bromochloroacetic-acid and Stomatitis

Radiation-induced oral mucositis is one of the most common adverse events in radiation therapy for head and neck cancers, but treatments for oral mucositis are limited to palliative and supportive care. New approaches are required to prevent radiation-induced mucositis and to improve treatments. The Keap1-Nrf2 system regulates cytoprotection against oxidative and electrophilic stresses. Nrf2 also regulates keratin layer thickness in mouse tongues. Therefore, we hypothesized that Nrf2 may protect the tongue epithelium against radiation-induced mucositis via elimination of reactive oxygen species and induction of keratin layer thickening. To test this hypothesis, we prepared a system for γ-ray exposure of restricted areas and irradiated the tongues of model mice with Nrf2 and Keap1 loss-of-function. We discovered that loss of Nrf2 expression indeed sensitized the tongue epithelium to radiation-induced ulcer formation with inflammation. Constitutive Nrf2 activation by genetic Keap1 knockdown alleviated radiation-induced DNA damage by increasing antioxidation. In agreement with the genetic Nrf2 activation model, the Nrf2 inducer CDDO-Im prevented irradiation damage to the tongue epithelium. These results demonstrate that Nrf2 activation has the potential to prevent the development of radiation-induced mucositis and that Nrf2 inducers are an important therapeutic drug for protection of the upper aerodigestive tract from radiation-induced mucositis.

Topics: Animals; Antioxidants; Cytoskeletal Proteins; Kelch-Like ECH-Associated Protein 1; Keratins; Mice; Mucositis; NF-E2-Related Factor 2; Oleanolic Acid; Radiation Injuries; Stomatitis

Whether a minimal width of keratinized mucosa (KM) is required to maintain peri-implant tissue health has been a topic of interest. This systematic review and meta-analysis aims to investigate the effect of KM on various peri-implant health-related parameters.. An electronic search of five databases (from 1965 to October 2012) and a hand search of peer-reviewed journals for relevant articles were performed. Human cross-sectional or longitudinal studies with data on the relationship between the amount of KM around dental implants and various peri-implant parameters, with a follow-up period of at least 6 months, were included.. Eleven studies, seven cross-sectional and four longitudinal, were included. Weighted mean difference (WMD) and confidence interval (CI) were calculated with meta-analyses for each clinical parameter. The results showed statistically significant differences in plaque index (PI) and modified PI (WMD = -0.27, 95% CI = -0.43 to -0.11), modified gingival index (mGI) (WMD = -0.48, 95% CI = -0.70 to -0.27), mucosal recession (MR) (WMD = -0.60 mm, 95% CI = -0.85 to -0.36 mm), and attachment loss (AL) (WMD = -0.35 mm, 95% CI = -0.65 mm to -0.06 mm), all favoring implants with wide KM. However, comparisons of other parameters (bleeding on probing, modified bleeding index, GI, probing depth, and radiographic bone loss) did not reach statistically significant differences. The result of heterogeneity test showed only one parameter (AL, P value for the χ(2) test = 0.30 and I(2) test = 18%) had a low degree of heterogeneity among analyzed studies; meta-analyses of other parameters presented moderate-to-high degree of heterogeneity. Limitations of the present review include limited number of selected studies (n = 11), existence of heterogeneity and publication bias, and only English-written articles searched.. Based on current available evidence, a lack of adequate KM around endosseous dental implants is associated with more plaque accumulation, tissue inflammation, MR, and AL.

Topics: Alveolar Bone Loss; Dental Implants; Dental Plaque Index; Gingiva; Gingival Recession; Humans; Keratins; Periodontal Attachment Loss; Periodontal Index; Stomatitis

Several different types of interactions are possible between a chemical, a mixture of chemicals, and associated extrinsic factors (i.e., mechanical irritation) in the oral mucosa. These interactions can be broadly classified as irritative or allergenic in nature. In each case, the pathology usually includes mucosal inflammation. The information compiled and reviewed in this article suggests that, given the broad definition of surface lesions/mucosal abnormalities, there may be a continuum of irritation that can be termed "irritant contact stomatitis." This may be due to the fact that the mouth is lined with highly vascular mucosa that turns over rapidly compared to the skin, and may or may not be covered by keratin. Some regions in the mouth are uniquely sensitive to irritants because they can penetrate through the tissue easily. Key factors involved in the potential development of irritation are: inherent irritation potential of the agent, amount of exposure (concentration, duration, and frequency), ability to penetrate the tissue, and inherent reactivity of the subject as well as other extrinsic factors. Irritation leading to oral mucosal alterations is a common occurrence caused by a wide variety of exposures and insults to the oral cavity. Various irritants such as foods, chemicals, friction, thermal/mechanical injury, metals, spices, and oral care products have been documented to cause irritant reactions in susceptible individuals, particularly if used under exaggerated exposure conditions. It is important to note that most irritation in the oral cavity tends to reverse quickly when the causative agent is removed. Oral irritation is a commonly occurring phenomenon. Thus, it is important that the clinician be aware of the clinical manifestations and etiology of the condition.

Topics: Allergens; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Food; Friction; Hot Temperature; Humans; Irritants; Keratins; Metals; Mouth Mucosa; Skin; Spices; Stomatitis

Topics: Adolescent; Adult; Age Factors; Aged; Candidiasis, Oral; Child; Female; Follow-Up Studies; Humans; Hyperplasia; Keratins; Keratosis; Leukoplakia, Oral; Male; Middle Aged; Mouth Neoplasms; Nicotine; Precancerous Conditions; Retrospective Studies; Sex Factors; Smoking; Stomatitis

To analyze the influence of the width of keratinized mucosa (KM) on the development and resolution of experimental peri-implant mucositis lesions at abutments with different microstructures in humans.. In a randomized, controlled study, a total of 28 patients had received 28 target implants exhibiting a KM ≥2 mm. These were randomly connected with either partially microgrooved- (test) (n = 15) or machined (control) (n = 13) healing abutments. The study protocol included a wound healing period (WH) following implant placement (12 weeks), a plaque exposure phase (EP) of 21 days (EPd21) and a resolution phase (RP) including visits at 2, 4, and 16 weeks (RPw2; RPw4; RPw16) following plaque removal. Linear regression analyses were used to analyze the relationship between the width of KM and clinical outcomes (i.e., modified plaque index [mPI], modified gingival index [mGI], bleeding on probing [BOP], and probing depth [PD]).. Mean and median KM values (end of WH) were 5.9 ± 2.6 and 5.0 mm (min: 2 mm; max: 10 mm; interquartile range: 5 mm) at test- and 5.5 ± 2.6 and 4.0 mm (min: 3 mm; max: 11 mm interquartile range: 4 mm) at control abutments. The linear regression analysis revealed significant correlations between the width of KM and mPI (test: RPw2; control: RPw16), mGI (test: RPw16), BOP (both: RPw16), and PD (test: RPw16; control: EPd21, RPw2, RPw4, RPw16) scores.. The width of KM (≥2 mm) had some effects on the development (i.e., at 21 days) and resolution of experimental peri-implant mucositis lesions at both abutment types.

Topics: Adult; Dental Abutments; Dental Implantation, Endosseous; Dental Plaque; Dental Plaque Index; Female; Humans; Keratins; Male; Mouth Mucosa; Peri-Implantitis; Periodontal Index; Stomatitis

During head and neck cancer radiotherapy, oral mucositis is the most frequent early side effect. Systemic dermatan sulfate (DS) administration has been shown to significantly decrease oral mucosal radiation reactions during daily fractionated irradiation (IR) in an established mouse model. The aim of this study was to investigate the mechanism of the oral epithelial differentiation process, during IR alone and in combination with DS treatment in the same mouse model.. Fractionated IR 5 × 3 Gy/week was given to the snouts of mice over two weeks, either alone (IR) or in combination with daily DS treatment of 4 mg/kg (IR + DS). Groups of mice (n = 3) were sacrificed every second day over the course of 14 days in both experimental arms. Their tongue was excised and subjected to immunohistochemical processing.. In the p16 analysis as a proliferation marker, the difference between IR alone and IR + DS in the germinal (proliferation) layer was not significant, not stimulating the proliferation process. For the p21 analysis as a differentiation marker on the functional (differentiation) layer, the difference between IR alone and IR + DS arms was significant, indicating that DS inhibited the differentiation process. In the cytokeratin (CK) analysis as the indicator of cellular skeletal integrity, the percentage of antibody-positive cells was above the normal level in both experimental arms and significantly superior in the IR + DS arm.. The mucosal protective activity of DS, instead of stimulating proliferation, is based on prevention of cell loss by a combination of effects leading to the inhibition of cellular differentiation and an increase in the expression of epithelial mechanical strength between intercellular mechanical junctions.

Topics: Animals; Cell Death; Cell Differentiation; Cell Proliferation; Dermatan Sulfate; Dose Fractionation, Radiation; Intercellular Junctions; Keratins; Mice; Mouth Mucosa; Radiation Injuries, Experimental; Stomatitis

The aim of this work was to study cytokeratin (Ck) expression in initial radiation-induced oral mucositis.. Eleven cases of initial radiomucositis of the buccal mucosa and 9 normal specimens were immunostained for Ck 1, 5, 6, 7, 8, 10, 14, 16, 18, and 19 by immunoperoxidase method.. Expression of Ck 1, 6, 10, and 16 was stronger in mucositis than in normal mucosa. Ck 7, 8, and 18 were negative for both control and study groups. Ck 5, 13, and 14 were positive for both groups, nevertheless suprabasal staining for Ck 14 was more evident in mucositis than in the control group. Sporadic staining for Ck 19 was observed in 1 case of mucositis and in 2 controls.. Increased Ck expression can be associated with the reactive proliferation of the epithelium and increasing resistance of the oral mucosa during the initial phases of radiotherapy.

Topics: Adult; Cranial Irradiation; Female; Humans; Immunoenzyme Techniques; Keratin-1; Keratin-10; Keratin-14; Keratin-16; Keratin-6; Keratins; Male; Middle Aged; Mucositis; Radiation Injuries; Radiotherapy Dosage; Stomatitis

Lupus erythematosus (LE) is an autoimmune disease of unknown cause. Prevalence of oral involvement in patients with LE is uncertain but may vary from 9 to 45% in patients with systemic disease and from 3 to 20% in patients with chronic cutaneous involvement.. Incidence of oral lesions of LE and their clinical aspects were investigated. Their histopathologic features were analyzed, and the status of epithelial maturation was assessed through the expression patterns of cytokeratins.. Twenty-six patients (from 188 examined) presented oral lesions of LE. Most of them were females (19) with systemic disease (11). Clinical aspects of these lesions varied, and lips and buccal mucosa were most affected. Histologically, lesions revealed lichenoid mucositis with perivascular infiltrate and thickening of basement. Cytokeratins profile showed hyperproliferative epithelium, with expression of CK5/6, and CK14 on all epithelial layers, CK16 on all suprabasal layers and CK10 on prickle cell layers only.. Oral lesions of LE show a variety of aspects, and their microscopic features are of a lichenoid mucositis with deep inflammatory infiltrate. Cytokeratins expression patterns are of hyperproliferative epithelium, and this phenomenon must be analyzed in relation to the inflammatory cytokines for a better understanding of the mechanisms of the disease.

Topics: Adult; Aged; Female; Humans; Immunohistochemistry; Keratins; Lichenoid Eruptions; Lupus Erythematosus, Systemic; Male; Middle Aged; Stomatitis

Oral ulcerative mucositis is a common toxicity associated with drug and radiation therapy for cancer. It impacts on quality of life and economic outcomes, as well as morbidity and mortality. Mucositis is often associated with dose limitations for chemotherapy or is a cause for dose interruption for radiation. The complexity of mucositis as a biological process has only been recently appreciated. It has been suggested that the condition represents a sequential interaction of oral mucosal cells and tissues, pro-inflammatory cytokines and local factors such as saliva and the oral microbiota. The recognition that the pathophysiology of mucositis is a multifactorial process was partially suggested by the observation that interleukin-11 (IL-11), a pleotropic cytokine, favorably altered the course of chemotherapy-induced mucositis in an animal model. In the current study, we evaluated a series of biologic and morphologic outcomes to determine their roles and sequence in the development of experimental radiation-induced mucositis and to evaluate the effects of IL-11 in attenuating them. Our results suggest that IL-11 favorably modulates acute radiation-induced mucositis by attenuating pro-inflammatory cytokine expression. Data are also presented which help define the pathobiological sequence of mucositis.

Topics: Animals; Apoptosis; Cricetinae; Disease Progression; Head and Neck Neoplasms; Immunohistochemistry; Interleukin-1; Interleukin-11; Keratins; Male; Mast Cells; Mesocricetus; Mouth Mucosa; Oral Ulcer; Radiation Injuries, Experimental; Stomatitis

In recent years, the use of mouthwash has become widespread as a part of routine oral hygiene. However, there have been no fundamental studies on the influence of mouthwashes on the human oral mucosae. One hundred and twenty-five subjects (50 males and 75 females) were selected for this study. The effects of mouthwash was assessed with the use of exfoliative cytological and cytomorphometric analyses of smears obtained from clinically normal upper labium and cheek mucosae before mouthwashing, 30 s, 10 min and 1 h after mouthwashing. The independent variables examined were oral site, sex and smoking (smokers versus never-smokers). In all subjects and sites, the appearance rate of exfoliated cells stained by light green SFY decreased just after mouthwashing, and the rate after 1 h was lower than that of the untreated controls. The oral mucosae of smokers were more irritated action by mouthwashing than that of the never-smokers. Even after 1 h, decreases in the nuclear and cytoplasmic areas of cells and increases in inflammatory cells were observed. In conclusion, the use of mouthwash was so inflamed the human oral mucosae that more attention should be paid when it is used daily in oral hygiene.

Topics: Adult; Cell Nucleus; Cell Size; Cheek; Coloring Agents; Cytodiagnosis; Cytoplasm; Female; Follow-Up Studies; Humans; Irritants; Keratins; Leukocyte Count; Lip; Male; Mouth Mucosa; Mouthwashes; Neutrophils; Oral Hygiene; Sex Characteristics; Smoking; Stomatitis

The palatal mucosa of the guinea pig contained in the normal state a certain number of binucleated cells. Injections of substances inducing inflammation (carrageenan, calcium pyrophosphate dihydrate, monosodium urate) were made in order to produce an inflammatory reaction in the palatal mucosa of young male and adult guinea pigs. The percentage of binucleated epithelial cells was estimated at different time intervals after injections. For the three injected substances, a significant increase of the binucleated epithelial cells was noted in the palatal injected mucosa, when compared with a healthy mucosa or a mucosa having been injected with saline.

Topics: Animals; Calcium Pyrophosphate; Carrageenan; Cell Count; Cell Nucleus; Epithelium; Guinea Pigs; Keratins; Male; Mouth Mucosa; Palate; Stomatitis; Uric Acid

A quantitative histological investigation was carried out on biopsy specimens taken from patients suffering from denture sore mouth. The results were compared with those obtained in investigations on denture and non-denture wearers. The sections were studied by standardized quantitative morphometric methods. After 4 years the denture bearing palatal epithelium from both groups, normal denture wearers and the patients suffering from denture sore mouth did not show changes in mean thickness of the epithelium as compared with the controls. The mitotic index in denture bearing epithelium from patients suffering from denture sore mouth was three times lower than in the epithelium of the normal denture wearers. The number of Langerhans cells correlated with the mitotic indices of the group of denture wearers and non-denture wearers. The group of denture sore mouth patients showing a low mitotic index showed a high number of Langerhans cells in their palatal epithelium. The three groups of patients investigated did not show differences in density of mast cells in the lamina propria of their palatal epithelium.

Topics: Adult; Aged; Cell Count; Denture, Complete, Upper; Epithelial Cells; Female; Humans; Keratins; Langerhans Cells; Male; Mast Cells; Middle Aged; Mitotic Index; Mouth Mucosa; Palate; Stomatitis; Stomatitis, Denture

Topics: Candidiasis, Oral; Carcinoma in Situ; Diagnosis, Differential; Epithelium; Erythroplasia; Humans; Keratins; Keratosis; Leukoedema, Oral; Leukoplakia, Oral; Lichen Planus; Lupus Erythematosus, Discoid; Melanins; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Nevus; Precancerous Conditions; Risk; Sebaceous Glands; Smoking; Stomatitis

Topics: Aspirin; Candidiasis; Cheilitis; Denture, Complete; Diagnosis, Oral; Foreign Bodies; Hyperplasia; Keratins; Leukoplakia; Lichen Planus; Palatal Neoplasms; Phenols; Salivary Duct Calculi; Stomatitis; Stomatitis, Aphthous; Stomatitis, Denture

Hamster cheek pouches were painted thrice weekly with 50% v/v turpentine in liquid paraffin over periods ranging from 1 day to 16 weeks. Pouch mucosa was examined histologically for changes and measurements of epithelial thickness were made with a calibrated eyepiece micrometer. An increase in epithelial thickness was first observed 48 hrs. after a single painting and was accompanied by inflammatory changes in both epithelium and connective tissue. Maximal epithelial thickening occurred after 9 weeks of thrice weekly painting. Cheek pouches of animals left without further treatment for up to 1 year following 9 weeks painting were indistinguishable from controls. The epithelial response to treatment with turpentine is that of a reversible benign epithelial hyperplasia with hyperkeratosis.

Topics: Animals; Connective Tissue; Cricetinae; Epithelium; Hyperplasia; Keratins; Keratosis; Male; Models, Biological; Mouth Mucosa; Stomatitis; Time Factors; Turpentine

The alveolar mucosa in the upper jaw from 12 patients suffering from severe denture stomatitis was examined histologically and microradiographically using ultrasoft X-rays. Pathological changes of the epithelial cell layers were observed in all cases. In 10 of the 12 cases examined no keratinization was found. A reduction in the number of epithelial cell layers was commonly observed. In most cases the connective tissue showed signs of moderate to severe inflammation. The inflammatory reaction and the degenerative changes of the tissue were presumably due to a combined effect of microorganisms and mechanical trauma.

Topics: Alveolar Process; Cell Nucleus; Connective Tissue; Connective Tissue Cells; Cytoplasm; Cytoplasmic Granules; Epithelial Cells; Epithelium; Female; Humans; Keratins; Keratosis; Male; Microradiography; Middle Aged; Mouth Mucosa; Stomatitis; Stomatitis, Denture

Pedicled skin flaps of 22 patients which had been exposed for many years to the environment of the oral cavity were examined clinically and histologically. The results permit statements to be made on the nature of the changes which occur on the surface, and in the histological picture of the graft. The superficial skin changes, as well as the typical histological structures of the external skin are shown in the micro-photographs presented, to be still preserved after many years.

Topics: Aged; Epithelium; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Mouth Mucosa; Skin; Skin Transplantation; Stomatitis; Transplantation, Autologous

Topics: Adolescent; Adult; Blood Vessels; Chromium Alloys; Collagen; Denture Bases; Denture, Partial, Removable; Female; Gingiva; Gingival Diseases; Gingival Pocket; Gingivitis; Humans; Keratins; Lymphocytes; Male; Methylmethacrylates; Middle Aged; Plasma Cells; Stomatitis; Stomatitis, Denture