Új mechanizmusok a fog gyulladásainak patogenezisében. A cukorbetegségnek, mint súlyosbító tényezőnek egy lehetséges patológiai útvonala = New mechanisms in the pathogenesis of dental inflammations. One possible pathogenetic role of diabetes as an aggravating risc factor

A fogágybetegség és a fogszuvasodás népbetegség hazánkban, szinte mindenkit érintenek. Az újabb epidemiológiai és klinikai vizsgálatok alapján megerősítést nyert, hogy a fogászati fertőzések nem csupán lokális problémákat okoznak, hanem általános szervezeti betegségek, elsősorban a kardiovaszkuláris betegségek kiemelkedő rizikófaktorai is lehetnek. A kardiovaszkuláris betegségek a vezető halálok hazánkban, ezért a fogazati állapottal kapcsolatos kutatásokra nagyobb hangsúlyt kellene helyezni! Ezért megvizsgáltuk 1) a különböző vazoaktív anyagok (NO, CO, H2S, VEGF, endothelin-1) a szájüregi képletek (fogbél, ínyszövet, nyálmirigyek) vérkeringésének regulációjában betöltött szerepét ép és kóros körülmények között, 2) a fogágygyulladás patomechanizmusában a bakteriális lizindekarboxiláz, a hemoxigenáz és a cukorbetegség egy eddig ismeretlen aspektusának a jelentőségét, valamint 3) a fogágygyulladás terápiájához új kiegészítő (oszteogenetikus hatású BPC157, gyulladáscsökkentő inozin és lizindekarboxiláz blokkolás) eljárások alapjait fektettük le. Vizsgálatainkhoz új módszert (lizin/kadeverin kapilláris elektroforézissel kombinált lézer indukálta fluoreszcencia detekcióval) is kidolgoztunk és a konvenciális eljárásokon kívül a legmodernebb mikroCT és nanoSPECT analízist is alkalmaztuk. | Periodontitis and caries are widespread diseases in Hungary. According to the latest epidemiologic and clinical investigations it was proven beyond the fact, that dental infections result in local problems, they can serve as prominent risk factors especially of cardiovascular diseases. Cardiovascular diseases are the leading causes of death in our country. For this reason the role of studies in connection with the oral status should be emphasized! In the present project we investigated 1) the effects of the vasoactive materials (such as NO, CO, H2S, VEGF, endothelin-1) on the regulation of blood circulation of oral structures (dental pulp, gingiva, salivary gland) under physiological and pathological circumstances, 2) the role of bacterial lysine decarboxylase, heamoxygenase and a new aspect of diabetes in the pathogenesis of periodontal disease. 3) Last but not least we also tried to find new complementary therapeutic pathways to periodontitis with the help of gastric osteogenic BPC157, anti-inflammatory inosine and lysine decarboxylase inhibitor. We developed a new technique (lysine/cadaverine capillary electrophoresis with laser induced fluorescence detection) for our study and besides conventional methods we performed cutting-edge techniques e.g. microCT or nanoSPECT analyses as well

Assessment of heat provocation tests on the human gingiva: the effect of periodontal disease and smoking.

Periodontal inflammation is associated with morphological changes in the blood vessels which may influence the regulation of gingival blood flow (GBF). Our aim was to adapt the heat provocation test to the human gingiva to assess vascular reactivity in periodontal inflammation. METHOD: GBF was recorded by Laser Doppler Flowmetry before and after heat provocation in healthy volunteers (n = 50). Heat was generated either by warm saline or a halogen lamp. The latter method was also utilized for a heat test in non-smoking and smoking patients with periodontal inflammation. The circulatory parameters were correlated to the inflammatory marker, i.e. gingival crevicular fluid (GCF) production measured by Periotron. RESULTS: Local application of heat caused a rapid, significant and transient increase in GBF regardless of the method used. The increase in the speed and not in the concentration of moving blood cells was responsible for increased GBF. Higher GCF values were correlated with increased peak flow, flux pulse amplitude and faster restoration of GBF after the test in non-smokers, but not in smokers. CONCLUSIONS: The heat test could be a valuable tool to check the vascular reactivity of gingival vessels. Moderate periodontal inflammation may facilitate gingival vascular responsiveness which can be suppressed by smoking

Resolving the Contradictory Functions of Lysine Decarboxylase and Butyrate in Periodontal and Intestinal Diseases

Periodontal disease is a common, bacterially mediated health problem worldwide. Mastication (chewing) repeatedly traumatizes the gingiva and periodontium, causing traces of inflammatory exudate, gingival crevicular fluid (GCF), to appear in crevices between the teeth and gingiva. Inadequate tooth cleaning causes a dentally adherent microbial biofilm composed of commensal salivary bacteria to appear around these crevices where many bacteria grow better on GCF than in saliva. We reported that lysine decarboxylase (Ldc) from Eikenella corrodens depletes the GCF of lysine by converting it to cadaverine and carbon dioxide. Lysine is an amino acid essential for the integrity and continuous renewal of dentally attached epithelium acting as a barrier to microbial products. Unless removed regularly by oral hygiene, bacterial products invade the lysine-deprived dental attachment where they stimulate inflammation that enhances GCF exudation. Cadaverine increases and supports the development of a butyrate-producing microbiome that utilizes the increased GCF substrates to slowly destroy the periodontium (dysbiosis). A long-standing paradox is that acid-induced Ldc and butyrate production support a commensal (probiotic) microbiome in the intestine. Here, we describe how the different physiologies of the respective tissues explain how the different Ldc and butyrate functions impact the progression and control of these two chronic diseases

Evidence of spreading vasodilation in the human gingiva evoked by nitric oxide

Spreading vasodilation is an important means of increasing local blood flow effectively during increased metabolic demands or in case of vascular injury. Our aim was to develop a technique proving the presence of spreading vasodilation in the human keratinized gingiva.Local vasodilation was evoked by the application of nitric oxide (NO) donor nitroglycerin into a well, fixed 2 mm above the marginal gingiva, in 20 subjects with healthy periodontal tissue. Either 1 or 8 mg/mL nitroglycerin solutions were dropped into the test well at the upper right second incisor, and saline was applied into the control well at the upper left first incisor. The gingival blood flow (GBF) was recorded for 15 minutes by a laser speckle contrast imager below the well and in the surrounding area in the mesial, distal, apical and coronal directions. Gingival thickness was measured by an ultrasonic biometer.Peak GBF increase was similar after 1 mg/mL and after 8 mg/mL nitroglycerin application in the well (51% ± 12% vs 42% ± 8%) and in the apical region (33 ± 9% vs 55% ± 13%). While the lower dose of nitroglycerin increased GBF only in the apical region around the well, the higher dose induced significant elevations in all surrounding regions, with apical prominence. Hyperaemia lasted 10-14 minutes in the low-dose group whereas it extended beyond the observation period in the high-dose group. Neither the baseline nor the NO-induced peak GBF were correlated with gingival thickness.The role of the direct effect of NO in the regulation of perfusion was demonstrated in the human gingiva as well as the propagation of local vasodilation to distant, especially apical areas, probably by the mechanism of flow-mediated dilation. This mechanism may have a clinical importance for flap survival or wound healing

Zinc chloride inhibits lysine decarboxylase production from Eikenella corrodens in vitro and its therapeutic implications

Objectives Dentifrices containing zinc reduce gingival inflammation and bleeding better than control dentifrices (no zinc). How zinc might work is not understood. We have shown that lysine decarboxylase (LdcE), an enzyme from Eikenella corrodens, converts lysine to cadaverine in dental biofilms. The lack of lysine impairs the dentally attached cell barrier to biofilm, causing biofilm products to leak into junctional epithelium and stimulate inflammation. In year-old beagle dogs, immunization with LdcE, induces antibodies that inhibit LdcE activity and retard gingivitis development. We therefore examined whether a zinc-mediated loss of LdcE activity could explain the beneficial effect of zinc dentifrices. Methods We grew E. corrodens in modified tryptic soy broth with or without zinc chloride, and extracted LdcE from the cell surface using a Potter Elvehjem homogenizer. Results Up to 0.96 mM zinc chloride in the bacterial growth medium did not change cell yield, but reduced the extracted protein content by 41 % (R2 = 0.27, p < 0.05) and LdcE activity/mg extracted protein by 85 % (R2 = 0.90, p < 0.001). In extracts from cells grown without zinc, 78 times this zinc chloride concentration (73 mM) was required to reduce LdcE activity by 75 %. Conclusions Zinc ions inhibit the production of protein with LdcE activity at E. corrodens cell surfaces. The zinc ions may attach to cysteine residues that are unique to the N-terminal region of LdcE by interfering with the non-covalent polypeptide assembly that produces enzyme activity. Clinical significance Zinc ion-mediated inhibition of LdcE assembly may provide a rationale for the improved control of gingival inflammation by zinc dentifrices

Evaluation of Laser Speckle Contrast Imaging for the Assessment of Oral Mucosal Blood Flow following Periodontal Plastic Surgery: An Exploratory Study

The laser speckle contrast imaging (LSCI) is proved to be a reliable tool in flap monitoring in general surgery; however, it has not been evaluated in oral surgery yet. We applied the LSCI to compare the effect of a xenogeneic collagen matrix (Geistlich Mucograft®) to connective tissue grafts (CTG) on the microcirculation of the modified coronally advanced tunnel technique (MCAT) for gingival recession coverage. Gingival microcirculation and wound fluid were measured before and after surgery for six months at twenty-seven treated teeth. In males, the flap microcirculation was restored within 3 days for both grafts followed by a hyperemic response. During the first 8 days the blood flow was higher at xenogeneic graft comparing to the CTG. In females, the ischemic period lasted for 7-12 days depending on the graft and no hyperemic response was observed. Females had more intense and prolonged wound fluid production. The LSCI method is suitable to capture the microcirculatory effect of the surgical intervention in human oral mucosa. The application of xenogeneic collagen matrices as a CTG substitute does not seem to restrain the recovery of graft bed circulation. Gender may have an effect on postoperative circulation and inflammation

A poli (ADP-ribóz) polimeráz enzim szerepe diabeteszes komplikációk patogenezisében = Poly (ADP-ribose) polymerase and diabetic complications

A jelen munkában a PARP fehérje szerepét vizsgáltuk a cukobetegség szövődményeinek kialakulásában. Kimutattuk, hogy az erek és a vese károsodásában fontos szerepe van ennek a fehérjének, és a fehérje aktivitásának gátlása állatokban javítja a betegség lefolyását. Összefüggést találtunk a PARP aktivációja, valamint a rosszul beállított cukorbetegség között, és kimutattuk különféle sejten belüli szignál transzdukciós út szerepét ezekben a folyamatokban. A munka számos nemzetközi szintű közleményt eredményezett. | In the present project, we have investigated the role of the PARP enzyme in the pathogenesis of diabetic complications. We have demonstrated that the vascular and renal damage associated with diabetes is importantly mediated by the activation of the PARP enzyme. We have demonstrated a relationship between poorly controlled diabetes and the activation of PARP and we have demonstrated the role of several intracellular signal transduction pathways in the process. The work has resulted in a number of internationally significant publications

Antimicrobial Efficacy of Chlorhexidine and Sodium Hypochlorite in Root Canal Disinfection: A Systematic Review and Meta-analysis of Randomized Controlled Trials

We aimed to compare the antimicrobial efficacy of chlorhexidine (CHX) and sodium hypochlorite (NaOCl), two irrigants routinely used in root canal therapy of permanent teeth.Electronic databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, were searched for randomized controlled trials published until March 2020. The meta-analysis of relative risk (RR) and standardized mean difference (SMD) was performed using a random-effect model with a 95% confidence interval (CI). Subgroup analysis was performed for culture and molecular methods of bacterial detection.The literature search yielded 2,110 records without duplicates. Eight studies were eligible for a systematic review. No significant differences in the incidence of samples with positive bacterial growth after irrigation (RR=1.003, 95% CI: 0.729-1.380, p=0.987) and mean bacterial number changes (SMD=0.311, 95% CI: -0.368-0.991, p=0.369) were observed between CHX and NaOCl in the culture and molecular subgroups. Heterogeneity in RR (I2=0%, p=0.673) was low among studies, while considerable heterogeneity was observed in the analysis of SMD (I2=76.336%, p=0.005).Our findings suggest that both CHX and NaOCl can reduce bacterial infections after irrigation, without any significant difference in antimicrobial efficacy between them. Although CHX and NaOCl showed similar efficacy, their molecular mechanisms were different. Therefore, they can be used as the main antibacterial root canal irrigants. However, our results were limited by inconsistencies among retrieved articles and a lack of clinically relevant outcomes. Further well-designed clinical studies are warranted to supplement our results

Szemelvények a Semmelweis Egyetem, az Országos Onkológiai Intézet és az Országos Korányi Tbc és Pulmonológiai Intézet együttműködésén alapuló tüdőrák-kutatási programból

Lung cancer places a significant socio-economic burden on the Hungarian population. This overview summarizes the findings of collaborative translational lung cancer research efforts of three Hungarian flagship academic institutions, the Semmelweis University, the National Institute of Oncology and the National Koranyi Institute of TB and Pulmonology. With regards to the molecular factors regulating tumor angiogenesis, we identified the prognostic significance of apelin and erythropoietin receptor (EPOR) expression in non-small cell lung cancer (NSCLC). Furthermore, the impact of KRAS mutation subtypes and ERCC1 (excision repair cross-complementation group 1) expression on the response to platinum-based chemotherapy have been studied. We also described the epidemiology and predictive power of rare EGFR (epidermal growth factor receptor) mutations in a large Hungarian patient cohort. Lastly, the expression of molecular factors associated with NSCLC progression was studied specifically in brain metastatic matched cases series. These preclinical and clinical studies provide clinically relevant information that hopefully will contribute to the improvement of lung cancer patient care