Inhibition of protease-ENaC signaling improves mucociliary function in cystic fibrosis airways

Rationale: In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height
compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of ENaC have therapeutic potential in CF airways to reduce the hyperstimulated sodium and fluid absorption to levels which can restore airways hydration.

Objectives: To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function.

Methods: Protease activity was measured using fluorogenic activity assays. Differentiated primary airway epithelial cell cultures (F508del homozygotes) were used to determined ENaC activity (Ussing chamber recordings), ASL height (confocal microscopy) and mucociliary function (by tracking the surface flow of apically applied microbeads). Cell toxicity was measured by LDH assay.

Measurements and Results: QUB-TL1 inhibits extracellularly-located CAPs, including prostasin, matriptase and furin, the activities of which are observed at excessive levels at the apical surface of CF airway epithelial cells (AECs). QUB-TL1-mediated CAPs inhibition results in diminished ENaC-mediated Na+ absorption in CF AECs due to internalization of a prominent pool of cleaved (active) ENaCγ from the cell surface. Importantly, diminished ENaC activity correlates with improved airway hydration status and mucociliary clearance. We further demonstrate QUB-TL1-mediated furin inhibition, which is in contrast to other serine protease inhibitors (camostat mesylate and aprotinin), affords protection against neutrophil elastase-mediated ENaC activation and Pseudomonas aeruginosa exotoxin A induced cell death.

Conclusions: QUB-TL1 corrects aberrant CAP activities providing a mechanism to delay or prevent the development of CF lung disease in a manner independent of CFTR mutation.

The effect of long-chain polyunsaturated fatty acids intake during pregnancy on adiposity of healthy full-term offspring at birth

Objective - The adjusted effect of long-chain polyunsaturated fatty acid (LCPUFA) intake during pregnancy on adiposity at birth of healthy full-term appropriate-for-gestational age neonates was evaluated. Study Design - In a cross-sectional convenience sample of 100 mother and infant dyads, LCPUFA intake during pregnancy was assessed by food frequency questionnaire with nutrient intake calculated using Food Processor Plus. Linear regression models for neonatal body composition measurements, assessed by air displacement plethysmography and anthropometry, were adjusted for maternal LCPUFA intakes, energy and macronutrient intakes, prepregnancy body mass index and gestational weight gain. Result - Positive associations between maternal docosahexaenoic acid intake and ponderal index in male offspring (β=0.165; 95% confidence interval (CI): 0.031–0.299; P=0.017), and between n-6:n-3 LCPUFA ratio intake and fat mass (β=0.021; 95% CI: 0.002–0.041; P=0.034) and percentage of fat mass (β=0.636; 95% CI: 0.125–1.147; P=0.016) in female offspring were found. Conclusion - Using a reliable validated method to assess body composition, adjusted positive associations between maternal docosahexaenoic acid intake and birth size in male offspring and between n-6:n-3 LCPUFA ratio intake and adiposity in female offspring were found, suggesting that maternal LCPUFA intake strongly influences fetal body composition.

The removal of xenobiotic compounds from wastewater through the use of biological processes and advanced oxidation technologies

Dissertação apresentada para obtenção do Grau de Doutor em Engenharia Química e Bioquímica pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

The Effect of Long-Chain Polyunsaturated Fatty Acids Intake During Pregnancy on Adiposity of Healthy Full-Term Offspring at Birth

OBJECTIVE: The adjusted effect of long-chain polyunsaturated fatty acid (LCPUFA) intake during pregnancy on adiposity at birth of healthy full-term appropriate-for-gestational age neonates was evaluated. STUDY DESIGN: In a cross-sectional convenience sample of 100 mother and infant dyads, LCPUFA intake during pregnancy was assessed by food frequency questionnaire with nutrient intake calculated using Food Processor Plus. Linear regression models for neonatal body composition measurements, assessed by air displacement plethysmography and anthropometry, were adjusted for maternal LCPUFA intakes, energy and macronutrient intakes, prepregnancy body mass index and gestational weight gain. RESULT: Positive associations between maternal docosahexaenoic acid intake and ponderal index in male offspring (β=0.165; 95% confidence interval (CI): 0.031-0.299; P=0.017), and between n-6:n-3 LCPUFA ratio intake and fat mass (β=0.021; 95% CI: 0.002-0.041; P=0.034) and percentage of fat mass (β=0.636; 95% CI: 0.125-1.147; P=0.016) in female offspring were found. CONCLUSION: Using a reliable validated method to assess body composition, adjusted positive associations between maternal docosahexaenoic acid intake and birth size in male offspring and between n-6:n-3 LCPUFA ratio intake and adiposity in female offspring were found, suggesting that maternal LCPUFA intake strongly influences fetal body composition.

Estimating the risk of developing type 2 diabetes: a comparison of several risk scores: the Cohorte Lausannoise study.

To compare in the Swiss population the results of several scores estimating the risk of developing type 2 diabetes. This was a single-center, cross-sectional study conducted between 2003 and 2006 in Lausanne, Switzerland. Overall, 3,251 women and 2,937 men, aged 35-75 years, were assessed, of which 5,760 (93%) were free from diabetes and included in the current study. The risk of developing type 2 diabetes was assessed using seven different risk scores, including clinical data with or without biological data. Participants were considered to be eligible for primary prevention according to the thresholds provided for each score. The results were then extrapolated to the Swiss population of the same sex and age. The risk of developing type 2 diabetes increased with age in all scores. The prevalence of participants at high risk ranged between 1.6 and 24.9% in men and between 1.1 and 15.7% in women. Extrapolated to the Swiss population of similar age, the overall number of participants at risk, and thus susceptible to intervention, ranged between 46,708 and 636,841. In addition, scores that included the same clinical variables led to a significantly different prevalence of participants at risk (4.2% [95% CI 3.4-5.0] vs. 12.8% [11.5-14.1] in men and 2.9% [2.4-3.6] vs. 6.0% [5.2-6.9] in women). CONCLUSIONS; The prevalence of participants at risk for developing type 2 diabetes varies considerably according to the scoring system used. To adequately prevent type 2 diabetes, risk-scoring systems must be validated for each population considered.

Notulae biographicae præpositorum generalium carmelitarum discalceatorum congregationis italicae, 1600-1787.

Ce ms. constitue la mise au net du ms. B. n. F., lat. 17652 qui a servi de brouillon. F. 1 Titre : «Series chronologica præpositorum generalium carmelitarum discalceatorum congregationis italicae, cum singulorum effigie ad vivum nitidissime æri incisa [ce dernier membre de phrase est cancellé], necnon elogio manuscripto». F. 3-14v Notice biographique de chacun des préposés généraux des Carmes déchaux de la congrégation d'Italie de 1600 à 1787; chaque nom est précédé d'un ou plusieurs chiffres romains donnant le numéro d'ordre du préposé. Pour les derniers, seul figure le nom et le numéro d'ordre. Chaque page est divisée en deux cadres, et chaque notice en occupe un, rarement deux. «I. IV. IX. Ferdinandus a Sancta Maria. In saeculo dictus Ferdinandus Martinez...-... LIII. Hilarion ab Omnibus Sanctis» (14v); cf. A. Fortes, Acta capituli generalis O. C. D. congregationis s. Eliae, 3 vol., Rome, 1990-1992 (Monumenta historica Carmeli Teresiani 11, 13-14). À noter, parmi les références bibliographiques, celles qui concernent directement les Carmes déchaux : elles sont données ci-dessous sous une forme normalisée (entre parenthèses le feuillet où figure la première occurrence), alors que l'auteur donne en général le titre et le nom de l'auteur, sous une forme latinisée approximative, avec parfois le lieu et la date d'impression : Juan Caramuel Lobkowitz, Caramuelis Dominicus..., Vienne, 1655 (3v); Jean Chardin, Voyages de Monsieur le chevalier Chardin en Perse, Paris, 1723 (4v); Daniel a Virgine Maria, Speculum carmelitanum, Anvers, 1680 (3); Eusebius ab Omnibus Sanctis, Enchyridion chronologicum carmelitarum discalceatorum congregationis Italiae, Rome, 1737 (4), cet ouvrage est le plus fréquemment cité, on en trouve un exemplaire à la Vaticane et un microfilm à la Library of Congress; Francisco de Santa Maria, Historia general profetica de la orden de Nuestra Señora del Carmen, Madrid, 1630 (3); Franciscus Joseph a Sancta Margarita, Necrologium præpositorum generalium, non identifié (5); Isidore de Saint-Joseph, Historia reformationis s. Theresiae, non identifié (4v); Isidore de Saint-Joseph et Pierre de Saint-André, Historia generalis Fratrum discalceatorum ordinis B. M. V. de Monte Carmelo congregationis s. Eliae, Rome, 1668-1671 (4v); Louis Jacob, Bibliotheca carmelitana manuscripta, non identifié (5v); Juan de Jesus Maria, Historia missionum; Vita Petri a Matre Dei (3), ces deux ouvrages n'ont pu être identifiés, ils ne figurent pas dans les Opera omnia publiées à Cologne en 1622; Aubert Le Mire, Bibliotheca ecclesiastica, 2e partie, Anvers, 1649 (3v); Louis de Sainte-Thérèse, Annales carmelitarum excalceatorum Galliae (4v), non identifié; Martial de Saint-Jean-Baptiste, Bibliotheca scriptorum utriusque congregationis et sexus carmelitarum discalceatorum, Bordeaux, 1730 (3); Paulus ab Omnibus Sanctis, Clavis aurea thesauri partheno-carmelitici..., Vienne, 1669, si ce titre correspond au «Catalogus scriptorum» du f. 3; Philippe de la Très Sainte Trinité, Decus carmelitanum, ouvrage non identifié (4v); Id., Historia carmelitani ordinis..., Lyon, 1656 (3); Id., Itinerarium orientale R.P.F. Philippi a SS. Trinitate, Lyon, 1649 (4v); Id., La Vie du vénérable père Dominique de Jésus Maria..., Lyon, 1669 (5); le P.Théophile Raynaud, Scapulare partheno-carmeliticum, Paris, 1654 (3v); [Cosme de Villiers de Saint-Étienne] «editor anonymus», Bibliotheca carmelitana, Orléans, 1752 (5).

Étymologies d'Isidore.

N° 3 de la liste des manuscrits saisis à Dijon en 1804 par Chardon de la Rochette; — Saint-Bénigne de Dijon, cf. ex-libris du XVIIIe s. "ex pmss. biblioth. Divio Benigniana" (2); Delisle, Cab. des mss., II, 17, 402

Le chevalier de Saint-Jean. Tome 2 / , traduit de l'anglais, de Miss Porter, par Jean Cohen

Titre original : The knight of St. John

Le chevalier de Saint-Jean. Tome 3 / , traduit de l'anglais, de Miss Porter, par Jean Cohen

Titre original : The knight of St. John

Le chevalier de Saint-Jean. Tome 1 / , traduit de l'anglais, de Miss Porter, par Jean Cohen

Titre original : The knight of St. John

Le chevalier de Saint-Jean. Tome 4 / , traduit de l'anglais, de Miss Porter, par Jean Cohen

Titre original : The knight of St. John

An analysis of Ibn al-'Arabi's al-Insan al-Kamil, the Perfect Individual, with a brief comparison to the thought of Sir Muhammad Iqbal

This thesis analyzes four philosophical questions surrounding Ibn al-'Arabi's concept of the al-iman al-kamil, the Perfect Individual. The Introduction provides a definition of Sufism, and it situates Ibn al-'Arabi's thought within the broader context of the philosophy of perfection. Chapter One discusses the transformative knowledge of the Perfect Individual. It analyzes the relationship between reason, revelation, and intuition, and the different roles they play within Islam, Islamic philosophy, and Sufism. Chapter Two discusses the ontological and metaphysical importance of the Perfect Individual, exploring the importance of perfection within existence by looking at the relationship the Perfect Individual has with God and the world, the eternal and non-eternal. In Chapter Three the physical manifestations of the Perfect Individual and their relationship to the Prophet Muhammad are analyzed. It explores the Perfect Individual's roles as Prophet, Saint, and Seal. The final chapter compares Ibn al-'Arabi's Perfect Individual to Sir Muhammad Iqbal's in order to analyze the different ways perfect action can be conceptualized. It analyzes the relationship between freedom and action.