RESUMO
OBJECTIVE: LL-37 contributes to maintaining the balance between health and disease. Smoking is a risk factor for periodontitis that impairs neutrophil functions. The aim of the present study was to comparatively evaluate gingival crevicular fluid (GCF) LL-37 levels in smoker and non-smoker chronic periodontitis (CP) patients and controls, as well as the effect of non-surgical periodontal treatment on GCF LL-37 levels. DESIGN: Thirty-one CP patients (16 smokers, 15 non-smokers) and thirty-one controls (16 smokers, 15 non-smokers) were included in the study. CP patients received non-surgical treatment. GCF LL-37 levels and periodontal parameters were assessed at baseline, 1 and 3 months after completion of non-surgical periodontal treatment. GCF LL-37 levels were analyzed by ELISA. RESULTS: No significant difference was observed in GCF LL-37 levels between smoker and non-smoker controls (p>0.05). Smoker CP group had significantly lower GCF LL-37 level than non-smoker CP group at baseline (p<0.05). GCF LL-37 levels significantly decreased in non-smoker CP group at first week, 1 and 3 months after completion of non-surgical periodontal treatment (p<0.05) although no significant decrease in GCF LL-37 levels was observed in smoker CP group (p>0.05). Periodontal parameters were correlated with GCF LL-37 levels in non-smoker CP group (p<0.05), but not in smoker CP group (p>0.05). CONCLUSIONS: GCF LL-37 levels do not seem to be affected from smoking in periodontal health. However, smoking might have a suppressive effect on GCF LL-37 levels in CP. Non-surgical treatment is effective in decreasing GCF LL-37 levels in non-smoker CP patients but not in smokers with CP.
Assuntos
Catelicidinas/metabolismo , Periodontite Crônica/terapia , Líquido do Sulco Gengival/química , Fragmentos de Peptídeos/metabolismo , Fumar , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: The aim of this study was to evaluate histologically the following treatment of bilateral localized gingival recessions with coronally advanced flap (CAF) combined with platelet-rich fibrin (PRF) or subepithelial connective tissue graft (SCTG). MATERIALS AND METHODS: Tissue samples were harvested from 14 subjects either 1 or 6 months after the surgeries. The 2-mm punch biopsies were obtained from the mid-portion of the grafted sites. Neutral buffered formalin fixed, paraffin-embedded 5-µm thick tissue sections were stained with hematoxylin eosin and Masson's trichrome in order to analyze the collagen framework, epithelium thickness and rete-peg length. Multiple sequential sections were cut from paraffin-embedded blocks of tissue and immunohistochemically prepared for detection of vascular endothelial growth factor, CD31 and CD34, for the assessment of vascularization. RESULTS: Rete peg formation was significantly increased in the sites treated with PRF compared to the SCTG group after 6 months (p < 0.05). On the contrary, the number of vessels was increased in the SCTG group compared to the PRF group after 6 months (p < 0.05). No statistically significant differences were observed in the collagen density. Staining intensity of CD31 increased in submucosal area of PRF group than SCTG group after 1 month. Higher staining intensity of CD34 was observed in the submucosal area of PRF group compared with SCTG group after 6 months. CONCLUSIONS: The results of the present study suggest that in histological evaluation because of its biological compounds, PRF results earlier vessel formation and tissue maturation compared to connective tissue graft. CLINICAL RELEVANCE: PRF regulated the vascular response associated with an earlier wound healing.
Assuntos
Plaquetas/fisiologia , Tecido Conjuntivo/transplante , Fibrina/fisiologia , Gengiva/irrigação sanguínea , Retração Gengival/terapia , Retalhos Cirúrgicos , Adolescente , Adulto , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Cicatrização/fisiologiaRESUMO
BACKGROUND: Interleukin (IL)-6 family of cytokines, including IL-6, oncostatin M (OSM), leukemia inhibitory factor (LIF), and IL-11, have fibrogenic features. The current study determines gingival crevicular fluid (GCF) levels of fibrosis-related IL-6-type cytokines in cyclosporine A (CsA)-induced gingival overgrowth (GO). METHODS: Eighty non-smokers were included (40 CsA-medicated renal transplant patients with GO [GO+; n = 20] or without GO [GO-; n = 20], 20 individuals with gingivitis, and 20 healthy participants). Probing depth and plaque, papilla bleeding, and hyperplastic index scores were recorded. GCF samples were obtained from the mesio-buccal aspects of two teeth. GCF IL-6, IL-1ß, OSM, LIF, and IL-11 levels were analyzed by enzyme-linked immunosorbent assay. RESULTS: The GO+ and GO- groups had higher IL-6 total amounts than the healthy group (P <0.008). IL-1ß total amounts in the GO+ group were significantly higher than in both the healthy and GO- groups (P <0.008). OSM total amount was elevated in the GO+ and GO- groups compared with both the gingivitis and healthy groups (P <0.008). All groups had similar LIF and IL-11 total amounts (P >0.008). Moderate positive correlations were detected among IL-6, IL-1ß, OSM, and IL-11 total amount in GCF and clinical parameters (P <0.05). CONCLUSIONS: IL-6 and OSM increases in GCF as a result of CsA usage or an immunosuppressed state irrespective of the severity of inflammation and the presence of GO. The IL-6 family of cytokines might not be directly involved in biologic mechanisms associated with CsA-induced GO. Lack of an association between assessed IL-6 cytokines and CsA-induced GO might indicate distinct effects of these cytokines on fibrotic changes of different tissues.
Assuntos
Ciclosporina/efeitos adversos , Líquido do Sulco Gengival/imunologia , Crescimento Excessivo da Gengiva/induzido quimicamente , Imunossupressores/efeitos adversos , Interleucina-6/análise , Transplante de Rim , Adulto , Índice de Placa Dentária , Feminino , Hiperplasia Gengival/classificação , Crescimento Excessivo da Gengiva/imunologia , Gengivite/classificação , Humanos , Interleucina-11/análise , Interleucina-1beta/análise , Fator Inibidor de Leucemia/análise , Masculino , Pessoa de Meia-Idade , Oncostatina M/análise , Índice Periodontal , Bolsa Periodontal/classificação , Adulto JovemRESUMO
BACKGROUND: The aim of the present study is to investigate gingival crevicular fluid (GCF) and plasma acute-phase cytokines, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-11 (IL-11), oncostatin M (OSM), and leukemia inhibitory factor (LIF) levels in patients with different periodontal diseases. METHODS: Eighty individuals were included in this study; 20 with chronic periodontitis (CP), 20 with generalized aggressive periodontitis (GAgP), 20 with gingivitis, and 20 classified as healthy (H). Probing depth, clinical attachment level, plaque index, and papilla bleeding index were recorded. Plasma and GCF IL-1ß, IL-6, IL-11, OSM, and LIF levels were analyzed by enzyme-linked immunosorbent assay. RESULTS: CP and GAgP groups had significantly higher GCF IL-1ß, IL-6, and IL-11 levels when compared with the H group (P <0.05). Conversely, GCF LIF levels of the CP and GAgP groups were lower than those of the H group (P <0.05). GCF OSM levels did not differ significantly among study groups. Plasma levels of all the cytokines studied were not significantly different among the study groups. CONCLUSIONS: Based on the present data, elevated IL-1ß, IL-6, and IL-11 GCF levels, but not plasma levels, are suggested as reliable inflammatory biomarkers in periodontal diseases. Decreased LIF levels in diseased groups might reflect the possible beneficial effects of LIF in the modulation of inflammatory response in gingiva.
Assuntos
Proteínas de Fase Aguda/análise , Periodontite Agressiva/metabolismo , Biomarcadores/análise , Periodontite Crônica/metabolismo , Citocinas/análise , Líquido do Sulco Gengival/química , Gengivite/metabolismo , Adulto , Periodontite Agressiva/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Periodontite Crônica/sangue , Citocinas/sangue , Feminino , Gengivite/sangue , Humanos , Interleucina-11/análise , Interleucina-11/sangue , Interleucina-1beta/análise , Interleucina-1beta/sangue , Interleucina-6/análise , Interleucina-6/sangue , Fator Inibidor de Leucemia/análise , Fator Inibidor de Leucemia/sangue , Masculino , Pessoa de Meia-Idade , Oncostatina M/análise , Oncostatina M/sangue , Estatísticas não Paramétricas , Adulto JovemRESUMO
Periodontitis is a disease of infectious aetiology that causes inflammatory destruction of the tooth-supporting tissues. Activated T cells are central to the pathogenesis of the disease, by producing receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) that stimulates bone resorption. Antigenic activation of T cells is regulated by the induction of transcription factor nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). There is as yet no information on the potential involvement of NFATc1 in periodontal diseases. This study aimed to investigate NFATc1 gene expression levels in periodontal diseases, and analyse the potential correlation with RANKL expression and clinical periodontal parameters. In this cross-sectional study, gingival tissue biopsies were obtained from healthy (n = 10) and periodontally diseased (n = 58) sites. NFATc1 and RANKL gene expression levels in these samples were analysed by quantitative real-time polymerase chain reaction. Compared with healthy subjects, patients with gingivitis, chronic and aggressive periodontitis, exhibited higher NFATc1 expression, which proved to be statistically significant in the periodontitis groups. NFATc1 and RANKL expression levels strongly correlated with each other, and with clinical periodontal parameters. The increased expression of NFATc1 in periodontitis denotes a role for this transcription factor in the pathogenesis of the disease.
Assuntos
Fatores de Transcrição NFATC/genética , Doenças Periodontais/genética , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Periodontite Agressiva/genética , Periodontite Agressiva/imunologia , Estudos de Casos e Controles , Periodontite Crônica/genética , Periodontite Crônica/imunologia , Estudos Transversais , Feminino , Expressão Gênica , Gengivite/genética , Gengivite/imunologia , Humanos , Ativação Linfocitária/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Doenças Periodontais/etiologia , Doenças Periodontais/imunologia , Ligante RANK/genética , Linfócitos T/imunologia , Adulto JovemRESUMO
BACKGROUND: The aim of this cross-sectional study is to investigate gingival crevicular fluid (GCF) osteocalcin, cross-linked N-terminal telopeptide (NTx), and calprotectin levels in cyclosporin A (CsA)-induced gingival overgrowth (GO). METHODS: Forty medicated patients with CsA including 20 with GO (CsA GO+), 10 without GO (CsA GO-), 10 with GO and chronic periodontitis (CsA CP) and 60 patients with CP alone, 20 patients with gingivitis, and 20 healthy patients were enrolled. Probing depth, clinical attachment level, plaque index, and papillary bleeding index were recorded. GCF calprotectin, osteocalcin, and NTx levels were analyzed by enzyme-linked immunosorbent assay. Parametric tests were used for statistical analysis. RESULTS: The CsA GO+ and CP groups had significantly lower GCF osteocalcin levels and osteocalcin/NTx ratio than the healthy group, whereas GCF osteocalcin levels and osteocalcin/NTx ratio in the gingivitis group were higher than the CsA GO+, CsA GO-, CsA CP, and CP groups (P <0.05). The CP group had elevated GCF calprotectin levels compared to the other study groups (P <0.05). The CsA GO+ and CsA GO- groups also had higher GCF calprotectin levels compared to the CsA CP, gingivitis, and healthy groups (P <0.05). CONCLUSIONS: Increased GCF calprotectin and decreased GCF osteocalcin levels in the CsA GO+ and CsA GO- groups might suggest that CsA plays a role on the levels of these markers. The similarity of GCF osteocalcin, NTx, and calprotectin levels in the CsA GO+ and CsA GO- groups might suggest that these molecules are not involved in the pathogenesis of GO.
Assuntos
Periodontite Crônica/metabolismo , Colágeno Tipo I/metabolismo , Crescimento Excessivo da Gengiva/induzido quimicamente , Crescimento Excessivo da Gengiva/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Osteocalcina/metabolismo , Peptídeos/metabolismo , Adulto , Processo Alveolar/metabolismo , Estudos de Casos e Controles , Colágeno Tipo I/análise , Estudos Transversais , Ciclosporina/efeitos adversos , Feminino , Líquido do Sulco Gengival/química , Gengivite/metabolismo , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Osteocalcina/análise , Peptídeos/análise , Estatísticas não ParamétricasRESUMO
AIM: Receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) have an established role in the pathogenesis of periodontitis, which is characterized by an increased RANKL/OPG ratio. The present study aims to investigate changes of RANKL, OPG and their relative ratio in gingival crevicular fluid (GCF) of periodontitis patients after non-surgical periodontal treatment. MATERIALS AND METHODS: GCF was obtained from chronic periodontitis (n=14), generalized aggressive periodontitis (G-AgP; n=13) patients at baseline. The patients received scaling and root planing and were recalled after 2, 3 and 4 months for follow-up clinical examination and sampling. The total amounts and concentrations of RANKL and OPG in GCF were measured by enzyme-linked immunosorbent assay, and their relative ratio was calculated. RESULTS: The RANKL/OPG ratio remained unchanged and did not correlate with clinical parameters throughout the monitoring period, despite the improved clinical outcome. This trend was similar in both chronic and G-AgP. CONCLUSIONS: Although the RANKL/OPG ratio has a potential diagnostic value for untreated periodontitis, it may not be a suitable predictor of clinically successful treatment outcome. As conventional therapy does not negatively modulate this ratio, the host could still be susceptible to further periodontal tissue destruction, warranting the consideration of adjunctive treatments.
Assuntos
Periodontite Crônica/metabolismo , Líquido do Sulco Gengival/metabolismo , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Adolescente , Adulto , Periodontite Agressiva/metabolismo , Periodontite Agressiva/terapia , Biomarcadores/metabolismo , Periodontite Crônica/terapia , Profilaxia Dentária , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Immune cell recognition of lipopolysaccharides via CD14 and Toll-like receptor 4 (TLR4) complexes plays a crucial role in linking innate and adaptive immune responses. This study was aimed to investigate the expression of TLR4 and membrane-bound CD14 (mCD14) in the gingival tissues of patients with gingivitis, periodontitis and CsA-induced gingival overgrowth. DESIGN: Gingival tissues were obtained from 10 renal transplant patients receiving cyclosporine-A (CsA) and having gingival overgrowth (GO), 10 patients with chronic periodontitis, 10 generalized aggressive periodontitis, 10 gingivitis and 10 healthy subjects. Immunohistochemistry was performed in order to determine the localization of TLR4 and mCD14 in tissue specimens. RESULTS: TLR4 and mCD14 expressions were detected in all tissues including healthy gingival biopsies. TLR4 and mCD14 positive cells were predominantly confined to the epithelium-connective tissue interface area, and were highly expressed in the basal cell layer of patients with CsA GO and chronic periodontitis, compared to healthy group (P<0.05). CONCLUSION: The present study suggests that TLR4 and mCD14 protein expressions may be interrelated and appear to be associated with periodontal disease. CsA usage seemed not to affect TLR4 and mCD14 expressions in CsA induced GO tissues.
Assuntos
Crescimento Excessivo da Gengiva/metabolismo , Gengivite/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Periodontite/metabolismo , Receptor 4 Toll-Like/metabolismo , Adulto , Análise de Variância , Biópsia , Estudos de Casos e Controles , Ciclosporina/efeitos adversos , Feminino , Crescimento Excessivo da Gengiva/induzido quimicamente , Gengivite/imunologia , Humanos , Imuno-Histoquímica , Imunossupressores/efeitos adversos , Receptores de Lipopolissacarídeos/imunologia , Masculino , Periodontite/imunologia , Receptor 4 Toll-Like/imunologiaRESUMO
BACKGROUND: The present randomized, double-masked, placebo-controlled, parallel-arm study examines the impact of adjunctive subantimicrobial-dose doxycycline (SDD) on the local inflammatory response through cytokine and chemokine levels in gingival crevicular fluid (GCF) samples from patients with chronic periodontitis. METHODS: Forty-six patients with chronic periodontitis received scaling and root planing with or without adjunctive SDD. GCF samples were collected and clinical parameters including probing depth, clinical attachment level, gingival index, and plaque index were recorded every 3 months for 12 months. GCF tumor necrosis factor-α, interleukin (IL)-6, IL-4, IL-10, IL-13, IL-17, macrophage inhibitory protein 1α, macrophage inhibitory protein 1ß, monocyte chemoattractant protein 1, and regulated on activated normal T-cell expressed and secreted protein levels were determined by xMAP multiplex immunoassay. RESULTS: Significant improvements were observed in all clinical parameters in both groups over 12 months (P <0.0125), whereas the SDD group showed significantly better reduction in gingival index, probing depth, and gain in clinical attachment compared to the placebo group (P <0.05). Decrease in IL-6 in the SDD group was significantly higher compared to the placebo group at 6 and 9 months in deep pockets (P <0.05), whereas tumor necrosis factor-α was significantly reduced in moderately deep pockets (P <0.05). SDD resulted in a stable IL-4 and IL-10 response while reducing the monocyte chemoattractant protein 1 levels at 3 months (P <0.05). CONCLUSIONS: These results show that SDD, as an adjunct to non-surgical periodontal therapy, stabilizes the inflammatory response by promoting the suppression of proinflammatory cytokines and increasing the anti-inflammatory cytokines. The chemokine activity would account for the regulation of the inflammatory response to SDD therapy.
Assuntos
Antibacterianos/uso terapêutico , Periodontite Crônica/tratamento farmacológico , Periodontite Crônica/imunologia , Citocinas/análise , Doxiciclina/uso terapêutico , Líquido do Sulco Gengival/química , Imunomodulação/efeitos dos fármacos , Adulto , Quimiocina CCL2/análise , Quimiocina CCL4/análise , Quimiocina CCL5/análise , Raspagem Dentária , Método Duplo-Cego , Feminino , Fator 15 de Diferenciação de Crescimento/análise , Humanos , Imunoensaio/métodos , Interleucinas/análise , Masculino , Microesferas , Pessoa de Meia-Idade , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/análiseRESUMO
BACKGROUND: Fluctuations in sex steroid hormones, which are also noticeable through the menstrual cycle of women, may impact periodontal health. The aim of this study is to evaluate the effect of hormonal changes occurring in the menstrual cycle on gingival inflammation and the gingival crevicular fluid (GCF) levels of interleukin 6 (IL-6), prostaglandin E(2) (PGE(2)), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-2 (PAI-2). METHODS: Twenty-five gingivitis patients and 25 periodontally healthy subjects having regular menstrual cycles were seen at menstruation (ME) (1 to 2 days of menstruation), ovulation (OV) (12 to 14 days), and premenstrual phases (PM) (22 to 24 days). GCF and saliva samples were collected and clinical parameters including plaque index and bleeding on probing were recorded at each menstrual phase. Salivary estrogen and progesterone levels were analyzed to determine exact menstrual cycle days. GCF levels of IL-6, PGE(2), t-PA, and PAI-2 were measured by enzyme-linked immunosorbent assay. RESULTS: The percentages of sites with bleeding on probing were significantly higher in ME (60.85 +/- 18.36) and OV (58.92 +/- 25.04) than in the PM (40.12 +/- 20.10) phase in the gingivitis group (P <0.001; repeated measures analysis of variance), whereas it was similar for all phases in the healthy group (P >0.05; repeated measures analysis of variance). GCF levels of IL-6 were significantly elevated in gingivitis patients compared to healthy subjects in all phases (P = 0.004, P = 0.041, and P = 0.046 for ME, OV, and PM, respectively; Mann-Whitney U test). GCF levels of IL-6, PGE(2), t-PA, and PAI-2 were unchanged in different menstrual phases in both groups (P >0.05; Friedman test). CONCLUSION: The present study suggests that changes in the sex steroid hormones during menstrual cycles might have a limited effect on the inflammatory status of gingiva, but GCF cytokine levels were not affected.
Assuntos
Líquido do Sulco Gengival/química , Gengivite/fisiopatologia , Hormônios Esteroides Gonadais/análise , Ciclo Menstrual/fisiologia , Adulto , Biomarcadores/análise , Índice de Placa Dentária , Dinoprostona/análise , Estrogênios/análise , Feminino , Hemorragia Gengival/classificação , Gengivite/classificação , Humanos , Interleucina-6/análise , Menstruação/fisiologia , Ovulação/fisiologia , Índice Periodontal , Inibidor 2 de Ativador de Plasminogênio/análise , Progesterona/análise , Saliva/química , Ativador de Plasminogênio Tecidual/análise , Adulto JovemRESUMO
BACKGROUND: The contribution of nitric oxide (NO) to immune response and matrix degradation in the periodontal environment suggests a role for NO and NO-synthase (NOS) activity in the pathogenesis of cyclosporin A (CsA)-induced gingival overgrowth (GO). However, current knowledge on this topic is limited to experimental animal studies. The present study was undertaken on the basis of a hypothesis whether altered nitrite/nitrate levels in gingival crevicular fluid (GCF) and endothelial NOS (eNOS) and inducible NOS (iNOS) immunoreactivity in gingiva of CsA-treated patients contribute to the pathogenesis of CsA-induced GO. METHODS: Twenty-four CsA-medicated renal transplant patients with GO (GO+; n = 12) or without GO (GO-; n = 12), 10 gingivitis, and 10 healthy subjects were included in the study. GCF samples from two proximal sites facing interdental papilla were collected, and papilla was excised. iNOS and eNOS were determined by immunohistochemistry. GCF nitrite/nitrate levels were analyzed based on the Griess reaction. RESULTS: Weak iNOS immunostaining was observed in the healthy and GO- groups. In the gingivitis and GO+ groups, iNOS immunostaining significantly increased in connective tissue. Epithelial immunostaining of iNOS was localized to basal keratinocytes and the lower layer of stratum (str.) spinosum in the gingivitis group. In the GO+ group, iNOS immunostaining was differentially localized to keratinocytes of str. superficiale but considerably decreased in the str. basale. Weak eNOS immunostaining was found in the healthy and GO- groups, whereas higher immunostaining was observed in the gingivitis and GO+ groups. No intergroup differences were observed regarding nitrite/nitrate levels in GCF. CONCLUSION: CsA differentially upregulated iNOS, but not eNOS, in overgrown gingiva, which may play a pivotal role in the pathogenesis of CsA-induced GO.
Assuntos
Ciclosporina/efeitos adversos , Crescimento Excessivo da Gengiva/induzido quimicamente , Imunossupressores/efeitos adversos , Óxido Nítrico Sintase Tipo III/análise , Óxido Nítrico Sintase Tipo II/análise , Adolescente , Adulto , Tecido Conjuntivo/efeitos dos fármacos , Tecido Conjuntivo/enzimologia , Tecido Conjuntivo/patologia , Índice de Placa Dentária , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Epitélio/efeitos dos fármacos , Epitélio/enzimologia , Epitélio/patologia , Feminino , Gengiva/efeitos dos fármacos , Gengiva/enzimologia , Gengiva/patologia , Líquido do Sulco Gengival/química , Líquido do Sulco Gengival/enzimologia , Crescimento Excessivo da Gengiva/enzimologia , Crescimento Excessivo da Gengiva/patologia , Gengivite/enzimologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imuno-Histoquímica , Queratinócitos/efeitos dos fármacos , Queratinócitos/enzimologia , Queratinócitos/patologia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Nitratos/análise , Nitritos/análise , Índice Periodontal , Adulto JovemRESUMO
BACKGROUND: The aim of the present study was to evaluate the therapeutic efficacy of vasoactive intestinal peptide (VIP), an immunoregulatory molecule, in experimental periodontitis. METHODS: Sixty-three male Sprague-Dawley rats were divided into five groups: control; lipopolysaccharide (LPS); LPS + 0.1 nmol VIP; LPS + 1 nmol VIP; and LPS + 10 nmol VIP. Saline was injected into the gingiva of control rats on days 1, 3, and 5, whereas the other groups received injections of Escherichia coli LPS. VIP groups received intraperitoneal injections of relevant dosages on days 2, 4, 6, 8, and 10. The control and LPS groups were given saline instead of VIP in the same manner. On day 11, serum samples were obtained, and rats were sacrificed. Alveolar bone loss; serum levels of tumor necrosis factor-alpha, interleukin (IL)-1beta, -10, and -18, soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), and osteoprotegerin (OPG); and the immune expression of RANKL and OPG were evaluated. RESULTS: The application of VIP caused a dose-dependent decline in alveolar bone loss compared to the LPS group, but the differences were not significant (P >0.05). A reduction in the histologic findings of inflammation was observed in all VIP groups. The 1- and 10-nmol VIP groups showed significantly lower serum sRANKL and OPG levels compared to the LPS group (P <0.05). The number of positively stained vessels for endothelial OPG was greater in the 1-nmol VIP group than in the LPS group (P <0.05). CONCLUSION: When periodontitis was induced by E. coli LPS, VIP downregulated the inflammatory response and inhibited alveolar bone loss, possibly by differentially regulating the tissue levels of RANKL and OPG.
Assuntos
Escherichia coli , Fatores Imunológicos/uso terapêutico , Lipopolissacarídeos/efeitos adversos , Periodontite/prevenção & controle , Peptídeo Intestinal Vasoativo/uso terapêutico , Perda do Osso Alveolar/prevenção & controle , Animais , Relação Dose-Resposta a Droga , Regulação para Baixo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Fatores Imunológicos/administração & dosagem , Injeções Intraperitoneais , Interleucina-10/sangue , Interleucina-18/sangue , Interleucina-1beta/sangue , Masculino , Osteoprotegerina/sangue , Periodontite/sangue , Periodontite/patologia , Ligante RANK/sangue , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Cloreto de Sódio , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Peptídeo Intestinal Vasoativo/administração & dosagemRESUMO
BACKGROUND: Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) are involved in the pathogenesis of periodontitis by controlling proteolytic events in the extracellular matrix. This study was designed to investigate the association of t-PA and PAI-1 gene polymorphisms with chronic periodontitis (CP). METHODS: One hundred eighty-nine subjects were included. Genomic DNA was obtained from the peripheral blood of 84 patients with CP and 105 periodontally healthy subjects. Polymerase chain reaction and endonuclease digestion was used to genotype the 4G/5G polymorphism in the promoter region of the PAI-1 gene and the Alu-repeat insertion (I)/deletion (D) polymorphism in intron 8 of the t-PA gene. RESULTS: The genotype distributions and allele frequencies of t-PA polymorphism were not different between patients with CP and healthy subjects (24.7% I/I, 45.7% I/D, and 29.6% D/D and 30.3% I/I, 45.5% I/D, and 24.2% D/D, respectively; P >0.05). The t-PA D allele frequency was similar in patients with CP (52.4%) and healthy subjects (46.5%). PAI-1 genotype distribution in patients with CP (30.9% 4G/4G, 35.8% 4G/5G, and 33.3% 5G/5G) and healthy subjects (36.2% 4G/4G, 41.9% 4G/5G, and 21.9% 5G/5G) was also similar. The 4G allele frequency was not different between patients with CP (48.8%) and healthy subjects (57.1%) (P >0.05). The 4G allele frequency in non-smoking CP patients was significantly lower than in non-smoking, healthy subjects (chi(2) = 4.201; P = 0.040). Non-smoking CP patients also had a significantly lower percentage of 4G-positive genotypes compared to non-smoking healthy subjects (chi(2) = 5.046; P = 0.025). CONCLUSIONS: t-PA or PAI-1 genotypes are not associated with susceptibility to CP in Turkish subjects. Conversely, the 4G allele of the PAI-1 gene could be related to a decreased susceptibility to CP in non-smokers.
Assuntos
Periodontite/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Ativador de Plasminogênio Tecidual/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fumar/genética , TurquiaRESUMO
AIM: Receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) are a system of molecules that regulate bone resorption. This study aims to compare the levels of RANKL, OPG and their relative ratio in gingival crevicular fluid (GCF) of healthy and periodontal disease subjects. MATERIAL AND METHODS: GCF was obtained from healthy (n=21), gingivitis (n=22), chronic periodontitis (n=28), generalized aggressive periodontitis (n=25) and chronic periodontitis subjects under immunosuppressant therapy (n=11). RANKL and OPG concentrations in GCF were measured by enzyme-linked immunosorbent assays. RESULTS: RANKL levels were low in health and gingivitis groups, but increased in all three forms of periodontitis. OPG levels were higher in health than all three periodontitis, or gingivitis groups. There were no differences in RANKL and OPG levels between chronic and generalized aggressive periodontitis groups, whereas these were lower in the immunosuppressed chronic periodontitis group. The RANKL/OPG ratio was significantly elevated in all three periodontitis forms, compared with health or gingivitis, and positively correlated to probing pocket depth and clinical attachment level. CONCLUSION: GCF RANKL and OPG levels were oppositely regulated in periodontitis, but not gingivitis, resulting in an enhanced RANKL/OPG ratio. This ratio was similar in all three periodontitis groups and may therefore predict disease occurrence.
Assuntos
Perda do Osso Alveolar/metabolismo , Osteoprotegerina/metabolismo , Periodontite/metabolismo , Ligante RANK/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Líquido do Sulco Gengival/química , Gengivite/metabolismo , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/análise , Ligante RANK/análise , Estatísticas não ParamétricasRESUMO
BACKGROUND: Matrix metalloproteinases (MMPs) play important roles in tissue destruction mechanisms of periodontitis. MMP-8 and -13 are the major collagenases that act in extracellular matrix degradation in periodontal tissues. MMP-14 is a membrane-type MMP, and laminin (Ln)-5 is a basal membrane component. The aim of the present study was to evaluate the effects of doxycycline and alendronate on gingival tissue expression of MMP-8, -13, and -14; tissue inhibitors of MMP (TIMP)-1; and Ln-5 gamma2 chain in experimental periodontitis induced by Escherichia coli endotoxin (LPS) in rats. METHODS: Experimental periodontitis was induced by repeated injection of LPS. Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, LPS + doxycycline, LPS + alendronate, and LPS + doxycycline + alendronate. Doxycycline and alendronate were given as a single agent or as combination therapy during the 7 days of the experimental study period. On day 7, the rats were sacrificed, and the gingival tissues were analyzed immunohistochemically for expression of MMP-8, -13, and -14, Ln-5 gamma2 chain, and TIMP-1. Alveolar bone loss was evaluated morphometrically under a stereomicroscope. Data were tested statistically by Kruskal-Wallis and Mann-Whitney tests and Spearman correlation analysis. RESULTS: Alveolar bone loss was significantly higher in the LPS, doxycycline, alendronate, and combination groups than in the saline control group (all P <0.01). MMP-8 expression was significantly higher in the LPS group than in the saline control group (P = 0.001). Individual administration of doxycycline or alendronate significantly decreased the expression of MMP-8 compared to LPS (P = 0.01). Combined drug administration reduced MMP-14 significantly compared to doxycycline (P = 0.004). No significant differences in Ln-5 gamma2 chain expression were found between the study groups (P >0.05). MMP-14 significantly correlated with the Ln-5 gamma2 chain in the LPS + alendronate group (P = 0.04) and with the amount of alveolar bone loss in the LPS + doxycycline + alendronate group (P = 0.03). CONCLUSIONS: Our findings suggest that alendronate and/or doxycycline may inhibit MMP-8 expression significantly; particularly, their combined administration may provide beneficial effects in periodontal treatment. Moreover, individual administration of alendronate and doxycycline results in significant increases in TIMP-1 expression in gingiva. However, these effects of combined low-dose doxycycline and alendronate on MMPs and TIMP should be verified by clinical human trials before these agents are used in dental practice.
Assuntos
Moléculas de Adesão Celular/biossíntese , Metaloproteinases da Matriz/biossíntese , Periodontite/tratamento farmacológico , Periodontite/enzimologia , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Alendronato/uso terapêutico , Perda do Osso Alveolar/enzimologia , Animais , Antibacterianos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Moléculas de Adesão Celular/análise , Doxiciclina/uso terapêutico , Combinação de Medicamentos , Escherichia coli , Gengiva/enzimologia , Técnicas Imunoenzimáticas , Lipopolissacarídeos , Masculino , Inibidores de Metaloproteinases de Matriz , Metaloproteinases da Matriz/análise , Inibidores de Proteases/uso terapêutico , Ratos , Ratos Sprague-Dawley , Estatísticas não Paramétricas , Inibidor Tecidual de Metaloproteinase-1/análise , CalininaRESUMO
AIM: Levels of interleukin-1alpha (IL-1alpha) are elevated in periodontal inflammation. IL-1A gene polymorphisms are associated with inflammatory diseases. This study aimed to investigate IL-1A gene polymorphism in Cyclosporin A (CsA)-treated renal transplant patients and investigate the association between this polymorphism and gingival crevicular fluid (GCF) levels of several cytokines. MATERIALS AND METHODS: Fifty-one renal transplant patients on CsA treatment (25 with and 26 without gingival overgrowth) and 29 healthy controls were recruited for the study. Demographic, pharmacological and periodontal parameters were recorded and gingival overgrowth was assessed. RESULTS: Multiple regression analysis showed that genotype was significantly associated with gingival overgrowth (p=0.02). Carriage of the IL-1A (-889) T allele was strongly protective [95% confidence interval (CI): 0.046-0.77], although not significantly associated with IL-1alpha protein levels in GCF. IL-1alpha, IL-1beta and IL-8, but not IL-6, were detected in GCF of CsA-treated patients, but none of them was significantly associated with gingival overgrowth. CONCLUSIONS: This study is the first to associate a gene polymorphism as a risk factor for CsA-induced gingival overgrowth in renal transplant patients, demonstrating that IL-1A polymorphism might alter individual susceptibility to CsA. However, there was no association between GCF cytokine levels and the presence of gingival overgrowth or patient IL-1A genotype.
Assuntos
Ciclosporina/efeitos adversos , Hiperplasia Gengival/induzido quimicamente , Imunossupressores/efeitos adversos , Interleucina-1alfa/genética , Transplante de Rim , Polimorfismo Genético/genética , Adulto , Fatores Etários , Alelos , Citosina , Feminino , Predisposição Genética para Doença , Genótipo , Líquido do Sulco Gengival/química , Hiperplasia Gengival/genética , Humanos , Interleucina-1alfa/análise , Interleucina-1beta/análise , Interleucina-6/análise , Interleucina-8/análise , Masculino , Fatores de Risco , TiminaRESUMO
BACKGROUND: Periodontal diseases may differ, which could be attributed to the factors that might modify the host response to microbial pathogens. The aim of this study was to examine gingival crevicular fluid (GCF) levels of EMAP-II, MIP-1alpha and MIP-1beta in patients with different periodontal diseases (EMAP-II, endothelial-monocyte activating polypeptide; MIP-1alpha, macrophage inflammatory protein-1alpha; MIP-1beta, macrophage inflammatory protein-1beta). METHODS: Eighty-two subjects were included in this study. GCF samples were collected from 26 patients with generalized aggressive periodontitis (G-AgP), 26 patients with chronic periodontitis (CP), 15 with gingivitis and 15 periodontally healthy subjects. Clinical periodontal parameters were recorded. GCF EMAP-II, MIP-1alpha and MIP-1beta levels were quantified by enzyme immunoassay. RESULTS: GCF EMAP-II levels of G-AgP group were higher than those of gingivitis and healthy groups (p<0.008). G-AgP group showed a trend for higher GCF EMAP-II levels compared with CP group (p>0.008). G-AgP, CP, gingivitis and healthy groups had comparable GCF MIP-1alpha and MIP-1beta levels. CONCLUSIONS: Our results suggest that elevated GCF EMAP-II could contribute to the pathogenesis of G-AgP. Alternatively, EMAP-II reflects the extent of the inflammatory activity in the periodontal tissues. At this point, MIP-1alpha and MIP-1beta levels in GCF do not seem to play a discriminatory role in periodontitis. Our data document for the first time the essential role of EMAP-II in the pathogenesis of different periodontal diseases.
Assuntos
Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Proteínas Inflamatórias de Macrófagos/metabolismo , Proteínas de Neoplasias/metabolismo , Periodontite/metabolismo , Proteínas de Ligação a RNA/metabolismo , Doença Aguda , Adulto , Estudos de Casos e Controles , Quimiocina CCL3 , Quimiocina CCL4 , Doença Crônica , Citocinas/análise , Feminino , Líquido do Sulco Gengival/química , Gengivite/metabolismo , Humanos , Técnicas Imunoenzimáticas , Mediadores da Inflamação/análise , Proteínas Inflamatórias de Macrófagos/análise , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Índice Periodontal , Proteínas de Ligação a RNA/análise , Estatísticas não ParamétricasRESUMO
BACKGROUND: The aim of the present study was 1) to evaluate the possible effects of therapeutic usage of omega-3 fatty acid on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), platelet activating factor (PAF), and leukotriene B4 (LTB4) in endotoxin-induced periodontitis in rats and 2) to investigate whether prophylactic usage provides any additional benefits to therapeutic doses of omega-3 fatty acid. METHODS: Experimental periodontitis was induced by repeated injection of Escherichia coli lipopolysaccharide (LPS). Thirty-six adult male Sprague-Dawley rats were divided into four study groups: 1) saline controls; 2) LPS; 3) therapeutic omega-3 fatty acid (TO3); and 4) prophylactic plus therapeutic omega-3 fatty acid (P + TO3) groups. In TO3 group, omega-3 fatty acid was given for 15 days following induction of experimental periodontitis. In P + TO3 group, omega-3 fatty acid was started 15 days before baseline, and then periodontitis was induced at baseline and omega-3 fatty acid was continued for 15 days after baseline. On day 15 after baseline, all rats were anesthetized and sacrificed. PGE2, PGF2alpha, and LTB4 levels in gingival tissue samples were analyzed by enzyme immunoassay and PAF levels were analyzed by radioimmonoassay. Data were evaluated statistically by using parametric tests. RESULTS: LPS injection resulted in significant amount of bone loss (P<0.05). Neither therapeutic nor prophylactic plus therapeutic administration of omega-3 fatty acid with the doses and duration of therapy used in the present study was effective in preventing endotoxin-induced alveolar bone loss. TO3 group exhibited significant decreases in the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF compared to the LPS group (P<0.05). PGE2 and PGF2alpha levels in TO3 group were similar to those of the saline group (P>0.05), while LTB4 and PAF levels were statistically higher than the saline group (P<0.05). Prophylactic plus therapeutic usage of omega-3 fatty acid provided similar levels of all these mediators to those of the saline controls (P>0.05). CONCLUSIONS: Therapeutic omega-3 fatty acid significantly reduced the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF in experimental periodontitis. Furthermore, prophylactic usage of omega-3 fatty acid provided additional beneficial effects to the therapeutic administration by decreasing the gingival tissue levels of these mediators to levels of healthy tissue. These findings should be verified by longitudinal clinical trials investigating clinical and biochemical periodontal parameters to better define the possible role of omega-3 fatty acids in periodontal treatment.
Assuntos
Perda do Osso Alveolar/prevenção & controle , Ácidos Graxos Ômega-3/uso terapêutico , Mediadores da Inflamação/metabolismo , Periodontite/tratamento farmacológico , Periodontite/metabolismo , Perda do Osso Alveolar/metabolismo , Análise de Variância , Animais , Dinoprosta/análise , Dinoprosta/biossíntese , Dinoprostona/análise , Dinoprostona/biossíntese , Endotoxinas/farmacologia , Gengiva/química , Gengiva/metabolismo , Técnicas Imunoenzimáticas , Leucotrieno B4/análise , Leucotrieno B4/biossíntese , Masculino , Periodontite/induzido quimicamente , Fator de Ativação de Plaquetas/análise , Fator de Ativação de Plaquetas/biossíntese , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Estatísticas não ParamétricasRESUMO
BACKGROUND: Apoptosis plays an important role in the maintenance of tissue homeostasis. Considering that apoptosis mediators may play a role in the pathogenesis of drug-induced gingival overgrowth, this study was conducted to evaluate p53, bcl-2, and interleukin-15 (IL-15) levels in gingival crevicular fluid (GCF) of cyclosporin A (CsA)-treated patients. METHODS: Twenty renal transplant patients exhibiting CsA-induced gingival overgrowth and 15 systemically healthy gingivitis patients were included in the study; 15 systemically and periodontally healthy volunteer subjects served as the healthy control group. GCF samples were obtained from one interdental site with gingival overgrowth (GO+) and one site without (GO-) from each CsA-treated patient; hyperplasia index, probing depth, papilla bleeding index, and plaque presence were recorded. One site from each gingivitis patient and healthy control was selected, GCF samples were obtained, and the same clinical parameters were recorded. GCF p53, bcl-2, and IL-15 levels were analyzed by enzyme-linked immunosorbent assay. The results were tested statistically. RESULTS: p53 and bcl-2 levels were below the minimum detectable level in all GCF samples analyzed. CsA GO+ and CsA GO- sites, as well as gingivitis sites, exhibited significantly higher GCF levels of IL-15 compared to healthy controls (P<0.05). The difference between CsA GO+ sites and gingivitis sites was not statistically significant, although the total amount of IL-15 in CsA GO+ sites was lower than gingivitis sites (P>0.05). The total amount of IL-15 in CsA GO- sites was significantly lower than gingivitis sites (P<0.05). No significant correlation was found between the clinical parameters and GCF IL-15 levels (P>0.05). CONCLUSIONS: The pathogenesis of CsA-induced gingival overgrowth is multifactorial. The findings of the present study indicate that IL-15 may play a role in the pathogenesis of CsA-induced gingival overgrowth due to its interactions with CsA and its role in apoptosis and inflammation.