- Bacterial Infection Increases the Risk of Alzheimer's Disease: An Evidence-Based Assessment. [JOURNAL ARTICLE]
- J Alzheimers Dis 2016 Aug 18.
The possibility of an infectious etiology for Alzheimer's disease (AD) has been repeatedly postulated over the past three decades, with the roles of both viruses and bacteria having been investigated. Chlamydophila (formerly Chlamydia) pneumoniae (Cpn) and spirochetal bacteria have been two of the most frequently implicated bacterial groups in AD pathogenesis.A meta-analysis was performed where data was combined from 25 studies examining the association between AD and spirochetal bacteria or Cpn.Comprehensive search of several electronic databases. Data was extracted from published studies and a random-effects model was used to analyze the data.A statistically significant association between AD and detectable evidence of infection of either bacterial group was demonstrated. Over a ten-fold increased occurrence of AD was noted when there is detectable evidence of spirochetal infection (OR: 10.61; 95% CI: 3.38-33.29), with a more conservative risk estimate demonstrating over a four-fold increased occurrence of AD (OR 4.45; 95% CI: 2.33-8.52). Over a five-fold increased occurrence of AD was noted with Cpn infection (OR 5.66; 95% CI: 1.83-17.51).There appears to be a strongly positive association between bacterial infection and AD.
- [The role of reflectance confocal microscopy in the diagnosis of secondary syphilis of the vulva and anus: A first case report]. [JOURNAL ARTICLE, ENGLISH ABSTRACT]
- Ann Dermatol Venereol 2016 Aug 23.
Herein we report the case of an 18-year-old pregnant patient presenting with plantar and ano-genital lesions of syphilis, pharyngitis, erythematosus and scalynasolabial intertrigo and angular cheilitis.In vivo reflectance confocal microscopy examination (Vivascope 3000(®); Caliber Inc, Rochester, NY, USA, distributed in France by Mavig, Munich) of ano-genital lesions enabled us to identify hyper-reflective elongated rods in the papillary dermis suggesting spirochetes. The diagnosis was confirmed by TPHA and VDRL as well as immunohistological examination.We identified for the first time rod shaped structures in ano-genital lesions of secondary syphilis, regularly alternating hyper-reflective and non-reflective areas corresponding to helix-shaped treponemes visualized by darkfield microscopy, which may not be confused with other cell structures.
- Periodontitis contributes to adipose tissue inflammation through the NF-<kappa>B, JNK and ERK pathways to promote insulin resistance in a rat model. [JOURNAL ARTICLE]
- Microbes Infect 2016 Aug 23.
This study aimed to investigate the mechanism by which periodontitis affects the inflammatory response and systemic insulin resistance in the white adipose and liver tissues in an obese rat model. The obese model was generated by feeding rats a high fat diet. The periodontitis model was induced by ligatures and injection of "red complex", which consisted of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, for two weeks. When compared with rats without periodontitis, fasting glucose levels and homeostasis model assessment index were significantly increased in rats with periodontitis, suggesting that periodontitis promotes the development of insulin resistance in obese rats. Gene and protein expression analysis in white adipose and liver tissue revealed that experimental periodontitis stimulated the expression of inflammatory cytokines, such as tumor necrosis factors-alpha, interleukin-1 beta, toll-like receptor 2 and toll-like receptor 4. Signals associated with inflammation and insulin resistance, including nuclear factor-<kappa> B, c-Jun amino-terminal kinase and extracellular-signal regulated kinase were significantly activated in the white adipose tissue from obese rats with periodontitis compared to obese rats without periodontitis. Taken together, these findings suggest that periodontitis plays an important role in aggravating the development of local white adipose inflammation and systemic insulin resistance in rat models.
- Persistence of Porphyromonas gingivalis is a negative predictor in patients with moderate to severe periodontitis after nonsurgical periodontal therapy. [JOURNAL ARTICLE]
- Clin Oral Investig 2016 Aug 24.
The aim of this study was to evaluate the quality of prediction for stable results after nonsurgical periodontal therapy by several microbiological variables of the subgingival biofilm and biomarkers of gingival crevicular fluid or oral lavage.Forty-six individuals with moderate or severe chronic periodontitis receiving nonsurgical periodontal therapy were monitored for clinical variables, selected microorganisms, and biomarkers at baseline and 3 and 6 months thereafter. Logistic regression analysis and general linear model (GLM) were applied for analysis of variance and covariance.At 6 months, 20 patients showed a high response (HR) to treatment (at least 60 % of reduction of numbers of sites with PD >4 mm), whereas 26 did not (low response, LR). All clinical variables were significantly improved at 3 and 6 months within each group (p < 0.001, each compared with baseline). Modeling the impact of Porphyromonas gingivalis, Treponema denticola, and median of MMP-8 on to the response to treatment as continuous variables by GLM showed a significant influence of these variables (p = 0.045) with the strongest influence of P. gingivalis (p = 0.012) followed by T. denticola (p = 0.045) and no association with MMP-8 (p = 0.982). Samples tested positively for P. gingivalis decreased only in HR (3 months: p = 0.003; 6 months: p = 0.002). Calprotectin levels in GCF were lower in the HR group compared with the LR group at 3 months (p = 0.008) and at 6 months (p = 0.018).Persistence of P. gingivalis combined with a high GCF level of calprotectin may have a negative predictive value on response to periodontal therapy.Microbiological diagnostics for P. gingivalis before and 3 months after SRP may have a predictive value on response to periodontal therapy. The combination with MMP-8 in oral lavage or preferably calprotectin in GCF might give additional information.
- Immunologic characteristics of human gingival fibroblasts in response to oral bacteria. [JOURNAL ARTICLE]
- J Periodontal Res 2016 Aug 24.
There is ample evidence that gingival fibroblasts (GFs) participate in the immune response to oral bacteria and serve as immune-regulatory cells. The objective of this study was to investigate the innate immune response of GFs to oral bacteria.Human GFs were cocultured with relatively less-pathogenic (Leptotrichia wadei, Fusobacterium nucleatum and Campylobacter gracilis) and pathogenic red-complex bacteria. The expression of mRNA for antimicrobial peptides [AMPs; namely human beta defensins (HBDs)], chemokines with antimicrobial activity [chemokine C-X-C motif (CXCL)10, CXCL11 and chemokine C-C motif ligand 20 (CCL20)] and proinflammatory mediators [interleukin (IL)6 and IL8] and the levels of CXCL11, CCL20, IL-6 and IL-8 accumulated in supernatants were analyzed using real-time PCR and ELISA, respectively. The proteolytic activities of CXCL11, CCL20, IL-6 and IL-8 produced by six species of bacteria were also determined.The relatively less-pathogenic bacteria strongly up-regulated the expression of antimicrobial chemokines and proinflammatory mediators, whereas the red-complex bacteria stimulated low levels, or often suppressed, expression of these factors. Regarding the regulation of AMPs, the inhibition of HBD3, HBD106 and HBD107 mRNAs by Porphyromonas gingivalis was noticeable; however, differences between the two bacterial groups were not conspicuous. Differential degradation of proteins by the six bacterial species was observed: P. gingivalis and Treponema denticola degraded proteins well, whereas the other species degraded proteins to a relatively lower degree.The invasion of red-complex bacteria into gingival connective tissue can suppress the immune response of GFs and can be a source of persistent infection in connective tissue.
- First report of tertiary syphilis presenting as lipoatrophic panniculitis in an immunocompetent patient. [JOURNAL ARTICLE]
- Int J STD AIDS 2016 Aug 24.
We describe herein a woman who developed subcutaneous gummas in her trochanteric regions, bilaterally, although she had been treated for syphilis two decades earlier. Evidence of Treponema pallidum latent late infection was the presence of IgG antibodies against T. pallidum and the positive non-treponemal and treponemal tests. Moreover, immunohistochemical staining for T. pallidum detected some spirochetes close to the atrophic adipocytes allowing the diagnosis of lypo-atrophic panniculitis tertiary syphilis. This is the first case of tertiary syphilis presenting as panniculitis in an immunocompetent patient, demonstrating that subcutaneous fat may be another organ infected in tertiary syphilis.
- Longitudinal study on clinical and microbial analysis of periodontal status in pregnancy. [Journal Article]
- Braz Oral Res 2016; 30(1):e87.
This study was aimed to provide a longitudinal overview of the subgingival bacterial microbiome using fluorescence in situ hybridization (FISH) technique, in women in the second trimester of pregnancy (between 14 and 24 weeks), and 48 h and 8 weeks postpartum. Of 31 women evaluated during pregnancy, 24 returned for the 48-h and 18 for their 8-week exams postpartum. Probing depth (PD), bleeding on probing, clinical attachment level, and presence of calculus were recorded. Subgingival plaque samples were collected, and FISH was used to identify the numbers of eight periodontal pathogens. Friedman test was used to compare differences between follow-up examinations, followed by a multiple comparison test for a post hoc pairwise comparison. Clinically, a significantly greater number of teeth with PD = 4-5 mm were found during pregnancy than on postpartum examinations. Microbial analysis showed a statistically significant decrease in cell count over the study period for Prevotella nigrescens. P. intermedia, Campylobacter rectus, and Porphyromonas gingivalis also decrease, although not significantly, and Aggregatibacter actinomycetemcomitans increased. No significant changes were found for Fusobacterium nucleatum, Treponema denticola, or Tannerella forsythia. Our data demonstrate a change in the subgingival microbiota during pregnancy, at least for P. nigrescens.
- Essential Role of the Linker Region in Higher Catalytic Efficiency of a Bifunctional MsrA-MsrB Fusion Protein. [JOURNAL ARTICLE]
- Biochemistry 2016 Aug 23.
Many bacteria, particularly pathogens, possess methionine sulfoxide reductase A (MsrA) and B (MsrB) as a fusion form (MsrAB). However, it is not clear why they possess a fusion MsrAB form rather than the separate enzymes that exist in most organisms. In this study, we performed biochemical and kinetic analyses of MsrAB from Treponema denticola (TdMsrAB), single domain forms (TdMsrA and TdMsrB), and catalytic Cys mutants (TdMsrAB(C11S) and TdMsrAB(C285S)). We found that the catalytic efficiency of both MsrA and MsrB increased by fusing the domains, and that the linker region (iloop) that connects TdMsrA and TdMsrB is required for the higher catalytic efficiency of TdMsrAB. We also determined the crystal structure of TdMsrAB at 2.3 Å, showing that the iloop mainly interacts with TdMsrB via hydrogen bonds. Further kinetic analysis using the iloop mutants revealed that the iloop-TdMsrB interactions are critical to MsrB and MsrA activities. We also report the structure in which oxidized form of dithiothreitol, an in vitro reductant for MsrA and MsrB, is present in the active site of TdMsrA. Collectively, the results of this study reveal an essential role of the iloop in maintaining the higher catalytic efficiency of MsrAB fusion enzyme and provide a better understanding as to why MsrAB enzyme exists as a fused form.
- Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma. [Journal Article]
- PLoS Negl Trop Dis 2016 Aug; 10(8):e0004927.
Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination.This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1-14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test.A total of 1,284 children were enrolled in the study. Amongst children aged 5-14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6-47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1-8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005). Amongst children aged 1-4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6-7.1%). This did not differ significantly from the seroprevalence in this age group that had been predicted based on our previous surveys (3.5% vs 5%, p = 0.11). Fourteen children (1.1%) were considered to have a skin lesion clinically consistent with yaws, but none of these individuals was seropositive for yaws. Of nine cases where a swab could be collected for PCR, all were negative for Treponema pallidum subsp. pertenue DNA.In this study we have shown that the benefit of a single round of mass treatment with azithromycin 20mg/kg appears to extend to 18 months without any further intervention. The lack of a significant change in seroprevalence from 6 to 18 months after mass treatment might suggest that interventions could be spaced at yearly intervals without a significant loss of impact, and that this might facilitate integration of yaws eradication with other neglected tropical disease (NTD) control programmes. MDA coverage above 90% was associated with significantly better outcomes than coverages lower than this threshold, and strategies to improve coverage at all stages of yaws eradication efforts should be investigated.