Search

Numerical simulation of the coupled heat transfers by conduction, convection, and radiation through two kinds of the alveolar structures used in the construction are numerically investigated. Owing to the low-temperature differences involved, the tridimensional model is based on the Boussinesq approximation and constant thermophysical fluid properties at mean temperature. The alveolar walls are assumed grey and diffuse. The symmetric and periodic boundary conditions for flows governed by the incompressible Navier-Stokes equations are considered. Equations governing the natural convection in the alveolars, the radiative heat exchanges between their internal surfaces and the heat conduction in the surrounding walls are solved using a finite volume method. The pressure-velocity coupling is solved by SIMPLE algorithm. The objective of this study is to improve the effects of wall conduction and radiation heat exchange between surfaces on the decrease of the thermal resistance in the alveolar walls. Two kinds of concrete blocks with three and six-hole numbers are chosen and their thermal resistances are numerically predicted. The comparison between the thermal resistances, specified in terms of thermal regulations for buildings and numerical solutions, is presented. Keywords: Alveolar, Natural convection, Surface radiation, Combined heat transfer, Thermal resistance

GM‐CSF is important in regulating acute, persistent neutrophilic inflammation in certain settings, including lung injury. Ligand binding induces rapid internalization of the GM‐CSF receptor (GM‐CSFRα) complex, a process essential for signaling. Whereas GM‐CSF controls many aspects of neutrophil biology, regulation of GM‐CSFRα expression is poorly understood, particularly the role of GM‐CSFRα in ligand clearance and whether signaling is sustained despite major down‐regulation of GM‐CSFRα surface expression. We established a quantitative assay of GM‐CSFRα surface expression and used this, together with selective anti‐GM‐CSFR antibodies, to define GM‐CSFRα kinetics in human neutrophils, and in murine blood and alveolar neutrophils in a lung injury model. Despite rapid sustained ligand‐induced GM‐CSFRα loss from the neutrophil surface, which persisted even following ligand removal, pro‐survival effects of GM‐CSF required ongoing ligand‐receptor interaction. Neutrophils recruited to the lungs following LPS challenge showed initially high mGM‐CSFRα expression, which along with mGM‐CSFRβ declined over 24 hr; this was associated with a transient increase in bronchoalveolar lavage fluid (BALF) mGM‐CSF concentration. Treating mice in an LPS challenge model with CAM‐3003, an anti‐mGM‐CSFRα mAb, inhibited inflammatory cell influx into the lung and maintained the level of BALF mGM‐CSF. Consistent with neutrophil consumption of GM‐CSF, human neutrophils depleted exogenous GM‐CSF, independent of protease activity. These data show that loss of membrane GM‐CSFRα following GM‐CSF exposure does not preclude sustained GM‐CSF/GM‐CSFRα signaling and that this receptor plays a key role in ligand clearance. Hence neutrophilic activation via GM‐CSFR may play an important role in neutrophilic lung inflammation even in the absence of high GM‐CSF levels or GM‐CSFRα expression., GM‐CSF released during ALI stimulates neutrophil recruitment, induces down‐regulation of GM‐CSFR, and GM‐CSF consumption by neutrophils, yet sustained anti‐apoptotic signals require continued GM‐CSF stimulation.

The direct delivery of antibiotics to the lung has been considered an effective approach to treat pulmonary tuberculosis, which represents approximately 80% of total cases. In this sense, this work aimed at producing inhalable chitosan microparticles simultaneously associating isoniazid and rifabutin, for an application in pulmonary tuberculosis therapy. Spray-dried chitosan microparticles were obtained with adequate flow properties for deep lung delivery (aerodynamic diameter of 4 µm) and high drug association efficiencies (93% for isoniazid and 99% for rifabutin). The highest concentration of microparticles that was tested (1 mg/mL) decreased the viability of macrophage-differentiated THP-1 cells to around 60% after 24 h exposure, although no deleterious effect was observed in human alveolar epithelial (A549) cells. The release of LDH was, however, increased in both cells. Chitosan microparticles further evidenced capacity to activate macrophage-like cells, inducing cytokine secretion well above basal levels. Moreover, the propensity of macrophages to internalize microparticles was demonstrated, with uptake levels over 90%. Chitosan microparticles also inhibited bacterial growth by 96%, demonstrating that the microencapsulation preserved drug antibacterial activity in vitro. Overall, the obtained data suggest the potential of chitosan microparticles for inhalable lung tuberculosis therapy. PTDC/DTP-486 FTO/0094/2012 info:eu-repo/semantics/publishedVersion

Rationale: Rhabdomyosarcoma (RMS) has known as a highly malignant soft tissue sarcoma, representing 5% to 10% of all solid tumors in childhood. Alveolar rhabdomyosarcoma (ARMS) of the retrorectal-presacral space is an extremely rare lesion for adult, no study has been reported in the English literature. Patient concerns: A 51-year-old male presented with abdominal pain for 1 month, significantly worse when having a bowel movement. Diagnosis: Computed tomography (CT) and magnetic resonance imaging (MRI) of the pelvis showed a solid-cystic, enhancing lesion of dimension located in retrorectal-presacral space. The surgical specimen was reported as ARMS after pathological evaluation. Interventions: The tumor was complete surgical resection, and after surgery, the patient was treated with combination chemotherapy. Outcomes: At 23 months follow up, the patient was asymptomatic with no evidence of metastases or local recurrence. Lessons: Improvements in imaging in addition to early surgical intervention and chemotherapy treatment are crucial to improve survival chances against RMS.

Tissue fibrosis is a major cause of mortality that results from the deposition of matrix proteins by an activated mesenchyme. Macrophages accumulate in fibrosis, but the role of specific subgroups in supporting fibrogenesis has not been investigated in vivo. Here we used single-cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of macrophages in bleomycin-induced lung fibrosis in mice. A novel computational framework for the annotation of scRNA-seq by reference to bulk transcriptomes (SingleR) enabled the subclustering of macrophages and revealed a disease-associated subgroup with a transitional gene expression profile intermediate between monocyte-derived and alveolar macrophages. These CX3CR1+SiglecF+ transitional macrophages localized to the fibrotic niche and had a profibrotic effect in vivo. Human orthologues of genes expressed by the transitional macrophages were upregulated in samples from patients with idiopathic pulmonary fibrosis. Thus, we have identified a pathological subgroup of transitional macrophages that are required for the fibrotic response to injury.

The use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs) shows great potential for intracellular delivery of DNA. Currently, its application is limited due to the potential toxicity and unknown long-term side effects. In this study NPs prepared using a biodegradable polymer, poly(lactic&ndash, co&ndash, glycolic acid (PLGA) in association with a CPP, was assessed on two lung epithelial cell lines (adenocarcinomic human alveolar basal epithelial cells (A549) and normal bronchial epithelial cells (Beas-2B cells)). Addition of CPP was essential for intracellular internalization. No effects were observed on the mitochondrial activity and membrane integrity. Cells exposed to the NPs&ndash, DNA&ndash, CPP showed low inflammatory response, low levels of apoptosis and no activation of caspase-3. Increase in necrotic cells (between 10%&ndash, 15%) after 24 h of incubation and increase in autophagy, induced by NPs&ndash, CPP, are likely to be related to the lysosomal escape mechanism. Although oxidative stress is one of the main toxic mechanisms of NPs, NPs&ndash, CPP showed decreased reactive oxygen species (ROS) production on Beas-2B cells, with potential antioxidant effect of CPP and no effect on A549 cells. This NP system appears to be safe for intracellular delivery of plasmid DNA to the lung epithelial cells. Further investigations should be conducted in other lung-related systems to better understand its potential effects on the lungs.

[EN] The main objective of this Final Master's Project is the design of the structural elements (slabs, pillars and foundations) that make up a commercial building located in the industrial estate of Torrente. This building has use for the business intermediation office activity with showroom. And this one is located in G Street of the Toll sector L'Alberca in Torrente (Valencia). Previously, a study of solutions is carried out in order to choose the type of floor that best suits the conditions of the land, as well as other aspects such as facility of construction, execution times and assembly costs. The types of slab to be analyzed were: solid slab, waffle slab and alveolar plate slab. After the study of the 3 types of floors, it is decided by the alveolar plate. From here, we proceed to the calculation of the two floors, analyzing a type slab. For its analysis, it is used different types of structural calculatio, including the manual method of isostatic and hyperstatic sections; through the calculation program of Cype Ingenieros structures and through Aidepla. After analyzing the floor type according to the previous methods, Cype Ingenieros is chosen since it provides higher bending laws, and therefore it will be the most restrictive method, and we will be more on the security side. Finally, it has carried out an economic evaluation of the works in its construction, including only the foundations, pillars, beams and slabs., [CA] El present Treball de Fi de Màster té com a principal objectiu el disseny dels elements estructurals (forjats, pilars i fonamentacions) que componen un edifici d'ús comercial localitzat en el polígon industrial de Torrent. El dit edifici té ús destinat a l'activitat d'oficina d'intermediació comercial amb sala d'exposició. I este es localitza en el carrer G del sector Toll L'Alberca de Torrent (València). Prèviament es realitza un estudi de solucions a fi de triar el tipus de forjat que més s'adapte a les condicions del terreny, així com altres aspectes com ara facilitat en la construcció, terminis d'execució i costos de muntatge. Les tipologies de forjat a analitzar han sigut: llosa massissa, reticular i llosa alveolar. Després de l'estudi de les 3 tipologies de forjat, es decidix pel de placa alveolar. A partir d'ací, es procedix al càlcul dels dos forjats de planta primera i de coberta, analitzant un forjat tipus Per a la seua anàlisi, s'empren diferents tipologies de càlcul estructural, entre elles el mètode manual de trams isostàtics i hiperestàtics; per mitjà del programa de càlcul d'estructures Cype Enginyers i per mitjà d'Aidepla. Després d'analitzar el forjat tipus d'acord amb els mètodes anteriors, es tria Cype Enginyers atés que proporciona unes lleis de flectores superiors, i per tant serà el mètode més restrictiu, i estarem més del costat de la seguretat. Per a finalitzar, es proporciona una valoració econòmica dels treballs duts a terme en la seua construcció, incloent únicament la fonamentació, pilars, bigues i forjats, [ES] El presente Trabajo de Fin de Master tiene como principal objetivo el diseño de los elementos estructurales (forjados, pilares y cimentaciones) que componen un edificio de uso comercial localizado en el polígono industrial de Torrente. Dicho edificio tiene uso destinado a la actividad de oficina de intermediación comercial con sala de exposición. Y éste se localiza en la calle G del sector Toll L'Alberca de Torrente (Valencia). Previamente se realiza un estudio de soluciones con el fin de elegir el tipo de forjado que más se adapte a las condiciones del terreno, así como otros aspectos tales como facilidad en la construcción, plazos de ejecución y costes de montaje. Las tipologías de forjado a analizar han sido: losa maciza, reticular y losa alveolar. Tras el estudio de las 3 tipologías de forjado, se decide por el de placa alveolar. A partir de aquí, se procede al cálculo de los dos forjados de planta primera y de cubierta, analizando un forjado tipo. Para su análisis, se emplean diferentes tipologías de cálculo estructural, entre ellas el método manual de tramos isostáticos e hiperestáticos; mediante el programa de cálculo de estructuras Cype Ingenieros y mediante Aidepla. Tras analizar el forjado tipo de acuerdo a los métodos anteriores, se elige Cype Ingenieros dado que proporciona unas leyes de flectores superiores, y por tanto será el método más restrictivo, y estaremos más del lado de la seguridad. Para finalizar, se proporciona una valoración económica de los trabajos llevados a cabo en su construcción, incluyendo únicamente la cimentación, pilares, vigas y forjados.

The aim of this study was to analyze malpractice claims related to tooth extractions in order to identify areas requiring emphasis and eventually to reduce the number of complications. We compiled a file of all malpractice claims related to tooth extractions (EBA code) between 1997 and 2010 from the Finnish Patient Insurance Centre. We then examined the data with respect to date, tooth, surgery, injury diagnosis, and the authority's decision on the case. The material consisted of 852 completed patient cases. Most of the teeth were third molars (66 %), followed by first molars (8 %), and second molars (7 %). The majority of claims were related to operative extraction (71 %) followed by ordinary extraction (17 %) and apicoectomy of a single-rooted tooth (7 %) or multi-rooted tooth (2 %). The most common diagnosis was injury of the lingual or inferior alveolar nerve. According to the authority's decision, the patient received compensation more often in cases involving a third molar than other teeth (56 vs. 46 %, P

Aim: To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. Materials & methods: Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SP-loaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. Results: Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6Chi monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. Conclusion: Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis.

Increasing affinity to lung tissue is an important strategy to achieve pulmonary retention and to prolong the duration of effect in the lung. As the lung is a very heterogeneous organ, differences in structure and blood flow may influence local pulmonary disposition. Here, a novel lung preparation technique was employed to investigate regional lung distribution of four drugs (salmeterol, fluticasone propionate, linezolid, and indomethacin) after intravenous administration in rats. A semi-mechanistic model was used to describe the observed drug concentrations in the trachea, bronchi, and the alveolar parenchyma based on tissue specific affinities (Kp) and blood flows. The model-based analysis was able to explain the pulmonary pharmacokinetics (PK) of the two neutral and one basic model drugs, suggesting up to six-fold differences in Kp between trachea and alveolar parenchyma for salmeterol. Applying the same principles, it was not possible to predict the pulmonary PK of indomethacin, indicating that acidic drugs might show different pulmonary PK characteristics. The separate estimates for local Kp, tracheal and bronchial blood flow were reported for the first time. This work highlights the importance of lung physiology- and drug-specific parameters for regional pulmonary tissue retention. Its understanding is key to optimize inhaled drugs for lung diseases.

Recent studies have revealed biologically-significant differences between human and mouse lung development and highlighted new in vitro systems to allow experimental manipulation of human lung models. At the same time, emerging clinical data suggests that the origins of some adult lung diseases are found in embryonic development and childhood. The convergence of these research themes has fuelled a resurgence of interest in human lung developmental biology. This review discusses our current understanding of human lung development, which has been profoundly influenced by studies in mice and, more recently, by experiments in human in vitro lung developmental models and RNA-sequencing of human foetal lung tissue. Together, these approaches are helping to shed light on mechanisms of human lung development and disease, and may help pave the way for new therapies to be developed and tested., Rutherford Fund Fellowship allocated by the Medical Research Council and the UK Regenerative Medicine Platform MR/5005579/1 to MZN; Academic Clinical Lectureship, University of Cambridge to MZN; Wellcome Trust PhD studentship 109146/Z/15/Z to DS; Medical Research Council G0900424 to ELR.

Fractional exhaled nitric oxide (F-ENO) is used to assess eosinophilic inflammation of the airways. F-ENO values are influenced by the expiratory flow rate and orally produced NO. We measured F-ENO at four different expiratory flow levels after two different mouthwashes: tap water and carbonated water. Further, we compared the alveolar NO concentration (C-ANO), maximum airway NO flux (J(awNO)) and airway NO diffusion (D-awNO) after these two mouthwashes. F-ENO was measured in 30 volunteers (healthy or asthmatic) with a chemiluminescence NO-analyser at flow rates of 30, 50, 100 and 300mL/s. A mouthwash was performed before the measurement at every flow rate. The carbonated water mouthwash significantly reduced F-ENO compared to the tap water mouthwash at all expiratory flows: 50mL/s (p

Resistin-like molecule α (RELMα) is a highly secreted protein in type 2 (Th2) cytokine-induced inflammation including helminth infection and allergy. In infection with Nippostrongylus brasiliensis (Nb), RELMα dampens Th2 inflammatory responses. RELMα is expressed by immune cells, and by epithelial cells (EC); however, the functional impact of immune versus EC-derived RELMα is unknown. We generated bone marrow (BM) chimeras that were RELMα deficient (RELMα−/−) in BM or non BM cells and infected them with Nb. Non BM RELMα−/− chimeras had comparable inflammatory responses and parasite burdens to RELMα+/+ mice. In contrast, both RELMα−/− and BM RELMα−/− mice exhibited increased Nb-induced lung and intestinal inflammation, correlated with elevated Th2 cytokines and Nb killing. CD11c+ lung macrophages were the dominant BM-derived source of RELMα and can mediate Nb killing. Therefore, we employed a macrophage-worm co-culture system to investigate whether RELMα regulates macrophage-mediated Nb killing. Compared to RELMα+/+ macrophages, RELMα−/− macrophages exhibited increased binding to Nb and functionally impaired Nb development. Supplementation with recombinant RELMα partially reversed this phenotype. Gene expression analysis revealed that RELMα decreased cell adhesion and Fc receptor signaling pathways, which are associated with macrophage-mediated helminth killing. Collectively, these studies demonstrate that BM-derived RELMα is necessary and sufficient to dampen Nb immune responses, and identify that one mechanism of action of RELMα is through inhibiting macrophage recruitment and interaction with Nb. Our findings suggest that RELMα acts as an immune brake that provides mutually beneficial effects for the host and parasite by limiting tissue damage and delaying parasite expulsion. Employing hookworm infection of RELMα−/− bone marrow chimeras, co-culture assays, and gene expression analysis, we show that lung macrophage-derived RELMα downregulates inflammation and parasite killing.

Background: Clinical significance of small airway obstruction in mild pediatric asthma is unclear. Objective: To evaluate small airway properties in children with mild to moderate asthmatic symptoms and the association of small airway function with asthma control and exercise-induced bronchoconstriction (EIB). Methods: Children (5-10 years old) with recurrent wheezing (n = 42) or persistent troublesome cough (n = 16) and healthy controls (n = 19) performed impulse oscillometry (IOS), spirometry, and a multiple-breath nitrogen washout (MBNW) test. Exhaled nitric oxide (NO) was measured at multiple flow rates to determine alveolar NO concentration (CAIN). Asthma control was evaluated with the Childhood Asthma Control Test (C-ACT), short-acting beta(2)-agonist (SABA) use within the past month, and asthma exacerbations within the past year. Results: IOS, spirometry, and exhaled NO indexes that are related to small airway function differed between children with recurrent wheezing and healthy controls, whereas only forced expiratory flow at 25% to 75% of the forced vital capacity was associated with persistent cough. The MBNW indexes showed no difference between the groups. Among symptomatic children, conducting airway ventilation inhomogeneity and CALV were associated with asthma exacerbations (P = .03 and P = .002, respectively), and lung clearance index and CALV were associated with EIB (P = .04 and P = .004, respectively). None of the proposed small airway indexes was associated with the C-ACT score or SABA use. Conclusion: Subtle changes were observed in the proposed small airway indexes of IOS, spirometry, and exhaled NO among children with mild to moderate recurrent wheezing. Small airway dysfunction, expressed as ventilation inhomogeneity indexes and CALV, was also associated with asthma exacerbations and EIB. (C) 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Porcine circovirus type 2 (PCV2) is associated with various diseases which are designated as PCV2-associated diseases (PCVADs). Their severity varies among breeds. In the diseased pigs, virus is present in monocytes, without replication or full degradation. PCV2 entry and viral outcome in primary porcine monocytes and the role of monocytes in PCV2 genetic susceptibility have not been studied. Here, virus uptake and trafficking were analyzed and compared among purebreds Pi&eacute, train, Landrace and Large White and hybrid Pi&eacute, train &times, Topigs20. Viral capsids were rapidly internalized into monocytes, followed by a slow disintegration to a residual level. PCV2 uptake was decreased by chlorpromazine, cytochalasin D and dynasore. The internalized capsids followed the endosomal trafficking pathway, ending up in lysosomes. PCV2 genome was nicked by lysosomal DNase II in vitro, but persisted in monocytes in vivo. Monocytes from purebred Pi&eacute, train and the hybrid showed a higher level of PCV2 uptake and disintegration, compared to those from Landrace and Large White. In conclusion, PCV2 entry occurs via clathrin-mediated endocytosis. After entry, viral capsids are partially disintegrated, while viral genomes largely escape from the pathway to avoid degradation. The degree of PCV2 uptake and disintegration differ among pig breeds.

Mucormycosis is a life-threatening respiratory fungal infection predominantly caused by Rhizopus species. Mucormycosis has incompletely understood pathogenesis, particularly how abnormalities in iron metabolism compromise immune responses. Here we show how, as opposed to other filamentous fungi, Rhizopus spp. establish intracellular persistence inside alveolar macrophages (AMs). Mechanistically, lack of intracellular swelling of Rhizopus conidia results in surface retention of melanin, which induces phagosome maturation arrest through inhibition of LC3-associated phagocytosis. Intracellular inhibition of Rhizopus is an important effector mechanism, as infection of immunocompetent mice with swollen conidia, which evade phagocytosis, results in acute lethality. Concordantly, AM depletion markedly increases susceptibility to mucormycosis. Host and pathogen transcriptomics, iron supplementation studies, and genetic manipulation of iron assimilation of fungal pathways demonstrate that iron restriction inside macrophages regulates immunity against Rhizopus. Our findings shed light on the pathogenetic mechanisms of mucormycosis and reveal the role of macrophage-mediated nutritional immunity against filamentous fungi., Mucormycosis is a life-threatening respiratory fungal infection that typically occurs in patients with abnormalities in iron metabolism. Here the authors show that iron restriction inside the phagosome of macrophages is an essential component of the host defense against Rhizopus, the main species causing mucormycosis.

Pulmonary alveolar proteinosis (PAP) is a syndrome of reduced GM-CSF-dependent, macrophage-mediated surfactant clearance, dysfunctional foamy alveolar macrophages, alveolar surfactant accumulation, and hypoxemic respiratory failure for which the pathogenetic mechanism is unknown. Here, we examine the lipids accumulating in alveolar macrophages and surfactant to define the pathogenesis of PAP and evaluate a novel pharmacotherapeutic approach. In PAP patients, alveolar macrophages have a marked increase in cholesterol but only a minor increase in phospholipids, and pulmonary surfactant has an increase in the ratio of cholesterol to phospholipids. Oral statin therapy is associated with clinical, physiological, and radiological improvement in autoimmune PAP patients, and ex vivo statin treatment reduces cholesterol levels in explanted alveolar macrophages. In Csf2rb−/− mice, statin therapy reduces cholesterol accumulation in alveolar macrophages and ameliorates PAP, and ex vivo statin treatment increases cholesterol efflux from macrophages. These results support the feasibility of statin as a novel pathogenesis-based pharmacotherapy of PAP., Pulmonary alveolar proteinosis (PAP) is associated with defective macrophage clearance of surfactant. Here, the authors show that patients with PAP have altered cholesterol-to-phospholipid ratio in their surfactant, and that more importantly, statin therapy and reduction of cholesterol accumulation in macrophages can ameliorate PAP in both humans and mice.

Acute respiratory distress syndrome (ARDS) is characterized by an excessive pulmonary inflammatory response. Removal of excess cholesterol from the plasma membrane of inflammatory cells helps reduce their activation. The secreted apolipoprotein A-I binding protein (AIBP) has been shown to augment cholesterol efflux from endothelial cells to the plasma lipoprotein HDL. Here, we find that AIBP was expressed in inflammatory cells in the human lung and was secreted into the bronchoalveolar space in mice subjected to inhalation of LPS. AIBP bound surfactant protein B and increased cholesterol efflux from alveolar macrophages to calfactant, a therapeutic surfactant formulation. In vitro, AIBP in the presence of surfactant reduced LPS-induced p65, ERK1/2 and p38 phosphorylation, and IL-6 secretion by alveolar macrophages. In vivo, inhalation of AIBP significantly reduced LPS-induced airspace neutrophilia, alveolar capillary leak, and secretion of IL-6. These results suggest that, similar to HDL in plasma, surfactant serves as a cholesterol acceptor in the lung. Furthermore, lung injury increases pulmonary AIBP expression, which likely serves to promote cholesterol efflux to surfactant and reduce inflammation.

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial lung disease with a poor prognosis and limited therapeutic options. Over the past decade, research efforts have focused on the pathogenetic mechanisms involved in this enigmatic lung disease. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease often complicated by the development of interstitial lung disease (ILD), leading to high mortality and morbidity. Autophagy is a process regulating the turnover of subcellular components and organelles, and represents a major cellular homeostatic mechanism. Recent evidence suggests a role of autophagy and mitochondrial dysfunction in the development of IPF, focusing on lung fibroblasts and epithelial cells. The aim of this study was to examine the mRNA levels of molecules involved inthe autophagy pathway in bronchoalveolar lavage fluid (BALF)-derived cellsfrom patients with IPF in comparison topatients with RA demonstrating lung involvement (ILD) by RT-qPCR. The significant upregulation of BECLIN1 was observed in patients with RA-ILD compared with those with IPF. Other genes involved in the autophagy pathway were also examined, such as Unc-51 like autophagy activating kinase 1 (ULK1), BCL2 interacting protein 3 (BNIP3) and p62. No differences in the mRNA expression levels of these genes were observed. As regards the selective degradation of mitochondria and mitophagy, similar PTEN-induced putative kinase 1 (PINK1) and PARKIN; E3 ubiquitin ligase (PRKN) expression, as well as PINK1 protein levels, were observed. On the whole, the findings of this study demonstrate an increased expression of BECLIN1 in BALF cells from patients with RA-ILD compared with those from patients with IPF, while similar levels in other key molecules implicating in the autophagy pathway were observed in patients with IPF and RA-ILD.

BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) profoundly affect the immune system and synergistically accelerate disease progression. It is believed that CD4(+) T-cell depletion by HIV is the major cause of immunodeficiency and reactivation of latent TB. Previous studies demonstrated that blood monocyte turnover concurrent with tissue macrophage death from virus infection better predicted AIDS onset than CD4(+) T-cell depletion in macaques infected with simian immunodeficiency virus (SIV). METHODS: In this study, we describe the contribution of macrophages to the pathogenesis of Mycobacterium tuberculosis (Mtb)/SIV coinfection in a rhesus macaque model using in vivo BrdU labeling, immunostaining, flow cytometry, and confocal microscopy. RESULTS: We found that increased monocyte and macrophage turnover and levels of SIV-infected lung macrophages correlated with TB reactivation. All Mtb/SIV-coinfected monkeys exhibited declines in CD4(+) T cells regardless of reactivation or latency outcomes, negating lower CD4(+) T-cell levels as a primary cause of Mtb reactivation. CONCLUSIONS: Results suggest that SIV-related damage to macrophages contributes to Mtb reactivation during coinfection. This also supports strategies to target lung macrophages for the treatment of TB.

A 12-year-old farmer’s boy presented with 4 weeks of left flank pain. On examination, a palpable mass below the right costal margin was noted. Investigations, including full blood count, C-reactive protein, and kidney and liver tests, were normal, except for mild eosinophilia (0.53×109/L). Immunological work-up was normal including immunoglobulins, lymphocyte subsets and serology for HIV. Ultrasonography and abdominal CT revealed an extensive lesion originating from segment V/VI to segment VIII with encasement and stenosis of the portal vein (figure 1). The boy reported contact with animals on the family’s farm, such as dogs …

To our knowledge, this study demonstrates for the first time that the AIDS virus differentially impacts two distinct subsets of lung macrophages. The predominant macrophages harvested by bronchoalveolar lavage (BAL), alveolar macrophages (AMs), are routinely used in studies on human lung macrophages, are long-lived cells, and exhibit low turnover. Interstitial macrophages (IMs) inhabit the lung tissue, are not recovered with BAL, are shorter-lived, and exhibit higher baseline turnover rates distinct from AMs. We examined the effects of SIV infection on AMs in BAL fluid and IMs in lung tissue of rhesus macaques. SIV infection produced massive cell death of IMs that contributed to lung tissue damage. Conversely, SIV infection induced minimal cell death of AMs, and these cells maintained the lower turnover rate throughout the duration of infection. This indicates that SIV produces lung tissue damage through destruction of IMs, whereas the longer-lived AMs may serve as a virus reservoir to facilitate HIV persistence.