Periodontal pathogens affect the level of protease inhibitors in gingival crevicular fluid

In periodontitis, an effective host-response is primarily related to neutrophils loaded with serine proteases, including elastase (NE) and protease 3 (PR3), the extracellular activity of which is tightly controlled by endogenous inhibitors. In vitro these inhibitors are degraded by gingipains, cysteine proteases produced by Porphyromonas gingivalis. The purpose of this study was to determine the level of selected protease inhibitors in gingival crevicular fluid (GCF) in relation to periodontal infection. The GCF collected from 31 subjects (nine healthy controls, seven with gingivitis, five with aggressive periodontitis and 10 with chronic periodontitis) was analyzed for the levels of elafin and secretory leukocyte protease inhibitor (SLPI), two main tissue-derived inhibitors of neutrophil serine proteases. In parallel, activity of NE, PR3 and arginine-specific gingipains (Rgps) in GCF was measured. Finally loads of P. gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola were determined. The highest values of elafin were found in aggressive periodontitis and the lowest in controls. The quantity of elafin correlated positively with the load of P. gingivalis, Ta. forsythia and Tr. denticola, as well as with Rgps activity. In addition, NE activity was positively associated with the counts of those bacterial species, but not with the amount of elafin. In contrast, the highest concentrations of SLPI were found in periodontally healthy subjects whereas amounts of this inhibitor were significantly decreased in patients infected with P. gingivalis. Periodontopathogenic bacteria stimulate the release of NE and PR3, which activities escape the control through degradation of locally produced inhibitors (SLPI and elafin) by host-derived and bacteria-derived proteases.

Wegener's granulomatosis presenting as pyoderma gangrenosum

Half of the patients with Wegener's granulomatosis develop skin lesions due to the systemic vasculitis. Wegener's granulomatosis should be included in the differential diagnostic considerations for necrotic ulcers, including leg ulcers. We present a case which demonstrates the importance of histological evaluation of a skin biopsy from the margin of the ulcer for establishing the diagnosis. Antineutrophil cytoplasmic antibodies with antigen specificity for proteinase 3 (PR3-ANCA) were detected supporting the diagnosis of Wegener granulomatosis. Further evaluation showed involvement of the eyes and kidneys. The ulcer rapidly healed under treatment with cyclophosphamide and corticosteroids.

Cellular Uptake of Neutrohpil Elastase Links Inflammation to Adaptive Immunity

Many tumors arise from sites of inflammation providing evidence that innate immunity is a critical component in the development and progression of cancer. Neutrophils are primary mediators of the innate immune response. Upon activation, an important function of neutrophils is release of an assortment of proteins from their granules including the serine protease neutrophil elastase (NE). The effect of NE on cancer has been attributed primarily to its ability to degrade the extracellular matrix thereby promoting invasion and metastasis. Recently, it was shown that NE could be taken up by lung cancer cells leading to degradation of insulin receptor substrate-1 thereby promoting hyperactivity of the phosphatidylinositol-3 kinase (PI3K) pathway and tumor cell proliferation. To our knowledge, nobody has investigated uptake of NE by other tumor types. In addition, NE has broad substrate specificity suggesting that uptake of NE by tumor cells could impact processes regulating tumorigenensis other than activation of the PI3K pathway. Neutrophil elastase has been identified in breast cancer specimens where high levels of NE have prognostic significance. These studies have assessed NE levels in whole tumor lysates. Because the major source of NE is from activated neutrophils, we hypothesized that breast cancer cells do not have endogenous NE but may take up NE released by tumor associated neutrophils in the tumor microenvironment and that this could provide a link between the innate immune response to tumors and specific adaptive immune responses. In this thesis, we show that breast cancer cells lack endogenous NE expression and that they are able to take up NE resulting in increased generation of low molecular weight cyclin E (CCNE) and enhanced susceptibility to lysis by CCNE-specific cytotoxic T lymphocytes. We also show that after taking up NE and proteinase 3 (PR3), a second primary granule protease with significant homology to NE, breast cancer cells cross-present the NE- and PR3-derived peptide PR1 rendering them susceptible to PR1-targeted therapies. Taken together, our data support a role for NE uptake in modulating adaptive immune responses against breast cancer.

Converting enzyme-independent release of tumor necrosis factor �� and IL-1�� from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3

Two important cytokines mediating inflammation are tumor necrosis factor �� (TNF��) and IL-1��, both of which require conversion to soluble forms by converting enzymes. The importance of TNF��-converting enzyme and IL-1��-converting enzyme in the production of circulating TNF�� and IL-1�� in response to systemic challenges has been demonstrated by the use of specific converting enzyme inhibitors. Many inflammatory responses, however, are not systemic but instead are localized. In these situations release and/or activation of cytokines may be different from that seen in response to a systemic stimulus, particularly because associations of various cell populations in these foci allows for the exposure of procytokines to the proteolytic enzymes produced by activated neutrophils, neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (Cat G). To investigate the possibility of alternative processing of TNF�� and/or IL-1�� by neutrophil-derived proteinases, immunoreactive TNF�� and IL-1�� release from lipopolysaccharide-stimulated THP-1 cells was measured in the presence of activated human neutrophils. Under these conditions, TNF�� and IL-1�� release was augmented 2- to 5-fold. In the presence of a specific inhibitor of NE and PR3, enhanced release of both cytokines was largely abolished; however, in the presence of a NE and Cat G selective inhibitor, secretory leucocyte proteinase inhibitor, reduction of the enhanced release was minimal. This finding suggested that the augmented release was attributable to PR3 but not NE nor Cat G. Use of purified enzymes confirmed this conclusion. These results indicate that there may be alternative pathways for the production of these two proinflammatory cytokines, particularly in the context of local inflammatory processes.

Recent landscape evolution at the "Barranco del R��o Dulce Natural Park" (Spain). Landscape units and mapping

Landscape units based on the visual features of the relief have been distinguished in the ���Barranco del R��o Dulce Natural Park��� (Spain). These units are geomorphic entities composed of several elementary landforms and characterized by a visual internal homogeneity, and contrast with other landscape units in their location, height, profile and gradients, reflecting their different evolution and genesis. Landscape units bear some subjectivity in their definition and in their boundary location due to the overlapping of geomorphic processes along time. Visual, compositional and conventional boundaries have been used for mapping. Neogene landscape evolution mainly occurred through thrust faulting at the Iberian Ranges-Tagus Basin boundary, driving tectonic uplift and erosion of the Ranges and correlative sedimentation in the Basin. Erosion of the Ranges occurred with the development of planation surfaces, leaving minor isolated reliefs in the upland plains landscape. The lowering of the base level, caused by the endorheic���exorheic transition of the Tagus Basin in the Pliocene, originates fluvial entrenchment and water table lowering with development of the first fluvial valleys and the capture of karstic depressions. Two subsequent phases of renewed fluvial incision (Pleistocene) lead to abandonment of some Pliocene valleys, fluvial captures, and development and reincision of tributaries

NOx storage and reduction over copper-based catalysts. Part 2: Ce0.8M0.2O�� supports (M = Zr, La, Ce, Pr or Nd)

5% copper catalysts with Ce0.8M0.2O�� supports (M = Zr, La, Ce, Pr or Nd) have been studied by rapid-scan operando DRIFTS for NOx Storage and Reduction (NSR) with high frequency (30 s) CO, H2 and 50%CO + 50%H2 micropulses. In the absence of reductant pulses, below 200���250 ��C NOx was stored on the catalysts as nitrite and nitro groups, and above this temperature nitrates were the main species identified. The thermal stability of the NOx species stored on the catalysts depended on the acid/basic character of the dopant (M more acidic = NOx stored less stable ��� Zr4+ < none < Nd3+ < Pr3+ < La3+ ��� M more basic = NOx stored more stable). Catalysts regeneration was more efficient with H2 than with CO, and the CO + H2 mixture presented an intermediate behavior, but with smaller differences among the series of catalyst than observed using CO alone. N2 is the main NOx reduction product upon H2 regeneration. The highest NOx removal in NSR experiments performed at 400 ��C with CO + H2 pulses was achieved with the catalyst with the most basic dopant (CuO/Ce0.8La0.2O��) while the poorest performing catalyst was that with the most acidic dopant (CuO/Ce0.8Zr0.2O��). The poor performance of CuO/Ce0.8Zr0.2O�� in NSR experiments with CO pulses was attributed to its lower oxidation capacity compared to the other catalysts.

Methyl jasmonate induced gene expression in wheat delays symptom development by the crown rot pathogen Fusarium pseudograminearum

The necrotrophic fungal pathogen Fusarium pseudograminearum (F. pseudograminearum) causes crown rot disease (CR) in wheat. This host-pathogen interaction has not been studied previously at the molecular level. In this study. using real-time quantitative PCR, the expression of 26 selected wheat genes was examined 1, 2 and 4 days after inoculation of wheat seedlings of the CR susceptible cultivar Kennedy and the partially field-resistant cultivar Sunco. Reproducible induction of eight defence genes consisting of PR1.1, PR2 (beta,1-3 glucanase), PR3 (chitinase), PR4 (wheativin), PR5 (thaumatin-like protein). TaPERO (peroxidase), PR10 and TaGLP2a (germin-like) was observed. These genes were induced in both cultivars, however. some genes were induced more rapidly in Sunco than in Kennedy. MJ treatment also induced the above pathogen responsive defence genes in both cultivars while benzo(1,2,3)thiadiazole-7-carbothionic acid S-methyl ester (BTH) treatment weakly induced them in Kennedy only. Similarly. treatment with MJ before inoculation significantly delayed the development of necrotic symptoms for 2 weeks in both wheat cultivars, while BTH pre-treatments delayed symptom development in Kennedy only. The chemically induced protection, therefore, correlated with induction of the F. pseudograminearum-responsive genes. These results support the emerging role of jasmonate signalling in defence against necrotrophic fungal pathogens in monocots and future manipulation of this pathway may improve CR resistance in wheat. (c) 2006 Elsevier Ltd. All rights reserved.

Efficient 2.87 ��m fiber laser passively switched using a semiconductor saturable absorber mirror

A passively switched Ho3+, Pr3+ codoped fluoride fiber laser using a semiconductor saturable absorber mirror (SESAM) is demonstrated. Q-switching and partial mode-locking were observed with the output power produced at a slope efficiency of 24% with respect to the absorbed pump power. The partially mode-locked 2.87 ��m pulses operated at a repetition rate of 27.1 MHz with an average power of 132 mW, pulse energy of 4.9 nJ, and pulse width of 24 ps.

The influence of photon excitation and proton irradiation on the luminescence properties of yttria stabilized zirconia doped with praseodymium ions

Lanthanide doped zirconia based materials are promising phosphors for lighting applications. Transparent yttria stabilized zirconia fibres, in situ doped with Pr3+ ions, were grown by the laser floating zone method. The single crystalline doped fibres were found to be homogeneous in composition and provide an intense red luminescence at room temperature. The stability of this luminescence due to transitions between the 1D2 ��� 3H4 multiplets of the Pr3+ ions (intra-4f2 configuration) was studied by photo- and iono-luminescence. The evolution of the red integrated photoluminescence intensity with temperature indicates that the overall luminescence decreases to ca. 40% of the initial intensity at 14 K when heated to room temperature (RT). RT analysis of the iono-luminescence dependence on irradiation fluence reveals a decrease of the intensity (to slightly more than ���60% of the initial intensity after 25 min of proton irradiation exposure). Nevertheless the luminescence intensity saturates at non-zero values for higher irradiation fluences revealing good potential for the use of this material in radiation environments.

Development of Zirconia based phosphors for application in lighting and as luminescent bioprobes

The strong progress evidenced in photonic and optoelectronic areas, accompanied by an exponential development in the nanoscience and nanotechnology, gave rise to an increasing demand for efficient luminescent materials with more and more exigent characteristics. In this field, wide band gap hosts doped with lanthanide ions represent a class of luminescent materials with a strong technological importance. Within wide band gap material, zirconia owns a combination of physical and chemical properties that potentiate it as an excellent host for the aforementioned ions, envisaging its use in different areas, including in lighting and optical sensors applications, such as pressure sensors and biosensors. Following the demand for outstanding luminescent materials, there is also a request for fast, economic and an easy scale-up process for their production. Regarding these demands, laser floating zone, solution combustion synthesis and pulsed laser ablation in liquid techniques are explored in this thesis for the production of single crystals, nanopowders and nanoparticles of lanthanides doped zirconia based hosts. Simultaneously, a detailed study of the morphological, structural and optical properties of the produced materials is made. The luminescent characteristics of zirconia and yttria stabilized zirconia (YSZ) doped with different lanthanide ions (Ce3+ (4f1), Pr3+ (4f2), Sm3+ (4f5), Eu3+ (4f6), Tb3+ (4f8), Dy3+ (4f9), Er3+ (4f11), Tm3+ (4f12), Yb3+ (4f13)) and co-doped with Er3+,Yb3+ and Tm3+,Yb3+ are analysed. Besides the Stokes luminescence, the anti- Stokes emission upon infrared excitation (upconversion and black body radiation) is also analysed and discussed. The comparison of the luminescence characteristics in materials with different dimensions allowed to analyse the effect of size in the luminescent properties of the dopant lanthanide ions. The potentialities of application of the produced luminescent materials in solid state light, biosensors and pressure sensors are explored taking into account their studied characteristics.

Proton conductivity and luminiscence properties of lanthanide aminotriphosphonates

Metal phosphonates are multifunctional solids with tunable properties, such as internal H-bond networks, and high chemical and thermal stability [1]. In the present work, we describe the synthesis, structural characterization, luminescent properties and proton conduction performance of a new family of isostructural cationic compounds with general formula [Ln(H4NMP)(H2O)2]Cl��2H2O [Ln = La3+, Pr3+, Sm3+, Gd3+, Tb3+, Dy3+, Ho3+, H6NMP = nitrilotris(methylphosphonic acid)]. These solids are formed by positively charge layers, which consist of isolated LnO8 polyhedra and bridge chelating NMP2- ligands, held apart by chloride ions and water molecules. This arrangement result in extended interlayer hydrogen networks with possible proton transfer pathways. The proton conductivity of Gd3+ sample, selected as prototype of the series, was measured. In the range between range 25�� and 80 ��C, the conductivity increase with the temperature up to a maximum value of 3.10-4 S��cm-1, at relative humidity of 95 %. The activation energy obtained from the Arrhenius plot (Figure 1) is in the range corresponding to a Grotthuss transfer mechanism.

Factors influencing dental appearance satisfaction in adolescents: a cross-sectional study conducted in Southern Brazil

The perception of dental aesthetic appearance may affect social interaction and psychological status, influencing dental needs and the search for treatments. Aim: To investigate the satisfaction with dental appearance and influencing factors among adolescents. Methods: The study was carried out among adolescents aged 14 to 19 years attending a private high school in Brazil. Data on demographic information, the perception of dental appearance, previous aesthetic treatments and wish to perform dental treatments were collected in the school. Data were analyzed using Pearson���s chi-square test or Linear Trend. Multivariate analysis was performed using the Poisson regression. Results: A total of 531 adolescents (Response rate = 98.3%) answered the questionnaire. The prevalence of dissatisfaction with dental appearance was 17.4%. Almost 65% had history of previous orthodontic treatment and 16% performed dental bleaching. Approximately 45% of children wished to undergo orthodontics and 54.8% to bleach their teeth. Dissatisfaction with dental appearance was associated with individuals unsatisfied with dental color (95% IC[1.73;4.32]), those perceiving poor dental alignment (PR3.16 95% IC[2.11;4.72]) and those wishing orthodontic treatment (PR2.9; 95% IC[1.79; 4.70]). Conclusions: The prevalence of dissatisfaction was considerable and was associated with aesthetic concerns such as tooth color, dental alignment and with the wish for orthodontics. In this young population, a large part of adolescents had already performed orthodontic and bleaching treatments and wished to perform those treatments again. Satisfaction with dental appearance could affect the adolescents��� behavior regarding search for dental treatment, thus causing possible overtreatment.

An��lisis de la participaci��n ciudadana en la localidad de Santa Fe en el proceso de formulaci��n del plan zonal centro de Bogot�� en el periodo 2004-2007

Este trabajo de grado es un estudio de caso, del proceso participativo para la formulaci��n del Plan Zonal Centro de Bogot�� entre 2004 y 2007, con el fin de observar los efectos de la participaci��n ciudadana de la Localidad de Santa Fe, en la formulaci��n de una pol��tica p��blica. En la investigaci��n se hace un an��lisis mediante las variables: contexto, las condiciones institucionales, el funcionamiento de los espacios de participaci��n, los actores que participaron y los efectos de la participaci��n ciudadana en el proceso decisional. Asimismo, el presente estudio de caso se vali�� de la teor��a de la racionalidad limitada para entender las decisiones del actor p��blico y sus l��mites, reconstruyendo el desarrollo del proceso participativo, para comprender la relaci��n entre el proceso decisional, que hace parte de la formulaci��n de la pol��tica p��blica, y las expectativas para tomar decisiones, que generan estos espacios de participaci��n a los ciudadanos que participan. El presente trabajo usa herramientas conceptuales adquiridos en los programas de Ciencia Pol��tica y Gesti��n y Desarrollo Urbanos.