Citrullination in the periodontium-a possible link between periodontitis and rheumatoid arthritis

OBJECTIVES The aim of the present study was to assess human and bacterial peptidylarginine deiminase (PAD) activity in the gingival crevicular fluid (GCF) in the context of serum levels of antibodies against citrullinated epitopes in rheumatoid arthritis and periodontitis. MATERIALS AND METHODS Human PAD and Porphyromonas gingivalis-derived enzyme (PPAD) activities were measured in the GCF of 52 rheumatoid arthritis (RA) patients (48 with periodontitis and 4 without) and 44 non-RA controls (28 with periodontitis and 16 without). Serum antibodies against citrullinated epitopes were measured by ELISA. Bacteria being associated with periodontitis were determined by nucleic-acid-based methods. RESULTS Citrullination was present in 26 (50 %) RA patients and 23 (48 %) controls. PAD and PPAD activities were detected in 36 (69 %) and 30 (58 %) RA patients, respectively, and in 30 (68 %) and 21 (50 %) controls, respectively. PPAD activity was higher in RA and non-RA patients with periodontitis than in those without (p = 0.038; p = 0.004), and was detected in 35 of 59 P. gingivalis-positive samples, and in 16 of 37 P. gingivalis-negative samples in association with high antibody levels against that species. CONCLUSIONS PAD and PPAD activities within the periodontium are elevated in RA and non-RA patients with periodontitis. PPAD secreted by P. gingivalis residing in epithelial cells may exert its citrullinating activity in distant regions of the periodontium or even distant tissues. CLINICAL RELEVANCE In periodontitis, the citrullination of proteins/peptides by human and bacterial peptidylarginine deiminases may generate antibodies after breaching immunotolerance in susceptible individuals.

Serum antibodies to oral anaerobic bacteria in patients with rheumatoid arthritis

BACKGROUND: This study was conducted to determine the component that causes the disease in rheumatoid arthritis (RA), which shows great resemblance to periodontitis in a pathologic context. MATERIALS AND METHODS: Within this study, the pathogen-specific IgG levels formed against Porphyromonas gingivalis FDC 381, Prevotella melaninogenica ATCC 25845, Actinobacillus actinomycetemcomitans Y4, Bacteroides forsythus ATCC 43047, and Prevotella intermedia 25611 oral bacteria were researched from the blood serum samples of 30 RA patients and 20 healthy controls with the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The IgG levels of P gingivalis, P intermedia, P melaninogenica, and B forsythus were found to be significantly higher in RA patients when compared with those of the controls. Of the other bacteria antibodies, A actinomycetemcomitans was not found at greater levels in RA serum samples in comparison with the healthy samples. CONCLUSION: The antibodies formed against P gingivalis, P intermedia, P melaninogenica, and B forsythus could be important to the etiopathogenesis of RA.

The role of CD4(+) and CD8(+) T cells on antibody production by murine Peyer's patch cells following mucosal presentation of Actinomyces viscosus

The aim of this study was to determine the role of CD4 and CD8 cells on specific antibody production by murine Peyer's patch (PP) cells after oral immunization with Actinomyces viscosus in mice. Female DBA/2 mice were orally immunized with three low doses of heat-killed A. viscosus. Sham-immunized mice served as a control group. Mice were depleted of CD4 or CD8 cells by intraperitoneal injection of anti-CD4 or anti-CD8 antibodies daily for 3 days before oral immunization. One week after the last oral immunization, PPs were removed and cell suspensions were cultured with A. viscosus. Specific antibody production in the culture supernatants was assessed by enzyme-linked immunosorbent assay. The results showed that oral immunization with A. viscosus induced a predominant specific immunoglobulin A (IgA) response by PP cells and, to a lesser extent, IgM antibodies. Depletion of CD4 but not CD8 cells suppressed the production of specific antibodies. These results suggest that oral immunization with low doses of A. viscosus may induce the production of specific antibodies by murine PP cells in a CD4-cell-dependent fashion.

Non-enterobacterial endotoxins stimulate human coronary artery but not venous endothelial cell activation via toll-like receptor 2

To determine whether non-enterobacterial endotoxins, which are likely to constitute the majority of the circulating endotoxin pool, may stimulate coronary artery endothelial cell activation. Interleukin-8 secretion, monocyte adhesion, and E-selectin expression were measured in human umbilical vein endothelial cells (HUVECs) and coronary artery endothelial cells (HCAECs) challenged in vitro with highly purified endotoxins of common host colonisers Escherichia coli, Porphyromonas gingivalis, Pseudomonas aeruginosa, and Bacteroides fragilis. HCAECs but not HUVECs expressed Toll-like receptor (TLR)-2 and were responsive to non-enterobacterial endotoxins. Transfection of TLR-deficient HEK-293 cells with TLR2 or TLR4/MD2 revealed that while E. coli endotoxin utilised solely TLR4 to signal, the endotoxins, deglycosylated endotoxins (lipid-A), and whole heat-killed bacteria of the other species stimulated TLR2-but not TLR4-dependent cell-signalling. Blockade of TLR2 with neutralizing antibody prevented HCAEC activation by non-enterobacterial endotoxins. Comparison of each endotoxin with E. coli endotoxin in limulus amoebocyte lysate assay revealed that the non-enterobacterial endotoxins are greatly underestimated by this assay, which has been used in all previous studies to estimate plasma endotoxin concentrations. Circulating non-enterobacterial endotoxins may be an underestimated contributor to endothelial activation and atherosclerosis in individuals at risk of increased plasma endotoxin burden.

Avaliação comparativa da remodelação óssea periimplantar em implantes com junção cone-morse e hexágono externo: estudo clínico randomizado controlado, duplo cego, boca dividida

Background: Several theories, such as the biological width formation, the inflammatory reactions due to the implant-abutment microgap contamination, and the periimplant stress/strain concentration causing bone microdamage accumulation, have been suggested to explain early periimplant bone loss. However, it is yet not well understood to which extent the implant-abutment connection type may influence the remodeling process around dental implants. Aim: to evaluate clinical, bacteriological, and biomechanical parameters related to periimplant bone loss at the crestal region, comparing external hexagon (EH) and Morse-taper (MT) connections. Materials and methods: Twelve patients with totally edentulous mandibles received four custom made Ø 3.8 x 13 mm implants in the interforaminal region of the mandible, with the same design, but different prosthetic connections (two of them EH or MT, randomly placed based on a split-mouth design), and a immediate implant- supported prosthesis. Clinical parameters (periimplant probing pocket depth, modified gingival index and mucosal thickness) were evaluated at 6 sites around the implants, at a 12 month follow-up. The distance from the top of the implant to the first bone-to-implant contact – IT-FBIC was evaluated on standardized digital peri-apical radiographs acquired at 1, 3, 6 and 12 months follow-up. Samples of the subgingival microbiota were collected 1, 3 and 6 months after implant loading. DNA were extracted and used for the quantification of Tanerella forsythia, Porphyromonas gingivalis, Aggragatibacter actinomycetemcomitans, Prevotella intermedia and Fusobacterium nucleatum. Comparison among multiple periods of observation were performed using repeated-measures Analysis of Variance (ANOVA), followed by a Tukey post-hoc test, while two-period based comparisons were made using paired t- test. Further, 36 computer-tomographic based finite element (FE) models were accomplished, simulating each patient in 3 loading conditions. The results for the peak EQV strain in periimplant bone were interpreted by means of a general linear model (ANOVA). Results: The variation in periimplant bone loss assessed by means of radiographs was significantly different between the connection types (P<0.001). Mean IT-FBIC was 1.17±0.44 mm for EH, and 0.17±0.54 mm for MT, considering all evaluated time periods. All clinical parameters presented not significant differences. No significant microbiological differences could be observed between both connection types. Most of the collected samples had very few pathogens, meaning that these regions were healthy from a microbiological point of view. In FE analysis, a significantly higher peak of EQV strain (P=0.005) was found for EH (mean 3438.65 µ∑) compared to MT (mean 840.98 µ∑) connection. Conclusions: Varying implant-abutment connection type will result in diverse periimplant bone remodeling, regardless of clinical and microbiological conditions. This fact is more likely attributed to the singular loading transmission through different implant-abutment connections to the periimplant bone. The present findings suggest that Morse-taper connection is more efficient to prevent periimplant bone loss, compared to an external hexagon connection.

Relación entre enfermedad periodontal y artritis reumatoide

Introducción: La periodontitis crónica y la artritis reumatoide (AR) son desórdenes inflamatorios crónicos caracterizados por la destrucción de tejidos, la reabsorción ósea y la producción de citoquinas proinflamatorias. Objetivos: Analizar la relación entre ambas enfermedades y la posible influencia del tratamiento de una sobre la otra. Material y métodos: Se realiza una revisión bibliográfica acerca de la patogénesis de la AR y la EP y los aspectos relacionados. Resultados: La patogénesis de ambas enfermedades muestra semejanzas notables. Bacterias periodontopatógenas, como Porphyromonas gingivalis, y mediadores inflamatorios, como el factor de necrosis tumoral y la proteína C reactiva, juegan un papel importante en la AR. La EP es un factor importante en la respuesta a la terapia en pacientes con AR. Conclusiones: Ambas enfermedades tienen una patogenia común. La prevalencia de enfermedad periodontal (EP) es mayor en pacientes con AR y viceversa. Aunque el control de la EP mediante tratamiento periodontal no quirúrgico parece mejorar los signos y síntomas en ambas enfermedades, hacen falta estudios más rigurosos con mayor número de casos y de mayor tiempo de evolución.

Relação da doença periodontal com o cancro do pâncreas: diagnóstico do cancro do pâncreas com recurso a testes salivares

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Antigenicity of Primary Endodontic Infection against Macrophages by the Levels of PGE(2) Production

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antigenic Activity of Bacterial Endodontic Contents from Primary Root Canal Infection with Periapical Lesions against Macrophage in the Release of Interleukin-1 beta and Tumor Necrosis Factor alpha

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Halicephalobus gingivalis (H.deletrix) in the brain of a horse

Um eqüino macho, com 10 anos, Mangalarga, apresentou uma infecção por um nematódeo rabditiforme no cérebro. Os sinais clínicos limitaram-se ao fato de o animal andar em círculos e apresentar paralisia do lado direito. O exame histológico do cérebro revelou acentuada gliose e discreto edema intersticial. O infiltrado inflamatório mononuclear perivascular era composto por poucas camadas de linfócitos, plasmócitos, macrófagos e raros eosinófilos, associados aos nematódeos rabditiformes. Áreas de malácia e trajetos com esferóides axonais são vistos ao redor de vasos e do agente etiológico, sendo mais evidentes na substância branca. Nas meninges, o infiltrado inflamatório foi moderado e associado a parasitas perivasculares. A identificação do nematódeo foi baseada no exame histológico do cérebro do cavalo.

Occurrence and antimicrobial susceptibility of Porphyromonas spp. and Fusobacterium spp. in dogs with and without periodontitis

The occurrence of Porphyromonas gulae, Porphyromonas macacae, Fusobacterium nucleatum and Fusobacterium canifelinum in subgingival plaque from dogs with and without periodontitis as well as their antimicrobial susceptibility were evaluated. From 50 dogs with periodontitis were identified 38 P. gulae, 8 P. macacae, 26 F. nucleatum and 15 F. canifelinum, and from 50 dogs without periodontitis were identified 15 P. gulae, 12 F. nucleatum and 11 F. canifelinum. All strains were susceptible to most of the antibiotics tested, however, different resistance rates to clarithromycin, erythromycin and metronidazole among strains were observed. The role of P. gulae, P. macacae, F. nucleatum and F. canifelinum in periodontal disease of household pets needs to be defined to a better prevention and treatment of the canine periodontitis. (c) 2012 Elsevier Ltd. All rights reserved.

Hypertrophic Adenoid Is A Major Infection Site Of Human Bocavirus 1.

Human bocavirus 1 (HBoV1) is associated with respiratory infections worldwide, mainly in children. Similar to other parvoviruses, it is believed that HBoV1 can persist for long periods of time in humans, probably through maintaining concatemers of the virus single-stranded DNA genome in the nuclei of infected cells. Recently, HBoV-1 was detected in high rates in adenoid and palatine tonsils samples from patients with chronic adenotonsillar diseases, but nothing is known about the virus replication levels in those tissues. A 3-year prospective hospital-based study was conducted to detect and quantify HBoV1 DNA and mRNAs in samples of the adenoids (AD), palatine tonsils (PT), nasopharyngeal secretions (NPS), and peripheral blood (PB) from patients undergoing tonsillectomy for tonsillar hypertrophy or recurrent tonsillitis. HBoV1 was detected in 25.3% of the AD samples, while the rates of detection in the PT, NPS, and PB samples were 7.2%, 10.5%, and 1.7%, respectively. The viral loads were higher in AD samples, and 27.3% of the patients with HBoV had mRNA detectable in this tissue. High viral loads and detectable mRNA in the AD were associated with HBoV1 detection in the other sample sites. The adenoids are an important site of HBoV1 replication and persistence in children with tonsillar hypertrophy. The adenoids contain high HBoV1 loads and are frequently positive for HBoV mRNA, and this is associated with the detection of HBoV1 in secretions.

Impact Of Pharmacist Interventions On Drug-related Problems And Laboratory Markers In Outpatients With Human Immunodeficiency Virus Infection.

Substantial complexity has been introduced into treatment regimens for patients with human immunodeficiency virus (HIV) infection. Many drug-related problems (DRPs) are detected in these patients, such as low adherence, therapeutic inefficacy, and safety issues. We evaluated the impact of pharmacist interventions on CD4+ T-lymphocyte count, HIV viral load, and DRPs in patients with HIV infection. In this 18-month prospective controlled study, 90 outpatients were selected by convenience sampling from the Hospital Dia-University of Campinas Teaching Hospital (Brazil). Forty-five patients comprised the pharmacist intervention group and 45 the control group; all patients had HIV infection with or without acquired immunodeficiency syndrome. Pharmaceutical appointments were conducted based on the Pharmacotherapy Workup method, although DRPs and pharmacist intervention classifications were modified for applicability to institutional service limitations and research requirements. Pharmacist interventions were performed immediately after detection of DRPs. The main outcome measures were DRPs, CD4+ T-lymphocyte count, and HIV viral load. After pharmacist intervention, DRPs decreased from 5.2 (95% confidence interval [CI] =4.1-6.2) to 4.2 (95% CI =3.3-5.1) per patient (P=0.043). A total of 122 pharmacist interventions were proposed, with an average of 2.7 interventions per patient. All the pharmacist interventions were accepted by physicians, and among patients, the interventions were well accepted during the appointments, but compliance with the interventions was not measured. A statistically significant increase in CD4+ T-lymphocyte count in the intervention group was found (260.7 cells/mm(3) [95% CI =175.8-345.6] to 312.0 cells/mm(3) [95% CI =23.5-40.6], P=0.015), which was not observed in the control group. There was no statistical difference between the groups regarding HIV viral load. This study suggests that pharmacist interventions in patients with HIV infection can cause an increase in CD4+ T-lymphocyte counts and a decrease in DRPs, demonstrating the importance of an optimal pharmaceutical care plan.

Urinary Tract Infection In Renal Transplant Recipients: Incidence, Risk Factors, And Impact On Graft Function.

Urinary tract infection (UTI) is the most common infection posttransplant. However, the risk factors for and the impact of UTIs remain controversial. The aim of this study was to identify the incidence of posttransplant UTIs in a series of renal transplant recipients from deceased donors. Secondary objectives were to identify: (1) the most frequent infectious agents; (2) risk factors related to donor; (3) risk factors related to recipients; and (4) impact of UTI on graft function. This was a retrospective analysis of medical records from renal transplant patients from January to December 2010. Local ethics committee approved the protocol. The incidence of UTI in this series was 34.2%. Risk factors for UTI were older age, (independent of gender), biopsy-proven acute rejection episodes, and kidneys from deceased donors (United Network for Organ Sharing criteria). For female patients, the number of pretransplant pregnancies was an additional risk factor. Recurrent UTI was observed in 44% of patients from the UTI group. The most common infectious agents were Escherichia coli and Klebsiella pneumoniae, for both isolated and recurrent UTI. No difference in renal graft function or immunosuppressive therapy was observed between groups after the 1-year follow-up. In this series, older age, previous pregnancy, kidneys from expanded criteria donors, and biopsy-proven acute rejection episodes were risk factors for posttransplant UTI. Recurrence of UTI was observed in 44%, with no negative impact on graft function or survival.