratinocyte and gingival fibroblast cells seeded onto human de-epidermidised dermal scaffolds. Nickel-chromium (Ni-Cr) and cobalt-chromium (Co-Cr) base-metal alloy immersion solutions were exposed to oral mucosal models for increasing time periods (2-72h). Analysis methodologies (histology, viable cell counts, oxidative stress, cytokine expression and toxicity) were performed following exposure. Ni-based alloy immersion solutions elicited significantly decreased cell viability (P0.4755) or cellular toxicity (Pcasting alloys through discriminatory experimental parameters. Increasing incidences of Ni hypersensitivity in the general population warrants serious consideration from dental practitioners and patients alike where fixed prosthodontic/orthodontic dental treatments are the treatment modality involved. The novel and analytical oral mucosal model has the potential to significantly contribute to the advancement of reproducible dental medical device and dental material appraisals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mucosal Immune Regulation in Early Infancy: Monitoring and Intervention

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J. Hol (Jeroen)

2011-01-01

textabstractThe mucosal immune system of infants is dependent on the maintenance of mucosal homeostasis. Homeostasis results from the interaction between the mucosa and exogenous factors such as dietar and microbial agents. Induction and maintenance of homeostasis is a highly regluated system that

Oesophageal baseline impedance values are decreased in patients with eosinophilic oesophagitis

NARCIS (Netherlands)

van Rhijn, Bram D.; Kessing, Boudewijn F.; Smout, Andreas J. P. M.; Bredenoord, Albert J.

2013-01-01

Background: Gastro-oesophageal reflux has been suggested to play a role in eosinophilic oesophagitis (EoO). Oesophageal acid exposure decreases baseline intraluminal impedance, a marker of mucosal integrity, in patients with gastro-oesophageal reflux disease (GORD). Objectives: The aim of this study

The identification of plant lectins with mucosal adjuvant activity

Science.gov (United States)

Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O'hagan, D T

2001-01-01

To date, the most potent mucosal vaccine adjuvants to be identified have been bacterial toxins. The present data demonstrate that the type 2 ribosome-inactivating protein (type 2 RIP), mistletoe lectin I (ML-I) is a strong mucosal adjuvant of plant origin. A number of plant lectins were investigated as intranasal (i.n.) coadjuvants for a bystander protein, ovalbumin (OVA). As a positive control, a potent mucosal adjuvant, cholera toxin (CT), was used. Co-administration of ML-I or CT with OVA stimulated high titres of OVA-specific serum immunoglobulin G (IgG) in addition to OVA-specific IgA in mucosal secretions. CT and ML-I were also strongly immunogenic, inducing high titres of specific serum IgG and specific IgA at mucosal sites. None of the other plant lectins investigated significantly boosted the response to co-administered OVA. Immunization with phytohaemagglutinin (PHA) plus OVA elicited a lectin-specific response but did not stimulate an enhanced response to OVA compared with the antigen alone. Intranasal delivery of tomato lectin (LEA) elicited a strong lectin-specific systemic and mucosal antibody response but only weakly potentiated the response to co-delivered OVA. In contrast, administration of wheatgerm agglutinin (WGA) or Ulex europaeus lectin 1 (UEA-I) with OVA stimulated a serum IgG response to OVA while the lectin-specific responses (particularly for WGA) were relatively low. Thus, there was not a direct correlation between immunogenicity and adjuvanticity although the strongest adjuvants (CT, ML-I) were also highly immunogenic. PMID:11168640

Vitamin E and L-carnitine, separately or in combination, in the prevention of radiation-induced oral mucositis and myelosuppression. A controlled study in a rat model

International Nuclear Information System (INIS)

Uecuencue, H.; Ertekin, M.V.; Yoeruek, O.; Sezen, O.; Oezkan, A.; Erdogan, F.; Kiziltunc, A.; Guendogdu, C.

2006-01-01

The aim of this study was to determine the effects of vitamin E (VE) and L-carnitine (LC) supplementation, separately or in combination, on radiation-induced oral mucositis and myelosuppression. Group 1 received no treatment (control). Group 2 received 15 Gray of 60 Co gamma irradiation as a single dose to total cranium (IR). Group 3, 4, and 5 received irradiation plus 40 mg/kg/day VE (IR+VE) or 200 mg/kg day LC (IR+LC) or in combination (IR+VE+LC) respectively. Clinically and histopathologically, assessments of mucosal reactions were performed by two independent experts in Radiation Oncology and Pathology, respectively. Hematologic analyses and antioxidant enzyme evaluations were also performed. Irradiation significantly increased oral mucositis, and decreased thrombocyte and White Blood Cell counts. A significant increase in malondialdehyde (MDA) levels and decrease in superoxide dismutase (SOD) and catalase (CAT) activities in plasma were found in the IR group. VE and LC administration, separately, plus irradiation significantly delayed the starting day, and reduced the severity of, oral mucositis. This administration also reduced a fall in the numbers of thrombocyte and white blood cell (WBC) caused by irradiation, and decreased the MDA level, and increased the activity of SOD and CAT enzymes in the plasma. VE and LC, in combination, plus irradiation did not provide a superior radioprotection against radiation-induced toxicities. (author)

Shuidouchi (Fermented Soybean Fermented in Different Vessels Attenuates HCl/Ethanol-Induced Gastric Mucosal Injury

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Huayi Suo

2015-11-01

Full Text Available 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.

Pilot study of ice-ball cryotherapy for radiation-induced oral mucositis

Energy Technology Data Exchange (ETDEWEB)

Ohyama, Waichiro; Ebihara, Satoshi [National Cancer Center Hospital, Tokyo (Japan)

1996-02-01

Oral mucositis caused by radiotherapy is intractable and may worsen the patient`s nutritional condition and interrupt treatment. To reduce the incidence and severity of oral mucositis induced by cancer therapy and promote early improvement of its symptoms, we devised cryotherapy by ice balls using Elase (fibrinolysin and deoxyribonuclease, combined). The therapeutic effect of ice-ball cryotherapy was evaluated in 10 patients with carcinoma of the oral cavity and pharynx who were undergoing radiotherapy. Cryotherapy was continued from the development of oral mucositis until its disappearance. The severity of various symptoms of mucositis were reduced by cryotherapy. Healing required 3 to 16 days (median, 7 days) after the end of radiotherapy. Radiotherapy was not interrupted in any cases. This preliminary report suggests that ice-ball cryotherapy is an effective treatment for radiation-induced oral mucositis. (author).

Primary prevention of peri-implantitis: managing peri-implant mucositis.

Science.gov (United States)

Jepsen, Søren; Berglundh, Tord; Genco, Robert; Aass, Anne Merete; Demirel, Korkud; Derks, Jan; Figuero, Elena; Giovannoli, Jean Louis; Goldstein, Moshe; Lambert, France; Ortiz-Vigon, Alberto; Polyzois, Ioannis; Salvi, Giovanni E; Schwarz, Frank; Serino, Giovanni; Tomasi, Cristiano; Zitzmann, Nicola U

2015-04-01

Over the past decades, the placement of dental implants has become a routine procedure in the oral rehabilitation of fully and partially edentulous patients. However, the number of patients/implants affected by peri-implant diseases is increasing. As there are--in contrast to periodontitis--at present no established and predictable concepts for the treatment of peri-implantitis, primary prevention is of key importance. The management of peri-implant mucositis is considered as a preventive measure for the onset of peri-implantitis. Therefore, the remit of this working group was to assess the prevalence of peri-implant diseases, as well as risks for peri-implant mucositis and to evaluate measures for the management of peri-implant mucositis. Discussions were informed by four systematic reviews on the current epidemiology of peri-implant diseases, on potential risks contributing to the development of peri-implant mucositis, and on the effect of patient and of professionally administered measures to manage peri-implant mucositis. This consensus report is based on the outcomes of these systematic reviews and on the expert opinion of the participants. Key findings included: (i) meta-analysis estimated a weighted mean prevalence for peri-implant mucositis of 43% (CI: 32-54%) and for peri-implantitis of 22% (CI: 14-30%); (ii) bleeding on probing is considered as key clinical measure to distinguish between peri-implant health and disease; (iii) lack of regular supportive therapy in patients with peri-implant mucositis was associated with increased risk for onset of peri-implantitis; (iv) whereas plaque accumulation has been established as aetiological factor, smoking was identified as modifiable patient-related and excess cement as local risk indicator for the development of peri-implant mucositis; (v) patient-administered mechanical plaque control (with manual or powered toothbrushes) has been shown to be an effective preventive measure; (vi) professional intervention

Abnormalities of magnesium homeostasis in patients with chemotherapy-induced alimentary tract mucositis

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Neven Baršić

2016-03-01

Full Text Available Purpose: Hypomagnesemia contributes to morbidity in a significant proportion of hospitalized and severely ill patients, but it could also have beneficial anticancer effects. Alimentary tract mucositis is a frequent complication of cytotoxic chemotherapy. The aim of this study was to determine frequency and severity of hypomagnesemia in patients with different grades of chemotherapy-induced alimentary tract mucositis and to assess its clinical manifestations. Methods: Multicentric observational study included 226 adult patients with alimentary mucositis treated at 3 different institutions. Patients were evaluated for severity of mucositis and the presence of hypomagnesemia, symptoms associated with hypomagnesemia, hypocalcemia, ECG changes and granulocytopenia. Subgroup analysis related to mucositis severity and presence of hypomagnesemia was performed. Results: Patients with grade 3 or 4 alimentary mucositis expectedly had more frequent and more severe granulocytopenia than patients with milder mucositis (49.6% vs. 35.4%, P = 0.043, but there were no differences in rate of hypomagnesemia (24.8% vs. 26.5%. When compared to patients with normal magnesium levels, patients with hypomagnesemia had higher rates of hypocalcemia (50.0% vs. 32.7%, P = 0.026, QTc prolongation (15.5% vs. 3.0%, P = 0.002 and granulocytopenia (77.6% vs. 39.9%, P < 0.001, while there was no difference in symptoms or other ECG features among these subgroups. Conclusions: Hypomagnesaemia is not associated with the severity of chemotherapy-induced mucositis. However, hypomagnesaemia was associated with higher rates of granulocytopenia and hypocalcemia. Our study failed to identify the link between hypomagnesaemia and chemotherapy-induced mucositis.

The mucosal adjuvant cholera toxin B instructs non-mucosal dendritic cells to promote IgA production via retinoic acid and TGF-β.

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Anouk K Gloudemans

Full Text Available It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA, and how T cell-dependent (TD or -independent (TI pathways might be involved. Mucosal dendritic cells (DCs are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL, B cell activating factor (BAFF, Retinoic Acid (RA, TGF-β or nitric oxide (NO. We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-β signaling inhibitor or neutralizing anti-TGF-β was added, demonstrating the involvement of RA and TGF-β in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant.

The mucosal adjuvant cholera toxin B instructs non-mucosal dendritic cells to promote IgA production via retinoic acid and TGF-β.

Science.gov (United States)

Gloudemans, Anouk K; Plantinga, Maud; Guilliams, Martin; Willart, Monique A; Ozir-Fazalalikhan, Arifa; van der Ham, Alwin; Boon, Louis; Harris, Nicola L; Hammad, Hamida; Hoogsteden, Henk C; Yazdanbakhsh, Maria; Hendriks, Rudi W; Lambrecht, Bart N; Smits, Hermelijn H

2013-01-01

It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL), B cell activating factor (BAFF), Retinoic Acid (RA), TGF-β or nitric oxide (NO). We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB) could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR) ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-β signaling inhibitor or neutralizing anti-TGF-β was added, demonstrating the involvement of RA and TGF-β in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant.

The role of sucralfate oral suspension in prevention of radiation induced mucositis

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Hamid Emami

2008-12-01

Full Text Available

• BACKGROUND: Mucositis is one of the most common complications of radiotherapy in head and neck cancers. The aim of this study was to evaluate sucralfate mouthwash in prevention of radiation induced mucositis.
• METHODS: A clinical randomized trial performed on 52 patients with head and neck cancers in Sayyed-Al-Shohada Hospital of Isfahan University of Medical Sciences. These patients randomly assigned in 2 groups of 26 patients. Placebo and sucralfate was used for control and experimental patients respectiv ly, from the beginning of radiotherapy. Patients were visited weekly until the end of treatment. Grade of the mucositis was evaluated according to WHO grading scale.
• RESULTS: Sucralfate significantly reduced the mean grade of mucositis in weeks one to four (with P-values of 0.02, 0.02, 0.001 and 0.004, respectively. Development of grade3 mucositis was also lower in sucralfate group (P-value = 0.0001. But, time interval between radiotherapy and appearance of mucositis was not statistically different in the two groups (P-value = 0.9
• CONCLUSIONS: This study indicated that using oral suspension of sucralfate reduced the grade of radiation-induced mucositis, but did not prevent or delay it.
• KEYWORDS: Mucositis, radiotherapy, sucralfate, head and neck cancers.

Salivary glands act as mucosal inductive sites via the formation of ectopic germinal centers after site-restricted MCMV infection.

Science.gov (United States)

Grewal, Jasvir S; Pilgrim, Mark J; Grewal, Suman; Kasman, Laura; Werner, Phillip; Bruorton, Mary E; London, Steven D; London, Lucille

2011-05-01

We investigated the hypothesis that salivary gland inoculation stimulates formation of ectopic germinal centers (GCs), transforming the gland into a mucosal inductive site. Intraglandular infection of mice with murine cytomegalovirus (MCMV; control: UV-inactivated MCMV) induces salivary gland ectopic follicles comprising cognate interactions between CD4(+) and B220(+) lymphocytes, IgM(+) and isotype-switched IgG(+) and IgA(+) B cells, antigen presenting cells, and follicular dendritic cells. B cells coexpressed the GC markers GCT (57%) and GL7 (52%), and bound the lectin peanut agglutinin. Lymphoid follicles were characterized by a 2- to 3-fold increase in mRNA for CXCL13 (lymphoid neogenesis), syndecan-1 (plasma cells), Blimp-1 (plasma cell development/differentiation), and a 2- to 6-fold increase for activation-induced cytidine deaminase, PAX5, and the nonexcised rearranged DNA of an IgA class-switch event, supporting somatic hypermutation and class-switch recombination within the salivary follicles. Intraglandular inoculation also provided protection against a systemic MCMV challenge, as evidenced by decreased viral titers (10(5) plaque-forming units to undetectable), and restoration of normal salivary flow rates from a 6-fold decrease. Therefore, these features suggest that the salivary gland participates in oral mucosal immunity via generation of ectopic GCs, which function as ectopic mucosal inductive sites.

Comparison of Alloderm and mucosal graft in mandibular vestibuloplasty

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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.

Oral mucositis frequency in head and neck chemoradiotherapy

International Nuclear Information System (INIS)

Hata, Hironobu; Ota, Yojiro; Ueno, Takao; Kurihara, Kinue; Nishimura, Tetsuo; Onozawa, Yusuke; Zenda, Sadamoto

2007-01-01

A retrospective study was performed to determine the frequency and risk factors of oral mucositis in patients receiving radiotherapy or chemoradiotherapy for head and neck tumors. We classified all patients into three groups according to the radiation dose given in the oral cavity (Group A: 0 Gy; 73 patients, Group B: <40 Gy; 66 patients, Group C: ≥40 Gy; 110 patients). In group C, the odds ratio of oral mucositis (≥Gr.2) was 5.6 times in the concomitant chemotherapy group (62 patients) (odds ratio (OR) of 5.6; 95% confidence interval (CI): 2.1-14.9) compared with the radiotherapy (RT) only group (48 patients). In the case of concomitant chemotherapy group in Group C, the odds ratio of oral mucositis (≥Gr.2) was 17 times (OR of 17.1; 95% CI: 2.8-106.0) that in the group using 5-fluorouracil (FU) (50 patients) compared with the group that did not use it (12 patients). For patients whose accumulated radiation dose in the oral cavity was more than 40 Gy, 5-FU was found to be a significant risk factor for oral mucositis. (author)

Fisetin administration improves LPS-induced acute otitis media in mouse in vivo

Science.gov (United States)

Li, Peng; Chen, Dan; Huang, Yang

2018-01-01

Acute otitis media is one of the most common infectious diseases worldwide in spite of the widespread vaccination. The present study was conducted to explore the effects of fisetin on mouse acute otitis media models. The animal models were established by lipopolysaccharide (LPS) injection into the middle ear of mice via the tympanic membrane. Fisetin was administered to mice for ten days through intragastric administration immediate after LPS application. Hematoxylin and eosin (H&E) staining was performed and the pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 and VEGF, were measured through enzyme-linked immunosorbent assay (ELISA) method and RT-qPCR analysis. Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway was detected by immunoblotting assays. Reactive oxygen species (ROS) generated levels were determined through assessment of anti-oxidants, and TXNIP/MAPKs signaling pathways were explored to reveal the possible molecular mechanism for acute otitis media progression and the function of fisetin. Fisetin reduced mucosal thickness caused by LPS. In fisetin-treated animals, pro-inflammatory cytokine release was downregulated accompanied with TLR4/NF-κB inactivation. ROS production was significantly decreased in comparison to the LPS-treated group. The TXNIP/MAPKs signaling pathway was inactivated for fisetin treatment in LPS-induced mice with acute otitis media. The above results indicated that fisetin improved acute otitis media through inflammation and ROS suppression via inactivating TLR4/NF-κB and TXNIP/MAPKs signaling pathways. PMID:29568876

Fisetin administration improves LPS-induced acute otitis media in mouse in vivo.

Science.gov (United States)

Li, Peng; Chen, Dan; Huang, Yang

2018-07-01

Acute otitis media is one of the most common infectious diseases worldwide in spite of the widespread vaccination. The present study was conducted to explore the effects of fisetin on mouse acute otitis media models. The animal models were established by lipopolysaccharide (LPS) injection into the middle ear of mice via the tympanic membrane. Fisetin was administered to mice for ten days through intragastric administration immediate after LPS application. Hematoxylin and eosin (H&E) staining was performed and the pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 and VEGF, were measured through enzyme-linked immunosorbent assay (ELISA) method and RT-qPCR analysis. Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway was detected by immunoblotting assays. Reactive oxygen species (ROS) generated levels were determined through assessment of anti-oxidants, and TXNIP/MAPKs signaling pathways were explored to reveal the possible molecular mechanism for acute otitis media progression and the function of fisetin. Fisetin reduced mucosal thickness caused by LPS. In fisetin-treated animals, pro-inflammatory cytokine release was downregulated accompanied with TLR4/NF-κB inactivation. ROS production was significantly decreased in comparison to the LPS-treated group. The TXNIP/MAPKs signaling pathway was inactivated for fisetin treatment in LPS-induced mice with acute otitis media. The above results indicated that fisetin improved acute otitis media through inflammation and ROS suppression via inactivating TLR4/NF-κB and TXNIP/MAPKs signaling pathways.

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

The therapeutic effect of PLAG against oral mucositis in hamster and mouse model

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Ha-Reum Lee

2016-10-01

Full Text Available Chemotherapy-induced mucositis can limit the effectiveness of cancer therapy and increase the risk of infections. However, no specific therapy for protection against mucositis is currently available. In this study, we investigated the therapeutic effect of PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride in 5-fluorouracil (5-FU-induced oral mucositis animal models. Hamsters were administered 5-FU (80 mg/kg intraperitoneally on days 0, 6, and 9. The animals’ cheek pouches were then scratched equally with the tip of an 18-gauge needle on days 1, 2, and 7. PLAG was administered daily at 250 mg/kg/day. PLAG administration significantly reduced 5-FU/scratching–induced mucositis. Dramatic reversal of weight loss in PLAG-treated hamsters with mucositis was observed. Histochemical staining data also revealed newly differentiated epidermis and blood vessels in the cheek pouches of PLAG-treated hamsters, indicative of recovery. Whole blood analyses indicated that PLAG prevents 5-FU–induced excessive neutrophil transmigration to the infection site and eventually stabilizes the number of circulating neutrophils. In a mouse mucositis model, mice with 5-FU–induced disease treated with PLAG exhibited resistance to body-weight loss compared with mice that received 5-FU or 5-FU/scratching alone. PLAG also dramatically reversed mucositis-associated weight loss and inhibited mucositis-induced inflammatory responses in the tongue and serum. These data suggest that PLAG enhances recovery from 5-FU–induced oral mucositis and may therefore be a useful therapeutic agent for treating side effects of chemotherapy, such as mucositis and cachexia.

Chemotherapy-induced oral mucositis and associated infections in a novel organotypic model.

Science.gov (United States)

Sobue, T; Bertolini, M; Thompson, A; Peterson, D E; Diaz, P I; Dongari-Bagtzoglou, A

2018-06-01

Oral mucositis is a common side effect of cancer chemotherapy, with significant adverse impact on the delivery of anti-neoplastic treatment. There is a lack of consensus regarding the role of oral commensal microorganisms in the initiation or progression of mucositis because relevant experimental models are non-existent. The goal of this study was to develop an in vitro mucosal injury model that mimics chemotherapy-induced mucositis, where the effect of oral commensals can be studied. A novel organotypic model of chemotherapy-induced mucositis was developed based on a human oral epithelial cell line and a fibroblast-embedded collagen matrix. Treatment of organotypic constructs with 5-fluorouracil (5-FU) reproduced major histopathologic characteristics of oral mucositis, such as DNA synthesis inhibition, apoptosis and cytoplasmic vacuolation, without compromising the three-dimensional structure of the multilayer organotypic mucosa. Although structural integrity of the model was preserved, 5-FU treatment resulted in a widening of epithelial intercellular spaces, characterized by E-cadherin dissolution from adherens junctions. In a neutrophil transmigration assay we discovered that this treatment facilitated transport of neutrophils through epithelial layers. Moreover, 5-FU treatment stimulated key proinflammatory cytokines that are associated with the pathogenesis of oral mucositis. 5-FU treatment of mucosal constructs did not significantly affect fungal or bacterial biofilm growth under the conditions tested in this study; however, it exacerbated the inflammatory response to certain bacterial and fungal commensals. These findings suggest that commensals may play a role in the pathogenesis of oral mucositis by amplifying the proinflammatory signals to mucosa that is injured by cytotoxic chemotherapy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oral and intestinal mucositis - causes and possible treatments.

Science.gov (United States)

Duncan, M; Grant, G

2003-11-01

Chemotherapy and radiotherapy, whilst highly effective in the treatment of neoplasia, can also cause damage to healthy tissue. In particular, the alimentary tract may be badly affected. Severe inflammation, lesioning and ulceration can occur. Patients may experience intense pain, nausea and gastro-enteritis. They are also highly susceptible to infection. The disorder (mucositis) is a dose-limiting toxicity of therapy and affects around 500 000 patients world-wide annually. Oral and intestinal mucositis is multi-factorial in nature. The disruption or loss of rapidly dividing epithelial progenitor cells is a trigger for the onset of the disorder. However, the actual dysfunction that manifests and its severity and duration are greatly influenced by changes in other cell populations, immune responses and the effects of oral/gut flora. This complexity has hampered the development of effective palliative or preventative measures. Recent studies have concentrated on the use of bioactive/growth factors, hormones or interleukins to modify epithelial metabolism and reduce the susceptibility of the tract to mucositis. Some of these treatments appear to have considerable potential and are at present under clinical evaluation. This overview deals with the cellular changes and host responses that may lead to the development of mucositis of the oral cavity and gastrointestinal tract, and the potential of existing and novel palliative measures to limit or prevent the disorder. Presently available treatments do not prevent mucositis, but can limit its severity if used in combination. Poor oral health and existing epithelial damage predispose patients to mucositis. The elimination of dental problems or the minimization of existing damage to the alimentary tract, prior to the commencement of therapy, lowers their susceptibility. Measures that reduce the flora of the tract, before therapy, can also be helpful. Increased production of free radicals and the induction of inflammation are

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...

Mucosal innate immune cells regulate both gut homeostasis and intestinal inflammation.

Science.gov (United States)

Kurashima, Yosuke; Goto, Yoshiyuki; Kiyono, Hiroshi

2013-12-01

Continuous exposure of intestinal mucosal surfaces to diverse microorganisms and their metabolites reflects the biological necessity for a multifaceted, integrated epithelial and immune cell-mediated regulatory system. The development and function of the host cells responsible for the barrier function of the intestinal surface (e.g., M cells, Paneth cells, goblet cells, and columnar epithelial cells) are strictly regulated through both positive and negative stimulation by the luminal microbiota. Stimulation by damage-associated molecular patterns and commensal bacteria-derived microbe-associated molecular patterns provokes the assembly of inflammasomes, which are involved in maintaining the integrity of the intestinal epithelium. Mucosal immune cells located beneath the epithelium play critical roles in regulating both the mucosal barrier and the relative composition of the luminal microbiota. Innate lymphoid cells and mast cells, in particular, orchestrate the mucosal regulatory system to create a mutually beneficial environment for both the host and the microbiota. Disruption of mucosal homeostasis causes intestinal inflammation such as that seen in inflammatory bowel disease. Here, we review the recent research on the biological interplay among the luminal microbiota, epithelial cells, and mucosal innate immune cells in both healthy and pathological conditions. © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Trophic factors in the treatment and prevention of alimentary tract mucositis

DEFF Research Database (Denmark)

Rathe, Mathias; Shen, Rene L; Sangild, Per T

2018-01-01

PURPOSE OF REVIEW: Mucositis is a common adverse effect of cytotoxic anticancer treatment with serious implications for the quality of life, morbidity and mortality of cancers patients. Although, evidence supporting the use of certain treatments exists there is no gold standard for preventing...... clinical trials and uniform reporting of mucositis, are important elements to help establish new standard interventions that can be included into the continuously updated clinical recommendations for treatment of mucositis....

Prophylactic and therapeutic management of acute radiation related morbidity of the skin and mucosa. Part I. Results of a German multicenter questionnaire

International Nuclear Information System (INIS)

Zimmermann, J.S.; Wilhelm, R.; Niehoff, P.; Schneider, R.; Kovacs, G.; Kimmig, B.

1998-01-01

In this work, it was to evaluate the remedies, which are used for prevention and therapeutic management of acute radiation related morbidity of the skin and mucosa (mouth, pharynx, esophagus, small and large bowel, rectum and vagina). A questionnaire was sent to 130 radiotherapeutic departments in Germany in Juli 1995. The questionnaire had been designed with 22 open questions concerning the preventive and therapeutic management of acute radiation related morbidity of skin and mucosal sites. From 130 questionnaires, 89 (68.4%) were sent back till August 1995. All of them were evaluable. The recommendations showed a broad spectrum for each site. Especially the oral mucositis was treated in many different ways and combinations. The prevention and therapy of complicating superinfections seem to be the joint principle of most of the recommendations. The management of the acute radiation related morbidity has a wide clinical spectrum among different radiation therapy centers. Systematic prospectively designed investigations are necessary in order to achieve a further reduction in the radiation related acute morbidity. Therefore, a multicenter collaborative working group has been founded. (orig./MG) [de

Dual oxidase in mucosal immunity and host-microbe homeostasis.

Science.gov (United States)

Bae, Yun Soo; Choi, Myoung Kwon; Lee, Won-Jae

2010-07-01

Mucosal epithelia are in direct contact with microbes, which range from beneficial symbionts to pathogens. Accordingly, hosts must have a conflicting strategy to combat pathogens efficiently while tolerating symbionts. Recent progress has revealed that dual oxidase (DUOX) plays a key role in mucosal immunity in organisms that range from flies to humans. Information from the genetic model of Drosophila has advanced our understanding of the regulatory mechanism of DUOX and its role in mucosal immunity. Further investigations of DUOX regulation in response to symbiotic or non-symbiotic bacteria and the in vivo consequences in host physiology will give a novel insight into the microbe-controlling system of the mucosa. Copyright 2010 Elsevier Ltd. All rights reserved.

Effects of adding butyric acid to PN on gut-associated lymphoid tissue and mucosal immunoglobulin A levels.

Science.gov (United States)

Murakoshi, Satoshi; Fukatsu, Kazuhiko; Omata, Jiro; Moriya, Tomoyuki; Noguchi, Midori; Saitoh, Daizoh; Koyama, Isamu

2011-07-01

Parenteral nutrition (PN) causes intestinal mucosal atrophy, gut-associated lymphoid tissue (GALT) atrophy and dysfunction, leading to impaired mucosal immunity and increased susceptibility to infectious complications. Therefore, new PN formulations are needed to maintain mucosal immunity. Short-chain fatty acids have been demonstrated to exert beneficial effects on the intestinal mucosa. We examined the effects of adding butyric acid to PN on GALT lymphocyte numbers, phenotypes, mucosal immunoglobulin A (IgA) levels, and intestinal morphology in mice. Male Institute of Cancer Research mice (n = 103) were randomized to receive either standard PN (S-PN), butyric acid-supplemented PN (Bu-PN), or ad libitum chow (control) groups. The mice were fed these respective diets for 5 days. In experiment 1, cells were isolated from Peyer's patches (PPs) to determine lymphocyte numbers and phenotypes (αβTCR(+), γδTCR(+), CD4(+), CD8(+), B220(+) cells). IgA levels in small intestinal washings were also measured. In experiment 2, IgA levels in respiratory tract (bronchoalveolar and nasal) washings were measured. In experiment 3, small intestinal morphology was evaluated. Lymphocyte yields from PPs and small intestinal, bronchoalveolar, and nasal washing IgA levels were all significantly lower in the S-PN group than in the control group. Bu-PN moderately, but significantly, restored PP lymphocyte numbers, as well as intestinal and bronchoalveolar IgA levels, as compared with S-PN. Villous height and crypt depth in the small intestine were significantly decreased in the S-PN group vs the control group, however Bu-PN restored intestinal morphology. A new PN formula containing butyric acid is feasible and would ameliorate PN-induced impairment of mucosal immunity.

Cryopreservation of Human Mucosal Leukocytes.

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Sean M Hughes

Full Text Available Understanding how leukocytes in the cervicovaginal and colorectal mucosae respond to pathogens, and how medical interventions affect these responses, is important for developing better tools to prevent HIV and other sexually transmitted infections. An effective cryopreservation protocol for these cells following their isolation will make studying them more feasible.To find an optimal cryopreservation protocol for mucosal mononuclear leukocytes, we compared cryopreservation media and procedures using human vaginal leukocytes and confirmed our results with endocervical and colorectal leukocytes. Specifically, we measured the recovery of viable vaginal T cells and macrophages after cryopreservation with different cryopreservation media and handling procedures. We found several cryopreservation media that led to recoveries above 75%. Limiting the number and volume of washes increased the fraction of cells recovered by 10-15%, possibly due to the small cell numbers in mucosal samples. We confirmed that our cryopreservation protocol also works well for both endocervical and colorectal leukocytes. Cryopreserved leukocytes had slightly increased cytokine responses to antigenic stimulation relative to the same cells tested fresh. Additionally, we tested whether it is better to cryopreserve endocervical cells on the cytobrush or in suspension.Leukocytes from cervicovaginal and colorectal tissues can be cryopreserved with good recovery of functional, viable cells using several different cryopreservation media. The number and volume of washes has an experimentally meaningful effect on the percentage of cells recovered. We provide a detailed, step-by-step protocol with best practices for cryopreservation of mucosal leukocytes.

Minocycline down-regulates topical mucosal inflammation during the application of microbicide candidates.

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Liangzhu Li

Full Text Available An effective anti-human immunodeficiency virus-1 (HIV-1 microbicide should exert its action in the absence of causing aberrant activation of topical immunity that will increase the risk of HIV acquisition. In the present study, we demonstrated that the vaginal application of cellulose sulfate (CS gel induced topical mucosal inflammatory responses; the addition of minocycline to CS gel could significantly attenuate the inflammation in a mice model. The combined gel of CS plus minocycline not only reduced the production of inflammatory cytokines in cervicovaginal lavages (CVLs, also down-regulated the activation of CD4+ T cells and the recruitment of other immune cells including HIV target cells into vaginal tissues. Furthermore, an In vitro HIV-1 pseudovirus infection inhibition assay showed that the combined gel decreased the infection efficacy of different subtypes of HIV-1 pseudoviruses compared with that of CS gel alone. These results implicate that minocycline could be integrated into microbicide formulation to suppress the aberrant activation of topical mucosal immunity and enhance the safety profile during the application of microbicides.

Role of serotonin in the intestinal mucosal epithelium barrier in weaning mice undergoing stress-induced diarrhea.

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Dong, Yulan; Wang, Zixu; Qin, Zhuoming; Cao, Jing; Chen, Yaoxing

2018-02-01

Stress-induced diarrhea is a frequent and challenging threat to humans and domestic animals. Serotonin (5-HT) has been shown to be involved in the pathological process of stress-induced diarrhea. However, the role of 5-HT in stress-induced diarrhea remains unclear. A stress-induced diarrhea model was established in 21-day-old ICR weaning mice through an intragastric administration of 0.25 mL of 0.4 g/mL folium sennae and restraint of the hind legs with adhesive tape for 4 h to determine whether 5-HT regulates the mucosal barrier to cause diarrhea. Mice with decreased levels of 5-HT were pretreated with an intraperitoneal injection of 300 mg/kg p-chlorophenylalanine (PCPA), a 5-HT synthesis inhibitor. After 5 days of treatment, the stress level, body weight and intestinal mucosal morphology indexes were measured. Compared to the controls, the mice with stress-induced diarrhea displayed a stress reaction, with increased corticosterone levels, as well as increased 5-HT-positive cells. However, the mice with stress-induced diarrhea exhibited decreased body weights, villus height to crypt depth ratios (V/C), and Occludin and Claudin1 expression. The PCPA injection reversed these effects in mice with different degrees of stress-induced diarrhea. Based on these findings, inhibition of 5-HT synthesis relieved the stress response and improved the health of the intestinal tract, including both the intestinal absorption capacity, as determined by the villus height and crypt depth, and the mucosal barrier function, as determined by the tight junction proteins of epithelial cell.

Increased intestinal mucosal turnover and radiosensitivity to supralethal whole-body irradiation resulting from cholic acid-induced alterations of the intestinal microecology of germfree CFW mice

International Nuclear Information System (INIS)

Mastromarino, A.J.; Wilson, R.

1976-01-01

The prolonged mean survival time of germfree mice, compared to conventional mice, after exposure to 1000-10,000 rad whole-body irradiation has been postulated to be a function of an increased turnover time of the intestinal mucosal cells caused by the absence of free bile acids. To test this hypothesis, the diet of germ-free CFW mice was supplemented with 0.15 percent cholic acid for 2 weeks. The turnover of thymidine-labeled intestinal mucosal cells and the radiosensitivity to supralethal whole-body irradiation were significantly increased compared to germfree controls. There was a positive correlation between increased survivial time after supralethal whole-body irradiation and slower intestinal mucosal turnover time. Germfree mice supplemented with cholic acid had intestinal mucosal turnover times comparable to those of conventionalized controls. Although cholic acid reduces the mean survival time of germfree mice after suppralethal whole-body irradiation, the mean survival value is significantly greater than the conventionalized controls. Supplementing the diet of conventionalized CFW mice with cholic acid did not significantly decrease the intestinal mucosal turnover time nor did it significantly alter their radiosensitivity to supralethal whole-body irradiation. The data suggest that cholic acid is one of the microecological factors responsible for controlling the mucosal renewal rate and the mean survival time after whole-body irradiation

Cocoa and cocoa fibre differentially modulate IgA and IgM production at mucosal sites.

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Massot-Cladera, Malen; Franch, Àngels; Pérez-Cano, Francisco J; Castell, Margarida

2016-05-01

Previous studies have shown that a 10 % cocoa (C10) diet, containing polyphenols and fibre among others, modifies intestinal and systemic Ig production. The present study aimed at evaluating the impact of C10 on IgA and IgM production in the intestinal and extra-intestinal mucosal compartments, establishing the involvement of cocoa fibre (CF) in such effects. Mechanisms by which C10 intake may affect IgA synthesis in the salivary glands were also studied. To this effect, rats were fed either a standard diet, a diet containing C10, CF or inulin. Intestinal (the gut wash (GW), Peyer's patches (PP) and mesenteric lymph nodes (MLN)) and extra-intestinal (salivary glands) mucosal tissues and blood samples were collected for IgA and IgM quantification. The gene expressions of IgA production- and homing-related molecules were studied in the salivary glands. The C10 diet decreased intestinal IgA and IgM production. Although the CF diet decreased the GW IgA concentration, it increased PP, MLN and serum IgA concentrations. Both the C10 and the CF diets produced a down-regulatory effect on IgA secretion in the extra-intestinal tissues. The C10 diet interacted with the mechanisms involved in IgA synthesis, whereas the CF showed particular effects on the homing and transcytosis of IgA across the salivary glands. Overall, CF was able to up-regulate IgA production in the intestinal-inductor compartments, whereas it down-regulated its production at the mucosal-effector ones. Further studies must be directed to ascertain the mechanisms involved in the effect of particular cocoa components on gut-associated lymphoid tissue.

Investigation of how to prevent mucositis induced by chemoradiotherapy

International Nuclear Information System (INIS)

Tosaka, Chihiro; Tajima, Hakuju; Inoue, Tadao

2011-01-01

Chemoradiotherapy for head and neck cancer is associated with a high incidence of severe oral mucositis; an adverse, painful event. Oral mucositis also causes nutritional deficiency by making oral feeding difficult. This may lead to prolongation of hospitalization due to complications caused by malnutrition. However, an effective way to prevent oral mucositis completely, remains to be found. In this study, we evaluated the occurrence of oral mucositis, and nutritional conditions such as hypoalbuminemia, reduction of body weight, and length of hospital stay (days) when the mouth was rinsed using rebamipide solution (R solution), or Poraprezinc-alginate sodium solution (P-A solution) (both considered to be effective for oral mucositis). A mouth rinsed with sodium azulene sulfonate (S solution) was used as a control. The mouth was rinsed out six times per day continuously during chemoradiotherapy. In the study, 31 patients were assigned to rinse their mouths using R solution, 11 patients using P-A solution, and 15 patients using S solution (reduction rate of body weight in 14 patients). For the evaluation, the criteria for adverse drug reactions CTCAE (v3.0) were used. Grade 1 and over, oral mucositis occurred in 48% of the R solution group, 36% of the P-A solution group, and 80% of the S solution group, indicating that the P-A solution group significantly prevented the occurrence of oral mucositis as opposed to the S solution group. A reduction in body weight was observed in 81% of the R solution group, 82% of the P-A solution group, and 79% of the S solution group, indicating a similar weight reduction rate among individual solution groups. Hypoalbuminemia equal to grade 2 or higher occurred in 3% of the R solution group, 18% of the P-A solution group, and 29% of the S solution group, indicating that the R group significantly prevented the occurrence of hypoalbuminemia compared to the S solution group. In addition, the length of hospital stays were 44±8.0 days for

Absorption of iron in the aged; investigation of mucosal-uptake, mucosal-transfer and retention of a physiological dose of inorganic iron

International Nuclear Information System (INIS)

Marx, J.J.M.

1976-01-01

Iron (II) and iron (III) uptake by the mucosal cells, the retention in the body, and the mucosal-transport fraction were studied in 40 healthy people over 65 years old, in 30 young adults and in 20 patients with iron-deficiency. The study was performed with 59 Fe as a tracer and 51 Cr as an inert indicator. The radioactivity was measured with a whole body scanner 24 hours and 24 days after ingestion

Mucosal complications of modified osteo-odonto keratoprosthesis in chronic Stevens-Johnson syndrome.

Science.gov (United States)

Basu, Sayan; Pillai, Vinay Sukumara; Sangwan, Virender S

2013-11-01

To describe clinical outcomes of complications afflicting the autologous oral mucous membrane graft after modified osteo-odonto keratoprosthesis surgery in chronic Stevens-Johnson syndrome (SJS). Prospective case series. This study included 30 eyes of 30 patients with SJS-induced dry keratinized ocular surfaces; the patients underwent various stages of this procedure between August 2009 and February 2012. Mucosal complications were classified as either necrosis or overgrowth. Mucosal necrosis was managed according to a predesigned algorithm based on timing (pre- and postimplantation) and location (central or peripheral) of necrosis. Cases with mucosal overgrowth underwent mucosal debulking and trimming. Mucosal necrosis developed in 15 (50%) eyes and overgrowth in 4 (13.3%) eyes. Preimplantation necrosis (n = 7) was initially managed conservatively, but 2 eyes required free labial-mucous membrane grafting for persistent corneal exposure. Free labial-mucous membrane grafting was performed in all cases of postimplantation necrosis (n = 10), but 8 eyes required additional tarsal pedicle flaps (n = 6, for peripheral necrosis) or through-the-lid revisions (n = 2, for central necrosis). Debulking and trimming effectively managed all cases of mucosal overgrowth, but 3 eyes required repeat procedures. At 24.1 ± 6.5 months postimplantation, the keratoprosthesis was retained in all eyes, and the probability of maintaining 20/60 or better vision was similar in eyes with or without mucosal necrosis (86 ± 8.8% vs 80 ± 10.3%). Mucosal complications, especially necrosis, occurred commonly following modified osteo-odonto keratoprosthesis surgery in dry keratinized post-SJS eyes. The algorithm-based management approach described in this study was successful in treating these complications, retaining the prosthesis and preserving useful vision. Copyright © 2013 Elsevier Inc. All rights reserved.

Mucosal T cells in gut homeostasis and inflammation

OpenAIRE

van Wijk, Femke; Cheroutre, Hilde

2010-01-01

The antigen-rich environment of the gut interacts with a highly integrated and specialized mucosal immune system that has the challenging task of preventing invasion and the systemic spread of microbes, while avoiding excessive or unnecessary immune responses to innocuous antigens. Disruption of the mucosal barrier and/or defects in gut immune regulatory networks may lead to chronic intestinal inflammation as seen in inflammatory bowel disease. The T-cell populations of the intestine play a c...

Oral mucositis: recent perspectives on prevention and treatment

Directory of Open Access Journals (Sweden)

Paulo Sérgio da Silva Santos

2009-10-01

Full Text Available Oral mucositis is a result of toxicity and one of the most common side effects of radiotherapy and chemotherapy in cancer treatment and in hematopoietic stem cell transplantation. Clinically these changes are characterized by epithelial atrophy, edema, erythema and the appearance of ulcerations that can affect the entire oral mucosa, causing pain and discomfort, impairing speech, and swallowing food. In addition to the major symptoms, the ulcers increase the risk of local and systemic infection, compromising function and interfering with oral antineoplastic treatment and may lead to it being discontinued. The diagnosis, prevention and therapeutic strategies in providing support in cases of oral mucositis are the dentist’s responsibility. Through critical analysis of literature, the aim of this article is to present oral mucositis, its pathogenesis, clinical features and treatments offered today to address or control the condition, highlighting the importance of dentists’ role in its management.

A High Grain Diet Dynamically Shifted the Composition of Mucosa-Associated Microbiota and Induced Mucosal Injuries in the Colon of Sheep

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Yue Wang

2017-10-01

Full Text Available This study investigated the dynamic shifts in mucosa-associated microbiota composition and mucosal morphology in the colon of sheep fed a high grain (HG diet. A total of 20 male sheep were randomly assigned to four groups (n = 5 for each. The sheep in first group received hay diet. The animals in other 3 groups were fed an HG diet for 7 (HG7, 14 (HG14, or 28 (HG28 days, respectively. Colonic digesta samples were collected to determine the pH and the concentrations of volatile fatty acid (VFA and lactate. The colonic mucosa was sampled to characterize the bacterial communities using Illumina MiSeq sequencing and to determine mRNA expression levels of cytokines and tight junction protein genes using quantitative real-time PCR. As time advanced, results revealed that colonic pH linearly decreased (P = 0.007, and the concentrations of total VFA linearly increased (P < 0.001. Microbial analysis showed that an HG diet linearly reduced (P < 0.050 the diversity and richness of the colonic microbiota. The principal coordinate analysis results showed that the colonic mucosa-associated bacterial communities of the four groups significantly shifted with number of days fed an HG diet. At the genus level, HG feeding significantly increased the relative abundance of some taxa including Prevotella, Coprococcus, Roseburia, and Clostridium_sensu_stricto_1, and decreased the proportion of Treponema, and the percentage of these taxa was not affected by days fed an HG diet. The microscopic examination showed that HG feeding caused the mucosal epithelial injury. The RT-PCR results showed that the mRNA expression of claudin-1 (P = 0.038, IL-1β (P = 0.045, IL-6 (P = 0.050, and TNF-α (P = 0.020 increased linearly with number of days fed an HG diet. The correlation analysis revealed significant correlation between the colonic mucosal mRNA expression of cytokines and mucosal bacterial composition. Generally, HG feeding increased colonic fermentation and altered colonic

Colonization and effector functions of innate lymphoid cells in mucosal tissues

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Kim, Myunghoo; Kim, Chang H.

2016-01-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193

Improvement in quality of life of children with acute Crohn's disease does not parallel mucosal healing after treatment with exclusive enteral nutrition

NARCIS (Netherlands)

Afzal, N. A.; van der Zaag-Loonen, H. J.; Arnaud-Battandier, F.; Davies, S.; Murch, S.; Derkx, B.; Heuschkel, R.; Fell, J. M.

2004-01-01

Crohn's disease is a chronic debilitating disorder affecting a child's physical and emotional well-being. Recent emphasis on 'quality of life' (QOL) has led to re-evaluation of available medical treatments. To assess prospectively change in QOL, clinical disease activity and intestinal mucosal

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.

Mucosal IgA Responses: Damaged in Established HIV Infection—Yet, Effective Weapon against HIV Transmission

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Viraj Kulkarni

2017-11-01

Full Text Available HIV infection not only destroys CD4+ T cells but also inflicts serious damage to the B-cell compartment, such as lymphadenopathy, destruction of normal B-cell follicle architecture, polyclonal hypergammaglobulinemia, increased apoptosis of B cells, and irreversible loss of memory B-cell responses with advanced HIV disease. Subepithelial B cells and plasma cells are also affected, which results in loss of mucosal IgG and IgA antibodies. This leaves the mucosal barrier vulnerable to bacterial translocation. The ensuing immune activation in mucosal tissues adds fuel to the fire of local HIV replication. We postulate that compromised mucosal antibody defenses also facilitate superinfection of HIV-positive individuals with new HIV strains. This in turn sets the stage for the generation of circulating recombinant forms of HIV. What can the mucosal B-cell compartment contribute to protect a healthy, uninfected host against mucosal HIV transmission? Here, we discuss proof-of-principle studies we have performed using passive mucosal immunization, i.e., topical administration of preformed anti-HIV monoclonal antibodies (mAbs as IgG1, dimeric IgA1 (dIgA1, and dIgA2 isotypes, alone or in combination. Our data indicate that mucosally applied anti-HIV envelope mAbs can provide potent protection against mucosal transmission of simian-human immunodeficiency virus. Our review also discusses the induction of mucosal antibody defenses by active vaccination and potential strategies to interrupt the vicious cycle of bacterial translocation, immune activation, and stimulation of HIV replication in individuals with damaged mucosal barriers.

Investigation of mucosal pattern of gastric antrum using magnifying narrow-band imaging in patients with chronic atrophic fundic gastritis.

Science.gov (United States)

Yamasaki, Yasushi; Uedo, Noriya; Kanzaki, Hiromitsu; Kato, Minoru; Hamada, Kenta; Aoi, Kenji; Tonai, Yusuke; Matsuura, Noriko; Kanesaka, Takashi; Yamashina, Takeshi; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Ishihara, Ryu; Tomita, Yasuhiko; Iishi, Hiroyasu

2017-01-01

Magnifying narrow-band imaging (M-NBI) can reportedly help predict the presence and distribution of atrophy and intestinal metaplasia in the gastric corpus. However, the micro-mucosal pattern of the antrum shown by M-NBI differs from that of the corpus. We studied the distribution and histology of the micro-mucosal pattern in the antrum based on magnifying endoscopy. Endoscopic images of the greater curvature of the antrum were evaluated in 50 patients with chronic atrophic fundic gastritis (CAFG). The extent of CAFG was evaluated by autofluorescence imaging. The micro-mucosal pattern was evaluated by M-NBI and classified into groove and white villiform types. The localization of white villiform type mucosa was classified into three types in relation to the areae gastricae : null, central, and segmental types. Biopsies were taken from regions showing different micro-mucosal patterns. Associations among the extent of CAFG, micro-mucosal pattern, and histology were examined. As the extent of CAFG increased, the proportion of white villiform type mucosa increased, whereas that of groove type mucosa decreased (P=0.022). In patients with extensive CAFG, most of the areae gastricae was composed of the segmental or central type of white villiform type mucosa (P=0.044). The white villiform type mucosa had significantly higher grades of atrophy (P=0.002) and intestinal metaplasia (P<0.001) than did the groove type mucosa. White villiform type mucosa is indicative of atrophy and intestinal metaplasia in the gastric antrum. It extends to the whole or central part of the areae gastricae as CAFG becomes more extensive.

Effect of lactobacillus acidophilus combined with iso-malto-oligosaccharide on the intestinal mucosal secretion of SlgA in rat models with antibiotic-associated diarrhea (AAD)

Energy Technology Data Exchange (ETDEWEB)

Dan, Du; Lichao, Fang; Bingbo, Chen; Hong, Wei [Third Military Medical Univ., Chongqing (China). Laboratory Animal Center

2005-02-15

Objective: To investigate the corrective effect of synbiotic (Lactobacillus acidophilus combined with iso-malto-oligosaccharide) on the decreased intestinal mucosal secretion of SlgA in rat models with antibiotic-associated diarrhea (AAD). Methods: Rat models of AAD were prepared with lincomycin gavage for 6 days. One group of models were left with natural recovery and three other groups were given gavage with different strengths of synbiotic for 7 days. In each group, stool specimens were taken from 6-8 rats for flora examination, then the animals sacrificed and intestinal mucus contents of SIgA determined (with RIA) on d6, d9 and d13. Results: The intestinal flora in rat models of AAD was greatly altered with marked reduction in probiotics. Also, the intestinal mucus contents of SIgA were significantly decreased. Treatment with different strengths of synbiotic (Lactobacillus acidophilus combined with iso-malto-oligosaccharide) would significantly improve the condition with SIgA contents approaching normal. Conclusion: Synbiotic treatment could increase the intestinal mucosal secretion of SIgA with restoration of the mucosal immuno-barrier function in rat models with AAD. (authors)

Effect of lactobacillus acidophilus combined with iso-malto-oligosaccharide on the intestinal mucosal secretion of SlgA in rat models with antibiotic-associated diarrhea (AAD)

International Nuclear Information System (INIS)

Du Dan; Fang Lichao; Chen Bingbo; Wei Hong

2005-01-01

Objective: To investigate the corrective effect of synbiotic (Lactobacillus acidophilus combined with iso-malto-oligosaccharide) on the decreased intestinal mucosal secretion of SlgA in rat models with antibiotic-associated diarrhea (AAD). Methods: Rat models of AAD were prepared with lincomycin gavage for 6 days. One group of models were left with natural recovery and three other groups were given gavage with different strengths of synbiotic for 7 days. In each group, stool specimens were taken from 6-8 rats for flora examination, then the animals sacrificed and intestinal mucus contents of SIgA determined (with RIA) on d6, d9 and d13. Results: The intestinal flora in rat models of AAD was greatly altered with marked reduction in probiotics. Also, the intestinal mucus contents of SIgA were significantly decreased. Treatment with different strengths of synbiotic (Lactobacillus acidophilus combined with iso-malto-oligosaccharide) would significantly improve the condition with SIgA contents approaching normal. Conclusion: Synbiotic treatment could increase the intestinal mucosal secretion of SIgA with restoration of the mucosal immuno-barrier function in rat models with AAD. (authors)

Oral cryotherapy reduces mucositis and opioid use after myeloablative therapy--a randomized controlled trial.

Science.gov (United States)

Svanberg, Anncarin; Birgegård, Gunnar; Ohrn, Kerstin

2007-10-01

Mucositis is a major complication in myeloablative therapy, which often necessitates advanced pharmacological pain treatment, including i.v. opioids. Attempts to prevent oral mucositis have included oral cryotherapy, which has been shown to reduce mucositis, but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation (BMT). The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v. opioids among patients who receive myeloablative therapy before BMT. Eighty patients 18 years and older, scheduled for BMT, were included consecutively and randomised to oral cryotherapy or standard oral care. A stratified randomisation was used with regard to type of transplantation. Intensity of pain, severity of mucositis and use of opioids were recorded using pain visual analogue scale (VAS) scores, mucositis index scores and medical and nursing charts. This study showed that patients receiving oral cryotherapy had less pronounced mucositis and significantly fewer days with i.v. opioids than the control group. In the autologous setting, cryotherapy patients also needed significantly lower total dose of opioids. Oral cryotherapy is an effective and well-tolerated therapy to alleviate mucositis and consequently reduce the number of days with i.v. opioids among patients treated with myeloablative therapy before BMT.

The effect of a supersaturated calcium phosphate mouth rinse on the development of oral mucositis in head and neck cancer patients treated with (chemo)radiation: a single-center, randomized, prospective study of a calcium phosphate mouth rinse + standard of care versus standard of care.

Science.gov (United States)

Lambrecht, Maarten; Mercier, Carole; Geussens, Yasmyne; Nuyts, Sandra

2013-10-01

Mucosal damage is an important and debilitating side effect when treating head and neck cancer patients with (chemo-)radiation. The aim of this randomized clinical trial was to investigate whether the addition of a neutral, supersaturated, calcium phosphate (CP) mouth rinse benefits the severity and duration of acute mucositis in head and neck cancer patients treated with (chemo)radiation. A total of 60 patients with malignant neoplasms of the head and neck receiving (chemo)radiation were included in this study. Fifty-eight patients were randomized into two treatment arms: a control group receiving standard of care (n = 31) and a study group receiving standard of care + daily CP mouth rinses (n = 27) starting on the first day of (chemo-)radiation. Oral mucositis and dysphagia were assessed twice a week using the National Cancer Institute common toxicity criteria scale version 3, oral pain was scored with a visual analogue scale. No significant difference in grade III mucositis (59 vs. 71 %; p = 0.25) and dysphagia (33 vs. 42 %, p = 0.39) was observed between the study group compared to the control group. Also no significant difference in time until development of peak mucositis (28.6 vs. 28.7 days; p = 0.48), duration of peak mucositis (22.7 vs. 24.6 days; p = 0.31), recuperation of peak dysphagia (20.5 vs 24.2 days; p = 0.13) and occurrence of severe pain (56 vs. 52 %, p = 0.5). In this randomized study, the addition of CP mouth rinse to standard of care did not improve the frequency, duration or severity of the most common acute toxicities during and early after (chemo)radiation. There is currently no evidence supporting its standard use in daily practice.

Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection.

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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.

Colonization and effector functions of innate lymphoid cells in mucosal tissues.

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Kim, Myunghoo; Kim, Chang H

2016-10-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Rectal mucosal electrosensitivity - what is being tested?

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Meagher, A P; Kennedy, M L; Lubowski, D Z

1996-01-01

The results of rectal mucosal electrosensitivity (RME) testing have been used to support theories regarding the aetiology of both idiopathic constipation and bowel dysfunction following rectopexy. The aim of this study was to assess the validity of tests of RME. Sixty-eight patients, comprising three groups (group 1: 50 patients undergoing assessment in the Anorectal Physiology Unit, group 2: 10 patients with coloanal or ileoanal anastomosis, group 3: 8 patients with a stoma) underwent mucosal electrosensitivity testing, with the threshold stimulus required to elicit sensation being recorded. In addition the RME was measured in groups 1 and 2 when placing the electrode, mounted on a catheter with a central wire, against the anterior, posterior, right and left rectal or neorectal walls. To asses the influence on this test of loss of mucosal contact due to faeces, a further 8 cases with a normal rectum had RME performed with and without a layer of water soaked gauze around the electrode to stimulate faeces and prevent the electrode from making contact with the rectal mucosa. There was marked variance in the sensitivity of the different regions of rectal wall tested (P < 0.001). In group 1 patients the mean sensitivities were: central 36.6 mA, anterior 27.4 mA, posterior 37.9 mA, right 22.3 mA and left 25.6 mA. This circumferential variation suggests that the pelvic floor rather than rectal mucosa was being stimulated. All patients in group 2 had recordable sensitivities, and the mean sensitivity threshold was significantly higher than group 1 patients in the central (P = 0.03), right (P = 0.03) and left (P = 0.007) positions. In group 3 the sensitivity was greater within the stoma at the level of the abdominal wall muscle than intra-abdominally or subcutaneously, again suggesting an extra-colonic origin of the sensation. The sensitivity threshold was significantly greater with the electrode wrapped in gauze (P < 0.01), and loss of mucosal contact was not detected by

Dietary N-Carbamylglutamate Supplementation Boosts Intestinal Mucosal Immunity in Escherichia coli Challenged Piglets.

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Fengrui Zhang

Full Text Available N-carbamylglutamate (NCG has been shown to enhance performance in neonatal piglets. However, few studies have demonstrated the effect of NCG on the intestinal mucosal barrier. This study was conducted to determine the effects of dietary NCG supplementation on intestinal mucosal immunity in neonatal piglets after an Escherichia coli (E. coli challenge. New-born piglets (4 d old were assigned randomly to one of four treatments (n = 7, including (I sham challenge, (II sham challenge +50 mg/kg NCG, (III E. coli challenge, and (IV E. coli challenge +50 mg/kg NCG. On d 8, pigs in the E. coli challenge groups (III and IV were orally challenged with 5 mL of E. coli K88 (10(8 CFU/mL, whereas pigs in the sham challenge groups (I and II were orally dosed with an equal volume of water. On d 13, all piglets were sacrificed, and samples were collected and examined. The results show that average daily gain in the E. coli challenged piglets (III and IV was decreased (PE.coli<0.05. However, it tended to be higher in the NCG treated piglets (II and IV. Ileum secretory IgA, as well as IFN-γ, IL-2, IL-4 and IL-10 in ileal homogenates, were increased in E. coli challenged piglets (III and IV. Similarly, ileum SIgA and IL-10 levels, and CD4(+ percentage in NCG treated piglets (II and IV were higher than no-NCG treated piglets (PNCG<0.05. However, the IL-2 level was only decreased in the piglets of E. coli challenge + NCG group (IV compared with E. coli challenge group (III (P<0.05. No change in the IL-2 level of the sham challenged piglets (III was observed. In conclusion, dietary NCG supplementation has some beneficial effects on intestinal mucosal immunity in E. coli challenged piglets, which might be associated with stimulated lymphocyte proliferation and cytokine synthesis. Our findings have an important implication that NCG may be used to reduce diarrhea in neonatal piglets.

Candidiasis and other oral mucosal lesions during and after interferon therapy for HCV-related chronic liver diseases.

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Nagao, Yumiko; Hashimoto, Kouji; Sata, Michio

2012-11-02

Oral lichen planus (OLP) is seen frequently in patients with hepatitis C virus (HCV) infection. The aim of this study was to evaluate the occurrence of oral candidiasis, other mucosal lesions, and xerostomia during interferon (IFN) therapy for HCV infection. Of 124 patients with HCV-infected liver diseases treated with IFN therapy in our hospital, 14 (mean age 56.00 ± 12.94 years) who attended to receive administration of IFN once a week were identified and examined for Candida infection and other oral lesions and for the measurement of salivary flow. Serological assays also were carried out. Cultures of Candida from the tongue surfaces were positive in 7 (50.0%) of the 14 patients with HCV infection at least once during IFN therapy. C. albicans was the most common species isolated. The incidence of Candida during treatment with IFN did not increase above that before treatment. Additional oral mucosal lesions were observed in 50.0% (7/14) of patients: OLP in three (21.4%), angular cheilitis in three (21.4%) and recurrent aphthous stomatitis in one (7.1%). OLP occurred in one patient before treatment with IFN, in one during treatment and in one at the end of treatment. 85.7% of the oral lesions were treated with topical steroids. We compared the characteristics of the 7 patients in whom Candida was detected at least once during IFN therapy (group 1) and the 7 patients in whom Candida was not detected during IFN therapy (group 2). The prevalence of oral mucosal lesions (P=0.0075) and incidence of external use of steroids (P=0.0308) in group 1 were significantly higher than in group 2. The average body weight of group 1 decreased significantly compared to group 2 (P=0.0088). Salivary flow decreased in all subjects throughout the course of IFN treatment and returned at 6th months after the end of treatment. In group 1, the level of albumin at the beginning of the 6th month of IFN administration was lower than in group 2 (P=0.0550). According to multivariate analysis

Identification of risk factors for mucosal injury during laparoscopic Heller myotomy for achalasia.

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Tsuboi, Kazuto; Omura, Nobuo; Yano, Fumiaki; Hoshino, Masato; Yamamoto, Se-Ryung; Akimoto, Shusuke; Masuda, Takahiro; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2016-02-01

Mucosal injury during myotomy is the most frequent complication seen with the Heller-Dor procedure for achalasia. The present study aimed to examine risk factors for such mucosal injury during this procedure. This was a retrospective analysis of patients who underwent the laparoscopic Heller-Dor procedure for achalasia at a single facility. Variables for evaluation included patient characteristics, preoperative pathophysiological findings, and surgeon's operative experience. Logistic regression was used to identify risk factors. We also examined surgical outcomes and the degree of patient satisfaction in relation to intraoperative mucosal injury. Four hundred thirty-five patients satisfied study criteria. Intraoperative mucosal injury occurred in 67 patients (15.4%). In univariate analysis, mucosal injury was significantly associated with the patient age ≥60 years, disease history ≥10 years, prior history of cardiac diseases, preoperative esophageal transverse diameter ≥80 mm, and surgeon's operative experience with fewer than five cases. In multivariate analysis involving these factors, the following variables were identified as risk factors: age ≥60 years, esophageal transverse diameter ≥80 mm, and surgeon's operative experience with fewer than five cases. The mucosal injury group had significant extension of the operative time and increased blood loss. However, there were no significant differences between the two groups in the incidence of reflux esophagitis or the degree of symptom alleviation postoperatively. The fragile esophagus caused by advanced patient age and/or dilatation were risk factor for mucosal injury during laparoscopic Heller-Dor procedure. And novice surgeon was also identified as an isolated risk factor for mucosal injury.

Dermoscopic appearance of an amelanotic mucosal melanoma

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Blum, Andreas; Beck-Zoul, Ulrike; Held, Laura; Haase, Sylvie

2016-01-01

Background Hypomelanotic or amelanotic melanomas are challenging to identify, especially at mucosal sites. The dermoscopic clues to the diagnosis of mucosal melanomas have been reported to be structureless zones with the presence of blue, gray, or white colors. Case A female in her seventies noted a new lesion on the inside of her right labia that first appeared two months prior. Her past medical history was significant for rheumatoid arthritis requiring ongoing treatment with methotrexate for 20 years and adalimumab for 10 years. After no response to two weeks of local treatment for suspected herpes simplex infection, her gynecologist performed a skin biopsy. Based on the histopathological diagnosis of an amelanotic melanoma (Breslow thickness of 1.3 mm) the patient was referred to dermatology for further assessment. Polarized dermoscopy revealed a distinct asymmetric, sharply demarcated homogenous white papule (4 × 5 mm) as well as polymorphous vessels. Conclusion Dermoscopy may aid in the diagnosis of amelanotic mucosal melanomas. Our case revealed a structureless white area and polymorphous vessels. Additional clues to the diagnosis were the advanced age of the patient and the clinical presentation of a new lesion. PMID:27867742

Prevalence of oral mucosal lesions among chewing tobacco users: A cross-sectional study

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Sujatha S Reddy

2015-01-01

Statistical Analysis Used: Chi-square and Fisher′s exact tests were used to assess the statistical significance. Results: Of the 901 subjects with CT habits, 55.8% revealed no clinically detectable oral mucosal changes and 44.1% showed mucosal changes of which 63.8% were males and 36.1% were females. The most common finding was chewers mucositis (59.5% followed by submucous fibrosis (22.8%, leukoplakia (8%, lichenoid reaction (6.5%, oral cancer (2.7%, and lichen planus (0.5%. Conclusion: This study provides information about different CT habits and associated mucosal lesions among this population.

Eosinophils in mucosal immune responses

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Travers, J; Rothenberg, M E

2015-01-01

Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

Phase II multicenter randomized study of amifostine for prevention of acute radiation rectal toxicity: Topical intrarectal versus subcutaneous application

International Nuclear Information System (INIS)

Kouloulias, Vassilis E.; Kouvaris, John R.; Pissakas, George; Mallas, Elias; Antypas, Christos; Kokakis, John D.; Matsopoulos, George; Michopoulos, Spyros; Mystakidou, Kyriaki; Vlahos, Lambros J.

2005-01-01

Purpose: To investigate the cytoprotective effect of subcutaneous vs. intrarectal administration of amifostine against acute radiation toxicity. Methods and materials: Patients were randomized to receive amifostine either intrarectally (Group A, n = 27) or a 500-mg flat dose subcutaneously (Group B, n = 26) before irradiation. Therapy was delivered using a four-field technique with three-dimensional conformal planning. In Group A, 1,500 mg of amifostine was administered intrarectally as an aqueous solution in 40 mL of enema. Two different toxicity scales were used: the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group (RTOG) rectal and urologic toxicity criteria and the Subjective-RectoSigmoid scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy. Objective measurements with rectosigmoidoscopy were performed at baseline and 1-2 days after radiotherapy completion. The area under the curve for the time course of mucositis (RTOG criteria) during irradiation represented the mucositis index. Results: Intrarectal amifostine was feasible and well tolerated without any systemic or local side effects. According to the RTOG toxicity scale, Group A had superior results with a significantly lower incidence of Grades I-II rectal radiation morbidity (11% vs. 42%, p 0.04) but inferior results concerning urinary toxicity (48% vs. 15%, p 0.03). The mean rectal mucositis index and Subjective-RectoSigmoid score were significantly lower in Group A (0.44 vs. 2.45 [p = 0.015] and 3.9 vs. 6.0 [p = 0.01], respectively), and the mean urinary mucositis index was lower in Group B (2.39 vs. 0.34, p < 0.028). Conclusions: Intrarectal administration of amifostine (1,500 mg) seemed to have a cytoprotective efficacy in acute radiation rectal mucositis but was inferior to subcutaneous administration in terms of urinary toxicity. Additional randomized studies are needed for definitive decisions concerning the

The efficacy of sucralfate suspension in the prevention of oral mucositis due to radiation therapy

International Nuclear Information System (INIS)

Epstein, J.B.; Wong, F.L.W.

1994-01-01

The purpose of this study was to assess the value of sucralfate suspension in prevention of oral mucositis and for reduction of oral pain in patients who develop mucositis during radiation therapy. The study was a double-blind, placebo-controlled, randomized prospective trial of a sucralfate suspension in the prevention and management of oral mucositis during radiation therapy. Oral mucositis was assessed using a quantitative scale and symptoms were assessed using visual analogue scales. The statistical model was developed to detect a 40% reduction in mucositis. No statistically significant reduction in mucositis was seen. Early during radiation therapy less oral pain was reported in the sucralfate group, but as treatment progressed all patients experienced pain. Patients in the sucralfate group were prescribed topical and systemic analgesics later in the course of radiation therapy. Prophylactic oral rinsing with sucralfate did not prevent oral ulcerative mucositis. Sucralfate may reduce the experience of pain during radiation therapy. 32 refs., 3 tabs

The efficacy of sucralfate suspension in the prevention of oral mucositis due to radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Epstein, J.B.; Wong, F.L.W. (British Columbia Cancer Agency, Vancouver (Canada))

1994-02-01

The purpose of this study was to assess the value of sucralfate suspension in prevention of oral mucositis and for reduction of oral pain in patients who develop mucositis during radiation therapy. The study was a double-blind, placebo-controlled, randomized prospective trial of a sucralfate suspension in the prevention and management of oral mucositis during radiation therapy. Oral mucositis was assessed using a quantitative scale and symptoms were assessed using visual analogue scales. The statistical model was developed to detect a 40% reduction in mucositis. No statistically significant reduction in mucositis was seen. Early during radiation therapy less oral pain was reported in the sucralfate group, but as treatment progressed all patients experienced pain. Patients in the sucralfate group were prescribed topical and systemic analgesics later in the course of radiation therapy. Prophylactic oral rinsing with sucralfate did not prevent oral ulcerative mucositis. Sucralfate may reduce the experience of pain during radiation therapy. 32 refs., 3 tabs.

Evaluation of edaravone against radiation-induced oral mucositis in mice.

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Nakajima, Noriko; Watanabe, Shinichi; Kiyoi, Takeshi; Tanaka, Akihiro; Suemaru, Katsuya; Araki, Hiroaki

2015-03-01

Oral mucositis induced by radiotherapy for cancers of the head and neck reduce the quality of life of patients. However, effective therapeutic agents are lacking. Symptomatic treatment involves local anesthesia and analgesia. We focused on the antioxidant effects of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut(®)). Oral mucositis was induced on the tongue tips of mice using a single dose of X-rays (20 Gy). To evaluate the protective effect of edaravone (30 and 300 mg/kg), administration was carried out 30 min before irradiation. Survival, oral mucositis score, myeloperoxidase activity, and levels of 2-Thiobarbituric acid reactive substances were measured, and all were improved compared with those of control mice. A significant difference was not found in terms of survival due to edaravone. Histopathologic findings also highlighted the beneficial features of edaravone. Edaravone reduced the production of reactive oxygen species. These findings suggest that the protective effect of edaravone against radiation-induced oral mucositis is through an antioxidant effect. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Evaluation of edaravone against radiation-induced oral mucositis in mice

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Noriko Nakajima

2015-03-01

Full Text Available Oral mucositis induced by radiotherapy for cancers of the head and neck reduce the quality of life of patients. However, effective therapeutic agents are lacking. Symptomatic treatment involves local anesthesia and analgesia. We focused on the antioxidant effects of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut®. Oral mucositis was induced on the tongue tips of mice using a single dose of X-rays (20 Gy. To evaluate the protective effect of edaravone (30 and 300 mg/kg, administration was carried out 30 min before irradiation. Survival, oral mucositis score, myeloperoxidase activity, and levels of 2-Thiobarbituric acid reactive substances were measured, and all were improved compared with those of control mice. A significant difference was not found in terms of survival due to edaravone. Histopathologic findings also highlighted the beneficial features of edaravone. Edaravone reduced the production of reactive oxygen species. These findings suggest that the protective effect of edaravone against radiation-induced oral mucositis is through an antioxidant effect.

A new technique for continuous measurement and recording of gastric potential difference in the rat: evaluation of NSAID-induced gastric mucosal damage.

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Scarpignato, C; Corradi, C; Gandolfi, M A; Galmiche, J P

1995-10-01

Disruption of the gastric mucosal barrier by the so-called "barrier breakers" such as ethanol, aspirin, and bile is associated with an increase in gastric potential difference (GPD), that is, a decrease in its negativity. Because a good correlation between the degree of histological damage and changes in GPD has been observed, this parameter has been used increasingly as an index of mucosal integrity. However, the current methodology for measuring GPD is laborious due to the preparation and checking of KCl-agarose bridges prior to each experiment, and calculations--usually handmade--are time-consuming and inaccurate. In this paper, a new method allowing simultaneous measurement and recording of GPD in the rat is described. The method allows a simultaneous recording of intragastric pH and an automatic data analysis. The new technique has been validated by studying mucosal damage induced by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) (namely indomethacin and droxicam) as well as the mucosal protective activity of an antacid and sucralfate. The similarity between the results obtained in this rat model and those derived from human experiments clearly show that the developed methodology yields results that are predictive for human pharmacology.

Clinical assessment of oral mucositis and candidiasis compare to chemotherapic nadir in transplanted patients.

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Patussi, Cleverson; Sassi, Laurindo Moacir; Munhoz, Eduardo Ciliao; Zanicotti, Roberta Targa Stramandinoli; Schussel, Juliana Lucena

2014-01-01

Oral mucositis is a chief complication in patients undergoing hematopoietic stem cell transplantation (HSCT). It is considered a toxic inflammatory reaction that interferes with the patient's recuperation and quality of life. Oral candidiasis is a common fungal infection observed in dental practice, particularly in immunocompromised patients. The aim of this study was to evaluate the presence of oral mucositis and oral candidiasis in patients who underwent HSCT and their correlation with the chemotherapeutic nadir (lowest possible outcome). We evaluated patients with different diagnoses who underwent HSCT at the Hospital Erasto Gaertner. No chemotherapeutic nadir curves could be associated with mucositis, and patients had different presentations of mucositis. No patient developed oral candidiasis during hospitalization. Together with cell counts, we collected demographic data including age, oral hygiene, habits harmful to health, and the use of oral prostheses. It was observed that patients who smoked cigarettes before hospitalization showed less mucositis, resulting in no feeding problems or other comorbid conditions due to the effect of mucositis. However, the nadir of the chemotherapy curve, in isolation, is not a predictive tool for the appearance (or no appearance) of oral mucositis.

Treatment of Helicobacter pylori infection favourably affects gastric mucosal superoxide dismutases

NARCIS (Netherlands)

Götz, J. M.; Thio, J. L.; Verspaget, H. W.; Offerhaus, G. J.; Biemond, I.; Lamers, C. B.; Veenendaal, R. A.

1997-01-01

Excessive production of reactive oxygen metabolites (ROMs) by phagocytic cells is thought to contribute to the mucosal pathology of Helicobacter pylori infection. Previously, H pylori infection was shown to have a differential effect on some gastric mucosal scavenger enzymes of ROMs-namely,

Neonatal Cytokine Profile in the Airway Mucosal Lining Fluid Is Skewed by Maternal Atopy

DEFF Research Database (Denmark)

Folsgaard, Nilofar V.; Chawes, Bo L.; Rasmussen, Morten A.

2012-01-01

on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. Objectives: To study parental atopic imprinting on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. Methods: Eighteen cytokines and chemokines were quantified in nasal mucosal...

Evaluation of mast cells, eosinophils, blood capillaries in oral lichen planus and oral lichenoid mucositis.

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Reddy, D Santhosh; Sivapathasundharam, B; Saraswathi, T R; SriRam, G

2012-01-01

Mast cells are granule containing secretory cells present in oral mucosal and connective tissue environment. Oral lichen planus and oral lichenoid lesions are commonly occurring oral diseases and have some similarity clinically and histologically. Both are characterized by an extensive sub epithelial infiltrate of T cells, together with mast cells, eosinophils and blood capillaries. In this study mast cell and eosinophil densities along with number of blood capillaries were studied to find out if they could aid in histopathological distinction between oral lichen planus and lichenoid mucositis. To enumerate mast cells and compare the status of Mast Cells (Intact or Degranulated) in Lichen planus, Lichenoid mucositis and normal buccal mucosa in tissue sections stained with Toluidine Blue, and also to enumerate Eosinophils and blood capillaries in tissue sections stained with H and E. The study group included 30 cases each of oral lichen planus and oral lichenoid mucositis. 10 cases of clinically normal oral buccal mucosa formed the control group. All the sections were stained with Toluidine blue and H and E separately. Histopathological analysis was done using binocular light microscope equipped with square ocular grid to standardize the field of evaluation. The result of the study showed. · Significant increase in number of mast cells in oral lichen planus and oral lichenoid mucositis compared to normal buccal mucosa. · Significant increase of intact mast cells suepithelially within the inflammatory cell infiltrate in oral lichen planus compared to oral lichenoid mucositis. · Significant increase of degranulated mast cells in oral lichenoid mucositis to oral lichen planus, and increase in number of eosinophil densities in oral lichenoid mucositis compared to oral lichen planus. · Significant increase in number of capillaries in oral lichenoid mucositis compared to oral lichen planus. The findings of increased number of intact mast cells sub epithelially in oral

Simultaneous approach using systemic, mucosal and transcutaneous routes of immunization for development of protective HIV-1 vaccines.

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Belyakov, I M; Ahlers, J D

2011-01-01

Mucosal tissues are major sites of HIV entry and initial infection. Induction of a local mucosal cytotoxic T lymphocyte response is considered an important goal in developing an effective HIV vaccine. In addition, activation and recruitment of memory CD4(+) and CD8(+) T cells in systemic lymphoid circulation to mucosal effector sites might provide the firewall needed to prevent virus spread. Therefore a vaccine that generates CD4(+) and CD8(+) responses in both mucosal and systemic tissues might be required for protection against HIV. However, optimal routes and number of vaccinations required for the generation of long lasting CD4(+) and CD8(+) CTL effector and memory responses are not well understood especially for mucosal T cells. A number of studies looking at protective immune responses against diverse mucosal pathogens have shown that mucosal vaccination is necessary to induce a compartmentalized immune response including maximum levels of mucosal high-avidity CD8(+) CTL, antigen specific mucosal antibodies titers (especially sIgA), as well as induction of innate anti-viral factors in mucosa tissue. Immune responses are detectable at mucosal sites after systemic delivery of vaccine, and prime boost regimens can amplify the magnitude of immune responses in mucosal sites and in systemic lymphoid tissues. We believe that the most optimal mucosal and systemic HIV/SIV specific protective immune responses and innate factors might best be achieved by simultaneous mucosal and systemic prime and boost vaccinations. Similar principals of vaccination may be applied for vaccine development against cancer and highly invasive pathogens that lead to chronic infection.

Suppressed Gastric Mucosal TGF-β1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response

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Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin

2010-01-01

Background/Aims Loss of transforming growth factor β1 (TGF-β1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-β1 levels could be used to determine the outcome after H. pylori infection. Methods Northern blot for the TGF-β1 transcript, staining of TGF-β1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-β1 levels were performed at different times after H. pylori infection. Results The TGF-β1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-β1 levels. SNU-16 cells showing intact TGF-β signaling exhibited a marked decrease in TGF-β1 expression, whereas SNU-638 cells defective in TGF-β signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-β1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-β1 is a host defense mechanism to avoid attachment of H. pylori. Conclusions H. pylori infection was associated with depressed gastric mucosal TGF-β1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation. PMID:20479912

Suppressed Gastric Mucosal TGF-beta1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response.

Science.gov (United States)

Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin; Hahm, Ki-Baik

2010-03-01

Loss of transforming growth factor beta1 (TGF-beta1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-beta1 levels could be used to determine the outcome after H. pylori infection. Northern blot for the TGF-beta1 transcript, staining of TGF-beta1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-beta1 levels were performed at different times after H. pylori infection. The TGF-beta1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-beta1 levels. SNU-16 cells showing intact TGF-beta signaling exhibited a marked decrease in TGF-beta1 expression, whereas SNU-638 cells defective in TGF-beta signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-beta1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-beta1 is a host defense mechanism to avoid attachment of H. pylori. H. pylori infection was associated with depressed gastric mucosal TGF-beta1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation.

Mucosal Immune Regulation in Early Infancy: Monitoring and Intervention

OpenAIRE

Hol, Jeroen

2011-01-01

textabstractThe mucosal immune system of infants is dependent on the maintenance of mucosal homeostasis. Homeostasis results from the interaction between the mucosa and exogenous factors such as dietar and microbial agents. Induction and maintenance of homeostasis is a highly regluated system that involves different cell types. If homeostasis is lost this may lead to disease, including allergy and chronic intestinal inflammation. In this thesis we observed whether loss of homeostasis leading ...

Genetic variants alter T-bet binding and gene expression in mucosal inflammatory disease.

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Katrina Soderquest

2017-02-01

Full Text Available The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection, but aberrant T cell polarization can cause autoimmunity. The transcription factor T-bet (TBX21 specifies the Th1 lineage and represses alternative T cell fates. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs that may be causative for autoimmune diseases. The majority of these polymorphisms are located within non-coding distal regulatory elements. It is considered that these genetic variants contribute to disease by altering the binding of regulatory proteins and thus gene expression, but whether these variants alter the binding of lineage-specifying transcription factors has not been determined. Here, we show that SNPs associated with the mucosal inflammatory diseases Crohn's disease, ulcerative colitis (UC and celiac disease, but not rheumatoid arthritis or psoriasis, are enriched at T-bet binding sites. Furthermore, we identify disease-associated variants that alter T-bet binding in vitro and in vivo. ChIP-seq for T-bet in individuals heterozygous for the celiac disease-associated SNPs rs1465321 and rs2058622 and the IBD-associated SNPs rs1551398 and rs1551399, reveals decreased binding to the minor disease-associated alleles. Furthermore, we show that rs1465321 is an expression quantitative trait locus (eQTL for the neighboring gene IL18RAP, with decreased T-bet binding associated with decreased expression of this gene. These results suggest that genetic polymorphisms may predispose individuals to mucosal autoimmune disease through alterations in T-bet binding. Other disease-associated variants may similarly act by modulating the binding of lineage-specifying transcription factors in a tissue-selective and disease-specific manner.

Evaluation of concordance between CAD/CAM and clinical positions of abutment shoulder against mucosal margin: an observational study.

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Pietruski, Jan K; Skurska, Anna; Bernaczyk, Anna; Milewski, Robert; Pietruska, Maria Julia; Gehrke, Peter; Pietruska, Małgorzata D

2018-05-02

While working on CAD/CAM-customized abutments, the use of standard impression copings with a circular diameter produces inconsistency within the emergence profile. It may begin with a collapse of the supra-implant mucosa during impression taking, then lead to a computer-generated mismatch of the position and outline of the abutment shoulder, and consequently result in a compromised outcome of anticipated treatment. The aim of the study was to compare the virtual and clinical positions of the abutment shoulder in relation to the mucosal margin after the abutment delivery. Conventional open-tray impression takings followed uncovering surgery. Master casts were scanned with a desktop scanner. Clinical examinations took place after abutment's insertion and temporization (T1) and prior to cementation of the definitive crown (T2). The distances between the abutment shoulder and marginal soft tissue were measured intraorally in four aspects and juxtaposed with those on the virtual model. The study evaluated 257 dental implants and CAD/CAM-customized abutments. As T1 and T2 showed, there was a positive correlation between the virtually designed abutment shoulder position and matching clinical location relative to the mucosal margin. In 42.1% of cases, the distance between the mucosal margin and the abutment shoulder did not change. It increased in 36.3% of cases while a decrease occurred in 21.6% of them. Computer-set position of the abutment shoulder in relation to the mucosal margin can be predictably implemented in clinical practice.

Chemotherapy-Induced and/or Radiation Therapy-Induced Oral Mucositis-Complicating the Treatment of Cancer

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Maddireddy Umameshwar Rao Naidu

2004-09-01

Full Text Available The term mucositis is coined to describe the adverse effects of radiation and chemotherapy treatments. Mucositis is one of the most common adverse reactions encountered in radiation therapy for head and neck cancers, as well as in chemotherapy, in particular with drugs affecting DNA synthesis (Sphase-specific agents such as fluorouracil, methotrexate, and cytarabine. Mucositis may limit the patient's ability to tolerate chemotherapy or radiation therapy, and nutritional status is compromised. It may drastically affect cancer treatment as well as the patient's quality of life. The incidence and severity of mucositis will vary from patient to patient. It will also vary from treatment to treatment. It is estimated that there is 40% incidence of mucositis in patients treated with standard chemotherapy and this will not only increase with the number of treatment cycles but also with previous episodes. Similarly, patients who undergo bone marrow transplantation and who receive high doses of chemotherapy have a 76% chance of getting mucositis. Patients receiving radiation, in particular to head and neck cancers, have a 30% to 60% chance. The exact pathophysiology of development is not known, but it is thought to be divided into direct and indirect mucositis. Chemotherapy and/or radiation therapy will interfere with the normal turnover of epithelial, cells leading to mucosal injury; subsequently, it can also occur due to indirect invasion of Gram-negative bacteria and fungal species because most of the cancer drugs will cause changes in blood counts. With the advancement in cytology, a more precise mechanism has been established. With this understanding, we can select and target particular mediators responsible for the mucositis. Risk factors such as age, nutritional status, type of malignancy, and oral care during treatment will play important roles in the development of mucositis. Many treatment options are available to prevent and treat this

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

micrograms/kg/min) induced an increase in mucosal blood flow and a similar increase in acid secretion. If the dopamine infusion was preceded by alpha-receptor blockade, a pronounced increase in mucosal blood flow was observed without a similar increase in acid secretion. beta-adrenergic stimulation...

Substitution urethroplasty for anterior urethral strictures: buccal versus lingual mucosal graft.

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Kumar, Abhay; Das, Suren K; Trivedi, Sameer; Dwivedi, Udai S; Singh, Pratap B

2010-01-01

To compare the results of substitution urethroplasty and donor site morbidity between buccal mucosal graft (BMG) and lingual mucosal graft (LMG). Patients who underwent single-stage dorsal onlay free oral mucosal graft substitution urethroplasty by Barbagli's technique between January 2004 and August 2008 were included in this study. Patients who underwent buccal (cheek, lip) mucosal graft urethroplasty were included in group I and those who underwent LMG urethroplasty (tongue) were included in group II. All patients underwent complete evaluation of the stricture including inspection of the oral cavity. Exclusion criteria were stricture length speech complications was seen in group II, but not in group I. The long-term complications of persistent oral discomfort, perioral numbness and tightness of the mouth were seen only in group I. LMG urethroplasty is a good substitute for BMG urethroplasty with equally good results of urethroplasty with lower donor site morbidity. Copyright 2010 S. Karger AG, Basel.

Endomicroscopy for assessing mucosal healing in patients with ulcerative colitis.

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Gheorghe, Cristian; Cotruta, Bogdan; Iacob, Razvan; Becheanu, Gabriel; Dumbrava, Mona; Gheorghe, Liana

2011-12-01

The assessment of tissue healing has emerged as an important treatment goal in patients with inflammatory bowel disease. In patients with ulcerative colitis (UC), mucosal healing may represent the ultimate therapeutic goal due to the fact that the inflammation is limited to the mucosal layer. Mucosal and histological healing may indicate a subset of UC patients in long-term clinical, endoscopic and histological remission in whom immunomodulators, biologics, and even aminosalicylates may be withdrawn. Confocal laser endomicroscopy allows the assessment of residual cellular inflammation, crypt and vessel architecture distortion during ongoing endoscopy, and therefore permits a real-time evaluation of histological healing in patients with ulcerative proctitis. Images of conventional optical microscopy and confocal laser endomicroscopy in patients with ulcerative proctitis in remission are presented.

Mucosal healing and deep remission: What does it mean?

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Rogler, Gerhard; Vavricka, Stephan; Schoepfer, Alain; Lakatos, Peter L

2013-01-01

The use of specific terms under different meanings and varying definitions has always been a source of confusion in science. When we point our efforts towards an evidence based medicine for inflammatory bowel diseases (IBD) the same is true: Terms such as “mucosal healing” or “deep remission” as endpoints in clinical trials or treatment goals in daily patient care may contribute to misconceptions if meanings change over time or definitions are altered. It appears to be useful to first have a look at the development of terms and their definitions, to assess their intrinsic and context-independent problems and then to analyze the different relevance in present-day clinical studies and trials. The purpose of such an attempt would be to gain clearer insights into the true impact of the clinical findings behind the terms. It may also lead to a better defined use of those terms for future studies. The terms “mucosal healing” and “deep remission” have been introduced in recent years as new therapeutic targets in the treatment of IBD patients. Several clinical trials, cohort studies or inception cohorts provided data that the long term disease course is better, when mucosal healing is achieved. However, it is still unclear whether continued or increased therapeutic measures will aid or improve mucosal healing for patients in clinical remission. Clinical trials are under way to answer this question. Attention should be paid to clearly address what levels of IBD activity are looked at. In the present review article authors aim to summarize the current evidence available on mucosal healing and deep remission and try to highlight their value and position in the everyday decision making for gastroenterologists. PMID:24282345

Understanding the Oral Mucosal Absorption and Resulting Clinical Pharmacokinetics of Asenapine

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Bartlett, Jeremy A.; Maarschalk, Kees van der Voort

2012-01-01

Absorption of drugs from the oral cavity into the mucosal tissues is typically a fast event. Dissolved drugs partition into the mucosal membranes and within minutes will reach equilibrium with drug in solution in the oral cavity. However, this does not always equate to rapid drug appearance in the

Bladder Mucosal Graft Vaginoplasty: A Case Report.

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Chiaramonte, Cinzia; Vestri, Elettra; Tripi, Flavia; Giannone, Antonino Giulio; Cimador, Marcello; Cataliotti, Ferdinando

2018-06-18

Female vaginoplasty reconstruction, by choice, is usually performed with adjacent tissue. However in some clinical conditions such as high urogenital confluence sinus, cloacal malformation with extreme vaginal hypoplasia, local tissue may not be available. When vaginal replacement is performed in pediatric patients intestinal segments is preferred to non-operative procedures that require continuative dilations. However mucus production, malignant transformation risk and diversion colitis are important side effects. We present a nouvel technique for vaginoplasty in a female child presenting with an isolated urogenital sinus malformation without virilization. The patient at 20 months underwent vaginoplasty using tubularized bladder mucosal graft. Surgical procedure was devoid of complications. Pubertal development occurred at age of 15. She underwent regular follow up until 18 years of age. At this age we performed clinical evaluation: absence of vaginal introitus stenosis and good cosmetic results were observed. Then she underwent vaginoscopy with multiple biopsies. Pathology examination of the bladder mucosal graft evidenced a normal structure of the mucosa, with a stratified squamous epithelium. Different techniques are taken into account for vaginal reconstruction according to the severity and to the type of malformation. We describe the use of bladder mucosal graft with favorable results after long term follow-up. Copyright © 2018. Published by Elsevier Inc.

The Mucosal Immune System and Its Regulation by Autophagy.

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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.

Pharmacological Protection From Radiation ± Cisplatin-Induced Oral Mucositis

International Nuclear Information System (INIS)

Cotrim, Ana P.; Yoshikawa, Masanobu; Sunshine, Abraham N.; Zheng Changyu; Sowers, Anastasia L.; Thetford, Angela D.; Cook, John A.; Mitchell, James B.; Baum, Bruce J.

2012-01-01

Purpose: To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation ± cisplatin. Methods and Materials: Female C3H mice, ∼8 weeks old, were irradiated with five fractionated doses ± cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. Results: Significant lingual ulcers resulted from 5 × 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. Conclusions: Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.

Mucus reduction promotes acetyl salicylic acid-induced small intestinal mucosal injury in rats.

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Suyama, Yosuke; Handa, Osamu; Naito, Yuji; Takayama, Shun; Mukai, Rieko; Ushiroda, Chihiro; Majima, Atsushi; Yasuda-Onozawa, Yuriko; Higashimura, Yasuki; Fukui, Akifumi; Dohi, Osamu; Okayama, Tetsuya; Yoshida, Naohisa; Katada, Kazuhiro; Kamada, Kazuhiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Konishi, Hideyuki; Itoh, Yoshito

2018-03-25

Acetyl salicylic acid (ASA) is a useful drug for the secondary prevention of cerebro-cardiovascular diseases, but it has adverse effects on the small intestinal mucosa. The pathogenesis and prophylaxis of ASA-induced small intestinal injury remain unclear. In this study, we focused on the intestinal mucus, as the gastrointestinal tract is covered by mucus, which exhibits protective effects against various gastrointestinal diseases. ASA was injected into the duodenum of rats, and small intestinal mucosal injury was evaluated using Evans blue dye. To investigate the importance of mucus, Polysorbate 80 (P80), an emulsifier, was used before ASA injection. In addition, rebamipide, a mucus secretion inducer in the small intestine, was used to suppress mucus reduction in the small intestine of P80-administered rats. The addition of P80 reduced the mucus and exacerbated the ASA-induced small intestinal mucosal injury. Rebamipide significantly suppressed P80-reduced small intestinal mucus and P80-increased intestinal mucosal lesions in ASA-injected rats, demonstrating that mucus is important for the protection against ASA-induced small intestinal mucosal injury. These results provide new insight into the mechanism of ASA-induced small intestinal mucosal injury. Mucus secretion-increasing therapy might be useful in preventing ASA-induced small intestinal mucosal injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Mucosal versus muscle pain sensitivity in provoked vestibulodynia

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Witzeman K

2015-08-01

Full Text Available Kathryn Witzeman,1 Ruby HN Nguyen,2 Alisa Eanes,3 Sawsan As-Sanie,4 Denniz Zolnoun51Department of Obstetrics and Gynecology, Denver Health Medical Center, Denver, CO, 2Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, 3Pelvic Pain Research Unit, Division of Advanced Laparoscopy and Pelvic Pain, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC, 4Department of Obstetrics and Gynecology, Division of Minimally Invasive Gynecologic Surgery, University of Michigan, Ann Arbor, MI, 5Department of Obstetrics and Gynecology and Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, NC, USABackground: An estimated 8.3%–16% of women experience vulvovaginal discomfort during their lifetime. Frequently these patients report provoked pain on contact or with attempted intercourse, commonly referred to as provoked vestibulodynia (PVD. Despite the burden of this condition, little is known about its potential etiologies including pelvic floor muscular dysfunction and mucosal components. This knowledge would be beneficial in developing targeted therapies including physical therapy.Objective: To explore the relative contribution of mucosal versus muscle pain sensitivity on pain report from intercourse among women with PVD.Design: In this proof of concept study, 54 women with PVD underwent a structured examination assessing mucosal and pelvic muscle sensitivity.Methods: We examined three mucosal sites in the upper and lower vestibule. Patients were asked to rate their pain on cotton swab palpation of the mucosa using a 10-point visual analog scale. Muscle pain was assessed using transvaginal application of pressure on right and left puborectalis, and the perineal muscle complex. The Gracely pain scale (0–100 was used to assess the severity of pain with intercourse, with women rating the lowest, average, and highest pain levels; a 100 rating the

Esophageal acid sensitivity and mucosal integrity in patients with functional heartburn.

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Weijenborg, P W; Smout, A J P M; Bredenoord, A J

2016-11-01

Patients with functional heartburn (FH) experience troublesome heartburn that is not related to gastroesophageal reflux. The etiology of the heartburn sensation in FH patients is unknown. In patients with reflux disease, esophageal hypersensitivity seems associated with impaired mucosal integrity. We aimed to determine esophageal sensitivity and mucosal integrity in FH and non-erosive reflux disease (NERD) patients. In this prospective experimental study, we performed an acid perfusion test and upper endoscopy with biopsies in 12 patients with NERD and nine patients with FH. Mucosal integrity was measured during endoscopy using electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance and transepithelial permeability. Lag time to heartburn perception was significantly longer in FH patients (median 12 min) than in NERD patients (median 3 min). Once perceived, intensity of heartburn was scored equal with median visual analog scale 6.5 and 7.1 respectively. Esophageal mucosal integrity was also comparable between FH and NERD patients, both in vivo extracellular impedance and ex vivo transepithelial resistance and permeability were similar. Patients with FH did not show acid hypersensitivity as seen in patients with NERD. However, once perceived, intensity of heartburn is similar. Esophageal mucosal integrity is similar between NERD and FH patients, and is therefore unlikely to be the underlying cause of the observed difference in esophageal acid perception. © 2016 John Wiley & Sons Ltd.

Host responses to Candida albicans: Th17 cells and mucosal candidiasis

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Conti, Heather R.; Gaffen, Sarah L.

2010-01-01

Candida albicans causes mucosal and disseminated candidiasis, which represent serious problems for the rapidly expanding immunocompromised population. Until recently, Th1-mediated immunity was thought to confer the primary protection, particularly for oral candidiasis. However, emerging data indicate that the newly-defined Th17 compartment appears to play the predominant role in mucosal candidiasis.

Candidiasis and other oral mucosal lesions during and after interferon therapy for HCV-related chronic liver diseases

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Nagao Yumiko

2012-11-01

Full Text Available Abstract Background Oral lichen planus (OLP is seen frequently in patients with hepatitis C virus (HCV infection. The aim of this study was to evaluate the occurrence of oral candidiasis, other mucosal lesions, and xerostomia during interferon (IFN therapy for HCV infection. Methods Of 124 patients with HCV-infected liver diseases treated with IFN therapy in our hospital, 14 (mean age 56.00 ± 12.94 years who attended to receive administration of IFN once a week were identified and examined for Candida infection and other oral lesions and for the measurement of salivary flow. Serological assays also were carried out. Results Cultures of Candida from the tongue surfaces were positive in 7 (50.0% of the 14 patients with HCV infection at least once during IFN therapy. C. albicans was the most common species isolated. The incidence of Candida during treatment with IFN did not increase above that before treatment. Additional oral mucosal lesions were observed in 50.0% (7/14 of patients: OLP in three (21.4%, angular cheilitis in three (21.4% and recurrent aphthous stomatitis in one (7.1%. OLP occurred in one patient before treatment with IFN, in one during treatment and in one at the end of treatment. 85.7% of the oral lesions were treated with topical steroids. We compared the characteristics of the 7 patients in whom Candida was detected at least once during IFN therapy (group 1 and the 7 patients in whom Candida was not detected during IFN therapy (group 2. The prevalence of oral mucosal lesions (P=0.0075 and incidence of external use of steroids (P=0.0308 in group 1 were significantly higher than in group 2. The average body weight of group 1 decreased significantly compared to group 2 (P=0.0088. Salivary flow decreased in all subjects throughout the course of IFN treatment and returned at 6th months after the end of treatment. In group 1, the level of albumin at the beginning of the 6th month of IFN administration was lower than in group 2 (P=0

Esophageal mucosal breaks in gastroesophageal reflux disease partially responsive to proton pump inhibitor therapy.

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Shaheen, Nicholas J; Denison, Hans; Björck, Karin; Silberg, Debra G

2013-04-01

Approximately 20-30% of patients with gastroesophageal reflux disease (GERD) do not experience complete symptom resolution during proton pump inhibitor (PPI) therapy. The aim of this study was to determine the prevalence of esophageal mucosal breaks among patients who have a partial response to PPI therapy. This was an analysis of data from a phase 2b clinical trial carried out to assess the efficacy and safety of a reflux inhibitor, lesogaberan (AZD3355), as an add-on to PPI therapy in this patient population (clinicaltrials.gov reference: NCT01005251). A total of 661 patients with persistent GERD symptoms who had received a minimum of 4 weeks of PPI therapy were included in the study. The prevalence of esophageal mucosal breaks was assessed according to (i) the most recent endoscopy results from within the previous 24 months, if available ("historical" endoscopies), and (ii) the results of endoscopies performed at study baseline ("baseline" endoscopies). Baseline endoscopies were not carried out in patients who had a historical endoscopy showing an absence of esophageal mucosal breaks. Historical endoscopy results were available for 244 patients, of whom 48 (19.7%) had esophageal mucosal breaks. Baseline endoscopies were carried out in 465 patients, of whom 146 (31.4%) had esophageal mucosal breaks. Sensitivity analyses showed a prevalence of esophageal mucosal breaks of 20-30%. In both the historical and baseline endoscopies, most esophageal mucosal breaks were Los Angeles grades A or B. In patients with GERD symptoms partially responsive to PPI therapy, mild-to-moderate severity esophageal mucosal breaks are common (prevalence 20-30%), and may contribute to symptom etiology.

Clinical effectiveness of Ancer 20 injection for prevention of radiation-induced oral mucositis

International Nuclear Information System (INIS)

Suzuki, Tsubura; Shimoyama, Tetsuo; Nasu, Daisuke; Kaneko, Takahiro; Horie, Norio

2000-01-01

Although radiotherapy is very useful for treatment of oral cancer, it can cause radiation-induced oral mucositis as a troublesome side effect. Ancer 20 injection is useful for enhancing macrophage function, and apart from its inductive effect on IL-3, it also enhances G-CSF production. Therefore, Ancer 20 injection might also prevent mucositis. This effect was tested by administering the drug to prevent oral mucositis during radiotherapy. Eleven patients (5 males and 6 females, aged 39 to 84 yr, mean 64.5 yr) with squamous cell carcinoma were examined. Radiation was applied externally with a linear accelerator up to a total dose of 20-70 Gy, mean 38.2 Gy. All patients received a small dose of cisplatin concomitantly. Ancer 20 injection 1 ml twice weekly was administered subcutaneously. There was almost no objective or subjective abnormality up to a dose of 30 Gy, and at doses higher than that, the symptoms were mild in comparison with general mucosal reactions. This showed that Ancer 20 injection is useful for prevention of radiation-induced oral mucositis during radiotherapy of oral cancer. (author)

Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats

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Pedro M. G. Soares

2011-03-01

Full Text Available CONTEXT: Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. OBJECTIVES: To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. METHODS: Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration. Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. RESULTS: After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. CONCLUSION: Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats.

Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination.

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Holechek, Susan A; McAfee, Megan S; Nieves, Lizbeth M; Guzman, Vanessa P; Manhas, Kavita; Fouts, Timothy; Bagley, Kenneth; Blattman, Joseph N

2016-11-04

In order for vaccines to induce efficacious immune responses against mucosally transmitted pathogens, such as HIV-1, activated lymphocytes must efficiently migrate to and enter targeted mucosal sites. We have previously shown that all-trans retinoic acid (ATRA) can be used as a vaccine adjuvant to enhance mucosal CD8 + T cell responses during vaccination and improve protection against mucosal viral challenge. However, the ATRA formulation is incompatible with most recombinant vaccines, and the teratogenic potential of ATRA at high doses limits its usage in many clinical settings. We hypothesized that increasing in vivo production of retinoic acid (RA) during vaccination with a DNA vector expressing retinaldehyde dehydrogenase 2 (RALDH2), the rate-limiting enzyme in RA biosynthesis, could similarly provide enhanced programming of mucosal homing to T cell responses while avoiding teratogenic effects. Administration of a RALDH2- expressing plasmid during immunization with a HIVgag DNA vaccine resulted in increased systemic and mucosal CD8 + T cell numbers with an increase in both effector and central memory T cells. Moreover, mice that received RALDH2 plasmid during DNA vaccination were more resistant to intravaginal challenge with a recombinant vaccinia virus expressing the same HIVgag antigen (VACVgag). Thus, RALDH2 can be used as an alternative adjuvant to ATRA during DNA vaccination leading to an increase in both systemic and mucosal T cell immunity and better protection from viral infection at mucosal sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant.

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Chen, Joey; Seabrook, Jamie; Fulford, Adrienne; Rajakumar, Irina

2017-03-01

Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well-tolerated practice.

Regeneration of Vocal Fold Mucosa Using Tissue-Engineered Structures with Oral Mucosal Cells

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Fukahori, Mioko; Chitose, Shun-ichi; Sato, Kiminori; Sueyoshi, Shintaro; Kurita, Takashi; Umeno, Hirohito; Monden, Yu; Yamakawa, Ryoji

2016-01-01

Objectives 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. Study Design Animal experiment using eight beagles (including three controls). Methods 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. Results 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. Conclusion 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. PMID:26730600

The Molecular Immunology of Mucositis: Implications for Evidence-Based Research in Alternative and Complementary Palliative Treatments

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Francesco Chiappelli

2005-01-01

Full Text Available The terms ‘mucositis’ and ‘stomatitis’ are often used interchangeably. Mucositis, however, pertains to pharyngeal-esophago-gastrointestinal inflammation that manifests as red, burn-like sores or ulcerations throughout the mouth. Stomatitis is an inflammation of the oral tissues proper, which can present with or without sores, and is made worse by poor dental hygiene. Mucositis is observed in a variety of immunosuppressed patients, but is most often consequential to cancer therapy. It appears as early as the third day of intervention, and is usually established by Day 7 of treatment. Mucositis increases mortality and morbidity and contributes to rising health care costs. The precise immune components involved in the etiology of mucositis are unclear, but evidence-based research (EBR data has shown that applications of granulocyte–macrophage-colony stimulating factor prevent the onset or the exacerbation of oropharyngeal mucositis. The molecular implications of this observation are discussed from the perspective of future developments of complementary and alternative treatments for this condition. It must be emphasized that this article is meant to be neither a review on mucositis and the various treatments for it, nor a discussion paper on its underlying molecular immunology. It is a statement of the implications of EBR for CAM-based interventions for mucositis. It explores and discusses the specific domain of molecular immunology in the context of mucositis and its direct implications for EBR research in CAM-based treatments for mucositis.

Functional and structural characteristics of secretory IgA antibodies elicited by mucosal vaccines against influenza virus.

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Suzuki, Tadaki; Ainai, Akira; Hasegawa, Hideki

2017-09-18

Mucosal tissues are major targets for pathogens. The secretions covering mucosal surfaces contain several types of molecules that protect the host from infection. Among these, mucosal immunoglobulins, including secretory IgA (S-IgA) antibodies, are the major contributor to pathogen-specific immune responses. IgA is the primary antibody class found in many external secretions and has unique structural and functional features not observed in other antibody classes. Recently, extensive efforts have been made to develop novel vaccines that induce immunity via the mucosal route. S-IgA is a key molecule that underpins the mechanism of action of these mucosal vaccines. Thus, precise characterization of S-IgA induced by mucosal vaccines is important, if the latter are to be used successfully in a clinical setting. Intensive studies identified the fundamental characteristics of S-IgA, which was first discovered almost half a century ago. However, S-IgA itself has not gained much attention of late, despite its importance to mucosal immunity; therefore, some important questions remain. This review summarizes the current understanding of the molecular characteristics of S-IgA and its role in intranasal mucosal vaccines against influenza virus infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effectiveness of triclosan in the management of radiation-induced oral mucositis: A randomized clinical trial

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Satheeshkumar P

2010-01-01

Full Text Available Introduction: Oral care in cancer patients is an important aspect in the quality of life of patients undergoing cancer therpay. Mucositis, trismus, salivary gland dysfunction are the main complications of the cancer therapy, which lead to long-term comlications such as radiation caries, poor oral hygiene and osteoradionecrosis. A timely oral evaluation and intervention in these patients can reduce the severity of the potential complications. Triclosan is an antibacterial agent widely used in periodontal therapy, the effectiveness of triclosan in the management of radiation induced oral mucositis is evaluated here. Aims: 1 To determine the effectiveness of triclosan in the management of radiation-induced oral mucositis. 2 To compare the effectiveness of triclosan mouth rinse with conventional sodium bicarbonate mouth rinse. Materials and Methods: Twenty-four patients who underwent radiation therapy for oral cancer and subsequently developed oral mucositis were included in the study. They were randomly allocated into two groups on noticing grade I mucositis (erythema. The study group was advised to use triclosan mouthwash containing triclosan 0.03% W/V and sodium bicarbonate 2 mg mouth wash for the control group. A weekly follow-up evaluation of body weight, food intake, pain and grading of mucositis were made during the radiation treatment period and post radiation treatment period. Results: Both the groups were statistically identical. All the 24 patients in both the groups passed through grade 3 mucositis on the last day of radiotherapy. However, 10 patients in the control group and only one patient in the study group entered to grade 4 mucositis. A definite change was noticed in the severity of the mucositis, food intake and weight loss. The control group took more than 45 days to resolve while the study group took only less than 28 days. Discussion: The results of the study were evaluated and tried to formulate a hypothesis so as to explain

Effects of Mycotoxins on Mucosal Microbial Infection and Related Pathogenesis

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

2015-01-01

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. PMID:26529017

Intestinal dendritic cells in the regulation of mucosal immunity

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Bekiaris, Vasileios; Persson, Emma K.; Agace, William Winston

2014-01-01

immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive....... The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality...

Acute exercise does not induce an acute phase response (APR) in Standardbred trotters

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Kristensen, Lena; Buhl, Rikke; Nostell, Katarina

2014-01-01

), and iron], muscle enzymes [creatinine kinase (CK) and aspartate transaminase (AST)], and hemoglobin were assessed in 58 Standardbred trotters before and after racing. Hemoglobin levels increased and iron levels decreased 12 to 14 h after racing and haptoglobin concentrations, white blood cell counts......, and iron levels were decreased 2 and/or 7 d after racing. Concentrations of CK, AST, SAA, and fibrinogen were unaltered in response to racing. Acute strenuous exercise did not elicit an acute phase reaction. The observed acute increase in hemoglobin levels and decreases in haptoglobin and iron levels may...

The etiological structure, biological properties of causative agents of peri-implant mucositis

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M. O. Faustova

2017-10-01

Full Text Available The purpose was to examine the peri-implant mucositis microflora and sensitivity of dominant pathogens to antibiotics and antiseptics. Materials and methods. The study involved 43 patients with peri-implant mucositis. During the study 162 clinical strains of microorganisms were isolated and identified. Cultivation of clinical isolates was performed by the standard method, final identification was carried out with using bacteriological automatic analyzer Vitec – 2compact bioMérieux (France. Determination of sensitivity to antibiotics of pathogens was carried with disc-diffusion method; the study of sensitivity to antiseptics was carried by means of double serial dilutions method by the standard procedure approved by the Order № 167 of the Ministry of Public Health of Ukraine on “On Approval of Training Guidance “Assessment of the sensitivity of microorganisms to antibiotics”, dated by April, 5, 2007. Results. It is The microflora of peri-implant area of patients with mucositis was revealed to consist of opportunistic species. Representatives of Streptococcus spp. and Staphylococcus spp. were dominating among them, although Kocuria spp., Enterobacter spp. and yeast-like fungi Candida spp. were detected quite common. Investigated clinical strains of microorganisms had different sensitivity to antibiotics. All cultures were sensitive to fluoroquinolones, but very significant number of them showed resistance to penicillins, macrolides and lincosamides. In turn, horosten, dekasan and chlorhexidine had powerful antimicrobial effect on dominant pathogens of periimplant mucositis in patients. Moreover, the effect of decametoxine-based antiseptics on some of them significantly exceeded the activity of chlorhexidine. Conclusions. Microflora from peri-implant area of patients with peri-implant mucositis consists mainly of aerobic and facultative anaerobic microorganisms, belonging to normal oral microflora. Most of pathogens of mucositis obtaine

EPIGLOTTIS MICROFLORA OF ADULT PATIENTS WITH ACUTE EPIGLOTTITIS

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Golovko NA

2016-12-01

Full Text Available Introduction. Nowadays acute infectious-inflammatory processes of upper respiratory tract, including acute epiglottitis retain a high proportion among human pathology. In the literature acute epiglottitis is allocated into an independent nosology as severe acute phlegmonous bacterial inflammation of the epiglottis and hypopharynx. There are currently no clear guidelines on how to classify an acute epiglottitis, as well as protocols for patients at various stages of the pathological process. According to common belief, Haemophilus influenzae type -B (Haemophilus influenza type b (Hib is the most common cause of epiglottitis. At present, the main etiological role in the genesis of acute epiglottitis in children belongs to haemophilus influenzae. In adults the causes of the disease are beta hemolytic streptococci groups A, B, pneumococcus, Klebsiella, Pseudomonas, Staphylococcus aureus, herpes simplex virus (type 1 and parainfluenza, and others.The aim of this work is to study: the mucosal microflora of the epiglottis in adult patients with acute epiglottitis and to study sensitivity of certain isolates to antimicrobial agents. Material & methods. 86 adult patients with acute epiglottitis were observed: 36 with abscess form of epiglottitis and 50 - with infiltrative. Microbiological analysis of mucosal swab samples taken from hypopharynx were conducted by the conventional technology: for seeding solid or liquid nutrient medium, followed by allocation of isolith and its microscopic, biochemical and serological identification. Microorganisms were classified according to schemes of Bergy. Antimicrobial susceptibility of each strain was determined in accordance with the guidelines. We used discs with antibacterial drugs. The availability of sensitive and resistant strains of microorganisms to antibiotics was assessed. A mucous membrane of the epiglottis was analyzed through microbiological investigation in 86 patients with acute epiglottitis. As a

Current possibilities of anti-inflammatory therapy in children with acute respiratory diseases

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E. E. Lokshina; O. V. Zaytseva

2017-01-01

The paper gives an update on the pathogenesis of acute respiratory diseases, the basis for which is inflammation of the airway mucosal lining. It reflects the results of a comparative clinical trial of the efficacy and safety of the anti-inflammatory drug fenspiride used in the combination therapy for respiratory diseases in children. The findings allow one to recommend the use of fenspiride to treat this condition in children.

Current possibilities of anti-inflammatory therapy in children with acute respiratory diseases

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E. E. Lokshina

2017-01-01

Full Text Available The paper gives an update on the pathogenesis of acute respiratory diseases, the basis for which is inflammation of the airway mucosal lining. It reflects the results of a comparative clinical trial of the efficacy and safety of the anti-inflammatory drug fenspiride used in the combination therapy for respiratory diseases in children. The findings allow one to recommend the use of fenspiride to treat this condition in children.

The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats.

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Yoo, Yeong-Min; Jung, Eui-Man; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

2011-10-01

In the present study, we examined whether Acer okamotoanum (A. okamotoanum) sap decreased the serum alcohol and acetaldehyde levels after acute ethanol treatment in a rat model. Male rats were orally administered 25, 50 or 100% A. okamotoanum sap 30 min prior to oral challenge with 3 ml of ethanol (15 ml/kg of a 20% ethanol solution in water), and the blood concentrations of alcohol and acetaldehyde were analyzed up to 7 h after the treatment. Pre-treatment with the sap significantly decreased the blood ethanol and acetaldehyde concentrations after 5 h when compared with ethanol treatment alone (a negative control). The expression levels of liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) mRNA were increased significantly in animals pre-treated with A. okamotoanum sap when compared with negative and positive controls. The data suggest that sap pre-treatment enhanced the alcohol metabolism rate in the rat liver. To investigate the involvement of mitochondrial regulation in the ethanol-induced hepatocyte apoptosis, we carried out an immunohistochemical analysis of Bax and Bcl-2. Pre-treatment with sap significantly decreased Bax expression and increased Bcl-2 expression 7 h after ethanol administration when compared with the negative control. The data suggest that A. okamotoanum sap pre-treatment may reduce the alcohol-induced oxidative stress in the rat liver.

Acute suppurative appendicitis associated with Enterobius vermicularis: an incidental finding or a causative agent? A case report.

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Efared, Boubacar; Atsame-Ebang, Gabrielle; Soumana, Boubacar Marou; Tahiri, Layla; Hammas, Nawal; El Fatemi, Hinde; Chbani, Laila

2017-10-06

Histological acute appendicitis patterns associated with Enterobius vermicularis is an extremely rare finding. The exact role of this parasite in acute appendicitis is controversial as usually resected specimens show no evidence of histological inflammation. We present herein a case of a 21-year-old male Arabic patient who presented with clinical syndrome of acute appendicitis. Emergency appendectomy was performed and the histopathological examination of the resected specimen showed the presence of E. vermicularis as well as intense acute inflammatory patterns such as mucosal ulceration and suppurative necrosis. The post-operative course was uneventful and the patient was discharged with appropriate anti-helmintic drug prescription. Acute appendicitis due to E. vermicularis is a very rare occurrence. The histopathological analysis of resected specimens should pay special attention to search for this parasite for adequate post-operative treatment of patients.

Mechanisms of gastroprotection by lansoprazole pretreatment against experimentally induced injury in rats: role of mucosal oxidative damage and sulfhydryl compounds

International Nuclear Information System (INIS)

Natale, Gianfranco; Lazzeri, Gloria; Lubrano, Valter; Colucci, Rocchina; Vassalle, Cristina; Fornai, Matteo; Blandizzi, Corrado; Del Tacca, Mario

2004-01-01

This study investigated the mechanisms involved in the protective actions exerted by lansoprazole against experimental gastric injury. Following the intraluminal injection of ethanol-HCl, the histomorphometric analysis of rat gastric sections demonstrated a pattern of mucosal lesions associated with a significant increase in the mucosal contents of malondialdehyde and 8-iso-prostaglandin F 2α (indices of lipid peroxidation), as well as a decrease in the levels of mucosal sulfhydryl compounds, assayed as reduced glutathione (GSH). Pretreatment with lansoprazole 90 μmol/kg, given intraduodenally as single dose or once daily by intragastric route for 8 days, significantly prevented ethanol-HCl-induced gastric damage. The concomitant changes in the mucosal levels of malondialdehyde, 8-iso-prostaglandin F 2α and GSH elicited by ethanol-HCl were also counteracted by lansoprazole. In separate experiments, performed on animals undergoing 2-h pylorus ligation, lansoprazole did not enhance the concentration of prostaglandin E 2 , bicyclo-prostaglandin E 2 , or nitric oxide (NO) metabolites into gastric juice. Western blot analysis revealed the expression of both type 1 and 2 cyclooxygenase (COX) isoforms in the gastric mucosa of pylorus-ligated rats. These expression patterns were not significantly modified by single-dose or repeated treatment with lansoprazole. Lansoprazole also exhibited direct antioxidant properties by reducing 8-iso-prostaglandin F 2α generation in an in vitro system where human native low-density lipoproteins were subjected to oxidation upon exposure to CuSO 4 . The present results suggest that the protective effects of lansoprazole can be ascribed to a reduction of gastric oxidative injury, resulting in an increased bioavailability of mucosal sulfhydryl compounds. It is also proposed that lansoprazole does not exert modulator effects on the gastric expression of COX isoforms as well as on the activity of NO pathways

Prevention and treatment of radiotherapy-induced oral mucositis: a literature review

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Albuquerque, Ieda Lessa de Souza; Camargo, Teresa Caldas

2007-01-01

The prevention and treatment of radiotherapy-induced oral mucositis have still not been fully defined. The current study thus involved a literature search aimed at identifying preventive and therapeutic measures in relation to oral mucositis in patients submitted to radiotherapy, analyzing the level of evidence in the selected studies, identifying which indications for prevention and treatment in the literature pertain to the field of nursing, and critically analyzing the results and their implications for nursing care. This was a systematic literature survey without a meta analysis, consulting the following databases: BIREME, Medline, CancerLit, Scirus, CAPES, Free medical journal, High wire press, SCIELO, and Medscape, from 2000 to 2005. According to observations, nursing care was capable of improving patient's quality of life, promoting education of patients, implementing and supervising oral care programs, and providing guidance on hygiene, prevention, and treatment of oral mucositis, including pain management. However, no Brazilian nursing publications were found on the subject. Research and publications focusing on nursing experience in the prevention and treatment of radiotherapy-related oral mucositis and the implications for patients and nurses are important to provide evidence-based nursing guidelines. (author)

Effect of bupivacaine lozenges on oral mucositis pain

DEFF Research Database (Denmark)

Mogensen, Stine; Treldal, Charlotte; Kristensen, Claus A

2017-01-01

Introduction: A nonblinded parallel-group randomized controlled study investigated the efficacy and tolerability of repeated administration of a bupivacaine lozenge (25 mg) as pain management for oral mucositis pain in head and neck cancer patients as add-on to standard systemic pain management...... with bupivacaine lozenges (taken up to every 2 hours) plus standard pain treatment minus topical lidocaine (Lozenge group) or standard pain treatment including topical lidocaine (Control group). The efficacy analysis included 38 patients, as 12 patients were excluded because of changes in study design and missing...... that the bupivacaine lozenge as an add-on to standard pain treatment had a clinically significant pain-relieving effect in patients with oral mucositis. ClinicalTrialsgov: NCT02252926....

Imaging of Mucosal Inflammation: Current Technological Developments, Clinical Implications, and Future Perspectives

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Maximilian J. Waldner

2017-10-01

Full Text Available In recent years, various technological developments markedly improved imaging of mucosal inflammation in patients with inflammatory bowel diseases. Although technological developments such as high-definition-, chromo-, and autofluorescence-endoscopy led to a more precise and detailed assessment of mucosal inflammation during wide-field endoscopy, probe-based and stationary confocal laser microscopy enabled in vivo real-time microscopic imaging of mucosal surfaces within the gastrointestinal tract. Through the use of fluorochromes with specificity against a defined molecular target combined with endoscopic techniques that allow ultrastructural resolution, molecular imaging enables in vivo visualization of single molecules or receptors during endoscopy. Molecular imaging has therefore greatly expanded the clinical utility and applications of modern innovative endoscopy, which include the diagnosis, surveillance, and treatment of disease as well as the prediction of the therapeutic response of individual patients. Furthermore, non-invasive imaging techniques such as computed tomography, magnetic resonance imaging, scintigraphy, and ultrasound provide helpful information as supplement to invasive endoscopic procedures. In this review, we provide an overview on the current status of advanced imaging technologies for the clinical non-invasive and endoscopic evaluation of mucosal inflammation. Furthermore, the value of novel methods such as multiphoton microscopy, optoacoustics, and optical coherence tomography and their possible future implementation into clinical diagnosis and evaluation of mucosal inflammation will be discussed.

Short-term stress, but not mucosal healing nor depression was predictive for the risk of relapse in patients with ulcerative colitis: a prospective 12-month follow-up study.

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Langhorst, Jost; Hofstetter, Anna; Wolfe, Fred; Häuser, Winfried

2013-10-01

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. Psychological factors such as depression and stress are under debate to contribute to the risk of relapse. The impact of mucosal healing to reduce the risk of relapse had not been studied prospectively. The aim of this study was to identify whether depression and stress increase and mucosal healing reduces the risk of clinical relapse in patients with UC in clinical remission. Patients in clinical remission were followed prospectively for 1 year, or less if they relapsed. Endoscopy and histology score and long-term perceived stress (Perceived Stress Questionnaire) were measured at baseline. Mucosal healing was defined by a Mayo Endoscopy score of 0-1. Depression (Hospital Anxiety and Depression Scale) and acute perceived stress (Cohen Perceived Stress Scale) were measured at baseline and after 1, 3, 6, 9, and 12 months. A time-dependent multivariate Cox regression model determined the predictors of time to relapse. Seventy-five patients were included into final analysis, of which 28 (37.3%) relapsed. Short-term stress at the last visit before relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.01-1.10) and male gender (HR = 2.38, 95% CI = 1.01-5.61), but not baseline mucosal healing (HR = 0.86, 95% CI = 0.35-2.11), baseline long-term stress (HR = 0.20, 95% CI = 0.01-3.31), and depression at the last visit before relapse (HR = 1.08, 95% CI = 0.95-1.22) were predictive for a relapse. Short-term stress but not depression nor mucosal healing was predictive for the risk of relapse in patients with UC in clinical remission. Larger multicentre studies are necessary to confirm our findings.

Hematuria screening test for urinary bladder mucosal infiltration in cervical cancer.

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Chuttiangtum, Ayuth; Udomthavornsuk, Banchong; Chumworathayi, Bandit

2012-01-01

To determine the diagnostic performance of hematuria as a screening test for urinary bladder infiltration in cervical cancer patients with a prospective study design. Newly diagnosed cervical cancer patients at Srinagarind hospital from 14 June 2011 to 30 April 2012 were enrolled in this study. We collected midstream urine samples for urinalysis from every patient before routine cystoscopic exam for clinical staging. The presence of 3 or more red blood cells (RBCs) per high power field was defined as positive for hematuria. A two-by-two table was used to determine the diagnostic performance of hematuria to detect urinary bladder mucosal infiltration using cystoscopy and biopsy as the gold standard. A total of 130 were patients included, 54 of which (41.5%) had hematuria. Of these, four patients (3.08%) had pathological report from cystoscopic biopsy confirmed metastatic squamous cell carcinoma. The sensitivity, specificity, PPV, NPV, and accuracy of hematuria as a screening test to detect urinary bladder mucosal infiltration of cervical cancer were 100%, 60.3%, 7.4%, 100%, and 61.5%, respectively. There was no single case of urinary bladder mucosal infiltration in patients initially staged less than stage III. Hematuria can be used as a screening test to detect urinary bladder mucosal infiltration of cervical cancer. This can reduce the number of cervical cancer patients who really need to undergo cystoscopy as a staging procedure to less than half and to less than 20% if stage III or more were included without missing a single case of urinary bladder mucosal infiltration.

Psittacid herpesviruses associated with mucosal papillomas in neotropical parrots

International Nuclear Information System (INIS)

Styles, Darrel K.; Tomaszewski, Elizabeth K.; Jaeger, Laurie A.; Phalen, David N.

2004-01-01

Mucosal papillomas are relatively common lesions in several species of captive neotropical parrots. They cause considerable morbidity and in some cases, result in mortality. Previous efforts to identify papillomavirus DNA and proteins in these lesions have been largely unsuccessful. In contrast, increasing evidence suggests that mucosal papillomas may contain psittacid herpesviruses (PsHVs). In this study, 41 papillomas from 30 neotropical parrots were examined by PCR with PsHV-specific primers. All 41 papillomas were found to contain PsHV DNA. This 100% prevalence of PsHV infection in the papilloma population was found to be significantly higher than PsHV infection prevalence observed in other surveys of captive parrots. PsHV genotypes 1, 2, and 3, but not 4 were found in these lesions. Psittacus erithacus papillomavirus DNA and finch papillomavirus DNA were not found in the papillomas. A papilloma from a hyacinth macaw (Anodorhynchus hyacinthinus) was found to contain cells that had immunoreactivity to antiserum made to the common antigenic region of human papillomavirus (HPV) L1 major capsid protein. However, four other mucosal papillomas were negative for this immunoreactivity, and negative control tissues from a parrot embryo showed a similar staining pattern to that seen in the cloaca papilloma of the hyacinth macaw, strongly suggesting that the staining seen in hyacinth macaw papilloma was nonspecific. Based on these findings, it was concluded that specific genotypes of PsHV play a direct role in the development of mucosal papillomas of neotropical parrots and there is no evidence to suggest the concurrent presence of a papillomavirus in these lesions

Voice disorders in mucosal leishmaniasis.

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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

Collagenous mucosal inflammatory diseases of the gastrointestinal tract.

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Freeman, Hugh J

2005-07-01

Collagenous mucosal inflammatory diseases involve the columnar-lined gastric and intestinal mucosa and have become recognized increasingly as a significant cause of symptomatic morbidity, particularly in middle-aged and elderly women, especially with watery diarrhea. Still, mechanisms involved in the pathogenesis of this diarrhea remain poorly understood and require further elucidation. The prognosis and long-term outcome of these disorders has been documented only to a limited extent. Recent clinical and pathologic studies have indicated that collagenous mucosal inflammatory disease is a more extensive pathologic process that concomitantly may involve several sites in the gastric and intestinal mucosa. The dominant pathologic lesion is a distinct subepithelial hyaline-like deposit that has histochemical and ultrastructural features of collagen overlying a microscopically defined inflammatory process. An intimate relationship with other autoimmune connective tissue disorders is evident, particularly celiac disease. This is intriguing because these collagenous disorders have not been shown to be gluten dependent. Collagenous mucosal inflammatory disorders may represent a relatively unique but generalized inflammatory response to a multitude of causes, including celiac disease, along with a diverse group of pharmacologic agents. Some recent reports have documented treatment success but histopathologic reversal has been more difficult to substantiate owing to the focal, sometimes extensive nature, of this pathologic process.

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

International Nuclear Information System (INIS)

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

1985-01-01

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

Ketoprofen-loaded Eudragit electrospun nanofibers for the treatment of oral mucositis

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Reda RI

2017-03-01

Full Text Available Rana Ihab Reda,1 Ming Ming Wen,2 Amal Hassan El-Kamel1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 2Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt Purpose: The purpose of this study was to formulate ketoprofen (KET-loaded Eudragit L and Eudragit S nanofibers (NFs by the electrospinning technique for buccal administration to treat oral mucositis as a safe alternative to orally administered KET, which causes gastrointestinal tract (GIT side effects. Materials and methods: NFs were prepared by electrospinning using Eudragit L and Eudragit S. Several variables were evaluated to optimize NF formulation, such as polymer types and concentrations, applied voltage, flow rate and drug concentrations. Differential scanning calorimetry (DSC, Fourier transform infrared spectroscopy (FTIR and scanning electron microscopy (SEM and analyses of drug contents, hydration capacity, surface pH, drug release and ex vivo permeation were performed to evaluate the NFs. The selected formulation (F1 was evaluated in vivo on induced oral mucositis in rabbits. Results: SEM revealed that 20% polymer formed smooth and bead-free NFs. DSC results confirmed the amorphous nature of KET in the NFs. FTIR confirmed hydrogen bond formation between the drug and polymer, which stabilized the NFs. Both formulations (F1 and F2 had an acceptable surface pH. The drug loading was >90%. The amount of KET released from NF formulations was statistically significantly higher (P≤0.001 than that released from the corresponding solvent-casted films. The complete release of KET from F1 occurred within 2 hours. Ex vivo permeation study revealed that only a small fraction of drug permeated from F1, which was a better candidate than F2 for local buccal delivery. In vivo evaluation of F1 on oral mucositis induced in rabbits demonstrated that F1 reduced the clinical severity of mucositis in

Psychological factors in oral mucosal and orofacial pain conditions.

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Alrashdan, Mohammad S; Alkhader, Mustafa

2017-01-01

The psychological aspects of chronic pain conditions represent a key component of the pain experience, and orofacial pain conditions are not an exception. In this review, we highlight how psychological factors affect some common oral mucosal and orofacial pain conditions (namely, oral lichen planus, recurrent aphthous stomatitis, burning mouth syndrome, and temporomandibular disorders) with emphasis on the significance of supplementing classical biomedical treatment modalities with appropriate psychological counseling to improve treatment outcomes in targeted patients. A literature search restricted to reports with highest relevance to the selected mucosal and orofacial pain conditions was carried out to retrieve data.

Experiences with Pontal syrup in mucositis caused by radiotherapy

International Nuclear Information System (INIS)

Miyamoto, Hiroshi; Yamashita, Shoji; Hashimoto, Teisuke; Kunieda, Etsuo; Hashimoto, Shozo

1983-01-01

Pontal syrup was administered at daily dose of 30 ml t. i. d. to 17 patients of mucositis developed due to radiotherapy against malignant tumor. Results were: Remarkably effective-5 cases, effective-8 cases, slightly effective-3 cases, and non-effective-1 case. Certain effects were observed in 16 cases out of 17 cases/94.1%, excluding only one non-effective case. No side-effects were observed in all cases. It is considered that Pontal syrup is a drug useful for mucositis caused by radiotherapy because of its easiness of administration and also of its characteristic of non-stimulant. (author)

Plasma and Mucosal Immunoglobulin M, Immunoglobulin A, and Immunoglobulin G Responses to the Vibrio cholerae O1 Protein Immunome in Adults With Cholera in Bangladesh.

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Charles, Richelle C; Nakajima, Rie; Liang, Li; Jasinskas, Al; Berger, Amanda; Leung, Daniel T; Kelly, Meagan; Xu, Peng; Kovác, Pavol; Giffen, Samantha R; Harbison, James D; Chowdhury, Fahima; Khan, Ashraful I; Calderwood, Stephen B; Bhuiyan, Taufiqur Rahman; Harris, Jason B; Felgner, Philip L; Qadri, Firdausi; Ryan, Edward T

2017-07-01

Cholera is a severe dehydrating illness of humans caused by toxigenic strains of Vibrio cholerae O1 or O139. Identification of immunogenic V. cholerae antigens could lead to a better understanding of protective immunity in human cholera. We probed microarrays containing 3652 V. cholerae antigens with plasma and antibody-in-lymphocyte supernatant (ALS, a surrogate marker of mucosal immune responses) from patients with severe cholera caused by V. cholerae O1 in Bangladesh and age-, sex-, and ABO-matched Bangladeshi controls. We validated a subset of identified antigens using enzyme-linked immunosorbent assay. Overall, we identified 608 immunoreactive V. cholerae antigens in our screening, 59 of which had higher immunoreactivity in convalescent compared with acute-stage or healthy control samples (34 in plasma, 39 in mucosal ALS; 13 in both sample sets). Identified antigens included cholera toxin B and A subunits, V. cholerae O-specific polysaccharide and lipopolysaccharide, toxin coregulated pilus A, sialidase, hemolysin A, flagellins (FlaB, FlaC, and FlaD), phosphoenolpyruvate-protein phosphotransferase, and diaminobutyrate-2-oxoglutarate aminotransferase. This study is the first antibody profiling of the mucosal and systemic antibody responses to the nearly complete V. cholerae O1 protein immunome; it has identified antigens that may aid in the development of an improved cholera vaccine. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Radiological evaluation about the effects of acute and chronic pancreatitis on the stomach patterns

International Nuclear Information System (INIS)

Jaun, Woo Ki; Han, Chang Yul; Park, Soo Sung

1983-01-01

The present study was intended to examine the spectrum of radiographic patterns of the stomach associated with acute and chronic pancreatitis and their complications. Subjects served for the study consisted of 70 cases of pancreatitis (36 cases in acute stage and 34 cases in chronic stage). Intramural and perigastric permeation of extravasated pancreatic enzymes and secondary inflammatory reaction that follows are responsible for the radiographic change observed. 1. Generalized rugal thickening and particularly selective mucosal prominences in greater curvature of body and antrum are characteristically seen in acute (14 of 36 cases- 39%) and chronic pancreatitis (11 of 34 cases- 32%) 2. The only finding of the chronic pancreatitis includes patterns mimicking limits plastica, indurated and nondistensible rugae induced by perigastric adhesion (11 of 34 cases- 32%) Familiarization with these patterns of involvement contributes to the radiographic diagnosis of acute pancreatitis and avoides serious diagnostic errors in case of chronic pancreatitis

Mucosal application of gp140 encoding DNA polyplexes to different tissues results in altered immunological outcomes in mice.

Directory of Open Access Journals (Sweden)

Jamie F S Mann

Full Text Available Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+ and IgA(+ antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge.

A Survey of Chinese Medicinal Herbal Treatment for Chemotherapy-Induced Oral Mucositis

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Gesa Meyer-Hamme

2013-01-01

Full Text Available Oral mucositis is one of the common side effects of chemotherapy treatment with potentially severe implications. Despite several treatment approaches by conventional and complementary western medicine, the therapeutic outcome is often not satisfactory. Traditional Chinese Medicine (TCM offers empirical herbal formulas for the treatment of oral ulceration which are used in adaptation to chemotherapy-induced mucositis. While standard concepts for TCM treatment do not exist and acceptance by conventional oncologists is still low, we conducted a review to examine the evidence of Chinese herbal treatment in oral mucositis. Eighteen relevant studies on 4 single herbs, 2 combinations of 2 herbs, and 11 multiherbal prescriptions involving 3 or more compounds were included. Corresponding molecular mechanisms were investigated. The knowledge about detailed herbal mechanisms, especially in multi-herbal prescriptions is still limited. The quality of clinical trials needs further improvement. Meta-analysis on the existent database is not possible but molecular findings on Chinese medicinal herbs indicate that further research is still promising for the treatment of chemotherapy-induced oral mucositis.

Sucralfate mouthwash for prevention and treatment of 5-fluorouracil-induced mucositis: a randomized, placebo-controlled trial.

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Nottage, Michelle; McLachlan, Sue-Anne; Brittain, Mary-Anne; Oza, Amit; Hedley, David; Feld, Ronald; Siu, Lillian L; Pond, Gregory; Moore, Malcolm J

2003-01-01

A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of a sucralfate mouthwash in preventing and alleviating oral mucositis induced by 5-fluorouracil (5FU). A total of 81 patients with colorectal cancer were enrolled. Patients were studied during their first cycle of chemotherapy with 5FU and leucovorin (LV) daily for 5 days every 4 weeks (Mayo Clinic schedule). Patients were randomly allocated to receive either a sucralfate suspension or a placebo suspension that was identical in appearance. Patients were instructed to use the suspension as a mouthwash four times daily from the beginning of the chemotherapy cycle. All patients received oral cryotherapy. Patients graded the severity of their own symptoms on a daily basis, and this was the primary outcome measure. There was no difference in the frequency or severity of oral mucositis between the sucralfate- and the placebo-treated group. Some mucositis was reported by 79% of the patient group. Assessment of mucositis by trial staff underestimated the incidence of this problem. Results of this trial do not support the hypothesis that a sucralfate mouthwash can prevent or alleviate oral mucositis induced by 5FU. Patient reporting of mucositis is a more sensitive instrument for assessment of mucositis than review by medical staff.

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

, was suggested as potential target for transmitting immune-mediated repression of the gonadotropic axis during acute inflammation, and yet key facets of such a phenomenon remain ill defined. Using lipopolysaccharide S (LPS)-treated male rats as model of inflammation, we document herein the pattern......-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...

Systematic review of agents for the management of gastrointestinal mucositis in cancer patients

NARCIS (Netherlands)

Gibson, Rachel J.; Keefe, Dorothy M. K.; Lalla, Rajesh V.; Bateman, Emma; Blijlevens, Nicole; Fijlstra, Margot; King, Emily E.; Stringer, Andrea M.; van der Velden, Walter J. F. M.; Yazbeck, Roger; Elad, Sharon; Bowen, Joanne M.

The aim of this study was to review the available literature and define clinical practice guidelines for the use of agents for the prevention and treatment of gastrointestinal mucositis. A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive

Systematic review of agents for the management of gastrointestinal mucositis in cancer patients.

NARCIS (Netherlands)

Gibson, R.J.; Keefe, D.M.; Lalla, R.V.; Bateman, E.; Blijlevens, N.M.; Fijlstra, M.; King, E.E.; Stringer, A.M.; Velden, W.J.F.M. van der; Yazbeck, R.; Elad, S.; Bowen, J.M.

2013-01-01

PURPOSE: The aim of this study was to review the available literature and define clinical practice guidelines for the use of agents for the prevention and treatment of gastrointestinal mucositis. METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association

Effectivity of 0.15% benzydamine on radiation-induced oral mucositis in nasopharynx carcinoma

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Remita Adya Prasetyo

2011-06-01

Full Text Available Background: Nasopharynx carcinoma is the most common malignant tumour in head and neck region. Radiotherapy is the first choice of treatment for nasopharynx carcinoma that had not been metastases. The most common oral complications in radiotherapy is mucositis (± 80%. 0.15% benzydamine hydrochloride (HCl oral rinse can be used to prevent radiation-induced oral mucositis. Purpose: The aim of this research was to study the effectivity of 0.15% benzydamine HCl oral rinse for prevention of radiation-induced oral mucositis in nasopharynx carcinoma. Methods: Samples were divided into 2 groups. Group A was using 0.15% benzydamine HCl oral rinse for 10 days. Group B was using placebo oral rinse for 10 days. Evaluation was conducted 3 times: first day, fifth day and tenth day of radiotherapy. The scoring used Spijkervet’s mucositis α score. Results: Independent t test analysis for initial occurrence of oral mucositis showed no significant difference between 2 groups. Paired t test analysis showed significant difference between initial mucositis α score and mucositis α score in tenth day in each group. Independent t test analysis showed no significant difference in mucositis α score in tenth day between 2 groups. Conclusion: In conclusion 0.15% benzydamine HCl oral rinse was not effective to prevent radiation-induced oral mucositis in nasopharynx carcinoma.Latar belakang: Karsinoma nasofaring (KNF merupakan tumor ganas terbanyak di daerah kepala-leher. Radioterapi merupakan terapi pilihan utama KNF yang belum mempunyai metastasis jauh. Komplikasi akibat radioterapi dalam rongga mulut yang terbanyak adalah mukositis (± 80%. Salah satu obat untuk pencegahan mukositis akibat radioterapi adalah benzydamine hydrochloride (HCl 0,15%. Tujuan: Tujuan penelitian ini adalah untuk mempelajari efektivitas penggunaan obat kumur benzydamine HCl 0,15% sebagai pencegah mukositis akibat radioterapi pada karsinoma nasofaring. Metode: Sampel dibagi ke dalam 2

Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy.

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Riley, Philip; Glenny, Anne-Marie; Worthington, Helen V; Littlewood, Anne; Clarkson, Jan E; McCabe, Martin G

2015-12-23

Oral mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high risk patients. Ulceration can lead to severe pain and difficulty eating and drinking, which may necessitate opioid analgesics, hospitalisation and nasogastric or intravenous nutrition. These complications may lead to interruptions or alterations to cancer therapy, which may reduce survival. There is also a risk of death from sepsis if pathogens enter the ulcers of immunocompromised patients. Ulcerative oral mucositis can be costly to healthcare systems, yet there are few preventive interventions proven to be beneficial. Oral cryotherapy is a low-cost, simple intervention which is unlikely to cause side-effects. It has shown promise in clinical trials and warrants an up-to-date Cochrane review to assess and summarise the international evidence. To assess the effects of oral cryotherapy for preventing oral mucositis in patients with cancer who are receiving treatment. We searched the following databases: the Cochrane Oral Health Group Trials Register (to 17 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 5), MEDLINE via Ovid (1946 to 17 June 2015), EMBASE via Ovid (1980 to 17 June 2015), CANCERLIT via PubMed (1950 to 17 June 2015) and CINAHL via EBSCO (1937 to 17 June 2015). We searched the US National Institutes of Health Trials Registry, and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching databases. We included parallel-design randomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment. We used outcomes from a published core outcome set registered on the COMET website. Two review authors independently screened the results of electronic searches, extracted data and assessed risk of bias. We contacted study authors for information

Multiscale modeling of mucosal immune responses

Science.gov (United States)

2015-01-01

Computational modeling techniques are playing increasingly important roles in advancing a systems-level mechanistic understanding of biological processes. Computer simulations guide and underpin experimental and clinical efforts. This study presents ENteric Immune Simulator (ENISI), a multiscale modeling tool for modeling the mucosal immune responses. ENISI's modeling environment can simulate in silico experiments from molecular signaling pathways to tissue level events such as tissue lesion formation. ENISI's architecture integrates multiple modeling technologies including ABM (agent-based modeling), ODE (ordinary differential equations), SDE (stochastic modeling equations), and PDE (partial differential equations). This paper focuses on the implementation and developmental challenges of ENISI. A multiscale model of mucosal immune responses during colonic inflammation, including CD4+ T cell differentiation and tissue level cell-cell interactions was developed to illustrate the capabilities, power and scope of ENISI MSM. Background Computational techniques are becoming increasingly powerful and modeling tools for biological systems are of greater needs. Biological systems are inherently multiscale, from molecules to tissues and from nano-seconds to a lifespan of several years or decades. ENISI MSM integrates multiple modeling technologies to understand immunological processes from signaling pathways within cells to lesion formation at the tissue level. This paper examines and summarizes the technical details of ENISI, from its initial version to its latest cutting-edge implementation. Implementation Object-oriented programming approach is adopted to develop a suite of tools based on ENISI. Multiple modeling technologies are integrated to visualize tissues, cells as well as proteins; furthermore, performance matching between the scales is addressed. Conclusion We used ENISI MSM for developing predictive multiscale models of the mucosal immune system during gut

Multiscale modeling of mucosal immune responses.

Science.gov (United States)

Mei, Yongguo; Abedi, Vida; Carbo, Adria; Zhang, Xiaoying; Lu, Pinyi; Philipson, Casandra; Hontecillas, Raquel; Hoops, Stefan; Liles, Nathan; Bassaganya-Riera, Josep

2015-01-01

Computational techniques are becoming increasingly powerful and modeling tools for biological systems are of greater needs. Biological systems are inherently multiscale, from molecules to tissues and from nano-seconds to a lifespan of several years or decades. ENISI MSM integrates multiple modeling technologies to understand immunological processes from signaling pathways within cells to lesion formation at the tissue level. This paper examines and summarizes the technical details of ENISI, from its initial version to its latest cutting-edge implementation. Object-oriented programming approach is adopted to develop a suite of tools based on ENISI. Multiple modeling technologies are integrated to visualize tissues, cells as well as proteins; furthermore, performance matching between the scales is addressed. We used ENISI MSM for developing predictive multiscale models of the mucosal immune system during gut inflammation. Our modeling predictions dissect the mechanisms by which effector CD4+ T cell responses contribute to tissue damage in the gut mucosa following immune dysregulation.Computational modeling techniques are playing increasingly important roles in advancing a systems-level mechanistic understanding of biological processes. Computer simulations guide and underpin experimental and clinical efforts. This study presents ENteric Immune Simulator (ENISI), a multiscale modeling tool for modeling the mucosal immune responses. ENISI's modeling environment can simulate in silico experiments from molecular signaling pathways to tissue level events such as tissue lesion formation. ENISI's architecture integrates multiple modeling technologies including ABM (agent-based modeling), ODE (ordinary differential equations), SDE (stochastic modeling equations), and PDE (partial differential equations). This paper focuses on the implementation and developmental challenges of ENISI. A multiscale model of mucosal immune responses during colonic inflammation, including CD4+ T

Influence of bedding type on mucosal immune responses.

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Sanford, Amy N; Clark, Stephanie E; Talham, Gwen; Sidelsky, Michael G; Coffin, Susan E

2002-10-01

The mucosal immune system interacts with the external environment. In the study reported here, we found that bedding materials can influence the intestinal immune responses of mice. We observed that mice housed on wood, compared with cotton bedding, had increased numbers of Peyer's patches (PP) visible under a dissecting microscope. In addition, culture of lymphoid organs revealed increased production of total and virus-specific IgA by PP and mesenteric lymph node (MLN) lymphocytes from mice housed on wood, compared with cotton bedding. However, bedding type did not influence serum virus-specific antibody responses. These observations indicate that bedding type influences the intestinal immune system and suggest that this issue should be considered by mucosal immunologists and personnel at animal care facilities.

An Epidemiological Study of Oral Mucosal Lesions in Karnataka State, India

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K. V. V Prasad

2004-01-01

Full Text Available This article presents oral mucosal lesions findings from a state oral health survey of Karnataka, India. A total of 46,579 subjects aged 1-4 to 65+ years were selected by using multistage-cluster-stratified random sampling method and subjects were examined by 32 dentists trained in standardized clinical diagnostic criteria for oral mucosal lesions. In the present study, 7.53% of subjects had one or more oral mucosal lesions, in which, male subjects (9.41 % had a significantly higher prevalence of lesions compared to female subjects (4.38%; urban subjects (11.61% had a significantly higher prevalence than rural subjects (5.01 % and the Christian subjects had a significantly higher prevalence of lesions than the Hindus, Muslims and others (F=211.594, <0.001, S. The observed prevalence of oral mucosal lesions increased with age (r=0.8174, P<0.05, S, which is statistically significant. The most prevalent lesions observed were Leukoplakia (1.73%, Lichen planus (2.02% Ulceration (0.73%, Candidiasis (0.94% and Abscess (1.05%. The maximum number of lesions was seen in sulci (7.33% and the minimum number of lesions was seen in lips (0.02%. Differences in prevalence were analyzed by sex, religion, location and geographical area.

Probiotics as Antifungals in Mucosal Candidiasis.

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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.

Mucosal immunology and virology

National Research Council Canada - National Science Library

Tyring, Stephen

2006-01-01

.... A third chapter focuses on the proximal end of the gastrointestinal tract (i.e. the oral cavity). The mucosal immunology and virology of the distal end of the gastrointestinal tract is covered in the chapter on the anogenital mucosa. Mucosa-associated lymphoid tissue (MALT) plays a role in protection against all viral (and other) infections except those that enter the body via a bite (e.g. yellow fever or dengue from a mosquito or rabies from a dog) or an injection or transfusion (e.g. HIV, Hepatitis B). ...

Autofluorescence guided diagnostic evaluation of suspicious oral mucosal lesions: opportunities, limitations, and pitfalls

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Vigneswaran, Nadarajah

2011-03-01

Wide-filed autofluorescence examination is currently considered as a standard of care for screening and diagnostic evaluation of early neoplastic changes of the skin, cervix, lung, bladder, gastrointestinal tract and oral cavity. Naturally occurring fluorophores within the tissue absorb UV and visible light and can re-emit some of this light at longer wavelengths in the form of fluorescence. This non-invasive tissue autofluorescence imaging is used in optical diagnostics, especially in the early detection of cancer. Usually, malignant transformation is associated with thickening of the epithelium, enhanced cellular density due to increased nuclear cytoplasmic ratio which may attenuate the excitation leading to a decrease in collagen autofluorescence. Hence, dysplastic and cancerous tissues often exhibit decreased blue-green autofluorescence and appear darker compared to uninvolved mucosa. Currently, there are three commercially available devices to examine tissue autofluorescence in the oral cavity. In this study we used the oral cancer screening device IdentafiTM 3000 to examine the tissue reflectance and autofluorescence of PML and confounding lesions of the oral cavity. Wide-field autofluorescence imaging enables rapid inspection of large mucosal surfaces, to aid in recognition of suspicious lesions and may also help in discriminate the PML (class 1) from some of the confounding lesions (class II). However, the presence of inflammation or pigments is also associated with loss of stromal autofluorescence, and may give rise to false-positive results with widefield fluorescence imaging. Clinicians who use these autofluorescence based oral cancer screening devices should be aware about the benign oral mucosal lesions that may give false positivity so that unnecessary patient's anxiety and the need for scalpel biopsy can be eliminated.

Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection.

Science.gov (United States)

Byrareddy, Siddappa N; Kallam, Brianne; Arthos, James; Cicala, Claudia; Nawaz, Fatima; Hiatt, Joseph; Kersh, Ellen N; McNicholl, Janet M; Hanson, Debra; Reimann, Keith A; Brameier, Markus; Walter, Lutz; Rogers, Kenneth; Mayne, Ann E; Dunbar, Paul; Villinger, Tara; Little, Dawn; Parslow, Tristram G; Santangelo, Philip J; Villinger, Francois; Fauci, Anthony S; Ansari, Aftab A

2014-12-01

α4β7 integrin-expressing CD4(+) T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-α4β7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4(+) T cell numbers were maintained in both the blood and the GALT. Thus, targeting α4β7 reduces mucosal transmission of SIV in macaques.

Does defibrotide prophylaxis decrease the risk of acute graft versus host disease following allogeneic hematopoietic cell transplantation?

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Tekgündüz, Emre; Kaya, Ali Hakan; Bozdağ, Sinem Civriz; Koçubaba, Şerife; Kayıkçı, Ömür; Namdaroğlu, Sinem; Uğur, Bilge; Akpınar, Seval; Batgi, Hikmetullah; Bekdemir, Filiz; Altuntaş, Fevzi

2016-02-01

There is some preliminary evidence, that veno-occlusive disease prophylaxis with defibrotide (DF) may also have a role in decreasing risk of acute graft-versus-host disease (aGvHD) by preventing tissue damage. In this study, we aimed to investigate the role of DF prophylaxis on the development of aGvHD at D+180. One hundred ninety-five consecutive adult patients receiving allogeneic HCT were retrospectively evaluated in 3 groups: no DF, DF/post-HCT (DF D+1 to D+14) and DF/pre-HCT (DF for 14 days concurrently with conditioning). The total (p: 0.057) and grades III/IV (p: 0.051) aGvHD rates at D+180 were 46.5%, 40%, 25.5% and 15.5%, 11.2%, 0% in patients on no DF, DF/post-HCT and DF/pre-HCT. DF may have a role in decreasing incidence and severity of aGvHD, especially if used concurrently with conditioning regimen. Copyright © 2016 Elsevier Ltd. All rights reserved.

Polysaccharides of Dendrobium officinale Kimura & Migo protect gastric mucosal cell against oxidative damage-induced apoptosis in vitro and in vivo.

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Zeng, Qiang; Ko, Chun-Hay; Siu, Wing-Sum; Li, Long-Fei; Han, Xiao-Qiang; Yang, Liu; Bik-San Lau, Clara; Hu, Jiang-Miao; Leung, Ping-Chung

2017-08-17

Dendrobium officinale Kimura & Migo (DO) is a valuable Traditional Chinese Medicine to nourish stomach, in which polysaccharides are identified as active ingredients. However, limited scientific evidences have been reported on the gastroprotective efficacy of DO. The aim of the current study was to investigate the protective effects and underlying mechanism of polysaccharides from DO(DOP) on gastric mucosal injury. For in vitro study, HFE145 cells were pretreated with DOP before induction of cell apoptosis by H 2 O 2 . Cell apoptosis and related proteins expression were detected. In the in vivo study, absolute ethanol was administered orally to induce gastric mucosal injury in rat. The gastric mucosal injury area and histological examination were used to evaluate the effects of DOP treatment on the recovery of the gastric mucosal injury. H 2 O 2 treatment for 6h significantly induced cell apoptosis in HFE145 cells. However, the destructive effects of H 2 O 2 on HFE 145 cells could be reversed by the pretreatment with DOP. The increased ROS level induced by H 2 O 2 for 4h was reduced after DOP pretreatment. The number of apoptotic cells in both early and late apoptosis stages decreased significantly and the nuclei morphology changes were improved with DOP pretreatment. Furthermore, DOP inhibited caspase 3 activation and PARP cleavage, downregulated Bax expression and upregulated Bcl2 expression in cell model. Further study revealed that pretreatment of DOP inhibited p -NF-κBp65/NF-κBp65 level, indicating DOP inhibited H 2 O 2 -mediated apoptosis via suppression of NF-κB activation. In addition, DOP treatment could ameliorate gastric mucosal injury and inhibit mucin loss induced by ethanol in animal model. DOP treatment also interfered with ethanol-induced apoptosis process by downregulating Bax/Bcl2 ratio in gastric mucosa. The present study was the first one to demonstrate the gastroprotective effect of DOP through inhibiting oxidative stress-induced apoptosis

Acceptability and feasibility of repeated mucosal specimen collection in clinical trial participants in Kenya.

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Gloria Omosa-Manyonyi

Full Text Available Mucosal specimens are essential to evaluate compartmentalized immune responses to HIV vaccine candidates and other mucosally targeted investigational products. We studied the acceptability and feasibility of repeated mucosal sampling in East African clinical trial participants at low risk of HIV and other sexually transmitted infections.The Kenya AIDS Vaccine Initiative (KAVI enrolled participants into three Phase 1 trials of preventive HIV candidate vaccines in 2011-2012 at two clinical research centers in Nairobi. After informed consent to a mucosal sub-study, participants were asked to undergo collection of mucosal secretions (saliva, oral fluids, semen, cervico-vaginal and rectal, but could opt out of any collection at any visit. Specimens were collected at baseline and two additional time points. A tolerability questionnaire was administered at the final sub-study visit. Of 105 trial participants, 27 of 34 women (79% and 62 of 71 men (87% enrolled in the mucosal sub-study. Nearly all sub-study participants gave saliva and oral fluids at all visits. Semen was collected from about half the participating men (47-48% at all visits. Cervico-vaginal secretions were collected by Softcup from about two thirds of women (63% at baseline, increasing to 78% at the following visits, with similar numbers for cervical secretion collection by Merocel sponge; about half of women (52% gave cervico-vaginal samples at all visits. Rectal secretions were collected with Merocel sponge from about a quarter of both men and women (24% at all 3 visits, with 16% of men and 19% of women giving rectal samples at all visits.Repeated mucosal sampling in clinical trial participants in Kenya is feasible, with a good proportion of participants consenting to most sampling methods with the exception of rectal samples. Experienced staff members of both sexes and trained counselors with standardized messaging may improve acceptance of rectal sampling.

Respuesta inmune mucosal inducida por proteoliposoma y cocleato derivados de N. meningitidis serogrupo B

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Judith del Campo

2009-08-01

Full Text Available Mucosal vaccination offers attractive advantages to conventional systemic vaccination. Most pathogens enter or establish infection at mucosal surfaces. This represents an enormous challenge for vaccine development. Nevertheless, the availability of safe and effective adjuvants that function mucosally is the major limitation. Therefore, we investigated the impact of mucosal immunization with the Neisseria meningitidis B proteoliposome (AFPL1, Adjuvant Finlay Proteoliposome 1 and its-derived cochleate (Co, AFCo1. They contain multiple PAMPs as immunopotentiators and have delivery system ability as well as Th1 polarization activity. Groups of female mice were immunized by nasal, oral, intravaginal, or intramuscular routes with three doses with AFPL1/AFCo1 alone or containing ovalbumin or glycoprotein (g D2 from Herpes Simplex Virus type 2 (HSV-2. High levels of specific IgG antibodies were detected in sera of mice vaccinated with either route. However, specific IgA antibodies were produced in saliva and vaginal wash only following mucosal delivering. The polarization to a Th1 pattern was confirmed by testing the induction of IgG2a/IgG2c antibody, positive delayed-type hypersensitivity reactions, and gIFN production. Additionally, AFCo1gD2 showed practically no vaginal HSV-2 replication and 100% protection against lethal vaginal HSV-2 challenge. In conclusion, the results support the use of AFCo1 as potent Th1 adjuvant for mucosal vaccines, particularly for nasal route.

Double-blinded, placebo-controlled trial on intravenous L-alanyl-L-glutamine in the incidence of oral mucositis following chemoradiotherapy in patients with head-and-neck cancer

International Nuclear Information System (INIS)

Cerchietti, Leandro C.A.; Navigante, Alfredo H.; Lutteral, Maribel A.; Castro, Monica A.; Kirchuk, Ricardo; Bonomi, Marcelo; Cabalar, Maria Esther; Roth, Berta; Negretti, Graciela; Sheinker, Beatriz; Uchima, Patricia

2006-01-01

Purpose: We performed this double-blinded, placebo-controlled study to determine the safety and efficacy of L-alanyl-L-glutamine in the prevention of mucositis in patients with head-and-neck cancer. Methods and Materials: Thirty-two patients with head-and-neck cancer were treated with chemoradiotherapy (CRT) (radiotherapy daily up to 70 Gy plus cisplatin/5-fluoruracil once a week) and were asked to participate. Twenty-nine patients received the CRT schedule and were double-blindly assigned to receive either intravenous L-alanyl-L-glutamine 0.4 g/kg weight/day or an equal volume of saline (placebo) during chemotherapy days. Results: Fourteen patients received L-alanyl-L-glutamine and 15 received placebo. Mucositis was assessed by the Objective Mucositis Score (OMS) and the World Health Organization (WHO) grading system. There was a significant difference in incidence of mucositis developed in patients receiving placebo compared with those who received L-alanyl-L-glutamine (p = 0.035). The number of patients with severe objective mucositis (OMS >1.49) was higher in the placebo group compared with the L-alanyl-L-glutamine group (67% vs. 14%, p 0.007). L-alanyl-L-glutamine patients experienced less pain (three highest Numeric Rating Scale scores of 1.3/10 vs. 6.3/10 respectively, p = 0.008) and need for feeding tubes (14% vs. 60% respectively, p = 0.020) compared with placebo patients. No adverse effects related to the drug or the infusions were noted in either group. Conclusion: For patients with head-and-neck cancer receiving CRT, intravenous L-alanyl-L-glutamine may be an effective preventive measure to decrease the severity of mucositis

Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences.

Directory of Open Access Journals (Sweden)

Lawrence J Tartaglia

2016-02-01

Full Text Available Simian-human immunodeficiency virus (SHIV challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need for the field has been the lack of a SHIV challenge stock expressing circulating recombinant form 01_AE (CRF01_AE env sequences. We therefore sought to develop mucosally transmissible SHIV challenge stocks containing HIV-1 CRF01_AE env derived from acutely HIV-1 infected individuals from Thailand. SHIV-AE6, SHIV-AE6RM, and SHIV-AE16 contained env sequences that were >99% identical to the original HIV-1 isolate and did not require in vivo passaging. These viruses exhibited CCR5 tropism and displayed a tier 2 neutralization phenotype. These challenge stocks efficiently infected rhesus monkeys by the intrarectal route, replicated to high levels during acute infection, and established chronic viremia in a subset of animals. SHIV-AE16 was titrated for use in single, high dose as well as repetitive, low dose intrarectal challenge studies. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines, monoclonal antibodies, and other interventions targeted at preventing HIV-1 CRF01_AE infection.

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

Sucralfate for radiation mucositis: results of a double-blind randomized trial

International Nuclear Information System (INIS)

Meredith, Ruby; Salter, Merle; Kim, Robert; Spencer, Sharon; Weppelmann, Burkhard; Rodu, Brad; Smith, Judy; Lee, Jeanette

1997-01-01

Purpose: To determine if addition of the ulcer-coating polysaccharide sucralfate could improve symptomatic relief of radiation mucositis over a popular combination of antacid, diphenhydramine, and viscous lidocaine alone. Methods and Materials: A double-blind study was conducted in which nurses and pharmacists coded patient groups and distributed medication in a manner blinded to both the patients and physicians. Eligible patients receiving radiation to the head and neck and/or chest sites that included the esophagus were randomized to a standard combination of antacid, diphenhydramine, and viscous lidocaine vs. the same solution plus sucralfate. Eligible patients were those receiving >40 Gy at 1.8 Gy/fraction, one fraction/day, five fractions/week. Participating patients were stratified between chest, small field head and neck, and large field head and neck. The observations and smears for Candidiasis screening. Medication was prescribed when the patient became symptomatic and concomitant use of other locally effective nonstudy agents was not allowed. The ability to eat various consistency of foods was graded 0-5, with 5 indicating no compromise of ability to ingest a food compared to baseline. Statistical analysis included mean + SD for food and soreness scores, paired t-test, and two-way analyses of variance to evaluate effects of site and treatment group on the changes in scores. Results: Over 2 years, 111 patients were entered. Because some withdrew and others did not require medication, results are presented for evaluable patients in each category. Mild adverse effects from the medication solution (usually mouth discomfort) were reported by <10% of patients in each treatment group among 106 patients evaluable for toxicity. There was a comparable incidence of mild-moderate mucositis for the two treatment groups. Severe mucositis was noted in two patients of the standard medication group and none among patients receiving sucralfate. The groups were comparable

Effectiveness of prophylactic percutaneous endoscopic gastrostomy on nutritional status and mucositis in oropharyngeal cancer patients undergoing concurrent chemoradiotherapy

International Nuclear Information System (INIS)

Takahashi, Miki; Takemoto, Naoko; Sano, Ayaka

2012-01-01

Recently, concurrent chemoradiotherapy (CCRT) is frequently used for the treatment of oropharyngeal cancer. However, CCRT induces mucositis and dysphagia and causes inadequate oral nutrition intake. Thus, percutaneous endoscopic gastrostomy (PEG) in advance is recently recommended. To evaluate the effectiveness of PEG on nutritional intake, nutritional status, blood test, and grade of mucositis of 29 patients who had CCRT with PEG were investigated retrospectively. The results were statistically compared with those of 13 patients who had CCRT without PEG as a control group. Regarding the total energy, no significant change was observed in the PEG group, while the total energy intake significantly decreased in the control group (P=0.026). A significant correlation was observed between the rate of body weight loss during CCRT and total energy intake (R=0.78). The total energy intake of patients who could maintain body weight was 34.1 kcal/kg/day. Taken together, these results suggested that early nutritional administration using PEG can reduce the weight loss during CCRT. (author)

Characterising the mucosal and systemic immune responses to experimental human hookworm infection.

Directory of Open Access Journals (Sweden)

Soraya Gaze

2012-02-01

Full Text Available The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13 and regulatory (IL-10 and TGF-β response, with some evidence of a Th1 (IFN-γ and IL-2 response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17 response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases.

Association of sex work with reduced activation of the mucosal immune system.

Science.gov (United States)

Lajoie, Julie; Kimani, Makubo; Plummer, Francis A; Nyamiobo, Francis; Kaul, Rupert; Kimani, Joshua; Fowke, Keith R

2014-07-15

Unprotected intercourse and seminal discharge are powerful activators of the mucosal immune system and are important risk factors for transmission of human immunodeficiency virus (HIV). This study was designed to determine if female sex work is associated with changes in the mucosal immunity. Cervicovaginal lavage and plasma from 122 HIV-uninfected female sex workers (FSW) and 44 HIV-uninfected low-risk non-FSW from the same socioeconomic district of Nairobi were analyzed for evidence of immune activation (IA). The cervico-mononuclear cells (CMC) were analyzed for cellular activation by flow cytometry. Lower IA was observed in FSW compared to the low-risk women as demonstrated by the lower level of MIP-3α (P sex work and increased with duration of sex work. This study showed that sex work is associated with important changes in the mucosal immune system. By analyzing chemokine/cytokine levels and CMC activation, we observed a lower mucosal IA in HIV-uninfected FSW compared to low-risk women. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mucosal immune response in broilers following vaccination with inactivated influenza and recombinant Bacillus subtilis

Science.gov (United States)

Mucosal and systemic immunity were observed in broilers vaccinated with mannosylated chitosan adjuvated (MCA) inactivated A/Turkey/Virginia/158512/2002 (H7N2) and administered with and without recombinant Bacillus subtilis to elicit heterologous influenza strain protection. Previously, mucosal immu...

Role of ABO secretor status in mucosal innate immunity and H. pylori infection.

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Sara Lindén

2008-01-01

Full Text Available The fucosylated ABH antigens, which constitute the molecular basis for the ABO blood group system, are also expressed in salivary secretions and gastrointestinal epithelia in individuals of positive secretor status; however, the biological function of the ABO blood group system is unknown. Gastric mucosa biopsies of 41 Rhesus monkeys originating from Southern Asia were analyzed by immunohistochemistry. A majority of these animals were found to be of blood group B and weak-secretor phenotype (i.e., expressing both Lewis a and Lewis b antigens, which are also common in South Asian human populations. A selected group of ten monkeys was inoculated with Helicobacter pylori and studied for changes in gastric mucosal glycosylation during a 10-month period. We observed a loss in mucosal fucosylation and concurrent induction and time-dependent dynamics in gastric mucosal sialylation (carbohydrate marker of inflammation, which affect H. pylori adhesion targets and thus modulate host-bacterial interactions. Of particular relevance, gastric mucosal density of H. pylori, gastritis, and sialylation were all higher in secretor individuals compared to weak-secretors, the latter being apparently "protected." These results demonstrate that the secretor status plays an intrinsic role in resistance to H. pylori infection and suggest that the fucosylated secretor ABH antigens constitute interactive members of the human and primate mucosal innate immune system.

Intravenous glutamine does not modify leucocyte count but shortens duration of mucositis after bone marrow transplant

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María Belén Andrade Hernández

2018-04-01

Full Text Available Rationale: Intravenous administration of Glutamine dipeptides (Gln has been proposed as treatment of oral mucositis following a bone marrow transplant (BMT. Objective: To establish the effects of intravenous Gln supplementation upon the severity of oral mucositis after BMT. Study design: Retrospective, analytical. Study serie: Records from 25 patients (Males: 56.0%; BMT cause: Leukemia: 64.0% who developed oral mucositis (Grades III – IV: 48.0% after BMT (Autologous: 44.0% at the "Juan Tanca Marengo" Hospital (Guayaquil, Ecuador between 2009 – 2017. Glutamine source: Dipeptiven©®: 13 grams of Gln suspended in 100 milliliters of a 20% solution of the alanine-glutamine dipeptide (Fresenius-Kabi©®, Germany. Materials and Methods: Gln-treated patients received 3(4.0% of the treatment leg, 5 (20.0%; 6 (12.0%; 7 (48.0%; or 10 (16.0% doses of the dipeptide until resolution of the symptoms. Impact of Gln was estimated from changes observed in the severity and duration of mucositis, white blood cell counts, and body weight regarding 25 non-Gln treated patients (Males: 68.0%; Leukemias: 32.0%; Autologous graft: 68.0%; Grade III – IV mucositis: 48.0%. Results: Intravenously-administered Gln shortened duration of oral mucositis: Gln-Treated: 12.5 ± 5.1 days vs. Non-Gln Treated: 21.3 ± 17.8 days (p < 0.05. Also, intravenous Gln marginally ameliorated loss of body weight: Gln-Treated -4.5 ± 5.5% vs. Non-Gln Treated: -7.5 ± 5.7% (p = 0.07. Conclusions: Intravenous Gln administration shortens duration of oral mucositis following BMT. Gln effect might be translated to a lesser weight loss in patients with oral mucositis.

A phase II randomized study of topical intrarectal administration of amifostine for the prevention of acute radiation-induced rectal toxicity

Energy Technology Data Exchange (ETDEWEB)

Kouloulias, V.E. [Dept. of Radiation Oncology, Aretaieion Univ. Hospital, Univ. of Athens Medical School, Athens (Greece); Dept. of Electrical and Computer Engineering, National Technical Univ. of Athens, Athens (Greece); Center of Radiation Oncology, YGEIA Diagnostic and Therapeutic Center of Athens, Athens (Greece); Kouvaris, J.R.; Kokakis, J.D.; Antypas, C.; Mallas, E.; Vosdoganis, S.P.; Vlahos, L.J. [Dept. of Radiation Oncology, Aretaieion Univ. Hospital, Univ. of Athens Medical School, Athens (Greece); Pissakas, G. [Radiotherapy Dept., Agios Savvas Anticancer Hospital, Athens (Greece); Matsopoulos, G. [Dept. of Electrical and Computer Engineering, National Technical Univ. of Athens, Athens (Greece); Michopoulos, S. [Gastroenterology Unit, Alexandra General Hospital, Athens (Greece); Kostakopoulos, A. [Urology Dept., Sismanoglio Hospital, Univ. of Athens Medical School, Athens (Greece)

2004-09-01

Purpose: to investigate the cytoprotective effect of intrarectal amifostine administration on acute radiation-induced rectal toxicity. Patients and methods: 67 patients with T1b-2 NO MO prostate cancer were randomized to receive amifostine intrarectally (group A, n - 33) or not (group B, n = 34) before irradiation. Therapy was delivered using a four-field technique with three-dimensional conformal planning. In group A, 1,500 mg amifostine was administered intrarectally as an aqueous solution in a 40-ml enema. Two different toxicity scales were used: EORTC/RTOG rectal and urologic toxicity criteria along with a Subjective-RectoSigmoid (S-RS) scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy. Objective measurements with rectosigmoidoscopy were performed at baseline and 1-2 days after the completion of radiotherapy. The area under curve for the time course of mucositis (RTOG criteria) during irradiation represented the mucositis index (MI). Results: intrarectal amifostine was feasible and well tolerated without any systemic or local side effects. According to the RTOG toxicity scale, five out of 33 patients showed grade 1 mucositis in group A versus 15 out of 34 patients with grade 1/2 in group B (p = 0.026). Mean rectal MI was 0.3 {+-} 0.1 in group A versus 2.2 {+-} 0.4 in group B (p < 0.001), while S-RS score was 3.9 {+-} 0.5 in group A versus 6.3 {+-} 0.7 in group B (p < 0.001). The incidence of urinary toxicity was the same in both groups. Conclusion: intrarectal administration of amifostine seems to have a cytoprotective efficacy in acute radiation-induced rectal mucositis. Further randomized studies are needed for definitive therapeutic decisions. (orig.)

Intestinal stromal cells in mucosal immunity and homeostasis.

Science.gov (United States)

Owens, B M J; Simmons, A

2013-03-01

A growing body of evidence suggests that non-hematopoietic stromal cells of the intestine have multiple roles in immune responses and inflammation at this mucosal site. Despite this, many still consider gut stromal cells as passive structural entities, with past research focused heavily on their roles in fibrosis, tumor progression, and wound healing, rather than their contributions to immune function. In this review, we discuss our current knowledge of stromal cells in intestinal immunity, highlighting the many immunological axes in which stromal cells have a functional role. We also consider emerging data that broaden the potential scope of their contribution to immunity in the gut and argue that these so-called "non-immune" cells are reclassified in light of their diverse contributions to intestinal innate immunity and the maintenance of mucosal homeostasis.

Radiation-induced mucositis: a randomized clinical trial of micronized sucralfate versus salt & soda mouthwashes.

Science.gov (United States)

Dodd, Marylin J; Miaskowski, Christine; Greenspan, Deborah; MacPhail, Laurie; Shih, Ai-Shan; Shiba, Gayle; Facione, Noreen; Paul, Steven M

2003-01-01

Oral mucositis is one of the major toxicities caused by radiation therapy (RT) treatments to the head and neck. The clinical efficacy of sucralfate (Carafate R) mouthwash for head and neck cancer patients (HNC) is not consistent across studies. In this study, it was hypothesized that if the particles in the original sucralfate suspension were micronized (i.e., < or = 25 microns) then the coating action of the mouthwash in the oral cavity would be enhanced. The purpose of this pilot study was to compare the efficacy of micronized sucralfate (Carafate R) mouthwash and salt & soda mouthwash in terms of the severity of the mucositis, the severity of mucositis-related pain, and the time required to heal RT-induced mucositis in patients with HNC. Severe mucositis and related pain can interfere with the ingestion of food and fluids, so patients' body weights were measured as well. All patients in this randomized clinical trial carried out a systematic oral hygiene protocol called the PRO-SELF: Mouth Aware (PSMA) Program. Patients who developed RT-induced mucositis anytime during their course of RT were randomized to one of the two mouthwashes and followed to the completion of RT and at one month following RT. Two referral sites were used for the study. Repeated measures occurred with the following instruments/variables: MacDibbs Mouth Assessment and weight. Demographic, disease, and cancer treatment information was also obtained. Thirty patients successfully completed the study. The typical participant was male (70%), married/partnered (70%), White (63%), not working or retired (73%), and had an average of 14.5 years of education (SD = 3.7). T-tests and Chi-square analyses with an alpha set at 0.05 were used to compare differences between the two mouthwashes. No significant differences were found in the number of days to onset of mucositis (i.e., 16 +/- 8.4 days). When patients had their worst MacDibbs score, (i.e., the most severe mucositis), there were no significant

Nutrition and Gut Mucositis in Pediatric Oncology

DEFF Research Database (Denmark)

Pontoppidan, Peter Erik Lotko

Childhood malignancies are the second most common cause of death in children. A major limitation of current therapies is the high toxicity. Alimentary tract toxicity (mucositis) is associated with increased risk of complication such as infections that may lead to death. In relation to HSCT, mucos...

Abnormalities of magnesium homeostasis in patients with chemotherapy-induced alimentary tract mucositis

OpenAIRE

Neven Baršić; Filip Grubišić-Čabo; Marko Nikolić; Neven Ljubičić

2016-01-01

Purpose: Hypomagnesemia contributes to morbidity in a significant proportion of hospitalized and severely ill patients, but it could also have beneficial anticancer effects. Alimentary tract mucositis is a frequent complication of cytotoxic chemotherapy. The aim of this study was to determine frequency and severity of hypomagnesemia in patients with different grades of chemotherapy-induced alimentary tract mucositis and to assess its clinical manifestations. Methods: Multicentric observat...

Identification of airway mucosal type 2 inflammation by using clinical biomarkers in asthmatic patients.

Science.gov (United States)

Silkoff, Philip E; Laviolette, Michel; Singh, Dave; FitzGerald, J Mark; Kelsen, Steven; Backer, Vibeke; Porsbjerg, Celeste M; Girodet, Pierre-Olivier; Berger, Patrick; Kline, Joel N; Chupp, Geoffrey; Susulic, Vedrana S; Barnathan, Elliot S; Baribaud, Frédéric; Loza, Matthew J

2017-09-01

The Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study profiled patients with mild, moderate, and severe asthma and nonatopic healthy control subjects. We explored this data set to define type 2 inflammation based on airway mucosal IL-13-driven gene expression and how this related to clinically accessible biomarkers. IL-13-driven gene expression was evaluated in several human cell lines. We then defined type 2 status in 25 healthy subjects, 28 patients with mild asthma, 29 patients with moderate asthma, and 26 patients with severe asthma based on airway mucosal expression of (1) CCL26 (the most differentially expressed gene), (2) periostin, or (3) a multigene IL-13 in vitro signature (IVS). Clinically accessible biomarkers included fraction of exhaled nitric oxide (Feno) values, blood eosinophil (bEOS) counts, serum CCL26 expression, and serum CCL17 expression. Expression of airway mucosal CCL26, periostin, and IL-13-IVS all facilitated segregation of subjects into type 2-high and type 2-low asthmatic groups, but in the ADEPT study population CCL26 expression was optimal. All subjects with high airway mucosal CCL26 expression and moderate-to-severe asthma had Feno values (≥35 ppb) and/or high bEOS counts (≥300 cells/mm 3 ) compared with a minority (36%) of subjects with low airway mucosal CCL26 expression. A combination of Feno values, bEOS counts, and serum CCL17 and CCL26 expression had 100% positive predictive value and 87% negative predictive value for airway mucosal CCL26-high status. Clinical variables did not differ between subjects with type 2-high and type 2-low status. Eosinophilic inflammation was associated with but not limited to airway mucosal type 2 gene expression. A panel of clinical biomarkers accurately classified type 2 status based on airway mucosal CCL26, periostin, or IL-13-IVS gene expression. Use of Feno values, bEOS counts, and serum marker levels (eg, CCL26 and CCL17) in combination might allow patient

MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy

NARCIS (Netherlands)

Lalla, Rajesh V.; Bowen, Joanne; Barasch, Andrei; Elting, Linda; Epstein, Joel; Keefe, Dorothy M.; McGuire, Deborah B.; Migliorati, Cesar; Nicolatou-Galitis, Ourania; Peterson, Douglas E.; Raber-Durlacher, Judith E.; Sonis, Stephen T.; Elad, Sharon; Al-Dasooqi, Noor; Brennan, Michael; Gibson, Rachel; Fulton, Janet; Hewson, Ian; Jensen, Siri B.; Logan, Richard; Öhrn, Kerstin E. O.; Sarri, Triantafyllia; Saunders, Deborah; von Bültzingslöwen, Inger; Yarom, Noam

2014-01-01

Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for mucositis.

Dysphagia and mucositis after concurrent chemoradiotherapy for head and neck cancer

International Nuclear Information System (INIS)

Tsuneyuki, Miki; Maeda, Tatsuyoshi; Yonezawa, Koichiro; Morimoto, Koichi; Tanimoto, Hitoshi; Saito, Miki; Otsuki, Naoki; Nibu, Ken-ichi

2010-01-01

A speech therapist performs swallowing rehabilitation in this hospital because concurrent chemoradiotherapy (CCRT) for head and neck cancer is commonly associated with, dysphagia. An evaluation of oral mucositis and dysphagia after CCRT was conducted to determine the relationship between swallowing rehabilitation and swallowing disability. A total of 51 patients (44 males and 7 females) with a mean age of 63 years (range, 39 to 80), underwent CCRT with or without neck dissection between April 2008 and November 2009. Oral mucositis and dysphagia were graded at the end of CCRT according to Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Seventeen of 51 patients underwent swallowing rehabilitation, exercise and education on muscle strengthening programs before and during CCRT. The average grades of oral mucositis of patients with nasopharyngeal, oropharyngeal, hypopharyngeal, and laryngeal cancer patients were 1.8, 2.1, 1.8, and 0.8, respectively. There was a lower incidence of oral mucositis in patients with laryngeal cancer than in those with oropharyngeal or hypopharyngeal cancer. The average grades of dysphagia of patients with nasopharyngeal, oropharyngeal, hypopharyngeal, and laryngeal cancer were 2.4, 2.7, 2.2, and 1.2. Dysphagia was most severe in the patients with oropharyngeal cancer, while it was minimal in those with laryngeal cancer. Seventeen diligent patients that underwent swallowing rehabilitation every day rarely developed severe dysphagia. (author)

Mucosal Ecological Network of Epithelium and Immune Cells for Gut Homeostasis and Tissue Healing.

Science.gov (United States)

Kurashima, Yosuke; Kiyono, Hiroshi

2017-04-26

The intestinal epithelial barrier includes columnar epithelial, Paneth, goblet, enteroendocrine, and tuft cells as well as other cell populations, all of which contribute properties essential for gastrointestinal homeostasis. The intestinal mucosa is covered by mucin, which contains antimicrobial peptides and secretory IgA and prevents luminal bacteria, fungi, and viruses from stimulating intestinal immune responses. Conversely, the transport of luminal microorganisms-mediated by M, dendritic, and goblet cells-into intestinal tissues facilitates the harmonization of active and quiescent mucosal immune responses. The bacterial population within gut-associated lymphoid tissues creates the intratissue cohabitations for harmonized mucosal immunity. Intermolecular and intercellular communication among epithelial, immune, and mesenchymal cells creates an environment conducive for epithelial regeneration and mucosal healing. This review summarizes the so-called intestinal mucosal ecological network-the complex but vital molecular and cellular interactions of epithelial mesenchymal cells, immune cells, and commensal microbiota that achieve intestinal homeostasis, regeneration, and healing.

Differentiation of mucosal disease from partial development of the paranasal sinuses in pediatric patients

International Nuclear Information System (INIS)

Duerinckx, A.J.; Whyte, A.M.; Lufkin, R.B.; Hall, T.R.; Kangarloo, H.

1988-01-01

On magnetic resonance (MR) images of pediatric patients, sinus mucosal disease may have an appearance similar to that of the normal partially developed sinus, leading to an increase in the number of patients labeled as having incidental sinusitis. The paranasal sinuses were retrospectively evaluated in 27 infants and children aged 0-11 years undergoing brain MR imaging for indications both unrelated and related to sinus disease. The authors developed criteria for grading paranasal sinus development and mucosal disease. Incidental mucosal disease is not uncommon, occurring in 28% of patients aged 0-7 years. In children under 3 years of age, inflammatory mucosal thickening and marrow surrounding the partially developed sinus have a high signal on many MR sequences and may be confused. Recognition of the low-intensity peripheral cortical margin of the sinus and awareness of the stages of normal sinus development allow differentiation

DNA Double-Strand Break Analysis by {gamma}-H2AX Foci: A Useful Method for Determining the Overreactors to Radiation-Induced Acute Reactions Among Head-and-Neck Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

Goutham, Hassan Venkatesh; Mumbrekar, Kamalesh Dattaram [Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka (India); Vadhiraja, Bejadi Manjunath [Manipal Hospital, Bangalore, Karnataka (India); Fernandes, Donald Jerard; Sharan, Krishna [Department of Radiotherapy and Oncology, Shiridi Sai Baba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka (India); Kanive Parashiva, Guruprasad; Kapaettu, Satyamoorthy [Division of Biotechnology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka (India); Bola Sadashiva, Satish Rao, E-mail: satishraomlsc@gmail.com [Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka (India)

2012-12-01

Purpose: Interindividual variability in normal tissue toxicity during radiation therapy is a limiting factor for successful treatment. Predicting the risk of developing acute reactions before initiation of radiation therapy may have the benefit of opting for altered radiation therapy regimens to achieve minimal adverse effects with improved tumor cure. Methods and Materials: DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of head-and-neck cancer patients undergoing chemoradiation therapy was analyzed by counting {gamma}-H2AX foci, neutral comet assay, and a modified version of neutral filter elution assay. Acute normal tissue reactions were assessed by Radiation Therapy Oncology Group criteria. Results: The correlation between residual DSBs and the severity of acute reactions demonstrated that residual {gamma}-H2AX foci in head-and-neck cancer patients increased with the severity of oral mucositis and skin reaction. Conclusions: Our results suggest that {gamma}-H2AX analysis may have predictive implications for identifying the overreactors to mucositis and skin reactions among head-and-neck cancer patients prior to initiation of radiation therapy.

Mucosal bridges of the upper esophagus after radiotherapy for Hodgkin's disease

International Nuclear Information System (INIS)

Papazian, A.; Capron, J.P.; Ducroix, J.P.; Dupas, J.L.; Quenum, C.; Besson, P.

1983-01-01

A 47-yr-old man developed dysphagia 4 yr after mediastinal radiotherapy for Hodgkin's disease. X-ray series, fiberoptic endoscopy, and computerized transverse tomography showed mucosal bridges in the upper esophagus. Histologically, these bridges were constituted from normal epithelium overlying a chronic inflammatory lamina propria, without evidence of Hodgkin's disease recurrence or of squamous cell carcinoma. Swallowing was improved by endoscopic electrocoagulation and Eder-Puestow dilatations. Several arguments favor the hypothesis that these mucosal bridges were the late sequelae of radiation esophagitis

Treatment modalities of oral mucositis after radiation of head and neck cancers; Prise en charge des mucites apres radiotherapie des cancers des voies aerodigestives superieures

Energy Technology Data Exchange (ETDEWEB)

Lapeyre, M.; Charra-Brunaud, C.; Kaminsky, M.C.; Geoffrois, L.; Dolivet, G.; Pourel, N.; Marchal, C.; Bey, P.; Maire, F.; Simon, M. [Centre Alexis-Vautrin, 54 - Vandoeuvre-les-Nancy (France); Toussaint, B. [Hopital Central, Service de Chirurgie ORL, 54 - Nancy (France)

2001-11-01

Acute mucositis is common after radiotherapy for head and neck cancers. During the past 3 decades, there was a gradual evolution in the treatment modalities for locally advanced carcinomas (concomitant radio-chemotherapy, accelerated radiotherapy). These new strategies are accompanied by an increase in early mucosal reactions. At the present time, there is no widely accepted prophylaxis or effective treatment. Many traditional remedies or new agents seem ineffective (Sucralfate, Chlorhexidine, GM-CSF, Silver nitrate, Prostaglandin, anti-oxidants, Benzydamine hydrochloride), while others seem promising (Povidone-iodine, nonabsorbable antibiotic lozenges and anti-fungal, local GM-CSF, Glutamide, Low-energy laser, corticosteroids). Radioprotectors are controversial and should be only used in experimental protocols and not in routine practice. However, some recommendations can be proposed: general prevention and global care before cancer therapy should be systematic (oral hygiene, dental and periodontal treatment, advice to avoid the use of tobacco and alcohol); frequent oral rinsing with a bland mouthwash (Povidone-iodine or others) should be used at the start of treatment because there are significant modifications of the oral microflora increased by a disturbed salivary flow; these mouthwashes could be associated with nonabsorbable antibiotic lozenges or anti-fungal topical (bicarbonates, Amphotericine B); Systematic percutaneous fluoroscopic gastrostomy should be decided before any aggressive treatments (concomitant radio-chemotherapy, accelerated radiotherapy); pain should be controlled; finally, the radiation technique should be optimized (mucosal sparing block, conformal radiotherapy and intensity modulated radiation therapy). (authors)

Clinical effects of flurbiprofen tooth patch on radiation-induced oral mucositis. A pilot study

NARCIS (Netherlands)

Stokman, MA; Spijkervet, FKL; Burlage, FR; Roodenburg, JLN

Background: Mucositis is an oral sequela of radiotherapy. In the development of mucositis several mechanisms play a role, such as inflammation and the effect of radiation on the high proliferation rate of oral basal epithelial cells. Therefore, administration of a drug with antiinflammatory and

Clinical, biological, histological features and treatment of oral mucositis induced by radiation therapy: a literature review

International Nuclear Information System (INIS)

Bonan, Paulo Rogerio Ferreti; Lopes, Marcio Ajudarte; Almeida, Oslei Paes de; Alves, Fabio de Abreu

2005-01-01

The oral mucositis is a main side effect of radiotherapy on head and neck, initiating two weeks after the beginning of the treatment. It is characterized by sensation of local burning to intense pain, leading in several cases, to the interruption of the treatment. The purpose of this work is to review the main published studies that discuss the clinical, biological and histopathological features of oral mucositis induced by radiation therapy and to describe the main approaches recommended to prevent or to treat it. Although the clinical features of mucositis are intensively described in the literature, few studies address the histopathological alterations in oral mucositis and only recently, its biological processes have been investigated. The biological mechanisms involved in the radiation tissue damage have been only recently discussed and there is no consensus among treatment modalities. Yet, the progressive knowledge in the histopathology and biological characteristics of oral mucositis probably will lead to more effective in prevention and control strategies. (author)

TREATMENT OF ORAL MUCOSAL LESIONS BY SCALPEL EXCISION AND PLATELET-RICH FIBRINMEMBRANE GRAFTING: A case report

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Ivan Chenchev

2016-07-01

Full Text Available Purpose: The treatment of oral mucosal lesions and mucosal hypertrophy in particular, is most often achieved by an excision with or without covering the surface of the wound. The platelet rich fibrin membrane (PRFm is an autogenous product containing platelets and leukocytes and their secreted growth factors and cytokines. The purpose of the presented clinical case is to describe a new, recent technique used for the covering of mucosal wounds left after the removal of pathological lesions. Material and Methods: On a single patient mucosal hypertrophy was removed by an excision with scalpel and the resulting surgical wound was covered with an autogenous PRF membrane. Postoperatively the healing process was followed on the 7th, 14th and 30th day. Results: The healing period went smoothly with minimal postoperative discomfort and no complications. Conclusion: The results of the presented clinical case demonstrate that the PRF membrane can successfully be used to cover postoperative mucosal defects.

[Rectal mucosal prolapse syndrome: study of cases. Hospital Daniel A Carrion, Lima, Peru, 2010-2013].

Science.gov (United States)

Arévalo Suarez, Fernando; Cárdenas Vela, Irene; Rodríguez Rodríguez, Kriss; Pérez Narrea, María Teresa; Rodríguez Vargas, Omar; Montes Teves, Pedro; Monge Salgado, Eduardo

2014-04-01

to describe the clinical, endoscopic, and histological characteristics of rectal mucosal prolapse syndrome, formerly known as Solitary rectal ulcer, in patients from a general hospital. All patient diagnosed as rectal mucosal prolapse syndrome during 2010-2013 was selected; the medical history war reviewed and the histological slides were reevaluated by two pathologists. 17 cases of rectal mucosal prolapse syndrome were selected, the majority were males under 50 years, the most common clinical findings were rectal bleeding (82%) and constipation (65%), the endocopic findings were heterogeneous,: erythema (41%), ulcers (35%) and elevated lesions (29%). All cases presented fibromuscularhyperplasia in lamina propia and crypt distortion in the microscopic evaluation. In our study of rectal mucosal prolapse syndrome. The most common clinical findings were rectal bleeding and constipation. Erythematous mucosa was the most common endoscopic finding.

CCR2 mediates Helicobacter pylori-induced immune tolerance and contributes to mucosal homeostasis.

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Sun, Xia; Zhang, Min; El-Zaatari, Mohamad; Huffnagle, Gray B; Kao, John Y

2017-04-01

We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H. pylori were examined to determine the impact of CCR2 signaling on dendritic cells function by qPCR, ELISA, and FACS analyses. Acute H. pylori infection was associated with a threefold increase in CCR2 mRNA expression in the gastric mucosa. H. pylori-infected CCR2KO mice exhibited a higher degree of mucosal inflammation, that is, increased gastritis scores and pro-inflammatory cytokine mRNA levels, but lower degree of H. pylori gastric colonization compared to infected Wt mice. Peripheral H. pylori-specific immune response measured in the CCR2KO spleen was characterized by a higher Th17 response and a lower Treg response. In vitro, CCR2KO bone marrow-derived DC was less mature and shown a lower Treg/Th17 ratio. Moreover, blockade of CCR2 signaling by MCP-1 neutralizing antibody inhibited H. pylori-stimulated bone marrow-derived DC maturation. Our results indicate that CCR2 plays an essential role in H. pylori-induced immune tolerance and shed light on a novel mechanism of CCR2-dependent DC Treg induction, which appears to be important in maintaining mucosal homeostasis during H. pylori infection. © 2016 John Wiley & Sons Ltd.

NHE8 plays important roles in gastric mucosal protection

Science.gov (United States)

Xu, Hua; Li, Jing; Chen, Huacong; Wang, Chunhui

2013-01-01

Sodium/hydrogen exchanger (NHE) 8 is an apically expressed membrane protein in the intestinal epithelial cells. It plays important roles in sodium absorption and bicarbonate secretion in the intestine. Although NHE8 mRNA has been detected in the stomach, the precise location and physiological role of NHE8 in the gastric glands remain unclear. In the current study, we successfully detected the expression of NHE8 in the glandular region of the stomach by Western blotting and located NHE8 protein at the apical membrane in the surface mucous cells by a confocal microscopic method. We also identified the expression of downregulated-in-adenoma (DRA) in the surface mucous cells in the stomach. Using NHE8−/− mice, we found that NHE8 plays little or no role in basal gastric acid production, yet NHE8−/− mice have reduced gastric mucosal surface pH and higher incidence of developing gastric ulcer. DRA expression was reduced significantly in the stomach in NHE8−/− mice. The propensity for gastric ulcer, reduced mucosal surface pH, and low DRA expression suggest that NHE8 is indirectly involved in gastric bicarbonate secretion and gastric mucosal protection. PMID:23220221

Low-level laser therapy in the prevention of radiotherapy-induced xerostomia and oral mucositis

International Nuclear Information System (INIS)

Lopes, Carlos de Oliveira; Mas, Josepa Rigau I.; Zangaro, Renato Amaro

2006-01-01

Objective: to verify if the use of InGaAIP laser with 685 nm wave length can reduce the xerostomy incidence, the oral mucositis severity and the pain related to mucositis in patients with head and neck cancer submitted to radiotherapy. Objective: sixty patients presenting head and neck carcinoma were submitted to radiotherapy with daily doses of 1.8 to 2.0 Gy and a final dose of 45 to 72 Gy. The salivary volume was evaluated in the first and fifteenth days, at the end of the treatment and after 15 and 30 days. The oral mucositis was evaluated on a weekly basis. Twenty-nine patients were submitted to radiotherapy without laser and 31 were submitted to radiotherapy and laser with daily doses of 2 joules/cm 2 in predetermined areas of the oral mucosa and the parotid and submandibular glands. Results: in the group submitted to radiotherapy and laser the incidence of mucositis (p < 0.001) and pain (p < 0.016) was significantly lower and the salivary volume (p < 0.001) was kept higher during and after the treatment. Conclusion: the group of patients submitted to radiotherapy and laser had lower incidence of xerostomy, oral mucositis and pain when compared to the group treated with radiotherapy without laser, producing statistically significant results. (author)

Intragastric inulin as a measure of mucosal damage caused by aspirin

International Nuclear Information System (INIS)

Wittmers, L.E. Jr.; Anderson, L.A.; Fall, M.M.; Alich, A.A.

1990-01-01

In an attempt to find a method of gastric mucosal damage assessment that yields consistent results, the experiments presented here employed the measurement of the movement of inulin out of the gastric contents into the stomach wall and vascular compartment as an estimate of mucosal damage. Anesthetized male Sprague-Dawley rats were functionally nephrectomized and were administered a control or test solution containing 3H-inulin. The test solutions contained one of three doses of aspirin. Blood samples were taken at 15-min intervals over a 90-min exposure period. The stomach was removed from the animal and full-thickness tissue samples taken for measurement of 3H-inulin content. When the gastric mucosa was exposed to the test agents, there was a significantly greater accumulation of inulin in the body and antrum as well as in the plasma when compared to controls. We conclude that intragastric inulin can be employed to estimate gastric mucosal damage

Side effects and opioid addiction in radiation-induced mucositis pain control in head and neck cancer

International Nuclear Information System (INIS)

Takahashi, Atsuhito; Shoji, Kazuhiko; Mizuta, Masanobu; Morita, Mami; Iki, Takehiro; Kojima, Tsuyoshi

2011-01-01

Radiation therapy in head and neck malignancy may trigger mucositis poorly controlled by nonsteroidal antiinflammatory drugs (NSAIDs). Having already reported early opioid efficacy in radiation-induced mucositis pain in head and neck cancer, we discuss whether this resulted in severe side effects and opioid addiction. Of 11 persons (26.2%) with nausea, 3 could not tolerate opioid. Of 33 (78.6%) with constipation, all were controlled by purgatives. Seven had mild sleepiness. None had severe opioid side effects in radiation-induced mucositis pain treatment, but I showed opioid dependence after 128-days opioid administration. While opioid administration in radiation-induced mucositis pain may not cause addiction, lomg-term opioid use should be carefully monitored. (author)

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

A prospective comparison of common toxicity criteria adverse events Version 3 and 4 in assessing oral mucositis for oral and oropharyngeal carcinoma

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M. Hickman

2017-03-01

Conclusion: Differences in grading of mucositis scored by V3 and V4 are frequent. Relationships between biologically effective dose and rates of grade 3 mucositis have historically been based on mucosal appearances. It is not known whether the same relationships apply when mucositis is graded based on symptomatic grading systems. Both V3 and V4 should be used in clinical trials to improve understanding of mucositis and its relationship to quality of life and late mucosal toxicity.

Esophageal Baseline Impedance Reflects Mucosal Integrity and Predicts Symptomatic Outcome With Proton Pump Inhibitor Treatment.

Science.gov (United States)

Xie, Chenxi; Sifrim, Daniel; Li, Yuwen; Chen, Minhu; Xiao, Yinglian

2018-01-30

Esophageal baseline impedance, which is decreased in gastroesophageal reflux disease (GERD) patients, is related to the severity of acid reflux and the integrity of the esophageal mucosa. The study aims to compare the baseline impedance and the dilated intercellular spaces (DIS) within patients with typical reflux symptoms and to evaluate the correlation of baseline impedance with DIS, esophageal acid exposure, as well as the efficacy of proton pump inhibitor (PPI) treatment. Ninety-two patients and 10 healthy controls were included in the study. Erosive esophagitis (EE) was defined by esophageal mucosal erosion under upper endoscopy. Patients without mucosa erosion were divided into groups with pathologic acid reflux (non-erosive reflux disease [NERD]) or with hypersensitive esophagus. The biopsies of esophageal mucosa were taken 2-4 cm above the gastroesophageal junction Z-line during upper endoscopy for DIS measurement. All the patients received esomeprazole 20 mg twice-daily treatment for 8 weeks. The efficacy of esomeprazole was evaluated among all patients. The intercellular spaces were dilated in both EE and NERD patients ( P baseline impedance was decreased in both EE patients and NERD patients, and negatively correlated to the acid exposure time ( r = -0.527, P baseline impedance ( r = -0.230, P Baseline impedance > 1764 Ω" was an independent predictor for PPI failure (OR, 11.9; 95% CI, 2.4-58.9; P baseline impedance was observed in patients with mucosa erosion or pathological acid reflux. The baseline impedance reflected the mucosal integrity, it was more sensitive to esophageal acid exposure. Patients with high impedance might not benefit from the PPI treatment.

Enhancement of mucosal immune responses by chimeric influenza HA/SHIV virus-like particles

International Nuclear Information System (INIS)

Guo Lizheng; Lu Xiaoyan; Kang, S.-M.; Chen Changyi; Compans, Richard W.; Yao Qizhi

2003-01-01

To enhance mucosal immune responses using simian/human immunodeficiency virus-like particles (SHIV VLPs), we have produced novel phenotypically mixed chimeric influenza HA/SHIV VLPs and used them to immunize C57BL/6J mice intranasally. Antibody and cytotoxic T-cell (CTL) responses as well as cytokine production in both systemic and mucosal sites were compared after immunization with SHIV VLPs or chimeric HA/SHIV VLPs. By using enzyme-linked immunosorbent assay (ELISA), the levels of serum IgG and mucosal IgA to the HIV envelope protein (Env) were found to be highest in the group immunized with chimeric HA/SHIV VLPs. Furthermore, the highest titer of serum neutralizing antibody against HIV Env was found with the group immunized with chimeric HA/SHIV VLPs. Analysis of the IgG1/IgG2a ratio indicated that a T H 1-oriented immune response resulted from these VLP immunizations. HA/SHIV VLP-immunized mice also showed significantly higher CTL responses than those observed in SHIV VLP-immunized mice. Moreover, a MHC class I restricted T-cell activation ELISPOT assay showed a mixed type of T H 1/T H 2 cytokines in the HA/SHIV VLP-immunized mice, indicating that the chimeric VLPs can enhance both humoral and cellular immune responses to the HIV Env protein at multiple mucosal and systemic sites. The results indicate that incorporation of influenza HA into heterotypic VLPs may be highly effective for targeting vaccines to mucosal surfaces

A metaproteomic approach to study human-microbial ecosystems at the mucosal luminal interface.

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Xiaoxiao Li

Full Text Available Aberrant interactions between the host and the intestinal bacteria are thought to contribute to the pathogenesis of many digestive diseases. However, studying the complex ecosystem at the human mucosal-luminal interface (MLI is challenging and requires an integrative systems biology approach. Therefore, we developed a novel method integrating lavage sampling of the human mucosal surface, high-throughput proteomics, and a unique suite of bioinformatic and statistical analyses. Shotgun proteomic analysis of secreted proteins recovered from the MLI confirmed the presence of both human and bacterial components. To profile the MLI metaproteome, we collected 205 mucosal lavage samples from 38 healthy subjects, and subjected them to high-throughput proteomics. The spectral data were subjected to a rigorous data processing pipeline to optimize suitability for quantitation and analysis, and then were evaluated using a set of biostatistical tools. Compared to the mucosal transcriptome, the MLI metaproteome was enriched for extracellular proteins involved in response to stimulus and immune system processes. Analysis of the metaproteome revealed significant individual-related as well as anatomic region-related (biogeographic features. Quantitative shotgun proteomics established the identity and confirmed the biogeographic association of 49 proteins (including 3 functional protein networks demarcating the proximal and distal colon. This robust and integrated proteomic approach is thus effective for identifying functional features of the human mucosal ecosystem, and a fresh understanding of the basic biology and disease processes at the MLI.

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

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Cielito C Reyes-Gibby

Full Text Available Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA, a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive and thymine degradation pathways (p = 1.06-08 were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis. The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67. In conclusion, gene network analysis identified novel molecules and

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

Science.gov (United States)

Reyes-Gibby, Cielito C; Melkonian, Stephanie C; Wang, Jian; Yu, Robert K; Shelburne, Samuel A; Lu, Charles; Gunn, Gary Brandon; Chambers, Mark S; Hanna, Ehab Y; Yeung, Sai-Ching J; Shete, Sanjay

2017-01-01

Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA), a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive) and thymine degradation pathways (p = 1.06-08) were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis). The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67). In conclusion, gene network analysis identified novel molecules and biological

Sucralfate for radiation mucositis: results of a double-blind randomized trial

International Nuclear Information System (INIS)

Meredith, R.; Salter, M.; Kim, R.; Spencer, S.; Weppelmann, B.; Rodu, B.; Smith, J.; Lee, J.

1995-01-01

Purpose: To determine if addition of the ulcer-coating polysaccharide sucralfate could improve symptomatic relief of radiation mucositis over a popular combination of Maalox, diphenhyrdramine and viscous lidocaine alone. Methods: A double-blind study was conducted in which nurses/pharmacists coded patient groups and distributed medication in a manner blinded to both the patients and physicians. Eligible patients receiving radiation to the head and neck and/or chest sites that included the esophagus were randomized to a standard combination of Maalox, diphenhydramime and viscous lidocaine verses the same solution plus sucralfate. Eligible patients were those receiving > 40 Gy at 1.8 Gy/fraction, 1 fraction/day, 5 fractions/week. Participating patients were stratified between chest, small field head and neck, and large field head and neck. Baseline information regarding use of tobacco, alcohol, and food intake was obtained prior to symptomatic mucositis. This was compared with similar information obtained weekly once symptoms occurred. The patients subjected evaluation of throat soreness and relief with medication was elicited as well as physician observations and smears for Candidiasis screening. Medication was prescribed when the patient became symptomatic and concomitant use of other locally effective non-study agents was not allowed. Subjective soreness was graded on a scale of 0-20 with 0 indicating no soreness and 20 designating severe soreness that compromised ability to swallow secretions. The ability to eat various consistency of foods was graded 0-5 with 5 indicating no compromise of ability to ingest a food compared to baseline. Statistical analysis included mean + S.D. for food and soreness scores, paired t-test and two-way analyses of variance to evaluate effects of site and treatment group on the changes in scores. Results: Over 2 years, 110 patients were entered. Since some withdrew and others did not require medication, results are presented for

Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant

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Shailbala Singh

2014-10-01

Full Text Available Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.

An endoscopic study of upper-GI mucosal changes in patients with congestive heart failure.

Science.gov (United States)

Raja, Kaiser; Kochhar, Rakesh; Sethy, Pradeepta K; Dutta, Usha; Bali, Harinder K; Varma, Jagmohan S

2004-12-01

Congestive heart failure results in an increase in systemic venous pressure that is transmitted to the inferior vena cava and to the hepatic veins. This can cause GI vascular and mucosal congestion. The aim of this study was to define upper-GI mucosal changes in patients with congestive heart failure. A total of 57 patients with congestive heart failure presenting with GI symptoms underwent upper endoscopy. Echocardiography was performed in all patients to determine the ejection fraction and the degree of tricuspid regurgitation. Transabdominal US was performed to measure the diameters of the hepatic veins, the inferior vena cava, and the portal vein. The presence and the severity of gastropathy and duodenopathy were compared with the parameters relating to severity of cardiac failure. Of the 57 patients studied, gastric mucosal changes were observed in 50 (88%), duodenal mucosal changes in 31 (54%), and esophageal mucosal changes in none. Gastric mucosal changes were the following: mosaic-like pattern (n = 50), punctate spots (n = 34), thickened folds (n = 5), watermelon stomach (n = 3), and telangiectasia (n = 10). Duodenal mucosal changes were the following: mosaic-like pattern (n = 29), thickened folds (n = 8), and telangiectasia (n = 2). Upper-GI symptoms were associated with gastropathy ( p = 0.027) and duodenopathy ( p = 0.003). The presence and the severity of duodenopathy showed a high degree of positive correlation with the presence and the severity of gastropathy (gamma value 0.690; p value <0.001). Patients with gastropathy and duodenopathy had higher mean inferior vena cava and hepatic vein diameters than those without gastropathy and duodenopathy. The severity of duodenopathy but not that of gastropathy was significantly associated with increasing severity of tricuspid regurgitation ( p = 0.001), larger portal vein diameter ( p = 0.02), and lower ejection fraction ( p = 0.008). Among patients with congestive cardiac failure with GI symptoms, changes

Effectiveness of India ink as a long-term colonic mucosal marker.

Science.gov (United States)

Fennerty, M B; Sampliner, R E; Hixson, L J; Garewal, H S

1992-01-01

We prospectively studied the use of India ink as a long-term or "permanent" mucosal marker as part of a study investigating the natural history of diminutive distal colorectal polyps. Twenty-six patients had 32 India ink tatoos implanted. The tatoo sites of the 19 patients who were followed at least 6 months continued to display intensely stained mucosa at the original sites. No side effects or complications were encountered. India ink appears to be a safe and effective long-term marker for colonic mucosal lesions.

Home-based humidification for mucositis in patients undergoing radical radiotherapy: preliminary report.

Science.gov (United States)

Morton, Randall P; Thomson, Vicki C; Macann, Andrew; Gerard, Catherine M; Izzard, Mark; Hay, K David

2008-04-01

Oropharyngeal mucositis is a frequent, severe complication of local irradiation for tumours in the head and neck. We postulated that heated humidification of inspired air via a nasal interface may palliate symptoms of mucositis by reducing the discomfort associated with dry, sticky secretions. We sought to review the effect of home-based humidification on hospital admissions and the patient reported experience of that humidification. This study was a retrospective review. A historical (control) group of patients did not receive home humidification at any stage (n = 55) and a study group (n = 53) received home humidification at or after the onset of grade 3 mucositis. A questionnaire was sent to study group patients to obtain information about their experience of using the humidifier at home. There were no demographic differences between the study and control groups, but the study group had significantly more advanced cancer (stage IV; p = .0307) and significantly higher total fractions and days treated (p humidification were admitted after starting that use (p humidification was of benefit, and 81% stated that it relieved mouth or throat pain. Humidification of inspired gas offers a simple, drug-free option for managing a number of the adverse mucosal effects of radiation and chemoradiation in head and neck cancer patients.

Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice

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Nobuhiro Nakamoto

2017-10-01

Full Text Available Summary: Gut-derived microbial antigens trigger the innate immune system during acute liver injury. During recovery, regulatory immunity plays a role in suppressing inflammation; however, the precise mechanism underlying this process remains obscure. Here, we find that recruitment of immune-regulatory classical dendritic cells (cDCs is crucial for liver tolerance in concanavalin A-induced acute liver injury. Acute liver injury resulted in enrichment of commensal Lactobacillus in the gut. Notably, Lactobacillus activated IL-22 production by gut innate lymphoid cells and raised systemic IL-22 levels. Gut-derived IL-22 enhanced mucosal barrier function and promoted the recruitment of regulatory cDCs to the liver. These cDCs produced IL-10 and TGF-β through TLR9 activation, preventing further liver inflammation. Collectively, our results indicate that beneficial gut microbes influence tolerogenic immune responses in the liver. Therefore, modulation of the gut microbiota might be a potential option to regulate liver tolerance. : Nakamoto et.al. find that Lactobacillus accumulates in the gut and activates IL-22 production by innate lymphoid cells during acute liver injury. Gut-derived IL-22 contributes to liver tolerance via induction of regulatory DCs. Keywords: immune tolerance, dendritic cell, innate lymphoid cell, acute liver injury, interleukin-10, interleukin-22, microbiota, dysbiosis

[Acute appendicitis and coinfection with enterobiasis and taeniasis: a case report].

Science.gov (United States)

Çallı, Gülhan; Özbilgin, Mücahit; Yapar, Nur; Sarıoğlu, Sülen; Özkoç, Soykan

2014-01-01

Parasites are rarely associated with inflammation of the appendix. Generally, parasites cause acute abdominal pain via blocking the gut lumen. In this article, we presented a case of appendicitis where Enterobius vermicularis was detected in the surgical specimen and Taenia was detected in the stool. A 31 year old male patient was admitted to the emergency room with severe abdominal pain, which has begun two days ago. On physical examination, tenderness was positive on palpation of the right lower abdominal quadrant and the patient was operated on with the diagnosis of acute appendicitis. Histopathological examination of the patient's appendectomy material revealed numerous parts of parasites resembling Enterobius vermicularis and slight mucosal erosion. On parasitological examination of the patient's stool, Taenia eggs and adult forms were determined. Antiparasitic therapy was started with niclosamide for taeniasis and albendazole for enterobiasis. Parasitic infections can mimic acute appendicitis clinically. Radiological and laboratory findings do not help to distinguish the diagnosis of acute appendicitis. In the histopathological examination of the appendix, the findings of acute inflammation of the appendix wall may not be defined. For patients with normal histopathological examination, screening for parasites should be done, and anti-parasitic treatment should be started after appendectomy.

Toxin-mediated effects on the innate mucosal defenses: implications for enteric vaccines

DEFF Research Database (Denmark)

Glenn, Gregory M; Francis, David H; Danielsen, E Michael

2009-01-01

mucosal barrier as a key step in enteric pathogen survival. We review key observations relevant to the roles of LT and cholera toxin in protective immunity and the effects of these toxins on innate mucosal defenses. We suggest either that toxin-mediated fluid secretion mechanically disrupts the mucus...... layer or that toxins interfere with innate mucosal defenses by other means. Such a breach gives pathogens access to the enterocyte, leading to binding and pathogenicity by enterotoxigenic E. coli (ETEC) and other organisms. Given the common exposure to LT(+) ETEC by humans visiting or residing...... unexpectedly broad protective effects against LT(+) ETEC and mixed infections when using a toxin-based enteric vaccine. If toxins truly exert barrier-disruptive effects as a key step in pathogenesis, then a return to classic toxin-based vaccine strategies for enteric disease is warranted and can be expected...

The Prevalence and Investigation of Risk Factors of Oral Mucositis in a Pediatric Oncology Inpatient Population; a Prospective Study.

Science.gov (United States)

Allen, Gabrielle; Logan, Richard; Revesz, Tom; Keefe, Dorothy; Gue, Sam

2018-01-01

Oral mucositis can be a frequent and severe complication of chemotherapy in children. It can result in pain, infection, depression, prolonged admission, treatment delays, increase in patient morbidity, and increased costs. To record the prevalence and severity of oral mucositis among inpatients and explore the relationship of risks factors and the development of oral mucositis. During an 18-month period 643 clinical inpatient assessments were completed on 73 children who were admitted and had received chemotherapy in the last 14 days. There were 43 episodes of oral mucositis in 31 children; 42.5% of the inpatient population. World Health Organization assessment identified 32.6% of episodes were grade 1, 34.9% grade 2, 14.0% grade 3, and 18.6% grade 4. Analysis revealed significant associations between patient diagnosis (P<0.0001), chemotherapy cycles (P<0.0001), day 8 and 9 of the chemotherapy cycle (P<0.05), and neutropenia (P<0.0001) and oral mucositis. Children had increased length of admission with increasing severity of oral mucositis (P=0.0005). The prevalence of oral mucositis was 42.5% among inpatients and admission length was increased with increasing severity. Patient diagnosis, chemotherapy treatment block, day of chemotherapy cycle, and neutropenic status were shown to influence the risk of developing oral mucositis.

Use of Curcumin Mouthrinse in Radio-Chemotherapy Induced Oral Mucositis Patients: A Pilot Study.

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Patil, Karthikeya; Guledgud, Mahima V; Kulkarni, P K; Keshari, Deepika; Tayal, Srishti

2015-08-01

Oral Mucositis is a complex and distinct pathobiologic entity resulting in injuries in mucosa that is a common complication in cancer patients undergoing chemotherapy (CT) and radiation therapy (RT). Phytochemicals, such as Curcumin, turmeric extract, has attracted great attention for its therapeutic benefits in clinical oncology due to its chemopreventive, antitumoral, chemosensibilizing and radiosensibilizing activities against various types of cancers and the complications associated with their management. To evaluate the efficacy and safety of curcumin mouthwash in the management of Oral Mucositis in cancer patients undergoing radio-chemotherapy. The research group consisted of 20 adult cancer patients undergoing radio-chemotherapy at the Regional Oncology Centre, who were evaluated for signs and symptoms of oral mucositis and then randomly divided into two groups. Standard preventive oral care i.e. chlorhexidine mouthwash 0.2% was given to one group while the other group was provided with freshly prepared curcumin mouthwash; each to be used thrice daily. Oral mucositis was assessed at days 0, 10 and 20. The World Health Organization (WHO) scale, the Oral Mucositis Assessment Scale (OMAS), and a Numerical Rating Scale (NRS; patient reporting scale of 0-10) were used. Adverse events were tracked. Descriptive statistics, Independent sample t-test and repeated measure ANOVA test were performed. Statistically significant difference was found in the NRS (p=0.000), Erythema (p=0.050), ulceration (p=0.000) and WHO scores (p=0.003) between the two groups. Curcumin was found to be better than chlorhexidine mouth wash in terms of rapid wound healing and better patient compliance in management of radio-chemotherapy induced oral mucositis. No oral or systemic complications were reported.

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

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

-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......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...

Acute Gastrointestinal Bleeding in Olmesartan-Associated Collagenous Gastroduodenitis: A Potential Endoscopic Complication

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Rachel Hudacko

2018-01-01

Full Text Available Collagenous gastroenteritis is a rare disease that is known to be associated with the drug olmesartan, an angiotensin II receptor antagonist used to treat hypertension. It is characterized histologically by increased subepithelial collagen deposition with associated inflammation and epithelial injury. Endoscopically, the mucosa appears inflamed and friable and may be nodular or atrophic. We report a case of acute gastric bleeding on direct mucosal contact during endoscopy in a patient with olmesartan-associated collagenous gastroduodenitis to raise awareness of this potential endoscopic complication.

Comparison of Mucosal, Subcutaneous and Intraperitoneal Routes of Rat Leptospira Infection

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Zilber, Anne-Laure; Belli, Patrick; Grezel, Delphine; Artois, Marc; Kodjo, Angeli; Djelouadji, Zoheira

2016-01-01

Leptospirosis is a zoonosis found worldwide that is caused by a spirochete. The main reservoirs of Leptospira, which presents an asymptomatic infection, are wild rodents, including the brown rat (Rattus norvegicus). Experimental studies of the mechanisms of its renal colonization in rats have previously used an intraperitoneal inoculation route. However, knowledge of rat-rat transmission requires the use of a natural route of inoculation, such as a mucosal or subcutaneous route. We investigated for the first time the effects of subcutaneous and mucosal inoculation routes compared to the reference intraperitoneal route during Leptospira infection in adult rats. Infection characteristics were studied using Leptospira renal isolation, serology, and molecular and histological analyses. Leptospira infection was asymptomatic using each inoculation route, and caused similar antibody production regardless of renal colonization. The observed renal colonization rates were 8 out of 8 rats, 5 out of 8 rats and 1 out of 8 rats for the intraperitoneal, mucosal and subcutaneous inoculation routes, respectively. Thus, among the natural infection routes studied, mucosal inoculation was more efficient for renal colonization associated with urinary excretion than the subcutaneous route and induced a slower-progressing infection than the intraperitoneal route. These results can facilitate understanding of the infection modalities in rats, unlike the epidemiological studies conducted in wild rats. Future studies of other natural inoculation routes in rat models will increase our knowledge of rat-rat disease transmission and allow the investigation of infection kinetics. PMID:27031867

Mucosal Healing and Risk of Lymphoproliferative Malignancy in Celiac Disease

Science.gov (United States)

Lebwohl, Benjamin; Granath, Fredrik; Ekbom, Anders; Smedby, Karin Ekström; Murray, Joseph A.; Neugut, Alfred I.; Green, Peter HR; Ludvigsson, Jonas F.

2013-01-01

Background Celiac disease (CD) is associated with an increased risk of lymphoproliferative malignancy (LPM). It is unknown whether this risk is affected by the results of the follow-up intestinal biopsy, performed to document mucosal healing. Objective To examine the association between mucosal healing in CD and later LPM. Design Population-based cohort study Setting We identified patients with CD from all of Sweden’s 28 pathology departments. Patients Individuals with CD who had a follow-up biopsy after initial diagnosis. Measurements We compared the risk of LPM to that of the general population using expected rates; and through Cox regression we compared the rate of LPM in those with persistent villous atrophy to those with mucosal healing. Results Among 7,625 patients with CD and a follow-up biopsy, persistent villous atrophy was present in 3,308 (43%). The overall risk of LPM was increased compared to the general population (Standardized incidence ratio, SIR 2.81; 95%CI 2.10–3.67), but this increase was greater among those with persistent villous atrophy (SIR 3.78; 95%CI 2.71–5.12) as compared to those with mucosal healing (SIR 1.50; 95%CI 0.77–2.62). Persistent villous atrophy compared to mucosal healing was associated with an increased risk of LPM (Hazard ratio, HR 2.26; 95%CI 1.18–4.34). We found an increased risk of T cell lymphoma (HR 3.51; 95%CI 0.75–16.34), but no excess risk of B cell lymphoma (HR 0.97; 95%CI 0.21–4.49). Limitation We had no data on dietary compliance. Conclusions The increased LPM risk in CD is associated with the results of the follow-up biopsy, with a higher risk among those with persistent villous atrophy. Follow-up biopsy may be a means to effectively stratify CD patients regarding subsequent LPM risk. Primary funding source the National Center for Advancing Translational Sciences, National Institutes of Health, The American Scandinavian Foundation, the Celiac Sprue Association, Örebro University Hospital, Karolinska

Protective Effect of Repeatedly Preadministered Brazilian Propolis Ethanol Extract against Stress-Induced Gastric Mucosal Lesions in Rats

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Tadashi Nakamura

2014-01-01

Full Text Available The present study was conducted to clarify the protective effect of Brazilian propolis ethanol extract (BPEE against stress-induced gastric mucosal lesions in rats. The protective effect of BPEE against gastric mucosal lesions in male Wistar rats exposed to water-immersion restraint stress (WIRS for 6 h was compared between its repeated preadministration (50 mg/kg/day, 7 days and its single preadministration (50 mg/kg. The repeated BPEE preadministration attenuated WIRS-induced gastric mucosal lesions and gastric mucosal oxidative stress more largely than the single BPEE preadministration. In addition, the repeated BPEE preadministration attenuated neutrophil infiltration in the gastric mucosa of rats exposed to WIRS. The protective effect of the repeated preadministration of BPEE against WIRS-induced gastric mucosal lesions was similar to that of a single preadministration of vitamin E (250 mg/kg in terms of the extent and manner of protection. From these findings, it is concluded that BPEE preadministered in a repeated manner protects against gastric mucosal lesions in rats exposed to WIRS more effectively than BPEE preadministered in a single manner possibly through its antioxidant and anti-inflammatory actions.

Digital gastrointestinal imaging: Effect of pixel size of subtle mucosal abnormalities on observer performance

International Nuclear Information System (INIS)

Kastan, D.J.; Ackerman, L.V.; Feczko, P.J.

1986-01-01

Radiographs from double-contrast colon examinations demonstrating subtle mucosal changes of inflammatory bowel disease and radiographs showing normal colon were digitized (0.1-mm, 0.2-mm, 0.4-mm and 0.8-mm pixel sizes). Ten radiologists interpreted the laser-printed images. Receiver operating characteristic analysis was performed. The results indicated that (1) the sensitivity of radiography in detecting subtle mucosal abnormalities improved as resolution improved; (2) more experience readers performed remarkably well even at the poorer levels of resolution; (3) the resolution necessary for evaluating the colonic mucosa was less than expected; and (4) at low noise levels, conventional television fluoroscopy may have sufficient resolution for mucosal evaluation

Effects of sucralflate on mucositis during and following radiotherapy of malignancies in the head and neck region. A double-blind placebo-controlled study

International Nuclear Information System (INIS)

Franzen, L.; Henriksson, R.; Littbrand, B.; Zackrisson, B.

1995-01-01

Radiotherapy of head and neck malignancies is accompanied by oral discomforts, such as epithelitis, pain and functional impairment. This can lead to chronic sequalae with subjective distress such as loss of taste and xerostomia and pronounced decrease in quality of life. Thus, the need to reduce the mucosal damage following radiotherapy is obvious. Therefore, we investigated the possible ability of sucralfate, an aluminium hydroxide complex of sulphated sucrose used in the treatment of gastric ulcer, in preventing oral discomfort in patients treated with curative intent for malignancies in the head and neck region. The study was double-blind, placebo-controlled and randomized and included 50 consecutive patients. The study demonstrated that the proportion of patients with severe mucosal reactions was significantly lower in the sucralfate group than in the placebo group. (orig.)

Characteristic patients with oral mucositis receiving 5-FU chemotherapy at Hasan Sadikin Hospital Bandung

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Syarifah Fatimah

2016-11-01

Full Text Available Introduction: Oral mucositis is an inflammatory reaction of oral mucous membrane that often appears in cancer patients due to the chemotherapeutic agents, such as 5-fluorouracil (5-FU. The aim of this study was to describe the characteristic patients who receive 5-FU and had oral mucositis. Methods: This study was conducted on 41 patients with cancer receiving 5-FU chemotherapy at Dr Hasan Sadikin Hospital Bandung. The data was retrieved through interviews to find out patient’s characteristic; nutritional status examination by using body mass index measurement; and oral examination. Severity level was determined by using National Cancer Institute’s Common Toxicity Criteria scale, and the level of pain was measured by Numeric Pain Intensity Rating scale. Results: This research have shown 60,98% patient with cancer had received 5-FU chemotherapy treatment, and 44% with poor nutritional status (underweight. Oral mucositis was only found at non-keratinised mucous. The finding of this study was patients that receiving 5-FU chemotherapy treatment diagnosed with oral mucositis was on the 1st stadium (52% and the 2nd stadium (44% with the level of pain was on the mild level (48% and moderate level (32%.Conclusion: Oral mucositis was found on patients with cancer that received 5-FU chemotherapy with a variety of characteristics, nutritional statuses, locations, levels of severity and pain.

The mucosal firewalls against commensal intestinal microbes.

Science.gov (United States)

Macpherson, Andrew J; Slack, Emma; Geuking, Markus B; McCoy, Kathy D

2009-07-01

Mammals coexist with an extremely dense microbiota in the lower intestine. Despite the constant challenge of small numbers of microbes penetrating the intestinal surface epithelium, it is very unusual for these organisms to cause disease. In this review article, we present the different mucosal firewalls that contain and allow mutualism with the intestinal microbiota.

Role of DNA damage and repair as predeterminant factor in the development of radiotherapy induced acute adverse reactions

International Nuclear Information System (INIS)

Satish Rao, B.S.; Kamalesh, D.M.; Goutham, H.V.; Donald, J.F.; Sharan, Krishna; Vadhiraja, B.M.; Satyamoorthy, K.

2013-01-01

Radiotherapy induced normal tissue toxicity is one of the major limitations for the compromised the therapeutic outcome and also worsens the quality of life of survivors. Further, the clinical experience demonstrated inter-individual variability with respect to their normal tissue toxicity. Therefore, the discovery of contributing key factors of variability or predicting the risk of developing acute reactions before the initiation of radiation therapy may serve as a powerful predictive biomarker for individualizing radiotherapy, anticipating increased therapeutic effect. DNA double-strand break (DSB) induction and its repair in lymphocytes of head-and-neck and breast cancer patients undergoing chemoradiation or radiation therapy alone were analyzed by performing γ-H2AX foci, neutral comet and a modified neutral filter elution assays. Treatment induced normal tissue adverse reactions (acute skin reaction, oral mucositis) were assessed by the criteria of Radiation Therapy Oncology Group. The residual damage (RD) at 6 hrs of post irradiation was used as parameters to measure cellular radiosensitivity and for its correlation with radiotherapy induced acute reactions in patients stratified as non-over responders (NOR) and over responders (OR). A large inter-individual variation in the radiosensitivity was observed in the cancer individuals with respect to their lymphocyte radiosensitivity and the severity of normal tissue adverse reactions. There was a significant difference in RD (p<0.05) between the NOR and OR in breast cancer radiotherapy. Further, the increased normal tissue toxicity such as oral mucositis and skin reactions was associated with the reduced DSB repair (p<0.05) in head-and-neck cancer patients. The percentile analysis was found to be useful in predicting the OR amongst the head-and-neck cancer patients. Our results suggest that γ-H2AX analysis may have its potential to be developed into a clinically useful predictive assay for identifying the

Mucosal immunity to poliovirus.

Science.gov (United States)

Ogra, Pearay L; Okayasu, Hiromasa; Czerkinsky, Cecil; Sutter, Roland W

2011-10-01

The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis.

Mucosal expression of basic fibroblastic growth factor, Syndecan 1 and tumor necrosis factor-alpha in diverticular disease of the colon: a case-control study.

Science.gov (United States)

Tursi, A; Elisei, W; Brandimarte, G; Giorgetti, G M; Inchingolo, C D; Nenna, R; Picchio, M; Giorgio, F; Ierardi, E

2012-09-01

Inflammation may be detected in diverticular disease (DD), and fibrosis may also develop. We assessed the mucosal expression of bFGF, SD1, and TNF-α in DD according to the severity of the disease. Moreover, we assessed the response to therapy of these cytokines in acute uncomplicated diverticulitis (AUD). Fifteen patients affected by AUD and seven patients affected by symptomatic uncomplicated diverticular disease (SUDD) were enrolled. Patients with asymptomatic diverticulosis (AD), segmental colitis associated with diverticulosis (SCAD), ulcerative colitis (UC), and healthy subjects (HC) served as control groups. The expression of bFGF, SD1, and TNF-α was significantly higher in diverticulitis than in healthy controls, in diverticulosis, and in uncomplicated diverticular disease. Cytokines were significantly higher in uncomplicated diverticular disease than in healthy controls. Cytokine expression in diverticulitis did not differ significantly from that of ulcerative colitis. After treatment, TNF-α expression dropped significantly. Mucosal TNF-α is overexpressed only in symptomatic DD, while SD1 and bFGF are already overexpressed in AD. Finally, TNF-α but not SD1 or bFGF expression seems to be influenced by the treatment in AUD. © 2012 Blackwell Publishing Ltd.

Short bowel mucosal morphology, proliferation and inflammation at first and repeat STEP procedures.

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Mutanen, Annika; Barrett, Meredith; Feng, Yongjia; Lohi, Jouko; Rabah, Raja; Teitelbaum, Daniel H; Pakarinen, Mikko P

2018-04-17

Although serial transverse enteroplasty (STEP) improves function of dilated short bowel, a significant proportion of patients require repeat surgery. To address underlying reasons for unsuccessful STEP, we compared small intestinal mucosal characteristics between initial and repeat STEP procedures in children with short bowel syndrome (SBS). Fifteen SBS children, who underwent 13 first and 7 repeat STEP procedures with full thickness small bowel samples at median age 1.5 years (IQR 0.7-3.7) were included. The specimens were analyzed histologically for mucosal morphology, inflammation and muscular thickness. Mucosal proliferation and apoptosis was analyzed with MIB1 and Tunel immunohistochemistry. Median small bowel length increased 42% by initial STEP and 13% by repeat STEP (p=0.05), while enteral caloric intake increased from 6% to 36% (p=0.07) during 14 (12-42) months between the procedures. Abnormal mucosal inflammation was frequently observed both at initial (69%) and additional STEP (86%, p=0.52) surgery. Villus height, crypt depth, enterocyte proliferation and apoptosis as well as muscular thickness were comparable at first and repeat STEP (p>0.05 for all). Patients, who required repeat STEP tended to be younger (p=0.057) with less apoptotic crypt cells (p=0.031) at first STEP. Absence of ileocecal valve associated with increased intraepithelial leukocyte count and reduced crypt cell proliferation index (pSTEP. Persistent inflammation and lacking mucosal growth may contribute to continuing bowel dysfunction in SBS children, who require repeat STEP procedure, especially after removal of the ileocecal valve. Level IV, retrospective study. Copyright © 2018 Elsevier Inc. All rights reserved.

Salivary Cytokine Levels and Oral Mucositis in Head and Neck Cancer Patients Treated With Chemotherapy and Radiation Therapy

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Bossi, Paolo, E-mail: Paolo.bossi@istitutotumori.mi.it [Department of Head and Neck Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Bergamini, Cristiana [Department of Head and Neck Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Miceli, Rosalba [Clinical Epidemiology and Trial Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Cova, Agata [Unity of Immunotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Orlandi, Ester [Radiotherapy 2 Unity, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Resteghini, Carlo; Locati, Laura; Alfieri, Salvatore; Imbimbo, Martina; Granata, Roberta [Department of Head and Neck Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Mariani, Luigi [Clinical Epidemiology and Trial Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Iacovelli, Nicola Alessandro [Radiotherapy 2 Unity, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Huber, Veronica [Unity of Immunotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Cavallo, Anna [Department of Physics and Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Licitra, Lisa [Department of Head and Neck Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Rivoltini, Licia [Unity of Immunotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy)

2016-12-01

Purpose: We assessed the presence of salivary cytokines, their modulation during chemoradiation therapy (CTRT), and their association with oral mucositis severity in patients with head and neck cancer (HNC). Methods and Materials: The present prospective observational study enrolled 55 patients with locally advanced HNC requiring CTRT. We also studied 10 healthy volunteers and 10 patients with other cancers. The salivary levels of 13 cytokines were analyzed. We constructed a cytokine predictive score of oral mucositis severity. Results: The baseline salivary cytokine levels were not associated with the severity of treatment-induced oral mucositis. The cytokine levels overall increased during treatment, especially in patients with worse mucositis. In particular, on univariable analysis, an increase of interleukin (IL)-1β (area under the curve [AUC] 0.733; P=.009), IL-6 (AUC 0.746; P=.005), and tumor necrosis factor-α (AUC 0.710; P=.005) at the third week of treatment was significantly associated with the development of severe oral mucositis. On multivariable analysis, the predictive score based on the IL-1β and IL-6 changes from baseline to week 3 was an early strong predictor of higher grade oral mucositis. Conclusions: The treatment of HNC patients with concurrent CTRT induces a significant increase in the salivary levels of IL-1β, IL-6, and tumor necrosis factor-α, all positively associated with the severity of mucosal toxicity. A greater increase of IL-1β and IL-6 3 weeks after treatment initiation is predictive of worse oral mucositis, representing a potential tool for the early identification of patients at risk.

Unprecedented Simultaneous and Rapid Reversal of Oral and Alimentary Mucositis using Polymerized Cross Linked Sucralfate: Two Case Reports

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Ricky Wayne McCullough

2014-12-01

Full Text Available The quest to optimize cancer treatments and to extend cancer survival is consistently thwarted by an unavoidable but expected consequence – mucositis of the oral and gastrointestinal tract. Prior to market approval our Translational Medicine Research Center clinically tested polymerized cross-linked sucralfate (PCLS on a cancer treatment patient who underwent 6 weeks chemo-radiation for squamous cell carcinoma of head and neck (SCCHN. This late-breaking Phase 4 observational experience from our Center discusses the post-approval use of PCLS (ProThelial™ in 2 patients: one with advanced oroesophageal mucositis from radiation and cetuximab for SCCHN and another patient with oral, esophageal, small and large bowel mucositis caused by Folfirinox (5- fluorouracil, folinic acid, irinotecan and oxaliplatin for inoperable metastatic pancreatic adenocarcinoma. Standard potency sucralfate is not recommended in the mucositis management guidelines of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC\\ISOO. This higher potency sucralfate, PCLS, used in these patients exhibited an unprecedented simultaneously and rapid (2-3 day reversal of oroesophageal mucositis and alimentary mucositis. These results raise the novel proposition of single-agent management of both oral and alimentary mucositis caused by radiation, classic and newer bioengineered oncolytics. If validated, PCLS should energize discussions regarding mucositis clinical guidelines. The experience of these patients has been accepted for presentation in the upcoming 2014 International Symposium of the MASCC\\ISOO. Distinctions between standard potency sucralfate and PCLS are reviewed and modes of action explanations are offered.

A characterization of anaerobic colonization and associated mucosal adaptations in the undiseased ileal pouch.

LENUS (Irish Health Repository)

Smith, F M

2012-02-03

INTRODUCTION: The resolution of pouchitis with metronidazole points to an anaerobic aetiology. Pouchitis is mainly seen in patients with ulcerative colitis pouches (UCP). We have recently found that sulphate reducing bacteria (SRB), a species of strict anaerobe, colonize UCP exclusively. Herein, we aimed to correlate levels of different bacterial species (including SRB) with mucosal inflammation and morphology. METHODS: Following ethical approval, fresh faecal samples and mucosal biopsies were taken from 9 patients with UCP and 5 patients with familial adenomatous polyposis pouches (FAPP). For the purposes of comparison, faecal samples and mucosal biopsies were also taken from the stomas of 7 of the 9 patients with UC (UCS). Colonization by four types of strict anaerobes (SRB, Clostridium perfringens, Bifidobacteria and Bacteroides) as well as by three types of facultative anaerobes (Enterococci, Coliforms and Lactobacilli) was evaluated. Inflammatory scores and mucosal morphology were assessed histologically in a blinded fashion by a pathologist. RESULTS: In general, strict anaerobes predominated over facultative in the UCP (P = 0.041). SRB were present in UCP exclusively. Even after exclusion of SRB from total bacterial counts, strict anaerobes still predominated. In the UCS, facultative anaerobes predominated. Strict and facultative anaerobes were present at similar levels in the FAPP. Enterococci were present at significantly reduced levels in the UCP when compared with the UCS (P = 0.031). When levels of SRB and other anaerobic species were individually correlated with mucosal inflammation and morphology, no trends were observed. CONCLUSION: We have previously identified that SRB exclusively colonize UCP. In addition we have now identified a novel increase in the strict\\/facultative anaerobic ratio within the UCP compared to UCS. These stark differences in bacterial colonization, however, appear to have limited impact on mucosal inflammation or morphology.

Systematic review of oral cryotherapy for management of oral mucositis caused by cancer therapy.

Science.gov (United States)

Peterson, Douglas E; Ohrn, Kerstin; Bowen, Joanne; Fliedner, Monica; Lees, Judith; Loprinzi, Charles; Mori, Takehiko; Osaguona, Anthony; Weikel, Dianna S; Elad, Sharon; Lalla, Rajesh V

2013-01-01

This systematic review analyzed the strength of the literature and defined clinical practice guidelines for the use of oral cryotherapy for the prevention and/or treatment of oral mucositis caused by cancer therapy. A systematic review on relevant oral cryotherapy studies indexed prior to 31 December 2010 was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using OVID/MEDLINE, with publications selected for review based on defined inclusion and exclusion criteria. Findings from the reviewed studies were integrated into guidelines based on the overall level of evidence for each intervention. Guidelines were classified into three types: recommendation, suggestion, or no guideline possible. Twenty-two clinical studies and two meta-analyses were analyzed. Results were compared with the MASCC/ISOO guidelines published in 2007. The recommendation for the use of oral cryotherapy to prevent oral mucositis in patients receiving bolus fluorouracil (5-FU) was maintained, in agreement with the 2007 guidelines. A suggestion for use of oral cryotherapy to prevent oral mucositis in patients receiving high-dose melphalan as conditioning regimen with or without total body irradiation for HCST was revised from the 2007 guidelines. No guideline was possible for any other intervention, due to insufficient evidence. The evidence continues to support the use of oral cryotherapy for prevention of oral mucositis in patients receiving bolus 5-FU chemotherapy or high-dose melphalan. This intervention is consistent with the MASCC/ISOO guidelines published in 2007. The literature is limited by the fact that utilization of a double-blind study design is not feasible. Future studies that compare efficacy of oral cryotherapy with other mucositis agents in patients receiving chemotherapy with relatively short plasma half-lives would be useful.

Alpha-Toxin Promotes Mucosal Biofilm Formation by Staphylococcus aureus

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Michele J Anderson

2012-05-01

Full Text Available Staphylococcus aureus causes numerous diseases in humans ranging from the mild skin infections to serious, life-threatening, superantigen-mediated Toxic Shock Syndrome (TSS. S. aureus may also be asymptomatically carried in the anterior nares, vagina or on the skin, which serve as reservoirs for infection. Pulsed-field gel electrophoresis clonal type USA200 is the most widely disseminated colonizer and a major cause of TSS. Our prior studies indicated that α-toxin was a major epithelial proinflammatory exotoxin produced by TSS S. aureus USA200 isolates. It also facilitated the penetration of TSS Toxin-1 (TSST-1 across vaginal mucosa. However, the majority of menstrual TSS isolates produce low α-toxin due to a nonsense point mutation at codon 113, designated hly, suggesting mucosal adaptation. The aim of this study was to characterize the differences between TSS USA200 strains [high (hla+ and low (hly+ α-toxin producers] in their abilities to infect and disrupt vaginal mucosal tissue. A mucosal model was developed using ex vivo porcine vaginal mucosa, LIVE/DEAD® staining and confocal microscropy to characterize biofilm formation and tissue viability of TSS USA 200 isolates CDC587 and MN8, which contain the α-toxin pseudogene (hly, MNPE (hla+ and MNPE isogenic hla knockout (hlaKO. All TSS strains grew to similar bacterial densities (1-5 x 108 CFU on the mucosa and were proinflammatory over 3 days. However, MNPE formed biofilms with significant reductions in the mucosal viability whereas neither CDC587, MN8 (hly+, or MNPE hlaKO, formed biofilms and were less cytotoxic. The addition of exogenous, purified α-toxin to MNPE hlaKO restored the biofilm phenotype. Our studies suggest α-toxin affects S. aureus phenotypic growth on vaginal mucosa, by promoting tissue disruption and biofilm formation; and α–toxin mutants (hly are not benign colonizers, but rather form a different type of infection, which we have termed high density pathogenic

Management of chronic mucosal otitis media in children

NARCIS (Netherlands)

van der Veen, E.L.

2010-01-01

Chronic mucosal otitis media (COM) is one of the most common infectious diseases in children worldwide. As it causes considerable morbidity and is a major global cause of hearing impairment, establishing its most effective treatment is important. It is generally accepted that antibiotic eardrops

Benzydamine HCl, a new agent for the treatment of radiation mucositis of the oropharynx

International Nuclear Information System (INIS)

Kim, J.H.; Chu, F.C.; Lakshmi, V.; Houde, R.

1986-01-01

Benzydamine HCl is a new nonsteroidal analgesic and anti-inflammatory compound which is not chemically related to local anesthetics such as procaine and xylocaine. A double-blind, randomized clinical investigation was carried out to determine the analgesic and anti-inflammatory effectiveness of benzydamine HCl in patients with radiation-induced mucositis of the oropharynx. Of the 67 patients in the study, 37 were on benzydamine and 30 on placebo. Patients developed radiation mucositis, hyperemia, and throat pain when the total radiation dose reached above 2000 rad over 2 weeks (200 rad per fraction, five treatments per week). Analysis of the data showed that benzydamine HCl used as a rinse/gargle provided a statistically significant and clinically meaningful alleviation of the symptoms of oropharyngeal mucositis. There was also significant improvement in terms of reduction in hyperemia and mucositis in benzydamine group. No systemic side effects associated with benzydamine medication were noted. In view of the relative ineffectiveness of systemic analgesics and topical anesthetics for these conditions, benzydamine HCl promises to be a useful addition to the therapeutic armamentarium

Changes in biochemical parameters of oral fluid in patients during the orthodontic treatment with a bracket system under the action of a developed mucosal gel with probiotic.

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Voronkova, Anna V; Smaglyuk, Lyubov V

2018-01-01

Introduction: Many research studies involving orthodontic patients focus on changes in levels of oral microbiocenosis after bracket placement. Based upon this the objective of the current study was to determine the effect of the developed mucosal gel with probiotics on the biochemical parameters of the oral fluid of patients during the orthodontic treatment with a bracket system. The aim: Aim of our study is to determine the effect of the developed mucosal gel with probiotics on the biochemical parameters of the oral fluid of patients during the orthodontic treatment with a bracket system. Materials and methods: 45 patients at the age of 18-24, with 15 people in each group (control, main and comparison group) were examined. The main group was presented by patients who, in order to prevent dysbiosis of the oral cavity during orthodontic treatment, were prescribed local use of the developed mucosal gel with probiotic. The statistical processing of the results of the study was carried out using methods of variation statistics using the EXCEL program (the standard package of Microsoft Office). Results: According to the results of biochemical studies, it was found that the use of orthodontic treatment of mucosal gel with probiotic in patients with crowded teeth contributes to the strengthening of antioxidant protection, an increase in nonspecific resistance, decrease in inflammation and normalization of microbiocenosis of the oral cavity. Conclusion: These studies indicated that the use of the developed mucosal gel with probiotic in patients with maxillofacial anomalies from the first day after fixation, as indicated by the level of biochemical markers of inflammation.

Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

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Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

1989-01-01

1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reactio...

Iron, lead, and cobalt absorption: similarities and dissimilarities

International Nuclear Information System (INIS)

Barton, J.C.; Conrad, M.E.; Holland, R.

1981-01-01

Using isolated intestinal segments in rats, the absorption of iron, lead, and cobalt was increased in iron deficiency and decreased in iron loading. Similarly, the absorption of these metals was decreased in transfusional erythocytosis, after intravenous iron injection and after parenteral endotoxin injection. Acute bleeding or abbreviated intervals of dietary iron deprivation resulted in increased iron absorption from isolated intestinal segments and in intact animals, while the absorption of lead and cobalt was unaffected. These results suggest that the specificity of the mucosal metal absorptive mechanism is either selectively enhanced for iron absorption by phlebotomy or brief periods of dietary iron deprivation, or that two or more mucosal pathways for iron absorption may exist

Use of inactivated E.Coli enterotoxins to enhance respiratory mucosal adjuvanticity during vaccination in swine

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In order to augment responses to respiratory vaccines in swine, various adjuvants were intranasally co-administered with an antigen to pigs. Detoxified E. coli enterotoxins LTK63 and LTR72 enhanced mucosal and systemic immunity to the model peptide, exhibiting their efficacy as mucosal adjuvants for...

Macrophage expression in acute radiation colitis in rats

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Tadami, Tokuma; Shichijo, Kazuko; Matsuu, Mutsumi; Niino, Daisuke; Nakayama, Toshiyuki; Nakashima, Masahiro; Sekine, Ichiro

2003-01-01

Although radiation therapy is important in the treatment of tumors in pelvic and abdominal region, it may cause radiation injury as a side effect. But there is no effective way of preventing or curing the damages. The mechanism of acute radiation colitis has not been elucidated yet. Our previous reports have revealed that X-ray irradiation induce apoptosis of epithelial stem cells in colon. Then a hypothesis of the radiation colitis can be put forward, DNA damage by irradiation, apoptosis of mucosal epithelial stem cells and degeneration of epithelial gland structure, macrophages phagocyte the debris, being activated and secreting various inflammatory cytokines, infiltration of inflammatory cells. Several recent reports show that macrophages may play an important role in the process of inflammatory bowel diseases such ulcerative colitis or Crohn's disease. We studied radiation colitis using rat animal models. Male Wister rats were irradiated by a single fraction dose of 22.5 Gy X-ray at laparotomy, shielding except for an approximately 2.5 cm length of rectum. Histological changes and macrophage accumulation in the rectum mucosa were evaluated by immunohistochemistry and western blot method with the specimens which were taken on the 1, 2, 3, 4, 5, 6, 7, 10, and 14th day after irradiation. Severe macrophage accumulation in the lamina propria of the rectum was observed on the 5th day. At the same time, severe destruction of mucosal structure and inflammatory cells infiltration were also observed. Based on the potent pro-inflammatory cytokine producing effects of macrophage in rat and the increased expression in inflammatory bowel disease patients, speculate that intervention in the macrophage-cytokine network could form a future target for the treatment of acute radiation colitis. (author)

Postconditioning attenuates acute intestinal ischemia–reperfusion injury

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Ilker Sengul

2013-03-01

Full Text Available The aim of this study was to test the hypothesis that postconditioning (POC would reduce the detrimental effects of the acute intestinal ischemia–reperfusion (I/R compared to those of the abrupt onset of reperfusion. POC has a protective effect on intestinal I/R injury by inhibiting events in the early minutes of reperfusion in rats. Twenty-four Wistar–Albino rats were subjected to the occlusion of superior mesenteric artery for 30 minutes, then reperfused for 120 minutes, and randomized to the four different modalities of POC: (1 control (no intervention; (2 POC-3 (three cycles of 10 seconds of reperfusion–reocclusion, 1 minute total intervention; (3 POC-6 (six cycles of 10 seconds of reperfusion–reocclusion, 2 minutes total intervention; and (4 sham operation (laparotomy only. The arterial blood samples [0.3 mL total creatine kinase (CK and 0.6 mL malondialdehyde (MDA] and the intestinal mucosal MDA were collected from each after reperfusion. POC, especially POC-6, was effective in attenuating postischemic pathology by decreasing the intestinal tissue MDA levels, serum total CK activity, inflammation, and total histopathological injury scores. POC exerted a protective effect on the intestinal mucosa by reducing the mesenteric oxidant generation, lipid peroxidation, and neutrophil accumulation. The six-cycle algorithm demonstrated the best protection.

Antioxidant capacity of calendula officinalis flowers extract and prevention of radiation induced oropharyngeal mucositis in patients with head and neck cancers: a randomized controlled clinical study.

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Babaee, Neda; Moslemi, Dariush; Khalilpour, Mohammad; Vejdani, Fatemeh; Moghadamnia, Yasaman; Bijani, Ali; Baradaran, Mahmoud; Kazemi, Mohammad Taghi; Khalilpour, Asieh; Pouramir, Mahdi; Moghadamnia, Ali Akbar

2013-03-07

This study was designed to determine the effect of Calendula officinalis flowers extract mouthwash as oral gel on radiation-induced oropharyngeal mucositis (OM) in patients with head-and-neck cancer. Forty patients with neck and head cancers under radiotherapy or concurrent chemoradiotherapy protocols were randomly assigned to receive either 2% calendula extract mouthwash or placebo (20 patients in each group). Patients were treated with telecobalt radiotherapy at conventional fractionation (200 cGy/fraction, five fractions weekly, 30-35 fractions within 4-7 weeks). The oropharyngeal mucositis was evaluated by two clinical investigators (a radiation oncologist and a dentist), using the oral mucositis assessment scale (OMAS). Trying to find out the possible mechanism of action of the treatment, total antioxidant, polyphenol and flavonoid contents, and quercetin concentration of the mouth wash were measured. Calendula mouthwash significantly decreased the intensity of OM compared to placebo at week 2 (score: 5.5 vs. 6.8, p = 0.019), week 3 (score: 8.25 vs. 10.95, p antioxidant, polyphenol and flavonoid contents and quercetin concentration of the 2% extract were 2353.4 ± 56.5 μM, 313.40 ± 6.52 mg/g, 76.66 ± 23.24 mg/g, and 19.41 ± 4.34 mg/l, respectively. Calendula extract gel could be effective on decreasing the intensity of radiotherapy- induced OM during the treatment and antioxidant capacity may be partly responsible for the effect.

Management of oral mucositis in patients with cancer.

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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 increase the need for total parenteral nutrition and opioid analgesics, prolong hospital stays, increase the risk of infection, and greatly diminish a patient's quality of life. Nurses play a critical role in

Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells.

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Jason A Neidleman

2017-02-01

Full Text Available Understanding early events of HIV transmission within mucosal tissues is vital for developing effective prevention strategies. Here, we report that primary stromal fibroblasts isolated from endometrium, cervix, foreskin, male urethra, and intestines significantly increase HIV infection of CD4+ T cells-by up to 37-fold for R5-tropic HIV and 100-fold for X4-tropic HIV-without themselves becoming infected. Fibroblasts were more efficient than dendritic cells at trans-infection and mediate this response in the absence of the DC-SIGN and Siglec-1 receptors. In comparison, mucosal epithelial cells secrete antivirals and inhibit HIV infection. These data suggest that breaches in the epithelium allow external or luminal HIV to escape an antiviral environment to access the infection-favorable environment of the stromal fibroblasts, and suggest that resident fibroblasts have a central, but previously unrecognized, role in HIV acquisition at mucosal sites. Inhibiting fibroblast-mediated enhancement of HIV infection should be considered as a novel prevention strategy.

Basis for the Age-related Decline in Intestinal Mucosal Immunity

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Douglas L. Schmucker

2003-01-01

Full Text Available The elderly are characterized by mucosal immunosenescence and high rates of morbidity and mortality associated with infectious diseases of the intestinal tract. Little is known about how the differentiation of immunoglobulin A (IgA plasma cells in Peyer's patches (PPs and their subsequent homing to the small intestinal lamina propria (LP is affected by aging. Quantitative immunohistochemical analyses demonstrated a 2-fold increase in the number of IgA+ cells in the PPs, coupled with significant declines in the numbers of IgA+ and antibody-positive cells in the intestinal LP of senescent rats compared to young adult animals. These data suggest that aging diminishes the emigration of IgA immunoblasts from these lymphoid aggregates, as well as their migration to the intestinal LP. Flow cytometry and lymphocyte adoptive transfer studies showed 3- to 4-fold age-related declines in the homing of antibody-containing cells and mesenteric lymph node lymphocytes to the small intestines of rhesus macaques and rats, respectively. The number of peripheral blood IgA immunoblasts expressing the homing molecule α4β7 declined 30% in senescent rats. This was accompanied by a >17% decrease in the areal density of LP blood vessels staining positive for the cell adhesion molecule MAdCAM-1. Cumulatively, declines in expression of these homing molecules constitute a substantial age-related diminution of IgA immunoblast homing potential. In vitro antibody secretion by LP plasma cells, i.e. antibody secreted per antibody-positive cell, remains unchanged as a function of donor age. Intestinal mucosal immunosenescence is a consequence of reduced homing of IgA plasma cells to the intestinal LP as a result of declines in homing molecule expression.

Ultrasound imaging in children with acute abdominal pain - can it help to decrease the rate of negative appendectomies?

International Nuclear Information System (INIS)

Niedzielski, J.; Miodek, M.; Kucharski, P.; Sokal, J.

2010-01-01

Background: The purpose of this study was to evaluate the accuracy of high-resolution ultrasound (US) with graded compression in the diagnosis of pediatric appendicitis.Material/Methods: The medical records of 664 consecutive children with acute abdominal pain treated between 2007 and 2009 were reviewed retrospectively and analyzed; 408 children (61.4 %) underwent appendectomy and 256 patients were treated conservatively (38.6 %). High-resolution US was performed in 570 out of 664 patients (85.8 %). The US data were verified by intraoperative findings or by clinical follow-up. Results: Out of 664 children, 408 underwent appendectomy and 256 were treated conservatively. US was performed in 570 out of 664 children (85.8 %); in 327/408 children (80.1 %) with AA and in 243/256 children (94.9 %) with negative diagnosis. The sensitivity and specificity for US was 66.6% and 77.4%, respectively. If histopathological diagnosis of catarrhal appendicitis was considered a negative (unnecessary) appendectomy, the sensitivity was 68.6 % (p=0.87), and specificity was 67 % (p=0.29). Positive and negative predictive values of US were 79.9 % and 63.1 %, respectively. After recalculating results, positive predictive value decreased to 59.8% (p=0.036) and negative predictive value increased to 74.8 % (p=0.2). The rate of false negative results was 13.1 % (75/572) and the rate of false positives was 19.2 % (110/572). The negative appendectomy rate was 27.4 % (112/408). Conclusions: High-resolution ultrasonography provides an accurate and specific test for acute appendicitis and is recommended by the authors as an examination of choice in children with acute abdominal pain. (authors)

Gut microbiota utilize immunoglobulin A for mucosal colonization.

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Donaldson, G P; Ladinsky, M S; Yu, K B; Sanders, J G; Yoo, B B; Chou, W-C; Conner, M E; Earl, A M; Knight, R; Bjorkman, P J; Mazmanian, S K

2018-05-18

The immune system responds vigorously to microbial infection while permitting lifelong colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We found that a regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA) in mice. Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis (and other commensal species) to occupy a defined mucosal niche that mediates stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A Novel Peptide to Treat Oral Mucositis Blocks Endothelial and Epithelial Cell Apoptosis

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Wu Xiaoyan; Chen Peili [Department of Medicine, University of Chicago, Chicago, Illinois (United States); Sonis, Stephen T. [Division of Oral Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Biomodels, Watertown, Massachusetts (United States); Lingen, Mark W. [Department of Pathology, University of Chicago, Chicago, Illinois (United States); Berger, Ann [NephRx Corporation, Kalamazoo, Michigan (United States); Toback, F. Gary, E-mail: gtoback@medicine.bsd.uchicago.edu [Department of Medicine, University of Chicago, Chicago, Illinois (United States)

2012-07-01

Purpose: No effective agents currently exist to treat oral mucositis (OM) in patients receiving chemoradiation for the treatment of head-and-neck cancer. We identified a novel 21-amino acid peptide derived from antrum mucosal protein-18 that is cytoprotective, mitogenic, and motogenic in tissue culture and animal models of gastrointestinal epithelial cell injury. We examined whether administration of antrum mucosal protein peptide (AMP-p) could protect against and/or speed recovery from OM. Methods and Materials: OM was induced in established hamster models by a single dose of radiation, fractionated radiation, or fractionated radiation together with cisplatin to simulate conventional treatments of head-and-neck cancer. Results: Daily subcutaneous administration of AMP-p reduced the occurrence of ulceration and accelerated mucosal recovery in all three models. A delay in the onset of erythema after irradiation was observed, suggesting that a protective effect exists even before injury to mucosal epithelial cells occurs. To test this hypothesis, the effects of AMP-p on tumor necrosis factor-{alpha}-induced apoptosis were studied in an endothelial cell line (human dermal microvascular endothelial cells) as well as an epithelial cell line (human adult low-calcium, high-temperature keratinocytes; HaCaT) used to model the oral mucosa. AMP-p treatment, either before or after cell monolayers were exposed to tumor necrosis factor-{alpha}, protected against development of apoptosis in both cell types when assessed by annexin V and propidium iodide staining followed by flow cytometry or ligase-mediated polymerase chain reaction. Conclusions: These observations suggest that the ability of AMP-p to attenuate radiation-induced OM could be attributable, at least in part, to its antiapoptotic activity.

Genetic modification to induce CXCR2 overexpression in mesenchymal stem cells enhances treatment benefits in radiation-induced oral mucositis.

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Shen, Zongshan; Wang, Jiancheng; Huang, Qiting; Shi, Yue; Wei, Zhewei; Zhang, Xiaoran; Qiu, Yuan; Zhang, Min; Wang, Yi; Qin, Wei; Huang, Shuheng; Huang, Yinong; Liu, Xin; Xia, Kai; Zhang, Xinchun; Lin, Zhengmei

2018-02-14

Radiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting. By systematically evaluating the expression patterns of chemokines in radiation/chemical-induced oral mucositis, we found that CXCL2 was highly expressed, whereas cultured MSCs negligibly express the CXCL2 receptor CXCR2. Thus, we explored the potential therapeutic benefits of the transplantation of CXCR 2 -overexpressing MSCs (MSCs CXCR2 ) for mucositis treatment. Indeed, MSCs CXCR2 exhibited enhanced targeting ability to the inflamed mucosa in radiation/chemical-induced oral mucositis mouse models. Furthermore, we found that MSC CXCR2 transplantation accelerated ulcer healing by suppressing the production of pro-inflammatory chemokines and radiogenic reactive oxygen species (ROS). Altogether, these findings indicate that CXCR2 overexpression in MSCs accelerates ulcer healing, providing new insights into cell-based therapy for radiation/chemical-induced oral mucositis.

The Potential Effect of Oral Microbiota in the Prediction of Mucositis During Radiotherapy for Nasopharyngeal Carcinoma

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Xiao-Xia Zhu

2017-04-01

Interpretation: Oral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy.

Successful BNCT for patients with cutaneous and mucosal melanomas. Report of 4 cases

International Nuclear Information System (INIS)

Morita, Norimasa; Hiratsuka, Junichi; Kuwabara, Chiaki; Aihara, Teruhito; Harada, Tamotsu; Imajo, Yoshinari; Ono, Koji; Fukuda, Hiroshi; Kumada, Hiroaki

2006-01-01

Since 2003 we have conducted BNCT clinical trials on melanomas at the Kyoto University Research Reactor (KUR) and Japan Research Reactor No.4 (JRR-4). We report 4 patients given BNCT for malignant melanomas: 2 with superficial spreading types on the heel, 1 with mucosal melanoma in the nasal cavity, and 1 with a melanoma on the vulva and in the vagina. The two cutaneous melanomas and the nasal cavity mucosal melanoma showed a complete response (CR) by 6 months after BNCT. The residual melanoma showed a partial response (PR) by 3 months after treatment and no regrowth since then. Although two patients experienced normal-tissue damage that exceeded the tolerance level, all the participants were cured within a few months of treatment. BNCT was shown to be a promising treatment for mucosal, as well as for cutaneous, melanomas. (author)

Hypersensitivity to acid is associated with impaired esophageal mucosal integrity in patients with gastroesophageal reflux disease with and without esophagitis.

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Weijenborg, Pim W; Smout, André J P M; Verseijden, Caroline; van Veen, Henk A; Verheij, Joanne; de Jonge, Wouter J; Bredenoord, Albert J

2014-08-01

Increased esophageal sensitivity and impaired mucosal integrity have both been described in patients with gastroesophageal reflux disease, but the relationship between hypersensitivity and mucosal integrity is unclear. The aim of the present study was to investigate acid sensitivity in patients with erosive and nonerosive reflux disease and control subjects to determine the relation with functional esophageal mucosal integrity changes as well as to investigate cellular mechanisms of impaired mucosal integrity in these patients. In this prospective experimental study, 12 patients with nonerosive reflux disease, 12 patients with esophagitis grade A or B, and 11 healthy control subjects underwent an acid perfusion test and upper endoscopy. Mucosal integrity was measured during endoscopy by electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance, transepithelial permeability and gene expression of tight junction proteins and filaggrin. Patients with nonerosive reflux disease and esophagitis were more sensitive to acid perfusion compared with control subjects, having a shorter time to perception of heartburn and higher perceived intensity of heartburn. In reflux patients, enhanced acid sensitivity was associated with impairment of in vivo and vitro esophageal mucosal integrity. Mucosal integrity was significantly impaired in patients with esophagitis, displaying higher transepithelial permeability and lower extracellular impedance. Although no significant differences in the expression of tight junction proteins were found in biopsies among patient groups, mucosal integrity parameters in reflux patients correlated negatively with the expression of filaggrin. In conclusion, sensitivity to acid is enhanced in patients with gastroesophageal reflux disease, irrespective of the presence of erosions, and is associated with impaired esophageal mucosal integrity. Mucosal integrity of the esophagus

Oral mucositis in patients treated with chemotherapy for solid tumors: a retrospective analysis of 150 cases

NARCIS (Netherlands)

Raber-Durlacher, J. E.; Weijl, N. I.; Abu Saris, M.; de Koning, B.; Zwinderman, A. H.; Osanto, S.

2000-01-01

The incidence and the severity of chemotherapy-associated oral mucositis were determined in a retrospective analysis of 150 patients with various solid tumors. In addition, possible risk factors for the development of mucositis were identified. Patients were treated with chemotherapeutic regimens

In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

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Hotchkiss, J A; Portereiko, J V; Harkema, J R

1988-12-01

Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

International Nuclear Information System (INIS)

Hotchkiss, J.A.; Portereiko, J.V.; Harkema, J.R.

1988-01-01

Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

Different healing process of esophageal large mucosal defects by endoscopic mucosal dissection between with and without steroid injection in an animal model.

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Nonaka, Kouichi; Miyazawa, Mitsuo; Ban, Shinichi; Aikawa, Masayasu; Akimoto, Naoe; Koyama, Isamu; Kita, Hiroto

2013-04-25

Stricture formation is one of the major complications after endoscopic removal of large superficial squamous cell neoplasms of the esophagus, and local steroid injections have been adopted to prevent it. However, fundamental pathological alterations related to them have not been well analyzed so far. The aim of this study was to analyze the time course of the healing process of esophageal large mucosal defects resulting in stricture formation and its modification by local steroid injection, using an animal model. Esophageal circumferential mucosal defects were created by endoscopic mucosal dissection (ESD) for four pigs. One pig was sacrificed five minutes after the ESD, and other two pigs were followed-up on endoscopy and sacrificed at the time of one week and three weeks after the ESD, respectively. The remaining one pig was followed-up on endoscopy with five times of local steroid injection and sacrificed at the time of eight weeks after the ESD. The esophageal tissues of all pigs were subjected to pathological analyses. For the pigs without steroid injection, the esophageal stricture was completed around three weeks after the ESD on both endoscopy and esophagography. Histopathological examination of the esophageal tissues revealed that spindle-shaped α-smooth muscle actin (SMA)-positive myofibroblasts arranged in a parallel fashion and extending horizontally were identified at the ulcer bed one week after the ESD, and increased contributing to formation of the stenotic luminal ridge covered with the regenerated epithelium three weeks after the ESD. The proper muscle layer of the stricture site was thinned with some myocytes which seemingly showed transition to the myofibroblast layer. By contrast, for the pig with steroid injection, esophageal stricture formation was not evident with limited appearance of the spindle-shaped myofibroblasts, instead, appearance of stellate or polygocal SMA-positive stromal cells arranged haphazardly in the persistent granulation

Dietary Lactobacillus rhamnosus GG Supplementation Improves the Mucosal Barrier Function in the Intestine of Weaned Piglets Challenged by Porcine Rotavirus.

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Xiangbing Mao

Full Text Available Lactobacillus rhamnosus GG (LGG has been regarded as a safe probiotic strain. The aim of this study was to investigate whether dietary LGG supplementation could alleviate diarrhea via improving jejunal mucosal barrier function in the weaned piglets challenged by RV, and further analyze the potential roles for apoptosis of jejunal mucosal cells and intestinal microbiota. A total of 24 crossbred barrows weaned at 21 d of age were assigned randomly to 1 of 2 diets: the basal diet and LGG supplementing diet. On day 11, all pigs were orally infused RV or the sterile essential medium. RV infusion increased the diarrhea rate, increased the RV-Ab, NSP4 and IL-2 concentrations and the Bax mRNA levels of jejunal mucosa (P<0.05, decreased the villus height, villus height: crypt depth, the sIgA, IL-4 and mucin 1 concentrations and the ZO-1, occludin and Bcl-2 mRNA levels of jejunal mucosa (P<0.05, and affected the microbiota of ileum and cecum (P<0.05 in the weaned pigs. Dietary LGG supplementation increased the villus height and villus height: crypt depth, the sIgA, IL-4, mucin 1 and mucin 2 concentrations, and the ZO-1, occludin and Bcl-2 mRNA levels of the jejunal mucosa (P<0.05 reduced the Bax mRNA levels of the jejunal mucosa (P<0.05 in weaned pigs. Furthermore, dietary LGG supplementation alleviated the increase of diarrhea rate in the weaned pigs challenged by RV (P<0.05, and relieve the effect of RV infection on the villus height, crypt depth and the villus height: crypt depth of the jejunal mucosa (P<0.05, the NSP4, sIgA, IL-2, IL-4, mucin 1 and mucin 2 concentrations of jejunal mucosa (P<0.05, the ZO-1, occludin, Bax and Bcl-2 mRNA levels of the jejunal mucosa (P<0.05, and the microbiota of ileum and cecum (P<0.05 in the weaned pigs challenged by RV. These results suggest that supplementing LGG in diets alleviated the diarrhea of weaned piglets challenged by RV via inhibiting the virus multiplication and improving the jejunal mucosal barrier

Vaginal mucosal flap as a sling preservation for the treatment of vaginal exposure of mesh.

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Kim, Sea Young; Park, Jong Yeon; Kim, Han Kwon; Park, Chang Hoo; Kim, Sung Jin; Sung, Gi Teck; Park, Chang Myon

2010-06-01

Tension-free vaginal tape (TVT) procedures are used for the treatment of stress urinary incontinence in women. The procedures with synthetic materials can have a risk of vaginal erosion. We experienced transobturator suburethral sling (TOT) tape-induced vaginal erosion and report the efficacy of a vaginal mucosal covering technique. A total of 560 female patients diagnosed with stress urinary incontinence underwent TOT procedures at our hospital between January 2005 and August 2009. All patients succeeded in follow-ups, among which 8 patients (mean age: 50.5 years) presented with vaginal exposure of the mesh. A vaginal mucosal covering technique was performed under local anesthesia after administration of antibiotics and vaginal wound dressings for 3-4 days. Seven of the 8 patients complained of persistent vaginal discharge postoperatively. Two of the 8 patients complained of dyspareunia of their male partners. The one remaining patient was otherwise asymptomatic, but mesh erosion was discovered at the routine follow-up visit. Six of the 8 patients showed complete mucosal covering of the mesh after the operation (mean follow-up period: 16 moths). Vaginal mucosal erosion recurred in 2 patients, and the mesh was then partially removed. One patient had recurrent stress urinary incontinence. Vaginal mucosal covering as a sling preservation with continued patient continence may be a feasible and effective option for the treatment of vaginal exposure of mesh after TOT tape procedures.

Evaluation of the effect of cryotherapy in preventing oral mucositis associated with chemotherapy - a randomized controlled trial.

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Katrancı, Nilgün; Ovayolu, Nimet; Ovayolu, Ozlem; Sevinc, Alper

2012-09-01

The goal of this study was to assess the effect of oral cryotherapy on the development of oral mucositis related to infusion of 5-fluorouracil (5-FU) with leucovorin. This study, a randomized controlled trial with random assignments to the experimental and control groups, was conducted with cancer patients. The study included 60 patients; 30 patients in the study group were instructed to hold ice cubes in their mouth shortly before, during, and shortly after infusion of 5-FU with leucovorin, the 30 patients in the control group received routine care. Oral mucositis in the patients was evaluated at 7, 14, and 21 days after chemotherapy. For analysis of data, chi-square, Fisher's tests were used; p cryotherapy, oral mucositis was not observed (Grade 0) at 7 and 14 days. Similarly, incidence of Grades 1, 2, and 3 oral mucositis in the experimental group was quite a bit lower when compared to the control group (p 0.05). We found that oral cryotherapy has a significant contribution to the protection of oral health by reducing mucositis score according to the WHO mucositis scale, especially on the 7th and 14th days. Nurses' awareness of how cryotherapy can affect patients and options for resolving problems will enable them to provide a higher standard of individualized care. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ghrelin may reduce radiation-induced mucositis and anorexia in head-neck cancer.

Science.gov (United States)

Guney, Yildiz; Ozel Turkcu, Ummuhani; Hicsonmez, Ayse; Nalca Andrieu, Meltem; Kurtman, Cengiz

2007-01-01

Body weight loss is common in cancer patients, and is often associated with poor prognosis, it greatly impairs quality of life (QOL). Radiation therapy (RT) is used in head and neck cancers (HNC) either as a primary treatment or as an adjuvant therapy to surgery. Patients with HNC are most susceptible to malnutrition especially due to anorexia, which is aggravated by RT. Multiple pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), interferon (IFN)-gamma and tumor necrosis factor-alpha(TNF-alpha), have been all associated with the development of both anorexia and oral mucositis. Radiation-induced mucositis occurs in almost all patients, who are treated for HNC, it could also cause weight loss. Ghrelin is a novel 28-amino acid peptide, which up-regulates body weight through appetite control, increase food intake, down-regulate energy expenditure and induces adiposity. Furthermore, ghrelin inhibits pro-inflammatory cytokines such as IL-1alpha, IL-1beta, TNF-alpha which may cause oral mucositis and aneroxia, which are the results of weight loss. Thus weight loss during RT is an early indicator of nutritional decline, we propose that recombinant ghrelin used prophylactically could be useful as an appetite stimulant; and preventive of mucositis because of its anti-inflammatory effect, it might help patients maintain weight over the course of curative RT of the HNC and can improve specific aspects of QOL. This issue warrants further studies.

Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

International Nuclear Information System (INIS)

Okunieff, Paul; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

2006-01-01

Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-α, and lymphotoxin-β) or fibrogenic cytokines (transforming growth factor [TGF]-β) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-α, and lymphotoxin-β) and the fibrogenic cytokine, TGF-β, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy