BACKGROUND: Recurrent aphthous stomatitis is one of the most prevalent oral mucosal immunological diseases. A recent case-control study in the Egyptian population suggested that single nucleotide polymorphism Gly54Asp (rs1800450) of the mannose-binding lectin 2 gene might affect the mannose-binding lectin serum level and recurrent aphthous stomatitis development. The aim of this study was to determine the distribution of six functional mannose-binding lectin 2 gene polymorphisms and analyse their role in recurrent aphthous stomatitis susceptibility in the Czech population. METHODS: The study included 227 subjects; 137 healthy people and 90 patients with recurrent aphthous stomatitis. Six mannose-binding lectin 2 gene polymorphisms (rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, rs1800451) were analysed by the SNaPshot assay method, mannose-binding lectin serum levels were determined by enzyme-linked immunosorbent assay (ELISA) method in a subgroup of subjects (N = 87). RESULTS: No significant differences in mean of mannose-binding lectin serum levels between healthy controls and patients with recurrent aphthous stomatitis were observed (383 ng/ml ± 249 standard deviation (SD) vs. 316 ng/ml ± 177 SD in remission phase vs. 343 ng/ml ± 254 SD in active phase; p > 0.05), also the allele and genotype frequencies of the studied mannose-binding lectin 2 polymorphisms did not differ significantly between the two groups (p > 0.05, odds ratio (OR): 0.75-1.23). Moreover, the distribution of mannose-binding lectin 2 haplotypes and haplogenotypes was similar in the healthy subjects and patients with recurrent aphthous stomatitis (p > 0.05, OR: 0.75-1.23). CONCLUSIONS: This study did not confirm the previously reported association of the mannose-binding lectin 2 Gly54Asp gene variant and low mannose-binding lectin serum level as the risk factors for susceptibility to recurrent aphthous stomatitis. In addition, no significant relationships between mannose-binding lectin 2 functional haplotypes or haplogenotypes and recurrent aphthous stomatitis were observed.

• MeSH
• aftózní stomatitida * genetika   MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus MeSH
• lektin vázající mannosu MeSH
• lidé MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Recurrent aphthous stomatitis (RAS) is multifactorial disease with unclear etiopathogenesis. The aim of this study was to determine distribution of the angiotensin I converting enzyme (ACE) gene polymorphisms and their influence on RAS susceptibility in Czech population. METHODS: The study included 230 subjects (143 healthy controls and 87 patients with RAS) with anamnestic, clinical and laboratory data. Five ACE gene polymorphisms (rs4291/rs4305/rs4311/rs4331/rs1799752 = ACE I/D) were determined by TaqMan technique. RESULTS: The allele and genotype distributions of the studied ACE I/D polymorphisms were not significantly different between subjects with/without RAS (Pcorr > 0.05). However, carriers of II genotype were less frequent in the RAS group (OR = 0.48, 95% CI = 0.21-1.12, P = 0.059). Stratified analysis by sex demonstrated lower frequency of II genotype in women (OR = 0.33, 95% CI = 0.09-1.17, P < 0.035, Pcorr > 0.05, respectively) than in men with RAS (P > 0.05). Moreover, the frequency of AGTGD haplotype was significantly increased in RAS patients (OR = 13.74, 95% CI = 1.70-110.79, P = 0.0012, Pcorr < 0.05). In subanalysis, TGD haplotype was significantly more frequent in RAS patients (P < 0.00001) and CGI haplotype was less frequent in RAS patients (P < 0.01), especially in women (P = 0.016, Pcorr > 0.05). CONCLUSIONS: Our study indicates that while the AGTGD and TGD haplotypes are associated with increased risk of RAS development, CGI haplotype might be one of protective factors against RAS susceptibility in Czech population.

• MeSH
• aftózní stomatitida * epidemiologie   genetika   MeSH
• angiotensin konvertující enzym * genetika   MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci genetika   MeSH
• lidé MeSH
• polymorfismus genetický genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

• MeSH
• antiastmatika terapeutické užití   MeSH
• antihistaminika terapeutické užití   MeSH
• artralgie * MeSH
• bronchiální astma farmakoterapie   MeSH
• diferenciální diagnóza MeSH
• imunologické testy MeSH
• lidé MeSH
• nesnášenlivost laktózy * diagnóza   MeSH
• senioři MeSH
• sezónní alergická rýma * farmakoterapie   MeSH
• Sjögrenův syndrom MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

OBJECTIVE: The aim of this study was to investigate five polymorphisms in the SLC6A4 gene in patients with recurrent aphthous stomatitis (RAS) and healthy controls. DESIGN: Totally, 239 subjects were enrolled in this case-control study: 86 patients with RAS and 153 healthy individuals were genotyped for serotonin transporter length polymorphic region (5-HTTLPR) polymorphism, variable number tandem repeat (STin2) and single nucleotide polymorphisms (rs25531, rs3813034, rs1042173) in the SLC6A4 gene by polymerase chain reaction with/without restriction analysis. RESULTS: No significant differences in the allele or genotype frequencies in all studied polymorphisms between RAS patients and healthy controls (P > 0.05) were detected. However, the haplotype analysis detected a higher frequency of LA12 (HTTLPR, rs25531, STin2) haplotype in RAS patients in comparison with healthy controls (P < 0.05, OR = 1.63, 95 % CI = 1.07-2.49). CONCLUSIONS: Our study indicates a possible relationship between SLC6A4 and susceptibility to RAS in the Czech population.

• MeSH
• aftózní stomatitida * genetika   MeSH
• frekvence genu MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• membránové transportní proteiny pro serotonin * genetika   MeSH
• recidiva MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

INTRODUCTION AND OBJECTIVE: Cytochrome P450 enzymes are the major drug-metabolizing enzymes in humans and the importance of drug transport proteins, in particular P-glycoprotein, in the variability of drug response has also been highlighted. Activity of cytochrome P450 enzymes and P-glycoprotein can vary widely between individuals and genotyping and/or phenotyping can help assess their activity. Several phenotyping cocktails have been developed. The Geneva cocktail is composed of a specific probe for six different cytochrome P450 enzymes and one for P-glycoprotein and was used in the context of a research aiming at exploring genotypes and phenotypes in distinct human populations (NCT02789527). The aim of the present study is to solely report the safety results of the Geneva cocktail in the healthy volunteers of these populations.MATERIALS AND METHODS: The Geneva cocktail is composed of caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, midazolam, and fexofenadine. The volunteers fasted and avoided drinking caffeine-containing beverages or food and grapefruit juice overnight before receiving the cocktail orally. They provided blood spots for the probes' concentrations at 2, 3, and 6 h after ingestion and were asked about adverse events. RESULTS: A total of 265 healthy adult volunteers were included from Ethiopia, Oman, and the Czech Republic. The mean plasma concentrations at the 2-h sampling time of each probe drug in the total sample were: 1663 ng/mL for caffeine, 8 ng/mL for bupropion, 789 ng/mL for flurbiprofen, 6 ng/mL for dextromethorphan, 2 ng/mL for midazolam, 35 ng/mL for fexofenadine, and 103 ng/mL for omeprazole. Four adverse events were observed representing an occurrence of 1.5%. All these events were categorized as mild to moderate, non-serious, and resolved spontaneously. A causal link with the cocktail cannot be excluded because of the temporal relationship but is at most evaluated as possible according to the World Health Organization-Uppsala Monitoring Centre causal assessment system. CONCLUSIONS: In this research, healthy volunteers from three different human populations were phenotyped with the Geneva cocktail. Four adverse events were observed, confirming the safety of this cocktail that is given at lower than clinically relevant doses and therefore results in concentrations lower than those reported to cause adverse events.

• MeSH
• dospělí MeSH
• fixní kombinace léků MeSH
• genotyp MeSH
• inhibitory cytochromu P450 MeSH
• léčivé přípravky metabolismus   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• P-glykoprotein genetika   metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• substrátová specifita MeSH
• systém (enzymů) cytochromů P-450 genetika   metabolismus   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Etiopie MeSH
• Omán MeSH

Beryllium has an impact on the human health of professionally or non-occupationally exposed people. Current evidence suggests that beryllium acts as a hapten with limited antigenic properties and is presented by antigen presenting cells to CD4+ T cells, which possess specific antigen receptors. The immunological changes in humoral immunoreactivity were considered biomarkers of beryllium exposure. In the present, due to the development of immunologic knowledge, tests of cellular immunity have promising potential for further research in this field. The historical view of the immune response to beryllium in acute and/or chronic beryllium disease is an example of the development of the interaction between mechanisms of innate and adaptive (specific), humoral and cellular immunity. The authors emphasize the increasing importance of immunological aspects in the studies of health impacts of human exposure to environmental pollutants.

• MeSH
• berylióza imunologie   MeSH
• beryllium škodlivé účinky   analýza   imunologie   MeSH
• lidé MeSH
• popel uhelný chemie   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The development of recurrent aphthous stomatitis (RAS), inflammatory disease of oral mucosa, is influenced by both environmental and genetic factors. The aim of this study was to investigate polymorphisms located in seven genes coding different types of matrix metalloproteinases (MMPs)-collagenases (MMP1, MMP8, and MMP13), gelatinases (MMP2 and MMP9), stromelysin (MMP3), and membrane-type metalloproteinase (MMP16) in patients with RAS and healthy controls. METHODS: Totally, 223 subjects were included in this case-control study and their detailed anamnestic, clinical, and laboratory parameters were recorded. Seventy-seven patients with RAS and 146 controls were genotyped for seventeen polymorphisms in the MMPs genes using the real-time polymerase chain reaction (PCR) or PCR with restriction analysis. RESULTS: Allele, genotype, and haplotype frequencies of the studied polymorphisms between RAS patients and controls were similar, except for allele distributions of MMP1 rs1144393, MMP9 rs3918242, and MMP16 rs10429371, which were different between patients with RAS and healthy controls (P = .023, P = .049 and P = .025, all Pcorr  > 0.05, respectively). Moreover, the comparison of genotype frequencies (TT vs CC + CT) of the MMP16 rs10429371 variant showed a marginally significant difference between RAS patients and controls (P = .05, Pcorr  > 0.05, OR = 1.68, 95% CI = 0.95-2.98). CONCLUSIONS: No significant relationship between investigated polymorphisms in seven MMPs genes and RAS development in the Czech population was observed in this study.

• MeSH
• aftózní stomatitida enzymologie   genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixové metaloproteinasy genetika   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Recurrent aphthous stomatitis (RAS) is the most common disease of the oral mucosa, and it has been recently associated with bacterial and fungal dysbiosis. To study this link further, we investigated microbial shifts during RAS manifestation at an ulcer site, in its surroundings, and at an unaffected site, compared with healed mucosa in RAS patients and healthy controls. We sampled microbes from five distinct sites in the oral cavity. The one site with the most pronounced differences in microbial alpha and beta diversity between RAS patients and healthy controls was the lower labial mucosa. Detailed analysis of this particular oral site revealed strict association of the genus Selenomonas with healed mucosa of RAS patients, whereas the class Clostridia and genera Lachnoanaerobaculum, Cardiobacterium, Leptotrichia, and Fusobacterium were associated with the presence of an active ulcer. Furthermore, active ulcers were dominated by Malassezia, which were negatively correlated with Streptococcus and Haemophilus and positively correlated with Porphyromonas species. In addition, RAS patients showed increased serum levels of IgG against Mogibacteriumtimidum compared with healthy controls. Our study demonstrates that the composition of bacteria and fungi colonizing healthy oral mucosa is changed in active RAS ulcers, and that this alteration persists to some extent even after the ulcer is healed.

• Publikační typ
• časopisecké články MeSH

The project is designed to specify the role of immune mechanisms in the pathogenesis of recurrent aphthous stomatitis (RAS). Its multifactorial etiopathogenesis is not satisfactorily explained and a really effective treatment of the disease is unknown. Immunologic and genetic factors are important in the interaction with the environment. The development of different allergic and immunopathological reactions can be associated with RAS. We will study the role of innate and adaptive arms of mucosal (salivary) immunity in oral cavity and changes of systemic immunologic reactivity in patients with RAS. We will also focus on the response of mononuclear blood cells to metal ions and selected food and bacterial antigens. The significance of individual ́s genetic predisposition will be monitored by analyzing the polymorphisms in genes for metalloproteinases and cytokines.

Projekt je zaměřen na upřesnění role imunitních mechanismů v patogenezi recidivujících aft (RAS). Jeho multifaktoriální etiopatogeneze není uspokojivě vysvětlena stejně jako není známé jeho skutečně účinné léčení. Imunologické a genetické faktory jsou důležité v interakci s prostředím. Rozvoj různých alergických a imunopatologických reakcí může souviset s RAS. Budeme sledovat úlohu přirozené a adaptivní složky slizniční (slinné) imunity v dutině ústní a změny systémové imunologické reaktivity pacientů s RAS. Zaměříme se také na odpověď mononukleárních buněk na ionty kovů a vybrané potravinové a bakteriální antigeny. Význam individuální genetické predispozice bude sledován prostřednictvím analýzy polymorfismů genů pro metaloproteinázy a cytokiny.

• MeSH
• aftózní stomatitida MeSH
• alergie MeSH
• genetická predispozice k nemoci MeSH
• rizikové faktory MeSH
• slizniční imunita MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• alergologie a imunologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR