Small Alveoli Research Articles

Viral infection induces inflammatory signals that coordinate YAP regulation of dysplastic cells in lung alveoli.

Severe viral pneumonia can induce rapid expansion of KRT5+ basal-like cells in small airways and alveoli; this forms a scar-like structure that persists in the injured alveoli and impedes normal alveolar epithelium regeneration. In this study, we investigated the mechanism by which viral infection induced this remodeling response. Through comparing different lung-injury models, we demonstrated that infection induced strong IFN-γ signal-stimulated dysplastic KRT5+ cell formation. Inactivation of interferon receptor 1 (Ifngr1) reduced dysplastic cell formation, ameliorated lung fibrosis, and improved lung-function recovery. Mechanistically, IFN-γ regulated dysplastic cell formation via the focal adhesion kinase (FAK)/Yes-associated protein 1 (YAP) pathway. Inhibiting FAK/Src diminished IFN-γ-induced YAP nuclear translocation and dysplastic cell formation. Inhibiting YAP during viral infection prevented dysplastic cell formation, whereas inhibiting YAP in persistent KRT5+ cells led to their conversion into distal club cells. Importantly, human dysplastic cells exhibited elevated FAK and YAP activity, and IFN-γ treatment promoted the transformation of human alveolar progenitor cells into dysplastic cells. These findings uncover the role of infection-induced inflammatory response in alveolar remodeling and may provide potential therapeutic avenues for the treatment of alveolar remodeling in patients with severe viral pneumonia.

Differential expression of mast cells in the small airways and alveolar septa of current smokers and patients with small airway disease and COPD.

COPD patients suffer from dysregulated and suppressed immune functionality, determined by their loss of degranulating capacity. Here we provide crucial information on the presence of degranulated mast cells (MCs) in COPD airways and demonstrate their relationship to lung physiology and airway remodelling. Small airway lung resections from non-smoking controls (NC), normal lung function smokers (NLFS), small airway disease (SAD), and mild-to-moderate COPD current smokers (COPD-CS) and ex-smokers (COPD-ES) were dual immuno-stained with MC tryptase and degranulation marker lysosome-associated membrane protein (LAMP)-1. Total MCs, degranulating MCs and non-MCs were enumerated in small airway epithelium and subepithelium, and in alveolar septa. In the small airway wall subepithelial areas, COPD-CS and COPD-ES patients had significantly lower MCs than the NC group (p<0.05), although the numbers were considerably higher in the small airway epithelium (p<0.01). Degranulating non-MCs were higher in SAD (p<0.05) than in COPD in the small airway subepithelium. In contrast, there were significant increases in total MCs (degranulated and non-degranulated) and degranulated non-MCs in the alveolar septum of COPD patients compared with the NC group (p<001). The lower numbers of MCs in the subepithelium correlated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (FEF25-75%), higher smoking rates in COPD patients, and increased small airway wall thickness and extracellular matrix. The increase in MCs in the alveolar septum negatively correlated with FEF25-75%. This study is the first to assess the differential pattern of MC, degranulating MC and non-MC populations in the small airways and alveoli of COPD patients. The spatial positioning of the MCs within the airways showed variable correlations with lung function.

Association between clinical, serological, functional and radiological findings and ventilatory distribution heterogeneity in patients with rheumatoid arthritis.

In rheumatoid arthritis (RA), the involvement of the pulmonary interstitium can lead to structural changes in the small airways and alveoli, leading to reduced airflow and maldistribution of ventilation. The single-breath nitrogen washout (SBN2W) test is a measure of the ventilatory distribution heterogeneity and evaluates the small airways. This study aimed to find out which clinical, serological, functional and radiological findings are useful to identify RA patients with pathological values of the phase III slope (SIII) measured by the SBN2W test. This was a cross-sectional study in which RA patients were assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the Clinical Disease Activity Index (CDAI) and underwent serological analysis of autoantibodies and inflammatory markers. In addition, they underwent pulmonary function tests (including the SBN2W test) and chest computed tomography (CT). Of the 60 RA patients evaluated, 39 (65%) had an SIII >120% of the predicted value. There were significant correlations between SIII and age (r = 0.56, p<0.0001), HAQ-DI (r = 0.34, p = 0.008), forced vital capacity (FVC, r = -0.67, p<0.0001), total lung capacity (r = -0.46, p = 0.0002), residual volume/total lung capacity (TLC) (r = 0.44, p = 0.0004), and diffusing capacity of the lungs for carbon monoxide (r = -0.45, p = 0.0003). On CT scans, the subgroup with moderate/severe disease had a significantly higher SIII than the normal/minimal/mild subgroup (662 (267-970) vs. 152 (88-283)% predicted, p = 0.0004). In the final multiple regression model, FVC, extent of moderate/severe involvement and age were associated with SIII, explaining 59% of its variability. In patients with RA, FVC, extent of lung involvement and age, all of which are easily obtained variables in clinical practice, identify poorly distributed ventilation. In addition, the presence of respiratory symptoms and deteriorated physical function are closely related to the distribution of ventilation in these patients.

Depletion of Extracellular Chemokines by Aspergillus Melanin.

Aspergillus fumigatus is an environmental fungus that can cause life-threatening pulmonary disease. Infections initiate when conidia are inhaled and land deep inside the small airways and alveoli of the lungs, where they interact with epithelial cells. These cells provide a physical barrier and secrete chemokines to attract innate immune cells to the site of infection. Melanin, a key constituent of the conidial cell wall, is required for the establishment of invasive infection due to its ability to inhibit the function of innate immune cells recruited to clear the infection. Here, we provide evidence for an additional mechanism by which A. fumigatus can alter host innate immune responses. In vitro infection of a normal human small airway epithelial cell line (HSAEC1-KT) caused a decrease in extracellular protein levels of CXCL10 and CCL20, two proinflammatory chemokines that are required for the host defense against aspergillosis, despite a dramatic increase in the levels of each mRNA. A. fumigatus depleted recombinant human CXCL10 and CCL20 from medium in the absence of host cells, suggesting that the block in accumulation is downstream of protein translation and secretion. Melanin is both necessary and sufficient for this chemokine-depleting activity because a dihydroxynaphthalene (DHN)-melanin-deficient strain of A. fumigatus is defective in depleting chemokines and purified melanin ghosts retain potent depletion activity. We propose that A. fumigatus, through the action of melanin, depletes important chemokines, thereby dampening the innate immune response to promote infection. IMPORTANCE Aspergillus fumigatus is the major airborne fungal pathogen that affects humans. In order to cause an invasive infection, inhaled spores must avoid killing by innate immune cells that are recruited to the site of infection. Understanding how A. fumigatus achieves immune evasion is important for the development of novel therapeutics. We provide evidence that melanin, a pigment contained in the spore cell wall, can remove certain chemokines from the extracellular space to suppress the host inflammatory response that is responsible for clearing fungal infection.

102 Insights Into the Molecular Underpinnings of Disrupted Mammary Development and Function Arising from Late-Gestation Heat Stress

Abstract Exposure to heat stress during a dairy cow’s dry period disrupts mammary gland remodeling impairing milk production during the subsequent lactation. The dry period coincides with late gestation, and Intrauterine hyperthermia affects offspring growth, physiology, and performance into adulthood. This presentation will highlight histological and molecular adaptations of the mammary gland under heat stress, emphasizing the carry-over effects in the dam and her progeny. Pregnant dams were either cooled (CL, fans and water soakers) or heat-stressed (HS, lack of access to cooling devices) in a free-stall setting during the dry period (~46 d) in summer. Heifers gestated under maternal heat stress or cooling (in utero heat stressed, IUHS vs. in utero cooled, IUCL) were euthanized at birth or weaning, or were followed until the first lactation to collect mammary tissue for histological, proteomics, and methylation analyses. In the dam’s mammary gland, 251 proteins and 224 phosphorylated proteins were differentially abundant in HS compared to CL. Top functions were related to immune function, inflammation, amino acid metabolism, reactive oxygen species production, tissue remodeling, and stress response. Intrauterine hyperthermia derailed mammary gland development inducing alterations in the size and weight of the whole udder and parenchyma and fat pad mass. Epithelial structures within the parenchyma of IUHS heifers were significantly underdeveloped, with reduced proliferative capacity. These early-life alterations in tissue microstructure persist through the first lactation, evidenced by IUHS mammary glands with smaller alveoli and fewer mammary epithelial cells that exhibited reduced proliferation capacity. Further, in utero hyperthermia epigenetically programed the udder. Over 130 differentially methylated genes were identified in the IUHS mammary gland with roles in development, innate immune defense, cell signaling, and transcription and translation. These studies provide insights into the molecular underpinnings of disrupted mammary structure and function arising from prior exposure to dry period/late-gestation heat stress, which led to lower milk yields of the dam and her offspring.

Investigating the Ovarian Microstructure in the Genera Helicolenus and Scorpaena (Teleostei, Sub-Order Scorpaenoidei) with Implications for Ovarian Dynamics and Spawning.

Simple SummaryThe diversity of reproductive mechanism in bony fishes is greater than in any other group of vertebrates. It ranges from oviparous, to several stages of viviparous forms. In this context, scorpaenoid fishes belonging to the families Scorpaenidae and Sebastidae are of particular interest, since they show extremely varied reproductive modes connected with ovarian structures. We describe here the ovarian morphology of five rockfish species showing different reproductive modalities, using histology. Specialized microscopic features were found during gametogenesis, strictly related to the production of gelatinous mass surrounding the eggs, typical of these species. Based on microscopic maturity stages here analyzed, we found that all species shed eggs more than once through the spawning season, and were characterized by continuous oogenesis with multiple oocyte deposition. Further ovarian dynamic observations supported the hypothesis that all species had an indeterminate fecundity.The sub-order Scorpenoidei appears to be particularly interesting due to the presence of intermediate stages between oviparity and viviparity in several species. The present study aims to describe the ovarian morphology, using a histological and histochemical approach, in four ovuliparous species belonging to Scorpaena genus compared with a zygoparous species, H. dactylopterus, focusing also on the assessment of the ovarian dynamics in the populations of such species in Sardinia waters (central–western Mediterranean). Ovarian sections of all species were examined using light microscopy. All species showed a specialized ovary, cystovarian type II-3, strictly related to the production of gelatinous matrices surrounding the eggs. Some microscopic peculiarities in the oogenesis process were found: thin zona pellucida, small and low cortical alveoli, and a specialized ovarian wall during the spawning period. All species analyzed were batch-spawners with an asynchronous ovarian organization. A continuous recruitment of oocytes and the occurrence of de novo vitellogenesis was also observed. During the spawning period, low atresia intensity was detected, while a marked increase in this intensity found in the ovaries at the end of spawning season. Our observations may support an indeterminate fecundity type for these species.

COPD, smoking, and social justice

It is 60 years since the UK Royal College of Physicians published its ground-breaking report Smoking and Health,1 and chronic obstructive pulmonary disease (COPD) and its underlying pathologies, chronic bronchitis and emphysema, are now well established as potential consequences of smoking. The inhalation of noxious materials contained in tobacco smoke drives lung inflammation, oxidative stress, premature ageing, and immune function impairment. These processes lead to damage to the airway epithelium and vascular endothelium, as well as destruction of small airways and alveoli.

Histoarchitectural study of mammary alveoli on lactation, involution and pregnant stage in Murrah buffalo

Present experiment was conducted on sixty Murrah buffalo divided into three groups: lactating, involution stage/dry and pregnant stage (non-lactating early pregnant stage, non-lactating mid pregnant stage and non-lactating late pregnant stage). Most of the alveoli were spherical to oval elongated in shape. In lactating stage, only small and medium sized alveoli were present. In involuting stage due to degeneration and inactiveness only small alveoli were recorded. In non-lactating late pregnant stage most of the alveoli were large sized. A highly significant statistical difference was noted among different stages of lactation in the diameter of alveoli. The active alveoli were lined by cuboidal epithelium to low cuboidal epithelium, while resting alveoli were lined by squamous epithelium with dark nuclei. The number of resting alveoli were found increased with the advancement of lactation. Up to two months of involution most of the alveoli were degenerative. A highly significant statistical difference was noted in the height of alveolar epithelium in different stages of lactation.

Synergistic Pathogenicity by Coinfection and Sequential Infection with NADC30-like PRRSV and PCV2 in Post-Weaned Pigs.

Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus (PCVs) are two major viruses that affect pigs. Coinfections between PRRSV and PCV2 are frequently reported in most outbreaks, with clinical presentations involving dyspnea, fever, reduced feed intake, weight loss, and death in fattening pigs. The NADC30-like PRRSV and PCV2d are the main circulating virus strains found in China. This study determines the impact of NADC30-like PRRSV and PCV2d mono-infection and coinfection on the immune system, organ pathology, and viral shedding in five-week-old post-weaned pigs. Pigs were randomly divided into six groups: PBS, PRRSV, PCV2, PRRSV-PCV2 coinfection (co), and PRRSV-PCV2 or PCV2-PRRSV sequential infections. Fever, dyspnea, decreased feed intake, weight loss, and pig deaths occurred in groups infected with PRRSV, Co-PRRSV-PCV2, and PRRSV-PCV2. The viral load was higher in Co-PRRSV-PCV2, PRRSV-PCV2, and PCV2-PRRSV than those mono-infected with PRRSV or PCV2. Additionally, cytokines (IFN-γ, TNF-α, IL-4, and IL-10) produced by pigs under Co-PRRSV-PCV2 and PRRSV-PCV2 groups were more intense than the other groups. Necropsy findings showed hemorrhage, emphysema, and pulmonary adhesions in the lungs of pigs infected with PRRSV. Smaller alveoli and widened lung interstitium were found in the Co-PRRSV-PCV2 and PRRSV-PCV2 groups. In conclusion, PRRSV and PCV2 coinfection and sequential infection significantly increased viral pathogenicity and cytokine responses, resulting in severe clinical signs, lung pathology, and death.

Aspiration pneumonia complicated by disseminated fungal sepsis in the setting of incidental esophagitis cystica: A rare autopsy case report with review of the literature

Abstract Introduction/Objective Esophageal retention cysts are presumed to arise from obstruction of the excretory ducts of the submucosal glands of the esophagus. Since the first description by Kuhne in 1899, different terminologies have been used to denote these lesions including retention cysts, mucocele, esophagitis cystica, and cyst of esophageal submucosal gland duct. Esophageal retention cysts are generally benign, asymptomatic and discovered incidentally. However, a few studies have reported symptomatic dysphagia and to date, only one autopsy case report described esophageal retention cysts contributing to aspiration pneumonia and cause of death. Methods/Case Report We present a case of aspiration pneumonia, associated with both reduced oropharyngeal tone secondary to alcohol consumption and esophageal dysphagia due to esophagitis cystica in a 69 year old female with alcohol use disorder complicated by alcoholic liver disease. The patient was found unresponsive at home with bloody oral secretions and evidence of head trauma. On autopsy all lung lobes demonstrated that large and small airways and alveoli were filled with vegetable matter, associated with prominent bacterial and fungal forms. EVG stain demonstrated vascular disruption with red blood cell extravasation, next to a focus of aspiration pneumonia. This explained the patient’s “bloody oral secretions”, originating from the respiratory tract. Demonstration of fungal hyphae in sections from lungs as well as necrotic colon was consistent with disseminated fungal sepsis. While sections from esophagus showed no varices which could explain the patient’s “bloody oral secretions” in the setting of alcoholic liver disease, there were numerous dilated esophageal submucosal cysts. Cysts were lined by a single to double layer of cuboidal epithelium with eosinophilic cytoplasm and basally-located, bland-appearing nuclei. Conclusion In summary, we present a rare case of esophageal retention cyst associated aspiration pneumonia complicated by pulmonary hemorrhage, adding to the growing body of knowledge regarding fatal complications of these usually incidental lesions.

Anatomical and Histological Revision of Bulbourethral Gland in Reproductive System of Male Hamster

The anatomical consequences revealed that the bulbourethral glands in Syrian hamsters are in the form of a pair of small, oval-shaped glands and have a white color, similar to the fruit of a pea, each gland has a single duct that flows into the urethra, and these glands are buried under the cavernous bulbar muscle on both sides of the urethra. The long , wide and weigh were respectively about 0.7 cm and 0.4 cm and 1 g. Histopathological outcomes presented that the bulbourethral glands are a complex tubular-alveolar gland, lined with simple columnar epithelium, these glands are multi-lobed, each lobe consists of small simple alveoli that are connected to each other directly or through narrow and short tube. The goal of this study to know more anatomical and histological information for this gland for its significant and important role in the sexual reproduction process.

Anti-hyperprolactinemic activities of aqueous extract of Uvaria chamae (P. Beauv) roots and associated biochemical changes in chlorpromazine-induced hyperprolactinemic female Wistar rats

Ethnopharamcological relevanceThe age-long folkloric use of Uvaria chamae roots in the management of nipple discharge that is not related to pregnancy, childbirth or nursing but as a result of excessive production of prolactin (hyperprolactinemia) is yet to be substantiated with scientific data. Aim of the studyThis study investigated the anti-hyperprolactinemic activities of aqueous extract of Uvaria chamae roots (AEUCR) and associated biochemical changes in chlorpromazine (CPZ)-induced hyperprolactinemic female Wistar rats. Materials and methodsA total of sixty female rats (207.40 ± 2.69 g) were assigned into 6 groups: A-F. Animals in Group A received 0.5 ml of distilled water only whilst the 7 days CPZ-treated female rats (to induce hyperprolactinemia) in groups B, C, D, E, and F also received distilled water, 2.5 mg/kg body weight of bromocriptine (reference drug), 0.71, 1.41 2.83 mg/kg body weight of AEUCR for 28 days. ResultsAEUCR contained a total of 15 (75%) amino acids with seven (46.67%) being essential amino acids and eight (53.33%) as non-essential amino acids. Administration of CPZ increased (p < 0.05) the levels of prolactin and testosterone, and reduced (p < 0.05) the levels of estradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), dopamine, triiodothyronine (T3) and tetraiodothyroxine (T4). Chlorpromazine also increased the levels of serum urea, creatinine, total protein, albumin, globulin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) of the animals. In contrast, AEUCR significantly (p < 0.05) reduced the CPZ-induced increases in the levels of prolactin and testosterone, and increased the levels of CPZ-induced reduction in the progesterone, estradiol, FSH, LH, dopamine, T3 and T4. The AEUCR also reversed (p < 0.05) the CPZ-induced related increases in the levels of urea, creatinine, total protein, albumin, globulin, bilirubin, ALT, AST and ALP similar to the trends in the distilled water- and bromocriptine-treated controls. The CPZ-induced remarkable increase in the size of lactating alveolus and lactiferous duct distribution in the mammary gland were restored to normal tubule-alveolar female pattern mammary glands, composed of branching ducts and small alveoli budding off the ducts. ConclusionThe study concluded that aqueous extract of Uvaria chamae root exhibited anti-hyperprolactinemic activity by restoring prolactin and dopamine levels and tubule-alveolar female pattern in female rats. It also ameliorated CPZ-induced changes in the liver and kidney function indices. This study justifies the folkloric use of Uvaria chamae root in the management of abnormal discharge by the nipples that is unrelated to pregnancy, childbirth and nursing.

Effect of Equal Ratio Ventilation on Respiratory Mechanics and Oxygenation During Volume-Controlled Ventilation in Pediatric Patients

PurposeChildren have few small alveoli, which reduce lung compliance; in contrast, their cartilaginous rib cage makes their chest wall highly compliant. This combination promotes lung collapse. Prolonged inspiratory to expiratory (I:E) ratio ventilation is used to optimize gas exchange and respiratory mechanics in surgery. However, the optimal ratio is unclear in children. We hypothesized that, compared to a 1:2 I:E ratio, a 1:1 I:E ratio would improve dynamic compliance and oxygenation, and affect the peak airway pressure in pediatric patients undergoing surgery.Materials and MethodsForty-eight patients aged ≤6 years who were scheduled to undergo surgery under general anesthesia with an arterial line were randomly allocated to receive 1:1 (group 1:1) or 1:2 (group 1:2) I:E ratio ventilation. Airway pressure, respiratory system compliance, and arterial blood gas analyses were compared between groups immediately after induction (T0), 30 min after induction (T1), 60 min after induction (T2), immediately after surgery (T3), and on arrival at the post-anesthesia care unit (T4).ResultsPeak and plateau airway pressures were significantly lower in group 1:1 than in group 1:2 at T1 (p=0.044 and 0.048, respectively). The dynamic and static compliances were significantly higher in group 1:1 than in group 1:2 at T1 (p=0.044 and 0.045, respectively). However, the partial pressure of oxygen did not significantly differ between groups.ConclusionCompared to a 1:2 I:E ratio, a 1:1 I:E ratio improved dynamic compliance and lowered the peak airway pressure without complications in pediatric patients. Nevertheless, our results do not support its use solely for improving oxygenation.

On modeling of airflow in human lungs: constitutive relations to describe deformation of porous medium

Within the framework of a multilevel mathematical model to describe the evolution of functional disorders of the human organism under the influence of environment factors, a mathematical model of the "meso-level" of the human respiratory system is developed. The article is deals with the development of the meso-level model - the formulation of a constitutive model to describe the airflow in a porous lung medium. Human lungs filled with small airways and alveoli, with air contained in them, are modeled by an elastically deformable saturated porous medium enclosed in an internal chamber with varying volume (movable walls). Conceptual and mathematical statements are presented. Air movement in the deformable porous medium of lungs is described by ratios of the mechanics of deformable solid body and filtration theory. As an element of this sub-model an analytical solution is obtained for an auxiliary geometrically linear problem of the all-round compression of an elastic thin-walled hollow sphere filled with air to determine the rate of mean stress of the two-phase medium of the lungs, taking into account the interaction between the lung tissue and the air contained in the lungs. To confirm the hypothesis on the acceptability of a linear solution of an auxiliary problem for large deformations, a similar problem was numerically solved in a geometrically nonlinear formulation. The results show that the obtained analytical solution is in satisfactory agreement with the solution of a similar problem in a nonlinear formulation both for calm and deep breathing, which indicates the possibility of using the former in the construction of the considered sub-model.

The autotaxin-lysophosphatidic acid pathway mediates mesenchymal cell recruitment and fibrotic contraction in lung transplant fibrosis

Chronic lung allograft dysfunction (CLAD) is the leading cause of mortality in lung transplant recipients. CLAD is characterized by respiratory failure owing to the accumulation of fibrotic cells in small airways and alveoli, inducing tissue contraction and architectural destruction. However, the source of the fibroblastic cells and the mechanism(s) underlying the accumulation and activation remain unexplained. Mesenchymal stromal cells (MSCs) are multipotent progenitors that are normally located in the lung tissue but can be isolated from the alveolar space in lung transplant recipients, where they have a profibrotic phenotype. Our objective was to identify the mediator(s) inducing migration and contractile differentiation of lung tissue MSCs. Bronchoalveolar lavage (BAL) (7 healthy controls and 21 lung transplant recipients), CCL2, HGF, TGFB, EGF, and PDGF-BB and autotaxin were measured by enzyme-linked immunosorbent assay. BAL (7 healthy controls and 31 lung transplant recipients) lysophosphatidic acid (LPA) (16:0, 18:0, 18:1, 22:4) was measured by liquid chromatography with tandem mass spectrometry. The effect of inhibition of candidate mediators on BAL-mediated chemoattraction of MSCs and contraction of MSC-spiked collagen gel assays was assessed. BAL cells from a lung transplant recipient with CLAD were analyzed by single-cell RNA sequencing. We first demonstrate that BAL fluid from lung transplant recipients and particularly those with CLAD is potently chemoattractive to human lung tissue‒derived MSCs and induces a contractile phenotype. After excluding several candidate mediators, we show that LPA blockade completely abrogated transplant recipient BAL‒mediated chemoattraction of MSCs and contraction of MSC-spiked collagen gels. Furthermore, LPA levels were enriched in transplant recipient BAL, and LPA replicated the observed in vitro profibrotic effects of transplant recipient BAL. Finally, we identify BAL monocyte‒derived macrophages with autotaxin (ENPP2) and fibrotic transcriptional signature. Autotaxin-expressing alveolar macrophages are present in CLAD BAL. These cells potentially provide a local source of autotaxin/LPA that drives MSC recruitment and tissue contraction in CLAD. These cells are analogous to an aberrant macrophage population recently identified in idiopathic pulmonary fibrosis, suggesting an overlap in pathogenesis between CLAD and other forms of lung fibrosis.

Ultra-rare cystic disease.

Diffuse cystic lung diseases include a group of heterogeneous disorders characterised by the presence of cysts within the lung parenchyma, sometimes showing a characteristic computed tomography scan pattern that allows diagnosis. The pathogenetic mechanisms underlying cyst formation in the lung are still not clear and a number of hypotheses have been postulated according to the different aetiologies: ball-valve effect, ischaemic dilatation of small airways and alveoli related to infiltration and obstruction of small vessels and capillaries that supply the terminal bronchioles and connective tissue degradation by matrix metalloproteases. A wide number of lung cyst diseases have been classified into six diagnostic groups according to the aetiology: neoplastic, congenital/genetic, lymphoproliferative, infective, associated with interstitial lung diseases, and other causes. This article focuses on lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and Erdheim-Chester disease, Birt-Hogg-Dubé, follicular bronchiolitis and lymphocytic interstitial pneumonia, light-chain deposition disease and amyloidosis, congenital lung disease associated with aberrant lung development and growth, and cystic lung disease associated with neoplastic lesion. These cystic diseases are epidemiologically considered as ultra-rare conditions as they affect fewer than one individual per 50 000 or fewer than 20 individuals per million. Despite the rarity of this group of disorders, the increasing use of high-resolution computed tomography has improved the diagnostic yield, even in asymptomatic patients allowing prompt and correct therapy and management without the need for a biopsy.

Nutritive and Bioactive Properties of Mesquite (Prosopis pallida) Flour and Its Technological Performance in Breadmaking.

Although the nutritional profile, bioactivities, and uses of mesquite pod flour from various Prosopis species have been studied, limited research has been conducted on Prosopis pallida (Humb, & Bonpl. Ex Willd.) Kunth mesquite flour. This study aimed to characterize the nutritional quality and bioactive properties of P. pallida pod flour and to assess its technological performance in breadmaking as a partial replacer of white wheat flour. Peruvian P. pallida mesquite flour was found to have an appealing nutritional profile, with high contents of dietary fiber (29.6% dw) and protein (9.5% dw), and low contents of fat (1.0% dw) and carbohydrates (57.6% dw). It is a source of palmitic (12.6%), oleic (35.5%), and linoleic acids (45.8%), α-, β-, and γ- tocopherols, and contains phenolic compounds such as apigenin glycoside derivatives with proven antioxidant capacities. Extracts of P. pallida flour were also found to have antimicrobial and antifungal effects and did not show hepatoxicity. When formulated as a wheat flour replacer, increasing mesquite flour levels yield composite doughs of lower stickiness and extensibility, and composite breads of lower elasticity (p < 0.01). However, up to a level of 10%, mesquite flour significantly increases loaf volume, reduces crumb hardness, and produces a more uniform crumb of small size alveoli (p < 0.01). Considering the purpose of improving the nutritional and technological quality of wheat flour bread, the addition of P. pallida pod flour can be highly recommended.

Pulmonary Hypoplasia Associated with Ascites and Hydrothorax in a Newborn Pig

Background: Pulmonary hypoplasia is characterized by incomplete development of the lungs, owing to congenital defectsor the action of toxic substances. Moreover, it has rarely been described in pigs. Ascites or hydroperitoneum is characterized by the presence of fluid inside the abdominal cavity and does not generally cause changes in the abdominal organs. However, hydrothorax, characterized by the presence of fluid within the thoracic cavity, is responsible for the compression of thoracic organs and consequent heart and respiratory failure. This study aims to describe a case of congenital pulmonary hypoplasia associated with ascites and hydrothorax in a newborn pig.Case: A male neonate Landrace pig that died shortly after delivery was presented for necropsy with increased abdominal volume and bilateral extension of the pelvic limbs. The pig belonged to a litter of 13 piglets, four of which died shortly after birth. The rest of the piglets were poorly developed, but only one was presented for necropsy. Significant external changes, along with permanent distension, interpreted as arthrogriposis, were observed in the pelvic limbs. The skin of the ventral abdominal region was thin, with evidence of all blood vessels, interpreted as telangectasis. An internal examination revealed the presence of a slightly yellowish liquid in the thoracic and abdominal cavities, interpreted as hydrothorax and ascites, respectively. The lungs were reduced in size, indicating pulmonary hypoplasia. The liver had rounded edges, which were dark red and firm, with an irregular surface. Significant microscopic findings were observed in the lungs, which were divided by fibrous connective tissue and showed evidence of small and atrophied alveoli. Furthermore, connective tissue was observed around the peribronchiolar regions and underdeveloped cartilage around the airways. The liver showed dilation of the centrilobular veins. Moreover, the sinusoids were filled with erythrocytes, indicating congestion.Discussion: Pulmonary hypoplasia is a rare birth defect in pigs and can be accompanied by malformations of other organs, including anasarca. Pulmonary hypoplasia is caused by conditions that compress the lungs, such as congenital diaphragmatic hernia, intrathoracic masses, and pleural effusion or malformations in the chest cavity. However, none of these conditions were observed in the current case. Instead, the histopathological changes observed in the lungs were characteristic of pulmonary hypoplasia. A microscopic examination revealed that the hypoplastic lungs showed a reduced number of alveoli, replacement of the peribronchiolar smooth muscle by the connective tissue, and underdeveloped cartilage around the airways, all of which are characteristic of pulmonary hypoplasia. Vascular telangiectasia is characterized by abdominal distention due to a marked ascitic condition. Invariably, ascitic fluid accumulation results from changes in hydrodynamic parameters. The hydrothorax observed in this animal was suggestive of changes in the hydrodynamic parameters, which consequently led to fluid accumulation in the chest cavity. This has been previously described in a newborn pig infected with Clostridium difficile. The permanently and bilaterally extended pelvic joints observed at birth in this animal were interpreted as arthrogriposis. This change is attributed to various factors, such as fetal paralysis in pigs that ingest toxic substances like alkaloids present in Conium maculatum and in the stalks of Nicotiana tabacum and Datura stramunium. The literature describes pelvic limb paralysis in Landrace pigs as a genetically inherited disorder. However, it was not possible for us to establish the cause of arthrogriposis for certain in this pig.

Случай криптогенной организующейся пневмонии

Cryptogenic organizing pneumonia is a diffuse lung disease characterized by excessive proliferation of granulomatous tissue in the small bronchi and alveoli and moderate interstitial inflammation. The diagnosis requires a multidisciplinary approach involving a pulmonologist, a radiologist and, in some cases, a mor-phologist. In most patients, cryptogenic organizing pneumonia is diagnosed on the basis of clinical symptoms, typical findings in computed tomography and cy-tology of the bronchoalveolar lavage fluid, after excluding the known causes of organizing pneumonia. Secondary confirmation of the diagnosis is a pronounced positive response to glucocorticosteroid therapy. The article presents a clinical case of a 58-year-old patient with progressive dyspnea and infiltrates in the lungs, which were initially interpreted as a manifestation of bilateral pneumonia. High-resolution computed tomography of the chest organs revealed a characteristic picture of "organizing pneumonia". Clinical and radiological changes regressed after glucocorticosteroid therapy.

Dry-yeast Extracts Curtails Pulmonary Inflammation and Tissue Destruction in a Model of Experimental Emphysema (P06-078-19)

ObjectivesPulmonary emphysema characterized by loss of alveolar integrity is caused by damage to the alveoli as a result of prolonged exposure to cigarette smoke, inhaled irritants, air pollution and fine dust. Emphysema entails pulmonary inflammation of the lungs, narrowing of the small airways, and destruction of the lung tissues. Our previous study found that dry-yeast extracts inhibited eosinophilia and mucus overproduction in a murine model of asthma. The current study examined whether dry-yeast extracts ameliorated pulmonary emphysema in mice evoked by cigarette smoke. MethodsEmphysema was induced by exposure of BALB/c mice to cigarette smoke for 30 min, five days a week for eight weeks. Mice were orally administrated with 50–200 mg/kg for 8 weeks. In the in vitro studies employing alveolar epithelial A549 cells 2 μg/ml lipopolysaccharide (LPS) was loaded in the absence and presence of 10–100 μg/ml dry-yeast extracts. ResultsOral supplementation of dry-yeast extracts reduced the influx of inflammatory cells such as neutrophils and eosinophils in lung promoted by cigarette smoke. H&E staining revealed that alveoli emphysema was evident in cigarette smoke-exposed lung, which was ameliorated by treating dry-yeast extracts to mice. Dry-yeast extract improved the apoptotic bax/antiapoptotic bcl-2 ratio of lung tissues damaged by cigarette smoke. In addition, the immunohistochemical analysis employing anti-MMP12 confirmed that dry-yeast extracts inhibited apoptotic damage of alveoli subjected to cigarette smoke. In lung tissues dry-yeast extracts attenuated the induction of cigarette smoke-promoted inducible cyclooxygenase-2, a key mediator of inflammatory pathways. In A549 cells exposed to LPS, dry-yeast extract attenuated alveolar inflammation. ConclusionsThese results demonstrated that dry-yeast extracts inhibited pulmonary inflammation leading to emphysema in small airways and alveoli exposed to cigarette smoke. Therefore, dry-yeast extracts may be a promising agent treating progressive pulmonary disorders including chronic obstructive pulmonary disease. Funding SourcesThis work (Grants No. C0501612) was supported by project for Cooperative R&D between Industry, Academy, and Research Institute funded Korea Ministry of SMEs and Startups in 20.