Abstract The possible role of B-cell growth and differentiation-related cytokines on the pathogenesis of diabetes-related periodontitis has not been addressed so far. The aim of this study was to evaluate the effects of diabetes mellitus (DM) on the gene expression of proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS), two major cytokines associated to survival, differentiation and maturation of B cells in biopsies from gingival tissue with periodontitis. Gingival biopsies were obtained from subjects with periodontitis (n = 17), with periodontitis and DM (n = 19) as well as from periodontally and systemically healthy controls (n = 10). Gene expressions for APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were evaluated using qPCR. The expressions APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were all higher in both periodontitis groups when compared to the control group (p < 0.05). Furthermore, the expressions of BLyS, TRAP and RANKL were significantly higher in the subjects with periodontitis and DM when compared to those with periodontitis alone (p < 0.05). The mRNA levels of BLyS correlated positively with RANKL in the subjects with periodontitis and DM (p < 0.05). BLyS is overexpressed in periodontitis tissues of subjects with type 2 DM, suggesting a possible role of this cytokine on the pathogenesis DM-related periodontitis.

Abstract The aim of this review is to summarize the evidence on associations between diabetes mellitus (DM) and complications around dental implants. Electronic database searches of MEDLINE, EMBASE, JBI Database of Systematic Reviews and Implementation Reports, Cochrane Database of Systematic Reviews and the PROSPERO register were performed from 1990 up to and including May 2018, using MeSH terms and other keywords. Systematic reviews and meta-analyses investigating the associations of DM and implant complications (failure, survival, bone loss, peri-implant diseases, and post-surgery infection) were eligible. The quality of the included reviews was determined using the Assessment of Multiple Systematic Reviews Tool 2 (AMSTAR 2). Twelve systematic reviews were included. Implant survival rates ranged from 83.5% to 100%, while implant failure rates varied from 0% to 14.3% for subjects with DM. The three meta-analyses performed for event “implant failure” reported no statistically significant differences between diabetic and non-diabetic subjects. An apparently increased risk of peri-implantitis is reported in patients with DM. According to the AMSTAR 2 classification, 50% of the reviews were classified as being of “critically low”, 25% as of “low” and 25% as of “moderate” quality. Evidence indicates high levels of survival and low levels of failure of implants inserted in patients with DM. However, DM was assessed as a whole in the majority of studies and, the actual influence of hyperglycemia on implant survival/failure is still uncertain. DM/hyperglycemia seems to be associated with a high risk of peri-implantitis. However, this conclusion is based on a limited number of systematic reviews.

RESUMO Objetivo: O objetivo desta revisão sistemática foi avaliar os desfechos do tratamento dos defeitos peri-implantares, por meio da técnica da Regeneração Óssea Guiada. Métodos: Uma pesquisa bibliográfica, baseada na metodologia PICO, foi realizada nas bases de dados eletrônica PubMed/Medline, SciELO, Lilacs periódicos Capes e Cochrane Library. Foram incluídos estudos que utilizaram matriz mineral bovina, associado a uma membrana de colágeno para o tratamento da peri-implantite por Regeneração Óssea Guiada. Resultados: De 1.163 estudos, 10 foram incluídos nesta revisão, após aplicação dos critérios de avaliação. Um total de 269 implantes foram tratados em 260 pacientes. O período de acompanhamento variou de 6 a 48 meses. Os estudos avaliados reportaram redução média da profundidade de sondagem, ganho de inserção clínica e preenchimento ósseo do defeito. Devido à heterogeneidade dos estudos não foi possível realizar metanálise. Conclusão: O tratamento das lesões peri-implantares, com a técnica da Regeneração Óssea Guiada é uma modalidade viável de tratamento, proporcionando redução do sangramento à sondagem, bem como o ganho de inserção clínica. Porém, o completo preenchimento do defeito, é um resultado imprevisível.

ABSTRACT Objective: The objective of this review was to evaluate the outcomes of the treatment of peri-implant defects, using Guided Bone Regeneration. Methods: A literature search was performed based on the PICO methodology in the PubMed/Medline, SciELO, Lilacs electronic databases, CAPES periodicals and the Cochrane Library. We included studies using bovine mineral matrix, associated to a collagen membrane for the treatment of peri-implantitis by Guided Bone Regeneration. Results: Of 1,163 studies, 10 were included in this review after applying the evaluation criteria. A total of 269 implants were treated in 260 patients. The follow-up period ranged from 6 to 48 months. The studies evaluated outcome in terms of reduction in probing depth, gain of clinical attachment and healing of the bony defect. Due to the heterogeneity of the studies, it was not possible to perform meta-analysis. Conclusion: Treatment of peri-implant lesions with Guided Bone Regeneration is a viable modality of treatment, providing reduction in bleeding on probing, as well as gain of clinical attachment. Complete filling of the defect is, however, an unpredictable result.

RESUMO Objetivo: Avaliar a associação do controle glicêmico e a produção de citocinas em indivíduos diabéticos tipo 2 com doença periodontal crônica. Métodos: Foram realizadas biópsias gengivais de 40 pacientes, distribuídos nos seguintes grupos: sistemicamente saudáveis sem doença periodontal (S); pacientes sistemicamente saudáveis com periodontite crônica (P); pacientes com diabetes mellitus (DM) tipo 2 controlado com periodontite crônica (C); pacientes com diabetes mellitus tipo 2 não controlado com periodontite crônica (D). Foram quantificadas através de ELISA, a produção das interleucinas (IL) -4, -6, -10, -17 e interferon (IFN) -γ. Resultados: A produção de IL-4, IL-10, IL-17 e INF-γ foi maior no grupo D quando comparada aos demais grupos (p<0.05), que por sua vez foram similares entre si (p≥0.05). Além disso, não houve diferença na produção de IL-6 em nenhum dos grupos avaliados (p≥0.05). Conclusão: Foram observados níveis significativamente elevados de citocinas pró-inflamatórias e anti-inflamatórias nos pacientes com diabetes mellitus tipo 2 não controlado e com periodontite crônica, demonstrando que o controle glicêmico pode estar associado com a resposta imunoinflamatória de sítios com periodontite crônica.

ABSTRACT Objective: To evaluate the association of glycemic control and cytokine production in type 2 diabetic subjects with chronic periodontitis Methods: Gingival biopsies were performed in 40 patients, divided into four groups: systemically healthy subjects without periodontal disease (S); systemically healthy patients with chronic periodontitis (P); patients with well-controlled type 2 diabetes mellitus (DM) with chronic periodontitis (C); poorly controlled type 2 diabetes mellitus with chronic periodontitis (D). The production of interleukin (IL) -4, -6, -10, -17 and interferon (IFN) -γ was quantified by ELISA. Results: The production of IL-4, IL-10, IL-17 and INF-γ was higher on group D when compared to other groups (p <0.05), which in turn were similar (p ≥0.05). In addition, there was no difference in the production of IL-6 in any of the evaluated groups (p≥0.05). Conclusion: Were observed significantly elevated levels of pro-inflammatory and anti-inflammatory cytokines in patients with poorly controlled type 2 diabetes and chronic periodontitis, demonstrating that glycemic control may be associated to the immune inflammatory response of sites with chronic periodontitis.

Abstract Objective This study evaluated the influence of glycemic control on the levels and frequency of subgingival periodontal pathogens in patients with type 2 diabetes mellitus (DM) and generalized chronic periodontitis (ChP). Material and Methods Fifty-six patients with generalized ChP and type 2 DM were assigned according to the levels of glycated hemoglobin (HbA1c) into one of the following groups: HbA1c<8% (n=28) or HbA1c≥8% (n=28). Three subgingival biofilm samples from sites with probing depth (PD)<5 mm and three samples from sites with PD≥5 mm were analyzed by quantitative Polymerase Chain Reaction (PCR) for the presence and levels of Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Eubacterium nodatum, Parvimona micra, Fusobacterium nucleatum ssp. and Prevotella intermedia. Results The mean counts of F. nucleatum ssp. were statistically significantly higher in the sites with PD≥5 mm of the HbA1c≥8% group (p<0.05). Frequencies of detection of T. forsythia, E. nodatum, P. micra and F. nucleatum ssp. were all higher in the sites with PD≥5 mm of the patients with HbA1c≥8%, compared with those of patients with HbA1c<8% (p<0.05). Frequency of detection of P. intermedia was higher in the sites with PD<5 mm of the patients with HbA1c≥8% than those of the patients with HbA1c<8% (p<0.05). Conclusions Poor glycemic control, as indicated by HbA1c≥8%, is associated with increased levels and frequencies of periodontal pathogens in the subgingival biofilm of subjects with type 2 DM and ChP.

Objetivo: Avaliar a associação do controle glicêmico e a produção de citocinas em indivíduos diabéticos tipo 2 com doença periodontal crônica. Métodos: Foram realizadas biópsias gengivais de 40 pacientes, distribuídos nos seguintes grupos: sistemicamente saudáveis sem doença periodontal (S); pacientes sistemicamente saudáveis com periodontite crônica (P); pacientes com diabetes mellitus (DM) tipo 2 controlado com periodontite crônica (C); pacientes com diabetes mellitus tipo 2 não controlado com periodontite crônica (D). Foram quantificadas através de ELISA, a produção das interleucinas (IL) -4, -6, -10, -17 e interferon (IFN) -g. Resultados: A produção de IL-4, IL-10, IL-17 e INF-g foi maior no grupo D quando comparada aos demais grupos (p<0.05), que por sua vez foram similares entre si (p³0.05). Além disso, não houve diferença na produção de IL-6 em nenhum dos grupos avaliados (p³0.05). Conclusão: Foram observados níveis significativamente elevados de citocinas pró-inflamatórias e anti-inflamatórias nos pacientes com diabetes mellitus tipo 2 não controlado e com periodontite crônica, demonstrando que o controle glicêmico pode estar associado com a resposta imunoinflamatória de sítios com periodontite crônica.

Objective: To evaluate the association of glycemic control and cytokine production in type 2 diabetic subjects with chronic periodontitis. Methods: Gingival biopsies were performed in 40 patients, divided into four groups: systemically healthy subjects without periodontal disease (S); systemically healthy patients with chronic periodontitis (P); patients with well-controlled type 2 diabetes mellitus (DM) with chronic periodontitis (C); poorly controlled type 2 diabetes mellitus with chronic periodontitis (D). The production of interleukin (IL) -4, -6, -10, -17 and interferon (IFN) -g was quantified by ELISA. Results: The production of IL-4, IL-10, IL-17 and INF-g was higher on group D when compared to other groups (p <0.05), which in turn were similar (p ³0.05). In addition, there was no difference in the production of IL-6 in any of the evaluated groups (p³0.05). Conclusion: Were observed significantly elevated levels of pro-inflammatory and anti-inflammatory cytokines in patients with poorly controlled type 2 diabetes and chronic periodontitis, demonstrating that glycemic control may be associated to the immune inflammatory response of sites with chronic periodontitis.

The aim of the present study was to evaluate the frequency of detection of Mogibacterium timidum in subgingival samples of subjects with generalized aggressive periodontitis (GAgP) and uncontrolled diabetic and non-diabetic subjects with generalized chronic periodontitis (GChP). 48 patients with GAgP, 50 non-diabetic and 39 uncontrolled (glycated hemoglobin >7%) type 2 diabetic subjects with GChP were enrolled in this study. Subgingival biofilm were collected from deep pockets (probing depth > 7 mm). After DNA extraction, M. timidum was detected by Nested Polymerase Chain Reaction and chi-square test was used to data analysis (p>0.05). There were no differences in the frequency of detection of M. timidum between subjects with GAgP (35%) and non-diabetic subjects with GChP (40%) (p>0.05). The frequency of detection of M. timidum was significantly higher in deep pockets of diabetic subjects with GChP (56%) when compared to GAgP (p<0.05), but similar to non-diabetic subjects with GChP (p>0.05). The frequency of detection of M. timidum was higher in subjects GChP presenting uncontrolled type 2 diabetes mellitus, when compared to GAgP subjects.

Antibiotics are important adjuncts in the treatment of infectious diseases, including periodontitis. The most severe criticisms to the indiscriminate use of these drugs are their side effects and, especially, the development of bacterial resistance. The knowledge of the biological mechanisms involved with the antibiotic usage would help the medical and dental communities to overcome these two problems. Therefore, the aim of this manuscript was to review the mechanisms of action of the antibiotics most commonly used in the periodontal treatment (i.e. penicillin, tetracycline, macrolide and metronidazole) and the main mechanisms of bacterial resistance to these drugs. Antimicrobial resistance can be classified into three groups: intrinsic, mutational and acquired. Penicillin, tetracycline and erythromycin are broad-spectrum drugs, effective against gram-positive and gram-negative microorganisms. Bacterial resistance to penicillin may occur due to diminished permeability of the bacterial cell to the antibiotic; alteration of the penicillin-binding proteins, or production of β-lactamases. However, a very small proportion of the subgingival microbiota is resistant to penicillins. Bacteria become resistant to tetracyclines or macrolides by limiting their access to the cell, by altering the ribosome in order to prevent effective binding of the drug, or by producing tetracycline/macrolide-inactivating enzymes. Periodontal pathogens may become resistant to these drugs. Finally, metronidazole can be considered a prodrug in the sense that it requires metabolic activation by strict anaerobe microorganisms. Acquired resistance to this drug has rarely been reported. Due to these low rates of resistance and to its high activity against the gram-negative anaerobic bacterial species, metronidazole is a promising drug for treating periodontal infections.

OBJECTIVES: This study evaluated the effects of coronally positioned flap (CPF) on the subgingival biofilm composition. MATERIAL AND METHODS: Twenty-two subjects with gingival recessions were treated with CPF. Clinical parameters were assessed before and at 6 months after surgery. Subgingival biofilms were analyzed by checkerboard DNA-DNA hybridization technique for 40 bacterial species. RESULTS: Recession height, clinical attachment level and bleeding on probing improved significantly (p<0.05) at 6 months post-CPF. The proportions of 10 periodontal pathogens and the proportions of red and orange complexes decreased at 6 months. CONCLUSION: In conclusion, CPF can induce beneficial effects on the composition of the subgingival microbiota after 6 months.

Clinical and experimental studies have demonstrated some negative effect of hypertension on bone mineral density. The aim of this study was to evaluate bone healing and trabecular bone area (TBA) in spontaneously hypertensive rats (SHR), a well-established model of essential hypertension, when compared to normotensive rats (NTR). A critical-size defect was surgically created in the right tibia of SHR (n = 12) and normotensive rats (NTR; n = 12), while the contralateral tibia was left intact. Eight days later, the animals were sacrificed and the specimens processed in order to obtain decalcified sections. The area of newly-formed bone (NB) within the defect of the right tibia and the TBA in the left tibia were histometrically evaluated. At 8 days post-operative, SHR presented a significantly smaller area of NB when compared to NTR (p < 0.05). In addition, SHR demonstrated a lower TBA than NTR group. In conclusion, the present study demonstrated that SHR rats presented a disturbed bone healing and reduced TBA.

O objetivo deste trabalho foi avaliar a influência da administração de ciclosporina A (CsA)/nifedipina e sua interrupção na densidade óssea em uma região lateral à superfície de implantes de titânio inseridos em coelhos. Dois implantes de titânio comercialmente puros foram inseridos bilateralmente em vinte e oito coelhos. Os animais foram aleatoriamente divididos em um dos seguintes grupos experimentais, recebendo injeções diárias subcutâneas por 14 dias: Grupos A e C: veículo (dimetil sulfóxido); Grupos B e D: CsA (10 mg/kg) e nifedipina (50 mg/kg). Os animais pertencentes aos Grupos A/B e C/D foram sacrificados 14 e 42 dias após a colocação dos implantes, respectivamente. Após o sacrifício, as tíbias foram removidas para a obtenção de secções não-descalcificadas. A densidade óssea foi obtida em uma zona de 500 mm lateral à superfície do implante através de análise histométrica. A análise intergrupo não revelou diferenças para os grupos teste e controle em 14 e 42 dias (p > 0,05). Dentro dos limites deste estudo podemos concluir que a associação CsA/nifedipina, administrada em um curto prazo, não apresenta uma influência negativa na densidade do osso preexistente ao redor de implantes de titânio inseridos em coelhos.

The aim of this study was to evaluate the influence of the administration and withdrawal of cyclosporin A/nifedipine on the bone density in a lateral area adjacent to implants placed in rabbits. Two screw-type titanium implants were placed bilaterally in twenty-eight New Zealand rabbits. The animals were assigned to one of the following groups and received daily subcutaneous injections for 14 days: Groups A and C: vehicle (dimethyl sulfoxide); Groups B and D: CsA (10 mg/kg) plus nifedipine (50 mg/kg). The animals in Groups A and B were sacrificed 14 days postoperatively and, in Groups C and D, 42 days postoperatively. After sacrifice, the tibiae were removed and undecalcified sections were obtained. Bone density was obtained in a 500 mm-wide zone lateral to the implant surface. Intergroup analysis showed no significant difference (p > 0.05) in the degree of bone density between control and test groups either on day 14 or on day 42. Thus, it appears that a short-term immunosuppressive therapy may not present a negative influence on the density of the pre-existing bone around titanium implants placed in rabbits.