Diabetes may affect the expression of matrix metalloproteinases and their inhibitors more than smoking in chronic periodontitis.

BACKGROUND AND OBJECTIVE: No previous study has directly compared the levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) between smokers and individuals with diabetes mellitus (DM) with periodontitis. Therefore, the aim of this study was to evaluate the gene expression of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 in tissues with chronic periodontitis (ChP) of smokers and individuals with type 2 DM. MATERIAL AND METHODS: Gingival biopsies were harvested from: non-smokers and non-diabetic individuals with ChP (n = 18) (ChP group); non-diabetic smokers (≥ 10 cigarettes per day for at least the past 5 years) with ChP (n = 18) (SChP group); non-smoking individuals with type 2 diabetes (glycated hemoglobin levels ≥ 7.5%) and ChP (n = 18) (DMChP group). The tissue levels of mRNA of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 were evaluated by quantitative real-time polymerase chain reaction. RESULTS: The MMP-8 expression was the lowest in the ChP group (p < 0.05). The DMChP group presented increased mRNA levels of MMP-2 and MMP-9, when compared to the SChP group (p < 0.05). MMP-1 expression and the MMP-1/TIMP-1, MMP-2/TIMP-1, MMP-8/TIMP-1, MMP-9/TIMP-1, MMP-1/TIMP-2 and MMP-2/TIMP-2 ratios were higher in the DMChP group than in the ChP and SChP groups (p < 0.05). The DMChP group presented lower mRNA levels of TIMP-1 than the ChP group (p < 0.05). The MMP-8/TIMP-2 ratio was the highest in the SChP group (p < 0.05). CONCLUSION: Uncontrolled type 2 DM upregulates the ratio of MMP/TIMPs in sites with ChP more than smoking, which may contribute to a greater extracellular matrix degradation and periodontal breakdown in DM-related periodontitis.

Could cytokine levels in the peri-implant crevicular fluid be used to distinguish between healthy implants and implants with peri-implantitis? A systematic review.

BACKGROUND AND OBJECTIVE: Despite investigative efforts to identify the levels of different types of cytokines in the peri-implant crevicular fluid (PICF), the efficacy of these biomarkers in assisting the diagnosis of peri-implantitis is still undetermined. This systematic review aimed to answer the following question: "Could cytokine levels in the PICF be used to distinguish between healthy implants and implants with peri-implantitis?" MATERIAL AND METHODS: This review was conducted and reported in accordance with the PRISMA statement. The MEDLINE and EMBASE databases were searched from 1990 up to and including March 2015, using MeSH terms and other keywords. Additional publications were searched using a hand search of reference lists of relevant studies. Titles and abstracts were screened and papers that fulfilled eligibility criteria were assessed. RESULTS: Out of 1212 titles, 18 studies reporting the levels of nine different cytokines were included. Proinflammatory cytokines [interleukin (IL)-1ß, IL-6, IL-12, IL-17 and tumor necrosis factor-α) were the cytokines studied most commonly, followed by anti-inflammatory cytokines (IL-4 and IL-10), osteoclastogenesis-related cytokines (RANKL) and chemokines (IL-8). Nine studies reported statistically significantly higher levels of proinflammatory cytokines in the PICF of implants with peri-implantitis than in the PICF of healthy implants. Most studies did not find any significant differences in the PICF levels of anti-inflammatory cytokines and RANKL between healthy implants and implants with peri-implantitis. IL-8 was the only chemokine studied and its levels did not differ significantly between healthy and diseased implants. The studies differed greatly in the manner in which they reported the results (e.g. concentrations or total amounts) and in the exclusion of confounders, such as smoking. CONCLUSION: The results of this systematic review indicate moderate evidence in the literature to support that implants with peri-implantitis present higher levels of proinflammatory cytokines in the PICF than do healthy implants. Evidence regarding the PICF levels of anti-inflammatory cytokines, osteoclastogenesis-related cytokines and chemokines as possible predictors of peri-implantitis is too limited.

Do subjects with aggressive and chronic periodontitis exhibit a different cytokine/chemokine profile in the gingival crevicular fluid? A systematic review.

BACKGROUND AND OBJECTIVE: Microbiological and immunological hypotheses have been raised to explain the differences in the clinical manifestations of aggressive periodontitis and chronic periodontitis. However, studies comparing the cytokine/chemokine profiles in gingival crevicular fluid between these two clinical conditions have so far not been compiled. This systematic review aimed to answer the following question: "Do subjects with aggressive periodontitis and chronic periodontitis have a different profile of cytokines/chemokines in the gingival crevicular fluid?" MATERIAL AND METHODS: An electronic database search of MEDLINE/PubMed and Embase was performed from 1990 up to and including August 2013, using MeSH terms and other keywords. Titles and abstracts were screened and the papers that satisfied eligibility criteria were assessed. RESULTS: Of 1954 titles, 17 studies reporting the levels of 21 different cytokines/chemokines were included. Most studies did not find any significant differences in the gingival crevicular fluid levels of cytokines/chemokines between aggressive periodontitis and chronic periodontitis. Some studies demonstrated that the levels of specific proinflammatory and anti-inflammatory cytokines/chemokines were higher (n = 5) and lower (n = 3), respectively, in aggressive periodontitis than in chronic periodontitis. The studies differed in the manner in which they reported the results (e.g. concentrations or total amounts). It was not clear in some studies whether the sample sites from both groups were matched for disease severity. Some studies did not take into account confounders, such as smoking. CONCLUSION: The current weight of evidence is not sufficient to prove that there are distinct gingival crevicular fluid cytokine/chemokine profiles for patients with aggressive periodontitis and chronic periodontitis.

Partial- and full-mouth scaling and root planing in type 2 diabetic subjects: a 12-mo follow-up of clinical parameters and levels of cytokines and osteoclastogenesis-related factors.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the effects of full-mouth scaling and root planing (FMSRP) and partial-mouth scaling and root planing (PMSRP), up to 12 mo after treatment, on clinical parameters, and levels of cytokines and osteoclastogenesis-related factors in type 2 diabetic subjects with chronic periodontitis. MATERIAL AND METHODS: Thirty-four subjects received FMSRP (n = 17) or PMSRP (n = 17) within 24 h or in multiple sessions, respectively. Clinical parameters and local levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-17, IL-23, IL-4, receptor activator of NF-ß ligand and osteoprotegerin were assessed at baseline, and 3, 6 and 12 mo after therapies. RESULTS: Clinical parameters improved after both therapies (p < 0.05), and no between-group differences were observed at any time-point (p > 0.05). Overall, there were no considerable differences in the local levels of the biomarkers studied between groups (p > 0.05). The IL-23 concentration and total amount of IFN-γ increased in the FMSRP group and decreased in the PMSRP group from baseline to 3 mo and from baseline to 6 mo, respectively (p < 0.05). CONCLUSION: Both PMSRP and FMSRP promoted benefits in clinical parameters and showed a similar modulation of cytokines and osteoclastogenesis-related factors at 12 mo in type 2 diabetic subjects.

A preliminary study on the FAM5C expression in generalized chronic periodontitis.

OBJECTIVE: The Family with sequence similarity 5 member C (FAM5C) has been suggested to contribute in aggressive periodontitis. However, there is no data regarding its role in chronic periodontitis. The aim of this study was to evaluate the FAM5C expression in chronic periodontitis and to study association of FAM5C with key immunoinflammatory markers. MATERIAL AND METHODS: Gingival biopsies were harvested from periodontally healthy subjects (n = 10) and chronic periodontitis subjects (n = 15). The levels of mRNA of FAM5C, interleukin (IL)-17, IL-6, IL-23, IL-10, IL-4, interferon-c, toll-like receptor (TLR)-2, TLR-4, osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), tumor necrosis factor (TNF)-a, transforming growth factor-b, transcription factor forkhead box p3, and transcription factor orphan nuclear receptor C2 were evaluated by real-time polymerase chain reaction. RESULTS: FAM5C mRNA levels were not different between periodontally healthy and diseased tissues (P > 0.05). Gene expressions of IL-17, TNF-a, OPG, RANKL, TLR-2, and TLR-4 were higher in periodontitis, when compared to periodontally healthy sites (P < 0.05), while no differences between groups were observed for the other genes evaluated (P > 0.05). There were no correlations between the gene expression of FAM5C and the other immunoinflammatory markers (P > 0.05). CONCLUSION: Within the limits of this study, it seems that FAM5C expression does not contribute to chronic periodontitis.

Possible involvement of IL-21 and IL-10 on salivary IgA levels in chronic periodontitis subjects.

Specific cytokines and the costimulatory protein CD40 play role in inducing immunoglobulin (Ig)A production by B cells in the humoral immune response. However, to date, the role of these mediators was not investigated in chronic periodontitis. Therefore, the aim of this study was to assess the local levels of interleukin (IL)-21, IL-21 receptor (IL-21R), IL-4, IL-10 and CD40 ligand (CD40L) on chronic periodontitis subjects and their relationship with the salivary levels of IgA. Gingival biopsies and un-stimulated saliva were collected from chronic periodontitis (n = 15) and periodontally healthy (n = 15) subjects. The mRNA levels of IL-4, IL-10, IL-21, IL-21R, CD40L in the gingival biopsies were evaluated by quantitative real-time polymerase chain reaction. The salivary levels of IgA and the levels of IL-4 and IL-10 in the gingival biopsies were analyzed by ELISA. The mean levels of IgA were significantly higher in the chronic periodontitis compared to periodontally healthy group (P < 0.05). The mRNA levels for IL-21 was higher (P < 0.05) in the chronic periodontitis when compared to the healthy group. However, the expression of IL-21R and CD40L did not differ between groups. The IL-10 was significantly elevated at mRNA and protein levels in chronic periodontitis when compared to periodontally healthy group (P < 0.05). Conversely, the mRNA levels as well as the protein amount of IL-4 were significantly lower (P < 0.05) in chronic periodontitis than healthy ones. In conclusion, the upregulation of IL-21 and IL-10 and downregulation of IL-4 in periodontitis tissues may be collectively involved in the increased levels of salivary IgA in chronic periodontitis subjects.

TNF-alpha and IL-4 levels in generalized aggressive periodontitis subjects.

OBJECTIVES: The aim of this study was to evaluate tumor necrosis factor (TNF)-alpha and interleukin (IL)-4 levels in healthy sites and sites exhibiting signs of moderate and advanced generalized aggressive periodontitis (GAgP) in the same subject. METHODS: The following sites were selected for crevicular fluid sampling in the same AgP subject (n = 14): Healthy sites (HS): no marginal bleeding or bleeding on probing (BOP) and probing depth (PD) or= 7 mm. One site from periodontally healthy subjects (n = 13) was sampled for use as a control. TNF-alpha and IL-4 levels were measured using ELISA. RESULTS: The total amount of TNF-alpha was lower for control sites, while there were no differences among healthy and diseased sites from GAgP subjects (P < 0.05). The concentration of TNF-alpha was higher in HS, in relation to the other sites (P < 0.05). There were no significant differences among the groups regarding total amounts of IL-4 (P > 0.05), while IL-4 concentration was significantly higher in control sites, when compared with sites from GAgP subjects (P < 0.05). CONCLUSION: In conclusion, high levels of TNF-alpha and low levels of IL-4 were observed in both healthy and diseased sites within the same generalized AgP individuals.

Detection and neutralization of venom by ovine antiserum in experimental envenoming by Bothrops jararaca

In this study we optimized an enzyme-linked immunosorbent assay (ELISA) to evaluate bothropic venom levels in biological samples. These samples were obtained by two distinct protocols. In the first one, Swiss mice were injected with 1 LD50 of Bothrops jararaca (B. jararaca) venom and 15 minutes later, animals were treated with ovine antibothropic serum. Blood and spleen homogenate samples were obtained 6 hours after antiserum therapy. Ovine antibothropic serum significantly neutralized venom levels in serum and spleen. In the second protocol, BALB/c mice were injected with 1 LD50 of bothropic venom by either intraperitoneal (IP) or intradermal (ID) route and venom levels were evaluated 1, 3 and 6 hours after, in blood, spleen homogenates and urine. Serum and splenic venom levels were significantly higher in animals envenomed by IP route comparing with animals envenomed by ID route. Higher venom levels were also detected in urine samples from animals envenomed by IP route. However, these differences were not statistically significant. These results demonstrated that the optimized ELISA was adequate to quantify venom levels in different biological samples. This assay could, therefore, substitute the in vivo neutralizing assay and also be useful to evaluate the severity of human and experimental envenomations.

Assessment of the neutralizing potency of ovine antivenom in a swiss mice model of Bothrops jararaca envenoming

Alternative sources of anti-ophidic serum are being investigated due to the secondary effects associated with types I and II hypersensitivity reactions. In the present study we raised and evaluated the protective effect of an ovine antibothropic serum in a Swiss mice envenoming model. Ovine antiserum was obtained by immunization with seven increasing doses of bothropic venom associated with adjuvants. The neutralizing ability was tested by the lethal activity (2 LD50) neutralization and serum and splenic venom levels after antivenom administration to experimentally envenomed mice. The antiserum effect on local edema was also tested by injection of venom/antivenom mixtures into the mice footpads. Ovine antiserum neutralized lethal activity and also significantly decreased serum and splenic venom levels. However, this antiserum was not able to mediate any protective effect on edema triggered by bothropic venom