Keratinocyte Growth-Factor Promotes Epithelial Survival and Resolution in a Human Model of Lung Injury

Rationale: Increasing epithelial repair and regeneration may hasten resolution of lung injury in patients with the Acute Respiratory Distress Syndrome (ARDS). In animal models of ARDS, Keratinocyte Growth Factor (KGF) reduces injury and increases epithelial proliferation and repair. The effect of KGF in the human alveolus is unknown.

Objectives: To test whether KGF can attenuate alveolar injury in a human model of ARDS.

Methods: Volunteers were randomized to intravenous KGF (60 μg/kg) or placebo for 3 days, before inhaling 50μg lipopolysaccharide. Six hours later, subjects underwent bronchoalveolar lavage (BAL) to quantify markers of alveolar inflammation and cell-specific injury.

Measurements and Main Results: KGF did not alter leukocyte infiltration or markers of permeability in response to LPS. KGF increased BAL concentrations of Surfactant Protein D (SP-D), MMP-9, IL-1Ra, GM-CSF and CRP. In vitro, BAL fluid from KGF-treated subjects (KGF BAL) inhibited pulmonary fibroblast proliferation, but increased alveolar epithelial proliferation. Active MMP-9 increased alveolar epithelial wound repair. Finally, BAL from the KGF pre-treated group enhanced macrophage phagocytic uptake of apoptotic epithelial cells and bacteria compared with BAL from the placebo-treated group. This effect was blocked by inhibiting activation of the GM-CSF receptor.

Conclusions: KGF treatment increases BAL SP-D, a marker of type II alveolar epithelial cell proliferation in a human model of ALI. Additionally KGF increases alveolar concentrations of the anti-inflammatory cytokine IL-1Ra, and mediators that drive epithelial repair (MMP-9) and enhance macrophage clearance of dead cells and bacteria (GM-CSF).

Postpartum GAD is a risk factor for postpartum MDD: the course and longitudinal relationships of postpartum GAD and MDD

Background The objective was to examine the course and longitudinal associations of generalized anxiety disorder (GAD) and major depressive disorder (MDD) in mothers over the postpartum 2 years. Method Using a prospective naturalistic design, 296 mothers recruited from a large community pool were assessed for GAD and MDD at 3, 6, 10, 14, and 24 months postpartum. Structured clinical interviews were used for diagnoses, and symptoms were assessed using self-report questionnaires. Logistic regression analyses were used to examine diagnostic stability and longitudinal relations, and latent variable modeling was employed to examine change in symptoms. Results MDD without co-occurring GAD, GAD without co-occurring MDD, and co-occurring GAD and MDD, displayed significant stability during the postpartum period. Whereas MDD did not predict subsequent GAD, GAD predicted subsequent MDD (in the form of GAD + MDD). Those with GAD + MDD at 3 months postpartum were significantly less likely to be diagnosis free during the follow-up period than those in other diagnostic categories. At the symptom level, symptoms of GAD were more trait-like than those of depression. Conclusions Postpartum GAD and MDD are relatively stable conditions, and GAD is a risk factor for MDD but not vice versa. Given the tendency of MDD and GAD to be persistent, especially when comorbid, and the increased risk for MDD in mothers with GAD, as well as the potential negative effects of cumulative exposure to maternal depression and anxiety on child development, the present findings clearly highlight the need for screening and treatment of GAD in addition to MDD during the postpartum period.

Computational simulation of the influence of inert particles on incomplete combustion of methane at a low air factor

It is well known that the gas–solid system plays a significant role in many industrial processes. It is a complex physical and chemical process, generally consisting of heat transfer, mass transfer, species diffusion, and chemical reactions. In this paper, the reaction of methane with air at a low air factor and the gas flow in a fluidized bed with 0.1 mm solid particles are computationally simulated to enable the study of the effect of the inert particles on the species diffusion and the chemical reactions. The reaction of methane and air is modeled by a two-step reaction mechanism that produces a continuous fluid phase composed of six gases (CH₄, CO, O₂, CO₂, H₂O, and N₂) and discrete solid particles in the reactor. The simulation results are compared with experiment and show that the finite rate model and the eddy dissipation model can well describe the reactions of gases in high-density gas–solid systems. The distribution of each gas and the particle behaviors are analyzed for incomplete combustion at different concentrations of loaded solid particles. The inert particles change the reactions by enhancing both the chemical kinetics and the species diffusion dynamics.

Mild gestational hyperglycaemia as a risk factor for metabolic syndrome in pregnancy and adverse perinatal outcomes

Objective The aims of this study were to evaluate the prevalence of metabolic syndrome (MS) in a cohort of pregnant women with a wide range of glucose tolerance, pre-pregnancy risk factors for MS during pregnancy and the effects of MS in the occurrence of adverse perinatal outcomes.Research Design and Methods One hundred and thirty six women with positive screening for gestational diabetes (GDM) were classified by two diagnostic methods: glycaemic profile and 100 g oral glucose tolerance test (OGTT) as normoglycaemic, mild gestational hyperglycaemic, GDM, and overt GDM. Markers of insulin resistance were measured between 24-28 and 36th week of gestation, and 6 weeks after delivery.Results The prevalence of MS was 0; 20.0; 23.5 and 36.4% in normoglycaemic, mild hyperglycaemic, GDM and overt GDM groups, respectively. Previous history of GDM with or without insulin use, body mass index (BMI) >= 25, hypertension, family history of diabetes in first-degree relatives, non-Caucasian ethnicity, history of prematurity and polyhydramnios were statistically significant pre-pregnancy predictors for MS in the index pregnancy, that by its turn increased the occurrence of adverse perinatal outcomes (p = 0.01).Conclusions The prevalence of MS increases with the worsening of glucose tolerance and is an independent predictor of adverse perinatal outcomes; impaired glycaemic profile identifies pregnancies with important metabolic abnormalities that are linked to the occurrence of adverse perinatal outcomes even in the presence of a normal OGTT, in patients that are not currently classified as having GDM. Copyright (C) 2008 John Wiley & Sons, Ltd.

Studies on the Expression of Fibroblast Growth Factor-2 from Odontoblast-like Cells

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

Cyclosporin but not tacrolimus significantly increases salivary cytokine contents in rats

Background: Cyclosporin (CsA) and tacrolimus (FK-506) are immunosuppressive drugs that specifically inhibit T-cell activation via calcineurin inhibition. Gingival overgrowth is a common side effect following the administration of CsA. The severity of gingival overgrowth seen in patients taking FK-506 is less than that observed with CsA. Little is known about the involvement of saliva in drug-induced gingival overgrowth. The purpose of this study was to investigate the salivary contents of tumor growth factor β1 (TGF-β1), epidermal growth factor (EGF), and interleukin-6 (IL-6) as well as the hystometry of gingival tissue obtained from rats treated with either FK-506 or CsA. Methods: For 30 or 60 days rats received daily subcutaneous injection doses of either CsA or FK-506 (10 mg/kg). The concentrations of TGF-β1, EGF, and IL-6 in saliva were determined by enzyme-linked immunosorbent assay, and after histological processing, the oral epithelium and connective tissue were assessed at the region of the lower first molars. Results: The levels of TGF-β1, EGF, and IL-6 in saliva were not significantly altered by any of the treatments after 30 days. After 60 days of treatment with CsA, gingival overgrowth and significant increase in salivary TGF-β1, EGF, and IL-6 concentrations were observed; no statistically significant changes were induced by FK-506. Conclusion: Within the limits of this experimental study, it can be concluded that CsA, but not FK-506, induced gingival overgrowth associated with an increase of the salivary levels of the cytokines TGF-β1, EGF, and IL-6.

Le(a-b-) phenotype: potential risk factor for infection by the RH strain of Toxoplasma gondii in pregnancy

The Lewis histo-blood group system is characterized by the expression of the Lea and Le(b) antigens in the gastrointestinal tract, whose synthesis results in interactions between alpha 2-L-fucosyltransferase (FUTII) and alpha 3/4-L-fucosyltransferase (FUTIII) enzymes coded by the FUT2 (19q. 13.3) and FUT3 (19p13.3) genes. FUTII and FUTIII fucosylate the type 1 oligosaccharide precursor (Gal beta 1 -> 3NAcGlc beta 1 -> 3-R) at distinct positions to form H type 1 (Fuc alpha 1. 2Gal beta 1. 3NAcGlc beta 1 -> 3-R) and Le(a) (Gal beta 1 -> 3[Fuc alpha 1 -> 4] NAcGlc beta 1 -> 3-R) antigens, respectively. The fucosylation of H type 1 antigens by FUTIII results in the Leb antigen (Fuc alpha 1. 2Gal beta 1. 3[Fuca1. 4] NAcGlc beta 1. 3-R). Thus, the presence of the FUTII and FUTIII enzymes leads to the expression of the Le(a+b+) phenotype, while the presence of only FUTIII allows the expression of the Le(a+b-) phenotype. The absence of the FUTIII enzyme leads to the expression of the Le(a-b-) phenotype, independent of the presence or absence of FUTII. Point mutations in FUT2 and FUT3 genes change the activity of these enzymes, impair the synthesis of Le(a) and Le(b) antigens, and contribute to the variability of Lewis phenotypes in the gastrointestinal tract. Toxoplasma gondii, an apicomplexan parasite that infects a large proportion of the world's population, utilizes the gastrointestinal tract as an infection route and seems to adhere to glycosylated molecules to invade human cells. These apparently independent events may be related. The aim of this study was to test the hypothesis that there is an association between the Lewis histo-blood group system and infection by T. gondii. Two hundred and nine serum samples collected from pregnant women were submitted to screening tests to detect anti-T. gondii antibodies, employing the indirect hemagglutination method. ELISA was utilized to identify IgG class anti-T. gondii antibodies specific for the RH strain. A hundred and ninety-five samples with concordant results for both methods were selected to form two groups: seropositive (G1) and seronegative (G2). The G428A mutation of the FUT2 gene, and T202C and C314T of the FUT3 gene, which allow inference of the gastrointestinal tract Lewis phenotypes, were identified using PCR-RFLP and PCR-SSP methods, respectively. Among the 195 samples selected, 116 (59.5%) were seropositive and 79 (40.5%) were seronegative. In G1, 68 (58.6%) were classified as Le(a+b+), 30 (25.9%) as Le(a+b-), and 18 (15.5%) as Le(a-b-), and in G2, 67 (84.8%) were classified as Le(a+b+), 12 (15.2%) as Le(a+b-), and 0 (0%) as Le(a-b-) (P < 0.0001). The Le(a-b-) phenotype is associated with a high risk of RH strain T. gondii infection when compared with the Le(a+b+) [P = 0.0001; OR = 36,460; 95%CI = 2.152-617,680] and Le(a+b-) phenotypes [P = 0.0118; OR = 15,165; 95%CI = 0.8463-271,710]. The Le(a+b-) phenotype showed a higher risk compared to the Le(a+b+) phenotype [P = 0.0206; OR = 2463; 95%CI = 2463-5214]. The results suggest that the Le(a-b-) phenotype is strongly associated with a greater risk of infection by the RH strain of T. gondii compared to the other phenotypes. It is possible that the absence of fucosylation of the type 1 oligosaccharide precursor as well as the variations in the structures of the Le(a) and Le(b) antigens influence susceptibility to infection by this parasite.

Purificação, imobilização e caracterização bioquímica de lipase produzida por Penicillium sect. Gracilenta CBMAI 1583 em cultivo submerso

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Dose-response effect of interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, and interferon-y on the in vitro production of epithelial neutrophil activating peptide-78 (ENA-78), IL-8, and IL-6 by human endometrial stromal cells

The production of epithelial neutrophil activating peptide-78 (NA-78) and the interleukins IL-8 and IL-6 by endometrial stromal cells is stimulated by pro-inflammatory interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α). IL-8 is suggested to play a role in the pathogenesis of endometriosis, and in these women the peritoneal fluid concentrations of ENA-78 and IL-8 are increased. TNF-α has been tested together with interferon-γ because of their cooperative stimulation of IL-6. The release of IL-8, however, is inhibited with increasing interferon levels. The aim of the study was the analysis of the production of ENA-78, IL-6 and IL-8 by cultured human endometrial stromal cells in the presence of varying concentrations of IL-1β, TNF-α, and interferon-γ.

Determinación de la actividad de la óxido nítrico sintetasa endotelial y del factor NF-kB, en la piel del paciente con pseudoangiomatosis eruptiva : informe preliminar

La pseudoangiomatosis eruptiva se caracteriza por la aparición brusca de múltiples pápulas eritematosas, asintomáticas, rodeadas de un halo blanquecino, con remisión espontánea. Histológicamente se observa dilatación vascular con escaso infiltrado inflamatorio. Su etiología permanece incierta a pesar de ser relacionada con virus o picaduras de insectos. Basados en el compromiso vascular, el objetivo del trabajo fue investigar la actividad de la enzima endotelial oxido nítrico sintetasa (eNOS) y la expresión del factor NF-kB por inmunohistoquimica en un intento de esclarecer su patogenia. Material y métodos: Se estudiaron diez pacientes con diagnóstico clínico de pseudoangiomatosis eruptiva (PAE) que presentaron la dermatosis en forma epidémica. Se realizaron biopsias teñidas con Hematoxilina-Eosina y Tricrómico de Masson. Se efectuó estudio virológico de los pacientes Nª 4, 9 y 10 mediante determinaciones serológicas para echovirus, enterovirus, citomegalovirus, parvovirus B19 y hepatitis A, B y C. En cinco pacientes se obtuvo material para determinación de eNOS y NF-kB. Resultados: Todos los pacientes, 5 hombres y 5 mujeres presentaron pápulas eritematosas rodeadas por un halo blanquecino, especialmente en las extremidades, alrededor de las rodillas. Histológicamente mostraron vasos dilatados y células endoteliales prominentes con un infiltrado discreto perivascular. Todos los estudios serológicos fueron negativos. La actividad de eNOS fue significativamente menor comparada con la piel normal (p= 0,002) y la expresión de NF- ĸB fue fuertemente positiva en los vasos de la dermis papilar y reticular. Conclusiones: Todos los pacientes fueron afectados en verano, por lo que la picadura del mosquito debe ser considerada como un factor etiológico. La baja expresión de eNOS está relacionada con la vasodilatación y la expresión aumentada de NF-ĸB confirma que el proceso es de tipo inflamatorio.

Cleopatra Hylly Opus [Material gráfico] : Carneolae incisum. Ex Fulvii Virsini Imag.

Resumen: Descripción: retrato de perfil hacia la derecha insertado en un medallón ovalado

S. Nicolás de Tolentino [Material gráfico] : Especial abogado contra las calenturas

Inscripción: "Venerado en su Ille. Cofradia en el Rl. Convto. de Sn. Agustin de de Val."

Glorias de Azara en el siglo XIX: acta de la solemne inauguración del monumento erigido en Barbuñales de Aragón, el 27 de noviembre de 1850, al ... Sr. Don José Nicolás de Azara y Perera, Primer Marqués de Nibbiano por su sobrino y sucesor ... Agustín de Azara ... /

Contiene: Primera Parte. Corona poetico-musical que una gran parte de literatos y algunos profesores de música españoles del siglo XIX, consagran a la buena memoria del célebre diplomatico y distinguido escritor español el Excmo. Sr. D. José Nicolas de Azara y Perera -- Segunda parte. Notas á la Corona poetica : traducciones a algumas de las poesias insertas en dialectos provinciales, aclaraciones y cartas que las esplican. Discurso historico-arqueológico sobre la musica en general, y en particular la española, escrito en honor á la buena memoria del siglo XVIII, el Excmo. Sr. D. Jose Nicolas de Azara y Perera ... / por su historiador Basilio Sebastian Castellanos de Losada. Discurso historico-arqueologico sobre el baile en general, y en particular del español, escrito en honor á la buena memoria del célebre diplomático y literato el Excmo. Sr. D. José Nicolas de Azara y Perera ... / por su historiador Basilio Sebastian Castellanos de Losada.

Compendio de la vida, virtudes, y milagros del Beato Padre Francisco Caraciolo, fundador de la sagrada religion de los Clerigos Menores /

Mode of access: Internet.