Clinical, immunological and microbial gingival profile of juvenile systemic lupus erythematosus patients.

Periodontal disease has been associated with rheumatic diseases; however, few studies have evaluated the association with systemic lupus erythematosus (SLE), and its impact on the local inflammatory and microbial profiles. Therefore, this study evaluated the levels of several cytokines in gingival crevicular fluid (GCF) and serum from juvenile SLE (jSLE) patients with gingival inflammation, compared with controls. In addition, we assessed their subgingival microbial profile. Thirty jSLE patients and 29 systemically healthy individuals were recruited. Participants were rheumatologically and periodontally examined, and GCF, serum and intrasulcular biofilm were collected. Cytokines were analysed by bead-based multiplex assays and the bacterial profile by checkerboard DNA-DNA hybridization. jSLE patients presented higher percentages of dental plaque and bleeding than controls, as well as increased mean probing depth and attachment loss. After adjustment for multiple comparisons, GCF levels of interleukin (IL)-1ß, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon-γ and monocyte chemoattractant protein-1 were significantly higher, whereas the levels of granulocyte-macrophage colony-stimulating factor were significantly lower in jSLE patients. In serum, G-CSF levels tended to be higher in jSLE patients (adjusted p-value = 0.06). Intrasulcular counts of Aggregatibacter actinomycetemcomitans were significantly higher in jSLE patients as compared with controls. We conclude that patients with jSLE present a worse periodontal condition associated with altered levels of pro-inflammatory cytokines in GCF and increased counts of A. actinomycetemcomitans in the intrasulcular biofilm.

Time-Stretched Spectroscopy by the Quantum Zeno Effect: The Case of Auger Decay.

A tenet of time-resolved spectroscopy is "faster laser pulses for shorter timescales". Here, we suggest turning this paradigm around, and slowing down the system dynamics via repeated measurements, to do spectroscopy on longer timescales. This is the principle of the quantum Zeno effect. We exemplify our approach with the Auger process, and find that repeated measurements increase the core-hole lifetime, redistribute the kinetic energy of Auger electrons, and alter entanglement formation. We further provide an explicit experimental protocol for atomic Li, to make our proposal concrete.

Oral-gut connection: one step closer to an integrated view of the gastrointestinal tract?

Although an enrichment of orally derived bacteria is reported in the gut microbiota of patients with several diseases, it is mostly unknown whether oral bacteria can colonize and induce intestinal inflammation. In a recent paper in Science, Atarashi et al.1 from Kenya Honda's laboratory show that a subset of orally derived bacteria colonizes and persists in the gut, leading to activation of the intestinal immune system and subsequent chronic inflammation in a susceptible host. The impact of oral health status as a potential contributor to inflammatory diseases at distal sites of the body deserves consideration.

Immune response profiling of primary monocytes and oral keratinocytes to different Tannerella forsythia strains and their cell surface mutants.

The oral pathogen Tannerella forsythia possesses a unique surface (S-) layer with a complex O-glycan containing a bacterial sialic acid mimic in the form of either pseudaminic acid or legionaminic acid at its terminal position. We hypothesize that different T. forsythia strains employ these stereoisomeric sugar acids for interacting with the immune system and resident host tissues in the periodontium. Here, we show how T. forsythia strains ATCC 43037 and UB4 displaying pseudaminic acid and legionaminic acid, respectively, and selected cell surface mutants of these strains modulate the immune response in monocytes and human oral keratinocytes (HOK) using a multiplex immunoassay. When challenged with T. forsythia, monocytes secrete proinflammatory cytokines, chemokines and vascular endothelial growth factor (VEGF) with the release of interleukin-1ß (IL-1ß) and IL-7 being differentially regulated by the two T. forsythia wild-type strains. Truncation of the bacteria's O-glycan leads to significant reduction of IL-1ß and regulates macrophage inflammatory protein-1. HOK infected with T. forsythia produce IL-1Ra, chemokines and VEGF. Although the two wild-type strains elicit preferential immune responses for IL-8, both truncation of the O-glycan and deletion of the S-layer result in significantly increased release of IL-8, granulocyte-macrophage colony-stimulating factor and monocyte chemoattractant protein-1. Through immunofluorescence and confocal laser scanning microscopy of infected HOK we additionally show that T. forsythia is highly invasive and tends to localize to the perinuclear region. This indicates, that the T. forsythia S-layer and attached sugars, particularly pseudaminic acid in ATCC 43037, contribute to dampening the response of epithelial tissues to initial infection and hence play a pivotal role in orchestrating the bacterium's virulence.

Salivary Colony Stimulating Factor-1 and Interleukin-34 in Periodontal Disease.

BACKGROUND: Colony-stimulating factor (CSF)-1 and interleukin (IL)-34 are macrophage growth factors and regulators of osteoclastogenesis. Their potential involvement in periodontal disease is yet unknown. The aim of this study is to explore the presence of CSF-1 and IL-34 in whole saliva in relation to periodontal disease. METHODS: Protocol validation was assessed in saliva of healthy donors (n = 21) by enzyme-linked immunosorbent assay. Salivary CSF-1, IL-34, and matrix metalloproteinase (MMP)-8, a biomarker candidate of periodontitis, were determined in 48 patients (29 patients with periodontitis, 12 with gingivitis, and seven healthy patients) and related to the following clinical periodontal parameters: bleeding on probing, probing depth, clinical attachment loss, and plaque index. An additional separate group of patients with gingivitis (n = 21) and some of the patients with periodontitis (n = 11) were subjected to non-surgical periodontal treatment, whereupon changes in salivary CSF-1, IL-34, and MMP-8 levels were determined and related to periodontal outcome. RESULTS: Patients with periodontitis displayed higher CSF-1 and MMP-8 levels in saliva compared with healthy patients, and IL-34 levels were lower. A higher CSF-1/IL-34 ratio was observed in patients with periodontitis compared with healthy patients. There was a positive correlation between CSF-1 and MMP-8, which both correlated negatively to IL-34, in patients with gingivitis and periodontitis. Clinical periodontal parameters correlated positively with CSF-1, MMP-8, and with the CSF-1/IL-34 ratio, and negatively with IL-34 in patients with periodontitis. After treatment CSF-1 and MMP-8 levels decreased together with observed clinical improvement in patients with gingivitis. CONCLUSION: CSF-1 and IL-34 are present in saliva and seem to have complementary roles in periodontal disease: IL-34 in steady-state and CSF-1 in inflammation.

Twentieth-century changes in the genetic composition of Swedish field pea metapopulations.

Landrace crops are formed by local adaptation, genetic drift and gene flow through seed exchange. In reverse, the study of genetic structure between landrace populations can reveal the effects of these forces over time. We present here the analysis of genetic diversity in 40 Swedish field pea (Pisum sativum L.) populations, either available as historical seed samples from the late nineteenth century or as extant gene bank accessions assembled in the late twentieth century. The historical material shows constant high levels of within-population diversity, whereas the extant accessions show varying, and overall lower, levels of within-population diversity. Structure and principal component analysis cluster most accessions, both extant and historical, in groups after geographical origin. County-wise analyses of the accessions show that the genetic diversity of the historical accessions is largely overlapping. In contrast, most extant accessions show signs of genetic drift. They harbor a subset of the alleles found in the historical accessions and are more differentiated from each other. These results reflect how, historically present metapopulations have been preserved during the twentieth century, although as genetically isolated populations.

Resistin is associated with breach of tolerance and anti-nuclear antibodies in patients with hepatobiliary inflammation.

Resistin is a cysteine-rich protein, which is abundantly expressed at the site of inflammation, and acts as a regulator of the NF-kB-dependent cytokine cascade. The aim of this study was to evaluate resistin levels in relation to inflammatory mediators, disease phenotype and autoantibody status in a spectrum of pathological conditions of the gastrointestinal tract. Resistin levels were measured with an ELISA in sera originated from 227 patients and 40 healthy controls (HC). Fifty patients diagnosed with non-alcoholic fatty liver disease (NAFLD), 53 ulcerative colitis (UC), 51 Crohn's disease (CD), 46 autoimmune hepatitis (AIH) and 27 primary sclerosing cholangitis (PSC) were included. The sera were analysed with respect to biochemical parameters of systemic inflammation and liver function and to the presence of antibodies to nuclear antigens (ANA), mitochondria (AMA) and smooth muscle (SMA). Compared with HC, resistin levels were raised in AIH (P = 0.017) and PSC (P = 0.03); compared with NAFLD, levels were elevated in CD (P = 0.041), AIH (P < 0.001) and PSC (P < 0.001). Patients with elevated levels of resistin were more often treated with corticosteroids, but no difference was found between active disease and clinical remission. Resistin levels were significantly higher in ANA-positive individuals compared with ANA-negative (P = 0.025). Resistin levels were directly correlated with IL-6 (r = 0.30, P = 0.02) and IL-8 (r = 0.51, P < 0.001). Elevated levels of resistin were prominent in patients with hepatobiliary inflammation and were associated with breach of self-tolerance, i.e. ANA positivity. Thus, we propose that resistin may be an important marker of disease severity in autoantibody-mediated gastrointestinal inflammatory diseases.

Selective presence of the chemokine growth-regulated oncogene alpha (GROalpha) in the human follicle and secretion from cultured granulosa-lutein cells at ovulation.

Ovulation is an inflammation-like reaction in which leukocytes are postulated to have a central role. The abundance of leukocytes in the ovary varies with the stage of the cycle and a marked influx of neutrophils and monocytes into the interior of the follicle during ovulation has been observed. The intraovarian signals causing this preovulatory influx are not known. In the present study we have investigated the presence in the ovary of two chemotactic cytokines, GROalpha (growth-regulated oncogene alpha) and RANTES (regulated upon activation, normal T-cell expressed and secreted), which have specific chemotactic activity towards neutrophils/basophils/T-cells and monocytes/T-cells/eosinophils respectively. The concentrations of these cytokines were first measured in follicular fluid and peripheral blood from a group of patients undergoing in-vitro fertilization (IVF) procedures. GROalpha was found in approximately 10-fold higher concentrations in follicular fluid than in blood plasma from the same patients (P < 0.001). The concentrations in peripheral blood of GROalpha were similar and without significant variations in women during the time of gonadotrophin stimulation for IVF and throughout the normal menstrual cycle. There was no correlation between follicular fluid concentrations of GROalpha and follicular fluid concentrations of progesterone or oestradiol. Cultured granulosa-lutein cells secreted detectable amounts of GROalpha. The concentrations of GROalpha in the medium were markedly increased by the presence of the proinflammatory cytokine interleukin (IL)-1beta, with approximately 10-fold higher concentrations in the medium, compared with the controls (P < 0.001). GROalpha was localized by immunohistochemistry predominantly in the theca layer but also in the granulosa layer of the dominant follicle during the late follicular phase. The concentrations of RANTES in follicular fluid were only 1/50 of those in blood plasma (P< 0.001). RANTES protein was not detectable in the culture medium of granulosa-lutein cells neither during basal nor IL-1beta stimulated conditions. In conclusion, these results suggest that the chemokine GROalpha is one of the chemotactic signals which cause recruitment and activation of specific leukocytes within the ovulating follicle.

Mutagenicity testing of organic extracts of diesel exhaust particles after spiking with polycyclic aromatic hydrocarbons (PAH).

In the present study, spiking was used as a strategy to evaluate the mutagenicity of individual compounds in a mixture. Mutagenicity of individual polycyclic aromatic hydrocarbons (PAH) was evaluated in an organic extract of diesel exhaust particles (DEP). The particles were extracted with dichloromethane (DCM). After replacing DCM with dimethylsulphoxide (DMSO), the extract was spiked with four individual PAH: benzo(a)pyrene, benzo(a)anthracene, pyrene and fluoroanthene. The PAH were added separately and in various combinations to the extract to determine the effects of each variable and to identify possible interactions between the individual PAH and between the PAH and the extract. The study was designed as a fractional factorial experiment with the five variables (the DEP extract and the four PAH), giving 16 (instead of 32) mixtures plus a triplicate centrepoint and background, i.e. a total of 20. The fractionated factorial design used in the present work supports a model with linear and interaction terms. The mixtures were tested for mutagenicity in the Ames assay using four strains of Salmonella typhimurium in the presence of rat liver xenobiotic enzymes (S9-mix). Projections to Latent Structures (PLS) was used to quantify the mutagenicity of each compound and possible interactions. The four individual PAH and the DEP extract acted additively in the Ames test with 10% S9-mix.

The human preovulatory follicle is a source of the chemotactic cytokine interleukin-8.

Mammalian ovulation has several similarities to local inflammatory reactions, involving participation of leukocytes and inflammatory mediators. In response to a preovulatory luteinizing hormone surge, there is an influx of leukocytes into the preovulatory follicle and uncharacterized chemotactic activity towards these cells has previously been reported in follicular fluid of several species, including the human. In the present study, we have investigated the presence and local production of interleukin-8 (IL-8), a potent leukocyte-chemotactic and neutrophil-activating cytokine, in the human preovulatory follicle. Immunoreactive IL-8 was present in the follicular fluid in all of 12 in-vitro fertilization (IVF) patients investigated. IL-8 concentrations in follicular fluid (1269 +/- 245 pg/ml) were approximately 30-fold higher than in plasma (41 +/- 14 pg/ml). Isolated granulosa cells in culture secreted large amounts of IL-8 protein. Basal secretion of IL-8 was dose-dependently enhanced by the presence of fetal calf serum and was further stimulated by the addition of the ovulation-associated cytokine IL-1 beta. Messenger RNA for IL-8 was detected by reverse transcription/polymerase chain reaction (RT-PCR) in all tested samples of granulosa cells of IVF patients (n = 8) and in all biopsies from preovulatory follicle walls obtained in natural cycles (n = 6). This is the first demonstration of IL-8 in the mammalian ovary. Local production, combined with high follicular fluid concentrations, suggests that this cytokine plays a role in cyclic ovarian events, such as ovulation.