Existencia y unicidad de solución y comportamiento asintótico para la ecuación de onda con condición de frontera del tipo Neumann y disipación localmente distribuido

En este trabajo se estudia la existencia y unicidad de solución de la ecuación de la onda con condiciones de frontera del tipo Neumann, con disipación localmente distribuida usando el método de Faedo Galerkin. Además analiza el decaimiento no exponencial de la energía asociado al sistema planteado. Se hacen las estimativas correspondientes basándose en propiedades del espacio donde se encuentra la solución de la ecuación, así como los teoremas correspondientes al sistema estudiado.Tesi

The effect of the MAPK inhibitors PD98059 or SB203580 on TNF-α-induced Cyp7b activity

<p><b>Copyright information:</b></p><p>Taken from "Tumour necrosis factor-α stimulates dehydroepiandrosterone metabolism in human fibroblast-like synoviocytes: a role for nuclear factor-κB and activator protein-1 in the regulation of expression of cytochrome p450 enzyme 7b"</p><p>Arthritis Research & Therapy 2005;7(6):R1271-R1280.</p><p>Published online 15 Sep 2005</p><p>PMCID:PMC1297571.</p><p>Copyright © 2005 Dulos et al.; licensee BioMed Central Ltd.</p> Fibroblast-like synoviocytes (FLS; SCRO.14.SF, passages 8–12) were incubated for 1 hour in the presence or absence (-) of the mitogen-activated protein kinase (MAPK) kinase (MEK)1 inhibitor PD98059 (PD) or the p38 inhibitor SB203580 (SB). Thereafter, cells were incubated in the presence or absence of 0.5 ng/ml tumour necrosis factor (TNF)-α plus 1.5 × 10mol/l [H]-dehydroepiandrosterone (DHEA) for 24 hours and processed using high-performance liquid chromatography. The amount of 7α-hydroxy-dehydroepiandrosterone (7α-OH-DHEA) is expressed as the percentage [H]-7α-OH-DHEA of the total amount of [H]-label measured. Results are expressed as the mean ± standard error of the mean of triplicate sample. Data are representative of three independent experiments. *< 0.05 versus TNF-α (Student's t-test). The data from panel a (three independent experiments) are combined for the highest inhibitor concentrations. PD98059 and SB23580 were dissolved in methanol (MeOH) and dimethylsulfoxide (DMSO), respectively, and used as controls. *< 0.05 (Student's t-test). Cyp7b = cytochrome p450 enzyme 7b

<i>Candida albicans</i> and Zymosan A aggravate the inflammation in the chronic SCW model.

<p>On days 0, 7, 14, and 21, streptococcal cell wall (SCW) fragments were injected intra-articularly (i.a.) into the knee joint. Joint swelling (ratio of ^{99 m}Tc uptake in the treated right knee joint to that in the untreated left knee joint) were determined 1 day after every injection (A) and during the chronic phase of the model on day 28 (B; n=6 mice/group). In addition, the inflammatory cell influx (C) on histological slides was quantified on day 28. H&E stained frontal knee sections (original magnification 100×) (D) are shown (n=8 mice/group. Values are the mean ± SEM; ns=non significant, * P<0.05, ** P<0.01, *** P<0.001, by One-way ANOVA.</p

Co-exposure to <i>C. albicans</i> induces Th17 cells in the joint.

<p>The mRNA expression of T-bet, GATA-3, RORγT and FOXP3 in synovial biopsies of the knee joints (n=3 mice/group) were measured by QPCR (A) The mRNA expression of IFNy, IL-17A, IL-17F, IL-21, IL-22 and IL-10 are shown (B). The knee joint synovium was dissected and prepared for enzymatic digestion. The cells were incubated with PMA/ionomycine and Golgiplug for 5 hours before flowcytometric analysis (n=6 mice/group) and stained for CD3, IL-17, and IFN-γ. Representative dot plots of the isolated cells gated on CD3+ are shown (C). The mean percentage of isolated IFN-γ and IL-17 producing T cells (CD3+ population) are shown (D). Results are mean ± SEM; ns=non significant *=P<0.05, **=P<0.01, by one-way ANOVA.</p

Exposure to <i>C. albicans</i> increases the cartilage destruction and bone erosion during chronic SCW arthritis.

<p>Analysis of destructive parameters after 4 relapsing flares of arthritis. On day 28, knee joints (n=8/group) were harvested for histological assessment. Knee joint sections were stained using Safranin O to determine the degree of proteoglycan (PG) depletion. H&E staining was used to score the degree of chondrocyte death, cartilage surface erosion and bone erosion (A). QPCR analysis of destructive related genes was performed on synovial biopsies (n=3/group) of day 22, one day after the last injection (B). Representative images of arthritic knee joints showing immunohistochemical staining for VDIPEN after the 4 repeated injections (day 28) (C). Besides, the quantitative measurement of VDIPEN expression (percentage of positively stained area) in the cartilage of the 3 groups of mice (n=8/group) was analyzed. Values are the mean ± SEM; ns=non significant * P<0.05, ** P<0.01, *** P<0.001, by One-way ANOVA.</p

<i>C. albicans</i> skews T-cell cytokine profile.

<p>Serum levels of anti-SCW-specific total IgG, IgG1, and IgG3 antibodies (A). Draining lymph node cells (1*10⁵/well) were stimulated with anti-CD3/anti-CD28 antibodies for 72 hours (n=6/group). Levels of IFN-γ, IL-17 and IL-10 were determined by Luminex in the supernatants of the stimulated lymph node cells (B) and washouts of synovial biopsies of day 22 (C). Results are the mean ± SEM; ns=non significant *=P<0.05; **=P<0.01, ***=P<0.001, by One-Way ANOVA.</p

Table_2_Bacillus Calmette–Guérin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice.docx

<p>Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an influenza pandemic, which may have severe consequences due to the absence of pre-existent immunity to this strain at population level. Currently there is no influenza A (H7N9) vaccine available. Therefore, in case of a pandemic outbreak, alternative preventive approaches are needed, ideally even independent of the type of influenza virus outbreak. Bacillus Calmette–Guérin (BCG) is known to induce strong heterologous immunological effects, and it has been shown that BCG protects against non-related infection challenges in several mouse models. BCG immunization of mice as well as human induces trained innate immune responses, resulting in increased cytokine responses upon subsequent ex vivo peripheral blood mononuclear cell restimulation. We investigated whether BCG (Statens Serum Institut-Denmark)-induced trained immunity may protect against a lethal avian influenza A/Anhui/1/2013 (H7N9) challenge. Here, we show that isolated splenocytes as well as peritoneal macrophages of BCG-immunized BALB/c mice displayed a trained immunity phenotype resulting in increased innate cytokine responses upon ex vivo restimulation. However, after H7N9 infection, no significant differences were found between the BCG immunized and the vehicle control group at the level of survival, weight loss, pulmonary influenza A nucleoprotein staining, or histopathology. In conclusion, BCG-induced trained immunity did not result in protection in an oseltamivir-sensitive influenza A/Anhui/1/2013 (H7N9) challenge mouse model.</p

Image_1_Bacillus Calmette–Guérin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice.tif

<p>Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an influenza pandemic, which may have severe consequences due to the absence of pre-existent immunity to this strain at population level. Currently there is no influenza A (H7N9) vaccine available. Therefore, in case of a pandemic outbreak, alternative preventive approaches are needed, ideally even independent of the type of influenza virus outbreak. Bacillus Calmette–Guérin (BCG) is known to induce strong heterologous immunological effects, and it has been shown that BCG protects against non-related infection challenges in several mouse models. BCG immunization of mice as well as human induces trained innate immune responses, resulting in increased cytokine responses upon subsequent ex vivo peripheral blood mononuclear cell restimulation. We investigated whether BCG (Statens Serum Institut-Denmark)-induced trained immunity may protect against a lethal avian influenza A/Anhui/1/2013 (H7N9) challenge. Here, we show that isolated splenocytes as well as peritoneal macrophages of BCG-immunized BALB/c mice displayed a trained immunity phenotype resulting in increased innate cytokine responses upon ex vivo restimulation. However, after H7N9 infection, no significant differences were found between the BCG immunized and the vehicle control group at the level of survival, weight loss, pulmonary influenza A nucleoprotein staining, or histopathology. In conclusion, BCG-induced trained immunity did not result in protection in an oseltamivir-sensitive influenza A/Anhui/1/2013 (H7N9) challenge mouse model.</p

Table_1_Bacillus Calmette–Guérin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice.docx

<p>Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an influenza pandemic, which may have severe consequences due to the absence of pre-existent immunity to this strain at population level. Currently there is no influenza A (H7N9) vaccine available. Therefore, in case of a pandemic outbreak, alternative preventive approaches are needed, ideally even independent of the type of influenza virus outbreak. Bacillus Calmette–Guérin (BCG) is known to induce strong heterologous immunological effects, and it has been shown that BCG protects against non-related infection challenges in several mouse models. BCG immunization of mice as well as human induces trained innate immune responses, resulting in increased cytokine responses upon subsequent ex vivo peripheral blood mononuclear cell restimulation. We investigated whether BCG (Statens Serum Institut-Denmark)-induced trained immunity may protect against a lethal avian influenza A/Anhui/1/2013 (H7N9) challenge. Here, we show that isolated splenocytes as well as peritoneal macrophages of BCG-immunized BALB/c mice displayed a trained immunity phenotype resulting in increased innate cytokine responses upon ex vivo restimulation. However, after H7N9 infection, no significant differences were found between the BCG immunized and the vehicle control group at the level of survival, weight loss, pulmonary influenza A nucleoprotein staining, or histopathology. In conclusion, BCG-induced trained immunity did not result in protection in an oseltamivir-sensitive influenza A/Anhui/1/2013 (H7N9) challenge mouse model.</p