The role of Actinomyces spp. and related organisms in cervicofacial infections: Pathomechanism, diagnosis and therapeutic aspects.

Members of the Actinomyces genus and Actinomyces-like organisms (ALOs; namely Actinotignum, Arcanobacterium, Schaalia and Varibaculum) are Gram-positive, non-spore-forming rods that are commensal members of the human oral cavity, gastrointestinal tract, female genital tract and skin microbiota. Cervicofacial actinomycosis or "lumpy jaw syndrome" - the chronic, suppurative granulomatous disease caused by Actinomyces spp. And ALOs - is characterized by an initially slow and unspecific disease-presentation, which often mimics other pathologies, followed by the formation of painful abscesses and severe tissue destruction. Actinomycosis has been described as a rare disease, however, reliable epidemiological data are lacking. In addition, there is increasing awareness regarding the role of Actinomyces spp. in the development of osteoradionecrosis and medication-related osteonecrosis of the jaw. The aim of this narrative review is to succinctly summarize the current advances regarding the microbiological, clinical, diagnostic and therapeutic aspects of cervicofacial actinomycosis, in addition to the roles of Actinomyces species and ALOs as members of the oral microbiota and in dental biofilm, in other dental infections (caries, root canal infection, periapical infection, periodontitis) and osteonecrosis of the jaw, in the context of recent taxonomic changes affecting the genus. Our paper aims to be a blueprint for dentists, other physicians, microbiologists and researchers regarding the multifaceted field of cervicofacial actinomycosis.

DNA Methylation-Governed Gene Expression in Autoimmune Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease hallmarked by progressive and irreversible joint destruction. RA pathogenesis is a T cell-regulated and B cell-mediated process in which activated lymphocyte-produced chemokines and cytokines promote leukocyte infiltration that ultimately leads to destruction of the joints. There is an obvious need to discover new drugs for RA treatment that have different biological targets or modes of action than the currently employed therapeutics. Environmental factors such as cigarette smoke, certain diet components, and oral pathogens can significantly affect gene regulation via epigenetic factors. Epigenetics opened a new field for pharmacology, and DNA methylation and histone modification-implicated factors are feasible targets for RA therapy. Exploring RA pathogenesis involved epigenetic factors and mechanisms is crucial for developing more efficient RA therapies. Here we review epigenetic alterations associated with RA pathogenesis including DNA methylation and interacting factors. Additionally, we will summarize the literature revealing the involved molecular structures and interactions. Finally, potential epigenetic factor-based therapies will be discussed that may help in better management of RA in the future.

[Proper oral health can protect from developing gingival hyperplasia induced by calcium channel blockers]. / A megfelelo szájegészség megvédhet a kalciumcsatorna-blokkoló készítmények okozta gingivahyperplasia kialakulásától.

Cardiovascular diseases including hypertension affect 40% of the adult population in Hungary. Calcium channel blockers are frequently prescribed for the treatment of hypertension either in monotherapy or in fixed-combination therapy. Their main effect is vasodilatation with gingival hyperplasia as a side effect. Our aim is to draw our colleagues' attention to the practical importance of the fact that calcium channel blocker-induced gingival hyperplasia correlates closely with the dental status and the quantity of plaque on the surface of teeth and dental implants. Once established, gingival hyperplasia makes it more difficult for the patient to maintain individual tooth cleaning and increases plaque formation. Thus proliferation of Gram-negative bacteria is enabled in the plaque which promotes gingival overgrowth and can pose a risk factor for further cardiovascular diseases. If proper individual oral hygiene and professional interventions are carried out, healthy and hyperplasia-free gingival state can be sustained in the long term in most cases, even with calcium channel blocker therapy. In order to protect patients' oral health, a closer cooperation of internists and dentists would be desirable. Orv Hetil. 2018; 159(29): 1183-1187.

[Prevalence and severity of chronic parodontitis and oral mucosal lesions in chronic obstructive lung disease]. / A krónikus parodontitis, illetve szájnyálkahártya-laesiók elofordulása és súlyossága krónikus obstruktív tüdobetegségben.

INTRODUCTION: Chronic parodontitis is a prevalent oral disease that may lead to the loss of teeth independently of caries. Some systemic diseases (e.g., diabetes mellitus, chronic renal failure) may aggravate chronic parodontitis. On the other hand, this oral disease may aggravate other systemic diseases. Earlier studies suggested a correlation between chronic parodontitis and very severe chronic obstructive pulmonary disease (COPD). AIM: The aim of our study was the investigation of the correlation between chronic parodontitis and chronic obstructive pulmonary disease. METHOD: We have recruited patients of the Department of Dentistry, Oral and Maxillofacial Surgery, Medical School, University of Pécs, in the study. Volunteers were assigned into a COPD (n = 29) and control group (n = 45). Airflow limitation of the COPD group (FEV1/FVC: 61.52 ± 3.2%) corresponded to GOLD 2 (global initiative for chronic obstructive lung disease; FEV1: 52.66 ± 3.57%). Oral health assessment included mean and maximal clinical attachment loss, mobility of teeth, decayed/filled and missing teeth, Löe-Silness, oral hygiene and bleeding on probing indexes. One-way ANOVA and non-parametric Mann-Whitney tests were used for statistical analysis. RESULTS: Oral health of the COPD group was worse than that of the controls. In this group the mean and maximal clinical attachment loss, mobility of teeth, the Löe-Silness, the oral hygiene and bleeding on probing indexes were higher. CONCLUSIONS: Our results confirm the positive correlation between chronic parodontitis and a moderate level of chronic obstructive pulmonary disease. However, it is not clear whether the COPD-associated systemic inflammation aggravated the oral status or the chronic parodontitis influenced negatively chronic obstructive pulmonary disease. Orv Hetil. 2018; 159(21): 831-836.

[Analysis of medical diagnostic reports (constats) on dental injuries from terminological, dental and forensic medical points of view]. / Fogászati sérülésekrol készült látleletek komplex terminológiai, fogászati és igazságügyi orvosszakértoi elemzése.

Writing a constat is a professional skill required of every general physician and dentist. Constats are issued by healthcare providers on the investigating authority's, court's or injured person's request. This document is an official judicial evidence, a record of medical examination, and it is also a medical opinion which can determine the outcome of the subsequent legal process. Incomplete and incorrect injury descriptions make it difficult for forensic experts to form accurate and appropriate opinions. The authors examined 147 dental and oral surgical constats from the Universities of Pécs and Debrecen using multidisciplinary approach (according to terminological, dental, surgical, forensic and criminal legal aspects). Several medical reports contained mistakes in terms of inaccuracies and self-contradictions, terminology and professional medical practice. The documents included 352 injuries (11.1% of which were tooth injuries, 47.7% bone injuries and 41.2% soft-tissue injuries). The low number of attributes per injury (0.64 on average) indicates insufficient documentation. As a result of the comparative analysis, significant differences were found between the documentation of dental injuries and that of other bone injuries pertaining to their information content. We can state that physicians are most consistent when describing bone injuries, while they are less articulate about tooth injuries. The authors provide an overview of the legal consequences of injuries as well as the legal practice regarding tooth injuries in Germany and Austria, and recommend the creation of a nationwide, unified terminology for both dental and trauma departments on nasal and dental injuries. Orv Hetil. 2018; 159(51): 2154-2161.

Role of Actinomyces spp. and related organisms in the development of medication-related osteonecrosis of the jaw (MRONJ): Clinical evidence based on a case series.

Medication-related osteonecrosis of the jaw (MRONJ) is an increasingly common consequence of antiresorptive treatment, which often leads to the development of necrotic exposed bone surfaces with inflammatory processes affecting the jawbone. Although the development of MRONJ is often associated with the inflammatory response or infections caused by the colonizing members of the oral microbiota, the exact pathogenesis of MRONJ is still not fully understood. In the present paper, we aimed to provide additional, microbiological culture-supported evidence, supporting the "infection hypothesis" that Actinomyces spp. and related organisms may play an important pathogenic role in the development of MRONJ and the resulting bone necrosis. In our case series, all patients presented with similar underlying conditions and anamnestic data, and have received antiresorptive medications (bisphosphonates or a RANK ligand (RANKL) inhibitor) to prevent the occurrence or progression of bone metastases, secondary to prostate cancer. Nevertheless, a few years into antiresorptive drug therapy, varying stages of MRONJ was identified in the mentioned patients. In all three cases, quantitative microbiological culture of the necrotic bone samples yielded a complex microbiota, dominated by Actinomyces and Schaalia spp. with high colony counts. Additionally, our followed-up case series document the treatment of these patients with a combination of surgical intervention and long-term antibiotic therapy, where favourable clinical responses were seen is all cases. If the "infection hypothesis" is valid, it may have significant consequences in the preventative and therapeutic strategies associated with this disease.

Can gingival hyperplasia caused by cyclosporin A be prevented by removing dental plaque? / Megelozheto-e a ciklosporin A okozta fogíny-hyperplasia a dentalis plakk eltávolításával?

In Hungary, there are around 3500 people living with a transplanted organ, there are around 400 total donations, including between 250 and 300 kidney transplants per year. Due to the development of immunosuppression and surgical techniques, the survival rate of patients has improved, and therefore dentists are increasingly confronted with gingival hyperplasia due to immunosuppressive therapy in addition to oro-dental lesions resulting from renal failure. The prevalence of gingival hyperplasia with cyclosporin A can be as high as 90%. The aim of our study is to raise awareness of the importance of dental plaque in the development of cyclosporin A induced gingival hyperplasia and to emphasize that gingival hyperplasia and the risk of organ rejection can be prevented or greatly reduced by the development of appropriate individual oral hygiene and successful periodontal outpatient therapy. Particular mention should be paid to the importance of interdisciplinary cooperation and regular patient care. Our examinations and treatments were carried out at the Division of Periodontology at the Department of Dentistry and Oral Surgery of the University of Pecs, Hungary.

Upregulation of transient receptor potential vanilloid type-1 receptor expression in oral lichen planus.

OBJECTIVES: Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa. Its etiology is still unclear. Neurogenic components might contribute to the inflammatory process. The oral mucosa is richly innervated by sensory fibers. Mediators secreted by inflammatory cells activate sensory nerves via transient receptor potential vanilloid receptor 1 (TRPV1) and lead to the release of neuropeptides. So far, TRPV1 receptor expression was detected on neurons. Only recently, TRPV1 receptors were identified in nonneuronal tissues. The aim of the present study was to detect the presence of TRPV1 receptors and peripheral expression of receptor mRNA in normal oral mucosa and mucous membranes from OLP patients. METHODS: Presence of TRPV1 receptor proteins in the mucosal tissue was assessed by immunohistochemistry. Expression of TRPV1 receptor mRNA was determined by quantitative RT-PCR. RESULTS: We provided qualitative and quantitative immunohistochemical evidence that TRPV1 receptors are present in normal human oral mucosa and that their expression is increased in OLP. The number of immunopositive cells was elevated in the epithelium, and vascular endothelial cells, lymphocytes and fibroblasts of the subepithelium were also labeled in samples obtained from OLP patients. The local expression of nonneuronal TRPV1 receptors was proven at mRNA level using quantitative real-time RT-PCR. CONCLUSIONS: Since the number of TRPV1 receptor-positive nonneural cells is increased in inflammatory conditions, we hypothesize that TRPV1-receptor-mediated processes might play role in the pathogenesis of OLP.

A randomized study to assess the effectiveness of orally administered pilocarpine during and after radiotherapy of head and neck cancer.

BACKGROUND: This prospective randomized study was undertaken to assess the effectiveness of oral pilocarpine chloratum (Salagen) during and after radiotherapy. PATIENTS AND METHODS: Between October 1999 and December 2003, 66 patients received 60 Gy of irradiation to their head and neck cancer. Half of the patients received 5 mg oral pilocarpine 3 times a day from the beginning of radiotherapy over a period of 12 weeks. The control group received similar doses of pilocarpine only in the second 6 weeks following irradiation. Patient saliva secretion was recorded, and a visual analog scale measuring overall and daily xerostomia, difficulty in sleeping, speaking, eating and wearing dentures was employed. RESULTS: Pilocarpine, given concomitantly with radiotherapy, statistically improved the salivary flow and induced better patient comfort by the end of radiotherapy. Patient comfort and symptoms related to xerostomia greatly decreased compared to patients receiving pilocarpine after irradiation in the second 6-week period of therapy. The patients' quality of life, saliva production and symptoms related to xerostomia showed significant progress by the end of the 12 weeks. CONCLUSION: The results suggest that stimulated salivary glands suffer less decrease in saliva production during radiotherapy. The stimulated saliva flow reduced the side-effects of irradiation.

[The effectiveness of a benzydamine rinse in the management of stomato-glossopyrosis]. / Benzidamin-tartalmú szájöblítovel szerzett klinikai tapasztalatok a stomato- glossopyrosis kezelésében.

Burning mouth syndrome (BMS) is a frequent source of oral discomfort and sensation mainly at middle-aged or elderly women without identifiable local pathology. Forty-two patients with stomato-glossopyrosis were registered at the Department of Periodontology, Dental School, University Pécs, between August 2002 and January 2003. Oral clinical examination failed to identify physical explanation for the complaint of painful or burning mouth. After complete examination (blood test included), scaling, root planning and oral hygiene instructions were given. Six patients reported decreasing mucosal pain or burning. Two patients had iron-deficiency and Sjögren's syndrome was suspected and verified at another two patients. Thirty-two patients completed the benzydamine-study. They were divided into two groups. The study group (16 patients) rinsed with benzydamine containing solution, the control group (16 patients) received placebo solution for rinsing the same way for ten days. Differences were found between the two groups favouring the benzydamine containing solution. Pain reduction, mouth dryness and diminution of burning sensation were detected by means of visual analog scale (VAS). Benzydamine rinses could be effective in the management of BMS, but clinicians need to monitor patients for possible side effects in the case of long-term use.

Effect of surgical and chemical sensory denervation on non-neural expression of the transient receptor potential vanilloid 1 (TRPV1) receptors in the rat.

Pretreatment with the ultrapotent capsaicin analog resiniferatoxin (RTX) has been applied as a selective pharmacological tool in inflammation and pain studies to desensitize transient receptor potential vanilloid 1 (TRPV1) receptor-expressing sensory nerve endings. The discovery of TRPV1 receptor on non-neural cells challenges systemic RTX desensitization as a method acting exclusively on a population of sensory neurons, but not on non-neural cells. Systemic RTX desensitization was used for chemical denervation and transection of the sciatic and saphenous nerves for surgical denervation in rats. Quantitative real-time PCR and immunohistochemistry were applied to investigate the presence and alterations of the TRPV1 receptor mRNA and protein following chemical and surgical denervation. We provided the first evidence for non-neural TRPV1 immunopositivity and mRNA expression in the rat dorsal paw and plantar skin as well as the oral mucosa. Neither chemical nor surgical denervation influenced the level of TRPV1 receptor mRNA and protein expression in non-neural cells of either skin regions or mucosa. Therefore, RTX and consequently capsaicin remain to be considered as selective neurotoxins for a population of primary afferent neurons.