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BackgroundEpithelial barrier dysfunction and increased permeability may contribute to antigen sensitization and disease progression in asthma. Claudin-18.1 is the only known lung-specific tight junction protein, but its contribution to airway barrier function or asthma is unclear.ObjectivesWe sought to test the hypotheses that claudin-18 is a determinant of airway epithelial barrier function that is downregulated by IL-13 and that claudin-18 deficiency results in increased aeroantigen sensitization and airway hyperresponsiveness.MethodsClaudin-18.1 mRNA levels were measured in airway epithelial brushings from healthy controls and patients with asthma. In patients with asthma, claudin-18 levels were compared with a three-gene-mean marker of TH2 inflammation. Airway epithelial permeability changes due to claudin-18 deficiency were measured in 16HBE cells and claudin-18 null mice. The effect of IL-13 on claudin expression was determined in primary human airway epithelial cells and in mice. Airway hyperresponsiveness and serum IgE levels were compared in claudin-18 null and wild-type mice following aspergillus sensitization.ResultsEpithelial brushings from patients with asthma (n = 67) had significantly lower claudin-18 mRNA levels than did those from healthy controls (n = 42). Claudin-18 levels were lowest among TH2-high patients with asthma. Loss of claudin-18 was sufficient to impair epithelial barrier function in 16HBE cells and in mouse airways. IL-13 decreased claudin-18 expression in primary human cells and in mice. Claudin-18 null mice had significantly higher serum IgE levels and increased airway responsiveness following intranasal aspergillus sensitization.ConclusionsThese data support the hypothesis that claudin-18 is an essential contributor to the airway epithelial barrier to aeroantigens. Furthermore, TH2 inflammation suppresses claudin-18 expression, potentially promoting sensitization and airway hyperresponsiveness.

The decision to use the optimal animal model to mimic the various types of cardiovascular disease is a critical one for a basic scientist. Clinical cardiovascular disease can be complex and presents itself as atherosclerosis, hypertension, ischemia/reperfusion injury, myocardial infarcts, and cardiomyopathies, amongst others. This may be further complicated by the simultaneous presence of two or more cardiovascular lesions (for example, atherosclerosis and hypertension) and co-morbidities (i.e., diabetes, infectious disease, obesity, etc). This variety and merging of disease states creates an unusually difficult situation for the researcher who needs to identify the optimal animal model that is available to best represent all of the characteristics of the clinical cardiovascular disease. The present manuscript reviews the characteristics of the various animal models of cardiovascular disease available today, their advantages and disadvantages, with the goal to allow the reader access to the most recent data available for optimal choices prior to the initiation of the study. The animal species that can be chosen, the methods of generating these models of cardiovascular disease, as well as the specific cardiovascular lesions involved in each of these models are reviewed. A particular focus on the JCR:LA-cp rat as a model of cardiovascular disease is discussed. [ABSTRACT FROM AUTHOR]

Purpose While there is significant mortality and morbidity with lung cancer, early stage diagnoses carry a better prognosis. As lung cancer screening programs increase with more pulmonary nodules detected, expediting definitive treatment initiation for newly diagnosed patients is imperative. The objective of our analysis was to determine if the use of a dedicated interventional pulmonology practice decreases time delay from new diagnosis of lung cancer or metastatic disease to the chest to treatment initiation. Methods Retrospective chart analysis was done of 87 consecutive patients with a new diagnosis of primary lung cancer or metastatic cancer to the chest from our interventional pulmonology procedures. Demographic information and time intervals from abnormal imaging to procedure and to treatment initiation were recorded. Results Patients were older (mean age 69) and former or current smokers (72%). A median of 27 days (1-127 days) passed from our diagnostic biopsy to treatment initiation. A median of 53 total days (2-449 days) passed from abnormal imaging to definitive treatment. Endobronchial ultrasound-guided transbronchial needle aspiration was the most commonly used diagnostic procedure (59%), with non-small cell lung cancer the majority diagnosis (64%). For surgical patients, all biopsy-negative lymph nodes from our procedures were cancer-free at surgical excision. Conclusions Compared to prior reports from international and United States cohorts, obtaining a tissue biopsy diagnosis through a gatekeeper interventional pulmonology practice decreases median delay from abnormal imaging to treatment initiation. This finding has the potential to positively impact patient outcomes and requires further evaluation., Author(s): Bryan S. Benn [sup.1] , Mihir Parikh [sup.2] , Pei H. Tsau [sup.3] , Eric Seeley [sup.4] , Ganesh Krishna [sup.4] [sup.5] Author Affiliations: (Aff1) 0000 0000 9632 6718, [...]

Flaxseed (Linum usitatissimum) is composed of a unique combination of bioactive components that appear to generate, through either an isolated or a synergistic action, a significant beneficial effect on the cardiovascular system. With a significant increase in the generation of data on the dietary impact of flaxseed on the cardiovascular system, a review of where we stand--what we know and what we still need to understand about these effects on the heart and the vasculature--was thought to be of value and the rationale for this paper. For example, although we now know how to deliver the bioactives most efficiently (oil versus ground seed versus whole seed), we do not know how different foods can influence that delivery. Further, we know flaxseed has anti-arrhythmic, anti-atherogenic, anti-hypertensive, and cholesterol-lowering actions in animal studies and some selected human trials but much more needs to be learned, particularly in human trials. These results have justified further commitment of resources to the initiation of human trials. Because of the impact of nutrition on many chronic diseases, this may not only be true for the effects of flaxseed on cardiovascular disease but may be just as relevant for many other disease conditions.Key words: diet, cardiovascular disease, nutrition, heart disease, flaxseed, linseed, alpha linolenic acid.Le lin (Linum usitatissimum) est compose d'une association unique de composantes bioactives semblant engendrer, par une action isolee ou encore synergique, un important effet benefique sur le systeme cardiovasculaire. Avec une augmentation notable de la production de donnees sur l'incidence alimentaire du lin sur le systeme cardiovasculaire, on a pense qu'un article de synthese faisant etat des connaissances actuelles--ce que nous savons et ce que nous avons toujours a comprendre quant a ces effets sur le coeur et les vaisseaux sanguins--serait valable et sous-tendrait cet article. Par exemple, bien que nous sachions maintenant comment administrer les produits bioactifs plus efficacement (en huiles plutot qu'en graines moulues ou entieres), nous ne savons pas comment des aliments peuvent influencer ces modes d'administration de maniere differentielle. En outre, nous savons que le lin a des actions antiarythmiques, antiatherogeniques, antihypertensives et d'abaissement des taux de cholesterol dans le cadre d'etudes chez les animaux et de certains essais chez l'humain, mais nous avons besoin d'en apprendre beaucoup plus, particulierement dans le cadre d'essais chez l'humain. Ces resultats ont justifie l'allocation de plus de ressources afin de commencer des essais chez l'humain. En raison de l'incidence de l'alimentation sur bien des maladies chroniques, cela pourrait etre tout aussi pertinents pour les effets du lin sur beaucoup de maladies chroniques que sur les maladies cardiovasculaires. [Traduit par la Redaction]Mots-cles : alimentation, maladie cardiaque, lin, graines de lin, acide alphalinolenique., An introduction to flaxseedLinum usitatissimum, more familiarly known as flaxseed, is an oilseed crop grown throughout most of the world (Caligiuri et al. 2014). It contains three bioactive compounds beneficial [...]