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

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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.

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

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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

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.

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

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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)

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

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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

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.

[Effect of Kou Yan Qing Ke Li on the prevention and treatment of radiation-induced oral mucositis in patients with nasopharyngeal carcinoma].

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Yun, Gong; Li, Zhang; Zehui, Feng; Xudong, He

2016-02-01

The effect of Kou Yan Qing Ke Li on the prevention and treatment of radiation-induced oral mucositis was investigated in patients with nasopharyngeal carcinoma. Sixty patients with nasopharyngeal carcinoma to be treated with radiotherapy were randomized into two groups: the experimental and control groups. The experimental group (30 patients) was treated with Kou Yan Qing Ke Li during the full course of radiotherapy. The control group (30 patients) rinsed their mouths in the same way with mouth washes containing 0.9% sodium chloride injection, lidocaine, dexamethasone, vitamin B2 and B2 gargle liquid mixture, when grade 2 and above radiation-induced oral mucositis appeared in the process of radiation. Radiation-induced oral mucositis was assessed according to the radiation therapy oncology group criteria. The time of occurrence and degree of pain grade were compared between the two groups. The first onset of oral mucositis in the experimental group (12.40 d ± 2.74 d) was later than that in the control group (9.46 d ± 1.39 d) (t = 5.241, P Qing Ke Li could delay the time of occurrence of radiation-induced oral mucositis, reduce the severity of radiation stomatitis, alleviate the pain of patients, improve the clinical symptoms of patients, and effectively prevent and treat radiation-induced oral mucositis in patients with nasopharyngeal carcinoma.

A pilot study of rebamipide-gargle for chemoradiotherapy-induced mucositis in oral cancer patients

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Yasuda, Takashi; Chiba, Hiroshige; Satomi, Takafumi; Matsuo, Akira; Kaneko, Tadayoshi; Miyamatsu, Hironobu

2008-01-01

Mucositis induced by chemoradiotherapy is one of the serious side effects of cancer therapy for oral cancer. It is caused by toxic free radicals (activated oxygen) produced by these therapeutic modalities. Rebamipide is a novel anti-ulcer drug which possesses various cytoprotective activities such as free radical scavenging, induction of prostaglandin-E and acceleration of ulcer healing. We report the results of a pilot study on rebamipide-gargle for inhibition of mucositis induced by chemo-radiotherapy. The present study was conducted on 13 patients (7 men and 6 women; age range 53-88) with oral cancer. They received radiotherapy (30-60 Gy) for the oro-facial area and chemotherapy (docetaxel: 11 cases; tegafur-uracil (UFT): 1 case; radiotherapy alone: 1 case) with simultaneous addition of 1% rebamipide-gargle treatment (10-15 times/day) to prevent the onset of mucositis. Informed consent was obtained prior to entry. Nine cases had grade 1-2 according to the World Health Organization (WHO) criteria, and 4 patients were classified as grade 3-4. No adverse reactions that could be caused by the rebamipide gargle were observed. These results suggested that rebamipide gargle could inhibit the occurrence of stomatitis induced by chemoradiotherapy. (author)

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

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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.

Anti-inflammatory and healing action of oral gel containing borneol monoterpene in chemotherapy-induced mucositis in rats ( Rattus norvegicus

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Braz José do Nascimento-Júnior

2017-07-01

Full Text Available ABSTRACT The aim of this study was to investigate the effect of gels containing the monoterpene borneol in induced oral mucositis using an animal model. Gels were prepared with borneol at 1.2% and 2.4% (w/w. Oral mucositis was induced by administration of three doses of 5-fluorouracil (30 mg/kg, i.p. and injury with acetic acid (50%, v/v soaked in filter paper applied to right cheek mucosa for 60s. Four subgroups comprising 12 animals each were formed. Six animals from each group were sacrificed at days seven and fourteen after oral mucositis induction. Mucous samples were processed and stained with hematoxylin-eosin and Masson’s Trichrome. The semiquantitative evaluation involved observation of inflammatory parameters. ImageJ® software was used in the quantitative evaluation. For statistical analyses, Two-way ANOVA, followed by Tukey’s post-test (p <0.05, were employed. Borneol 2.4% gel proved effective in the treatment of oral mucositis with statistically significant differences between groups for angiogenesis control, inflammatory cell count reduction and percentage neoformed collagen increase. The confirmation of anti-inflammatory and healing action of borneol in oral mucositis in rats renders it a good marker for predicting this activity for plant extracts rich in this substance.

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.

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

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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.

Effects of recombinant human epidermal growth factor (rhEGF) on experimental radiation-induced oral mucositis in rats

International Nuclear Information System (INIS)

Jung, Kwon Il; Kim, Sun Hee; Moon, Soo Young; Kim, Yeon Wha; Hong, Joon Pio; Lee, Sang Wook; Kim, Hyun Sook

2006-01-01

Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGF-treated groups. Rats were topically applied with rhEGF (15 or 30 μ g/oral cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. rhEGF-treated groups (15 or 30 μ g/day) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous of ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level

Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters.

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Ribeiro, Susana Barbosa; de Araújo, Aurigena Antunes; Araújo Júnior, Raimundo Fernandes de; Brito, Gerly Anne de Castro; Leitão, Renata Carvalho; Barbosa, Maisie Mitchele; Garcia, Vinicius Barreto; Medeiros, Aldo Cunha; Medeiros, Caroline Addison Carvalho Xavier de

2017-01-01

Oral mucositis (OM) is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT) on day 4. On day 10, the animals were euthanized. The experimental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction (qPCR). DEX (0.5 or 1 mg/kg) reduced inflammation and ulceration of the oral mucosa of hamsters. In addition, DEX (1 mg/kg) reduced the cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and macrophage migration inhibitory factor (MIF). DEX (1 mg/kg) also reduced the immunoexpression of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, transforming growth factor (TGF)-β, MIF, Smad 2/3, Smad 2/3 phosphorylated and NFκB p65 in the jugal mucosa. Finally, DEX (1 mg/kg) increased interleukin-1 receptor-associated kinase 3 (IRAK-M), glucocorticoid-induced leucine zipper (GILZ), and mitogen-activated protein kinase (MKP1) gene expression and reduced NFκB p65 and serine threonine kinase (AKt) gene expression, relative to the 5-FU group. Thus, DEX improved OM induced by 5-FU in hamsters.

Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters.

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Susana Barbosa Ribeiro

Full Text Available Oral mucositis (OM is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX on OM induced by 5-fluorouracil (5-FU in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT on day 4. On day 10, the animals were euthanized. The experimental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg. Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction (qPCR. DEX (0.5 or 1 mg/kg reduced inflammation and ulceration of the oral mucosa of hamsters. In addition, DEX (1 mg/kg reduced the cytokine levels of tumor necrosis factor (TNF-α, interleukin (IL-1β, and macrophage migration inhibitory factor (MIF. DEX (1 mg/kg also reduced the immunoexpression of cyclooxygenase (COX-2, matrix metalloproteinase (MMP-2, transforming growth factor (TGF-β, MIF, Smad 2/3, Smad 2/3 phosphorylated and NFκB p65 in the jugal mucosa. Finally, DEX (1 mg/kg increased interleukin-1 receptor-associated kinase 3 (IRAK-M, glucocorticoid-induced leucine zipper (GILZ, and mitogen-activated protein kinase (MKP1 gene expression and reduced NFκB p65 and serine threonine kinase (AKt gene expression, relative to the 5-FU group. Thus, DEX improved OM induced by 5-FU in hamsters.

Prevention and treatment of radiotherapy-induced oral mucositis: a literature review; Prevencao e tratamento da mucosite oral induzida por radioterapia: revisao de literatura

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Albuquerque, Ieda Lessa de Souza [Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ (Brazil). Hospital do Cancer I. Servico de Enfermagem]. E-mail: iedalessa@yahoo.com.br; Camargo, Teresa Caldas [Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ (Brazil). Hospital do Cancer III. Servico de Enfermagem]. E-mail: tcamargo@inca.gov.br

2007-04-15

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)

Therapeutic management of radiation-induced oral mucositis

International Nuclear Information System (INIS)

Doerr, W.; Doelling-Jochem, I.; Baumann, M.; Herrmann, T.

1997-01-01

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) [de

Elemental Diet Accelerates the Recovery From Oral Mucositis and Dermatitis Induced by 5-Fluorouracil Through the Induction of Fibroblast Growth Factor 2.

Science.gov (United States)

Harada, Koji; Ferdous, Tarannum; Kobayashi, Hiroaki; Ueyama, Yoshiya

2018-06-01

Mucositis and dermatitis induced by anticancer agents are common complications of anticancer therapies. In this study, we evaluated the efficacy of Elental (Ajinomoto Pharmaceutical Ltd, Tokyo, Japan), an elemental diet with glutamine in the treatment of 5-fluorouracil (5-FU)-induced oral mucositis and dermatitis in vivo and tried to clarify the underlying mechanisms of its action. Oral mucositis and dermatitis was induced through a combination of 5-FU treatment and mild abrasion of the cheek pouch in hamsters and the dorsal skin in nude mice respectively. These animals received saline, dextrin or Elental suspension (18 kcal/100 g) by a gastric tube daily until sacrifice. Elental reduced oral mucositis and dermatitis more effectively than dextrin in the animal model. Moreover, growth facilitating effects of Elental on HaCaT cells were examined in vitro. MTT assay, wound healing assay, and migration assay revealed that Elental could enhance the growth, invasion, and migration ability of HaCaT. ELISA and Western blotting showed upregulated FGF2 in Elental-treated HaCaT. These findings suggest that Elental is effective for the treatment of mucositis and dermatitis, and may accelerate mucosal and skin recovery through FGF2 induction and reepithelization.

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)

Risk, Outcomes, and Costs of Radiation-Induced Oral Mucositis Among Patients With Head-and-Neck Malignancies

International Nuclear Information System (INIS)

Elting, Linda S.; Cooksley, Catherine D.; Chambers, Mark S.; Garden, Adam S.

2007-01-01

Purpose: To study the risk, outcomes, and costs of radiation-induced oral mucositis (OM) among patients receiving radiotherapy (RT) to head and neck primary cancers. Methods and Materials: A retrospective cohort consisting of 204 consecutive head-and-neck cancer patients who received RT with or without chemotherapy during 2002 was formed; their records were reviewed for clinical and resource use information. Patients who had received prior therapy, had second primary cancers, or received palliative radiation therapy were excluded. The risk of OM was analyzed by multiple variable logistic regression. The cost of care was computed from the provider's perspective in 2006 U.S. dollars and compared among patients with and without OM. Results: Oral mucositis occurred in 91% of patients; in 66% it was severe (Grade 3-4). Oral mucositis was more common among patients with oral cavity or oropharynx primaries (odds ratio [OR], 44.5; 95% confidence interval [CI], 5.2 to >100; p < 0.001), those who received chemotherapy (OR = 7.8; 95% CI, 1.5-41.6; p 0.02), and those who were treated with altered fractionation schedules (OR 6.3; 95% CI, 1.1-35.1; p = 0.03). Patients with OM were significantly more likely to have severe pain (54% vs. 6%; p < 0.001) and a weight loss of ≥5% (60% vs. 17%; p < 0.001). Oral mucositis was associated with an incremental cost of $1700-$6000, depending on the grade. Conclusions: Head-and-neck RT causes OM in virtually all patients. Oral mucositis is associated with severe pain, significant weight loss, increased resource use, and excess cost. Preventive strategies are needed

Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation

International Nuclear Information System (INIS)

Schmidt, M.; Haagen, J.; Noack, R.; Siegemund, A.; Gabriel, P.; Doerr, W.

2014-01-01

Oral mucositis is a severe and dose limiting early side effect of radiotherapy for head-and-neck tumors. This study was initiated to determine the effect of bone marrow- and mesenchymal stem cell transplantation on oral mucositis (mouse tongue model) induced by fractionated irradiation. Daily fractionated irradiation (5 x 3 Gy/week) was given over 1 (days 0-4) or 3 weeks (days 0-4, 7-11, 14-18). Each protocol was terminated (day 7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to generate complete dose-effect curves. The incidence of mucosal ulceration, corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were transplanted intravenously at various time points within these fractionation protocols. Transplantation of 6 x 10 6 , but not of 3 x 10 6 bone marrow stem cells on day -1, +4, +8, +11 or +15 significantly increased the ED 50 values (dose, at which an ulcer is expected in 50% of the mice); transplantation on day +2, in contrast, was ineffective. Mesenchymal stem cell transplantation on day -1, 2 or +8 significantly, and on day +4 marginally increased the ED 50 values. Transplantation of bone marrow or mesenchymal stem cells has the potential to modulate radiation-induced oral mucositis during fractionated radiotherapy. The effect is dependent on the timing of the transplantation. The mechanisms require further investigation. (orig.)

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).

Efficacy of Traditional Chinese Medicine in Treatment and Prophylaxis of Radiation-Induced Oral Mucositis in Patients Receiving Radiotherapy: A Randomized Controlled Trial.

Science.gov (United States)

Wang, Cong; Wang, Peiguo; Ouyang, Huaqiang; Wang, Jing; Sun, Lining; Li, Yanwei; Liu, Dongying; Jiang, Zhansheng; Wang, Bin; Pan, Zhanyu

2018-06-01

To estimate the efficacy of traditional Chinese medicine (Chining decoction, CHIN) for radiation-induced oral mucositis in patients with head and neck cancer. From May 2014 to December 2015, 70 consecutive patients were randomly assigned to receive CHIN (treatment group) or recombinant human epidermal growth factor (rhEGF) spray (control group) at a 1:1 ratio. CHIN was administered to treatment group from the first day of radiotherapy until the completion of radiotherapy. Simultaneously, the rhEGF spray was administered to control group on the oral mucosa of irradiated area. The clinical benefit was determined by gradation of mucositis (Common Terminology Criteria for Adverse Events v4.0), oral pain, and xerostomia (visual analysis scale) for each week during radiotherapy. Body mass index was evaluated before and after radiotherapy. Patients in the treatment group had prominent remission of oral pain and grade of mucositis on each observing point compared with those in control group ( P .05). CHIN presented an obvious advantage in preventing radiation-induced oral mucositis compared with rhEGF spray.

Oral mucosal lesions, microbial changes, and taste disturbances induced by adjuvant chemotherapy in breast cancer patients

DEFF Research Database (Denmark)

Jensen, Siri Beier; Mouridsen, Henning T.; Bergmann, Olav Jonas

2008-01-01

OBJECTIVE: The aim of the study was to examine oral mucosal lesions, microbial changes, and taste disturbances induced by adjuvant chemotherapy (CT) in breast cancer patients during and 1 year after treatment. STUDY DESIGN: Forty-five consecutive breast cancer patients, eligible for adjuvant CT...... with cyclophosphamide, epirubicin or methotrexate, and 5-fluorouracil were followed before, during, 6 months and 1 year after CT and were compared to a control group of 31 breast cancer patients not receiving adjuvant CT. RESULTS: During CT, oral mucosal lesions developed including erythema (n = 10, 22%) and ulceration...... (n = 7, 16%). Five patients (11%) were diagnosed with oral candidosis. Scores of dental bacterial plaque and gingival inflammation increased during CT and the oral microbial composition changed towards a more acidophilic flora. Taste disturbances were experienced by 84% (n = 38) of the patients...

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-07-01

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

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

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

Directory of Open Access Journals (Sweden)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-07-01

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

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)

Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis.

Science.gov (United States)

Chitapanarux, Imjai; Tungkasamit, Tharatorn; Petsuksiri, Janjira; Kannarunimit, Danita; Katanyoo, Kanyarat; Chakkabat, Chakkapong; Setakornnukul, Jiraporn; Wongsrita, Somying; Jirawatwarakul, Naruemon; Lertbusayanukul, Chawalit; Sripan, Patumrat; Traisathit, Patrinee

2018-03-01

The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2 weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value < 0.001). There was no difference in median pain score, (p value = 0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value = 0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms. For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.

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

Science.gov (United States)

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

2015-12-23

where feasible. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random-effects meta-analyses. We reported adverse effects in a narrative format. We included 14 RCTs analysing 1280 participants. The vast majority of participants did not receive radiotherapy to the head and neck, so this review primarily assesses prevention of chemotherapy-induced oral mucositis. All studies were at high risk of bias. The following results are for the main comparison: oral cryotherapy versus control (standard care or no treatment). Adults receiving fluorouracil-based (5FU) chemotherapy for solid cancersOral cryotherapy probably reduces oral mucositis of any severity (RR 0.61, 95% CI 0.52 to 0.72, 5 studies, 444 analysed, moderate quality evidence). In a population where 728 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 444 (95% CI 379 to 524). The number needed to treat to benefit one additional person (NNTB), i.e. to prevent them from developing oral mucositis, is 4 people (95% CI 3 to 5).The results were similar for moderate to severe oral mucositis (RR 0.52, 95% CI 0.41 to 0.65, 5 studies, 444 analysed, moderate quality evidence). NNTB 4 (95% CI 4 to 6).Severe oral mucositis is probably reduced (RR 0.40, 95% CI 0.27 to 0.61, 5 studies, 444 analysed, moderate quality evidence). Where 300 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 120 (95% CI 81 to 183), NNTB 6 (95% CI 5 to 9). Adults receiving high-dose melphalan-based chemotherapy before haematopoietic stem cell transplantation (HSCT)Oral cryotherapy may reduce oral mucositis of any severity (RR 0.59, 95% CI 0.35 to 1.01, 5 studies, 270 analysed, low quality evidence). Where 824 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 486 (95% CI reduced to 289 to increased to 833). The NNTB is 3

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

A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis

Directory of Open Access Journals (Sweden)

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.

Allopurinol gel mitigates radiation-induced mucositis and dermatitis

International Nuclear Information System (INIS)

Kitagawa, Junichi; Nasu, Masanori; Okumura, Hayato; Matsumoto, Shigeji; Shibata, Akihiko; Makino, Kimiko; Terada, Hiroshi

2008-01-01

It has not been verified whether allopurinol application is beneficial in decreasing the severity of radiation-induced oral mucositis and dermatitis. Rats were divided into 4 groups and received 15 Gy irradiation on the left whisker pad. Group 1 received only irradiation. Group 2 was maintained by applying allopurinol/carrageenan-mixed gel (allopurinol gel) continuously from 2 days before to 20 days after irradiation. Group 3 had allopurinol gel applied for 20 days after radiation. Group 4 was maintained by applying carrageenan gel continuously from 2 days before to 20 days after irradiation. The intra oral mucosal and acute skin reactions were assessed daily using mucositis and skin score systems. The escape thresholds for mechanical stimulation to the left whisker pad were measured daily. In addition, the irradiated tissues at the endpoint of this study were compared with naive tissue. Escape threshold in group 2 was significantly higher than that in group 1, and mucositis and skin scores were much improved compared with those of group 1. Concerning escape threshold, mucositis and skin scores in group 3 began to improve 10 days after irradiation. Group 4 showed severe symptoms of mucositis and dermatitis to the same extent as that observed in group 1. In the histopathological study, the tissues of group 1 showed severe inflammatory reactions, compared with those of group 2. These results suggest that allopurinol gel application can mitigate inflammation reactions associated with radiation-induced oral mucositis and dermatitis. (author)

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)

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

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

Science.gov (United States)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2000-09-01

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

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

International Nuclear Information System (INIS)

Katsura, Kouji; Masuko, Noriko; Hayashi, Takafumi; Sugita, Tadashi; Sakai, Kunio; Tsuchida, Emiko; Matsumoto, Yasuo; Sasamoto, Ryuta

2000-01-01

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

The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate.

Science.gov (United States)

Kuduban, Ozan; Mazlumoglu, Muhammed Recai; Kuduban, Selma Denktas; Erhan, Ertugrul; Cetin, Nihal; Kukula, Osman; Yarali, Oguzhan; Cimen, Ferda Keskin; Cankaya, Murat

2016-01-01

To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.

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)

A decrease in vitamin D levels is associated with methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia.

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Oosterom, N; Dirks, N F; Heil, S G; de Jonge, R; Tissing, W J E; Pieters, R; van den Heuvel-Eibrink, M M; Heijboer, A C; Pluijm, S M F

2018-06-19

Children with acute lymphoblastic leukemia (ALL) are at increased risk of vitamin D deficiency, which might make them more susceptible to developing adverse events. Previous studies showed that low vitamin D levels were associated with an increased inflammatory mucosal state and impaired mucosal tissue barriers. We examined the prevalence of vitamin D deficiency and studied the association between vitamin D levels and methotrexate (MTX)-induced oral mucositis in pediatric ALL. We assessed 25-hydroxyvitamin D (25(OH)D 3 ) and 24,25-dihydroxyvitamin D (24,25(OH) 2 D 3 ) levels in 99 children with ALL before the start of 4 × 5 g/m 2 high-dose methotrexate (HD-MTX) (T0) and in 81/99 children after discontinuation of HD-MTX (T1). Two cutoff values for vitamin D deficiency exist: 25(OH)D 3 levels D deficiency occurred in respectively 8% ( 4 years of age as compared to children between 1 and 4 years of age. A decrease in 25(OH)D 3 levels during HD-MTX therapy was associated with developing severe oral mucositis (OR 1.6; 95% CI [1.1-2.4]). 25(OH)D 3 and 24,25(OH) 2 D 3 levels at T0 and the change in 24,25(OH) 2 D 3 levels during therapy were not associated with the development of severe oral mucositis. This study showed that vitamin D deficiency occurs frequently in pediatric ALL patients above the age of 4 years. A decrease in 25(OH)D 3 levels during MTX therapy was observed in children with ALL that developed severe oral mucositis.

Factors associated with acute oral mucosal reaction induced by radiotherapy in head and neck squamous cell carcinoma: A retrospective single-center experience.

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Tao, Zhenchao; Gao, Jin; Qian, Liting; Huang, Yifan; Zhou, Yan; Yang, Liping; He, Jian; Yang, Jing; Wang, Ru; Zhang, Yangyang

2017-12-01

To investigate risk factors for acute oral mucosal reaction during head and neck squamous cell carcinoma radiotherapy.A retrospective study of patients with head and neck squamous cell carcinoma who underwent radiotherapy from November 2013 to May 2016 in Anhui Provincial Cancer Hospital was conducted. Data on the occurrence and severity of acute oral mucositis were extracted from clinical records. Based on the Radiation Therapy Oncology Group (RTOG) grading of acute radiation mucosal injury, the patients were assigned into acute reaction (grades 2-4) and minimum reaction (grades 0-1) groups. Preradiotherapy characteristics and treatment factors were compared between the 2 groups. Multivariate logistic regression analysis was used to detect the independent factors associated with acute oral mucosal reactions.Eighty patients completed radiotherapy during the study period. Oral mucosal reactions were recorded as 25, 31, and 24 cases of grades 1, 2, and 3 injuries, respectively. Significant differences between acute reaction and minimum reaction groups were detected in cancer lymph node (N) staging, smoking and diabetes history, pretreatment platelet count and T-Helper/T-Suppressor lymphocyte (Th/Ts) ratio, concurrent chemotherapy, and total and single irradiation doses.Multivariate analysis showed that N stage, smoking history, single dose parapharyngeal irradiation, and pretreatment platelet count were independent risk factors for acute radiation induced oral mucosal reaction. Smoking history, higher grading of N stage, higher single dose irradiation, and lower preirradiation platelet count may increase the risk and severity of acute radiation oral mucosal reaction in radiotherapy of head and neck cancer patients. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate

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Ozan Kuduban

Full Text Available ABSTRACT Objective: To investigate the effect of HRE (Hippophae rhamnoides extract on oral mucositis induced in rats with MTX. Material and Methods: Experimental animals were divided into groups as healthy (HG, HRE+MTX (HMTX, and control group, which received MTX (MTXC. HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. Results: The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. Conclusion: This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.

Preliminary study on radio-chemo-induced oral mucositis and low level laser therapy

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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.

Base-metal dental casting alloy biocompatibility assessment using a human-derived three-dimensional oral mucosal model.

LENUS (Irish Health Repository)

McGinley, E L

2012-01-01

Nickel-chromium (Ni-Cr) alloys used in fixed prosthodontics have been associated with type IV Ni-induced hypersensitivity. We hypothesised that the full-thickness human-derived oral mucosa model employed for biocompatibility testing of base-metal dental alloys would provide insights into the mechanisms of Ni-induced toxicity. Primary oral keratinocytes and gingival fibroblasts were seeded onto Alloderm™ and maintained until full thickness was achieved prior to Ni-Cr and cobalt-chromium (Co-Cr) alloy disc exposure (2-72 h). Biocompatibility assessment involved histological analyses with cell viability measurements, oxidative stress responses, inflammatory cytokine expression and cellular toxicity analyses. Inductively coupled plasma mass spectrometry analysis determined elemental ion release levels. We detected adverse morphology with significant reductions in cell viability, significant increases in oxidative stress, inflammatory cytokine expression and cellular toxicity for the Ni-Cr alloy-treated oral mucosal models compared with untreated oral mucosal models, and adverse effects were increased for the Ni-Cr alloy that leached the most Ni. Co-Cr demonstrated significantly enhanced biocompatibility compared with Ni-Cr alloy-treated oral mucosal models. The human-derived full-thickness oral mucosal model discriminated between dental alloys and provided insights into the mechanisms of Ni-induced toxicity, highlighting potential clinical relevance.

Oral cryotherapy reduced oral mucositis in patients having cancer treatments.

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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.

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

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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.

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

Chamomile infusion cryotherapy to prevent oral mucositis induced by chemotherapy: a pilot study.

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Dos Reis, Paula Elaine Diniz; Ciol, Marcia A; de Melo, Nilce Santos; Figueiredo, Paulo Tadeu de Souza; Leite, André Ferreira; Manzi, Natália de Melo

2016-10-01

The aim of this study is to compare cryotherapy made only with water and cryotherapy made with chamomile infusion for prevention and reduction of intensity of oral mucositis in patients with cancer receiving 5-fluorouracil and leucovorin. This is a randomized pilot study with two groups: cryotherapy made only with water (control group, n = 18) and cryotherapy made with chamomile infusion (chamomile group, n = 20). Both groups were instructed to swish the ice around in their oral cavity for at least 30 min during chemotherapy. Assessment of oral mucosa occurred on days 8, 15, and 22 after the first day of chemotherapy. Fifty percent of the patients in the control and 30 % in the chamomile group developed oral mucositis. Mouth pain score was higher in patients in the control group on all evaluations (p = 0.02 for day 8, p = 0.09 for day 15, and p = 0.14 for day 22). Patients in the chamomile group never developed mucositis with grade 2 or higher. Presence of ulceration was statistically significant on day 8 (16 % in the control vs. 0 % in the chamomile group, p = 0.10), but not in days 15 and 22, although 11 % still had ulcerations in the control group and none in the chamomile group. The occurrence of oral mucositis was lower in patients in the chamomile group than in the control group. When compared to the controls, the chamomile group presented less mouth pain and had no ulcerations. Cryotherapy was well tolerated by both groups, and no toxicity related to chamomile was identified.

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.

Current practices for management of oral mucositis in cancer patients

NARCIS (Netherlands)

Raber-Durlacher, J. E.

1999-01-01

Many anticancer therapies induce oral mucositis, diminishing the patient's quality of life. Especially in neutropenic patients, it can lead to life-threatening systemic infection. Moreover, it can become a limiting factor in intensive treatment schedules. Many interventions are aimed at reducing

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.

Oral mucositis frequency in head and neck chemoradiotherapy

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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)

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

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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.

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.

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.

Oral mucositis: recent perspectives on prevention and treatment

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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.

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.

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)

The efficacy of a steroid mixture for chemoradiotherapy-induced acute mucositis

International Nuclear Information System (INIS)

Tamamura, Hiroyasu; Ohoguchi, Manabu; Ichioka, Kazuhiro; Ohta, Kiyotaka; Higashi, Kotarou; Tonami, Hisao

2005-01-01

Radiotherapy is an important therapeutic tool for malignant tumors in the head and neck and thoracic region. However, radiotherapy has also been known to cause acute mucositis and esophagitis during the early phase of treatment, for which there is no cure to date. A mixture of mucosal protective steroids has been shown to be beneficial in patients with these symptoms receiving radiotherapy alone. The purpose of this study was to examine the efficacy of this agent to treat the mucositis that accompanies chemoradiotherapy. Moreover, the differences between the curative effects were examined retrospectively, according to the region irradiated. Radiotherapy was administered to the head and neck, and thoracic region, and the steroid mixture was prescribed for patients in the radiotherapy alone and chemoradiotherapy groups that exhibited acute radiation-induced mucositis symptoms. We then evaluated daily food consumption, total serum-protein value, serum-albumin value and body weight of the radiation-induced mucositis patients that were treated with the mixture. Moreover, we also examined the efficacy in patients undergoing irradiation of the oral cavity, and of the esophagus (which did not entail irradiation of the oral cavity). Two hundred and fourteen patients treated with the steroid mixture in this study had no treatment-related adverse events. In comparison between the radiotherapy alone and chemoradiotherapy groups, no significant differences were observed for daily food consumption. However, differences were observed for daily food consumption between the groups undergoing irradiation of the oral cavity and irradiation of the esophagus (p=0.0008). In the group experiencing irradiation of the mouth, decreased ability to swallow and digest food associated with the primary disease was also observed. Total serum-protein values, serum-albumin values and body weight exhibited a slight decrease despite the onset of radiation-induced mucositis, compared with the values

MUCOSITIS PREVENTION BY SELECTIVE ELIMINATION OF ORAL FLORA IN IRRADIATED HEAD AND NECK-CANCER PATIENTS

NARCIS (Netherlands)

SPIJKERVET, FKL; VANSAENE, HKF; VANSAENE, JJM; PANDERS, AK; VERMEY, A; MEHTA, DM

1990-01-01

Mucositis induced by irradiation is the reactive inflammatory-like process of the oropharyngeal mucous membranes following irradiation. Bacteria colonizing the oral tissues are thought to contribute to this inflammatory process. The eradication of Gram-negative bacilli (selective elimination of oral

Mucosite bucal rádio e quimioinduzida Radiation therapy and chemotherapy-induced oral mucositis

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Luiz Evaristo Ricci Volpato

2007-08-01

Full Text Available O aumento da intensidade da quimioterapia e radioterapia no tratamento do câncer tem elevado a incidência de efeitos colaterais, em especial da mucosite bucal. OBJETIVO E MÉTODO: Através de revisão bibliográfica realizou-se atualizar informações quanto à definição, características clínicas, incidência, etiologia, patofisiologia, morbidade associada, prevenção e tratamento dessa manifestação clínica. RESULTADOS: Estudos atuais definem a mucosite bucal como uma inflamação e ulceração dolorosa bastante freqüente na mucosa bucal apresentando formação de pseudomembrana. Sua incidência e severidade são influenciadas por variáveis associadas ao paciente e ao tratamento a que ele é submetido. A mucosite é conseqüência de dois mecanismos maiores: toxicidade direta da terapêutica utilizada sobre a mucosa e mielossupressão gerada pelo tratamento. Sua patofisiologia é composta por quatro fases interdependentes: fase inflamatória/vascular, fase epitelial, fase ulcerativa/bacteriológica e fase de reparação. É considerada fonte potencial de infecções com risco de morte, sendo a principal causa de interrupção de tratamentos antineoplásicos. Algumas intervenções mostraram-se potencialmente efetivas para sua prevenção e tratamento. Entretanto, faz-se necessária a realização de novos estudos clínicos mais bem conduzidos para obtenção de melhor evidência científica acerca do agente terapêutico de escolha para o controle da mucosite bucal, permitindo a realização da quimioterapia e radioterapia do câncer em parâmetros ideais.Tincreasing the intensity of radiation therapy and chemotherapy in the management of cancer has increased the incidence of adverse effects, especially oral mucositis. AIM AND METHODS: a bibliographical review was conducted on the definition of oral mucositis, its clinical findings, the incidence, its etiology, the pathofisiology, associated morbidity, prevention and treatment

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.

ٍ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.

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

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.

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

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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.

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)

Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

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Thomas R Hird

Full Text Available Inactivated poliovirus vaccine (IPV may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24. In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11] or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]. There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

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.

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

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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)

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 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

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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.

Mucositis reduction by selective elimination of oral flora in irradiated cancers of the head and neck: a placebo-controlled double-blind randomized study

International Nuclear Information System (INIS)

Wijers, Oda B.; Levendag, Peter C.; Harms, Erik; Gan-Teng, A.M.; Schmitz, Paul I.M.; Hendriks, W.D.H.; Wilms, Erik B.; Est, Henri van der; Visch, Leo L.

2001-01-01

Purpose: The aim of the study was to test the hypothesis that aerobic Gram-negative bacteria (AGNB) play a crucial role in the pathogenesis of radiation-induced mucositis; consequently, selective elimination of these bacteria from the oral flora should result in a reduction of the mucositis. Methods and Materials: Head-and-neck cancer patients, when scheduled for treatment by external beam radiation therapy (EBRT), were randomized for prophylactic treatment with an oral paste containing either a placebo or a combination of the antibiotics polymyxin E, tobramycin, and amphotericin B (PTA group). Weekly, the objective and subjective mucositis scores and microbiologic counts of the oral flora were noted. The primary study endpoint was the mucositis grade after 3 weeks of EBRT. Results: Seventy-seven patients were evaluable. No statistically significant difference for the objective and subjective mucositis scores was observed between the two study arms (p=0.33). The percentage of patients with positive cultures of AGNB was significantly reduced in the PTA group (p=0.01). However, complete eradication of AGNB was not achieved. Conclusions: Selective elimination of AGNB of the oral flora did not result in a reduction of radiation-induced mucositis and therefore does not support the hypothesis that these bacteria play a crucial role in the pathogenesis of mucositis

A novel lozenge containing bupivacaine as topical alleviation of oral mucositis pain in patients with head and neck cancer

DEFF Research Database (Denmark)

Mogensen, Stine; Treldal, Charlotte; Sveinsdóttir, Kolbrún

2016-01-01

Introduction: Oral mucositis induces severe oral pain in head and neck cancer patients. There is at this point no effective pain treatment without considerable side effects.Objective:The aim of this pilot study was to investigate pain reduction in oral cavity and pharynx in patients with head...... and neck cancer (HNC) with oral mucositis, the location of anesthetic effect, and duration of pain relief, after a single-dose administration of a 25 mg bupivacaine lozenge.Methods:Ten patients with HNC suffering from oral mucositis pain were included. The patients assessed pain in the oral cavity...... and pharynx on a visual analogue scale (from 0 to 100 mm) at baseline and up to 3 hours after the lozenge was dissolved. Possible adverse events were registered.Results:The baseline pain was 51 mm (range: 30-73 mm) in the oral cavity and 58 mm (range: 35-70 mm) in the pharynx. When the lozenge was dissolved...

Prevalence of Deleterious Oral Habits and Oral Mucosal Lesions among Fishermen Population of Mahe, South India.

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Anzil, Ksa; Mathews, J; Sai, A G; Kiran, M; Kevin, S; Sunith, S

2016-09-01

Fishing is an occupation associated with uneven diet, strain, drunkenness, tobacco use, and deleterious habits. The physical state of laborers on a large scale will also be influenced by conditions at their work site. Oral mucosal lesions can occur as a result of infections, local shock or infuriation, systemic diseases, and uncontrolled usage of tobacco, betel quid, and alcohol. The aim of the present study is to assess the prevalence of deleterious oral habits and oral mucosal lesions among fishermen population of Mahe, South India. The study population consists of 362 fishermen aged between 15 and 54. The questionnaire consisted of questions on personal data, and information related to the subjects' oral habits were collected by the interview. The World Health Organization (WHO) Oral Health Assessment Form was designed for the assessment of oral mucosal lesions. Among the 362 fishermen, 266 (73.48%) were males and 96 (26.52%) were females. The overall prevalence of smoking, alcohol consumption, and gutka chewing was found to be 24.3, 48.85, and 32.4% respectively. Smokeless tobacco (32.4%) was the most prevalent habit followed by smoking tobacco (24.3%). The prevalence of oral mucosal lesions was 14.9%. There is a statistically significant association between age groups and habits considered. Findings of the present study suggest that oral health condition of the fisherfolk community was relatively poor, with high habit prevalence and oral mucosal lesions. This epi-demiological study has provided baseline data to plan further research in this area. Low socioeconomic status, strenuous working hours, inadequate diet and nutrition intake, stress, and use of tobacco and alcohol act as contributing factors for ill health and oral diseases. It is a challenging population to the clinician to identify and treat them.

Rehabilitation of exacerbated case of oral mucositis associated with renal failure following bone marrow transplantation

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Pavesi VCS

2009-01-01

Full Text Available Inflammation of oral mucosa induced by anti neoplastic drugs is an important, dose limiting and costly side effect of cancer therapy. Here is presented an exacerbated case of oral mucositis associated with renal failure in a patient who underwent bone marrow transplantation. The clinical aspects and an integrated rehabilitation program are discussed below.

Understanding the Oral Mucosal Absorption and Resulting Clinical Pharmacokinetics of Asenapine

NARCIS (Netherlands)

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

Oral mucosal lesions in denture wearers.

Science.gov (United States)

Jainkittivong, Aree; Aneksuk, Vilaiwan; Langlais, Robert P

2010-03-01

To determine the prevalence of oral mucosal lesions (OMLs) and denture-related mucosal lesions (DMLs) in denture wearers and to co-relate the prevalence with age, gender, type of denture and any systemic conditions. Dental records of 380 denture wearers were retrospectively reviewed for OMLs and DMLs. We found 45% of the denture wearers had DMLs and 60.8% had OMLs not related to denture wearing. Although the prevalence of DMLs was higher in complete denture wearers than in partial denture wearers (49% vs. 42.2%), this difference was not significant. The most common DMLs were traumatic ulcer (19.5%) and denture-induced stomatitis (18.1%). When analysed by type, traumatic ulcer, denture hyperplasia, frictional keratosis and candidiasis were more common in complete denture wearers, whereas denture-induced stomatitis was more common in partial denture wearers. Frictional keratosis was more common in men than in women. The prevalence of OMLs not related to denture wearing was higher in complete denture wearers than in partial denture wearers, and the most common OML was fissured tongue (27.6%). No association between DMLs and systemic conditions or xerostomic drugs was noted. No differences in the prevalence of DMLs in association with denture type were found. The prevalence of OMLs not related to denture wearing was higher in complete denture wearers than in partial denture wearers. This difference was affected by age, and the data were similar to the findings observed in the elderly.

Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study

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Yangkun Luo

2016-01-01

Full Text Available Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group or compound borax gargle (control group during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE v3.0 and the Verbal Rating Scale (VRS. Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P=0.01. The time to different grade of oral mucositis occurrence (grade 1, 2, or 3 was longer in test group (P<0.01, and the accumulated radiation dose was also higher in test group comparing to the control group (P<0.05. The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P<0.01. No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application.

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.

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

Efficacy of thiolated eudragit microspheres as an oral vaccine delivery system to induce mucosal immunity against enterotoxigenic Escherichia coli in mice.

Science.gov (United States)

Lee, Won-Jung; Cha, Seungbin; Shin, Minkyoung; Jung, Myunghwan; Islam, Mohammad Ariful; Cho, Chong-su; Yoo, Han Sang

2012-05-01

A vaccine delivery system based on thiolated eudragit microsphere (TEMS) was studied in vivo for its ability to elicit mucosal immunity against enterotoxigenic Escherichia coli (ETEC). Groups of mice were orally immunized with F4 or F18 fimbriae of ETEC and F4 or F18 loaded in TEMS. Mice that were orally administered with F4 or F18 loaded TEMS showed higher antigen-specific IgG antibody responses in serum and antigen-specific IgA in saliva and feces than mice that were immunized with antigens only. In addition, oral vaccination of F4 or F18 loaded TEMS resulted in higher numbers of IgG and IgA antigen-specific antibody secreting cells in the spleen, lamina propria, and Peyer's patches of immunized mice than other groups. Moreover, TEMS administration loaded with F4 or F18 induced mixed Th1 and Th2 type responses based on similarly increased levels of IgG1 and IgG2a. These results suggest that F4 or F18 loaded TEMS may be a promising candidate for an oral vaccine delivery system to elicit systemic and mucosal immunity against ETEC. Copyright © 2012 Elsevier B.V. All rights reserved.

Morphine mouthwash for the management of oral mucositis in patients with head and neck cancer

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Mostafa Sarvizadeh

2015-01-01

Conclusions: Topical morphine is more effective and more satisfactory to patients than the magic mouthwash in reducing severity of cancer treatment-induced oral mucositis. More studies with larger sample size and longer follow-up are required in this regard.

Preventive intervention possibilities in radiotherapy- and chemotherapy-induced oral mucositis : Results of meta-analyses

NARCIS (Netherlands)

Stokman, M A; Spijkervet, F K L; Boezen, H M; Schouten, J.P.; Roodenburg, J L N; de Vries, E. G. E.

The aim of these meta-analyses was to evaluate the effectiveness of interventions for the prevention of oral mucositis in cancer patients treated with head and neck radiotherapy and/or chemotherapy, with a focus on randomized clinical trials. A literature search was performed for reports of

The impact of oral herpes simplex virus infection and candidiasis on chemotherapy-induced oral mucositis among patients with hematological malignancies.

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Chen, Y-K; Hou, H-A; Chow, J-M; Chen, Y-C; Hsueh, P-R; Tien, H-F

2011-06-01

The aim of this study was to evaluate the influences of oral candidiasis and herpes simplex virus 1 (HSV-1) infections in chemotherapy-induced oral mucositis (OM). The medical records of 424 consecutive patients with hematological malignancies who had received chemotherapy at a medical center in Taiwan from January 2006 to November 2007 were retrospectively reviewed. The results of swab cultures of fungus and HSV-1 for OM were correlated with associated clinical features. Younger age, myeloid malignancies, and disease status other than complete remission before chemotherapy were significantly correlated with the development of OM. Risks of fever (p < 0.001) and bacteremia were higher in patients with OM. Among 467 episodes of OM with both swab cultures available, 221 were non-infection (47.3%) and 246 were related to either fungal infections, HSV-1 infections, or both (52.7%); of the 246 episodes, 102 were associated with fungal infections alone (21.8%), 98 with HSV-1 infections alone (21%), and 46 with both infections (9.9%). Patients who had received antifungal agents prior to OM occurrence tended to have HSV-1 infection (p < 0.001). Our results suggest that Candida albicans and HSV-1 play an important role in chemotherapy-induced OM in patients with hematological malignancies.

Mucosal immunogenicity of plant lectins in mice

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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

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.

Investigation of trefoil factor expression in saliva and oral mucosal tissues of patients with oral squamous cell carcinoma

DEFF Research Database (Denmark)

Chaiyarit, Ponlatham; Utrawichian, Akasith; Leelayuwat, Chanvit

2012-01-01

Objectives The aims of our study were to determine levels of trefoil factor (TFF) peptides in saliva and oral mucosal tissues from patients with oral squamous cell carcinoma (OSCC), and to evaluate whether individual members of TFFs (TFF1, TFF2, and TFF3) might act as biomarkers of disease....... Materials and methods Saliva samples were from 23 healthy subjects and 23 OSCC patients. Tissue samples were collected from 32 normal oral mucosa (NOM) and 32 OSCC biopsy specimens. ELISA and immunohistochemical methods were used to evaluate the expression of TFF1, TFF2, and TFF3 in saliva and oral mucosal...... tissues, respectively. Results Expression of TFF2 and TFF3 in oral mucosal tissues of OSCC patients was strongly downregulated when compared to healthy subjects (p 

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....

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.

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

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.

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

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.

Oral Immunization with Recombinant Norwalk Virus-Like Particles Induces a Systemic and Mucosal Immune Response in Mice

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Ball, Judith M.; Hardy, Michele E.; Atmar, Robert L.; Conner, Margaret E.; Estes, Mary K.

1998-01-01

Recombinant Norwalk virus-like particles (rNV VLPs) produced in insect cells were evaluated as an oral immunogen in CD1 and BALB/c mice by monitoring rNV-specific serum total and subclass immunoglobulin G (IgG) and intestinal IgA responses. Dose and kinetics of response were evaluated in the presence and absence of the mucosal adjuvant cholera toxin (CT). rNV-specific serum IgG and intestinal IgA were detected in the absence of CT, and the number of responders was not significantly different from that of mice administered VLPs with CT at most doses. The use of CT was associated with induction of higher levels of IgG in serum; this effect was greater at higher doses of VLPs. IgG in serum was detected in the majority of animals by 9 days postimmunization (dpi), and intestinal IgA responses were detected by 24 dpi. In the absence of CT, IgG2b was the dominant IgG subclass response in both mouse strains. Thus, nonreplicating rNV VLPs are immunogenic when administered orally in the absence of any delivery system or mucosal adjuvant. These studies demonstrate that rNV VLPs are an excellent model to study the oral delivery of antigen, and they are a potential mucosal vaccine for NV infections. PMID:9445035

Early inflammatory changes in radiation-induced oral mucositis. Effect of pentoxifylline in a mouse model

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Gruber, Sylvia; Bozsaky, Eva; Roitinger, Eva; Schwarz, Karoline [Medical University/AKH Vienna, Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Vienna (Austria); Schmidt, Margret [Technische Universitaet Dresden, Dept. Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany); Technische Universitaet Dresden, Helmholtz-Zentrum Dresden - Rossendorf, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany); Doerr, Wolfgang [Medical University/AKH Vienna, Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Vienna (Austria); Technische Universitaet Dresden, Dept. Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany); Technische Universitaet Dresden, Helmholtz-Zentrum Dresden - Rossendorf, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany)

2017-06-15

Early inflammation is a major factor of mucosal reactions to radiotherapy. Pentoxifylline administration resulted in a significant amelioration of radiation-induced oral mucositis in the mouse tongue model. The underlying mechanisms may be related to the immunomodulatory properties of the drug. The present study hence focuses on the manifestation of early inflammatory changes in mouse tongue during daily fractionated irradiation and their potential modulation by pentoxifylline. Daily fractionated irradiation with 5 fractions of 3 Gy/week (days 0-4, 7-11) was given to the snouts of mice. Groups of 3 animals per day were euthanized every second day between day 0 and 14. Pentoxifylline (15 mg/kg, s. c.) was administered daily from day 5 to the day before sacrifice. The expression of the inflammatory proteins TNFα, NF-κB, and IL-1β were analysed. Fractionated irradiation increased the expression of all inflammatory markers. Pentoxifylline significantly reduced the expression of TNFα and IL-1β, but not NF-κB. Early inflammation, as indicated by the expression of the inflammatory markers TNFα, NF-κB, and IL-1β, is an essential component of early radiogenic oral mucositis. Pentoxifylline differentially modulated the expression of different inflammatory markers. The mucoprotective effect of pentoxifylline does not appear to be based on modulation of NF-κB-associated inflammation. (orig.) [German] Fruehe entzuendliche Veraenderungen sind ein bedeutender Faktor waehrend der Strahlenreaktion der Schleimhaut. Die Behandlung mit Pentoxifyllin erzielte eine signifikante Minderung strahleninduzierter oraler Mukositis im Mauszungenmodel. Die zugrundeliegenden Mechanismen sind potenziell auf die immunomodulatorischen Eigenschaften des Wirkstoffs zurueckzufuehren. Die vorliegenden Untersuchungen fokussieren daher auf die Manifestation frueher entzuendlicher Veraenderungen in der Mauszunge waehrend taeglich fraktionierter Bestrahlung und deren potenzieller Modifikation

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

Science.gov (United States)

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.

Oral mucosal lesions and immune status in HIV-infected Indian children.

Science.gov (United States)

Subramaniam, Priya; Kumar, Krishna

2015-04-01

Pediatric HIV is growing at an alarming rate in developing countries. Due to their compromised immune status, children infected with HIV are prone to a number of opportunistic infections. Oral manifestations are the first signs of the disease in many of them. To assess the oral mucosal status of Indian children with HIV, based on their CD4 cell counts. Two hundred and twenty one HIV infected children aged 6-18 years from various HIV centers, were divided into three groups, based on their CD4 cell counts; Group 1: ≥500, Group 2: 201-499 and Group 3: ≤200 cells. The children in each group were further considered as 'prior to antiretroviral treatment (ART)' and 'on ART'. Oral mucosal examination was done based on presumptive criteria given by Ramos-Gomez for diagnosis of oro-facial lesions commonly associated with HIV infection in children. Data obtained was subjected to statistical analysis. Angular cheilitis and pseudomembranous candidiasis were the frequently seen oral lesions. Children with CD4 cell count ≥500 had significantly fewer oral lesions each. A high percentage of HIV-infected children were affected with oral mucosal lesions. There was a significant association between immune status and frequency of oral lesions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

Science.gov (United States)

Kawahara, Tomohiro; Makizaki, Yutaka; Oikawa, Yosuke; Tanaka, Yoshiki; Maeda, Ayako; Shimakawa, Masaki; Komoto, Satoshi; Moriguchi, Kyoko; Ohno, Hiroshi; Taniguchi, Koki

2017-01-01

Human rotavirus (RV) infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1), which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in mice administered

Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

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Tomohiro Kawahara

Full Text Available Human rotavirus (RV infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1, which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in

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.

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

Low energy helium-neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial

International Nuclear Information System (INIS)

Cowen, Didier; Tardieu, Corrine; Schubert, Mark; Peterson, Douglas; Resbeut, Michel; Faucher, Catherine; Franquin, Jean-Claude

1997-01-01

Purpose: To evaluate the efficiency of Helium-Neon (He-Ne) laser in the prevention of oral mucositis induced by high dose chemoradiotherapy before autologous bone marrow transplantation (BMT). Methods and Materials: Between 1993 and 1995, 30 consecutive patients receiving an autologous peripheral stem-cell or bone marrow transplant (BMT) after high dose chemoradiotherapy were randomized to possibly receive prophylactic laser to the oral mucosa after giving informed consent. Chemotherapy consisted of cyclophosphamide, 60 mg/kg intravenously (IV) on day (d)-5 and d-4 in 27 cases, or melphalan 140 mg/kg IV on d-4 in three cases. Total body irradiation (TBI) consisted of 12 Gy midplane dose in six fractions (4 Gy/day for three days). He-Ne laser (632.8 nm wavelength, power 60 mW) applications were performed daily from d-5 to d-1 on five anatomic sites of the oral mucosa. Oral examination was performed daily from d0 to d + 20. Mucositis was scored according to an oral exam guide with a 16 item scale of which four were assessed by the patients themselves. Mean daily self assessment scores for oral pain, ability to swallow and oral dryness were measured. A daily mucositis index (DMI) and a cumulative oral mucositis score (COMS) were established. Requirement for narcotics and parenteral nutrition was recorded. Results: The COMS was significantly reduced among laser treated (L+) patients (p = 0.04). The improvement of DMI in L+ patients was also statistically significant (p < 0.05) from d + 2 to d + 7. Occurrence and duration of grade III oral mucositis were reduced in L+ patients (p = 0.01). Laser applications reduced oral pain as assessed by patients (p = 0.05) and L+ patients required less morphine (p = 0.05). Xerostomia and ability to swallow were improved among the L+ patients (p = 0.005 and p = 0.01, respectively). Requirement for parenteral nutrition was not reduced (p = NS). Conclusion: Helium-Neon laser treatment was well tolerated, feasible in all cases, and

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-induced

The Prevalence and Investigation of Risk Factors of Oral Mucositis in a Pediatric Oncology Inpatient Population; a Prospective Study.

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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.

The prevalence of oral mucosal lesions in patients visiting a dental school in Southern India

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Mathew Anuna

2008-01-01

Full Text Available The purpose of the present study was to evaluate the prevalence of oral mucosal lesions in Manipal, Karnataka State, India. A total of 1190 subjects who visited the department of oral medicine and radiology for diagnosis of various oral complaints over a period of 3 months were interviewed and clinically examined for oral mucosal lesions. The result showed the presence of one or more mucosal lesions in (41.2% of the population. Fordyce′s condition was observed most frequently (6.55% followed by frictional keratosis (5.79%, fissured tongue (5.71%, leukoedema (3.78%, smoker′s palate (2.77%, recurrent aphthae, oral submucous fibrosis (2.01%, oral malignancies (1.76%, leukoplakia (1.59%, median rhomboid glossitis (1.50%, candidiasis (1.3%, lichen planus (1.20%, varices (1.17%, traumatic ulcer and oral hairy leukoplakia (1.008%, denture stomatitis, geographic tongue, betel chewer′s mucosa and irritational fibroma (0.84%, herpes labialis, angular cheilitis (0.58%, and mucocele (0.16%. Mucosal lesions like tobacco-related lesions (leukoplakia, smoker′s palate, oral submucous fibrosis, and oral malignancies were more prevalent among men than among women. Denture stomatitis, herpes labialis, and angular cheilitis occurred more frequently in the female population.

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

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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

Systematic review of basic oral care for the management of oral mucositis in cancer patients.

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McGuire, Deborah B; Fulton, Janet S; Park, Jumin; Brown, Carlton G; Correa, M Elvira P; Eilers, June; Elad, Sharon; Gibson, Faith; Oberle-Edwards, Loree K; Bowen, Joanne; Lalla, Rajesh V

2013-11-01

The purpose of this project was to evaluate research in basic oral care interventions to update evidence-based practice guidelines for preventing and treating oral mucositis (OM) in cancer patients undergoing radio- or chemotherapy. A systematic review of available literature was conducted by the Basic Oral Care Section of the Mucositis Study Group of MASCC/ISOO. Seven interventions--oral care protocols, dental care, normal saline, sodium bicarbonate, mixed medication mouthwash, chlorhexidine, and calcium phosphate--were evaluated using the Hadorn (J Clin Epidemiol 49:749-754, 1996) criteria to determine level of evidence, followed by a guideline determination of one of the following: recommendation, suggestion, or no guideline possible, using Somerfield's (Classic Pap Cur Comments 4:881-886, 2000) schema. Fifty-two published papers were examined by treatment population (radiotherapy, chemotherapy, and hematopoietic stem cell transplant) and by whether the intervention aimed to prevent or treat OM. The resulting practice suggestions included using oral care protocols for preventing OM across all treatment modalities and age groups and not using chlorhexidine mouthwash for preventing OM in adults with head and neck cancer undergoing radiotherapy. Considering inadequate and/or conflicting evidence, no guidelines for prevention or treatment of OM were possible for the interventions of dental care, normal saline, sodium bicarbonate, mixed medication mouthwash, chlorhexidine in patients receiving chemotherapy or hematopoietic stem cell transplant, or calcium phosphate. The evidence for basic oral care interventions supports the use of oral care protocols in patient populations receiving radiation and/or chemotherapy and does not support chlorhexidine for prevention of mucositis in head and neck cancer patients receiving radiotherapy. Additional well-designed research is needed for other interventions to improve the amount and quality of evidence guiding future clinical

Challenges in the local delivery of peptides and proteins for oral mucositis management.

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Campos, João C; Cunha, João D; Ferreira, Domingos C; Reis, Salette; Costa, Paulo J

2018-04-24

Oral mucositis, a common inflammatory side effect of oncological treatments, is a disorder of the oral mucosa that can cause painful ulcerations, local motor disabilities, and an increased risk of infections. Due to the discomfort it produces and the associated health risks, it can lead to cancer treatment restrains, such as the need for dose reduction, cycle delays or abandonment. Current mucositis management has low efficiency in prevention and treatment. A topical drug application for a local action can be a more effective approach than systemic routes when addressing oral cavity pathologies. Local delivery of growth factors, antibodies, and anti-inflammatory cytokines have shown promising results. However, due to the peptide and protein nature of these novel agents, and the several anatomic, physiological and environmental challenges of the oral cavity, their local action might be limited when using traditional delivering systems. This review is an awareness of the issues and strategies in the local delivery of macromolecules for the management of oral mucositis. Copyright © 2018. Published by Elsevier B.V.

Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis

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Lambros, Maria Polikandritou; Parsa, Cyrus; Mulamalla, HariChandana; Orlando, Robert; Lau, Bernard; Huang, Ying; Pon, Doreen; Chow, Moses

2011-01-01

Research highlights: → We irradiated a 3-D human oral cell culture of keratinocytes and fibroblasts with 12 and 2 Gy. → 6 h after irradiation the histopathology and apoptosis of the 3-D culture were evaluated. Microarrays were used to assess the gene expression in the irradiated 3-D tissue. → 12 Gy induced significant histopathologic changes and cellular apoptosis. → 12 Gy significantly affected genes of the NF-kB pathway, inflammatory cytokines and DAMPs. -- Abstract: Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this is an important first

Management of oral mucositis in patients with cancer.

NARCIS (Netherlands)

Stone, R.; Fliedner, M.C.; Smiet, A.C.M.

2005-01-01

Oral mucositis (OM) is a distressing toxic effect of chemotherapy and radiotherapy. It can 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

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.

Double-blind, placebo-controlled, randomized study of chlorhexidine prophylaxis for 5-fluorouracil-based chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy) in gastrointestinal malignancies.

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Sorensen, Jens Benn; Skovsgaard, Torben; Bork, Ellen; Damstrup, Lars; Ingeberg, Sten

2008-04-01

The purpose was to evaluate prevention of oral mucositis (OM) using chlorhexidine compared with placebo and with oral cooling (cryotherapy) during fluorouracil (5-FU)-based chemotherapy in gastrointestinal (GI) cancer. Patients with previously untreated GI cancer receiving bolus 5-FU/leucovorin chemotherapy were randomized to chlorhexidine mouthrinse 3 times a day for 3 weeks (Arm A), double-blind placebo (normal saline) with the same dose and frequency (Arm B), or cryotherapy with crushed ice 45 minutes during chemotherapy (Arm C). Patients self-reported on severity (CTC-grading) and duration of OM. Among 225 patients randomized, 206 answered the questionnaire (70, 64, and 63 patients in Arms A, B, and C, respectively) and were well balanced with respect to diagnoses, stage, age, sex, smoking habits, and performance status. Mucositis grade 3-4 occurred more frequently in Arm B (33%) than in A (13%, Pcryotherapy. The latter is easy and inexpensive but has limited use, as it is drug- and schedule-dependent. The current study is the first double-blind randomized evaluation of prophylactic chlorhexidine in a large adult patient population with solid tumors receiving highly OM-inducing chemotherapy. A role for chlorhexidine in the prevention of OM is suggested, which should be evaluated further.

A pilot study of the effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients during x-radiation therapy: a preliminary report

International Nuclear Information System (INIS)

Nicolatou, Ourania; Sotiropoulou-Lontou, Anastasia; Skarlatos, John; Kyprianou, Konstantinos; Kolitsi, Georgia; Dardoufas, Konstantinos

1998-01-01

Purpose: To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in reduction of radiotherapy-induced oral mucositis. Methods and Materials: Seventeen patients who were going to be irradiated with a total dose of 50-70 Gy for head and neck malignancies were included in the study. After the second week of radiotherapy, with the experience of oral pain, GM-CSF 400 μg was administered locally, once a day, until completion of radiotherapy. Patients were evaluated weekly for mucosal reaction and functional impairment. Results: Three patients with gross and functional mucositis grade I after the second week, completed the planned radiotherapy showing mucositis grade I. Eleven patients who experienced, after 2 weeks of radiotherapy, mucositis grade II and III, presented after the third week with gross mucositis grade I and II and functional impairment grade I. One of these 11 patients was then lost to follow-up and the remaining 10 completed their planned radiotherapy having an almost asymptomatic mucositis grade I. The 15th patient with gross mucositis grade III after the 2 weeks of radiotherapy, had a 2-day interruption because of painful mucositis and then continued and completed radiotherapy with gross and functional mucositis grade I. The 16th patient with mucositis grade III after the second week, did not show any improvement, and completed her planned radiotherapy with mucositis grade III which finally healed after the administration of acyclovir. The last, 17th patient discontinued radiotherapy at the third week because of mucositis grade IV and severe ulceration in apposition to an extensive gold prosthesis. Conclusion: The local administration of GM-CSF significantly reduced and almost healed radiation-induced oral mucositis in 14 of 17 patients during the radiotherapy, which was completed within the preplanned time and without any significant patient weight loss or functional impairment

Oral hygiene and number of oral mucosal lesion correlate with oral health-related quality of life in elderly communities

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Dewi Agustina

2014-03-01

Full Text Available Background: Quality of life assessment mostly is based on general health. Deterioration of physiologic condition, polypharmacy and the high occurrence of chronic disease in elderly may manifest in oral cavity that can affect oral function, in turn it will affect quality of life of elderly. Purpose: This study was aimed to determine the correlation of oral health status and oral health-related quality of life (OHRQoL in elderly communities of Yogyakarta city. Method: Seventy three elders were subjects of this study. Data of OHRQoL and oral health status were obtained from modification of questionnaire of Dental Impact of Daily Living (DIDL Index and from intraoral examination, respectively. Intraoral examination comprised oral mucosal lesion amount, oral hygiene, DMFT index and periodontal tissue status. The data then were analyzed statistically using Pearson Product Moment Correlation. Result: The results showed that mean of DMFT index was 16.9 and 63% of subjects were found with gingivitis, most subject had moderate oral hygiene and each subject at least had two oral mucosal lesions. Mean score of quality of life was 27.2 and classified as satisfying. Oral hygiene and number of oral mucosal lesion had correlation with OHRQoL with r were -0.236 (Sig. : 0.045 and -0.288 (Sig. : 0.013, respectively. Conclusion: The study suggested that oral hygiene and number of oral mucosal lesion correlate with oral health related-quality of life in elderly communities of Yogyakarta city.Latar belakang: Penilaian kualitas hidup terutama didasarkan pada kesehatan umum. Memburuknya kondisi fisiologis, polifarmasi dan tingginya kejadian penyakit kronis pada lansia dapat termanifestasi di dalam rongga mulut sehingga dapat mempengaruhi fungsi mulut yang pada gilirannya akan mempengaruhi kualitas hidup lansia. Tujuan: Penelitian ini bertujuan untuk meneliti hubungan antara status kesehatan mulut dan kualitas hidup berdasarkan kesehatan mulut pada masyarakat lanjut

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

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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.

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)

Oral mucosal color changes as a clinical biomarker for cancer detection.

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Latini, Giuseppe; De Felice, Claudio; Barducci, Alessandro; Chitano, Giovanna; Pignatelli, Antonietta; Grimaldi, Luca; Tramacere, Francesco; Laurini, Ricardo; Andreassi, Maria Grazia; Portaluri, Maurizio

2012-07-01

Screening is a key tool for early cancer detection/prevention and potentially saves lives. Oral mucosal vascular aberrations and color changes have been reported in hereditary nonpolyposis colorectal cancer patients, possibly reflecting a subclinical extracellular matrix abnormality implicated in the general process of cancer development. Reasoning that physicochemical changes of a tissue should affect its optical properties, we investigated the diagnostic ability of oral mucosal color to identify patients with several types of cancer. A total of 67 patients with several histologically proven malignancies at different stages were enrolled along with a group of 60 healthy controls of comparable age and sex ratio. Oral mucosal color was measured in selected areas, and then univariate, cluster, and principal component analyses were carried out. Lower red and green and higher blue values were significantly associated with evidence of cancer (all Pgreen coordinates. Likewise, the second principal component coordinate of the red-green clusters discriminated patients from controls with 98.2% sensitivity and 95% specificity (cut-off criterion≤0.4547; P=0.0001). The scatterplots of the chrominances revealed the formation of two well separated clusters, separating cancer patients from controls with a 99.4% probability of correct classification. These findings highlight the ability of oral color to encode clinically relevant biophysical information. In the near future, this low-cost and noninvasive method may become a useful tool for early cancer detection.

Granulocyte macrophage-colony stimulating factor (GM-CSF) and sucralfate in prevention of radiation-induced mucositis: a prospective randomized study

International Nuclear Information System (INIS)

Makkonen, Tuula A.; Minn, Heikki; Jekunen, Antti; Vilja, Pekka; Tuominen, Juhani; Joensuu, Heikki

2000-01-01

Purpose: To compare subcutaneously given molgramostim (GM-CSF) and sucralfate mouth washings to sucralfate mouth washings in prevention of radiation-induced mucositis. Methods and Materials: Forty head and neck cancer patients were randomly assigned to use either GM-CSF and sucralfate (n = 20) or sucralfate alone (n = 20) during radiotherapy. Sucralfate was used as 1.0 g mouth washing 6 times daily after the first 10 Gy of radiotherapy, and 150-300 μg GM-CSF was given subcutaneously. The grade of radiation mucositis and blood cell counts were monitored weekly. Salivary lactoferrin was measured as a surrogate marker for oral mucositis. Results: We found no significant difference between the molgramostim and the control groups in the oral mucositis grade, oral pain, use of analgesic drugs, weight loss, or survival. The median maximum neutrophil counts (median, 9.2 x 10 9 /L vs. 5.9 x 10 9 /L, p = 0.0005), eosinophil counts (median, 1.3 x 10 9 /L vs. 0.2 x 10 9 /L, p = 0.0004), and salivary lactoferrin concentrations were higher in patients who received GM-CSF. The most common toxicities in the GM-CSF plus sucralfate group were skin reactions at the GM-CSF injection site (65%), fever (30%), bone pain (25%), and nausea (15%), whereas the toxicity of sucralfate given alone was minimal. Conclusion: We found no evidence indicating that subcutaneously given GM-CSF reduces the severity of radiation-induced mucositis

Management of cancer therapy-induced oral mucositis pain and xerostomia with extra- and intra oral laser irradiation

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Libik, T. V.; Gileva, O. S.; Danilov, K. V.; Grigorev, S. S.; Pozdnyakova, A. A.

2017-09-01

This study evaluated the efficacy of combined (intra- and extraoral) low-level laser therapy (LLLT) and conventional pharmacological modalities in prevention and treatment of oral mucositis (OM) and associated pain and xerostomia in patients with head and neck cancer (HNC) undergoing concurrent chemoradiotherapy (CRT). A prospective comparative randomized study was conducted with 21 patients with head and neck cancer subjected to CRT. Eleven patients received extra- and intraoral LLLT daily from the 1st day until the end of CRT-course before each session during 5 consecutive days, and the other 10 patients received conventional preventive and treatment procedures based on the use of benzidamine 0.15% solution also throughout the duration of CRT, including weekends. OM was measured using an oral toxicity scale (OTS), oral pain was measured using the color-numeric visual analogue scale (VAS), unstimulated salivary flow rate measured by the spitting technique (ml/min), dry mouth symptoms were self-estimated by patients using The Xerostomia Inventory (XI). The LLLT group showed lower mean OTS and VAS scores, lower level of reduction of salivary flow rate during the course of CRT. In both groups, no interruption of CRT was needed. The prophylactic use of both treatments proposed in this study seems to reduce the incidence of severe OM lesions. However, the LLLT was more effective in delaying the appearance of severe OM, oral pain and xerostomia.

Variation of Energy in Photobiomodulation for the Control of Radiotherapy-Induced Oral Mucositis: A Clinical Study in Head and Neck Cancer Patients

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Cizelene do Carmo Faleiros Veloso Guedes

2018-01-01

Full Text Available Oral mucositis (OM is a frequent and severe adverse effect of therapy against head and neck cancer. Photobiomodulation with the low-power laser is known to be effective against OM, but the diversity of protocols and the possibility of stimulating residual tumor cells are still obstacles. The present study aimed to compare two doses of laser energy delivered to the oral mucosa of patients under oncologic treatment for head and neck cancer, looking for differences in the control of mucositis, as well as in the frequency of tumoral recurrences. Fifty-eight patients undergoing radiotherapy were randomized into two groups, distinguished according to the energy delivered by laser irradiation, namely, 0.25 J and 1.0 J. The groups were compared according to frequency, severity, or duration of OM, as well as the frequency of tumoral recurrences. OM was significantly less frequent in patients receiving 1.0 J of energy, but the groups did not differ regarding severity or duration of OM. Tumoral recurrence also did not vary significantly between the groups. Photobiomodulation with a higher dose of energy (1.0 J versus 0.25 J is associated with better control of radiotherapy-induced OM and does not significantly increase the risk of neoplastic recurrence.

The effects of sucralfate suspension and diphenhydramine syrup plus kaolin-pectin on radiotherapy-induced mucositis

International Nuclear Information System (INIS)

Barker, G.; Loftus, L.; Cuddy, P.; Barker, B.

1991-01-01

A prospective, double-blind study compared the effectiveness of sucralfate suspension with diphenhydramine syrup plus kaolin-pectin in reducing severity and pain of radiation-induced oropharyngeal mucositis. Fourteen patients who received at least 4600 cGy to the oral cavity used one of the mouth rinses four times a day, beginning at 1600 cGy. Data were collected on daily perceived pain and helpfulness of mouth rinse, weekly mucositis grade, weight change, and interruption of therapy. Analysis of data revealed no statistically significant differences between the two groups in any parameter. A retrospective review of 15 patients who had received at least 4600 cGy radiation to the oropharynx but had not used a daily mouth-coating rinse, was compared with the study group. Comparison of the two groups suggested that consistent daily oral hygiene and use of a mouth-coating agent will result in less pain and may reduce weight loss and interruption of radiation because of severe mucositis

The effects of sucralfate suspension and diphenhydramine syrup plus kaolin-pectin on radiotherapy-induced mucositis

Energy Technology Data Exchange (ETDEWEB)

Barker, G.; Loftus, L.; Cuddy, P.; Barker, B. (Univ. of Missouri, Kansas City (USA))

1991-03-01

A prospective, double-blind study compared the effectiveness of sucralfate suspension with diphenhydramine syrup plus kaolin-pectin in reducing severity and pain of radiation-induced oropharyngeal mucositis. Fourteen patients who received at least 4600 cGy to the oral cavity used one of the mouth rinses four times a day, beginning at 1600 cGy. Data were collected on daily perceived pain and helpfulness of mouth rinse, weekly mucositis grade, weight change, and interruption of therapy. Analysis of data revealed no statistically significant differences between the two groups in any parameter. A retrospective review of 15 patients who had received at least 4600 cGy radiation to the oropharynx but had not used a daily mouth-coating rinse, was compared with the study group. Comparison of the two groups suggested that consistent daily oral hygiene and use of a mouth-coating agent will result in less pain and may reduce weight loss and interruption of radiation because of severe mucositis.

Helicobacter pylori coinfection is a confounder, modulating mucosal inflammation in oral submucous fibrosis

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Rajendran R

2009-01-01

Full Text Available The oral cavity has been considered a potential reservoir for Helicobacter pylori (H pylori , from where the organism causes recurrent gastric infections. Aim: With this case-control study we tried to evaluate the role of H pylori in the etiology of mucosal inflammation, a condition that compounds the morbid state associated with oral submucous fibrosis (OSF. Materials and Methods : Subjects ( n = 150 were selected following institutional regulations on sample collection and grouped into test cases and positive and negative controls based on the presence of mucosal fibrosis and inflammation. The negative controls had none of the clinical signs. All patients underwent an oral examination as well as tests to assess oral hygiene/periodontal disease status; a rapid urease test (RUT of plaque samples was also done to estimate the H pylori bacterial load. We used univariate and mutivariate logistic regression for statistical analysis of the data and calculated the odds ratios to assess the risk posed by the different variables. Results : The RUT results differed significantly between the groups, reflecting the variations in the bacterial loads in each category. The test was positive in 52% in the positive controls (where nonspecific inflammation of oral mucosa was seen unassociated with fibrosis, in 46% of the test cases, and in 18% of the negative controls (healthy volunteers (χ2 = 13.887; P < 0.01. A positive correlation was seen between the oral hygiene/periodontal disease indices and RUT reactivity in all the three groups. Conclusions: The contribution of the H pylori in dental plaque to mucosal inflammation and periodontal disease was significant. Logistic regression analysis showed gastrointestinal disease and poor oral hygiene as being the greatest risk factors for bacterial colonization, irrespective of the subject groups. A positive correlation exists between RUT reactivity and the frequency of mucosal inflammation.

Novel engineered systems for oral, mucosal and transdermal drug delivery.

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Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

2013-08-01

Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

Comparative Efficacy of Aloe vera and Benzydamine Mouthwashes on Radiation-induced Oral Mucositis: A Triple-blind, Randomised, Controlled Clinical Trial.

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Sahebjamee, Mahnaz; Mansourian, Arash; Hajimirzamohammad, Mohammad; Mohammad, Haji Mirza Mohammad; Zadeh, Mohsen Taghi; Bekhradi, Reza; Kazemian, Ali; Manifar, Soheila; Ashnagar, Sajjad; Doroudgar, Kiavash

2015-01-01

To compare the efficacy of an Aloe vera mouthwash with a benzydamine mouthwash in the alleviation of radiation- induced mucositis in head and neck cancer patients using a triple-blind, randomised controlled trial. Twenty-six eligible head and neck cancer patients who were to receive conventional radiation therapy at the radiation oncology department were randomised to receive an Aloe vera mouthwash or a benzydamine mouthwash. Mucositis severity was assessed during the course of radiation therapy using the WHO grading system. At baseline, there was no difference in the distribution of mucositis severity between the two groups. The mean interval between radiation therapy and onset of mucositis was similar for both groups (Aloe vera 15.69±7.77 days, benzydamine 15.85±12.96 days). The mean interval between the start of radiation therapy and the maximum severity of mucositis were was also similar in both the Aloe vera and benzydamine groups (Aloe vera 23.38±10.75 days, benzydamine 23.54±15.45 days). Mean changes of mucositis severity over time in both groups were statistically similar and the effect of both treatments did not change signficantly with time (p=0.09). Aloe vera mouthwash was as beneficial as benzydamine mouthwash in alleviating the severity of radiation-induced mucositis and showed no side effects. The Aloe vera mouthwash could be an alternative agent in the treatment of radiation-induced mucositis in patients with head and neck cancers.

Clinical Effectiveness of Aloe Vera in the Management of Oral Mucosal Diseases- A Systematic Review

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Nair, Gopakumar Ramachandran; Naidu, Giridhar Seetharam; Jain, Supreet; Makkad, Ramanpal Singh; Jha, Abhishek

2016-01-01

Introduction Aloe vera is well known for its medicinal properties which lead to its application in treating various diseases. Its use in treating oral lesions has not been much documented in literature. Aim Although, systematic reviews on aloe vera and its extracts have been done earlier, but in relation to oral diseases this is the first systematic review. The aim of the present systematic review was to compile evidence based studies on the effectiveness of Aloe vera in treatment of various oral diseases. Materials and Methods Computerized literature searches were performed to identify all published articles in the subject. The following databases were used: PUBMED [MEDLINE], SCOPUS, COCHRANE DATABASE, EMBASE and SCIENCE DIRECT using specific keywords. The search was limited to articles published in English or with an English Abstract. All articles (or abstracts if available as abstracts) were read in full. Data were extracted in a predefined fashion. Assessment was done using Jadad score. Results Fifteen studies satisfied the inclusion criteria. Population of sample study ranged from 20 patients to 110 patients with clinically diagnosed oral mucosal lesions. Out of 15 studies, five were on patients with oral lichen planus, two on patients with oral submucous fibrosis, other studies were carried on patients with burning mouth syndrome, radiation induced mucositis, candida associated denture stomatitis, xerostomic patients and four were on minor recurrent apthous stomatitis. Most studies showed statistically significant result demonstrating the effectiveness of Aloe vera in treatment of oral diseases. Conclusion Although there are promising results but in future, more controlled clinical trials are required to prove the effectiveness of Aloe vera for management of oral diseases. PMID:27656587

Betel nut chewing behaviour and its association with oral mucosal lesions and conditions in Ghaziabad, India.

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Prasad, Sumanth; Anand, Richa; Dhingra, Chandan

2014-01-01

To assess the practices and behaviour among Betel nut users in Ghaziabad and to detect the clinically associated oral mucosal lesions and conditions. A community-based survey was conducted in Ghaziabad among 332 betel nut users. Data on betel nut use was obtained through a self-administered questionnaire. Oral mucosal lesions and conditions were recorded using WHO criteria. Out of 332 betel nut users, 32.8% consumed Gutkha. 62.3% users used betel nut with tobacco. Most of the study population started chewing betel nut because of peer pressure and the habit started at the workplace or school. A majority found that there was no physical discomfort due to the habit. The significant oral diseases detected were oral leukoplakia in 11.7% and oral submucous fibrosis in 6.1% of individuals. The findings of the present study revealed that 74.7% of the participants were current chewers. 30.4% of all participants had oral mucosal lesions and conditions.

Oral Mucosal Disorders in Pregnant versus Non-Pregnant Women

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Fahimeh Rezazadeh

2014-12-01

Full Text Available The effects of pregnancy on the Oral Mucosa Disorder (OMD have been sporadically documented in some developed countries. Less known is the status of OMD during pregnancy in less developed/developing countries. Iran is no exception. This study assesses the prevalence of OMD in 200 pregnant women and compares the findings with the findings from a 200 non-pregnant woman of similar age distribution in Iran. The participants had been referred to a clinic to receive reproductive age-related services. Participants suffering from systemic chronic diseases, those on medications/drugs, smokers, needing biopsies, and those with urgent Oral Mucosal Lesion (OML treatments were excluded from the study. Oral mucosal of all 400 participants were examined. The participants’ age ranges were from 17 to 47; with the average age of 33.14 for one group; and 30.23 for the other group. Both groups had the same level of formal education. Out of 400 examined women; 62 had lesions, including 47 pregnant (23.5%; and 15 non-pregnant (7.5% women. This result shows that the OMD rate of occurrence was significantly higher among the pregnant women. Higher OML prevalence in pregnant women, as compared to the non-pregnant women, indicates the importance of timely oral examination of pregnant women and subsequent treatment plans for them.

The effectiveness of a saline mouth rinse regimen and education programme on radiation-induced oral mucositis and quality of life in oral cavity cancer patients: A randomised controlled trial.

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Huang, B-S; Wu, S-C; Lin, C-Y; Fan, K-H; Chang, J T-C; Chen, S-C

2018-03-01

Radiation therapy (RT) and concurrent chemotherapy RT (CCRT) generate radiation-induced oral mucositis (OM) and lower quality of life (QOL). This study assessed the impact of a saline mouth rinse regimen and education programme on radiation-induced OM symptoms, and QOL in oral cavity cancer (OCC) patients receiving RT or CCRT. Ninety-one OCC patients were randomly divided into a group that received saline mouth rinses and an education programme and a control group that received standard care. OM symptoms and QOL were assessed with the WHO Oral Toxicity Scale, MSS-moo and UW-QOL. Data were collected at the first postoperative visit to the radiation department (T0) and at 4 weeks and 8 weeks after beginning RT or CCRT. Patients in both groups had significantly higher levels of physical and social-emotional QOL at 8 weeks after beginning RT or CCRT compared to the first visit. Patients in the saline rinse group had significantly better physical and social-emotional QOL as compared to the standard care group at 8 weeks. Radiation-induced OM symptoms and overall QOL were not different between the groups. We thus conclude the saline rinse and education programme promote better physical and social-emotional QOL in OCC patients receiving RT/CCRT. © 2018 John Wiley & Sons Ltd.

Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats

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Nelson, David W; Liu, Xiaowen; Holst, Jens Juul

2006-01-01

in mucosal mass, protein, DNA, and histology. Both systemic and perivagal capsaicin significantly attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein, and DNA in rats fed orally. Villus height was significantly reduced in resected rats given capsaicin compared with vehicle...

Radiation-induced mucositis pain in laryngeal cancer

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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)

A review of quality assessment of the methodology used in guidelines and systematic reviews on oral mucositis.

NARCIS (Netherlands)

Potting, C.; Mistiaen, P.; Poot, E.; Blijlevens, N.; Donnelly, P.; Achterberg, T. van

2009-01-01

Aims and objectives: The objective of this study was to identify and to assess the quality of evidence-based guidelines and systematic reviews we used in the case of oral mucositis, to apply general quality criteria for the prevention and treatment of oral mucositis in patients receiving

Prevention of oral mucositis in children receiving cancer therapy: a systematic review and evidence-based analysis.

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Qutob, Akram F; Gue, Sumant; Revesz, Tamas; Logan, Richard M; Keefe, Dorothy

2013-02-01

This systematic review investigated, critically appraised, and rated the evidence on agents used to prevent oral mucositis in children. A comprehensive search of the relevant literature was performed up to December 2011. Articles were included according to the inclusion/exclusion criteria and were critically appraised for validation and quality assessment using a checklist consisting of 18 categories. Each article was then rated for its strength of evidence. 16,471 articles were retrieved from 19 different databases and then reduced to 27 articles that fit the inclusion criteria. Five articles on oral care protocols supported their use to prevent oral mucositis in children. Seven articles on chlorhexidine mouthwash and three on laser therapy had conflicting evidence of its use. The preventative agents that were supported by one or two articles included: benzydamine mouthwash, iseganan mouthwash, granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash, oral/enteral glutamine, oral propantheline and cryotherapy, oral cryotherapy, oral sucralfate suspension, prostaglandin E2 tablets, and chewing gum. The reduction in the rates of occurrence of oral mucositis when using agents of fair (B) to good (A) evidence ranged from 22% to 52%. In conclusion, this review suggests the use of oral care protocols to prevent oral mucositis in children because of their strength of evidence (fair to good). The authors suggest avoiding agents with fair to good evidence against their use (oral sucralfate suspension, prostaglandin E2 tablets, and GM-CSF mouthwash). Agents with conflicting evidence (chlorhexidine mouthwash (used solely), laser therapy, and glutamine) should also be avoided until further research confirms their efficacy. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

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

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Sena Lee

2014-04-01

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

Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation.

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Onseng, Kittipong; Johns, Nutjaree Pratheepawanit; Khuayjarernpanishk, Thanut; Subongkot, Suphat; Priprem, Aroonsri; Hurst, Cameron; Johns, Jeffrey

2017-12-01

Oral mucositis is a major cause of pain and delayed cancer treatment leading to poor survival in head and neck cancer patients receiving concurrent chemoradiation. The study evaluated the effect of adjuvant melatonin on minimizing oral mucositis complications to reduce these treatment delays and interruptions. A randomized, double-blind, double dummy, placebo-controlled clinical trial. Ubon Ratchathani Cancer Hospital, Thailand. Thirty-nine head and neck cancer patients receiving concurrent chemoradiation (5 days/week of radiation plus chemotherapy three or six cycles). Patients were randomized to receive 20 mg melatonin gargle (or matched placebo) before each irradiation, and 20 mg melatonin capsules (or matched placebo) taken nightly during 7 weeks of concurrent chemoradiation. Endpoints were oral mucositis events (incidence and time to grade 3 mucositis or grade 2 xerostomia), pain medication consumption and quality of life (QOL). Melatonin group reported lower incidence of grade 3 oral mucositis (42% vs. 55%) and grade 2 xerostomia (20% vs. 21%); no statistical significance was detected. Melatonin regimen delayed onset of grade 3 mucositis (median 34 days vs. 50 days; p = 0.0318), allowing median time of 16 more patient visits before its onset and fewer interrupted treatments due to oral mucositis were reported (n = 1 vs. n = 5). There was no difference of grade 2 xerostomia (median 32 days vs. 50 days; p = 0.624). Morphine consumption was also reduced (median 57 mg vs. 0 mg; p = 0.0342), while QOL was comparable during the study period. Adjuvant melatonin delayed the onset of oral mucositis, which enables uninterrupted cancer treatment and reduced the amount of morphine used for pain treatment.

Low energy helium-neon laser prevents oral mucositis after high-dose chemo-radiotherapy: results of a double-blind randomized trial

International Nuclear Information System (INIS)

Cowen, Didier; Tardieu, Corinne; Resbeut, Michel; Hannoun-Levi, Jean-Michel; Alzieu, Claude; Schubert, Marc; Franquin, Jean-Claude

1996-01-01

Purpose: To evaluate the efficiency of Helium-Neon (He-Ne) laser in the prevention of oral mucositis (OM) induced by high dose chemoradiotherapy before bone marrow transplantation (BMT). Methods and materials: Between 1993 and 1995, 30 consecutive patients (pts) receiving an autologous peripheral stem-cell or bone marrow transplant (BMT) after high dose chemoradiotherapy were randomized to receive or not prophylactic laser applications to the oral mucosa. Chemotherapy consisted of cyclophosphamide, 60 mg/kg intravenously (IV) on day (d)-5 and d-4 in 27 cases, or melphalan 140 mg/kg IV on d-4 in 3 cases. Total body irradiation consisted of 12 Gy midplane dose in six fractions and 3 days. He-Ne laser (632.8 nm wavelength, power 60 mW) applications were performed daily from d-5 to d-1 on 5 anatomic sites of the oral mucosa. Oral examination was performed daily from d0 to d+20. Mucositis was scored according to an oral exam guide with a 16 items scale of which 4 were assessed by the pts themselves. Mean daily scores of pain, ability to swallow and saliva production were measured. A daily mucositis index (DMI) and a cumulative score of oral mucositis (CSOM) were established. Requirement for narcotics and parenteral nutrition were measured. Validation of the grading scale was carried out using the Cronbach alpha coefficient for the internal validation and the test-retest correlation coefficient for the reproducibility analysis. The U Mann Whitney test was used to test for differences among groups. Patients were assigned to either laser treatment (L+) or sham-treatment (L-) by computer blocked randomization. Results: No pt was excluded for failure to complete the laser application protocol. Laser applications were well tolerated and no side effects were reported. The items were highly interrelated as well as the index considered as a whole: over 21 days, α = 0.97. Reproducibility analysis between the nurses in charge with the oral examination showed a significant

Prevalence of Oral Mucosal Lesions in Patients with Dermatological Diseases Attending Tertiary Care Hospital in Central India

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K. M. Shivakumar

2017-07-01

Full Text Available Background: The oral cavity is a unique environment where systemic maladies may be amplified by the oral mucosa. Sometimes, oral lesions are the first indication of a systemic problem. Oral mucosal lesions may be the initial feature or the only clinical sign of mucocutaneous diseases commonly observed in a dermatologic practice. Aim and Objectives: To assess the frequency of the oral manifestations in patients who suffer from dermatologic diseases, emphasizing the aspects referring to their, sex and age of the patients. Material and Methods:A cross sectional hospital-based study was carried out focusing on patients with skin lesions, for data gathering only patients included in the research were clinically examined aiming at identifying oral and cuteneous alterations. Information was recorded in individual clinical cards, as well as personal information, health conditions, family diseases and current and previous diseases. The structured interview was done in the local language containing questions regarding socio-demographics (gender, age, education and occupation general and oral health related characteristics and lifestyle. Results: In our study, the prevalence rate of oral mucosal lesions in patients with dermatological diseases is relatively low (94/489. Our study results showed that there is a positive correlation of oral manifestations with their respective dermatological diseases Conclusion: Oral mucosal lesions in skin diseases deserve special attention, Documenting the frequency of oral mucosal lesions in dermatological diseases may alert the dental surgeons and gives scope for early diagnosis and progress for such diseases and a multidisciplinary approach

Oral mucosal lesions' impact on oral health-related quality of life in preschool children.

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de Oliveira, Luísa Jardim Corrêa; Torriani, Dione Dias; Correa, Marcos Britto; Peres, Marco Aurélio; Peres, Karen Glazer; Matijasevich, Alicia; Dos Santos, Iná da Silva; Barros, Aluisio J D; Demarco, Flávio Fernando; Tarquinio, Sandra Beatriz Chaves

2015-12-01

The aim of this study was to assess the prevalence of oral mucosal lesions and their impact on oral health-related quality of life (OHRQoL) in children aged 5 years. A sample of 1118 children from Pelotas' birth cohort, born in 2004 (response rate of 85.8%), were selected to participate in the study. Data were collected using a questionnaire applied to mothers and from the oral examinations of the children. OML were identified by type, site, and size. Early Childhood Oral Health Impact Scale (ECOHIS) was used to assess caregivers' perception on children's OHRQoL. Descriptive, bivariate, and multivariate Poisson regression analyses were carried out, considering the impact on OHRQoL (total ECOHIS score) as the outcome. The prevalence of the OML was 30.1% (95% CI 27.5-32.9). Ulcers were the more prevalent type of lesion (29.4%), and the most affected site was the gums (31.0%). In bivariate analysis, there was a positive association between the presence of OML and OHRQoL impact measured by the following: mean overall score of ECOHIS (P children with OML presented higher impact on OHRQoL [rate ratio (RR) 1.38 95% CI 1.11; 1.72] comparing with their counterparts. Analyzing specific domains, children with OML also presented higher impact on children symptoms (RR 1.46 95% CI 1.20; 1.66) and family functional (RR 3.14 95% CI 1.59; 6.22) domains. Almost one-third of children presented with oral mucosal lesions, and these lesions impaired children's oral health-related quality of life. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

The polymeric stability of the Escherichia coli F4 (K88) fimbriae enhances its mucosal immunogenicity following oral immunization.

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Verdonck, Frank; Joensuu, Jussi Joonas; Stuyven, Edith; De Meyer, Julie; Muilu, Mikko; Pirhonen, Minna; Goddeeris, Bruno Maria; Mast, Jan; Niklander-Teeri, Viola; Cox, Eric

2008-10-23

Only a few vaccines are commercially available against intestinal infections since the induction of a protective intestinal immune response is difficult to achieve. For instance, oral administration of most proteins results in oral tolerance instead of an antigen-specific immune response. We have shown before that as a result of oral immunization of piglets with F4 fimbriae purified from pathogenic enterotoxigenic Escherichia coli (ETEC), the fimbriae bind to the F4 receptor (F4R) in the intestine and induce a protective F4-specific immune response. F4 fimbriae are very stable polymeric structures composed of some minor subunits and a major subunit FaeG that is also the fimbrial adhesin. In the present study, the mutagenesis experiments identified FaeG amino acids 97 (N to K) and 201 (I to V) as determinants for F4 polymeric stability. The interaction between the FaeG subunits in mutant F4 fimbriae is reduced but both mutant and wild type fimbriae behaved identically in F4R binding and showed equal stability in the gastro-intestinal lumen. Oral immunization experiments indicated that a higher degree of polymerisation of the fimbriae in the intestine was correlated with a better F4-specific mucosal immunogenicity. These data suggest that the mucosal immunogenicity of soluble virulence factors can be increased by the construction of stable polymeric structures and therefore help in the development of effective mucosal vaccines.

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.

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.

GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis

DEFF Research Database (Denmark)

Coleman, Elizabeth Ann; Lee, Jeannette Y; Erickson, Stephen W

2015-01-01

PURPOSE: High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems, can...

Polymorphism of regulatory region of GHRL gene (-2531C>T) as a promising predictive factor for radiotherapy-induced oral mucositis in patients with head neck cancer.

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Brzozowska, Anna; Homa-Mlak, Iwona; Mlak, Radosław; Gołębiowski, Paweł; Mazurek, Marcin; Ciesielka, Marzanna; Małecka-Massalska, Teresa

2018-03-22

The purpose of this study was to investigate the relationship between single nucleotide polymorphisms (SNP; rs1629816) in the regulatory region (c.-2531C>T) of the ghrelin (GHRL) gene and the occurrence and severity of oral mucositis caused by radiotherapy (RT) in patients with head and neck cancer. Oral mucositis in 65 patients with head and neck cancer who underwent irradiation were assessed according to Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) scale. The DNA from patients with head and neck cancer was isolated from whole blood. The genotypes were determined using the minisequencing method (SNaPshot PCR). The frequency of occurrence of the GHRL gene (c.-2531C>T, rs1629816) genotypes were as follows: AA = 21.5%; GA = 40%; and GG = 38.5%. In case of AA genotype, there was a 7-fold decrease of the risk of occurrence of oral mucositis (of grades 2 and 3) in the sixth week of RT (AA vs GA or GG, respectively: 17.9% vs 82.1% patients; odds ratio [OR] 0.14; 95% confidence interval [CI] 0.02-0.98; P = .0481). No statistically significant differences were observed between the volume of oral cavity contours (V30, V40, and V50) depending on the GHRL genotype in patients with head and neck cancer. The study results have demonstrated an association between the AA genotype of the GHRL gene and the risk of more severe oral mucositis attributed to RT in patients with head and neck cancer. © 2018 Wiley Periodicals, Inc.

Efficacy of Wobe-Mugos registered E for reduction of oral mucositis after radiotherapy. Results of a prospective, randomized, placebo-controlled, triple-blind phase III multicenter study

International Nuclear Information System (INIS)

Doerr, W.; Herrmann, T.

2007-01-01

Purpose: To investigate the efficacy and safety of Wobe-Mugos registered E (proteolytic enzymes) for amelioration of early side effects of radiotherapy for head-and-neck tumors, particularly oral mucositis. Patients and Methods: The study was a prospective, randomized, multicenter, placebo-controlled, triple-blind phase III study with parallel groups. 69 patients with carcinomas of the oropharynx or the oral cavity were enrolled between 1996 and 2000 in five centers; 54 of these were recruited in Dresden. Of the 69 patients, 61 (Dresden: 46) were available for analysis. The proteolytic enzymes tested (Wobe-Mugos registered E) comprised papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg. Results: Wobe-Mugos registered E was well tolerated. For the maximum mucositis scores, no statistically significant differences were found between the placebo and the verum group. The average mucositis score over weeks 1-6 revealed a significant difference in favor of the placebo arm, based on an earlier onset of mucositis in the Wobe-Mugos registered E group. Conclusion: The present study failed to demonstrate any effect of treatment with Wobe-Mugos registered E on radiotherapy side effects in patients treated for head-and-neck tumors. In particular, there was no beneficial effect on radiation-induced early oral mucositis. (orig.)

A novel lozenge containing bupivacaine as tropical alleviation of oral mucositis pain in patients with head and neck cancer: apilot study

DEFF Research Database (Denmark)

Mogensen, Stine; Treldal, Charlotte; Sveinsdóttir, Kolbrún

2016-01-01

with head and neck cancer (HNC) with oral mucositis, the location of anesthetic effect, and duration of pain relief, after a single-dose administration of a 25 mg bupivacaine lozenge. Methods: Ten patients with HNC suffering from oral mucositis pain were included. The patients assessed pain in the oral......: +4 to −23 mm; P = 0.12). No adverse events were observed. Conclusion: The results indicate that the bupivacaine lozenge has a clinically significant and long-lasting pain-relieving effect on pain because of oral mucositis in patients with HNC....

Oral mucosal lesions in children from 0 to 12 years old: ten years' experience.

Science.gov (United States)

Majorana, Alessandra; Bardellini, Elena; Flocchini, Pierangela; Amadori, Francesca; Conti, Giulio; Campus, Guglielmo

2010-07-01

The exact prevalence of oral lesions in childhood is not well known. We sought to define the prevalence of oral mucosal lesions in a large group of children. A retrospective cross-sectional study was performed using clinical charts from January 1997 to December 2007. Data collected included age, gender, and pathologic diagnosis. In total, 10,128 children (0-12 years old) were enrolled. Clinical diagnostic criteria proposed by the World Health Organization were followed. The frequency of children presenting oral mucosal lesions was 28.9%, and no differences related to gender were observed. The most frequent lesions recorded were oral candidiasis (28.4%), geographic tongue and other tongue lesions (18.5%), traumatic lesions (17.8%), recurrent aphthous ulcerations (14.8%), herpes simplex virus type 1 infections (9.3%), and erythema multiforme (0.9%). Children suffering from chronic diseases had a higher frequency of oral lesions compared with healthy children (chi-square: P children are relatively common, and several oral disorders are associated with underlying medical conditions. Copyright (c) 2010 Mosby, Inc. All rights reserved.

[Treatment and prevention of cancer treatment related oral mucositis].

Science.gov (United States)

Ruiz-Esquide, Gonzalo; Nervi, Bruno; Vargas, Alex; Maíz, Alberto

2011-03-01

One of the most common and troublesome complications of modern intensive anticancer treatments is oral mucositis. The purpose of this review is to summarize current evidence and clinical guidelines regarding its prevention and therapy. The use of keratinocyte growth factor-1, supplementary glutamine and other recently developed treatment modalities are discussed. The injury of the oral mucosa caused by antineoplastic agents promotes the local expression of multiple pro-inflammatory and pro-apoptotic molecules and eventually leads to the development of ulcers. Such lesions predispose patients to several infectious and nutritional complications. Also, they lead to modification of treatment schedules, potentially affecting overall prognosis. Local cryotherapy with ice chips and phototherapy with low energy laser may be useful as preventive measures. Mouthwashes with allopurinol and phototherapy with low energy laser can be used as treatment. In radiotherapy, special radiation administration techniques should be used to minimize mucosal injury. Pain control should always be optimized, with the use of patient controlled analgesia and topical use of morphine. Supplemental glutamine should not be used outside of research protocols. Lastly, thorough attention should be paid to general care and hygiene measures.

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

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.

Effects of LEDs on oral mucositis prevention in a patient with classic Hodgkin's lymphoma - a case report

International Nuclear Information System (INIS)

Bicudo, Leticia Lang

2004-01-01

The purpose of this case report was to evaluate the efficacy of therapy using LEDs (light-emitting diodes), at a wavelength of 880 nm, in the prevention of oral mucositis in a patient with Hodgkin's disease treated with ABVD regimen. Mucositis is a dose limiting complication of cancer treatment, of high incidence, which severity can lead to alterations of treatment planning or even to suspension of cancer therapy, with serious consequences in tumor response and even survival. Lesions develop most commonly on the nonkeratinized mucosa and present symptoms that begin like mild burning and evolve to severe pain. For this reason, low power laser and, recently, LEDs have been considered for preventing and management of oral mucositis, with great results. In this study, a 34-year-old male received intraoral irradiations with an infrared LEDs array (3,6 J/cm 2 , 74 mW), for five consecutive days, starting on the day of chemotherapy. In each chemotherapy cycle, he received ABVD protocol on day 1 and day 15, and received LEDs treatment during five days on each ABVD infusion. To analyze results, the WHO (World Health Organization) scale was used for grading of mucositis and VAS (Visual Analogue Scale) for pain evaluation, on days 1, 3, 7, 10 and 13 post-chemotherapy. The results obtained showed the patient did not develop oral mucositis, during the five chemotherapy cycles and did not present any pain symptom. Therapy with LEDs was a safe and effective method for the prevention of oral mucositis in this case report. However, new studies are needed in order to prove the efficacy of this methodology with more patients, increasing their quality of life. (author)

Dentalmaterialer kan udløse orale allergiske reaktioner

DEFF Research Database (Denmark)

Røn Larsen, Kristine; Johansen, Jeanne Duus; Arenholt-Bindslev, Dorthe

2013-01-01

A large number of materials used in the diagnosis, treatment and prevention of dental, periodontal and oral mucosal diseases may induce acute or chronic reactions in the oral cavity including allergic reactions. Clinically, it may be difficult to discriminate oral mucosal changes caused by dental...

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

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)

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.

Frequency of fungal infection in biopsies of oral mucosal lesions: A prospective hospital-based study

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Thimmarasa Venkappa Bhovi

2015-01-01

Full Text Available Aims and Objectives: To determine the frequency and common site of fungal infection in biopsies of oral mucosal lesions and also to detect the lesions most likely to be infected with fungal infection. Materials and Methods: A total of 100 patients with oral mucosal lesions were advised routine hematological examination followed by incisional biopsy under local anesthesia. The specimen were fixed in 10% neutral buffered formalin and processed. One section from the specimen was stained with hematoxylin and eosin staining for histopathological diagnosis of the lesion and a second section was stained with Periodic acid-Schiff (PAS stain for detection of fungal infection. Results: Out of the 100 patients, the most common mucosal lesion encountered was carcinoma (56% followed by lesions with dysplastic changes (28%, benign lesions (9%, squamous papilloma (2% and oral submucous fibrosis (5%. The most common anatomic location affected by the mucosal lesions were buccal mucosa, followed by the tongue, gingiva, maxillary tuberosity and floor of the mouth with values of 73%, 16%, 6%, 4% and 1%, respectively. Squamous papilloma had the highest positive association with fungal infection (100% followed by lesions with dysplastic changes (17.9% and carcinoma (8.9%. The maximum fungal positive association was encountered in the mucosal lesions over the tongue (18.7% followed by the buccal mucosa (12.3%. Conclusion: There is statistically significant association of fungal infection with dysplastic lesions and papilloma with the tongue and buccal mucosa as the most common sites. Hence a PAS stain should be performed whenever epithelial dysplasia on the tongue and buccal mucosa is diagnosed.

Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis.

Science.gov (United States)

Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon

2015-02-01

Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.

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.

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,

Local application of GM-CSF for treatment of chemoirradiation-induced mucositis in patients with advanced carcinoma of the head and neck: results of controlled clinical trial

International Nuclear Information System (INIS)

Reichtomann, K.A.

2002-01-01

Purpose: the study was designed to assess prospectively the efficacy of GM-CSF (granulocyte-macrophage colony-stimulating factor) mouthwash solution in the management of chemoirradiation induced oral mucositis for head and neck cancer patients. Methods and materials: thirty-five patients with advanced carcinoma of the head and neck were evaluated for mucositis during the first cycle of chemoirradiation therapy. GM-CSF 400 μg in 250 cc of water for 1 h of mouth washing was prescribed. Active comparator was a conventional mucositis therapy combination. The procedure started once mucositis grade 1 (using the WHO grading) was detected. Patients, examined twice a week, were evaluated for oral mucositis and oral infections. Assessment of subjective pain was provided using a visual analogue scale. Blood tests were taken weekly. Results: the results of statistical evaluation of mucositis using the WHO-grading showed no significant differences between the two treatment groups. Local application of GM-CSF significantly reduced subjective pain during the second week of chemoirradiation therapy. Statistical analysis of the leucocytes-, platelet count, haemoglobin level and development of oral infections revealed no significant differences between the two treatment groups. Conclusion: in combined chemoirradiation therapy schemes the RTOG/EORTC toxicity scale should be used. In selected cases of mucositis attended with severe pain, GM-CSF should be observed within the therapeutic considerations. Controlled clinical trials with larger patient population are required to evaluate the role of GM-CSF in this indication. (author)

A phase II study of HMB/Arg/Gln against oral mucositis induced by chemoradiotherapy for patients with head and neck cancer.

Science.gov (United States)

Yokota, Tomoya; Hamauchi, Satoshi; Yoshida, Yukio; Yurikusa, Takashi; Suzuki, Miho; Yamashita, Aiko; Ogawa, Hirofumi; Onoe, Tsuyoshi; Mori, Keita; Onitsuka, Tetsuro

2018-04-07

This phase II trial assessed the clinical benefit of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine (HMB/Arg/Gln) for preventing chemoradiotherapy (CRT)-induced oral mucositis (OM) in patients with head and neck cancer (HNC). Patients with HNC receiving definitive or postoperative cisplatin-based CRT were enrolled. HMB/Arg/Gln was administered orally or per percutaneous endoscopic gastrostomy from the first day of CRT up to its completion. All patients received opioid-based pain control and oral care programs that we previously reported. The primary endpoint was the incidence of grade ≥ 3 OM (functional/symptomatic) according to the Common Terminology Criteria of Adverse Events version 3.0. Quality of life (EORTC QLQ-C30/PROMS) at baseline and upon radiotherapy at a dosage of 50 Gy were assessed. Thirty-five patients with HNC were enrolled. Sixteen of them (45.7%) developed grade ≥ 3 OM (i.e., functional/symptomatic). The incidence of grade ≤ 1 OM (functional/symptomatic) was 51.5% at 2 weeks and 82.9% at 4 weeks after radiotherapy completion. Clinical examination revealed that 10 patients (28.6%) developed grade ≥ 3 OM. The incidence of grade ≤ 1 OM (clinical exam) was 80.0% at 2 weeks and 100% at 4 weeks after radiotherapy completion. Adverse events related to HMB/Arg/Gln were an increase in blood urea nitrogen and diarrhea, but were easily managed. The addition of HMB/Arg/Gln to opioid-based pain control and oral care programs was feasible but still insufficient at reducing the incidence of CRT-induced severe OM. However, the benefit of HMB/Arg/Gln should not be neglected given the findings of clinical examinations and the rapid recovery from severe OM. UMIN000016453.

[Epidemiological investigation of chewing fresh or dried betel nut and oral mucosal disease].

Science.gov (United States)

Yongxiu, Du; Dongye, Sun; Xinchun, Jian; Qiuhua, Mao; Yanan, Cheng; Pu, Xu

2016-08-01

This study was conducted to investigate the effect of chewing fresh or dried betel nut on the inci-dence and canceration of oral mucosa disease in Haikou City in Hainan Province. Through a survey questionnaire, clinical examination, and regular follow-up, we collected clinical data from 1 722 cases and divided them into two groups, among which 704 of the afflicted people chew dried betel nut, whereas the other 1 018 chew fresh betel nut. The data were 
statistically analyzed using different variables which included age, number, time of onset of the disease, and the cancerous condition associated with common oral mucosa disease, including oral submucous fibrosis (OSF), oral leukoplakia (OLK), and oral Lichen planus (OLP). 1) The study found no significant difference in the prevalence of oral mucosa diseases between the dried betel nut group (n=704) and fresh betel nut group (n=1 018) among the 1 722 cases (P>0.05), but the peak age of oral mucosal disease was more advanced in the dried betel nut group (Pbetel nut group was significantly higher than that in the fresh betel nut group (Pbetel nut group was significantly higher than that in the fresh betel nut group (Pbetel nut is more pathogenic and carcinogenic than chewing fresh betel nut. The extremely harmful components of the dried betel nut synergistically play a vital role in the occurrence and carcinogenesis of oral mucosal diseases.

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

Status of oral ulcerative mucositis and biomarkers to monitor posttraumatic stress disorder effects in breast cancer patients.

Science.gov (United States)

Loo, Wings T Y; Liu, Qing; Yip, Michael C W; Wang, Min; Chow, Louis W C; Cheung, Mary N B; Yip, Adrian Y S; Ng, Elizabeth L Y

2013-06-28

This study was designed to assess oral ulcerative mucositis, C-reactive protein, blood pressure, heart rate and thyroid function in breast cancer patients in relation to the occurrence of posttraumatic stress disorder 
(PTSD). A total of 120 female breast cancer patients and women 100 healthy subjects were enrolled in this study. PTSD status was assessed by questionnaire. Before and after treatment (modified radical mastectomy and chemotherapy), serum samples were collected and measured for levels of triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) and high-sensitivity C-reactive protein (hs-CRP) by ELISA. Oral ulcerative mucositis was evaluated by the number and duration of oral ulcers and the degree of pain. Breast cancer patients experienced long-term PTSD and had elevated serum T3 and T4 levels. Patients experienced more severe pain and longer duration of oral ulcers compared with the healthy group. Oral ulcers were significantly associated with PTSD score in terms of the number of ulcers (p=0.0025), the degree of pain (pthyroid function is altered in breast cancer patients with PTSD. Elevation of T3 and T4 and oral ulcerative mucositis might be indicative of the emotional status of breast cancer patients.

Treatment of Oral Mucosal Lesions Associated With Overlapping Psychodermatologic Disorders.

Science.gov (United States)

Alfaris, Sausan; France, Katherine; Sollecito, Thomas P; Stoopler, Eric T

2018-04-01

Delusional infestations are psychodermatologic disorders in which those affected have a false belief they are infested by parasites and/or "growing" inanimate objects from cutaneous surfaces. Individuals with delusional parasitosis (DP) believe parasites, bacteria, worms, mites, or other living organisms are the source of cutaneous symptoms, while those with Morgellons disease (MD) attribute their symptoms to growth of small fibers or inorganic material. In both DP and MD, self-inflicted, non-healing cutaneous lesions caused by scratching at the affected areas to alleviate symptoms are commonly observed. This report describes a case of oral mucosal lesions in a patient demonstrating overlapping symptoms of DP and MD. It is important for oral healthcare providers to recognize oral signs and symptoms that may be associated with psychodermatologic disorders.

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

Directory of Open Access Journals (Sweden)

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.

Dentalmaterialer kan udløse orale allergiske reaktioner

DEFF Research Database (Denmark)

Røn Larsen, Kristine; Johansen, Jeanne Duus; Arenholt-Bindslev, Dorthe

2013-01-01

A large number of materials used in the diagnosis, treatment and prevention of dental, periodontal and oral mucosal diseases may induce acute or chronic reactions in the oral cavity including allergic reactions. Clinically, it may be difficult to discriminate oral mucosal changes caused by dental...... materials from changes related to oral mucosal diseases. Diagnosis and management of allergic reactions in the oral mucosa may therefore be a major challenge. The purpose of this paper is to draw attention to commonly used dental materials, which can trigger typical, but also atypical, symptoms and clinical...

Biochemical Evaluation of the Therapeutic Effectiveness of Honey in Oral Mucosal Ulcers

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Nergiz Yılmaz

2009-11-01

Full Text Available The aim of this study was to describe and quantify the therapeutic value of honey in oral mucosal ulcers healing in comparison with Glyceroloxytriester (TGO. We also aimed to biochemically evaluate the healing effects of honey which had been collected from the Blacksea region flora on mucosal ulcers resulting in material loss.Thirty wistar rats (240±30 g were enrolled in this study. Excisional wounds were performed in all rats for animal oral mucosal ulcer model. They were randomly allocated to three groups: group 1 was treated with Apitherapeutic agent or honey (0,1 ml, 2x1, group 2 was treated with TGO (0,1ml, 2x1 locally, Group 3 served as the control group.Following the surgical procedure on day 7, biopsy specimens were taken from right buccal mucosa and on day 14 biopsy specimens were taken from left bucal mucosa in all rats. Afterwards, hydroxy pyroline levels were measured. Data were analyzed statisticallyThere was no statistically significant difference between Group 1 and 2, and also between Group 2 and 3, but there was statistically significant difference between Group 1 and 3 on day 7. There was no statistically significant difference between Group 1, 2 and 3 on day 14.

Adverse event management of oral mucositis in patients with breast cancer.

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Seiler, Sabine; Kosse, Jens; Loibl, Sibylle; Jackisch, Christian

2014-04-01

Oral mucositis (OM) is a clinically important and frequent adverse event (AE) associated with cancer treatment with conventional chemotherapy as well as new targeted agents. Incidence and severity of OM vary from treatment to treatment and from patient to patient. The pathogenesis of chemotherapy-induced OM can be divided into 5 phases. OM induced by targeted therapies differs among other things in appearance, course, concomitant AEs and toxicity, and thus could be perceived as an entity distinct from chemotherapy-induced OM with an innate pathogenic mechanism. OM has a severe impact on a patient's quality of life (QoL) by causing complications such as pain and discomfort. Even more important are associated restrictions in nutrition and hydration. Thus, the efficacy of cancer therapy might be impaired due to the necessity of dose delays and dose reductions. Numerous preventive and therapeutic approaches have been evaluated, but currently no single agent has changed the standard of care in preventing and treating OM. Thus, the current management has evolved from clinical experience rather than clinical evidence. This article will review the AE 'OM' induced by breast cancer treatment with chemotherapy and targeted agents in order to provide practical guidance for management and prevention.

Oral Immunization with Recombinant Norwalk Virus-Like Particles Induces a Systemic and Mucosal Immune Response in Mice

OpenAIRE

Ball, Judith M.; Hardy, Michele E.; Atmar, Robert L.; Conner, Margaret E.; Estes, Mary K.

1998-01-01

Recombinant Norwalk virus-like particles (rNV VLPs) produced in insect cells were evaluated as an oral immunogen in CD1 and BALB/c mice by monitoring rNV-specific serum total and subclass immunoglobulin G (IgG) and intestinal IgA responses. Dose and kinetics of response were evaluated in the presence and absence of the mucosal adjuvant cholera toxin (CT). rNV-specific serum IgG and intestinal IgA were detected in the absence of CT, and the number of responders was not significantly different ...

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

Science.gov (United States)

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

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

Mineral derivatives in alleviating oral mucositis during cancer therapy: a systematic review

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Sonia Lee

2015-02-01

Full Text Available Objectives. Oral mucositis (mouth ulcers is a cancer therapy side effect. Costly treatment interventions are often neglected in favor of cost-effective agents. This review assessed the general efficacy of mineral derivatives (a cost-effective agent in alleviating oral mucositis (OM during cancer therapy compared to the standard care, or placebo—including a decision tree to aide healthcare workers.Data Sources. Electronic searches of MEDLINE via OVID, EMBASE, CENTRAL, CANCERLIT via PubMed, and CINAHL via EBSCO (year 2000 to 11 September 2014 were undertaken for randomised controlled trials. A meta-search strategy extracted content from aggregate online databases.Review Methods. Randomized controlled trials were assessed (participants, intervention, outcome, results, and risk of bias for inclusion. The author abstracted binary and continuous data synthesised to Hedges’ g in a random effects model. The primary outcome measures were severity (incidence of peak oral mucositis, duration of oral mucositis, and time to onset; secondary outcome measures were the incidence of pain, and analgesic use. Serum mineral levels, total parenteral nutrition, and adverse events were discussed. The decision tree was mapped using sensitivity, specificity, pre-test and post-test Bayesian probability.Results. 1027 citations were identified and 16 studies were included (n = 1120; mean age 49 years. Cancer therapies consisted of chemotherapy, radiotherapy, chemo-radiotherapy, or hematopoietic stem cell transplantation. Outcome mineral derivatives were zinc (n = 549, calcium phosphate (n = 227, povidone-iodine (n = 228, or selenium (n = 116. Severity was measured across variable OM grading systems: In 13 studies, individuals in treatment groups (n = 958 experienced peak OM less than controls (g = −0.47, 95% CI −0.7 to −0.2, p = 0.0006; time to OM onset was significantly delayed in treatment than controls (g = −0.51, 95% CI−0.8 to −0.2, p = 0.0002; five

Combination of Estrogen and Immunosuppressive Agents to Establish a Mouse Model of Candidiasis with Concurrent Oral and Vaginal Mucosal Infection.

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Wang, Le; Wang, Chong; Mei, Huan; Shen, Yongnian; Lv, Guixia; Zeng, Rong; Zhan, Ping; Li, Dongmei; Liu, Weida

2016-02-01

Mouse model is an appropriate tool for pathogenic determination and study of host defenses during the fungal infection. Here, we established a mouse model of candidiasis with concurrent oral and vaginal mucosal infection. Two C. albicans strains sourced from clinical candidemia (SC5314) and mucosal infection (ATCC62342) were tested in ICR mice. The different combinational panels covering estrogen and immunosuppressive agents, cortisone, prednisolone and cyclophosphamide were used for concurrent oral and vaginal candidiasis establishment. Prednisolone in combination with estrogen proved an optimal mode for concurrent mucosal infection establishment. The model maintained for 1 week with fungal burden reached at least 10(5) cfu/g of tissue. This mouse model was evaluated by in vivo pharmacodynamics of fluconazole and host mucosal immunity of IL-17 and IL-23. Mice infected by SC5314 were cured by fluconazole. An increase in IL-23 in both oral and vaginal homogenates was observed after infection, while IL-17 only had a prominent elevation in oral tissue. This model could properly mimic complicated clinical conditions and provides a valuable means for antifungal assay in vivo and may also provide a useful method for the evaluation of host-fungal interactions.

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

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

Influence of the application of platelet-enriched plasma in oral mucosal wound healing

NARCIS (Netherlands)

Lindeboom, Jerome A. H.; Mathura, Keshen R.; Aartman, Irene H. A.; Kroon, Frans H. M.; Milstein, Dan M. J.; Ince, Can

2007-01-01

PURPOSE: The aim of this study was to describe and quantify the therapeutic value of platelet concentrate on the capillary density in oral mucosal wound healing. MATERIAL AND METHODS: The subjects included 10 healthy edentulous patients who underwent bilaterally a sinus floor elevation procedure and

Double-blind, placebo-controlled, randomized study of chlorhexidine prophylaxis for 5-fluorouracil-based chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy) in gastrointestinal malignancies

DEFF Research Database (Denmark)

Skovsgaard, T.; Bork, E.; Damstrup, L.

2008-01-01

BACKGROUND: The purpose was to evaluate prevention of oral mucositis (OM) using chlorhexidine compared with placebo and with oral cooling (cryotherapy) during fluorouracil (5-FU)-based chemotherapy in gastrointestinal (GI) cancer. METHODS: Patients with previously untreated GI cancer receiving...... bolus 5-FU/leucovorin chemotherapy were randomized to chlorhexidine mouthrinse 3 times a day for 3 weeks (Arm A), double-blind placebo (normal saline) with the same dose and frequency (Arm B), or cryotherapy with crushed ice 45 minutes during chemotherapy (Arm C). Patients self-reported on severity (CTC...... (33%) than in A (13%, Pcryotherapy. The latter is easy and inexpensive but has...

Oral Mucosal Injection of a Local Anesthetic Solution Containing Epinephrine Enhances Muscle Relaxant Effects of Rocuronium

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Ninomiya, Asako; Terakawa, Yui; Matsuura, Nobuyuki; Ichinohe, Tatsuya; Kaneko, Yuzuru

2012-01-01

The purpose of this study was to examine how submucosal injection of a clinically relevant dose of a lidocaine hydrochloride solution containing epinephrine affects the muscle relaxant effects of rocuronium bromide. Sixteen patients scheduled for orthognathic surgery participated in this study. All patients were induced with fentanyl citrate, a target-controlled infusion of propofol and rocuronium bromide. Anesthesia was maintained by total intravenous anesthesia. After nasotracheal intubation, an infusion of rocuronium bromide was started at 7 µg/kg/min, and the infusion rate was then adjusted to maintain a train of four (TOF) ratio at 10 to 15%. The TOF ratio just prior to oral mucosal injection of a 1% lidocaine hydrochloride solution containing 10 µg/mL epinephrine (LE) was taken as the baseline. TOF ratio was observed for 20 minutes, with 1-minute intervals following the start of injection. Mean epinephrine dose was 85.6 ± 18.6 µg and mean infusion rate of rocuronium bromide was 6.3 ± 1.6 µg/kg/min. TOF ratio began to decrease 2 minutes after the injection of LE, reached the minimum value at 3.1 ± 3.6% 12 minutes after the injection, and then began to recover. We conclude that oral mucosal injection of LE enhances the muscle relaxant effects of rocuronium bromide. PMID:22428970

Clinical and histological evaluation of laser therapy in the treatment of oral mucositis in an animal model

Science.gov (United States)

Vitória, L. A.; Machado, R. M.; Oliveira, C. R. B.; Rodriguez, T. T.; Cangussu, M. C. T.; Mathias, C. C.; Ramalho, L. M. P.

2018-04-01

Oral mucositis (MO) is considered to be the most severe stomatologic complication associated with antineoplastic treatment, which may lead to its interruption. Several current clinical protocols have aproven the benefits of Laser Photobiomodulation (LP) in the prevention and control of MO, due to its analgesic and anti-inflammatory effects and its stimulation of mesenchymal cells proliferation. The objective of this study was to evaluate the action of laser in initial events of chemo-induced MO. Eight Hamsters were divided into 2 groups (G): GI positive control (induction of MO) and GII Laser (induction of MO + Laser therapy). MO was induced by two injections of 5-Fluorouracil followed by grooves in the mucosa of the cheek pouch. The PL (Diode Laser of Gallium and Aluminum Arsenide, λ660nm, 40mW, 2,4J/cm2 ) was performed on day 0 of the experiment and every 48 hours until day 6. On day 7 the mucosa was photographed for clinical analysis according to Lima et al., 2005 and the animals were killed, for bag removal and histological processing for Hematoxylin and Eosin (H / E) staining. After statistical analysis (Fischer's Exact) with a significance level 0.5%, it was concluded that the LP, according to the adopted protocol, was able to prevent MO, and most hamsters showed no visible clinical changes in the cheek pouch. Histologically, it was observed that LP reduced angiogenesis and recruitment of inflammatory cells in G2. According to the results obtained LP was effective in preventing and reducing the severity of oral mucositis.

Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis.

Science.gov (United States)

Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún; Treldal, Charlotte; Jensen, Kenneth; Jensen, Anders Bonde; Kristensen, Claus Andrup; Jacobsen, Jette; Kreilgaard, Mads; Petersen, Janne; Andersen, Ove

2017-01-01

The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single dose to 10 healthy individuals, and a lozenge containing 25 mg bupivacaine was administered as single dose to 10 HNC patients with oral mucositis and as multiple doses to five patients with HNC. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the patients with HNC, respectively, after administration. The plasma concentration-time profiles of bupivacaine were fitted to pharmacokinetic models using nonlinear mixed-effects modelling, evaluating demographics and health status as covariates. The population pharmacokinetics (PK) of bupivacaine lozenge was best described by a two-compartment distribution model with absorption transit compartments. All the observed plasma concentrations were well below the bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was two times higher in HNC patients with oral mucositis grade 1-2 and three times higher in HNC patients with oral mucositis grade 3-4 than in the healthy individuals. Simulations showed that the plasma concentrations would be below the toxic limit after repeated dosing every second hour with 25 mg bupivacaine for five days. The 25-mg bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

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

Science.gov (United States)

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.

Radioprotective agents to reduce BNCT (Boron Neutron Capture Therapy) induced mucositis in the hamster cheek pouch

International Nuclear Information System (INIS)

Monti Hughes, A.; Pozzi, E.C.C.; Thorp, S.

2013-01-01

Introduction: BNCT is based on the capture reaction between boron, selectively targeted to tumor tissue, and thermal neutrons which gives rise to lethal, short-range high linear energy transfer particles that selectively damage tumor tissue, sparing normal tissue. We previously evidenced a remarkable therapeutic success of BNCT mediated by boronophenylalanine (BPA) in the hamster cheek pouch oral cancer and pre cancer model. Despite therapeutic efficacy, mucositis induced in premalignant tissue was dose limiting and favored, in some cases, tumor development. In a clinical scenario, oral mucositis limits the dose administered to head and neck tumors. Aim: Our aim was to evaluate the effect of the administration of different radioprotective agents, seeking to reduce BNCT-induced mucositis to acceptable levels in dose-limiting premalignant tissue; without compromising therapeutic effect evaluated as inhibition on tumor development in premalignant tissue; without systemic or local side effects; and without negative effects on the biodistribution of the boron compound used for treatment. Materials and methods: Cancerized hamsters with DMBA (dimethylbenzanthracene) were treated with BPA-BNCT 5 Gy total absorbed dose to premalignant tissue, at the RA-3 Nuclear Reactor, divided into different groups: 1-treated with FLUNIXIN; 2- ATORVASTATIN; 3-THALIDOMIDE; 4-HISTAMINE (two concentrations: Low -1 mg/ml- and High -5 mg/ml-); 5-JNJ7777120; 6-JNJ10191584; 7-SALINE (vehicle). Cancerized animals without any treatment (neither BNCT nor radioprotective therapy) were also analyzed. We followed the animals during one month and evaluated the percentage of animals with unacceptable/severe mucositis, clinical status and percentage of animals with new tumors post treatment. We also performed a preliminary biodistribution study of BPA + Histamine “low” concentration to evaluate the potential effect of the radioprotector on BPA biodistribution. Results: Histamine �

Systematic review of natural agents for the management of oral mucositis in cancer patients

DEFF Research Database (Denmark)

Yarom, Noam; Ariyawardana, Anura; Hovan, Allan

2013-01-01

/or conflicting evidence. CONCLUSIONS: Of the various natural agents reviewed here, the available evidence supported a guideline only for two agents: a suggestion in favor of zinc and a recommendation against glutamine, in the treatment settings listed above. Well-designed studies of other natural agents......Abstract PURPOSE: The aim of this study was to review the available literature and define clinical practice guidelines for the use of natural agents for the prevention and treatment of oral mucositis. METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational...

Prevalence of oral mucosal lesions in dental patients with tobacco smoking, chewing, and mixed habits: A cross-sectional study in South India

Directory of Open Access Journals (Sweden)

Prashant B Patil

2013-01-01

Full Text Available Background: A variety of oral mucosal lesions and conditions are associated with the habit of smoking and chewing tobacco, and many of these carry a potential risk for the development of cancer. There have been no studies that report the prevalence of habits and associated oral changes in the population in Dharwad region, of Karnataka, south India. Materials and Methods: A hospital-based, cross-sectional study was carried out at SDM Dental College (Dharwad, Karnataka. A total of 2400 subjects (1200 subjects with and 1200 subjects without habits attending the dental hospital were interviewed and examined by trained professionals to assess any oral mucosal changes. Results: Oral mucosal lesions were found in 322 (26.8% subjects who had tobacco smoking and chewing habits as compared to 34 (2.8% subjects without those habits. Oral leukoplakia (8.2% and oral submucous fibrosis (OSF (7.1% were the prevalent oral mucosal lesions found in subjects who had those habits, while the other lesions (1.7% namely; oral candidiasis, median rhomboid glossitis, recurrent apthous ulcer, frictional keratosis, and oral lichen planus (0.9% were frequently reported among individuals without those habits. The odds of developing oral lesions in subjects with tobacco habits was nearly 11.92 times that of abstainers (odds ratio, OR = 11.92, 95% confidence intervals, CI = 10.61-14.59%. Conclusion: The study showed that the risk of the development of oral lesions associated with tobacco smoking, chewing, or both is quite high. Males who had one or more of these habits showed more frequent oral changes than females. The study reinforces the association of OSF with gutkha and areca nut chewing, and leukoplakia, erythroplakia, and oral cancer with tobacco smoking, chewing, or mixed habits.

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Low level laser therapy for concurrent chemoradiotherapy induced oral mucositis in head and neck cancer patients – A triple blinded randomized controlled trial

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Gautam, Ajay Prashad; Fernandes, Donald J.; Vidyasagar, Mamidipudi S.; Maiya, Arun G.; Vadhiraja, Bejadi M.

2012-01-01

Background and purpose: Oral mucositis (OM) is most cumbersome acute side effect of concurrent chemoradiotherapy (CCRT) for head and neck cancer (HNC). OM associated pain affects oral functions and nutrition of the patient that may result in discontinuity of treatment. Several modalities have been tried to prevent and treat OM, but none proved completely successful until date. We used prophylactic low level laser therapy (LLLT) for the prevention and treatment of CCRT induced OM. Materials and methods: In this triple blinded study, 221 HNC patients scheduled to undergo CCRT (Cisplatin (1, 22, 43 day) + RT = 66 Grays (2 Gy/fraction), 33 fractions, 5 fractions/week, for 45 days) were block randomized into laser (n = 111) and placebo (n = 110) group. Laser group received LLLT (HeNe, λ = 632.8 nm, power-density = 24 mW, dosage = 3.0 J/point, total dosage/session = 36–40 J, spot-size = 1 cm 2 , 5 sessions/week) while placebo received sham treatment daily prior to radiation. OM (RTOG/EORTC Scale), oral pain (VAS), dysphagia (FIS), weight loss and CCRT break were assessed. Data were analyzed using frequencies and percentage, generalized estimating equations (GEE) and odds ratio. Results: There was significant reduction in incidence of severe OM (F = 16.64, df = 8876, p < 0.0001) and its associated pain (F = 25.06, df = 8876, p < 0.0001), dysphagia (F = 20.17, df = 8876, p < 0.0001) and opioid analgesics use (p < 0.0001) in laser than placebo group patients. Conclusions: LLLT decreased the incidence of CCRT induced severe OM and its associated pain, dysphagia and opioid analgesics use.

Mucositis and oral infections secondary to gram negative rods in patients with prolonged neutropenia

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Mindy M. Sampson

2017-01-01

Full Text Available Patients with prolonged neutropenia are at risk for a variety of complications and infections including the development of mucositis and oral ulcers. The changes in oral flora during chemotherapy and its effects on the development of infections of the oral cavity have been studied with inconsistent results. However, there is evidence that supports the colonization of gram negative rods in patients undergoing chemotherapy. In this report, we present two leukemic patients who developed oral ulcers secondary to multi-drug resistant Pseudomonas aeruginosa. It is important to suspect multi-drug resistant gram negative rods in patients with prolonged neutropenia who develop gum infections despite appropriate antibiotic coverage.

The occurrence of oral-mucosal lesions among employees of a steelmill--a preliminary study.

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Zain, R B; Koh, L S

1988-11-01

A study has been conducted on 198 employees of a steel-mill industry. These participants were examined for mucosal lesions in the oral cavity and including the commissures and vermillion borders of the lips. The prevalences of 16 types of lesions are reported.

Azilsartan reduced TNF-α and IL-1β levels, increased IL-10 levels and upregulated VEGF, FGF, KGF, and TGF-α in an oral mucositis model.

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Aurigena Antunes de Araújo

Full Text Available Oral mucositis (OM is a common complication of treatments for head and neck cancer, particularly radiotherapy with or without chemotherapy. OM is characterised by oral erythema, ulceration, and pain. The aim of this study was to evaluate the effect of azilsartan (AZT, an angiotensin II receptor antagonist, on 5-fluorouracil (5-FU-induced oral mucositis (OM in Syrian hamsters. OM was induced by the intraperitoneal administration of 5-FU on experimental days 1 (60 mg/Kg and 2 (40 mg/Kg. Animals were pretreated with oral AZT (1, 5, or 10 mg/kg or vehicle 30 min before 5-FU injection and daily until day 10. Experimental treatment protocols were approved by the Animal Ethics Committee Use/CEUA (Number 28/2012 of the UFRN. Macroscopic analysis and cheek pouch samples were removed for histopathologic analysis. Myeloperoxidase (MPO, Malonyldialdehyde (MDA, interleukin-1 beta (IL-1β, interleukin-10 (IL-10, and tumour necrosis factor-alpha (TNF-α were analysed by Enzyme Linked Immuno Sorbent Assay (ELISA. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, keratinocyte growth factor (KGF, and transforming growth factor (TGF-α were measured by immunohistochemistry. Analysis of variance followed by Bonferroni's test was used to calculate the means of intergroup differences (p ≤ 0.05. Treatment with 1 mg/kg AZT reduced levels MPO (p<0.01, MDA (p<0.5 and histological inflammatory cell infiltration, and increased the presence of granulation tissue. AZT treatment at 1 mg/kg reduced the TNF-α (p<0.05 and IL-1β (p<0.05 levels, increased the cheek pouch levels of IL-10 (p<0.01, and upregulated VEGF, FGF, KGF, and TGF-α. Administration of AZT at higher doses (5 and 10 mg/kg did not significantly reverse the OM. AZT at a dose of 1 mg/kg prevented the mucosal damage and inflammation associated with 5-FU-induced OM, increasing granulation and tissue repair.

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

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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)

Sucralfate for the treatment of radiation induced mucositis

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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

Dental implants in patients with oral mucosal diseases - a systematic review.

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Reichart, P A; Schmidt-Westhausen, A M; Khongkhunthian, P; Strietzel, F P

2016-05-01

To reveal dental implants survival rates in patients with oral mucosal diseases: oral lichen planus (OLP), Sjögren's syndrome (SjS), epidermolysis bullosa (EB) and systemic sclerosis (SSc). A systematic literature search using PubMed/Medline and Embase databases, utilising MeSH and search term combinations identified publications on clinical use implant-prosthetic rehabilitation in patients with OLP, SjS, EB, SSc reporting on study design, number, gender and age of patients, follow-up period exceeding 12 months, implant survival rate, published in English between 1980 and May 2015. After a mean observation period (mOP) of 53·9 months (standard deviation [SD] ±18·3), 191 implants in 57 patients with OLP showed a survival rate (SR) of 95·3% (SD ±21·2). For 17 patients with SjS (121 implants, mOP 48·6 ± 28·7 months), 28 patients with EB (165 implants, mOP 38·3 ± 16·9 months) and five patients with SSc (38 implants, mOP 38·3 ± 16·9 months), the respective SR was 91·7 ± 5·97% (SjS), 98·5 ± 2·7% (EB) and 97·4 ± 4·8% (SSc). Heterogeneity of data structure and quality of reporting outcomes did not allow for further comparative data analysis. For implant-prosthetic rehabilitation of patients suffering from OLP, SjS, EB and SSc, no evidence-based treatment guidelines are presently available. However, no strict contraindication for the placement of implants seems to be justified in patients with OLP, SjS, EB nor SSc. Implant survival rates are comparable to those of patients without oral mucosal diseases. Treatment guidelines as for dental implantation in patients with healthy oral mucosa should be followed. © 2015 John Wiley & Sons Ltd.

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.

Mucosal immunity to poliovirus.

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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.

Oral mucosal lesions in Anorexia Nervosa, Bulimia Nervosa and EDNOS.

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Panico, Rene; Piemonte, Eduardo; Lazos, Jerónimo; Gilligan, Gerardo; Zampini, Anibal; Lanfranchi, Héctor

2018-01-01

The aim of this study is to describe oral lesions in patients with eating disorders (ED), including Anorexia Nervosa (AN), Bulimia Nervosa (BN) and eating disorders not otherwise specified (EDNOS). A prospective case-control study was carried out from April 2003 to May 2004. Inclusion criteria for the study group were individuals with a diagnosis of ED; age and sex-matched individuals without ED were included as controls. Clinical data regarding ED, medical complications and oral examination were performed by previously calibrated professionals. Study group (n = 65) presented 46 cases of BN (71%), 13 of EDNOS (20%) and 6 of AN (9%); also, 94% (n = 61) showed oral lesions. The most common were: labial erythema, exfoliative cheilitis, orange-yellow palate, hemorrhagic lesions, lip-cheek biting and non-specific oral atrophies. Only two patients of the study group had dental erosions, and no case of major salivary gland swelling was found. ED display a wide array of oral mucosal lesions that can be regarded as their early manifestations. The dentist could be the first professional to detect symptoms of eating disorders, potentially improving early detection and treatment of ED. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Efficacy of Plantago major, chlorhexidine 0.12% and sodium bicarbonate 5% solution in the treatment of oral mucositis in cancer patients with solid tumour: A feasibility randomised triple-blind phase III clinical trial.

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Cabrera-Jaime, Sandra; Martínez, Cristina; Ferro-García, Tarsila; Giner-Boya, Pilar; Icart-Isern, Teresa; Estrada-Masllorens, Joan M; Fernández-Ortega, Paz

2018-02-01

Oral mucositis is one of the most common adverse effects of chemotherapy and radiotherapy. The aim of this study was to compare the efficacy of Plantago major extract versus chlorhexidine 0.12% versus sodium bicarbonate 5% in the symptomatic treatment of chemotherapy-induced oral mucositis in solid tumour cancer patients. Multicentre randomised controlled trial estimated sample of 45 solid tumour patients with grade II-III mucositis. The participants were randomised to one of three treatments, consisting of sodium bicarbonate 5% aqueous solution together with: an additional dose of sodium bicarbonate 5% aqueous solution, Plantago major extract, or chlorhexidine 0.12%. The primary outcomes were severity of mucositis, pain intensity, oral intake capacity and quality of life. The independent variable was treatment group, and confounders included sociodemographic data, neutrophil count, chemotherapy drug and dose received. Of the 50 patients enrolled, 68% (n = 34) achieved grade 0 mucositis (none), with those using the double sodium bicarbonate rinse healing in five days on average (95% CI 3.9, 6.5) versus seven days (95% CI 5.3, 9,0) for the chlorhexidine group and seven days (95% CI 5.3, 8.5) for the Plantago major group. The pain experienced by the participants lessened over the 14 days of treatment, but differences in pain intensity between the three groups did not show statistical significance (p = 0.762). Healing time was shorter with the double sodium bicarbonate solution compared to the other two rinses, but the differences were not significant. Our results suggest it may be time to reconsider the use of Plantago major extract in the management of oral mucositis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Photographic documentation of acute radiation-induced side effects of the oral mucosa

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Riesenbeck, D.; Doerr, W.; Feyerabend, T.; Richter, E.; Fietkau, R.; Henne, K.; Schendera, A.

1998-01-01

Background: Radiotherapy in cancer of the head and neck induces cutaneous and mucosal reactions. These must be carefully assessed and documented to control the accuracy of individual treatment, the overall toxicity of particular treatment schedules, the efficacy of prophylaxis and treatment and to determine the adequate therapy of treatment sequelae depending on the severity of the reactions. The accurate classification of lesions according to internationally accepted schedules (WHO/RTOG/CTC) is indispensable for the comparison of radiotherapy treatment results and efficacy of supportive care. Methods: While the treatment of cancer depends on tumor stage and medical circumstances of the patient and is more or less standardized, prophylaxis and treatment of side-effects is highly variable. Discussing an optimized prophylaxis and therapy of oral mucositis, the problem of accurate classification and documentation emerged. The verbal description of mucosal lesions is open to many subjective interpretations. Photographic documentation seems a suitable method to optimize the grading of toxicity. Results: A photographic survey of typical lesions for each grade of toxicity is a tool to reach several aims in one step. Toxicity of an individual patient may be compared with representative photographic examples in daily routine to decide quickly on the grade of toxicity. Subjective differences due to intra- and interpersonal variability of the evaluating radiooncologist will be reduced. The efficacy of trof treatment can be proven by accurate documentation. Randomized clinical studies concerning prophylaxis and treatmen mucositis will provide more reliable results if evaluation of toxicity grading is standardized by photographs. Conclusions: Photographic documentation of lesions of the oral mucosa might be the best means to reduce interindividual subjectivity in grading. It is a valuable appendix to standard classification systems and only concerns the visible signs of mucosal

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

Microneedle and mucosal delivery of influenza vaccines

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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

Guideline for the prevention of oral and oropharyngeal mucositis in children receiving treatment for cancer or undergoing haematopoietic stem cell transplantation.

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Sung, Lillian; Robinson, Paula; Treister, Nathaniel; Baggott, Tina; Gibson, Paul; Tissing, Wim; Wiernikowski, John; Brinklow, Jennifer; Dupuis, L Lee

2017-03-01

To develop an evidence-based clinical practice guideline for the prevention of oral mucositis in children (0-18 years) receiving treatment for cancer or undergoing haematopoietic stem cell transplantation (HSCT). The Mucositis Prevention Guideline Development Group was interdisciplinary and included internationally recognised experts in paediatric mucositis. For the evidence review, we included randomised controlled trials (RCTs) conducted in either children or adults evaluating the following interventions selected according to prespecified criteria: cryotherapy, low level light therapy (LLLT) and keratinocyte growth factor (KGF). We also examined RCTs of any intervention conducted in children. For all systematic reviews, we synthesised the occurrence of severe oral mucositis. The Grades of Recommendation, Assessment, Development and Evaluation approach was used to describe quality of evidence and strength of recommendations. We suggest cryotherapy or LLLT may be offered to cooperative children receiving chemotherapy or HSCT conditioning with regimens associated with a high rate of mucositis. We also suggest KGF may be offered to children receiving HSCT conditioning with regimens associated with a high rate of severe mucositis. However, KGF use merits caution as there is a lack of efficacy and toxicity data in children, and a lack of long-term follow-up data in paediatric cancers. No other interventions were recommended for oral mucositis prevention in children. All three specific interventions evaluated in this clinical practice guideline were associated with a weak recommendation for use. There may be important organisational and cost barriers to the adoption of LLLT and KGF. Considerations for implementation and key research gaps are highlighted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[Studies on measurement of oral mucosal color with non-contact spectrum colorimeter].

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Ohata, Yohei

2006-03-01

Color inspection plays an important role in the diagnosis of oral mucosal lesions. However, it is sometimes difficult to diagnose by color, because color is always evaluated subjectively. In order to measure color objectively and quantitatively, we decided to use a newly developed spectrum colorimeter for the oral mucosa. To keep the same angle and distance, a special stick was utilized. Various experiments were performed and suitable conditions for accurate colorimetric measurement were decided, including room temperature with cooling fan, onset time of the device, calibration timing, and the angle between light and the measured surface. The reproducibility of this method was confirmed by measuring the color of the buccal mucosa in healthy persons.

Removable denture-related oral mucosal lesions: descriptive clinical study

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Gökçen Akçiçek

2017-05-01

Full Text Available Objective: The aim of this study was to investigate whether there was a relationship between removable denture-related oral mucosal lesions and denture type, and demographic characteristics. Materials and Method: The age, sex, denture type, systemic condition and medication use, presence of denture-related oral mucosal lesions (DROML, their locations and patients’ awareness of above mentioned lesions were recorded for 199 patients. Pearson chi-square test was used to analyse the relationship between the DROML and denture type, and demographic characteristics of the patients. Results: Among the patients included to the study, 122 (61.3% were female and 77 (38.7% were male. Ninety-six patients (48.2% exhibited DROML, whereas 103 patients (51.8% had no DROML. No relationship was detected between DROML and age, and sex (p>0.05. The most commonly detected DROML was denture stomatitis (34.7%. Denture stomatitis was significantly more frequently seen in partial denture wearers (p<0.05, while epulis fissuratum and flabby ridge were statistically more frequent in complete denture wearers (p<0.001. Traumatic ulcer was more frequently found in mandibular complete denture wearers (p<0.05, while epulis fissuratum and flabby ridge were significantly more common in maxillary complete denture wearers (p<0.001. Among the patients with DROML, 57.3% stated that they were unaware of these lesions. Conclusion: In this study sample, the rate of DROML was high in patients wearing removable dentures (48.2%, and more than half of the patients with DROML were not aware of these lesions. Upon these findings, it is considered that removable denture wearers should follow the denture usage instructions and should be informed about the importance of periodic controls.

Radiation induced muscositis as space flight risk. Model studies on X-ray and heavy ion irradiated typical oral mucosa models

International Nuclear Information System (INIS)

Tschachojan, Viktoria

2014-01-01

Humans in exomagnetospheric space are exposed to highly energetic heavy ion radiation which can be hardly shielded. Since radiation-induced mucositis constitutes a severe complication of heavy ion radiotherapy, it would also implicate a serious medical safety risk for the crew members during prolonged space flights such as missions to Moon or Mars. For assessment of risk developing radiation-induced mucositis, three-dimensional organotypic cultures of immortalized human keratinocytes and fibroblasts were irradiated with a 12 C particle beam at high energies or X-Rays. Immunofluorescence stainings were done from cryosections and radiation induced release of cytokines and chemokines was quantified by ELISA from culture supernatants. The major focuses of this study were on 4, 8, 24 and 48 hours after irradiation. The conducted analyses of our mucosa model showed many structural similarities with the native oral mucosa and authentic immunological responses to radiation exposure. Quantification of the DNA damage in irradiated mucosa models revealed about twice as many DSB after heavy-ion irradiation compared to X-rays at definite doses and time points, suggesting a higher gene toxicity of heavy ions. Nuclear factor κB activation was observed after treatment with X-rays or 12 C particles. An activation of NF κB p65 in irradiated samples could not be detected. ELISA analyses showed significantly higher interleukin 6 and interleukin 8 levels after irradiation with X-rays and 12 C particles compared to non-irradiated controls. However, only X-rays induced significantly higher levels of interleukin 1β. Analyses of TNF-α and IFN-γ showed no radiation-induced effects. Further analyses revealed a radiation-induced reduction in proliferation and loss of compactness in irradiated oral mucosa model, which would lead to local lesions in vivo. In this study we revealed that several pro-inflammatory markers and structural changes are induced by X-rays and heavy-ion irradiation

Comparison of granulocyte-macrophage colony-stimulating factor and sucralfate mouthwashes in the prevention of radiation-induced mucositis: a double-blind prospective randomized phase III study

International Nuclear Information System (INIS)

Saarilahti, Kauko; Kajanti, Mikael; Joensuu, Timo; Kouri, Mauri; Joensuu, Heikki

2002-01-01

Purpose: To compare granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes with sucralfate mouthwashes in the prevention of radiation-induced mucositis. Methods and Materials: Forty patients with radically operated head-and-neck cancer were randomly allocated to use either GM-CSF (n=21) or sucralfate (n=19) mouthwashes during postoperative radiotherapy (RT). All patients received conventionally fractionated RT to a total dose of 50-60 Gy in 2-Gy daily fractions during 5-6 weeks to the primary site and regional lymphatics. A minimum of 50% of the oral cavity and oropharyngeal mucosa was included in the clinical target volume. GM-CSF mouthwashes consisted of 37.5 μg GM-CSF and sucralfate mouthwashes of 1.0 g of sucralfate distilled in water. Both washes were used 4 times daily, beginning after the first week of RT and continued to the end of the RT course. Symptoms related to radiation mucositis and body weight, serum prealbumin level, and blood cell counts were monitored weekly. Results: Oral mucositis tended to be less severe in the GM-CSF group (p=0.072). Complete (n=1) or partial (n=4) healing of mucositis occurred during the RT course in 5 patients (24%) in the GM-CSF group and in none of the patients in the sucralfate group (p=0.049). Patients who received GM-CSF had less mucosal pain (p=0.058) and were less often prescribed opioids for pain (p=0.042). Three patients in the sucralfate group needed hospitalization for mucositis during RT compared with none in the GM-CSF group. Four patients (21%) in the sucralfate group and none in the GM-CSF group required an interruption in the RT course (p=0.042). No significant differences in weight, prealbumin level, or blood cell count were found between the groups, and both mouthwashes were well tolerated. Conclusion: GM-CSF mouthwashes may be moderately more effective than sucralfate mouthwashes in preventing radiation-induced mucositis and mucositis-related pain, and their use may lead to less frequent

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.

Patient and oncologist perceptions regarding symptoms and impact on quality-of-life of oral mucositis in cancer treatment: results from the Awareness Drives Oral Mucositis PercepTion (ADOPT) study.

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Kanagalingam, Jeevendra; Wahid, Mohamed Ibrahim A; Lin, Jin-Ching; Cupino, Nonette A; Liu, Edward; Kang, Jin-Hyoung; Bazarbashi, Shouki; Bender Moreira, Nicole; Arumugam, Harsha; Mueller, Stefan; Moon, Hanlim

2018-07-01

This descriptive cross-sectional survey aims to assess the level of concordance between the perspectives of oncologists and those of patients regarding oral mucositis (OM) symptoms, and the impact of OM on various aspects of daily living and concurrent cancer management. Oncologists involved in OM management (n = 105), and patients who developed OM during cancer treatment (n = 175), were recruited from seven Asian countries. Oncologists completed a face-to-face, quantitative interview; patients completed a face-to-face interview, and a self-reported questionnaire. Oncologists and patients ranked treatment-induced OM among the three most important toxicities of cancer therapy requiring intervention. The most frequent OM symptoms reported by patients were oral ulcers (74%), dry mouth (73%), and difficulty swallowing (62%). Oncologists expected mild OM symptoms to last slightly longer than 1 week, whereas patients reported mild symptoms for more than 2 weeks. In mild-to-moderate OM, oncologists underestimated patients' pain experience. Overall, only 45% of oncologists said they would initiate OM prophylaxis when cancer therapy started. Of the 87% of patients who said they used their prescribed medications, only 16% reported using prophylactically prescribed medication. While oncologists' concerns related to the delays and interruptions of cancer treatment, patients tended to focus on the effects of OM on eating, drinking, and talking. Oncologists' and patients' perceptions about treatment-induced OM differ. To overcome discordant perspectives, there is a need to raise general awareness and improve proactive management of OM. As noted in recent guidelines, supportive cancer care is critical for ensuring optimal therapy and for improving the patient's experience.

Two cases of radiotherapy-induced oral mucositis alleviated with hange-shashin-to

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Tanaka, Yuya; Yamashita, Taku; Matsunobu, Takeshi; Shiotani, Akihiro

2012-01-01

It has been reported that concurrent chemoradiotherapy (CCRT) can result in a superior treatment response and survival outcome compared with radiotherapy alone in patients with squamous cell carcinoma of the head and neck, and it has become the standard of care for locally advanced disease and organ preservation. However, the major limitation to radiotherapy or CCRT is locoregional treatment-related toxicities, particularly oral mucositis (OM). We experienced two cases of pain-uncontrolled OM in which the Traditional Oriental Medicine Hange-shashin-to (TJ-14) was effective. A 44-year-old man with nasopharyngeal carcinoma and neck metastases underwent CCRT and suffered from OM of grade 3 according to the Common Terminology Criteria for Adverse Effects (CTCAE). His pain was uncontrolled with a variety of analgesics, so we prescribed TJ-14 for him as a gargle. Even during CCRT, the pain significantly diminished and OM was improved to grade 1. TJ-14 contributed to completion of CCRT and improvement of the patient's nutrition status. A 67-year-old man with unknown primary and neck metastases underwent neck dissection and adjuvant radiotherapy. During adjuvant radiotherapy, he had OM of grade 3 and was unable to eat, so he was hospitalized and was started to have TJ-14. Although his OM remained grade 3 during the therapy, his pain was alleviated, leading to completion of the treatment. TJ-14 can be an effective supportive therapy for OM caused by radiotherapy. (author)

[BIPADDLED SPLIT PECTORALIS MAJOR MYOCUTANEOUS FLAPS FOR IMMEDIATE RECONSTRUCTION OF ORAL MUCOSAL DEFECTS AND NECK DEFECTS AFTER RESECTION OF RECURRENT ORAL CANCER].

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Chen, Jie; Jiang, Canhua; Li, Ning; Gao, Zhengyang; Chen, Lichun; Wu, Xiaoshan; Chen, Xinqun; Jian, Xinchun

2015-07-01

To investigate the feasibility of the bipaddled split pectoralis major myocutaneous flap for immediate reconstruction of oral mucosal defects and neck defects after resection of recurrent oral cancer. Six patients with oral mucosal defects combined with neck defects after recurrent oral cancer resection were treated with bipaddled split pectoralis major myocutaneous flap between September 2013 and September 2014. There were 5 males and 1 female with an average age of 54.7 years (range, 45-62 years), including 4 cases of recurrent tongue cancer, 1 case of recurrent mandibular gingival cancer, and 1 case of mouth floor carcinoma. All patients underwent local recurrence at 8 to 14 months after first operation, with no distant metastasis. The defects of the intraoral mucosa was 4.0 cm x 2.5 cm to 6.5 cm x 3.5 cm and the defect of the neck skin was 5.5 cm x 3.5 cm to 7.5 cm x 5.0 cm. The pectoralis major myocutaneous flaps (14.0 cm x 3.5 cm to 17.0 cm x 5.5 cm) were incised at the level of the 3rd to the 4th rib, and then split down along the muscle fiber till about 2 cm away from the thoracoacromial vessels, forming 2 independent skin paddles with 1-2 branch vessels to the pedicles of the distal ones. The distal skin paddles were used for oral reconstruction while the proximal paddles for repair of neck defects. The chest donor sites were sutured directly. Cervical haematoma and infection happened in 1 patient respectively after operation, and were cured after symptomatic treatment. All 6 split pectoralis major myocutaneous flaps with 12 skin paddles completely survived. All patients were followed up 6 to 18 months (mean, 11 months). One patient died of pulmonary metastasis at 8 months after operation and the other 5 survived without relapse or metastasis during follow-up. The intraoral paddles showed good shape with satisfactory speech function and swallowing recovery. The paddles also healed perfectly on the neck with flat outlooks, and all patients obtained full

Oral delivery of Bacillus subtilis spore expressing enolase of Clonorchis sinensis in rat model: induce systemic and local mucosal immune responses and has no side effect on liver function.

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Yu, Jinyun; Chen, Tingjin; Xie, Zhizhi; Liang, Pei; Qu, Honglin; Shang, Mei; Mao, Qiang; Ning, Dan; Tang, Zeli; Shi, Mengchen; Zhou, Lina; Huang, Yan; Yu, Xinbing

2015-07-01

Caused by the consumption of raw or undercooked freshwater fish containing infective metacercariae of Clonorchis sinensis, human clonorchiasis remains a major public health problem in China. In previous study, we had expressed enolase from C. sinensis (CsENO) on the surface of Bacillus subtilis spore and the recombinant spore induced a pronounced protection in terms of reduced worm burden and eggs per gram feces, suggesting B. subtilis spore as an ideal vehicle for antigen delivery by oral treatment and CsENO as a promising vaccine candidate against clonorchiasis. In the current study, we detected CsENO-specific IgG and IgA levels both in serum and in intestinal mucus from rats orally administrated with B. subtilis spore surface expressing CsENO by ELISA. Lysozyme levels in serum and in intestinal mucus were analyzed too. In addition, IgA-secreting cells in intestine epithelium of the rats were detected by immunohistochemistry assay. The intestinal villi lengths of duodenum, jejunum, and ileum were also measured. Rats orally treated with B. subtilis spore or normal saline were used as controls. Our results showed that, compared with the control groups, oral administration of B. subtilis spore expressing CsENO induced both systemic and local mucosal immune response. The recombinant spores also enhanced non-specific immune response in rats. The spores had no side effect on liver function. Moreover, it might facilitate food utilization and digestion of the rats. Our work will pave the way to clarify the involved mechanisms of protective efficacy elicited by B. subtilis spore expressing CsENO and encourage us to carry out more assessment trails of the oral treated spore to develop vaccine against clonorchiasis.

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.

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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

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

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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

Virulence factors and antibiotic susceptibility in enterococci isolated from oral mucosal and deep infections

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Gunnar Dahlén

2012-02-01

Full Text Available This study evaluates the presence of virulence factors and antibiotic susceptibility among enterococcal isolates from oral mucosal and deep infections. Forty-three enterococcal strains from oral mucosal lesions and 18 from deep infections were isolated from 830 samples that were sent during 2 years to Oral Microbiology, University of Gothenburg, for analysis. The 61 strains were identified by 16S rDNA, and characterized by the presence of the virulence genes efa A (endocarditis gene, gel E (gelatinase gene, ace (collagen binding antigen gene, asa (aggregation substance gene, cyl A (cytolysin activator gene and esp (surface adhesin gene, tested for the production of bacteriocins and presence of plasmids. MIC determination was performed using the E-test method against the most commonly used antibiotics in dentistry, for example, penicillin V, amoxicillin and clindamycin. Vancomycin was included in order to detect vancomycin-resistant enterococci (VRE strains. Sixty strains were identified as Enterococcus faecalis and one as Enterococcus faecium. All the virulence genes were detected in more than 93.3% (efa A and esp of the E. faecalis strains, while the presence of phenotypic characteristics was much lower (gelatinase 10% and hemolysin 16.7%. Forty-six strains produced bacteriocins and one to six plasmids were detected in half of the isolates. Enterococcal strains from oral infections had a high virulence capacity, showed bacteriocin production and had numerous plasmids. They were generally susceptible to ampicillins but were resistant to clindamycin, commonly used in dentistry, and no VRE-strain was found.

Evaluating the effectiveness of topical application of natural honey and benzydamine hydrochloride in the management of radiation mucositis

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Sadaksharam Jayachandran

2012-01-01

Conclusion: Pure natural honey can be an effective agent in managing radiation induced oral mucositis. Honey could be a simple, potent and inexpensive agent, which is easily available, and it can be a better therapeutic agent in managing radiation mucositis in developing countries like India for the management of this morbidity.

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

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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

Oral immunization with rotavirus VP7 expressed in transgenic potatoes induced high titers of mucosal neutralizing IgA

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Wu Yuzhang; Li Jintao; Mou Zhirong; Fei Lei; Ni Bing; Geng Miao; Jia Zhengcai; Zhou Wei; Zou Liyun; Tang Yan

2003-01-01

Rotaviruses (RV) are a common cause of severe diarrhea in young children, resulting in nearly one million deaths worldwide annually. Rotavirus VP7 was the rotavirus neutralizing protein. Previous study reported that VP7 DNA vaccine can induce high levels of IgG in mice but cannot protect mice against challenge (Choi, A.H., Basu, M., Rae, M.N., McNeal, M.M., Ward, R.L., 1998. Virology 250, 230-240). We found that rotavirus VP7 could maintain its neutralizing immunity when it was transformed into the potato genome. Mice immunized with the transformed tubers successfully elicited serum IgG and mucosal IgA specific for VP7. The mucosal IgA titer was as high as 1000, while serum IgG titer was only 600. Neutralizing assays indicated that IgA could neutralize rotavirus. These results indicate the potential usefulness of plants for production and delivery of edible rotavirus vaccines

A protective role for keratinocyte growth factor in a murine model of chemotherapy and radiotherapy-induced mucositis

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Borges, Luis; Rex, Karen L.; Chen, Jennifer N.; Wei, Ping; Kaufman, Stephen; Scully, Sheila; Pretorius, James K.; Farrell, Catherine L.

2006-01-01

Purpose: To evaluate the activity of palifermin (rHuKGF) in a murine model of mucosal damage induced by a radiotherapy/chemotherapy (RT/CT) regimen mimicking treatment protocols used in head-and-neck cancer patients. Methods and Materials: A model of mucosal damage induced by RT/CT was established by injecting female BDF1 mice with cisplatin (10 mg/kg) on Day 1; 5-fluorouracil (40 mg/kg/day) on Days 1-4, and irradiation (5 Gy/day) to the head and neck on Days 1-5. Palifermin was administered subcutaneously on Days -2 to 0 (5 mg/kg/day) and on Day 5 (5 mg/kg). Evaluations included body weight, organ weight, keratinocyte growth factor receptor expression, epithelial thickness, and cellular proliferation. Results: Initiation of the radiochemotherapeutic regimen resulted in a reduction in body weight in control animals. Palifermin administration suppressed weight loss and resulted in increased organ weight (salivary glands and small intestine), epithelial thickness (esophagus and tongue), and cellular proliferation (tongue and salivary glands). Conclusions: Administration of palifermin before RT/CT promotes cell proliferation and increases in epithelial thickness in the oral mucosa, salivary glands, and digestive tract. Palifermin administration before and after RT/CT mitigates weight loss and a trophic effect on the intestinal mucosa and salivary glands, suggesting that palifermin use should be investigated further in the RT/CT settings, in which intestinal mucositis and salivary gland dysfunction are predominant side effects of cytotoxic therapy

Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage?

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Wallace, J.L.; Beck, P.L.; Morris, G.P.

1988-01-01

The role of leukotriene (LT) C 4 as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis and agents that have previously been shown to reduce ethanol-induced damage prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC 4 synthesis. LTC 4 synthesis could be reduced significantly by pretreatment with L651,392 or dexamethosone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. Furthermore, changes in LBT 4 synthesis paralleled the changes in LTC 4 synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. These studies confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC 4 synthesis does not confer protection to the mucosa, suggesting that LTC 4 does not play an important role in the etiology of ethanol-induced gastric damage

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

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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).

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

Prevalence and Distribution of Oral Mucosal Lesions by Sex and Age Categories: A Retrospective Study of Patients Attending Lebanese School of Dentistry

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Sami El Toum

2018-01-01

Full Text Available Background. Prevalence and distribution of oral mucosal lesions in a sample of Lebanese population attending the School of Dentistry of Lebanese University is necessary to evaluate their oral health situation. Objectives. The aim of the present study was to determine the prevalence and distribution of oral mucosal lesions of patients attending the School of Dentistry. Methods. A descriptive study was carried out by retrospectively examining a total of 231 medical and clinical examination record files of patients, attending the School of Dentistry Lebanese University for multidisciplinary dental treatments. 178 medical records were retained. Each medical and clinical examination record was done by an undergraduate student and then evaluated by a doctor. The record file included a civil status, chief complaint, medical history, and extraoral and intraoral clinical examination during the period between October 2014 and May 2015. Exclusion criteria were lack of written information in their medical and clinical examination record and being nonevaluated by a doctor. Data regarding age, gender, socioeconomic status, chief complaint, systemic diseases, and drugs intake were collected by using a questionnaire while the type of extraoral and oral mucosal lesions by clinical examination. Results. The sample consisted of 102 (57.3% females and 76 (42.7% males. The age ranged from 10 to 92 years with a mean age of 40.1 years. Among these subjects, 110 (61.8% presented with one or more lesions. All patients were Lebanese. The most common lesion diagnosed was coated/hairy tongue affecting 17.4% of the subjects, followed by melanotic macule (11.2%, gingivitis (9.6, linea alba (6.2%, tongue depapillation (5.1, leukoplakia (5.1, traumatic fibroma (4.5, frictional keratosis (3.9%, fissured tongue (3.9%, hemangiomas (3.9%, Fordyce granules (3.9%, dry mucosa (3.4, angular cheilitis (2.2, gingival hyperplasia (2.2, and crenulated tongue (1.7%. Overall, the prevalence

Curcuminoids from Curcuma longaL. reduced intestinal mucositis induced by 5-fluorouracil in mice: Bioadhesive, proliferative, anti-inflammatory and antioxidant effects

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Edvande Xavier dos Santos Filho

Full Text Available Introduction: Intestinal mucositis is a frequent limiting factor in anticancer therapy and there is currently no broadly effective treatment targeted to cure this side effect. Objective: This study aimed to evaluate the effects of a mucoadhesive formulation containing curcuminoids (MFC from Curcuma longa L. on the pathogenesis of 5-fluorouracil (5-FU-induced intestinal mucositis. Methods: Three intraperitoneal 5-FU injections (200 mg/kg were used to induce intestinal mucositis in adult Swiss male mice. Treatment was provided orally (MFC 3.75, 7.5 and 15 mg/kg, thirty minutes before 5-FU injections, daily until euthanasia. Duodenal samples were collected to perform morphometric and histopathological analysis, to investigate the expression of Ki-67, p53, Bax and Bcl-2 by immunohistochemistry, to evaluate neutrophil activity myeloperoxidase (MPO-mediated and oxidative stress by malondialdehyde (MDA determination. Mice body weight was assessed as well. Results: As expected, 5-FU induced a significant weight loss (∼17%, P < 0.001, shortening in villi height (∼55.4% and crypts depth (∼47%, and increased (∼64% the histological severity score when compared to other groups (P < 0.05. These pathological changes were markedly alleviated by the three MFC treatment doses (P < 0.05, in special with the dose MFC 15 mg/kg. This dose also stimulated cell proliferation by ∼90% in the epithelial cells lining from villi and crypts (P < 0.05, reduced MPO levels and MDA formation by 60% and 44%, respectively (P < 0.05. Conclusions: Our data suggest the therapeutic potential of the formulation for treating intestinal mucositis in mice. Supplementary studies are underway searching for the elucidation of mechanisms involved in the protective effects of MFC in order to make this formulation a clinical tool for mucositis treatment. Keywords: Mucoadhesive formulation, Curcuminoids, Curcuma longa L, Intestinal mucositis, 5-Fluorouracil

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)

Analysis of incidence and nursing care for oral adverse events induced by chest or pelvic irradiation combined with chemotherapy

International Nuclear Information System (INIS)

Seki, Miyuki; Kitada, Yoko; Ishikawa, Hitoshi

2010-01-01

The aim of this study was to clarify incidence and severity of oral adverse events induced by chemoradiotherapy and to explore efficient nursing-intervention or oral-care for the oral complications. Seventy-nine subjects who were treated with chemoradiotherapy at the radiation oncology unit of Gunma University Hospital were retrospectively analyzed using collected data from patients' medical chart including location of tumor, details of treatment, incidence and care of oral adverse events. Oral adverse events occurred in 7 (9%) of 79 patients. The complication rate in patients with lung or esophageal cancer was much higher than that with rectal or cervical cancer. All patients with the events received a total irradiation dose of 60 Gy in 30 fractions or higher. Oral mucositis was observed in 5 patients given antimetabolic chemotherapeutic agents, but they were successfully treated with steroids and/or gargles. Our results suggest that early intervention of oral care may reduce risks of developing severe oral adverse effects induced by chemoradiotherapy. (author)

Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients.

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Mercadante, Sebastiano; Aielli, Federica; Adile, Claudio; Ferrera, Patrizia; Valle, Alessandro; Fusco, Flavio; Caruselli, Amanda; Cartoni, Claudio; Massimo, Pizzuto; Masedu, Francesco; Valenti, Marco; Porzio, Giampiero

2015-11-01

Oral symptoms can be a sign of an underlying systemic condition and have a significant impact on quality of life, nutrition, and cost of care, while these lesions are often studied in the context of cancer treatment. However, information regarding oral symptoms in advanced cancer patients is poor. The aim of this multicenter study was to determine the prevalence and the characteristics of oral symptoms in a large population of advanced cancer patients. A consecutive sample of patients with advanced cancer for a period of 6 months was prospectively assessed for an observational study. At time of admission, the epidemiological characteristics, surgery-radiotherapy of head and neck, and oncologic treatments in the last month were recorded. The presence of mucositis, dry mouth, and dysphagia was assessed by clinical examination and patients' report and their intensity recorded. Patients were also asked whether they had limitation on nutrition of hydration due to the local condition. Six hundred sixty-nine patients were surveyed in the period taken into consideration. The mean age was 72.1 years (SD 12.3), and 342 patients were males. The primary tumors are listed in Table 1. The prevalence of mucositis was 22.3 %. The symptom relevantly reduced the ingestion of food or fluids and was statistically associated with the Karnofsky level and head and neck cancer. The prevalence of dry mouth was 40.4 %, with a mean intensity of 5.4 (SD 2.1). Several drugs were concomitantly given, particularly opioids (78 %), corticosteroids (75.3 %), and diuretics (70.2 %). Various and nonhomogeneous treatments were given for dry mouth, that was statistically associated with current or recent chemotherapy, and hematological tumors. The prevalence of dysphagia was 15.4 % with a mean intensity of 5.34 (SD 3). Dysphagia for liquids was observed in 52.4 % of cases. A high level of limitation for oral nutrition due to dysphagia was found, and in 53.4 % of patients, alternative routes to the oral

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...

Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage

Science.gov (United States)

Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

2006-01-01

AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5’-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5’-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage. PMID:16865772

Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage.

Science.gov (United States)

Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

2006-07-21

To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5'-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5'-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

8-prenylnaringenin and tamoxifen inhibit the shedding of irradiated epithelial cells and increase the latency period of radiation-induced oral mucositis. Cell culture and murine model

Energy Technology Data Exchange (ETDEWEB)

Ryck, Tine de; Impe, Annouchka van; Bracke, Marc E. [Ghent University, Laboratory of Experimental Cancer Research, Department Radiation Oncology and Experimental Cancer Research, Ghent (Belgium); Vanhoecke, Barbara W. [Ghent University, Laboratory of Experimental Cancer Research, Department Radiation Oncology and Experimental Cancer Research, Ghent (Belgium); Ghent University, Laboratory of Microbial Ecology and Technology (LabMET), Ghent (Belgium); Heyerick, Arne [Ghent University, Laboratory of Pharmacognosy and Phytochemistry, Ghent (Belgium); Vakaet, Luc; Neve, Wilfried de [Ghent University Hospital, Department of Radiation Oncology, Ghent (Belgium); Mueller, Doreen [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Dresden (Germany); Schmidt, Margret [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Dresden (Germany); German Cancer Consortium (DKTK) partner site Dresden and German Cancer Center (DKFZ), Heidelberg (Germany); Doerr, Wolfgang [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Dresden (Germany); Medical University, Department of Radiation Oncology, CCC, and CD-Laboratory RadOnc, Vienna (Austria)

2015-05-01

The major component in the pathogenesis of oral radiation-induced mucositis is progressive epithelial hypoplasia and eventual ulceration. Irradiation inhibits cell proliferation, while cell loss at the surface continues. We conceived to slow down this desquamation by increasing intercellular adhesion, regulated by the E-cadherin/catenin complex. We investigated if 8-prenylnaringenin (8-PN) or tamoxifen (TAM) decrease the shedding of irradiated human buccal epithelial cells in vitro and thus delay the ulcerative phase of radiation-induced mucositis in vivo. In vitro, aggregates of buccal epithelial cells were irradiated and cultured in suspension for 11 days. 8-PN or TAM were investigated regarding their effect on cell shedding. In vivo, the lower tongue surface of mice was irradiated with graded single doses of 25 kV X-rays. The incidence, latency, and duration of the resulting mucosal ulcerations were analyzed after topical treatment with 8-PN, TAM or solvent. 8-PN or TAM prevented the volume reduction of the irradiated cell aggregates during the incubation period. This was the result of a higher residual cell number in the treated versus the untreated irradiated aggregates. In vivo, topical treatment with 8-PN or TAM significantly increased the latency of mucositis from 10.9 to 12.1 and 12.4 days respectively, while the ulcer incidence was unchanged. 8-PN and TAM prevent volume reduction of irradiated cell aggregates in suspension culture. In the tongues of mice, these compounds increase the latency period. This suggests a role for these compounds for the amelioration of radiation-induced mucositis in the treatment of head and neck tumors. (orig.) [German] Die wesentliche Komponente in der Pathogenese der radiogenen Mukositis ist eine progressive epitheliale Hypoplasie und letztendlich Ulzeration. Die Bestrahlung hemmt die Zellproliferation, waehrend der Zellverlust an der Oberflaeche fortbesteht. Wir versuchten, diese Desquamation durch eine Stimulation der

[Recurrent pulmonary infection and oral mucosal ulcer].

Science.gov (United States)

Kuang, Fei-Mei; Tang, Lan-Lan; Zhang, Hui; Xie, Min; Yang, Ming-Hua; Yang, Liang-Chun; Yu, Yan; Cao, Li-Zhi

2017-04-01

An 8-year-old girl who had experienced intermittent cough and fever over a 3 year period, was admitted after experiencing a recurrence for one month. One year ago the patient experienced a recurrent oral mucosal ulcer. Physical examination showed vitiligo in the skin of the upper right back. Routine blood tests and immune function tests performed in other hospitals had shown normal results. Multiple lung CT scans showed pulmonary infection. The patient had recurrent fever and cough and persistent presence of some lesions after anti-infective therapy. The antitubercular therapy was ineffective. Routine blood tests after admission showed agranulocytosis. Gene detection was performed and she was diagnosed with dyskeratosis congenita caused by homozygous mutation in RTEL1. Patients with dyskeratosis congenita with RTEL1 gene mutation tend to develop pulmonary complications. Since RTEL1 gene sequence is highly variable with many mutation sites and patterns and can be inherited via autosomal dominant or recessive inheritance, this disease often has various clinical manifestations, which may lead to missed diagnosis or misdiagnosis. For children with unexplained recurrent pulmonary infection, examinations of the oral cavity, skin, and nails and toes should be taken and routine blood tests should be performed to exclude dyskeratosis congenita. There are no specific therapies for dyskeratosis congenita at present, and when bone marrow failure and pulmonary failure occur, hematopoietic stem cell transplantation and lung transplantation are the only therapies. Androgen and its derivatives are effective in some patients. Drugs targeting the telomere may be promising for patients with dyskeratosis congenita.

Phenylbutyrate Mouthwash Mitigates Oral Mucositis During Radiotherapy or Chemoradiotherapy in Patients With Head-and-Neck Cancer

Energy Technology Data Exchange (ETDEWEB)

Yen, Sang-Hue; Wang, Ling-Wei [Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan (China); National Yang Ming University, School of Medicine, Taipei, Taiwan (China); Lin, Yi-Hsien [Division of Radiotherapy, Cheng Hsin General Hospital, Taipei, Taiwan (China); Jen, Yee-Min, E-mail: yeeminjen@yahoo.com.tw [Department of Radiation Oncology, Tri-Service General Hospital, Taipei, Taiwan (China); National Defense Medical Center, Taipei, Taiwan (China); Chung, Yih-Lin, E-mail: ylchung@kfsyscc.org [Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); National Yang Ming University, School of Medicine, Taipei, Taiwan (China)

2012-03-15

Purpose: Deleterious oral mucositis (OM) develops during radiotherapy (RT) or chemoradiotherapy for head-and-neck cancer (HNC) patients. There are currently no effective cytoprotective treatments for OM without a potential risk of tumor protection. This randomized, double-blind, placebo-controlled pilot study aimed to determine the therapeutic safety and efficacy of phenylbutyrate (an antitumor histone deacetylase inhibitor and chemical chaperone) 5% mouthwash for treating OM caused by cancer therapy. Methods and Materials: Between September 2005 and June 2006, 36 HNC patients were randomized to standard oral care plus 5 mL of either phenylbutyrate 5% mouthwash (n = 17) or placebo (mouthwash vehicle, n = 19) taken four times daily (swish and spit). Treatment began when mild mucositis (Radiation Therapy Oncology Group Grade 1) occurred, and ended 4 weeks after RT completion. Safety and efficacy were based on adverse events, physical examination, laboratory determinations, vital signs, Oral Mucosa Assessment Scale (OMAS) and World Health Organization scores, the ability to eat, body weight change, local control, and survival. Results: We found no severe drug-related side effect. At RT doses of 5500-7500 cGy, phenylbutyrate significantly mitigated the severity of mucositis compared with placebo, based on both the WHO score (severity {>=} 3; p = 0.0262) and the OMAS scale (ulceration score {>=} 2; p = 0.0049). The Kaplan-Meier estimates for 2- and 3-year local control, and overall survival were 100% and 80.8%, and 78.6% and 64.3%, respectively, in the phenylbutyrate group and 74.2% and 74.2%, and 57.4% and 50.2%, respectively, in the placebo group. Conclusions: This pilot trial suggested that phenylbutyrate mouthwash significantly decreased the impact of OM in HNC patients receiving RT or chemoradiotherapy and did not confront the tumor control. Larger Phase II randomized trials are needed to confirm these results.

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.

Science.gov (United States)

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.

Radiation-induced muscositis and neutrophil granulocytes in oral mucosa; Strahleninduzierte Mukositis und neutrophile Granulozyten in der Mundschleimhaut

Energy Technology Data Exchange (ETDEWEB)

Schmidberger, H.; Rave-Fraenk, M.; Kim, S.; Hille, A.; Pradier, O.; Hess, C.F. [Klinik fuer Strahlentherapie und Radioonkologie, Univ. Goettingen (Germany)

2003-10-01

Background: Chemotherapy-induced mucositis can be related to a decrease in oral neutrophils. We tested the relationship between radiation-induced mucositis and oral neutrophil counts. Patients and Methods: Oral neutrophil counts were obtained for ten patients with head and neck cancer who received radiotherapy of the pharynx and oral cavity. Four patients received additional chemotherapy (5-FU, Mitomycin). Counts were obtained before and during treatment; four healthy volunteers were included in the study as well. For evaluation, a quantitative mouth rinse assay, including neutrophil-staining with acridin-orange, was applied. Results: We observed large inter-individual variations with respect to neutrophil counts for patients and control persons (Table 1). During treatment (irradiation or chemoirradiation), large intra-individual variations were seen additionally (Figure 1). We found a correlation between neutrophil counts and clinical reaction grade. Neutrophil counts increased with increasing mucositis (Figure 2). This increase was more pronounced for patients treated with chemoirradiation compared to radiation alone. Treatment breaks at weekends had no clear influence on neutrophil counts. Conclusions: We observed a weak correlation between neutrophil counts and clinical reaction grade. However, the variations in neutrophil counts are too large to utilize this parameter as a surrogate for clinical mucositis grading. The assumption that a decrease in oral neutrophils is associated with radiation-induced mucositis was clearly negated. (orig.) [German] Hintergrund: Die chemotherapieinduzierte Mukositis kann mit einer Verarmung der Mundschleimhaut an neutrophilen Granulozyten vergesellschaftet sein. Wir ueberprueften den Zusammenhang zwischen der radiogenen Mukositis und der Anzahl neutrophiler Granulozyten. Patienten und Methoden: Bei zehn Patienten mit Tumoren der Kopf-Hals-Region, die sich einer Strahlentherapie unterzogen, wurde die Anzahl enoraler neutrophiler

BISPHOSPHONATE - RELATED MUCOSITIS (BRM: A CASE REPORT

Directory of Open Access Journals (Sweden)

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.

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.

Science.gov (United States)

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.

Radiation-induced changes in cellularity and proliferation in human oral mucosa

International Nuclear Information System (INIS)

Doerr, Wolfgang; Hamilton, Christopher S.; Boyd, Teresa; Reed, Barry; Denham, James W.

2002-01-01

Purpose: To quantify the oral mucosal cell density and proliferation rate during conventional radiotherapy of head-and-neck tumors and to compare these parameters with clinical scoring of oral mucositis. Methods and Materials: Between 1996 and 1999, 22 patients were included in this study. Mucosal biopsies were taken before or during the radiotherapy course (5 x 2 Gy/wk). Biopsies were incubated in vitro with tritiated thymidine immediately after excision to label DNA-synthesizing cells. Results: Epithelial cell density followed a biphasic radiation response. A steep decrease to about 50% of the preirradiation value (1000 cells/mm epithelium) during Week 1 was followed by a more gradual loss to about 400 cells at the end of treatment. The initial phase was based on the depression of proliferation, with 5-10 labeled cells/mm at the end of Week 1 vs. 60 labeled cells/mm in controls. Subsequently, proliferation was partially restituted at 20 labeled cells/mm. A significant difference in cell numbers was seen between Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Grade 0 (∼850 cell/mm) and Grade 2 (325/mm) or Grade 3 (370/mm). No significant differences were observed between reaction grades 1, 2, and 3. Conclusion: Conventionally fractionated radiotherapy induces a rapid suppression in cell production in Week 1, which results in a prompt reduction in cell numbers. Subsequently, a partial restoration of proliferation significantly reduces the rate of cell loss. These processes clearly precede the clinical response. Regeneration, defined as restoration of cellularity, is already under way when the maximal clinical response is observed. Clinical reaction grading corresponds poorly to cellular density measures during conventional fractionation

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...

Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis.

Science.gov (United States)

Sroussi, Herve Y; Epstein, Joel B; Bensadoun, Rene-Jean; Saunders, Deborah P; Lalla, Rajesh V; Migliorati, Cesar A; Heaivilin, Natalie; Zumsteg, Zachary S

2017-12-01

Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life-long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Acute mucositis in the stimulated oral mucosa of patients during radiotherapy for head and neck cancer

International Nuclear Information System (INIS)

Maciejewski, B.; Zajusz, A.; Pilecki, B.; Swiatnicka, J.; Skladowski, K.; Trott, K.R.

1991-01-01

In 16 patients treated for squamous cell carcinoma of the oral cavity or oropharynx with an accelerated split course regimen, acute mucosal reactions were significantly less in the left buccal mucosa which had been repeatedly painted with 2% silver-nitrate solution for several days before radiotherapy than in the unpainted right buccal mucosa. (author). 8 refs., 3 figs., 1 tab

Platelet lysate mucohadesive formulation to treat oral mucositis in graft versus host disease patients: a new therapeutic approach.

Science.gov (United States)

Del Fante, Claudia; Perotti, Cesare; Bonferoni, Maria Cristina; Rossi, Silvia; Sandri, Giuseppina; Ferrari, Franca; Scudeller, Luigia; Caramella, Carla Marcella

2011-09-01

Optimal treatment of oral mucositis (OM) due to graft versus host disease (GvHD) is currently not available. Platelet-derived growth factors (PDGFs) have high capability for tissue healing and may play a role in repairing the mucosal barrier. The aim of the present work was to develop a mucoadhesive formulation to administer platelet lysate to oral cavity prolonging contact time of platelet lysate with oral mucosa. The mucoadhesive formulation was characterized for in vitro properties (PDGF-AB concentration, mucoadhesive properties, cytotoxicity, fibroblast proliferation, wound healing). Moreover, a preliminary clinical study on seven GvHD patients with OM refractory to other therapies was conducted, to evaluate feasibility, safety, and efficacy. GVPL (mucoadhesive gel vehicle mixed with platelet lysate)showed good mucoadhesive properties; additionally, it was characterized by good biocompatibility in vitro on fibroblasts and it was able to enhance fibroblast proliferation and wound healing, maintaining the efficacy for up to 14 days following storage at 2-8°C. In vivo, clinical response was good-to-complete in five, fair in one, none in the remaining one. The in vitro results indicate that GVPL has optimal mucoadhesive and healing enhancer properties, maintained over time (up to 14 days); preliminary clinical results suggest that oral application of platelet lysate-loaded mucoadhesive formulation is feasible, safe, well tolerated, and effective. A larger controlled randomized study is needed.

A novel role for the NLRC4 inflammasome in mucosal defenses against the fungal pathogen Candida albicans.

Directory of Open Access Journals (Sweden)

Jeffrey Tomalka

2011-12-01

Full Text Available Candida sp. are opportunistic fungal pathogens that colonize the skin and oral cavity and, when overgrown under permissive conditions, cause inflammation and disease. Previously, we identified a central role for the NLRP3 inflammasome in regulating IL-1β production and resistance to dissemination from oral infection with Candida albicans. Here we show that mucosal expression of NLRP3 and NLRC4 is induced by Candida infection, and up-regulation of these molecules is impaired in NLRP3 and NLRC4 deficient mice. Additionally, we reveal a role for the NLRC4 inflammasome in anti-fungal defenses. NLRC4 is important for control of mucosal Candida infection and impacts inflammatory cell recruitment to infected tissues, as well as protects against systemic dissemination of infection. Deficiency in either NLRC4 or NLRP3 results in severely attenuated pro-inflammatory and antimicrobial peptide responses in the oral cavity. Using bone marrow chimeric mouse models, we show that, in contrast to NLRP3 which limits the severity of infection when present in either the hematopoietic or stromal compartments, NLRC4 plays an important role in limiting mucosal candidiasis when functioning at the level of the mucosal stroma. Collectively, these studies reveal the tissue specific roles of the NLRP3 and NLRC4 inflammasome in innate immune responses against mucosal Candida infection.

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.

Oral mucosal lesions in a Chilean elderly population: A retrospective study with a systematic review from thirteen countries.

Science.gov (United States)

Rivera, César; Droguett, Daniel; Arenas-Márquez, María-Jesús

2017-02-01

The oral examination is an essential part of the multidisciplinary medical care in elderly people. Oral mucosal lesions and normal variations of oral anatomy (OMLs) are very common in this people, but few studies have examined the frequency and prevalence of these conditions worldwide and less in Chile. The aim of this research was to evaluate the frequency of OMLs in a Chilean elderly population. It was conducted a retrospective study (Talca, Chile). Two hundred seventy-seven OMLs were classified in groups and anatomical sites. In order to contextualize our numbers, we made a systematic review using Publish or Perish software, Google Scholar and InteractiVenn. The most prevalent OMLs groups were soft tissue tumors, epithelial pathology, facial pain and neuromuscular diseases, and dermatologic diseases. The most frequent OMLs included irritation fibroma (30 patients, 10.8%), hemangioma (20, 7.2%), burning mouth syndrome (20 cases, 7.2%), oral lichen planus (12, 4.3%) and epulis fissuratum (12, 4.3%). In the systematic review, 75 OMLs were relevant and the more studied pathologies were traumatic ulcerations (11 of 15 articles), oral lichen planus (10/15), irritation fibroma, melanotic pigmentations, and recurrent aphthous stomatitis (9/10, respectively). Considering all included articles, most frequent OMLs in elderly people included denture-related stomatitis (13.3%), irritation fibroma (8.7%) and fissured tongue (6.3%). The results reflect the frequency of OMLs diagnosed in a specialized service in south of Chile and many countries around the world. These numbers will allow the establishment of preventive politics and adequacy of the clinical services. Key words: Oral mucosal lesions, elderly people, Chilean population, frequency, systematic review.

XRCC1 codon 399Gln polymorphism is associated with radiotherapy-induced acute dermatitis and mucositis in nasopharyngeal carcinoma patients

International Nuclear Information System (INIS)

Li, Haijun; You, Yanjie; Lin, Canfeng; Zheng, Mingzhang; Hong, Chaoqun; Chen, Jiongyu; Li, Derui; Au, William W; Chen, Zhijian

2013-01-01

To evaluate the association between single nucleotide polymorphisms (SNPs) at the 194 and 399 codons of XRCC1, and the risk of severe acute skin and oral mucosa reactions in nasopharyngeal carcinoma patients in China. 114 patients with nasopharyngeal carcinoma were sequentially recruited in this study. Heparinized peripheral blood samples were taken for SNPs analysis before the start of radiation treatment. SNPs in XRCC1 (194Arg/Trp and 399Arg/Gln) gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Dermatitis at upper neck and oral mucositis were clinically recorded according to the Common Terminology Criteria for Adverse Events v.3.0. The variant allele frequencies were 0.289 for XRCC1 194Trp and 0.263 for XRCC1 399Gln. Of the 114 patients, 24 experienced grade 3 acute dermatitis and 48 had grade 3 acute mucositis. The XRCC1 399Arg/Gln was significantly associated with the development of grade 3 dermatitis (Odds Ratio, 2.65; 95% CI, 1.04–6.73; p = 0.037, χ2 = 4.357). In addition, it was also associated with higher incidence of grade 3 mucositis with a borderline statistical significance (Odds Ratio, 2.11; 95% CI, 0.951–4.66; p = 0.065, χ2 = 3.411). The relationship between XRCC1 194Arg/Trp and acute dermatitis, and mucositis was not found. Our investigation shows, for the first time, that patients with the XRCC1 399Arg/Gln genotype were more likely to experience severe acute dermatitis and oral mucositis. With further validation, the information can be used to determine personalized radiotherapy strategy

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

Full text: Introduction: Mucositis affects approximately 80% of patients who receive chemotherapy combinations. The lesions are painful, restrict food intake and make patients more susceptible to systemic infections. Some agents and strategies are being studied for controlling mucositis, none of them is used in clinical practice. In Minas Gerais, many studies have addressed the popular use of the plant Arrabidaea chica in the form of tea, to treat intestinal cramps and diarrhea, the main symptoms of mucositis. Objective: To evaluate the potential of Arrabidaea chica extract in the management of the integrity of the intestinal mucosa, using the experimental model of gut mucositis induced by 5-Fluorouracila (5-FU). Methods: The UFMG Ethics Committee for Animal Experimentation (CETEA/UFMG) approved this study (nº 411/2015). Male BALB/c mice between 6-8 weeks of age were randomly divided into four groups (n=9) as follows: 1. Control (CTL) - oral administration of saline solution (10 days); 2. A. chica (AC) - oral administration of A. chica extract (10 days); 3. Mucositis (MUC) - underwent mucositis (5-FU) (10 days); 4. Mucositis + A. chica (MUC+ AC) - underwent mucositis and received oral administration of A. chica extract (10 days). At the 7 th day, mice in the MUC and MUC + AC groups received an intraperitoneal (IP) injection containing 300 mg/kg 5-FU, whereas the animals of the CTL and AC groups received a saline IP injection. After 72 hours (10 th experimental day), intestinal permeability was determined by measuring the radioactivity diffusion in the blood after oral administration of diethylenetriaminepentaacetic acid (DTPA) labelled with technetium-99m ( 99m Tc) and bacterial translocation was determined by measuring the radioactivity diffusion in the blood after oral administration of E. coli labelled with technetium-99m ( 99m Tc). After 4 hours, the mice were euthanized and assessed for intestinal permeability, bacterial translocation and intestinal histology

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

Full text: Introduction: Mucositis affects approximately 80% of patients who receive chemotherapy combinations. The lesions are painful, restrict food intake and make patients more susceptible to systemic infections. Some agents and strategies are being studied for controlling mucositis, none of them is used in clinical practice. In Minas Gerais, many studies have addressed the popular use of the plant Arrabidaea chica in the form of tea, to treat intestinal cramps and diarrhea, the main symptoms of mucositis. Objective: To evaluate the potential of Arrabidaea chica extract in the management of the integrity of the intestinal mucosa, using the experimental model of gut mucositis induced by 5-Fluorouracila (5-FU). Methods: The UFMG Ethics Committee for Animal Experimentation (CETEA/UFMG) approved this study (nº 411/2015). Male BALB/c mice between 6-8 weeks of age were randomly divided into four groups (n=9) as follows: 1. Control (CTL) - oral administration of saline solution (10 days); 2. A. chica (AC) - oral administration of A. chica extract (10 days); 3. Mucositis (MUC) - underwent mucositis (5-FU) (10 days); 4. Mucositis + A. chica (MUC+ AC) - underwent mucositis and received oral administration of A. chica extract (10 days). At the 7{sup th} day, mice in the MUC and MUC + AC groups received an intraperitoneal (IP) injection containing 300 mg/kg 5-FU, whereas the animals of the CTL and AC groups received a saline IP injection. After 72 hours (10{sup th} experimental day), intestinal permeability was determined by measuring the radioactivity diffusion in the blood after oral administration of diethylenetriaminepentaacetic acid (DTPA) labelled with technetium-99m ({sup 99m}Tc) and bacterial translocation was determined by measuring the radioactivity diffusion in the blood after oral administration of E. coli labelled with technetium-99m ({sup 99m}Tc). After 4 hours, the mice were euthanized and assessed for intestinal permeability, bacterial translocation and

A comparison of dioctahedral smectite and iodine glycerin cream with topical mouth rinse in treatment of chemotherapy induced oral mucositis: a pilot study.

Science.gov (United States)

Lin, Jin-Xiang; Fan, Zu-Yan; Lin, Qu; Wu, Dong-Hao; Wu, Xiang-Yuan; Chen, Yan-Ru; Fang, Heng-Ying; Wu, Dong-Bing; Wen, Jing-Yun; Dong, Min; Ma, Xiao-Kun; Wan, Xiang-Bo

2015-04-01

To compare the efficacy of dioctahedral smectite and iodine glycerin (DSIG) cream with topical mouth rinse (composed of saline, gentamicin and Vitamin B12) in treatment of chemotherapy induced oral mucositis (OM). A total of 130 intensive chemotherapy or stem cells transplantation induced OM patients were recruited. Among these patients, 67 patients received topical mouth rinse and 63 patients received DSIG cream treatment. The OM would be treated on the OM appearance and sustained for 5 days. OM severity was measured daily using The American Oncology Nursing Society recommended Oral Assessment Guideline (OAG) score system. Compared with topical mouth rinse treatment, a significant lower OAG score was observed in DSIG cream treated patients. Specifically, the OAG scores were respectively 12.1 ± 1.1, 12.0 ± 1.2, 11.3 ± 1.3 and 10.4 ± 1.3 from day 2 to day 5 in topical mouth rinse treatment subgroup. Correspondingly, the OAG scores were respectively 10.2 ± 1.0, 9.3 ± 0.9, 8.5 ± 0.6 and 8.0 ± 0.2 for DSIG cream treatment subset (all P < 0.05). Importantly, compared with topical mouth rinse treatment, the DSIG cream significantly shortened OM repair time (4.68 ± 0.98 vs. 8.76 ± 1.80 days, P < 0.001). After 5 days treatment, 54 patients (85.7%) obtained complete regression with an OAG score ≤8, and 7 patients (11.1%) had partial regression with an OAG score of 9-10 in DSIG cream treatment subgroup. However, only 2 patients (3.0%) obtained completed regression and 32 patients (47.8%) had partial regression in topical mouth rinse treatment cohort. Moreover, no serious side-effect was observed in both cohorts. Compared with topical mouth rinse, DSIG cream significantly lowered the OAG score and shortened OM duration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Systemic Immunization with Papillomavirus L1 Protein Completely Prevents the Development of Viral Mucosal Papillomas

Science.gov (United States)

Suzich, Joann A.; Ghim, Shin-Je; Palmer-Hill, Frances J.; White, Wendy I.; Tamura, James K.; Bell, Judith A.; Newsome, Joseph A.; Bennett Jenson, A.; Schlegel, Richard

1995-12-01

Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy.

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.

Transgenic Killer Commensal Bacteria as Mucosal Protectants

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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

Buccal mucosal cancer patient who failed to recover taste acuity after partial oral cavity irradiation

International Nuclear Information System (INIS)

Saito, Tsutomu; Fukushima, Shoko; Furuhashi, Satoru; Yoshinobu, Takashi; Takahashi, Motoichiro; Miyake, Masahiko; Kawamori, Jiro; Tanaka, Yoshiaki

2002-01-01

We report a patient who suffered from prolonged loss of taste acuity after partial oral cavity irradiation. The electric taste threshold (ETT) of each point in the oral cavity was measured with an electric gustometer to evaluate quantitative local taste acuity. A subjective total taste acuity (STTA) scale was used to evaluate subjective total taste acuity. A 61-year-old male patient with right buccal mucosal cancer underwent radiation therapy more than 11 years ago, and has suffered from loss of taste acuity since then. He received electron beam irradiation to part of the oral cavity and right upper neck, mainly the right buccal mucosa near the retromolar trigone and a metastatic right submandibular node. He did not receive irradiation to the anterior portion of the tongue or left side of the posterior portion of the tongue. His ETT scores for each point were equal to or greater than 26, and his STTA score was grade 3. The present case implies that radiation damage to part of the oral cavity can cause the loss of subjective total taste acuity. (author)

Buccal mucosal cancer patient who failed to recover taste acuity after partial oral cavity irradiation

Energy Technology Data Exchange (ETDEWEB)

Saito, Tsutomu; Fukushima, Shoko; Furuhashi, Satoru; Yoshinobu, Takashi; Takahashi, Motoichiro [Nihon Univ., Tokyo (Japan). Surugadai Hospital; Miyake, Masahiko [Nihon Univ., Tokyo (Japan). School of Dentistry; Kawamori, Jiro; Tanaka, Yoshiaki [Nihon Univ., Tokyo (Japan). School of Medicine

2002-10-01

We report a patient who suffered from prolonged loss of taste acuity after partial oral cavity irradiation. The electric taste threshold (ETT) of each point in the oral cavity was measured with an electric gustometer to evaluate quantitative local taste acuity. A subjective total taste acuity (STTA) scale was used to evaluate subjective total taste acuity. A 61-year-old male patient with right buccal mucosal cancer underwent radiation therapy more than 11 years ago, and has suffered from loss of taste acuity since then. He received electron beam irradiation to part of the oral cavity and right upper neck, mainly the right buccal mucosa near the retromolar trigone and a metastatic right submandibular node. He did not receive irradiation to the anterior portion of the tongue or left side of the posterior portion of the tongue. His ETT scores for each point were equal to or greater than 26, and his STTA score was grade 3. The present case implies that radiation damage to part of the oral cavity can cause the loss of subjective total taste acuity. (author)

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.

Effects of sucralfate on gastric irritant-induced necrosis and apoptosis in cultured guinea pig gastric mucosal cells.

Science.gov (United States)

Hoshino, Tatsuya; Takano, Tatsunori; Tomisato, Wataru; Tsutsumi, Shinji; Hwang, Hyun-Jung; Koura, Yuko; Nishimoto, Kiyo; Tsuchiya, Tomofusa; Mizushima, Tohru

2003-01-01

We previously reported that several gastric irritants, including ethanol, hydrogen peroxide, and hydrochloric acid, induced both necrosis and apoptosis in cultured gastric mucosal cells. In the present study, we examined the effects of sucralfate, a unique gastroprotective drug, on gastric irritant-induced necrosis and apoptosis produced in vitro. Sucralfate strongly inhibited ethanol-induced necrosis in primary cultures of guinea pig gastric mucosal cells. The preincubation of cells with sucralfate was not necessary for its cytoprotective effect to be observed, thus making its mechanism of action different from that of other gastroprotective drugs. Necrosis of gastric mucosal cells induced by hydrogen peroxide or indomethacin was also suppressed by sucralfate. On the other hand, sucralfate only weakly inhibited ethanol-induced apoptosis. These results suggest that the cytoprotective effect of sucralfate on gastric mucosa in vivo can be explained, at least in part, by its inhibitory effect on gastric irritant-induced necrosis.

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

OpenAIRE

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...

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

Directory of Open Access Journals (Sweden)

Wei Cheong Ngeow

2011-12-01

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

Semi-solid dosage form of clonazepam for rapid oral mucosal absorption.

Science.gov (United States)

Sakata, Osamu; Machida, Yoshiharu; Onishi, Hiraku

2011-07-01

In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration. Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.

Hydroalcoholic extract of Carum carvi L. in oral mucositis: a clinical trial in male golden hamsters.

Science.gov (United States)

Mardani, M; Afra, S M; Tanideh, N; Tadbir, A Andisheh; Modarresi, F; Koohi-Hosseinabadi, O; Iraji, A; Sepehrimanesh, M

2016-01-01

Several studies have attempted to prevent or improve oral mucositis (OM) but have not produced a qualified treatment yet. This study evaluates the effects of Carum carvi L. (caraway) hydroalcoholic extract (CHE) as one of the traditional medicinal plants in 5-fluorouracil (5-FU)-induced OM in golden hamsters. OM was induced in 54 male golden hamsters by 5-FU and cheek pouch scratching. Starting from day 12, 500 and 1000 mg kg(-1) per day topical CHE were administered. Pouch histopathology score, malondialdehyde and reduced glutathione contents, and activity of myeloperoxidase plus microbial cultures of cheek pouch, antimicrobial properties of CHE, and essential oil constituents were evaluated. Lower histopathology score (0, 1, and 2) and malondialdehyde level, higher reduced glutathione level and activities of myeloperoxidase were detected in 1000 and 500 mg kg(-1) per day topical CHE and control groups, respectively (P epidermidis and Streptococcus intermedius. γ-Terpinene (37.2%) was identified as the main constituent of essential oil. The use of CHE in topical form may be associated with reduced intensity of OM. This may be due to appropriate antibacterial activity and terpinene contents. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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....

Colonization of the oral cavity by probiotic bacteria.

Science.gov (United States)

Ravn, I; Dige, I; Meyer, R L; Nyvad, B

2012-01-01

The aim of this study was to investigate if three probiotic bacteria present in the milk product Cultura Dofilus® naturell could be detected in saliva and on oral mucosal surfaces, and if they colonized dental surfaces in situ in 8 caries-inactive individuals after 8 daily exposures to the milk product for up to 3 days. Bacteria were identified by fluorescence in situ hybridization and confocal laser scanning microscopy. While probiotic bacteria were present sporadically in the oral cavity on mucosal surfaces and in saliva after 3 days of frequent use of the probiotic milk, they were not detected on dental surfaces. Probiotic bacteria may thus contribute to general oral health, but their potential role in biofilm-induced dental diseases remains unclear. Copyright © 2012 S. Karger AG, Basel.

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

Directory of Open Access Journals (Sweden)

Mohammad Taghi Kazemi

2013-03-01

Full Text Available 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 < 0.0001 and week 6 (score: 11.4 vs. 13.35, p = 0.031. Total 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.

Radioprotective agents to reduce BNCT (Boron Neutron Capture Therapy) induced mucositis in the hamster cheek pouch; Agentes radioprotectores para reducir la mucositis inducida por la terapia por captura neutrónica en boro (BNCT) en la bolsa de la mejilla del hámster

Energy Technology Data Exchange (ETDEWEB)

Monti Hughes, A. [Dpto. de Radiobiología, Gerencia de Química Nuclear y Ciencias de la Salud, GAATEN, Comisión Nacional de Energía Atómica (CNEA) (Argentina); Pozzi, E. C.C. [Gerencia de Reactores de Investigación y Producción, GAATEN, CNEA (Argentina); Thorp, S., E-mail: andrea.monti@cnea.gov.ar [Sub-Gerencia Instrumentación y Control, GAEN, CNEA(Argentina)

2013-07-01

Introduction: BNCT is based on the capture reaction between boron, selectively targeted to tumor tissue, and thermal neutrons which gives rise to lethal, short-range high linear energy transfer particles that selectively damage tumor tissue, sparing normal tissue. We previously evidenced a remarkable therapeutic success of BNCT mediated by boronophenylalanine (BPA) in the hamster cheek pouch oral cancer and pre cancer model. Despite therapeutic efficacy, mucositis induced in premalignant tissue was dose limiting and favored, in some cases, tumor development. In a clinical scenario, oral mucositis limits the dose administered to head and neck tumors. Aim: Our aim was to evaluate the effect of the administration of different radioprotective agents, seeking to reduce BNCT-induced mucositis to acceptable levels in dose-limiting premalignant tissue; without compromising therapeutic effect evaluated as inhibition on tumor development in premalignant tissue; without systemic or local side effects; and without negative effects on the biodistribution of the boron compound used for treatment. Materials and methods: Cancerized hamsters with DMBA (dimethylbenzanthracene) were treated with BPA-BNCT 5 Gy total absorbed dose to premalignant tissue, at the RA-3 Nuclear Reactor, divided into different groups: 1-treated with FLUNIXIN; 2- ATORVASTATIN; 3-THALIDOMIDE; 4-HISTAMINE (two concentrations: Low -1 mg/ml- and High -5 mg/ml-); 5-JNJ7777120; 6-JNJ10191584; 7-SALINE (vehicle). Cancerized animals without any treatment (neither BNCT nor radioprotective therapy) were also analyzed. We followed the animals during one month and evaluated the percentage of animals with unacceptable/severe mucositis, clinical status and percentage of animals with new tumors post treatment. We also performed a preliminary biodistribution study of BPA + Histamine “low” concentration to evaluate the potential effect of the radioprotector on BPA biodistribution. Results: Histamine �

Treatment with Saccharomyces boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in 5-fluorouracil-induced intestinal mucositis in mice.

Science.gov (United States)

Justino, Priscilla F C; Melo, Luis F M; Nogueira, Andre F; Costa, Jose V G; Silva, Luara M N; Santos, Cecila M; Mendes, Walber O; Costa, Marina R; Franco, Alvaro X; Lima, Aldo A; Ribeiro, Ronaldo A; Souza, Marcellus H L P; Soares, Pedro M G

2014-05-01

Intestinal mucositis is an important toxic side effect of 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii is known to protect from intestinal injury via an effect on the gastrointestinal microbiota. The objective of the present study was to evaluate the effect of S. boulardii on intestinal mucositis induced by 5-FU in a murine model. Mice were divided into saline, saline (control)+5-FU or 5-FU+S. boulardii (16 × 10⁹ colony-forming units/kg) treatment groups, and the jejunum and ileum were removed after killing of mice for the evaluation of histopathology, myeloperoxidase (MPO) activity, and non-protein sulfhydryl group (mainly reduced glutathione; GSH), nitrite and cytokine concentrations. To determine gastric emptying, phenol red was administered orally, mice were killed 20 min after administration, and the absorbance of samples collected from the mice was measured by spectrophotometry. Intestinal permeability was measured by the urinary excretion rate of lactulose and mannitol following oral administration. S. boulardii significantly reversed the histopathological changes in intestinal mucositis induced by 5-FU and reduced the inflammatory parameters: neutrophil infiltration (control 1·73 (SEM 0·37) ultrastructural MPO (UMPO)/mg, 5-FU 7·37 (SEM 1·77) UMPO/mg and 5-FU+S. boulardii 4·15 (SEM 0·73) UMPO/mg); nitrite concentration (control 37·00 (SEM 2·39) μm, 5-FU 59·04 (SEM 11·41) μm and 5-FU+S. boulardii 37·90 (SEM 5·78) μm); GSH concentration (control 477·60 (SEM 25·25) μg/mg, 5-FU 270·90 (SEM 38·50) μg/mg and 5-FU+S. boulardii 514·00 (SEM 38·64) μg/mg). Treatment with S. Boulardii significantly reduced the concentrations of TNF-α and IL-1β by 48·92 and 32·21 % in the jejunum and 38·92 and 61·79 % in the ileum. In addition, S. boulardii decreased the concentrations of chemokine (C-X-C motif) ligand 1 by 5-fold in the jejunum and 3-fold in the ileum. Interestingly, S. boulardii reduced the delay in gastric emptying

Betel quid oral lichenoid lesions: a hospital based cross-sectional study.

Science.gov (United States)

Arya, Sugandha; Vengal, Manoj; Raju, Bina; Patil, Neelkant; Sathosker, Sujatha; Bateja, Sumit; David, Jamil

2017-02-01

The aim of this study was to assess the prevalence and risk indicators of betel quid oral lichenoid lesions in chewers. A total of 1209 chewers were identified and categorized into three main groups based on the type of lesion: betel quid oral lichenoid lesions only, betel quid oral lichenoid lesions in association with quid-induced other oral mucosal lesions, and no lesions. Multinomial regression analyses were used to determine associations between dependent and independent variables. Betel quid oral lichenoid lesions were more common in individuals who chewed quid comprising both tobacco and areca nut, and in those who chewed it two to three, or greater than three, times a day. Betel quid oral lichenoid lesions + quid-induced other oral mucosal lesions were more likely to occur in females, and in individuals who chewed quid containing both tobacco and areca nut, in their processed and unprocessed forms, and greater than three times a day. The prevalence of betel quid oral lichenoid lesions was higher than that reported in previous studies conducted in India. Increase in the frequency and duration of quid chewing was associated with increased likelihood of developing these oral lichenoid lesions. © 2015 Wiley Publishing Asia Pty Ltd.

Oral bacteria and yeasts in relationship to oral ulcerations in hematopoietic stem cell transplant recipients

NARCIS (Netherlands)

Laheij, A.M.G.A.; de Soet, J.J.; von dem Borne, P.A.; Kuijper, E.J.; Kraneveld, E.A.; van Loveren, C.; Raber-Durlacher, J.E.

2012-01-01

BACKGROUND: Oral mucositis is a serious and debilitating side effect of conditioning regimens for hematopoietic stem cell transplant (HSCT). Through HSCT, the homeostasis in the oral cavity is disrupted. The contribution of the oral microflora to mucositis remains to be clarified. The aim of our

/sup 32/P-postlabelling analysis of aromatic DNA adducts in human oral mucosal cells

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Dunn, B.P.; Stich, H.F.

1986-07-01

Exfoliated mucosal cells were collected from the oral cavity of three groups at high risk for oral cancer: Indian betel nut chewers, Filipino inverted smokers (burning end of cigar in mouth) and Indian Khaini tobacco chewers. DNA was extracted from these samples, as well as from samples of exfoliated cells of Canadian non-smoking controls. DNA was analyzed for the presence of aromatic DNA adducts using /sup 32/P-postlabelling analysis. Five chromatographically distinct adducts were found in samples from both the high risk groups and the nonsmoking controls. Individual adducts were detectable in approximately 30-95% of samples, depending on the adduct and population group. Estimated levels of specific adducts ranged from non-detectable (prevalence relative to normal nucleotides less than 1 X 10(-9)) to occasionally greater than 1 X 10(-7). No adducts were found in high risk groups which did not also appear in control subjects.

[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.

[Drug-induced oral ulcerations].

Science.gov (United States)

Madinier, I; Berry, N; Chichmanian, R M

2000-06-01

Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.

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Ye, Ting; Yue, Yan; Fan, Xiangmei; Dong, Chunsheng; Xu, Wei; Xiong, Sidong

2014-07-31

Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 μg pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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.

Oral bacteria and yeasts in relationship to oral ulcerations in hematopoietic stem cell transplant recipients

NARCIS (Netherlands)

Laheij, Alexa M. G. A.; de Soet, Johannes J.; von dem Borne, Peter A.; Kuijper, Ed J.; Kraneveld, Eefje A.; van Loveren, Cor; Raber-Durlacher, Judith E.

2012-01-01

Oral mucositis is a serious and debilitating side effect of conditioning regimens for hematopoietic stem cell transplant (HSCT). Through HSCT, the homeostasis in the oral cavity is disrupted. The contribution of the oral microflora to mucositis remains to be clarified. The aim of our study was to

Immunology of Gut Mucosal Vaccines

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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

How to prevent contamination with Candida albicans during the fabrication of transplantable oral mucosal epithelial cell sheets

Directory of Open Access Journals (Sweden)

Ryo Takagi

2015-06-01

Full Text Available We have utilized patients' own oral mucosa as a cell source for the fabrication of transplantable epithelial cell sheets to treat limbal stem cell deficiency and mucosal defects after endoscopic submucosal dissection of esophageal cancer. Because there are abundant microbiotas in the human oral cavity, the oral mucosa was sterilized and 40 μg/mL gentamicin and 0.27 μg/mL amphotericin B were added to the culture medium in our protocol. Although an oral surgeon carefully checked each patient's oral cavity and although candidiasis was not observed before taking the biopsy, contamination with Candida albicans (C. albicans was detected in the conditioned medium during cell sheet fabrication. After adding 1 μg/mL amphotericin B to the transportation medium during transport from Nagasaki University Hospital to Tokyo Women's Medical University, which are 1200 km apart, no proliferation of C. albicans was observed. These results indicated that the supplementation of transportation medium with antimycotics would be useful for preventing contamination with C. albicans derived from the oral mucosa without hampering cell proliferation.

Oral Lichen Planus.

Science.gov (United States)

Ion, Daniela I; Setterfield, Jane F

2016-02-01

Lichen planus (LP) is a relatively common autoimmune T-cell-mediated disease of unknown aetiology affecting the mucous membranes, skin and nails. Its prevalence varies between 0.5 and 2.2% of the population in epidemiological studies with a peak incidence in the 30-60 years range and with a female predominance of 2:1. Mucosal lichen planus tends to follow a chronic course with acute exacerbations. Spontaneous remission of oral lichen planus (OLP) is uncommon, and indeed mucosal LP may become worse with time. In contrast, cutaneous lichen planus may follow a milder clinical course though some variants may be severe such as those affecting the palms and soles and the scalp and the genital tract in females (vulvovaginal gingival LP) where scarring leads to significant complications. It is important to identify those cases that may be drug induced or be associated with a contact allergic or irritant reaction (lichenoid reaction) or the rarer oral presentation of discoid lupus erythematosus. There is a very small risk of malignancy (approximately 1:200 patients/year) associated with oral lichen planus; thus patients should be informed that long term monitoring via their general dental practitioner is appropriate. This review will focus on the clinical presentation and management of oral lichen planus.

Ten cases of severe oral lichen planus showing granular C3 deposition in oral mucosal basement membrane zone.

Science.gov (United States)

Hashimoto, Takashi; Fukuda, Aoi; Himejima, Akio; Morita, Shosuke; Tsuruta, Daisuke; Koga, Hiroshi; Krol, Rafal P; Ishii, Norito

2015-01-01

Oral lichen planus (OLP) may show depositions of immunoglobulins and complement components in oral mucosal basement membrane zone (BMZ) in direct immunofluorescence, although these finding are not frequently seen. We collected and examined ten cases of severe OLP showing granular C3 deposition in BMZ. In addition to clinical, histopathological and direct immunofluorescence assessments, we performed various immune-serological tests, including indirect immunofluorescence of normal human skin and 1M NaCl-split skin, immunoblotting of normal human epidermal and dermal extracts, recombinant proteins of BP180 NC16a and C-terminal domains, concentrated culture supernatant of HaCaT cells and purified human laminin-332, and enzyme-linked immunosorbent assays for BP230 and BP180. Direct immunofluorescence showed C3 deposition in BMZ exclusively of granular pattern in 7 cases and of both granular and linear patterns in 3 cases. The 10 cases showed no positive reactivity for either IgG or IgA antibodies in any immuno-serological tests. Detailed analyses of clinical, histopathological and immunological findings revealed striking female prevalence, although other parameters were in general characteristic of OLP. Granular C3 deposition in oral BMZ may be one of the characteristic features of severe OLP, although mechanisms for C3 deposition and its pathogenic role in OLP are currently unknown.

Role of lipoxygenases and the lipoxin A(4)/annexin 1 receptor in ischemia-reperfusion-induced gastric mucosal damage in rats.

Science.gov (United States)

Peskar, Brigitta M; Ehrlich, Karlheinz; Schuligoi, Rufina; Peskar, Bernhard A

2009-01-01

Rat gastric mucosal damage was induced by ischemia-reperfusion. The 5-lipoxygenase inhibitors MK886 and A63162, the 12-lipoxygenase inhibitor baicalein, the 15-lipoxygenase inhibitor PD146176 and the lipoxin (LX) A(4)/annexin 1 antagonist Boc1 increased mucosal damage in a dose-dependent manner. Low doses of these compounds, which have no effects on mucosal integrity, cause severe damage when combined with low doses of indomethacin, celecoxib or dexamethasone. 16,16-Dimethylprostaglandin (PG) E(2) and LXA(4) can replace each other in preventing mucosal injury induced by either cyclooxygenase or lipoxygenase inhibitors. The results suggest that not only cyclooxygenases, but also lipoxygenases have a role in limiting gastric mucosal damage during ischemia-reperfusion. Copyright 2009 S. Karger AG, Basel.

Calcitonin Gene-Related Peptide Induces HIV-1 Proteasomal Degradation in Mucosal Langerhans Cells.

Science.gov (United States)

Bomsel, Morgane; Ganor, Yonatan

2017-12-01

The neuroimmune dialogue between peripheral neurons and Langerhans cells (LCs) within mucosal epithelia protects against incoming pathogens. LCs rapidly internalize human immunodeficiency virus type 1 (HIV-1) upon its sexual transmission and then trans -infect CD4 + T cells. We recently found that the neuropeptide calcitonin gene-related peptide (CGRP), secreted mucosally from peripheral neurons, inhibits LC-mediated HIV-1 trans -infection. In this study, we investigated the mechanism of CGRP-induced inhibition, focusing on HIV-1 degradation in LCs and its interplay with trans -infection. We first show that HIV-1 degradation occurs in endolysosomes in untreated LCs, and functionally blocking such degradation with lysosomotropic agents results in increased trans -infection. We demonstrate that CGRP acts via its cognate receptor and at a viral postentry step to induce faster HIV-1 degradation, but without affecting the kinetics of endolysosomal degradation. We reveal that unexpectedly, CGRP shifts HIV-1 degradation from endolysosomes toward the proteasome, providing the first evidence for functional HIV-1 proteasomal degradation in LCs. Such efficient proteasomal degradation significantly inhibits the first phase of trans -infection, and proteasomal, but not endolysosomal, inhibitors abrogate CGRP-induced inhibition. Together, our results establish that CGRP controls the HIV-1 degradation mode in LCs. The presence of endogenous CGRP within innervated mucosal tissues, especially during the sexual response, to which CGRP contributes, suggests that HIV-1 proteasomal degradation predominates in vivo Hence, proteasomal, rather than endolysosomal, HIV-1 degradation in LCs should be enhanced clinically to effectively restrict HIV-1 trans -infection. IMPORTANCE During sexual transmission, HIV-1 is internalized and degraded in LCs, the resident antigen-presenting cells in mucosal epithelia. Yet during trans -infection, infectious virions escaping degradation are transferred

Oral Vaccination with the Porcine Rotavirus VP4 Outer Capsid Protein Expressed by Lactococcus lactis Induces Specific Antibody Production

Directory of Open Access Journals (Sweden)

Yi-jing Li

2010-01-01

Full Text Available The objective of this study to design a delivery system resistant to the gastrointestinal environment for oral vaccine against porcine rotavirus. Lactococcus lactis NZ9000 was transformed with segments of vP4 of the porcine rotavirus inserted into the pNZ8112 surface-expression vector, and a recombinant L. lactis expressing VP4 protein was constructed. An approximately 27 kDa VP4 protein was confirmed by SDS-PAGE , Western blot and immunostaining analysis. BALB/c mice were immunized orally with VP4-expression recombinant L. lactis and cellular, mucosal and systemic humoral immune responses were examined. Specific anti-VP4 secretory IgA and IgG were found in feces, ophthalmic and vaginal washes and in serum. The induced antibodies demonstrated neutralizing effects on porcine rotavirus infection on MA104 cells. Our findings suggest that oral immunization with VP4-expressing L. lactis induced both specific local and systemic humoral and cellular immune responses in mice.

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....

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

Directory of Open Access Journals (Sweden)

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.

Defective IL-17- and IL-22-dependent mucosal host response to Candida albicans determines susceptibility to oral candidiasis in mice expressing the HIV-1 transgene.

Science.gov (United States)

Goupil, Mathieu; Cousineau-Côté, Vincent; Aumont, Francine; Sénéchal, Serge; Gaboury, Louis; Hanna, Zaher; Jolicoeur, Paul; de Repentigny, Louis

2014-10-26

The tissue-signaling cytokines IL-17 and IL-22 are critical to host defense against oral Candida albicans infection, by their induction of oral antimicrobial peptide expression and recruitment of neutrophils. Mucosal Th17 cells which produce these cytokines are preferentially depleted in HIV-infected patients. Here, we tested the hypothesis that defective IL-17- and IL-22-dependent host responses to C. albicans determine the phenotype of susceptibility to oropharyngeal candidiasis (OPC) in transgenic (Tg) mice expressing HIV-1. Naïve CD4+ T-cells and the differentiated Th1, Th2, Th17, Th1Th17 and Treg lineages were all profoundly depleted in cervical lymph nodes (CLNs) of these Tg mice. However, naive CD4+ cells from Tg mice maintained the capacity to differentiate into these lineages in response to polarizing cytokines in vitro. Expression of Il17, Il22, S100a8 and Ccl20 was enhanced in oral mucosal tissue of non-Tg, but not of Tg mice, after oral infection with C. albicans. Treatment of infected Tg mice with the combination of IL-17 and IL-22, but not IL-17 or Il-22 alone, significantly reduced oral burdens of C. albicans and abundance of Candida hyphae in the epithelium of tongues of infected Tg mice, and restored the ability of the Tg mice to up-regulate expression of S100a8 and Ccl20 in response to C. albicans infection. These findings demonstrate that defective IL-17- and IL-22-dependent induction of innate mucosal immunity to C. albicans is central to the phenotype of susceptibility to OPC in these HIV transgenic mice.

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.

Effects of stimulated repopulation on oral mucositis during conventional radiotherapy

International Nuclear Information System (INIS)

Doerr, W.; Jacubek, A.; Kummermehr, J.; Herrmann, Th.; Doelling-Jochem, I.; Eckelt, U.

1995-01-01

The effect of local conditioning of human oral mucosa by silver nitrate solution (3%) on epithelial proliferation rates was tested in 11 healthy volunteers by in vitro labelling of biopsies with tritiated thymidine. Compared to control biopsies from 13 volunteers, stimulation over 3 days, 3 times per day, yielded a significant (p = 0.006) increase in the epithelial labelling index (LI) from 4.75 ± 0.32% to 6.85 ± 0.65%, i.e., by 44%. The increase in the absolute number of labelled cells per mm epithelial length was dependent on the overall cell density at the various intraoral sites and varied between 45% in the maxillary vestibule and 91% at the floor of the mouth. In an analysis of variance, stimulation turned out to be the most important source causing the effect (p = 0.011 for LI and 0.015 for labelled cells per mm). In a radiotherapy trial with conventional postoperative treatment with 5 x 2 Gy/week to a total dose of 60 Gy in 6 weeks, the left buccal mucosa in 10 patients with squamous cell carcinomas of the head and neck was conditioned (3% silver nitrate, 3 times per day, 5 days before and the first 2 days of radiotherapy) while the contralateral mucosa, receiving an identical dose, served as individual control. Mucositis scores according to the EORTC/RTOG or the Dische system showed that the time course and severity of the mucosal response was almost identical in both cheeks, which is in clear contrast to a previous clinical study (Maciejewski et al. Radiother. Oncol. 22, 7-11, 1991). Differences in radiation dose intensity, i.e., weekly dose, in these studies are discussed as a tentative explanation for the different clinical findings

A novel vitamin E derivative (TMG) protects against gastric mucosal damage induced by ischemia and reperfusion in rats.

Science.gov (United States)

Ichikawa, Hiroshi; Yoshida, Norimasa; Takano, Hiroshisa; Ishikawa, Takeshi; Handa, Osamu; Takagi, Tomohisa; Naito, Yuji; Murase, Hironobu; Yoshikawa, Toshikazu

2003-01-01

The aim of the present study was to investigate the antioxidative effects of water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), on ischemia-reperfusion (I/R) -induced gastric mucosal injury in rats. Gastric ischemia was induced by applying a small clamp to the celiac artery and reoxygenation was produced by removal of the clamp. The area of gastric mucosal erosion, the concentration of thiobarbituric acid-reactive substances, and the myeloperoxidase activity in gastric mucosa significantly increased in I/R groups compared with those of sham-operated groups. These increases were significantly inhibited by pretreatment with TMG. The contents of both mucosal TNF-alpha and CINC-2beta in I/R groups were also increased compared with the levels of those in sham-operated groups. These increases of the inflammatory cytokines were significantly inhibited by the treatment with TMG. It is concluded that TMG inhibited lipid peroxidation and reduced development of the gastric mucosal inflammation induced by I/R in rats.

Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

Energy Technology Data Exchange (ETDEWEB)

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

1987-09-01

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

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

Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy against PEDV.

Science.gov (United States)

Wang, Xiaona; Wang, Li; Huang, Xuewei; Ma, Sunting; Yu, Meiling; Shi, Wen; Qiao, Xinyuan; Tang, Lijie; Xu, Yigang; Li, Yijing

2017-10-25

Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is reported as a promising approach for inducing protective immunity against PEDV invasion. Furthermore, dendritic cells (DCs), professional antigen-presenting cells, link humoral and cellular immune responses for homeostasis of the intestinal immune environment. In this study, in order to explore an efficient oral vaccine against PEDV infection, a mucosal DC-targeting oral vaccine was developed using Lactobacillus casei to deliver the DC-targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE) antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in vivo. Significant differences ( p targeting peptide fused with PEDV COE antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances vaccine antigen delivery efficiency, providing a useful strategy to induce efficient immune responses against PEDV infection.

The effects of swallowing disorders, dysgeusia, oral mucositis and xerostomia on nutritional status, oral intake and weight loss in head and neck cancer patients: A systematic review.

Science.gov (United States)

Bressan, Valentina; Stevanin, Simone; Bianchi, Monica; Aleo, Giuseppe; Bagnasco, Annamaria; Sasso, Loredana

2016-04-01

Combined-modality treatment of head and neck cancer is becoming more common, driven by the idea that organ(s) preservation should maintain patient appearance and the function of organ(s) involved. Even if treatments have improved, they can still be associated with acute and late adverse effects. The aim of this systematic review was to retrieve current data on how swallowing disorders, dysgeusia, oral mucositis, and xerostomia affect nutritional status, oral intake and weight loss in head and neck cancer (HNC) patients. A systematic literature search covered four relevant electronic databases from January 2005 to May 2015. Retrieved papers were categorised and evaluated considering their methodological quality. Two independent reviewers reviewed manuscripts and abstracted data using a standardised form. Quality assessment of the included studies was performed using the Edwards Method Score. Of the 1459 abstracts reviewed, a total of 25 studies were included. The most studied symptom was dysphagia, even if symptoms were interconnected and affected one other. In most of the selected studies the level of evidence was between 2 and 3, and their quality level was from medium to low. There are limited data about dysgeusia, oral mucositis and xerostomia outcomes available for HNC patients. There is a lack of well-designed clinical trials and multicenter-prospective cohort studies, therefore further research is needed to ascertain which aspects of these symptoms should be measured. Copyright © 2016 Elsevier Ltd. All rights reserved.

Killed Whole-Cell Oral Cholera Vaccine Induces CCL20 Secretion by Human Intestinal Epithelial Cells in the Presence of the Short-Chain Fatty Acid, Butyrate

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Ju-Ri Sim

2018-01-01

Full Text Available Short-chain fatty acids (SCFAs, such as acetate, butyrate, and propionate, modulate immune responses in the gut. However, the effect of SCFAs on mucosal vaccine-induced immune cell migration is poorly understood. Here, we investigated whether SCFAs modulate chemokine expression induced by the killed whole-cell oral cholera vaccine, Shanchol™, in human intestinal epithelial cells. Shanchol™ induced expression of CCL2, CCL5, CCL20, and CXCL10 at the mRNA level, but not at the protein level. Interestingly, CCL20 secretion was substantially increased by co-stimulation with Shanchol™ and butyrate, while neither acetate nor propionate showed such effect. Enhanced CCL20 secretion was associated with GPR109A activation, and histone deacetylase (HDAC inhibition. In addition, co-treatment with Shanchol™ and butyrate synergistically increased the secretion of adenosine triphosphate (ATP. Moreover, CCL20 secretion was decreased by inhibiting the extracellular ATP receptor P2X7. However, neither inflammasomes nor caspases were involved in CCL20 production. The culture supernatant of cells treated with Shanchol™ and butyrate augmented human immature dendritic cell migration. Collectively, these results suggest that butyrate enhances Shanchol™-induced CCL20 production in human intestinal epithelial cells via HDAC inhibition and ATP-P2X7 signaling by activating GPR109A. These effects potentially enhance the mucosal immune responses in the gut induced by this oral cholera vaccine.

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

Science.gov (United States)

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

2017-10-01

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.

Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis

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Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún

2017-01-01

The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single...... bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit....

Recombinant interleukin 6 with M cell-targeting moiety produced in Lactococcus lactis IL1403 as a potent mucosal adjuvant for peroral immunization.

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Li, Hui-Shan; Piao, Da-Chuan; Jiang, Tao; Bok, Jin-Duck; Cho, Chong-Su; Lee, Yoon-Seok; Kang, Sang-Kee; Choi, Yun-Jaie

2015-04-15

Development and application of safe and effective mucosal adjuvants are important to improve immunization efficiency in oral vaccine. Here, we report a novel mucosal adjuvant, IL-6-CKS9, a recombinant cytokine generated by conjugating an M cell-targeting peptide (CKS9) with c-terminus of the murine interleukin 6 (IL-6), which facilitated enhancement of mucosal immune response. Lactococcus lactis IL1403, a food-grade strain of lactic acid bacteria (LAB) which is widely used in dairy industry, was used as a host cell to express and secrete the IL-6-CKS9 for a mucosal vaccine adjuvant. The recombinant L. lactis IL1403 secreting IL-6-CKS9 was orally administered with a model antigen protein, M-BmpB (Brachyspira membrane protein B conjugated with CKS9), to BALB/c mice for mucosal immunization. ELISA analyses showed consistent enhancement tendencies in induction of anti-M-BmpB antibody levels both with mucosal (IgA) and systemic (IgG) immune responses in IL-6-CKS9-LAB treated group compared with other groups tested by conducting two separated mice immunization assays. In addition, we characterized that the oral administration of model protein antigen with live LAB producing IL-6-CKS9 could induce both Th1 and Th2 type immune responses by analysis of the specific anti-BmpB IgG1 and IgG2a isotypes in the sera and also investigated possible oral tolerance in our vaccine strategy. Collectively, our results showed successful production and secretion of recombinant murine IL-6 with M cell-targeting moiety (IL-6-CKS9) from L. lactis IL1403 and demonstrated the live recombinant LAB producing IL-6-CKS9 could have a potential to be used as an efficient adjuvant for peroral vaccination. Copyright © 2015 Elsevier Ltd. All rights reserved.

Radiation induced muscositis as space flight risk. Model studies on X-ray and heavy ion irradiated typical oral mucosa models; Strahlungsinduzierte Mukositis als Risiko der Raumfahrt. Modelluntersuchungen an Roentgen- und Schwerionen-bestrahlten organotypischen Mundschleimhaut-Modellen

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Tschachojan, Viktoria

2014-07-29

Humans in exomagnetospheric space are exposed to highly energetic heavy ion radiation which can be hardly shielded. Since radiation-induced mucositis constitutes a severe complication of heavy ion radiotherapy, it would also implicate a serious medical safety risk for the crew members during prolonged space flights such as missions to Moon or Mars. For assessment of risk developing radiation-induced mucositis, three-dimensional organotypic cultures of immortalized human keratinocytes and fibroblasts were irradiated with a {sup 12}C particle beam at high energies or X-Rays. Immunofluorescence stainings were done from cryosections and radiation induced release of cytokines and chemokines was quantified by ELISA from culture supernatants. The major focuses of this study were on 4, 8, 24 and 48 hours after irradiation. The conducted analyses of our mucosa model showed many structural similarities with the native oral mucosa and authentic immunological responses to radiation exposure. Quantification of the DNA damage in irradiated mucosa models revealed about twice as many DSB after heavy-ion irradiation compared to X-rays at definite doses and time points, suggesting a higher gene toxicity of heavy ions. Nuclear factor κB activation was observed after treatment with X-rays or {sup 12}C particles. An activation of NF κB p65 in irradiated samples could not be detected. ELISA analyses showed significantly higher interleukin 6 and interleukin 8 levels after irradiation with X-rays and {sup 12}C particles compared to non-irradiated controls. However, only X-rays induced significantly higher levels of interleukin 1β. Analyses of TNF-α and IFN-γ showed no radiation-induced effects. Further analyses revealed a radiation-induced reduction in proliferation and loss of compactness in irradiated oral mucosa model, which would lead to local lesions in vivo. In this study we revealed that several pro-inflammatory markers and structural changes are induced by X-rays and heavy

Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7-specific antitumor effects in C57/BL6 mice.

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Poo, Haryoung; Pyo, Hyun-Mi; Lee, Tae-Young; Yoon, Sun-Woo; Lee, Jong-Soo; Kim, Chul-Joong; Sung, Moon-Hee; Lee, Seung-Hoon

2006-10-01

The mounting of a specific immune response against the human papillomavirus type 16 E7 protein (HPV16 E7) is important for eradication of HPV16 E7-expressing cancer cells from the cervical mucosa. To induce a mucosal immune response by oral delivery of the E7 antigen, we expressed the HPV16 E7 antigen on the surface of Lactobacillus casei by employing a novel display system in which the poly-gamma-glutamic acid (gamma-PGA) synthetase complex A (PgsA) from Bacillus subtilis (chungkookjang) was used as an anchoring motif. After surface expression of the HPV16 E7 protein was confirmed by Western blot, flow cytometry and immunofluorescence microscopy, mice were orally inoculated with L. casei-PgsA-E7. E7-specific serum IgG and mucosal IgA productions were enhanced after oral administration and significantly enhanced after boosting. Systemic and local cellular immunities were significantly increased after boosting, as shown by increased counts of lymphocytes (SI = 9.7 +/- 1.8) and IFN-gamma secreting cells [510 +/- 86 spot-forming cells/10(6)cells] among splenocytes and increased IFN-gamma in supernatants of vaginal lymphocytes. Furthermore, in an E7-based mouse tumor model, animals receiving orally administered L. casei-PgsA-E7 showed reduced tumor size and increased survival rate versus mice receiving control (L. casei-PgsA) immunization. These results collectively indicate that the oral administration of E7 displayed on lactobacillus induces cellular immunity and antitumor effects in mice. Copyright 2006 Wiley-Liss, Inc.

Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

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Ana M. C. Faria

2006-01-01

Full Text Available Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10 and Th3 (TGF-β regulatory T cells (Tregs plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB, Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE, uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral, formulation, mucosal adjuvants, combination therapy and early therapy.

Protective Effects of Vitamin E on Methotrexate-Induced Jejunal Mucosal Damage in Rats.

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Burcu, Busra; Kanter, Mehmet; Orhon, Zeynep Nur; Yarali, Oguzhan; Karabacak, Rukiye

2016-04-01

To investigate the possible protective effects of Vitamin E (Vit E) on oxidative stress and jejunal damage in the rat intestinal mucosa after methotrexate (MTX)-induced enterotoxicity. Rats were divided into 3 groups: control, MTX, and MTX+ Vit E; each group contained 8 animals. The control group was given physiological serum in addition to sunflower oil for 3 days. The second group was given sunflower oil with intragastric tube daily, followed by MTX injection (20 mg/kg intraperitoneally). To the third group, starting 3 days before injection, Vit E was given dissolved in sunflower oil (600 mg/kg orally) in addition to MTX injection. Four days after MTX injection the anesthetized rats were sacrificed, and the tissue samples obtained from their jejunums were investigated for histological and biochemical analysis. Vit E treatment significantly decreased the elevated tissue malondialdehyde levels and increased the reduced glutathione peroxidase and superoxide dismutase activities in comparison to the MTX-treated group. MTX treatment caused severe histopathological injury including mucosal erosions, inflammatory cell infiltration, necrosis, hemorrhage, and villous congestion. Vit E treatment significantly attenuated the severity of intestinal injury caused by MTX via inhibiting induced nitric oxide synthase levels and NF-κB p65 activation. Because of its reconstructing and antioxidant effects, Vit E pretreatment may have protective effects in the intestinal tissue of MTX-treated rats.

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)

Chimeric plant virus particles administered nasally or orally induce systemic and mucosal immune responses in mice

DEFF Research Database (Denmark)

Brennan, F.R.; Bellaby, T.; Helliwell, S.M.

1999-01-01

The humoral immune responses to the D2 peptide of fibronectin-binding protein B (FnBP) of Staphylococcus aureus, expressed on the plant virus cowpea mosaic virus (CPMV), were evaluated after mucosal delivery to mice. Intranasal immunization of these chimeric virus particles (CVPs), either alone...

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.

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

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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)

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

Science.gov (United States)

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

2015-09-01

Melphalan followed by hematopoietic stem-cell transplantation (HSCT) is the standard treatment for multiple myeloma and other hematopoietic neoplasms. However, high doses of melphalan cause severe oral mucositis (OM). The objective was to verify the efficacy of cryotherapy plus laser therapy on reduction of OM severity. HSCT patients undergoing melphalan chemotherapy (n = 71) were randomly divided into two groups according to OM treatment: oral cryotherapy performed with ice chips for 1 h 35 min followed by low-level laser therapy (InGaAIP, 660 nm, 40 mW, 6 J/cm(2) ) (n = 54) and laser therapy alone with the same protocol (n = 17). A control group (n = 33) was composed of HSCT patients treated with melphalan who received no specific treatment for OM. OM scores and clinical information were collected from D0 to D + 11. The cryotherapy/laser therapy group showed the lowest OM scores (maximum Grade I) and the lowest mean number of days (8 days) with OM in comparison with the other groups (p cryotherapy with laser therapy was effective in reducing OM severity in HSCT patients who underwent melphalan conditioning. Copyright © 2014 John Wiley & Sons, Ltd.

Systemic and Mucosal Antibody Responses to Soluble and Nanoparticle-Conjugated Antigens Administered Intranasally

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Savannah E. Howe

2016-10-01

Full Text Available Nanoparticles (NPs are increasingly being used for drug delivery, as well as antigen carriers and immunostimulants for the purpose of developing vaccines. In this work, we examined how intranasal (i.n. priming followed by i.n. or subcutaneous (s.c. boosting immunization affects the humoral immune response to chicken ovalbumin (Ova and Ova conjugated to 20 nm NPs (NP-Ova. We show that i.n. priming with 20 mg of soluble Ova, a dose known to trigger oral tolerance when administered via gastric gavage, induced substantial systemic IgG1 and IgG2c, as well as mucosal antibodies. These responses were further boosted following a s.c. immunization with Ova and complete Freund’s adjuvant (Ova+CFA. In contrast, 100 µg of Ova delivered via NPs induced an IgG1-dominated systemic response, and primed the intestinal mucosa for secretion of IgA. Following a secondary s.c. or i.n. immunization with Ova+CFA or NP-Ova, systemic IgG1 titers significantly increased, and serum IgG2c and intestinal antibodies were induced in mice primed nasally with NP-Ova. Only Ova- and NP-Ova-primed mice that were s.c.-boosted exhibited substantial systemic and mucosal titers for up to 6 months after priming, whereas the antibodies of i.n.-boosted mice declined over time. Our results indicate that although the amount of Ova delivered by NPs was 1000-fold less than Ova delivered in soluble form, the antigen-specific antibody responses, both systemic and mucosal, are essentially identical by 6 months following the initial priming immunization. Additionally, both i.n.- and s.c.-boosting strategies for NP-Ova-primed mice were capable of inducing a polarized Th1/Th2 immune response, as well as intestinal antibodies; however, it is only by using a heterogeneous prime-boost strategy that long-lasting antibody responses were initiated. These results provide valuable insight for future mucosal vaccine development, as well as furthering our understanding of mucosal antibody responses.

Innate Immunity and Saliva in Candida albicans–mediated Oral Diseases

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Salvatori, O.; Puri, S.; Tati, S.; Edgerton, M.

2016-01-01

The oral cavity is a unique niche where Candida albicans infections occur in immunocompetent as well as immunosuppressed individuals. Here we critically review the significance of human innate immune response in preventing oral candidiasis. One important line of defense against oropharyngeal candidiasis is the oral microbiota that prevents infection by competing for space and nutrients as well as by secreting antagonistic molecules and triggering local inflammatory responses. C. albicans is able to induce mucosal defenses through activation of immune cells and production of cytokines. Also, saliva contains various proteins that affect C. albicans growth positively by promoting mucosal adherence and negatively through immune exclusion and direct fungicidal activity. We further discuss the role of saliva in unifying host innate immune defenses against C. albicans as a communicating medium and how C. albicans overgrowth in the oral cavity may be a result of aberrations ranging from microbial dysbiosis and salivary dysfunction to epithelial damage. Last we underscore select oral diseases in which C. albicans is a contributory microorganism in immune-competent individuals. PMID:26747422

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

Science.gov (United States)

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.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact

DEFF Research Database (Denmark)

Jensen, Siri Beier; Pedersen, Anne Marie Lynge; Vissink, Arjan

2010-01-01

, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment....... Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant...... formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia...

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.

Immunodetection of rasP21 and c-myc oncogenes in oral mucosal swab preparation from clove cigarette smokers

Directory of Open Access Journals (Sweden)

Silvi Kintawati

2008-12-01

Full Text Available Background: Smoking is the biggest factor for oral cavity malignancy. Some carcinogens found in cigar will stimulate epithel cell in oral cavity and cause mechanism disturbance on tissue resistance and produce abnormal genes (oncogenes. Oncogenes ras and myc are found on malignant tumor in oral cavity which are associated with smoking. Purpose: This research is to find the expression of oncogenes rasP21 and c-myc in oral mucosa epithelial of smoker with immunocytochemistry reaction. Methods: An oral mucosal swab was performed to 30 smokers categorized as light, moderate, and chain, and 10 non smokers which was followed by immunocytochemistry reaction using antibody towards oncogene rasP21 and c-myc is reacted to identify the influence of smoking towards malignant tumor in oral cavity. The result is statistically analyzed using Kruskal-Wallis test. Result: Based on the observation result of oncogene rasP21reaction, it shows that there is significant difference between non smoker group and light smoker, compared to moderate and chain smoker group (p < 0.01. On the other side, the observation result of oncogene c-myc indicates that there is no significant difference between the group of non smokers and the group of light, moderate, and chain smokers (p > 0.05. Conclusion: The higher the possibility of oral cavity malignancy and that the antibody for rasP21 oncogene can be used as a marker for early detection of oral cavity malignancy caused by smoking.

Pathogenesis of oral FIV infection.

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Craig Miller

Full Text Available Feline immunodeficiency virus (FIV is the feline analogue of human immunodeficiency virus (HIV and features many hallmarks of HIV infection and pathogenesis, including the development of concurrent oral lesions. While HIV is typically transmitted via parenteral transmucosal contact, recent studies prove that oral transmission can occur, and that saliva from infected individuals contains significant amounts of HIV RNA and DNA. While it is accepted that FIV is primarily transmitted by biting, few studies have evaluated FIV oral infection kinetics and transmission mechanisms over the last 20 years. Modern quantitative analyses applied to natural FIV oral infection could significantly further our understanding of lentiviral oral disease and transmission. We therefore characterized FIV salivary viral kinetics and antibody secretions to more fully document oral viral pathogenesis. Our results demonstrate that: (i saliva of FIV-infected cats contains infectious virus particles, FIV viral RNA at levels equivalent to circulation, and lower but significant amounts of FIV proviral DNA; (ii the ratio of FIV RNA to DNA is significantly higher in saliva than in circulation; (iii FIV viral load in oral lymphoid tissues (tonsil, lymph nodes is significantly higher than mucosal tissues (buccal mucosa, salivary gland, tongue; (iv salivary IgG antibodies increase significantly over time in FIV-infected cats, while salivary IgA levels remain static; and, (v saliva from naïve Specific Pathogen Free cats inhibits FIV growth in vitro. Collectively, these results suggest that oral lymphoid tissues serve as a site for enhanced FIV replication, resulting in accumulation of FIV particles and FIV-infected cells in saliva. Failure to induce a virus-specific oral mucosal antibody response, and/or viral capability to overcome inhibitory components in saliva may perpetuate chronic oral cavity infection. Based upon these findings, we propose a model of oral FIV pathogenesis

Prevalence of oral mucosal lesions in dermatologically diseased patients: A cross-sectional study in Meerut

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Tanushree Keswani

2014-01-01

Full Text Available Introduction: It is a noted fact that dermatologic diseases have varied oral manifestations. By far, there have been inordinately few studies focusing on the prevalence of a wide spectrum of oral mucosal lesions (OML in patients with dermatologic diseases. This is significant as oral lesions may be the only or the primary feature of the skin disease, which could be neglected by dentists. This study aimed to estimate the frequency and sociobehavioral correlates of OML in skin disease patients attending outpatient′s facility of Subharti Hospital, Dermatology Clinic, Meerut, India. Materials and Methods: This was a cross-sectional hospital-based study conducted in Meerut during the period from August 2013 to October 2013. A total of 500 patients (mean age 37.2 ± 14.11 years, 41.4% females completed an oral examination and a personal interview. OML were recorded using the World Health Organization criteria. Data were analyzed using the Statistical Package for Social Science (version 15.0.1. Cross tabulation and Chi-square with Fisher′s exact test were used. Results: At least one kind of OML was registered in 11.8%, males (58.6%: 60.0% versus females (40.0%: 45.6%, P < 0.01 skin disease patients. Thus, a certain number of patients had more than one type of OML. Aphthae were the most frequently diagnosed OML (3.4%, followed in descending order by oral lichen planus (1.8% and geographic tongue (1.6%. Conclusion: OML were frequently diagnosed in skin disease patients (11.80% and varied systematically with the dermatologic disease, age, and gender. The substantial prevalence rates of OML emphasize the importance of routine examination of the oral mucosa in a dermatology clinic.

A regenerative approach towards mucosal fenestration closure

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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

Effect of Cissus quadrangularis on gastric mucosal defensive factors in experimentally induced gastric ulcer-a comparative study with sucralfate.

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Jainu, Mallika; Devi, C S Shyamala

2004-01-01

Cissus quadrangularis is an indigenous plant commonly mentioned in Ayurveda for treatment of gastric ulcers. The ulcer-protective effect of a methanolic extract of C. quadrangularis (CQE) was comparable to that of the reference drug sucralfate. Further, gastric juice and mucosal studies showed that CQE at a dose of 500 mg/kg given for 10 days significantly increased the mucosal defensive factors like mucin secretion, mucosal cell proliferation, glycoproteins, and life span of cells. The present investigation suggests that CQE not only strengthens mucosal resistance against ulcerogens but also promotes healing by inducing cellular proliferation. Thus, CQE has potential usefulness for treatment of peptic ulcer disease.

Oral damages in radiotherapy: dentistry prevention and treating

International Nuclear Information System (INIS)

Caielli, Cibelle; Martha, Patricia M.; Dib, Luciano L.

1995-01-01

The authors show the importance of the multidisciplinary participation in treatment of oncologic patients about the prevention and treatment of oral damage induced by head and neck irradiation. The main secondary effects are: xerostomy, mucositis, irradiation caries and osteoradionecrosis. The dentistry has to perform preventively to avoid the appearance of this sequel or reduce its effects. (author)

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

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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.

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.

Oral Topical Doxepin Rinse: Anesthetic Effect in Normal Subjects

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Joel B Epstein

2003-01-01

Full Text Available Oral doxepin rinse has been reported to provide pain relief in patients with oral mucosal lesions due to cancer or cancer therapy. The purpose of this study was to assess the anesthetic effect of doxepin oral rinse in normal subjects to identify the duration of effect and to contrast the anesthetic effect with reported pain relief in patients with oral mucosal lesions. Normal volunteers were provided a solution of doxepin (5 mg/mL for oral rinsing. Oral numbness and adverse effects were recorded for a period of 4 h after rinsing. Doxepin rinse resulted in mucosal anesthesia in all subjects. Sedation/fatigue was reported in four of seven subjects. There were no taste complaints and no nausea reported. The limited duration of numbness/anesthesia in normal subjects compared with prior studies showing pain relief for more than 3 h in patients with mucosal lesions, suggests that the extended duration of pain relief in patients was due to analgesic effects rather than anesthetic effects. The majority of normal subjects reported sedation after use, but this was less common in patients with mucosal lesions.

Selective binding of sucralfate to endoscopic mucosal resection-induced gastric ulcer: evaluation of aluminium adherence.

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Itoh, T; Kusaka, K; Kawaura, K; Kashimura, K; Yamakawa, J; Takahashi, T; Kanda, T

2004-01-01

We evaluated the effect of sucralfate in patients with early gastric cancer in endoscopic mucosal resection (EMR)-induced gastric ulcers, and in rats with acetic acid-induced ulcers, by measuring concentrations of aluminium adhering to mucosal lesions. Twenty-two patients who underwent EMR received sucralfate with or without ranitidine and were examined endoscopically after 1 week, 2 weeks and 3 weeks. Gastric juice pH and concentration of aluminium in samples of ulcerated and normal mucosa were measured at various time-points. Good ulcer healing was observed in all patients. Significantly higher concentrations of aluminium were found in ulcerated tissue compared with normal mucosa. This selective binding of sucralfate was even found 12 h after drug administration and was confirmed in acetic acid-induced ulcers in 40 rats. Neutral rather than acid gastric juice was observed up to 12 h after the administration of sucralfate alone. These results suggest that sucralfate with or without ranitidine may contribute to the healing of EMR-induced ulcers by selectively binding to lesions.

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.

Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials.

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Li Wang

Full Text Available Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT. The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT.PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN use, and length of hospital stay.Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99 and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25. In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively. However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively.Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT.

Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials.

Science.gov (United States)

Wang, Li; Gu, Zhenyang; Zhai, Ruiren; Zhao, Shasha; Luo, Lan; Li, Dandan; Zhao, Xiaoli; Wei, Huaping; Pang, Zhaoxia; Wang, Lili; Liu, Daihong; Wang, Quanshun; Gao, Chunji

2015-01-01

Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT. PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN) use, and length of hospital stay. Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99) and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25). In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively). However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively). Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT.

Immunological evaluation of bacterial derived Cochleate and proteoliposome as mucosal adjuvants.

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del Campo, Judith; Lastre, Miriam; Bracho, Gustavo; Rodríguez, Tamara; Gil, Danay; Zayas, Caridad; Taboada, Carlos; Acevedo, Reinaldo; Pérez, Danev Ricardo; Pérez, Oliver

2006-04-12

We evaluated the potential of two bacterial derived compounds, Cochleate and Proteoliposome (PL), administrated to mice by nasal or oral routes on induction of antibody and cytokine responses. Anti PL IgG and IgA responses were measured by ELISA in saliva, sera or vaginal fluids of immunized mice. Productions of gammaIFN and IL-5 were determined in spleen cells of immunized mice following a recall in vitro with Cochleate or PL. Intranasal administration elicited a higher anti PL IgA response in both saliva and vaginal fluids as compared with oral route. Mice immunized with Cochleate or PL via intranasal or oral route-induced anti PL IgG and IgG2a antibody responses in their sera and vaginal fluids. Spleen cells from these immunized mice produced gammaIFN, but not IL-5, after a recall in vitro with Cochleate or PL. These results show that Cochleate and PL are capable of inducing both systemic and mucosal antibody responses as well as a Th1 type of immunity as evidenced by high gammaIFN and IgG2a antibody responses.

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

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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

Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis.

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Alexandra L Whittaker

Full Text Available Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8. Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg and NSAID (carprofen; 15mg/kg in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg. Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001. Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.

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.

Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummary

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Jayaum S. Booth

2017-11-01

Full Text Available Background & Aims: Systemic cellular immunity elicited by the Ty21a oral typhoid vaccine has been extensively characterized. However, very limited data are available in humans regarding mucosal immunity at the site of infection (terminal ileum [TI]. Here we investigated the host immunity elicited by Ty21a immunization on terminal ileum–lamina propria mononuclear cells (LPMC and peripheral blood in volunteers undergoing routine colonoscopy. Methods: We characterized LPMC-T memory (TM subsets and assessed Salmonella enterica serovar Typhi (S Typhi–specific responses by multichromatic flow cytometry. Results: No differences were observed in cell yields and phenotypes in LPMC CD8+-TM subsets following Ty21a immunization. However, Ty21a immunization elicited LPMC CD8+ T cells exhibiting significant S Typhi–specific responses (interferon-γ, tumor necrosis factor-α, interleukin-17A, and/or CD107a in all major TM subsets (T-effector/memory [TEM], T-central/memory, and TEM-CD45RA+, although each TM subset exhibited unique characteristics. We also investigated whether Ty21a immunization elicited S Typhi–specific multifunctional effectors in LPMC CD8+ TEM. We observed that LPMC CD8+ TEM responses were mostly multifunctional, except for those cells exhibiting the characteristics associated with cytotoxic responses. Finally, we compared mucosal with systemic responses and made the important observation that LPMC CD8+ S Typhi–specific responses were unique and distinct from their systemic counterparts. Conclusions: This study provides the first demonstration of S Typhi–specific responses in the human terminal ileum mucosa and provides novel insights into the generation of mucosal immune responses following oral Ty21a immunization. Keywords: Lamina Propria Mononuclear Cells, Multifunctional T Cells, CD8+-T Memory Cells, Typhoid, Vaccines

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.

Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new ''B2'' configuration of the RA-6 nuclear reactor

International Nuclear Information System (INIS)

Monti Hughes, Andrea; Trivillin, Veronica A.; Schwint, Amanda E.; Longhino, Juan; Boggio, Esteban; Medina, Vanina A.; Martinel Lamas, Diego J.; Garabalino, Marcela A.; Heber, Elisa M.; Pozzi, Emiliano C.C.; Itoiz, Maria E.; Aromando, Romina F.; Nigg, David W.

2017-01-01

Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new ''B2'' configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in ''B1'' experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94-96%) than in control (16%) and BO groups (9-38%), and did not differ significantly from the ''B1'' results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control. (orig.)

Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new ''B2'' configuration of the RA-6 nuclear reactor

Energy Technology Data Exchange (ETDEWEB)

Monti Hughes, Andrea; Trivillin, Veronica A.; Schwint, Amanda E. [Constituyentes Atomic Center, National Atomic Energy Commission (CNEA), Department of Radiobiology, San Martin, Province Buenos Aires (Argentina); National Research Council (CONICET), Ciudad Autonoma de Buenos Aires (Argentina); Longhino, Juan; Boggio, Esteban [Bariloche Atomic Center, CNEA, Department of Nuclear Engineering, San Carlos de Bariloche, Province Rio Negro (Argentina); Medina, Vanina A.; Martinel Lamas, Diego J. [National Research Council (CONICET), Ciudad Autonoma de Buenos Aires (Argentina); Pontifical Catholic University of Argentina (UCA), Laboratory of Tumoral Biology and Inflammation, School of Medical Sciences, Institute for Biomedical Research (BIOMED CONICET-UCA), Ciudad Autonoma de Buenos Aires (Argentina); Garabalino, Marcela A.; Heber, Elisa M.; Pozzi, Emiliano C.C. [Constituyentes Atomic Center, National Atomic Energy Commission (CNEA), Department of Radiobiology, San Martin, Province Buenos Aires (Argentina); Itoiz, Maria E. [Constituyentes Atomic Center, National Atomic Energy Commission (CNEA), Department of Radiobiology, San Martin, Province Buenos Aires (Argentina); UBA, Department of Oral Pathology, Faculty of Dentistry, Ciudad Autonoma de Buenos Aires (Argentina); Aromando, Romina F. [UBA, Department of Oral Pathology, Faculty of Dentistry, Ciudad Autonoma de Buenos Aires (Argentina); Nigg, David W. [Idaho National Laboratory, Idaho Falls (United States)

2017-11-15

Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new ''B2'' configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in ''B1'' experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94-96%) than in control (16%) and BO groups (9-38%), and did not differ significantly from the ''B1'' results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control. (orig.)