RESUMO
BACKGROUND: Angiotensin-converting enzyme (ACE) downregulates the activity of bradykinin, a potent proinflammatory and immunostimulatory peptide liberated from an internal portion of kininogens. Here, we asked whether periodontitis is worsened in patients under antihypertensive treatment with ACE inhibitors. METHODS: Periodontal parameters were recorded from 30 individuals taking ACE inhibitors (case) and 35 taking a non-ACE inhibitor medication (control). Data were analyzed by nonparametric and parametric statistical tests. RESULTS: Most sociodemographic figures were similar in both groups. However, family income was statistically higher in the control group, and the percentage of sites with visible plaque (PL) was statistically higher in the case group (P = 0.043 and P = 0.005, respectively). The prevalence of individuals with chronic periodontitis varied from 31.5% in the control group to 63.4% in the case group (P = 0.001). Patients in the case group presented a 3.2-fold higher risk of having sites with pocket depth ≥5 mm and a 2.9-fold higher risk of having sites with clinical attachment loss ≥5 mm in comparison with those in the control group (P = 0.009 and P = 0.001, respectively; adjusted for family income and visible PL). CONCLUSION: Angiotensin-converting enzyme inhibitors may increase the prevalence and extent of chronic periodontitis in Brazilian patients.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Periodontite Crônica/induzido quimicamente , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Estudos de Casos e Controles , Periodontite Crônica/patologia , Feminino , Bolsa Gengival/induzido quimicamente , Bolsa Gengival/patologia , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVE: Hereditary gingival fibromatosis (HGF) is a benign disorder manifested by fibrous enlargement of keratinized gingiva. Evidence exists concerning the role of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in mediating normal and pathological processes, including HGF. Nevertheless, there are few and contradictory results on the analysis of MMPs and TIMPs transcripts in this pathology. MATERIAL AND METHODS: We studied the expression of the transcripts encoding MMP-1, -2 and -9 and TIMP-1 and -2 in gingival biopsies, obtained from three cases of HGF within a family, by semi-quantitative reverse transcriptase-polymerase chain reaction analysis. Samples were also processed for gelatin zymography. RESULTS: Except for MMP-9, most transcripts presented a higher level of expression in biopsies from HGF patients compared with control subjects. Accordingly, MMP-9 gelatinase activity was detected at low and similar levels among samples. Moreover, MMP-2 enzymatic activity was not detected at all. CONCLUSION: The mRNA expression of MMP-1 and -2 and TIMP-1 and -2 does not explain the gingival overgrowth presented in these cases. In addition, it is suggested that the gene expression of those molecules in the course of HGF is regulated at the translational or post-translational level.
Assuntos
Fibromatose Gengival/genética , Metaloproteinases da Matriz/análise , Inibidores Teciduais de Metaloproteinases/análise , Biópsia , Precursores Enzimáticos/análise , Precursores Enzimáticos/genética , Fibromatose Gengival/enzimologia , Regulação Enzimológica da Expressão Gênica/genética , Gengiva/enzimologia , Gengiva/patologia , Humanos , Metaloproteinase 1 da Matriz/análise , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/genética , Metaloproteinases da Matriz/genética , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidores Teciduais de Metaloproteinases/genética , Transcrição Gênica/genéticaRESUMO
OBJECTIVES: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are known to be involved in the periodontal disease process. Results of in vivo MMPs and TIMPs gene expressions in the gingiva, though, are still controversial. In the present study, we compared the gene expression of MMP-1, -2, -9, -13 and TIMP-1, -2 in healthy and inflamed gingiva. METHODS: 38 gingival samples were collected from gingivitis (n = 10), advanced chronic periodontitis (n = 10), generalized aggressive periodontitis (n = 8) and periodontally healthy individuals (n = 10). Total RNA isolated from those samples was subjected to reverse transcription followed by amplification by polymerase chain reaction (RT-PCR). Products were visualized in agarose gels and quantified by optical densitometry. Samples were also processed for gelatin zymography and Western blotting for MMP-2 and MMP-9 in order to assess for post-transcriptional MMP regulation at the protein level. RESULTS: The frequencies and levels of transcripts encoding MMPs and TIMPs were found to be not significantly different among groups (p > 0.05, Fisher's Exact and Kruskall-Wallis tests). There is a trend towards higher MMP-2 and -9 gelatinase activities in the inflamed samples, although not statistically significant. In contrast, zymography and Western blotting studies show that MMP-2 is virtually absent in the chronic periodontitis group. CONCLUSION: These results could reflect a complex regulation of MMPs and TIMPs' gene expression in the course of gingival inflammation. They also reveal a great biological diversity even among individuals with similar periodontal status.
Assuntos
Periodontite Agressiva/metabolismo , Periodontite Crônica/metabolismo , Gengivite/metabolismo , Metaloproteases/biossíntese , Inibidores Teciduais de Metaloproteinases/biossíntese , Adulto , Western Blotting , Estudos de Casos e Controles , Expressão Gênica , Humanos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Glycosaminoglycans in normal and cyclosporin-induced gingival overgrowth were extracted by papain digestion and purified by Mono Q-FPLC chromatography. The purified glycosaminoglycans were analyzed by agarose gel electrophoresis and by the pattern of degradation products formed by chondroitin lyases on HPLC chromatography. Our results on the glycosaminoglycan composition showed presence of chondroitin 4- and 6-sulfate, dermatan sulfate, heparan sulfate and hyaluronic acid in both normal gingiva and cyclosporin-induced gingival overgrowth. The total and relative amounts of glycosaminoglycans were similar between normal and overgrown gingiva. This suggests that the glycosaminoglycan composition is not changed in cyclosporin-induced gingival overgrowth. Our present biochemical results conflict with histochemical and biosynthetic data previously reported by other groups. Those studies suggested that the affected tissues contained higher levels of glycosaminoglycans and that cyclosporin induced comparably high levels of these compounds in in vitro cultures of gingival fibroblasts. Therefore, these discrepant results suggest that a cyclosporin-induced increase on gingival glycosaminoglycans still remains an open question. The implications of these conflicting results are discussed.
Assuntos
Ciclosporina/efeitos adversos , Crescimento Excessivo da Gengiva/induzido quimicamente , Crescimento Excessivo da Gengiva/metabolismo , Glicosaminoglicanos/análise , Imunossupressores/efeitos adversos , Adulto , Sulfatos de Condroitina/análise , Cromatografia Líquida de Alta Pressão , Dermatan Sulfato/análise , Eletroforese em Gel de Ágar , Proteínas da Matriz Extracelular/análise , Heparitina Sulfato/análise , Humanos , Ácido Hialurônico/análise , Pessoa de Meia-IdadeRESUMO
The aim of this study was to determine the effect of subgingival scaling and root planing on healing of the distal surface of second molars following extraction of third molars. Twenty-eight patients with contralateral erupted third molars and pocket depths greater than or equal to 3 mm on the distal surface of the second molars participated in this study. Measurements of supragingival bacterial plaque, bleeding on probing, pocket depth, and relative attachment level were performed at baseline and 2 months after treatment. Extraction of contralateral third molars was carried out simultaneously. The experimental site received thorough scaling and root planing of the distal surface of the second molar, while the control site received extraction alone. Experimental sites showed significant improvement in all clinical parameters assessed compared to the control sites. In conclusion, periodontal lesions on the distal of second molars can be significantly improved following scaling and root planing after extraction of third molars.
Assuntos
Raspagem Dentária , Dente Serotino/cirurgia , Aplainamento Radicular , Extração Dentária , Cicatrização/fisiologia , Adulto , Placa Dentária/fisiopatologia , Placa Dentária/cirurgia , Feminino , Hemorragia Gengival/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Dente Molar/fisiopatologia , Bolsa Periodontal/fisiopatologia , Bolsa Periodontal/cirurgia , Periodonto/fisiopatologia , Período Pós-OperatórioRESUMO
Lysyl oxidase catalyzes the final known enzymatic step required for collagen and elastin cross-linking. A cross-linked collagenous extracellular matrix is required for bone formation. This study investigated whether lysyl oxidase, like its type I collagen substrate, is down-regulated by basic fibroblast growth factor (bFGF) in osteoblastic MC3T3-E1 cells and determined the degree of post-transcriptional control. Steady-state lysyl oxidase mRNA levels decreased to 30% of control after 24 h of treatment with 1 and 10 nm bFGF. This regulation was time-dependent. COL1A1 mRNA levels declined to less than 10% of control after 24 h of bFGF treatment. Media lysyl oxidase activity decreased consistent with steady-state mRNA changes in cultures that were refed after 24 h of growth factor treatment. Interestingly, treatment of MC3T3-E1 cells with 0.01-0.1 nm bFGF for 24 h and treatment with 1 nm bFGF for up to 12 h resulted in a modest stimulation of lysyl oxidase gene expression and enzyme activity. At least 50% of the down-regulation of lysyl oxidase was shown to be posttranscriptional. New protein synthesis was not required for the down-regulation by bFGF, but cycloheximide did increase constitutive lysyl oxidase mRNA levels 2.5-fold. We conclude that lysyl oxidase and COL1A1 are regulated similarly by bFGF in these osteoblastic cells, consistent with the in vivo effects of this growth factor on bone collagen metabolism.
Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacologia , Proteína-Lisina 6-Oxidase/genética , Proteína-Lisina 6-Oxidase/metabolismo , Células 3T3 , Animais , Colágeno/genética , Cicloeximida/farmacologia , Relação Dose-Resposta a Droga , Regulação para Baixo , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Cinética , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/enzimologia , Inibidores da Síntese de Proteínas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/farmacologiaRESUMO
The final enzymatic step required for collagen cross-linking is the extracellular oxidative deamination of peptidyl-lysine and -hydroxylysine residues by lysyl oxidase. A cross-linked collagenous extracellular matrix is required for bone formation. The goals of this study were to compare the transforming growth factor (TGF)-beta 1 regulation of lysyl oxidase enzyme activity and steady state mRNA levels to changes in COL1A1 mRNA levels in MC3T3-E1 osteoblastic cells. TGF-beta 1 increased steady state lysyl oxidase and COL1A1 mRNA levels in a dose- and time-dependent manner. The increase in lysyl oxidase mRNA levels was transient, peaking at 12 h and 8.8 times controls in cells treated with 400 pM TGF-beta 1. COL1A1 steady state mRNA levels increased maximally to 3.5-fold of controls. Development of increased lysyl oxidase enzyme activity was delayed and was of slightly lower magnitude than the increase in its mRNA levels. This suggested limiting post-translational processing of lysyl oxidase proenzyme. Pulse-labeling/immunoprecipitation studies demonstrated slow proenzyme secretion and proteolytic processing. Development and application of an independent assay for lysyl oxidase proenzyme proteolytic processing activity verified its proportionately lower stimulation by 400 pM TGF-beta 1. Thus, lysyl oxidase regulation by TGF-beta 1 in osteoblastic cell cultures occurs at both pre- and post-translational levels. This regulation is consistent with increased production of a collagenous extracellular matrix.
Assuntos
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteína-Lisina 6-Oxidase/biossíntese , Fator de Crescimento Transformador beta/farmacologia , Células 3T3 , Animais , Colágeno/biossíntese , Eletroforese em Gel de Poliacrilamida , Endopeptidases/biossíntese , Humanos , Cinética , Camundongos , Osteoblastos , Proteína-Lisina 6-Oxidase/isolamento & purificação , Proteína-Lisina 6-Oxidase/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/metabolismo , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes/farmacologiaRESUMO
The cloning of the 3'-untranslated region of rat lysyl oxidase cDNA was completed. cDNA clones were generated by reverse transcriptase PCR from neonatal rat aorta smooth muscle cell RNA, and sequenced. Several polyadenylated clones were obtained, providing 2.1 kb of new sequence. Clones were polyadenylated at three different positions. The cDNA clones were verified by PCR-cloning and sequencing of genomic DNA, and by Northern blotting studies. Evidence is presented that the polyadenylation patterns of rat lysyl oxidase mRNAs are similar, but not identical to mouse or human transcripts. Interestingly, the nonconsensus polyadenylations in rat did not occur at the same positions as was found in mouse lysyl oxidase cDNAs. Multiple transcription initiation sites were found by primer extension mapping. Thus, the complex pattern of rat lysyl oxidase mRNAs on Northern blots is principally due to differential use of polyadenylation signals, and to the occurrence of multiple transcription initiation sites. All clones lacked a previously reported 258 bp segment nearly identical to a conserved segment of the 3'-untranslated region of elastin cDNA. We conclude that the elastin-like sequence previously reported in rat lysyl oxidase cDNA is not a species-specific sequence, and most probably resulted from spurious ligation reactions during construction of the cDNA library.