[Antioxidant activity of Euryale ferox seed shell extract and its therapeutic effects on oral ulcer in rats].

OBJECTIVE: To investigate the therapeutic effect of Euryale ferox seed shell extract on oral ulcer in rats and its underlying mechanism. METHODS: The contents of polyphenols and flavonoids in Euryale ferox seed shells were determined by Folin-phenol assay and aluminum nitrate colorimetry, respectively. DPPH·, ABTS+·, ·OH and·O2- scavenging experiments were performed to evaluate the antioxidant activities of Euryale ferox seed shell extract in vitro. In a rat model of oral ulcer induced by burning with glacial acetic acid, the therapeutic effect of Euryale ferox seed shell extract was assessed by detecting changes in serum levels of oxidative factors by enzyme-linked immunosorbent assay (ELISA) and observing pathological changes of the ulcerous mucosa using HE staining; the therapeutic mechanism of the extract was explored by detecting the expression levels of Keap1, Nrf2, Nes-Nrf2 and HO-1 proteins in ulcerous mucosa using Western blotting. RESULTS: The ethyl acetate extract of Euryale ferox seed shells contained 306.74±1.04 mg/g polyphenols and 23.43±0.61 mg/g flavonoids and had IC50 values for scavenging DPPH· and ABTS+· free radicals of 3.42 ± 0.97 µg/mL and 3.32 ± 0.90 µg/mL, respectively. In the rat models, the ethyl acetate extract significantly ameliorated oral mucosal ulcer, increased serum CAT level, and decreased serum MDA level. The protein expression levels of Nes-Nrf2 and HO-1 were increased and Keap1 protein expression was lowered significantly in the ulcerous mucosa of the rats after treatment with the extract (P<0.05 or 0.01). CONCLUSION: The therapeutic effect of Euryale ferox seed shell extract on oral ulcers in rats is mediated probably by activation of the Keap1/Nrf2/HO-1 signaling pathway.

Impact of Thermo-Responsive N-Acetylcysteine Hydrogel on Dermal Wound Healing and Oral Ulcer Regeneration.

This study investigates the efficacy of a thermo-responsive N-acetylcysteine (NAC) hydrogel on wound healing and oral ulcer recovery. Formulated by combining NAC with methylcellulose, the hydrogel's properties were assessed for temperature-induced gelation and cell viability using human fibroblast cells. In vivo experiments on Sprague Dawley rats compared the hydrogel's effects against saline, NAC solution, and a commercial NAC product. Results show that a 5% NAC and 1% methylcellulose solution exhibited optimal outcomes. While modest improvements in wound healing were observed, significant enhancements were noted in oral ulcer recovery, with histological analyses indicating fully regenerated mucosal tissue. The study concludes that modifying viscosity enhances NAC retention, facilitating tissue regeneration. These findings support previous research on the beneficial effects of antioxidant application on damaged tissues, suggesting the potential of NAC hydrogels in improving wound care and oral ulcer treatment.

Multifunctional hyaluronic acid/gelatin methacryloyl core-shell microneedle for comprehensively treating oral mucosal ulcers.

Oral ulceration is the most common oral mucosal disease. Oral mucosal ulcers are extremely painful, may interfere with eating and speaking, and potentially complicate systemic symptoms in severe cases. The humid and highly dynamic environment of the oral cavity makes local drug administration for treating oral mucosal ulcers challenging. To overcome these challenges, we designed and prepared a novel dissolving microneedle (MN) patch containing multiple drugs in a core-shell to promote oral ulcer healing. The MNs contained a methacrylate gelatin shell layer of basic fibroblast growth factor (bFGF), a hyaluronic acid (HA) core loaded with dexamethasone (DXMS), and zeolite imidazoline framework-8 (ZIF-8) encapsulated in the HA-based backplane. Progressive degradation of gelatin methacryloyl (GelMA) from the tip of the MN patch in the oral mucosa resulted in sustained bFGF release at the lesion site, significantly promoting cell migration, proliferation, and angiogenesis. Moreover, the rapid release of HA and, subsequently, DXMS inhibited inflammation, and the remaining MN backing after the tip dissolved behaved as a dressing, releasing ZIF-8 for its antimicrobial effects. This novel, multifunctional, transmucosal core-shell MN patch exhibited excellent anti-inflammatory, antimicrobial, and pro-healing effects in vivo and in vitro, suggesting that it can promote oral ulcer healing.

[Metabolomics of interventional effects of Coptidis Rhizoma and its processed products on oral ulcer due to excess heat in rats].

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1ß(IL-1ß), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1ß, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.

Oral manifestations associated with neutropenia in Syrian patients diagnosed with hematological malignancies and undergoing chemotherapy: A cross-sectional study.

Neutropenia can be caused by a variety of congenital and acquired factors, with Chemotherapy-induced myelosuppression being the most common cause. Neutropenia significantly affects oral health, leading to the manifestation of oral lesions such as ulcers, fungal and viral infections, and mucositis. This study aims to investigate oral lesions in patients with hematological malignancies who developed neutropenia after chemotherapy. This cross-sectional study included 50 patients with hematological malignancies. The participants were divided into 2 groups: the first group consisted of 25 patients with hematological malignancies who developed chemotherapy-induced neutropenia and the second group consisted of 25 patients with hematological malignancies who did not develop chemotherapy-induced neutropenia. Patients were assigned to one of the groups based on the absolute neutrophil count (ANC). Full oral clinical examination was performed to determine the presence of oral lesions. In the Chemotherapy-Induced Neutropenia group, the most common lesion was ulceration, observed in 12 patients (48%). Fungal infections were the second most common, present in 5 patients (20%), followed by viral infections in 4 patients (15%), and mucositis, which occurred in a single patient (4%). A statistically significant association was found between neutropenia and the presence of oral ulcers (P value = .015). In contrast, in the Chemotherapy group, oral changes were less frequent. Fungal infections were the most common, occurring in 4 patients (15%), followed by oral mucositis in 3 patients (12%). Ulceration and viral infections were the least common, each observed in 1 patient (4%). The frequency of various forms of oral ulcers increases with the severity of neutropenia. However, there was no significant increase in other oral lesions in patients with neutropenia.

Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.

Evaluation of the healing potential of Nile tilapia skin collagen in traumatic oral ulcers in male rats.

OBJECTIVE: To evaluate the healing potential of Nile tilapia skin collagen using a rat model with experimentally induced traumatic oral ulcers. DESIGN: Male Wistar rats were segregated into three experimental groups (n = 8/group/euthanasia day). Ulcers were induced using a dermatological punch on the left buccal mucosa. The rats were then euthanized on days 1, 5, 10, 15, and 20 (ntotal=120 rats). Each group received topical treatment, 2x/day, with 1 % Nile tilapia skin collagen orabase (experimental group), only orabase (negative control), or Oncilom-A® orabase (positive control). Ulcer area, closure percentage, and body mass variation were measured. Slides were prepared for histological analysis, which included Picrosirius red staining (collagen analysis), and immunohistochemistry (platelet endothelial cell adhesion molecule, alpha-smooth muscle actin, and transforming growth factor-beta). RESULTS: On day 15, the experimental and positive control groups displayed smaller ulcer areas, a higher percentage of closure, complete re-epithelialization, superior histological repair scores, and a reduced count of polymorphonuclear cells in comparison to the negative control group (p < 0.05). Additionally, the experimental group exhibited an increased number of blood vessels, total collagen (types I and III) and expression of platelet endothelial cell adhesion molecule, alpha-smooth muscle actin, and transforming growth factor-beta relative to the negative and positive control groups (p < 0.05). By day 20, the experimental group showed a more significant weight gain compared to the other groups (p < 0.0001). CONCLUSIONS: Nile tilapia skin collagen orabase optimizes the healing of traumatic ulcers by stimulating re-epithelialization, angiogenesis, and collagenesis. Transforming growth factor-beta plays a significant role in this process.

Thymus satureioides Coss. combats oral ulcer via inhibition of inflammation, proteolysis, and apoptosis.

Oral ulcer is a frequent condition that commonly affects the tongue and in which 75% of the patients experience pain, and 25% report taste changes. The available therapies are not sufficiently effective for rapid and complete healing of tongue ulcers. We previously annotated the metabolites of Thymus satureioides (TS) aerial parts and reported their antioxidant, dermacosmeceutical and hepatoprotective properties. In this study, we performed in silico analysis, by applying network pharmacology and molecular docking, followed by experimental validation of the effect of local application of T. satureioides (TS) gel at two different concentrations on the healing of acetic-acid-induced tongue ulcer in rats. Salvianolic acid A, phloretic acid caffeate, rosmarinic acid, apigenin, and luteolin were the top bioactive ingredients of TS extract. Network pharmacology showed that the most relevant targets of these active constituents were TLR4, COX-2, MMP-9, TNF-α, and Caspase-3. Molecular docking showed that rosmarinic acid and salvianolic acid had a relatively strong binding affinity, compared to the other compounds, toward all the target proteins. Experimental validation in tongue ulcer model in rats and immunohistochemistry experiments showed that application of a gel containing TS extract (5 and 10%) was effective in healing the tongue ulcer via downregulation of COX-2, TNF-α, MMP-9, and Caspase-3. This study suggests that T. satureioides extract could act as a topical treatment for tongue ulcers by combating inflammation, apoptosis, and proteolysis. The possible treatment potential of some constituents including rosmarinic acid and salvianolic acid in oral ulcerations awaits further investigations to confirm their potency.

Childhood granulomatous periorificial dermatitis in 31 Chinese children successfully treated with oral roxithromycin.

Data regarding the treatment of childhood granulomatous periorificial dermatitis (CGPD) using oral therapies are limited. This study included 31 Chinese children with CGPD treated with oral roxithromycin. After 12 weeks of treatment, 90.3% of the patients recovered, and there were no severe adverse effects. Our results suggest that oral roxithromycin is an effective and safe treatment for CGPD.

Oral lesions after infection by SARS CoV 2: two case reports / Lesiones bucales posteriores a infección por SARS CoV 2 presentación de dos casos

Introduction: The SARS CoV 2 infection has resulted in several health, economic, and social crises in all areas. The disease shows a substantial biological diversity in humans causing a series of sequels in the trans- or post-infection period in the entire organism. Case Report: The manifestations that occur in the oral cavity and pharynx have not been evaluated. In this study, two clinical cases are reported. The first patient, a 67-year-old male, presents erosive lesions on the dorsal surface of his tongue after SARS CoV 2 infection. Results: Therapy consisting of reinforcing oral cleaning, use of antifungal solutions, mouthwashes containing superoxidation solution and B complex was given to the patient. The reported lesions improved satisfactorily. The second case, a 47-year-old male patient, presented vesiculobullous lesions on the lingual and labial mucosa accompanied by severe painful symptoms after SARS CoV 2 infection. An incisional biopsy was performed. The histopathological result was compatible with pemphigus vulgaris, and the treatment protocol was started with 0.1% topical mometasone and 2g miconazole gel, observing adequate involution of the lesions after 20 days. Conclusions: The aim of this study is to report on the lesions affecting the oral cavity and pharynx in post-COVID patients with the aim of carrying out a thorough intraoral examination, establishing a clinical or histopathological diagnosis to implement a specific treatment plan in each case to improve the health and quality of life of the patients. Keywords: SARS-CoV-2; Oral manifestations; Oral ulcer; Pemphigus; Mouth; Mucous membrane.

Introducción: La infección por virus de SARS CoV 2 ha dejado a su paso una estela de crisis en materia de salud, económica, social y en todos los ámbitos a la fecha seguimos realizando la observación del comportamiento de la enfermedad en los seres humanos con una diversidad biológica importante y que ha traído como consecuencia una serie de secuelas que se presentan en el periodo trans o posterior a la infección en toda la economía corporal. Reporte de Caso: Se ha evaluado poco las manifestaciones que se presentan en la cavidad bucal y faringe; se presentan dos casos clínicos el primero paciente masculino de 67 años de edad posterior a la infección por SARS CoV 2 presenta diluciones de continuidad en bordes laterales de la lengua se indica terapia y refuerza limpieza bucal, antimicótico, colutorios con solución de superoxidación y complejo B, las úlceras involucionan de manera satisfactoria. Resultados: El segundo caso masculino de 47 años posterior a la infección por SARS CoV 2 debuta con lesiones vesículo-ampollosas en mucosa lingual, labial con sintomatología dolorosa severa, se realiza biopsia incisional donde el resultado histopatológico es compatible con pénfigo vulgar, se inicia protocolo de tratamiento con mometasona tópica al 0.1% y miconazol gel 2g observándose una adecuada involución de las lesiones a los 20 días. Conclusiones: El objetivo de este trabajo es poner en contexto de la comunidad médica y científica las lesiones concernientes a la cavidad bucal y faringe que están presentando los pacientes postcovid con el objetivo de realizar una exhaustiva exploración intraoral, establecer un diagnóstico clínico o histopatológico y con base en esto instaurar un plan de tratamiento específico en cada caso en particular con el fin fundamental de mejorar la salud y calidad de vida del paciente.

Study of hematoporphyrin monomethyl ether-mediated blue-light photodynamic therapy in the treatment of oral ulcers infected with Staphylococcus aureus: In vivo evaluation.

Clinical suppurative infection is mainly caused by Staphylococcus aureus. Although many antibiotics can be used to kill S. aureus, the resulting resistance problem is difficult to solve. Therefore, it is necessary to seek a new sterilizing method to solve the problem of drug resistance of S. aureus and improve the therapeutic effect of infectious diseases. Photodynamic therapy (PDT) has become an alternative for the treatment of a variety of drug-resistant infectious diseases due to its advantages of non-invasive, specific targeting, and no drug resistance. We have confirmed the advantages and experimental parameters of blue-light PDT sterilization in vitro experiments. This study aimed to treat buccal mucosa ulcer of hamster infected with S. aureus according to the parameters obtained in vitro experiment, and observe the bactericidal effect of hematoporphyrin monomethyl ether (HMME) mediated blue-light PDT in vivo and its therapeutic effect on tissue infection. The results indicated that HMME mediated blue-light PDT can effectively kill S. aureus in vivo and promote the healing of the oral infectious wound.The study findings lay a foundation for carrying out more HMME mediated blue-light PDT sterilizing therapy.

[Distribution and Drug Resistance of Pathogens in Oral Mucositis Associated with Chemotherapy in Patients with Malignant Hematopathy].

OBJECTIVE: To analyze the distribution and drug resistance of pathogens in oral mucositis associated with chemotherapy in hospitalized patients with malignant hematopathy, so as to provide scientific evidences for rational selection of antibiotics and infection prevention and control. METHODS: From July 2020 to June 2022, 167 patients with malignant hematopathy were treated with chemical drugs in the Department of Hematology, Hainan Hospital, and secretions from oral mucosal infected wounds were collected. VITEK2 COMPECT automatic microbial identification system (BioMerieux, France) and bacterial susceptibility card (BioMerieux) were used for bacterial identification and drug susceptibility tests. RESULTS: A total of 352 strains of pathogens were isolated from 167 patients, among which 220 strains of Gram-positive bacteria, 118 strains of Gram-negative bacteria and 14 strains of fungi, accounted for 62.50%, 33.52% and 3.98%, respectively. The Gram-positive bacteria was mainly Staphylococcus and Streptococcus, while Gram-negative bacteria was mainly Klebsiella and Proteus. The resistance of main Gram-positive bacteria to vancomycin, ciprofloxacin and gentamicin was low, and the resistance to penicillin, cefuroxime, ampicillin, cefotaxime, erythromycin and levofloxacin was high. The main Gram-negative bacteria had low resistance to gentamicin, imipenem and penicillin, but high resistance to levofloxacin, cefotaxime, cefuroxime, ampicillin and vancomycin. The clinical data of oral mucositis patients with oral ulcer (severe) and without oral ulcer (mild) were compared, and it was found that there were statistically significant differences in poor oral hygiene, diabetes, sleep duration less than 8 hours per night between two groups (P<0.05). CONCLUSION: Gram-positive bacteria is the main pathogen of oral mucositis in patients with malignant hematopathy after chemotherapy. It is sensitive to glycopeptide antibiotics and aminoglycosides antibiotics. Poor oral hygiene, diabetes and sleep duration less than 8 hours per night are risk factors for oral mucositis with oral ulcer (severe).

Betamethasone-loaded dissolvable microneedle patch for oral ulcer treatment.

Oral inflammatory disease (OID) is among the most common oral lesions, affecting people's quality of life and even leading to oral cancer. Oral ulcers are the most common OID. However, the pain and fear caused by the localized injection of hormones hinder the clinical treatment of oral ulcers. To address this problem, soluble hyaluronic acid (HA) microneedle patches (BSP-BDP@HAMN) containing betamethasone 21-phosphate sodium (BSP) and betamethasone 17,21-dipropionate (BDP) were fabricated for potential application in oral ulcers. BSP-BDP@HAMNs had the sufficient mechanical strength to penetrate the rat tongue abdomen mucosa with an insertion depth of approximately 207 ± 3 µm. The rapidly solubilized HA microneedle carrier released BSP and BDP into the ulcer base within 3 min of entering the mucosa. Cellular assays have shown that BDP@HAMNs have wound healing-promoting and anti-inflammatory effects. Compared with topical injections and creams, BSP-BDP@HAMNs not only penetrated the ulcer surface painlessly but also worked deep in the ulcer for a long time. In conclusion, the proposed BSP-BDP@HAMN patch can improve the comfort and efficacy of oral ulcer treatment, thus providing a new prospect for oral ulcer treatment.

Natural history of Behçet's disease focusing on remission of oral ulcers.

OBJECTIVES: To describe the long-term clinical course of each manifestation of Behçet's disease (BD) and clarify factors involved in oral ulcer (OU) remission using clinical information of BD patients. METHODS: We retrospectively studied 155 BD patients visiting our hospital (1989-2020). We defined remission criteria for each manifestation and examined long-term clinical changes. Classification and regression trees and multivariable analyses were performed to investigate OU prognostic factors; hazard ratios were used to assign scores to prognostic factors deemed significant [OU prognosis score (OuP score)]. Risk stratification was examined by dividing the OuP scores into four stages. RESULTS: OUs appeared earliest, with the slowest decline in prevalence observed post-BD diagnosis. OU presence was the most common factor inhibiting complete remission. Young age at OU onset, never smoker, presence of genital ulcers, positive pathergy test, no usage of tumour necrosis factor inhibitors or of immunosuppressants, and long-term non-treatment or symptomatic treatment for OUs were poor OU prognostic factors. Based on multivariable analysis, the area under the curve of the OuP score to predict OU prognosis was 0.678. CONCLUSIONS: Remission criteria for each symptom clarified that OU had the greatest impact on complete BD remission. Faster OU remission was associated with earlier OU therapeutic intervention other than symptomatic treatment.

Localized CO2 laser treatment of a recalcitrant oral ulceration in pemphigus vulgaris.

INTRODUCTION: Recalcitrant oral lesions of pemphigus vulgaris (PV), an autoimmune blistering disease, can result in significant discomfort, difficulty in eating, and maintaining oral hygiene. Increasing the dosage of systemic medications to control such localized lesions results in an increased risk of adverse effects. CASE PRESENTATION: We describe a male patient diagnosed at age 51 with PV by oral biopsy that included a direct immunofluorescence examination. After further baseline laboratory testing, he was started on prednisone and mycophenolate. These medications were slowly tapered with adjustments guided by clinical signs. Mycophenolate was replaced with intravenous immunoglobulin monthly infusions due to adverse effects about 2 years after initiation. During the 4.5-year follow-up period after diagnosis, his oral and skin lesions were well-controlled apart from minor transient flares. However, a painful ulcerated lesion on the facial gingiva between #11 and 12 was nonresponsive, even with the use of topical clobetasol in trays. A carbon dioxide (CO2 ) laser was used to vaporize the recalcitrant lesion under local anesthesia. The procedure resulted in complete healing of ulceration with no recurrence until the most recent examination, 2 years postlaser surgery. CONCLUSION: Adjunctive procedures that can facilitate a decrease in the cumulative dosage of corticosteroids and immunosuppressants have great value in the management of PV. CO2 laser vaporization is safe, with minimal morbidity and no long-term side effects. It should be considered an adjunctive treatment option for the management of recalcitrant lesions in patients with oral PV. KEY POINTS: Why is this case new information? To our knowledge, this is the second report on the use of a CO2 laser in the treatment of recalcitrant oral lesions of PV and the first report with a documented long-term resolution of the treated lesions. What are the keys to the successful management of this case? A localized recalcitrant lesion was treated with this approach. All other mucosal and cutaneous sites were well controlled on the patient's systemic medication regimen. What are the primary limitations to success in this case? This approach is only relevant for the management of recalcitrant lesions in patients whose disease activity is otherwise well controlled. The availability of specialized equipment and trained clinicians is necessary.

Effect of cisplatin on oral ulcer-induced nociception in rats.

OBJECTIVE: The aim of this study is to investigate effects of cisplatin preadministration on oral ulcerative mucositis-induced nociception by using an experimental model of rats. DESIGN: After two rounds of cisplatin administration, oral ulcers developed with topical acetic acid treatment in rats. Spontaneous mouth rubbing behavior was observed as spontaneous nociceptive behavior in a plastic cage. Head-withdrawal behavior was observed as mechanical allodynia by using von Frey test in the oral mucosa of conscious rats. Bacterial invasion and inflammatory cell infiltration into oral ulcerative region and systemic leukocyte phagocytic activity were assessed. RESULTS: Following cisplatin preadministration, oral ulcerative mucositis-induced spontaneous nociceptive behavior was not observed in the model. The preadministration enhanced leukocyte phagocytic activity, leading to reduce bacterial invasion and inflammatory cell infiltration in the oral ulcerative region. In contrast, oral ulcerative mucositis-induced mechanical allodynia was induced. The exaggerated mechanical allodynia in the oral ulcerative region was largely inhibited by topical treatment with the antioxidative drug, ɑ-lipoic acid, or the blocker of N-formyl peptide receptor 1, N-t-butoxycarbonyl-methionyl-leucyl-phenylalanine. CONCLUSIONS: These results suggest that cisplatin preadministration suppresses spontaneous nociception in oral ulcerative region, due to antiinflammatory effects by enhancement of leukocyte phagocytic activity, but exaggerates mechanical allodynia due to oxidative stress with N-formyl peptide receptor 1 activation. The suppression of spontaneous nociception is one of the advantages of cisplatin treatment for head and neck cancer patients although the exaggerated allodynia is a serious symptom.

Tumor necrosis factor alpha (TNF-α) blockage reduces acute inflammation and delayed wound healing in oral ulcer of rats.

Oral traumatic ulcers (OTU) are common in dental routine, and the control of proinflammatory cytokines, such as the tumor necrosis factor-alpha (TNF-α), may interfere with OTU repair. Our aim was to evaluate the role of TNF-α in the healing process of OTU in rats. Wistar male rats were divided into six groups: a control-group (treated with 0.1 mL/kg of saline) and five groups treated with anti-TNF-α infliximab (INF) at 1, 3, 5, 7, and 10 mg/kg immediately before OTU production. The animals were weighed (day 0) and euthanized on days 1, 3, 7, 14 and 21 after ulceration. The ulcers were clinically measured, and the mucosa samples were histologically (scores 0-4), histochemically (collagen assay (pircrosirius)), histomorphometrically (cell counting), and immunohistochemically (TNF-α, α-smooth-muscle-actin (α-SMA), monocyte-chemoattractive-protein-1 (MCP-1), interleukin-8 (IL-8), and fibroblast-growth-factor (FGF)) analyzed. The Evans blue assay was used to measure the vascular permeability. ANOVA-1-2-way/Bonferroni, Kruskal-Wallis/Dunn, and correlation analyses were performed (GraphPad Prism 5.0, p < 0.05). High doses of INF reduced the OTU area (p = 0.043), body mass loss (p = 0.023), vascular permeability (p < 0.001), and reduced delayed histologic scores (p < 0.05), polymorphonuclear (p < 0.001) and mononuclear (p < 0.001) cells, blood vessel counting (p = 0.006), and total (p < 0.001), type-I (p = 0.018), and type-III (p < 0.001) collagen. INF treatment reduced TNF-α immunostaining and delayed MPC-1, FGF, and α-SMA expression, with little/none influence in IL-8 immunostaining. TNF-α blockage by INF reduced acute inflammation in OTU but delayed cell migration and wound healing.

Efficacy and safety of apremilast and its impact on serum cytokine levels in patients with Behçet's disease.

To evaluate the long-term clinical efficacy of apremilast in Behçet's disease (BD) and its effect on serum cytokine levels. This study included 15 BD patients who were treated with apremilast. The rates of change in oral and genital ulcers, skin lesions, arthritis, and arthralgia were evaluated every 3 months for 12 months. The efficacy of apremilast was compared between patients with and without oral ulcer remission. Changes in the serum levels of interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-10, IL-17A, IL-6, IL-8, and IL-23 between baseline and 3 months after apremilast initiation were compared. After 3 months, oral and genital ulcers disappeared in most cases. The skin and joint lesions tended to improve for up to 6 months; however, recurrence was observed after 9 months. The improvement of genital ulcers was earlier in the oral ulcer remission group than the oral ulcer non-remission group, with the genital ulcers disappearing within the first 3 months. The baseline levels of serum cytokines, analyzed in seven patients, did not exhibit significant associations with specific organ lesions. After administration of apremilast, the TNF-α and IL-23 levels significantly decreased; however, the IFN-γ, IL-6, IL-8, and IL-10 levels did not show significant changes. The rates of decrease in the serum IL-6, IFN-γ, and IL-10 levels were greater in patients with improved oral ulcers. Modulation of serum cytokine levels with apremilast might underlie the efficacy of apremilast in oral ulcers in BD patients.

Rare paediatric cardiopulmonary presentation of Behcet's disease.

This case discusses a 10-year-old boy who presented in significant respiratory distress with cardiac tamponade with associated gross ascites and hepatomegaly, requiring urgent transfer for pericardiocentesis. On further investigation, he was found to have multiple pulmonary emboli and evidence of panserositis. An underlying rheumatological cause was suspected in the absence of any evidence of infection or malignancy, and blood tests were positive for anti-double stranded DNA, anticardiolipin and antiglycoprotein antibodies as well as HLA B51. In his medical history, he has previously had mouth ulcers, chronic anaemia of undetermined cause and erythema multiforme. These symptoms, along with clinical presentation, mean a diagnosis of Behcet's disease and associated antiphospholipid syndrome was felt to be most likely. Anticoagulation therapy was commenced for treatment of the emboli, and colchicine was started for management of Behcet's disease. The patient was discharged clinically well from the hospital and continues under specialist rheumatological and haematological follow-up.

CBD Promotes Oral Ulcer Healing via Inhibiting CMPK2-Mediated Inflammasome.

Oral ulcer is a common oral inflammatory lesion accompanied by severe pain but with few effective treatments. Cannabidiol (CBD) is recently emerging for its therapeutic potential in a range of diseases, including inflammatory conditions and cancers. Here we show that CBD oral spray on acid- or trauma-induced oral ulcers on mice tongue inhibits inflammation, relieves pain, and accelerates lesion closure. Notably, the enrichment of genes associated with the NOD, LRR, and NLRP3 pyrin domain-containing protein 3 (NLRP3) inflammasome pathway is downregulated after CBD treatment. The expression of cleaved-gasdermin D (GSDMD) and the percentage of pyroptotic cells are reduced as well. In addition, CBD decreases the expression of cytidine/uridine monophosphate kinase 2 (CMPK2), which subsequently inhibits the generation of oxidized mitochondria DNA and suppresses inflammasome activation. These immunomodulating effects of CBD are mostly blocked by peroxisome proliferator activated receptor γ (PPARγ) antagonist and partially antagonized by CB1 receptor antagonist. Our results demonstrate that CBD accelerates oral ulcer healing by inhibiting CMPK2-mediated NLRP3 inflammasome activation and pyroptosis, which are mediated mostly by PPARγ in the nucleus and partially by CB1 in the plasma membrane.