Impact of TNF and IL-33 Cytokines on Mast Cells in Neuroinflammation.

Mast cells (MCs) are derived from hematopoietic progenitors, mature in vascularized tissues, and participate in innate and acquired immunity. Neuroinflammation is a highly debated topic in the biomedical literature; however, the impact of tumor necrosis factor (TNF) and IL-33 on MCs in the brain has not been widely addressed. MCs can be activated by IgE binding to FcεRI, as well as by different antigens. After activation, MCs mediate various immunological and inflammatory responses through TNF and IL-33. TNF has two receptors: TNFR1, a p55 molecule, and TNFR2, a p75 molecule. This cytokine is the only one of its kind to be stored in the granules of MCs and can also be generated by de novo synthesis via mRNA. In the central nervous system (CNS), TNF is produced almost exclusively by microglial cells, neurons, astrocytes, and, minimally, by endothelial cells. After its release into brain tissue, TNF rapidly induces the adhesion molecules endothelial leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) in endothelial cells. TNF causes the chemoattraction of neutrophils by inducing several molecules, including CXC chemokines (IL-8). Both MCs and microglial cells act as a primary barrier against foreign molecules in the CNS, producing pro-inflammatory cytokines such as IL-33. IL-33 belongs to the IL-1 family, is activated through the ST2L/IL1-RAcP receptor complex, and mediates both the innate and adaptive immune response. IL-33 is a nuclear transcription factor expressed in the brain, where it induces pro-inflammatory cytokines (TNF and IL-1) and chemokines (CCL2, CCL3, CCL5, and CXCL10). Therefore, MCs and microglia in the CNS are a source of pro-inflammatory cytokines, including TNF and IL-33, that mediate many brain diseases. The inhibition of TNF and IL-33 may represent a new therapeutic approach that could complement existing neuroinflammatory therapies.

Activation of Mast Cells by Neuropeptides: The Role of Pro-Inflammatory and Anti-Inflammatory Cytokines.

Mast cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in the scientific literature; it is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptide substance P (SP), corticotropin-releasing hormone (CRH), and neurotensin, and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.

Peri-implantitis-like medication-related osteonecrosis of the jaw: Clinical considerations and histological evaluation with confocal laser scanning microscope.

OBJECTIVE: In the recent years, an increasing number of peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ) have been reported in literature, both in oncologic and osteoporotic patients. The aim of this study is to describe 19 cases of patients previously diagnosed as affected by peri-implantitis, who were treated for PI-MRONJ, with consideration on clinical and histopathological features. MATERIALS AND METHODS: Patients included were affected by postmenopausal osteoporosis and were administered with different antiresorptive drugs. Due to the presence of clinical and radiological signs of peri-implantitis not healed after non-surgical periodontal treatment, they were referred to the Complex Operating Unit of Odontostomatology of the University of Bari. Then, after a drug holiday of at least 3 months and cycles of antibiotics, and after other cycles of periodontal treatment, patients underwent the surgical removal of implant fixtures and surrounding bone. RESULTS: Although the previous diagnosis of peri-implantitis, the histopathological analysis with both conventional and confocal laser scanner microscopy confirmed the diagnosis of peri-implantitis-like MRONJ. CONCLUSION: Peri-implantitis not healed after conventional treatment in patients at risk on MRONJ occurrence should be considered as peri-implantitis-like PI-MRONJ and treated as required in order to get complete healing of the pathological condition, thus avoiding delay in the diagnosis.

ELISA detection of anti-desmoglein 1 and anti-desmoglein 3 and indirect immunofluorescence in oral pemphigus: A retrospective study.

OBJECTIVE: The aim of this study was to test the efficacy of autoantibodies to desmoglein 1 and desmoglein 3 detected by ELISA and indirect immunofluorescence in the diagnosis of oral pemphigus and to correlate the antibody titres with the severity of the disease. MATERIALS AND METHODS: We report a retrospective cohort study of 22 patients with oral pemphigus and 64 controls from a single tertiary centre. Data about histopathological examination, direct immunofluorescence, indirect immunofluorescence and ELISA were analysed. Global validation of ELISA and IIF both alone and combined was established by calculating sensitivity, specificity, accuracy and both positive predictive value and negative predictive value. The relationship between Oral Disease Severity Score values and ELISA titres was analysed using Pearson's coefficient. RESULTS: The best diagnostic performance was observed for anti-desmoglein 3 ELISA. The sensitivity was 75% and specificity 100% and positive predictive value and negative predictive value were 92.5% and accuracy 93.9%. The level of agreement with histopathology + direct immunofluorescence was substantial (k = .758). Anti-desmoglein 3 titres showed a significant correlation with Oral Disease Severity Score (p < .05). CONCLUSIONS: Serological tests are commonly employed during clinical practice as adjunctive tools. Anti-desmoglein 3 ELISA should be considered as a first-instance diagnostic test for oral pemphigus early detection.

Mast Cell Cytokines in Acute and Chronic Gingival Tissue Inflammation: Role of IL-33 and IL-37.

Much evidence suggests autoimmunity in the etiopathogenesis of periodontal disease. In fact, in periodontitis, there is antibody production against collagen, DNA, and IgG, as well as increased IgA expression, T cell dysfunction, high expression of class II MHC molecules on the surface of gingival epithelial cells in inflamed tissues, activation of NK cells, and the generation of antibodies against the azurophil granules of polymorphonuclear leukocytes. In general, direct activation of autoreactive immune cells and production of TNF can activate neutrophils to release pro-inflammatory enzymes with tissue damage in the gingiva. Gingival inflammation and, in the most serious cases, periodontitis, are mainly due to the dysbiosis of the commensal oral microbiota that triggers the immune system. This inflammatory pathological state can affect the periodontal ligament, bone, and the entire gingival tissue. Oral tolerance can be abrogated by some cytokines produced by epithelial cells and activated immune cells, including mast cells (MCs). Periodontal cells and inflammatory-immune cells, including mast cells (MCs), produce cytokines and chemokines, mediating local inflammation of the gingival, along with destruction of the periodontal ligament and alveolar bone. Immune-cell activation and recruitment can be induced by inflammatory cytokines, such as IL-1, TNF, IL-33, and bacterial products, including lipopolysaccharide (LPS). IL-1 and IL-33 are pleiotropic cytokines from members of the IL-1 family, which mediate inflammation of MCs and contribute to many key features of periodontitis and other inflammatory disorders. IL-33 activates several immune cells, including lymphocytes, Th2 cells, and MCs in both innate and acquired immunological diseases. The classic therapies for periodontitis include non-surgical periodontal treatment, surgery, antibiotics, anti-inflammatory drugs, and surgery, which have been only partially effective. Recently, a natural cytokine, IL-37, a member of the IL-1 family and a suppressor of IL-1b, has received considerable attention for the treatment of inflammatory diseases. In this article, we report that IL-37 may be an important and effective therapeutic cytokine that may inhibit periodontal inflammation. The purpose of this paper is to study the relationship between MCs, IL-1, IL-33, and IL-37 inhibition in acute and chronic inflamed gingival tissue.

Topical photodynamic therapy in the treatment of benign oral mucosal lesions: A systematic review.

BACKGROUND: The introduction of photodynamic therapy (PDT) in various branches of the dental field such as endodontics, implantology, periodontology, and restorative dentistry and oral medicine has become useful in recent decades. This systematic review presents an overview of the literature to evaluate the usefulness of topical PDT for the treatment of benign oral soft tissue lesions and to identify limitations in prior studies to improve PDT applications. METHODS: We performed a review of the literature using different search engines (PubMed, ISI Web of Science, and the Cochrane Library) employing MeSH terms such as "Photodynamic therapy" and "PDT" in conjunction with other terms. We utilized the Population, Intervention, Comparison, Outcomes, and Study design (PICOS) method to define our study eligibility criteria. RESULTS: Initial results were 1513. Finally, there were only 21 studies that met our selection criteria. We divided the 21 selected items into two groups: inflammatory diseases and infective diseases. CONCLUSIONS: Although topical PDT is an easy to perform and well-tolerated treatment and appears to be a valid method with promising results in the treatment of benign lesions of the oral cavity's soft tissues, further studies are needed to complete the current knowledge of this technique.

Cross-sectional study on the quality of oral lichen planus videos on YouTube™.

BACKGROUND: YouTube™ is one of the most used platforms for patients looking for health-related information. The purpose of this cross-sectional study was to analyze the available information about oral lichen planus on YouTube™ and how users interact with it. METHODS: A YouTube™ search for oral lichen planus was performed, setting English UK (language) and United Kingdom (country). Two hundred and fifteen results were screened, and 36 videos met the inclusion criteria. Videos' quality was evaluated using the DISCERN and the Global Quality Scale tools, and by categorizing them through quality assessment, source, duration, views, likes, and dislikes of each video were noted. RESULTS: According to quality assessments, 55.6% of the videos were classified as useful, while the 35.1% were classified as misleading/dangerous. The DISCERN and GQS values were generally low (31.56 ± 10.38 and 2.33 ± 1.07, respectively); DISCERN and GQS were positively correlated with the video length and negatively correlate with the data of upload (p < 0.05). CONCLUSIONS: This study corroborates the results of others that a great number of health-related videos available on YouTube™ feature misleading or potentially dangerous information; although the quality seems to slightly improve over time, medical associations and researchers ought to plan strategies aimed at improving the quality of the information delivered through YouTube™ and other social media.

Prevalence of HPV in patients affected by oral Lichen planus: A prospective study using two different chair-side sampling methods.

BACKGROUND: Human Papillomavirus (HPV) role in oral potentially malignant lesions remains unclear. Aims of this study were to evaluate the prevalence of HPV infection in a cohort of patients affected by oral lichen planus, to analyze the genotypes involved, and to compare the performance of two specimen collection methods: brushing and biopsy. METHODS: Consecutive patients with oral lichen planus were enrolled. Each patient's clinical and anamnestic data were recorded before he/she underwent brushing and biopsy procedures. The collected samples were analyzed using RT-PCR. Prevalence of HPV infection was evaluated considering cytobrush and biopsy outcomes alone and combined. Correlation between HPV presence and sex, age, smoke, alcohol, kind of lichen planus, Hepatitis C virus, and involved mucosae was analyzed using chi-square test (significance at P < .05). Cohen's k coefficient was employed to compare brushing and biopsy. RESULTS: Fifty-two patients affected by oral lichen planus were enrolled. Total HPV prevalence was 17%, when considering only the biopsy and the cytobrush the prevalence was 15% and 6%, respectively. None of the considered variables showed significant correlation with HPV (P > .05). The concordance between the two methods was "fair" (k = .305). CONCLUSIONS: The biopsy appears more reliable than cytobrush to detect HPV in course of oral lichen planus. No statistical correlation emerged with the analyzed variables. The most frequently detected genotypes were HPV 6 and 11, while only two cases presented with HPV 16 and 53, known as human oncogenic.

Evaluation of BP180-NC16A ELISA in exclusive oral pemphigoid diagnosis. A comparative study.

OBJECTIVE: Aims of this study were to test the efficacy of anti-BP180-NC160 ELISA in the diagnosis of oral pemphigoid compared to the gold standard, represented by direct immunofluorescence and pathological examination, to correlate the antibody titers with the severity of the disease and the demographical data. MATERIALS AND METHODS: Patients with a suspect of oral pemphigoid were enrolled and underwent biopsy and sera collection both, in order to perform histopathological examination, direct immunofluorescence and ELISA. The test outcomes were compared, and ELISA sensitivity, specificity, accuracy, and negative and positive predictive values were calculated. RESULTS: ELISA showed good specificity (83.3%), while sensitivity was only 50%. A moderate correlation between antibody titers and disease severity was recorded. CONCLUSIONS: Mucomembranous Pemphigoid is an autoimmune autoantibody-mediated blistering disease, often affecting exclusively the oral mucosa. Currently, the biopsy is required to diagnose this disease, but serological tests are also commonly employed during clinical practice as adjunctive tools. BP180-NC160 ELISA should be considered an ancillary diagnostic test in course of oral pemphigoid; direct immunofluorescence + histologic examination remains the diagnostic gold standard.

Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra.

Psoriasis (PS) is a skin disease with autoimmune features mediated by immune cells, which typically presents inflammatory erythematous plaques, and is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells, including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature, and reside in vascularized tissues. They can be activated by antigen-provoking overexpression of proinflammatory cytokines, and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophages to release IL-36-a powerful proinflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic proinflammatory diseases such as psoriasis. Suppression of IL-36 could result in a dramatic improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra, which binds to IL-36 receptor ligands, but suppression can also occur by binding IL-38 to the IL-36 receptor (IL-36R). IL-38 specifically binds only to IL-36R, and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs-a process that activates macrophages to secrete proinflammatory IL-36 inhibited by IL-38. IL-37 belongs to the IL-1 family, and broadly suppresses innate inflammation via IL-1 inhibition. IL-37, in murine models of inflammatory arthritis, causes the suppression of joint inflammation through the inhibition of IL-1. Therefore, it is pertinent to think that IL-37 can play an inhibitory role in inflammatory psoriasis. In this article, we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis, and hold promise as an innovative therapeutic tool.

Mast Cells Mediate Rheumatoid Arthritis-Inhibitory Role of IL-37.

Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory, disabling arthropathy that severely affects the quality of life. This disease involves several proinflammatory cytokines, including interleukin (IL)-1ß and tumor necrosis factor (TNF). IL-1 induces TNF and vice versa, causing joint damage and cartilage degradation. Current antirheumatic drugs may be effective, but they possess many unwanted side effects. In recent years, inhibitors of proinflammatory cytokines have increasingly entered mainstream clinical practice. Recent evidence indicates that IL-37, which has anti-inflammatory properties, is increased in the serum and is released from white blood cells in patients with RA. Mast cells (MCs), stimulated by the neuropeptide substance P (SP) and IL-33, release IL-1ß and TNF. Recent evidence indicates that large amounts of IL-1ß and TNF can be released from human MCs, which also secrete CXCL8, which promotes migration of immune cells, causing erosion of the bone and cartilage. Treatment with IL-37 can block the MC stimulation and release of inflammatory compounds, attenuating the severity of the disease and/or altering its progression.

ROCK1 is associated with non-syndromic cleft palate.

BACKGROUND: Craniofacial morphogenesis is the result of an intricate multistep network of tightly controlled spatial and temporal signalling that involves several molecules and transcription factors organized into highly coordinated pathways. Any alteration in even one step of this delicate process can lead to congenital malformations such as cleft palate. One of the first steps in embryonal orofacial development is the migration of cells from the neural crests to the branchial arches. Next, the cells have to proliferate, differentiate, move and connect to each other in order to correctly form the palate. Cell contraction, promoted by the interaction of non-muscle myosin II and actin A, is a crucial step in morphogenesis and is regulated by ROCK1 protein. METHODS: A family-based association study was carried out in order to verify whether or not genetic variants of ROCK1 were associated with non-syndromic cleft palate (nsCP). Two cohorts from Italy and Iran, a total of 189 nsCP cases and their parents were enrolled. RESULTS: The rs35996865-G allele was under-transmitted in cases of nsCP [P = .006, odds ratio (OR) = 0.63 (95% CI 0.45-0.88)]. CONCLUSION: This investigation reveals for the first time data supporting a role for ROCK1 in nsCP aetiology.

Detection of HPV in oral leukoplakia by brushing and biopsy: prospective study in an Italian cohort.

AIM: The aim of the present study was to evaluate the prevalence of HPV infection in oral leukoplakia, specifying the HPV genotypes eventually involved. We also compared the micro-biopsy and brushing HPV detecting efficacy. MATERIALS AND METHODS: Consecutive patients with a presumptive diagnosis of oral leukoplakia were enrolled. Demographical, behavioral data (smoking, alcohol) and lesion features were recorded. Each patient underwent a brushing procedure, performed with a cytobrush rubbed on the lesion, and then a biopsy was performed. The brushing and micro-biopsy specimens were both analyzed with the HPV 28 Anyplex II Seegene RT-PCR. The prevalence of HPV infection was calculated considering the two methods' outcomes separately and then combining both. Cohen's k coefficient was used to assess the agreement between the two methods. RESULTS: Sixty-five patients were enrolled with a mean age of 60 years. The HPV infection prevalence was 17%, decreasing to 5% considering the brushing outcomes alone. The most frequently detected genotypes were 6 (12%), 11 (3%), 42 (3%), and 16 (3%). No statistically significant correlation was found between HPV infection and the variables analyzed, except for smoking and the type of mucosa (p < 0.05). The strength of agreement between cytobrush and micro-biopsy was "fair" (k = 0.384). CONCLUSIONS: The present study showed a low prevalence of HPV infection in oral leukoplakia. The micro-biopsy appeared to be more reliable than brushing in detecting HPV DNA in oral leukoplakia, but the method invasiveness discourages its employ as a screening tool. The importance of HPV in the etiopathogenesis of oral potentially malignant lesions remains unclear; further studies are needed to establish the HPV role in oral leukoplakia. CLINICAL RELEVANCE: HPV involvement in oral leukoplakia and an effective and appropriate detecting technique are still a debated issue. From this study, the restricted use of brushing did not appear sufficient to assess the presence of HPV infection with PCR techniques in samples obtained from oral leukoplakia.

Role of Cyclosporine in Gingival Hyperplasia: An In Vitro Study on Gingival Fibroblasts.

BACKGROUND: Gingival hyperplasia could occur after the administration of cyclosporine A. Up to 90% of the patients submitted to immunosuppressant drugs have been reported to suffer from this side effect. The role of fibroblasts in gingival hyperplasia has been widely discussed by literature, showing contrasting results. In order to demonstrate the effect of cyclosporine A on the extracellular matrix component of fibroblasts, we investigated the gene expression profile of human fibroblasts after cyclosporine A administration. MATERIALS AND METHODS: Primary gingival fibroblasts were stimulated with 1000 ng/mL cyclosporine A solution for 16 h. Gene expression levels of 57 genes belonging to the "Extracellular Matrix and Adhesion Molecules" pathway were analyzed using real-time PCR in treated cells, compared to untreated cells used as control. RESULTS: Expression levels of different genes were significantly de-regulated. The gene CDH1, which codes for the cell adhesion protein E-cadherin, showed up-regulation. Almost all the extracellular matrix metalloproteases showed down-regulation (MMP8, MMP11, MMP15, MMP16, MMP24, MMP26). The administration of cyclosporine A was followed by down-regulation of other genes: COL7A1, the transmembrane receptors ITGB2 and ITGB4, and the basement membrane constituents LAMA2 and LAMB1. CONCLUSION: Data collected demonstrate that cyclosporine inhibits the secretion of matrix proteases, contributing to the accumulation of extracellular matrix components in the gingival connective tissue, causing gingival overgrowth. Patients affected by gingival overgrowth caused by cyclosporine A need to be further investigated in order to determine the role of this drug on fibroblasts.

Non-invasive analysis of bleaching effect of hydrogen peroxide on enamel by reflectance confocal microscopy (RCM): study of series of cases.

The aim of this study is to evaluate in vivo the effects of in-office tooth whitening hydrogen peroxide (HP) agent on enamel-microstructured surface by a reflectance confocal microscopy (RCM). Ten healthy volunteers assisted at the Dental School presenting teeth with vital pulp were selected. The 35% HP whiteness product was applied in two visits on discolored teeth, 1-week interval between, via 20-min applications. A commercially available hand-held RCM (Vivascope3000®, Lucid, Rochester, NY, USA) was used to image in vivo the dental surface of the selected tooth of each volunteer. Twenty upper central incisors' vestibular surfaces were imaged, before bleaching (T0), immediately after (T1) and 1 week later (T2). The peculiar structure of the enamel was seen at T0. After bleaching, white reflective circular bodies were found all over the teeth surfaces, which disappear 1 week later (T2). When the HP gel® was imaged, the same white circular areas were observed. Going deeper, the regular enamel architecture was preserved. Textural analysis of the images in T0 and T2 was performed: GLCM parameters were extracted. Mann-Whitney U test was performed to evaluate statistical differences between two groups of data (p > 0.05). Finally, 35 prisms were randomly selected from T0 and T2 image and diameters were measured; a paired t test was performed (p = 0.381). The RCM is a promisor tool for investigating the features of enamel in vivo, immediately after bleaching procedures, as well as longitudinally.

A New Strategy Against Peri-Implantitis: Antibacterial Internal Coating.

The bacterial biofilm formation in the oral cavity and the microbial activity around the implant tissue represent a potential factor on the interface between bone and implant fixture that could induce an inflammatory phenomenon and generate an increased risk for mucositis and peri-implantitis. The aim of the present clinical trial was to investigate the bacterial quality of a new antibacterial coating of the internal chamber of the implant in vivo at six months. The PIXIT implant (Edierre srl, Genova Italy) is prepared by coating the implant with an alcoholic solution containing polysiloxane oligomers and chlorhexidine gluconate at 1%. A total of 15 healthy patients (60 implants) with non-contributory past medical history (nine women and six men, all non-smokers, mean age of 53 years, ranging from 45-61 years) were scheduled to receive bilateral fixed prostheses or crown restorations supported by an implant fixture. No adverse effects and no implant failure were reported at four months. All experimental sites showed a good soft tissue healing at the experimental point times and no local evidence of inflammation was observed. Real-Time Polymerase Chain Reaction (PCR) analysis on coated and uncoated implants showed a decrease of the bacterial count in the internal part of the implant chamber. The mean of total bacteria loading (TBL) detected in each PCR reaction was lower in treated implants (81038 units/reaction) compared to untreated implants (90057 units/reaction) (p < 0.01). The polymeric chlorhexydine coating of the internal chamber of the implant showed the ability to control the bacterial loading at the level of the peri-implant tissue. Moreover, the investigation demonstrated that the coating is able to influence also the quality of the microbiota, in particular on the species involved in the pathogenesis of peri-implantitis that are involved with a higher risk of long-term failure of the dental implant restoration.

Molecular Aspects of Drug-Induced Gingival Overgrowth: An In Vitro Study on Amlodipine and Gingival Fibroblasts.

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast's function in gingival overgrowth. To determine whether amlodipine alters the fibrotic response, we investigated its effects on treated gingival fibroblast gene expression as compared with untreated cells. MATERIALS AND METHODS: Fibroblasts from ATCC® Cell Lines were incubated with amlodipine. The gene expression levels of 12 genes belonging to the "Extracellular Matrix and Adhesion Molecules" pathway was investigated in treated fibroblasts cell culture, as compared with untreated cells, by real time PCR. RESULTS: Most of the significant genes were up-regulated. (CTNND2, COL4A1, ITGA2, ITGA7, MMP10, MMP11, MMP12, MMP26) except for COL7A1, LAMB1, MMP8, and MMP16, which were down-regulated. CONCLUSION: These results seem to demonstrate that amlodipine has an effect on the extracellular matrix of gingival fibroblast. In the future, it would be interesting to understand the possible effect of the drug on fibroblasts of patients with amlodipine-induced gingival hyperplasia.

Salivary flow and xerostomia in patients with type 2 diabetes.

BACKGROUND: Saliva is secreted by the major and minor salivary glands. There are a number of physiological factors that can reduce this secretion such as age, sex, body weight, number of teeth present in the mouth or time of day. This decrease may also be caused by the use of certain drugs, radiotherapy for head and neck cancer, chronic rheumatic diseases such as Sjögren's syndrome and other systemic disorders such as diabetes mellitus (DM). Objective of this study was to investigate the effect of type 2 DM on salivary secretion and its relation to the sensation of xerostomia. METHODS: Forty-seven patients with type 2 DM and 46 healthy individuals, aged 40-80, participated in the study. Samples of saliva were collected, at rest and after stimulation, at baseline and after the administration of a meal. A questionnaire of 10 items was used to define the patients' sensations of xerostomia. For statistical analysis, the Mann-Whitney test was used to assess the difference in salivary flow between the two groups and the relationship between the response to each of the questions and salivary flow levels. The degree of the patients' sensation of xerostomia was analysed by the Fisher test. RESULTS AND CONCLUSIONS: There was a significant decrease in total saliva levels at rest in patients with type 2 DM compared to the control group. The study group also experienced higher levels of dryness at night and on waking as well as a greater sensation of lingual burning compared to the control group.

Non-invasive in vivo visualization of enamel defects by reflectance confocal microscopy (RCM).

The enamel defects (EDs) may present with a variety of clinical manifestations with increasing severity from the sole appearance of pale discoloration to remarkable structural alterations. EDs are responsible for higher caries receptivity. In vivo reflectance confocal microscopy (RCM) allows to image in vivo at microscopic resolution of the dental surface, thus avoiding the tooth extraction and the sample preparation because of its ability to optically scan living tissues along their depth. Aim of this study is the in vivo assessment at microscopic resolution of dental surfaces affected by EDs without resorting to invasive methods such as teeth extractions, to define histological findings occurring in chromatic and/or structural EDs. For the purpose, 15 children, referring at the Dental Clinic of the Second University of Naples, affected by several degrees of EDs, were enrolled and underwent in vivo RCM imaging to microscopically define the ED confocal features using a commercially available hand-held reflectance confocal microscope with neither injuries nor discomfort. Totally, 29 teeth were imaged. Results demonstrated images good in quality and the capability to detect EDs such as unevenness, grooves, and lack of mineralization according to their clinical degree of disarray. The present in vivo microscopic study on EDs allowed to highlight structural changes in dental enamel at microscopic resolution in real-time and in a non-invasive way, with no need for extraction or processing the samples. Further experiments could define the responsiveness to remineralizing procedures as therapeutic treatments.

Interradicular septum as guide for pilot drill in postextractive implantology: a technical note.

The extraction of teeth results in rapid bone resorption both vertically and horizontally in the first month. The loss of alveolar ridge reduces the chance of implant rehabilitation. The atraumatic extraction, implant placement in extraction socket, and an immediate prosthesis have been proposed as alternative therapies to maintain the volume and contours tissue and reduce time and cost of treatment. Thus, this paper aims to present a clinical case where the extraction was performed using interradicular septum as guide for pilot drill in postextractive implantology with implant placement and immediate provisionalization in a inferior molar. The advantages of this technique are to place the implant exactly in the center of the alveolar ridge, to mantain the edges of the alveolar ridge and reduce postextractive bone resorption, and has great advantages in final prosthetic rehabilitation.