Characterization of the innate immune response to chronic aspiration in a novel rodent model

<p>Abstract</p> <p>Background</p> <p>Although chronic aspiration has been associated with several pulmonary diseases, the inflammatory response has not been characterized. A novel rodent model of chronic aspiration was therefore developed in order to investigate the resulting innate immune response in the lung.</p> <p>Methods</p> <p>Gastric fluid or normal saline was instilled into the left lung of rats (n = 48) weekly for 4, 8, 12, or 16 weeks (n = 6 each group). Thereafter, bronchoalveolar lavage specimens were collected and cellular phenotypes and cytokine concentrations of IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, TNF-alpha, and TGF-beta were determined.</p> <p>Results</p> <p>Following the administration of gastric fluid but not normal saline, histologic specimens exhibited prominent evidence of giant cells, fibrosis, lymphocytic bronchiolitis, and obliterative bronchiolitis. Bronchoalveolar lavage specimens from the left (treated) lungs exhibited consistently higher macrophages and T cells with an increased CD4:CD8 T cell ratio after treatment with gastric fluid compared to normal saline. The concentrations of IL-1alpha, IL-1beta, IL-2, TNF-alpha and TGF-beta were increased in bronchoalveolar lavage specimens following gastric fluid aspiration compared to normal saline.</p> <p>Conclusion</p> <p>This represents the first description of the pulmonary inflammatory response that results from chronic aspiration. Repetitive aspiration events can initiate an inflammatory response consisting of macrophages and T cells that is associated with increased TGF-beta, TNF-alpha, IL-1alpha, IL-1beta, IL-2 and fibrosis in the lung. Combined with the observation of gastric fluid-induced lymphocyitic bronchiolitis and obliterative bronchiolitis, these findings further support an association between chronic aspiration and pulmonary diseases, such as obliterative bronchiolitis, pulmonary fibrosis, and asthma.</p

The END3 gene encodes a protein that is required for the internalization step of endocytosis and for actin cytoskeleton organization in yeast.

Two Saccharomyces cerevisiae mutants, end3 and end4, defective in the internalization step of endocytosis, have previously been isolated. The END3 gene was cloned by complementation of the temperature-sensitive growth defect caused by the end3 mutation and the END3 nucleotide sequence was determined. The END3 gene product is a 40-kDa protein that has a putative EF-hand Ca(2+)-binding site, a consensus sequence for the binding of phosphotidylinositol 4,5-bisphosphate (PIP2), and a C-terminal domain containing two homologous regions of 17-19 aa. The EF-hand consensus and the putative PIP2-binding sites are seemingly not required for End3 protein function. In contrast, different portions of the End3p N-terminal domain, and at least one of the two repeated regions in its C-terminus, are required for End3p activity. Disruption of the END3 gene yielded cells with the same phenotype as the original end3 mutant. An end3ts allele was obtained and this allowed us to demonstrate that End3p is specifically involved in the internalization step of endocytosis. In addition, End3p was shown to be required for proper organization of the actin cytoskeleton and for the correct distribution of chitin at the cell surface

Frequency, thermal and voltage supercapacitor characterization and modeling

International audienceA simple electrical model has been established to describe supercapacitor behaviour as a function of frequency, voltage and temperature for hybrid vehicle applications. The electrical model consists of 14 RLC elements, which have been determined from experimental data using electrochemical impedance spectroscopy (EIS) applied on a commercial supercapacitor.The frequency analysis has been extended for the first time to the millihertz range to take into account the leakage current and the charge redistribution on the electrode. Simulation and experimental results of supercapacitor charge and discharge have been compared and analysed. A good correlation between the model and the EIS results has been demonstrated from 1 mHz to 1 kHz, from −20 to 60 °C and from 0 to 2.5 V

Highlights du congrès 2022 de la Société suisse de médecine interne générale: partie 1 [Highlights of Swiss congress of internal general medicine : part 1]

From June 1 to 3, 2022, Lausanne held the spring congress of the Swiss Society of General Internal Medicine: "Changes and Opportunities". In this article, chief residents in internal medicine from the CHUV summarize presentations they attended. In this overview, we choose to focus on cardiovascular health, as it a central topic in general and internal medicine. Cardiovascular prevention becomes more personalized by using a step-by-step approach. The benefits of statin treatment in persons over 70 years old is still controversial. Ortho-static hypotension in hypertensive patients should not hold back antihypertensive therapy, but it should favor a combined pharmacological and non-pharmacological approach. Finally, screening for fibrosis in non-alcoholic fatty liver disease in high-risk cardiovascular patients should now part be part of a systematic ambulatory process

Reflux gastro-oesophagien et broncho-aspiration nocturne dans les bronchopathies chroniques. [Gastroesophageal reflux and nocturnal broncho-aspiration in chronic bronchopathies]

Although the relationship between chronic bronchopathies and gastro-esophageal reflux is known, the existence and role of nocturnal broncho-aspiration is controversial. 32 patients with chronic bronchopathy and 13 controls without digestive or respiratory symptoms were studied. Nocturnal broncho-aspiration was diagnosed by the demonstration of vegetable fibers in the morning expectorate and by the presence of radioactive pulmonary foci 15 hours following an isotopic meal. Vegetable fibers were found with equal frequency in both groups. On the other hand, positive pulmonary scintigraphy, reflecting nocturnal broncho-aspiration, was observed in 24 of the 32 patients (75%) and only in 2 of the 13 controls (15%) (p less than 0.001). Thus, broncho-aspiration is a frequent occurrence in chronic bronchopathies

An Essential Role for Insulin and IGF1 Receptors in Regulating Sertoli Cell Proliferation, Testis Size, and FSH Action in Mice.

Testis size and sperm production are directly correlated to the total number of adult Sertoli cells (SCs). Although the establishment of an adequate number of SCs is crucial for future male fertility, the identification and characterization of the factors regulating SC survival, proliferation, and maturation remain incomplete. To investigate whether the IGF system is required for germ cell (GC) and SC development and function, we inactivated the insulin receptor (Insr), the IGF1 receptor (Igf1r), or both receptors specifically in the GC lineage or in SCs. Whereas ablation of insulin/IGF signaling appears dispensable for GCs and spermatogenesis, adult testes of mice lacking both Insr and Igf1r in SCs (SC-Insr;Igf1r) displayed a 75% reduction in testis size and daily sperm production as a result of a reduced proliferation rate of immature SCs during the late fetal and early neonatal testicular period. In addition, in vivo analyses revealed that FSH requires the insulin/IGF signaling pathway to mediate its proliferative effects on immature SCs. Collectively, these results emphasize the essential role played by growth factors of the insulin family in regulating the final number of SCs, testis size, and daily sperm output. They also indicate that the insulin/IGF signaling pathway is required for FSH-mediated SC proliferation