Polimorfismo genético associado a doença renal crônica e periodontite: uma revisão sistemática de literatura / Genetic polymorphism associated with chronic kidney disease and periodontitis: a systematic literature review / Polimorfismo genético asociado a enfermedad renal crónica y periodontitis: una revisión sistemática de la literatura

A periodontite é uma doença infecto-inflamatória associada ao biofilme disbiótico que afeta os tecidos de proteção e de suporte dos dentes. O processo inflamatório que ocorre durante a periodontite tem sido associado à inflamação sistêmica em pacientes com doença renal crônica. Os polimorfismos genéticos são alterações no DNA que podem ter classificações diferentes dependendo da mutação gerada, e podem ser criados ou destruídos. Objetivo: O objetivo desta revisão sistemática da literatura foi elucidar a seguinte questão: os polimorfismos genéticos estão associados à doença renal crônica e à periodontite? Material e Métodos: A pesquisa foi realizada no PubMed, Biblioteca Cochrane, EMBASE, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Bibliografia Brasileira de Odontologia (BBO), Biblioteca Virtual em Saúde (BVS), SciELO, Scopus, Web of Science e bases de dados de literatura cinzenta (Google Scholar) sem restrições de data ou idioma em 28 de junho de 2021 e atualizada em 26 de janeiro de 2023. Os descritores padronizados (Medical Subject Headings, MeSH) utilizados foram: "polimorfismo genético", "doença renal crônica" e "periodontite", de acordo com o banco de dados consultado, utilizando os operadores booleanos "AND". Resultado: 25 publicações foram identificadas. Após a análise do título, do resumo e do texto completo, 6 estudos de caso-controle foram selecionados para análise. Todos incluíam artigos investigando o papel de diferentes polimorfismos genéticos em ambas as doenças. Alguns genes apresentavam uma relação próxima com o perfil inflamatório que caracteriza ambas as doenças. Conclusão: Entre os polimorfismos estudados, os polimorfismos VNTR no gene IL4 e MCP-1-2518 A/G apresentaram uma associação positiva tanto com a periodontite quanto com a doença renal crônica. Entretanto, são necessários mais estudos para melhor compreensão do papel dos polimorfismos genéticos nessas doenças.

Periodontitis is an infectious-inflammatory disease associated with dysbiotic biofilm that affects the protective and supporting tissues of the teeth. The inflammatory process that occurs during periodontitis has been associated with systemic inflammation in patients with chronic kidney disease. Genetic polymorphisms are changes in DNA that can have different classifications depending on the mutation generated, and can be created or destroyed. Objective: The aim of this systematic review of the literature was to elucidate the following question: are genetic polymorphisms associated with chronic kidney disease and periodontitis? Material and Methods: The search was conducted in PubMed, Cochrane Library, EMBASE, Latin American and Caribbean Literature on Health Sciences (LILACS), Brazilian Bibliography of Dentistry (BBO), Virtual Health Library (VHL), SciELO, Scopus, Web of Science and gray literature databases (Google Scholar) without date or language restrictions on June 28, 2021 and updated on January 26, 2023. The standardized descriptors (Medical Subject Headings, MeSH) used were: "genetic polymorphism", "chronic kidney disease" and "periodontitis", according to the database consulted, using the Boolean operators "AND". Result: 25 publications were identified. After reviewing the title, abstract, and full text, 6 case-control studies were selected for analysis. All included articles investigating the role of different genetic polymorphisms in both diseases. Some genes showed a close relationship with the inflammatory profile that characterizes both diseases. Conclusion: Among the polymorphisms studied, the VNTR polymorphisms in the IL4 gene and MCP- 1-2518 A/G showed a positive association with both periodontitis and chronic kidney disease. However, further studies are needed to better understand the role of genetic polymorphisms in these diseases.

La periodontitis es una enfermedad infeccioso-inflamatoria asociada a un biofilm disbiótico que afecta a los tejidos protectores y de soporte de los dientes. El proceso inflamatorio que se produce durante la periodontitis se ha asociado con la inflamación sistémica en pacientes con enfermedad renal crónica. Los polimorfismos genéticos son cambios en el ADN que pueden tener diferentes clasificaciones dependiendo de la mutación generada, pudiendo ser creados o destruidos. Objetivo: El objetivo de esta revisión sistemática de la literatura fue dilucidar la siguiente pregunta: ¿están asociados los polimorfismos genéticos con la enfermedad renal crónica y la periodontitis? Material y Métodos: La búsqueda fue realizada en PubMed, Cochrane Library, EMBASE, Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS), Bibliografía Brasileña de Odontología (BBO), Biblioteca Virtual en Salud (BVS), SciELO, Scopus, Web of Science y bases de datos de literatura gris (Google Scholar) sin restricciones de fecha o idioma el 28 de junio de 2021 y actualizada el 26 de enero de 2023. Los descriptores normalizados (Medical Subject Headings, MeSH) utilizados fueron: "polimorfismo genético", "enfermedad renal crónica" y "periodontitis", según la base de datos consultada, utilizando los operadores booleanos "AND". Resultado: Se identificaron 25 publicaciones. Tras analizar el título, el resumen y el texto completo, se seleccionaron 6 estudios de casos y controles para su análisis. Todos los trabajos incluidos investigaban el papel de diferentes polimorfismos genéticos en ambas enfermedades. Algunos genes mostraron una estrecha relación con el perfil inflamatorio que caracteriza a ambas enfermedades. Conclusión: Entre los polimorfismos estudiados, los polimorfismos VNTR en el gen IL4 y MCP-1-2518 A/G mostraron una asociación positiva tanto con la periodontitis como con la enfermedad renal crónica. Sin embargo, se necesitan más estudios para comprender mejor el papel de los polimorfismos genéticos en estas enfermedades.

Condição bucal de comunidades em vulnerabilidade social: análise descritiva de um projeto voluntário paranaense / Oral health condition of communities in social vulnerability: descriptive analysis of a volunteer project in Paraná

O presente trabalho relata o impacto social e o papel do cirurgião--dentista nas ações do Projeto Pró-Riso por meio de análise descritiva das ações. O projeto Pró-Riso é uma iniciativa voluntária, sem fins políticos, religiosos ou lucrativos, que leva atendimento odontológico, assistência médica e educação em saúde a comunidades em vulnerabilidade social. Foi realizada a análise dos prontuários dos pacientes atendidos pelo projeto em 2019. As ações ocorreram nas comunidades do Pilarzinho e Caximba (Bairros do município de Curitiba) e Amparo (comunidade isolada em Área de Proteção Ambiental no município litorâneo de Paranaguá), locais de elevada prevalência de doenças bucais. Tal situação reflete uma importante questão de Saúde Pública para o país. Os resultados mostram que foram atendidos 260 pacientes, com diversas necessidades de tratamento bucal. Destes, 63% tiveram seus tratamentos concluídos nas ações. Ressalta-se, assim, a importância de trabalhos sociais que proporcionem melhor qualidade de vida e saúde a comunidades em vulnerabilidade social. (AU)

This paper reports the social impact and role of the dentist in the actions of the Pró-Riso Project through descriptive actions analysis. The Pró-Riso project is a voluntary, non-political, religious or for profit initiative that takes dental care, medical assistance and health education to communities in social vulnerability. An analysis of the medical patients records assisted by the project in 2019 was carried out. The actions took place in the communities of Pilarzinho and Caximba (Curitiba Municipality neighborhoods) and Amparo (isolated community in an Environmental Protection Area in the coastal municipality of Paranaguá), places of high prevalence of oral diseases. This situation reflects an important Public Health issue for the country. The results show that 260 patients were treated, with different needs for oral treatment. Of these, 63% had their treatments completed in the actions. Thus, the importance of social work that provides better health life quality to communities in social vulnerability is highlighted. (AU)

The role of potassium channels in the endothelial dysfunction induced by periodontitis.

OBJECTIVE: Periodontitis is associated with endothelial dysfunction, which is clinically characterized by a reduction in endothelium-dependent relaxation. However, we have previously shown that impairment in endothelium-dependent relaxation is transient. Therefore, we evaluated which mediators are involved in endothelium-dependent relaxation recovery. MATERIAL AND METHODS: Rats were subjected to ligature-induced experimental periodontitis. Twenty-one days after the procedure, the animals were prepared for blood pressure recording, and the responses to acetylcholine or sodium nitroprusside were obtained before and 30 minutes after injection of a nitric oxide synthase inhibitor (L-NAME), cyclooxygenase inhibitor (Indomethacin, SC-550 and NS- 398), or calcium-dependent potassium channel blockers (apamin plus TRAM- 34). The maxilla and mandible were removed for bone loss analysis. Blood and gingivae were obtained for C-reactive protein (CRP) and myeloperoxidase (MPO) measurement, respectively. RESULTS: Experimental periodontitis induces bone loss and an increase in the gingival MPO and plasmatic CRP. Periodontitis also reduced endothelium-dependent vasodilation, a hallmark of endothelial dysfunction, 14 days after the procedure. However, the response was restored at day 21. We found that endothelium-dependent vasodilation at day 21 in ligature animals was mediated, at least in part, by the activation of endothelial calcium-activated potassium channels. CONCLUSIONS: Periodontitis induces impairment in endothelial-dependent relaxation; this impairment recovers, even in the presence of periodontitis. The recovery is mediated by the activation of endothelial calcium-activated potassium channels in ligature animals. Although important for maintenance of vascular homeostasis, this effect could mask the lack of NO, which has other beneficial properties.

The role of potassium channels in the endothelial dysfunction induced by periodontitis

Abstract Objective: Periodontitis is associated with endothelial dysfunction, which is clinically characterized by a reduction in endothelium-dependent relaxation. However, we have previously shown that impairment in endothelium-dependent relaxation is transient. Therefore, we evaluated which mediators are involved in endothelium-dependent relaxation recovery. Material and methods: Rats were subjected to ligature-induced experimental periodontitis. Twenty-one days after the procedure, the animals were prepared for blood pressure recording, and the responses to acetylcholine or sodium nitroprusside were obtained before and 30 minutes after injection of a nitric oxide synthase inhibitor (L-NAME), cyclooxygenase inhibitor (Indomethacin, SC-550 and NS- 398), or calcium-dependent potassium channel blockers (apamin plus TRAM- 34). The maxilla and mandible were removed for bone loss analysis. Blood and gingivae were obtained for C-reactive protein (CRP) and myeloperoxidase (MPO) measurement, respectively. Results: Experimental periodontitis induces bone loss and an increase in the gingival MPO and plasmatic CRP. Periodontitis also reduced endothelium-dependent vasodilation, a hallmark of endothelial dysfunction, 14 days after the procedure. However, the response was restored at day 21. We found that endothelium-dependent vasodilation at day 21 in ligature animals was mediated, at least in part, by the activation of endothelial calcium-activated potassium channels. Conclusions: Periodontitis induces impairment in endothelial-dependent relaxation; this impairment recovers, even in the presence of periodontitis. The recovery is mediated by the activation of endothelial calcium-activated potassium channels in ligature animals. Although important for maintenance of vascular homeostasis, this effect could mask the lack of NO, which has other beneficial properties.

Endothelial Cell Response to Fusobacterium nucleatum.

Vascular response is an essential aspect of an effective immune response to periodontal disease pathogens, as new blood vessel formation contributes to wound healing and inflammation. Gaining a greater understanding of the factors that affect vascular response may then contribute to future breakthroughs in dental medicine. In this study, we have characterized the endothelial cell response to the common bacterium Fusobacterium nucleatum, an important bridging species that facilitates the activity of late colonizers of the dental biofilm. Endothelial cells were infected with Fusobacterium nucleatum (strain 25586) for periods of 4, 12, 24, or 48 h. Cell proliferation and tube formation were analyzed, and expression of adhesion molecules (CD31 and CD34) and vascular endothelial growth factor (VEGF) receptors 1 and 2 was measured by fluorescence-activated cell sorter (FACS) analysis. Data indicate that F. nucleatum impaired endothelial cell proliferation and tube formation. The findings suggest that the modified endothelial cell response acts as a mechanism promoting the pathogenic progression of periodontal diseases and may potentially suggest the involvement of periodontopathogens in systemic diseases associated with periodontal inflammation.

Autogenous bone graft combined with buccal fat pad as barrier in treatment of Class II furcation defect: a case report.

The treatment of furcation defects is a complex and difficult task that may compromise the success of periodontal therapy. Here we report a new clinical treatment of a Class II furcation defect using an autogenous bone graft associated with a buccal fat pad (BFP) used as a membrane. The surgical treatment was performed following initial periodontal therapy. Post-operative follow-up appointments were performed at 3, 7, and 12 months. Clinically, after 3 and 7 months, a reduction in probing depth without bleeding on probing and an increase in vertical and horizontal clinical attachment level were observed. After 7 post-operative months, an increase in keratinized gingiva was observed. Radiographically, a significant improvement was noted, with the furcation defect almost completely closed. These results could also be observed after 12 postoperative months. It can be concluded that the combined use of autogenous bone graft and a BFP yielded clinically favorable outcome in the treatment of a mandibular Class II furcation defect.

Selective inhibition of cyclooxygenase-2: risks and benefits.

The cyclooxygenase (COX) inhibitors are the most common drugs used worldwide. COX corresponds to an evolutionarily conserved class of enzymes and has two main isoforms: COX-1, which is largely associated with physiological functions, and COX-2, which is largely associated with pathological functions. Their subproducts have an important role in inflammation and pain perception. The COX-2 selective inhibition was designed to minimize gastrointestinal complications of non-selective inhibition. However, this exclusive COX-2 inhibition was associated with serious cardiovascular events, for causing an imbalance between prostacyclin and thromboxane production. The objective of this study is to discuss the mechanisms underlying the cardiovascular effects, pointing out the advantages and disadvantages of the selective or nonselective COX inhibitors.

Inibição seletiva da ciclo-oxigenase-2: riscos e benefícios / Selective inhibition of cyclooxygenase-2: risks and benefits

Os anti-inflamatórios inibidores das ciclo-oxigenases (COX) representam a classe de fármacos mais comumente utilizada. A COX corresponde a uma classe de enzimas conservadas evolutivamente e tem duas isoformas principais: a COX-1 e a COX-2. Seus subprodutos têm papel fundamental na inflamação e na percepção da dor. Há uma grande discussão entre a inibição seletiva ou não da COX pelo fato de a mesma, além de participar dos eventos inflamatórios, ter papel fundamental na manutenção da homeostase do organismo. A inibição seletiva da COX-2 surgiu com o intuito de reduzir os efeitos deletérios gastrintestinais de uma inibição não seletiva; em contrapartida, a inibição exclusiva da COX-2 associou-se a sérios eventos cardiovasculares, por causar um desequilíbrio entre a produção de prostaciclina e tromboxano. O objetivo deste trabalho é revisar a literatura a esse respeito, apontando os prós e os contras da inibição seletiva ou não das enzimas ciclo-oxigenases.

The cyclooxygenase (COX) inhibitors are the most common drugs used worldwide. COX corresponds to an evolutionarily conserved class of enzymes and has two main isoforms: COX-1, which is largely associated with physiological functions, and COX-2, which is largely associated with pathological functions. Their subproducts have an important role in inflammation and pain perception. The COX-2 selective inhibition was designed to minimize gastrointestinal complications of non-selective inhibition. However, this exclusive COX-2 inhibition was associated with serious cardiovascular events, for causing an imbalance between prostacyclin and thromboxane production. The objective of this study is to discuss the mechanisms underlying the cardiovascular effects, pointing out the advantages and disadvantages of the selective or nonselective COX inhibitors.

Tratamento periodontal em pacientes com diabetes mellitus tipo 1 e tipo 2: caso clínico / Periodontal treatment in patients with diabetes mellitus type 1 and type 2: Case report

Introdução: é comprovado o papel do diabetes mellitus (DM) na patogenia da doença periodontal, havendo entre as duas condições uma relação bidirecional na resposta inflamatória. Pacientes portadores de diabetes mellitus com descontrole glicêmico apresentam quadro periodontal inflamatório exacerbado, observando-se, também, maior dificuldade de controle metabólico. Os tipos 1 e 2 do diabetes mellitus tem suas peculiaridades e diferenças clínicas, tanto para o controle glicêmico como para a terapia periodontal. Objetivo: apresentar dois casos clínicos de pacientes com diabetes e doença periodontal, sendo um referente a uma paciente portadora de diabetes mellitus tipo 1 e outro de um paciente portador de diabetes mellitus tipo 2. Conclusão: o resultado pós-operatório de ambos demonstrou resolução da inflamação periodontal, observando-se ausência de bolsas periodontais, supuração e sangramento à sondagem. No entanto, a abordagem clínica para cada uma das formas de diabetes foi individualizada. O uso de antibióticos sistêmicos concomitante à terapia mecânica foi necessário apenas no caso de diabetes Tipo 1.

Introduction: It is unquestionable the influence of diabetes mellitus (DM) on the pathogenesis of periodontaldisease. Both conditions have got a bidirectional relation on the inflammatory response. Patients with diabetes mellitus and without a proper metabolic control show a worse status of the periodontal disease and also more difficult in the glicemic control of DM. Types 1 and 2 of DM have their particularities and clinical differences related to the metabolic control or to the periodontal therapy. Objective: This paper reports two cases of patients with diabetes mellitus and periodontal disease, being one of DM type 1 and the other of DM type 2. Conclusion: The post-operatory result showed resolution of the periodontal inflammation in both cases. After therapy, there were no periodontal pockets nor suppuration or bleeding on probing. However,the clinical management of both forms of DM was individualized. The use of systemic antibiotics associated to periodontal therapy was necessary only for the patient with type 1 DM.

Disfunção endotelial induzida pela periodontite: envolvimento da COX-2 / Endothelial dysfunction induced by periodontitis: role of COX-2

Estudos têm mostrado um aumento do risco de doenças cardiovasculares, principalmente aterosclerose e hipertensão, entre indivíduos expostos à doença periodontal. Recentemente alguns trabalhos apontam para a presença de disfunção endotelial em pacientes com periodontite. Os dados sugerem que a inflamação sistêmica induzida pela microbiota presente na doença periodontal e a diminuição na biodisponibilidade do óxido nítrico podem ser a causa da disfunção endotelial, que por sua vez leva a doenças cardiovasculares. Um aumento na expressão vascular da ciclooxigenase-2 (COX-2) tem sido demonstrado em patologias que apresentam disfunção endotelial. A expressão da COX-2 em células endoteliais pode representar uma importante contribuição para produção de prostacilina, um derivado do ácido araquidônico com propriedades vasodilatadoras e antitrombóticas. Desta forma a indução da COX-2 em células endoteliais pode contrabalancear a redução na produção de óxido nítrico, um mediador importante no controle do tônus vascular e agregação plaquetária. Diante deste cenário, a inibição da COX-2 pode apresentar aspectos cardiovasculares deletérios durante condições inflamatórias crônicas.

Studies have shown an increased of cardiovascular diseases, mainly atherosclerosis and hypertension among subjects with periodontal disease. Recently, some works have demonstrated the presence of endothelial dysfunction in patients with periodontal disease. These data suggest the systemic inflammation induced by periodontal microbiota leads to a reduction of nitric oxide availability, the key characteristic of endothelial dysfunction, which leads to cardiovascular diseases. An increase in the vascular expression of ciclooxygenase-2 (COX-2) has been reported in some diseases that present endothelial dysfunction. Thus, endothelial cells COX-2 expression may improve prostaciclin production, an arachidonic acid derivative which has vasodilator and antitrombotic properties. Therefore, COX-2- derived prostaciclin may counteract the reduction on nitric oxide production, an important mediator on vascular tone and platelets aggregation control. Though, COX-2 selective inhibitors may be related to unexpected adverse effects in patients with endothelial dysfunction, especially during a chronic inflammatory process.

Doença periodontal x estresse: revisão de literatura / Periodontal disease versus stress: literature review

A resposta ao estresse parece estar relacionada a um mecanismo mediador entre condições psicológicas desfavoráveis e doença periodontal inflamatória. Todavia, essa relação pode ser desencadeada através de dois modelos: modelo comportamental, em que ocorre aumento no consumo de nicotina, higiene bucal menos efetiva, mudanças nos hábitos nutricionais; ou modelo biológico, através da redução do fluxo salivar, alteração da circulação gengival e alterações na resposta imune-inflamatória. Vários estudos têm realizado a associação entre a severidade da doença periodontal e fatores comportamentais como o estresse. O presente estudo teve por objetivo fazer um levantamento da literatura sobre os principais estudos envolvendo fatores psicológicos e a resposta dos tecidos periodontais frente a patógenos. Os estudos mostram, em grande parte os de corte transversal, uma tendência de relação positiva entre estresse e doença periodontal, porém uma pesquisa mais representativa é necessária para determinar o impacto do estresse e de fatores psicológicos como fatores de risco para a doença periodontal.

The stress response appears to be related to a mediating mechanism between unfavorable psychological conditions and inflammatory periodontal disease. However, this relationship can be triggered through two models: behavioral model, in which there is an increase in nicotine intake, less effective oral hygiene, changes in nutritional habits: or biological model, by reducing salivary flow, changes in gingival circulation and changes in immune-inflammatory response. Several studies have made the association between periodontal disease severity and behavioral factors such as stress. This study aimed to survey the literature on the major studies involving psychological factors and the response of periodontal tissues due to pathogens. Studies show, in large part the cross-sectional, a trend of positive relationship between stress and periodontal disease. A more representative research is necessary to determine the impact of stress and psychological factors as risks factors of periodontal disease.