Morphological Changes In Lungs Research Articles

Evolution and developmental plasticity of lung structure in high-altitude deer mice.

Hypoxia at high altitudes can constrain the ability of endotherms to maintain sufficient rates of pulmonary O2 transport to support exercise and thermogenesis. Hypoxia can also impede lung development during early post-natal life in some mammals, and could thus accentuate constraints on O2 transport at high altitude. We examined how these challenges are overcome in deer mice (Peromyscus maniculatus) native to high altitude. Lung structure was examined in highland and lowland populations of deer mice and lowland populations of white-footed mice (P. leucopus; a congener restricted to low altitude) that were bred in captivity. Among mice that were born and raised to adulthood in normoxia, highland deer mice had higher alveolar surface density and more densely packed alveoli. The increased alveolar surface density in highlanders became fully apparent at juvenile life stages at post-natal day 30 (P30), after the early developmental period of intense alveolus formation before P21. Alveolar surface density was maintained in highlanders that were conceived, born, and raised in hypoxia (~ 12kPa O2), suggesting that lung development was not impaired by post-natal hypoxia as it is in many other lowland mammals. However, developmental hypoxia increased lung volume and thus augmented total alveolar surface area from P14. Overall, our findings suggest that evolutionary adaptation and developmental plasticity lead to changes in lung morphology that should improve pulmonary O2 uptake in deer mice native to high altitude.

COVID-19 pathology: experience of 2000 autopsies

Background: Pathological anatomy, patogenesis and the morphogenesis of manifestations and complications of COVID-19 remain insufficiently studied. The fullest information on structural bases of organs and tissues alterations by new coronavirus disease can be obtained as a result of autopsies.
 Aims: The aim of the study was to study the morphological changes of lungs and other organs of the autopsies of COVID-19 deceased persons. Results of 2000 autopsies of people who died of a severe form of COVID-19 in Moscow, consisting of 1212 men and 788 women, from March 20 to May 22, 2020 (a ratio 1.54:1) aged from 20 to 99 years (on average 68.515.63 years) were presented. This experience was previously generalized in the Atlas COVID-19 pathology. Autopsies were made in the converted interstationary pathoanatomical offices at strict observance of rules of biosafety according to standard and legal documents of WHO, Russian Ministry of Health and Rospotrebnadzor.
 Results: Morphological changes of lungs with varying severity and extent were detected in all examined cases; however, damage to other organs was also common, which in some cases prevailed over pulmonary changes and was the cause of death. The main morphological changes in lungs were diffuse alveolar damage and microangiopathy, alveolar hemorrhage syndrome, thrombosis, and thromboembolism.
 Conclusion: The involvement of the lungs, other organs, and vascular system in the pathological process is a result of multiple factors. It is advisable to implement clinical and morphological masks of COVID-19.

Immuno-epidemiology and pathophysiology of coronavirus disease 2019 (COVID-19).

Occasional zoonotic viral attacks on immunologically naive populations result in massive death tolls that are capable of threatening human survival. Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent that causes coronavirus disease (COVID-19), has spread from its epicenter in Wuhan China to all parts of the globe. Real-time mapping of new infections across the globe has revealed that variable transmission patterns and pathogenicity are associated with differences in SARS-CoV-2 lineages, clades, and strains. Thus, we reviewed how changes in the SARS-CoV-2 genome and its structural architecture affect viral replication, immune evasion, and transmission within different human populations. We also looked at which immune dominant regions of SARS-CoV-2 and other coronaviruses are recognized by Major Histocompatibility Complex (MHC)/Human Leukocyte Antigens (HLA) genes and how this could impact on subsequent disease pathogenesis. Efforts were also placed on understanding immunological changes that occur when exposed individuals either remain asymptomatic or fail to control the virus and later develop systemic complications. Published autopsy studies that reveal alterations in the lung immune microenvironment, morphological, and pathological changes are also explored within the context of the review. Understanding the true correlates of protection and determining how constant virus evolution impacts on host-pathogen interactions could help identify which populations are at high risk and later inform future vaccine and therapeutic interventions.

The impact of pulse currents on morphological changes in lung and heart tissue underchronic purulent pneumonia

We examined outbred rats with a model of chronic purulent pneumonia We detected the damages to the interstitial tissue with the development of granulations and foci of inflammation pneumosclerosis in the lung tissue Uneven hypertrophy of cardiomyocytes thickening of the walls of blood vessels and an increase in their quantitative ratio moderate proliferation of connective tissue layers in the perivascular zones intermuscular edema with impaired circulation of the muscle wall were manifested in the heart tissue After electrical myostimulation pulse currents of the respiratory muscles in the lung tissue revealed increased amount of connective tissue in the septa increase in the number of macrophages and in cardiac tissue focal dissociation of cardiomyocytes irregular interstitial edema hypertrophy of the walls of arterioles hyperemia poor circulation in the appearance of focal hemorrhages in the myocardium and epicardium

Клинико-анатомическое наблюдение первого летального исхода от коронавирусной инфекции в Новосибирской области

Clinical and anatomical case study of the first death from the novel coronavirus infection in the Novosibirsk Region is presented The matter of etiology, epidemiology COVID-19 are also briefly taken up, data on pathological anatomy in COVID-19 are generalized, with the emphasis on morphological changes in lungs in pneumonia caused by coronavirus infection

Presence of N-acetylgalactosamine/galactose residues on bronchioloalveolar cells during rat postnatal development.

In mammals, the alveolarization process develops predominantly after birth. Airway cells display a complex assemblage of glycans on their surface. These glycans, particularly terminal glycan extensions, are important effective carriers of information that change during the differentiation process. Nevertheless, few systematic data are reported about the cell surface sugar residue content during postnatal lung development. In the present work, we aimed to identify and semi-quantify N-acetylgalactosamine (GalNAc)/galactose (Gal) residues on the bronchioloalveolar cell surface in rat lung sections from 1-, 4-, 8- day old and adult animals and link these data with the lung glycocalyx composition. Horseradish peroxidase- conjugated lectin from Glycine max (soybean agglutinin, SBA) was used, and light microscopy methodologies were performed. SBA labelling intensity was studied before and after sialidase pre-treatment, in 1-, 4-, and 8-day-old animals and adult animals. For semi-quantitative evaluation of SBA binding intensity, two investigators performed the analysis independently, blinded to the type of experiment. Reactivity of the lectin was assessed in bronchiolar and respiratory portion/alveolar epithelial cell surfaces. We evidenced a stronger positive reaction when lung sections were pre-treated with neuraminidase before incubation with the lectin in 1- and 4-day-old animals and adult animals. These results were not so manifest in 8- day-old animals. This binding pattern, generally points towards the presence of terminal but mainly sub-terminal GalNAc/Gal residues probably capped by sialic acids on the rat bronchiolar/respiratory tract epithelial cells. As this glycan extension is common in Oand N-glycans, our results suggest that these glycan classes can be present in bronchioloalveolar cells immediately after birth and exist during the postnatal period. The results observed in eight-day-old rat lung sections may be due to the dramatic lung morphologic changes and the possible underlying biological mechanisms that occur during this age-moment.

Effect of electroacupuncture at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) on perinatal nicotine-exposure-induced lung function and morphology of neonatal rats

To compare the effects of electroacupuncture (EA) at "Zusanli" (ST 36) versus "Yanglingquan" (GB 34) in the pregnant rats on perinatal nicotine-exposure-induced lung function and morphology of newborn rats and explore the rule of acupoint effect in EA for the prevention from lung dysplasia in newborn rats. A total of 24 female SD rats were randomized into a normal saline group (S group), a nicotine group (N group), a nicotine-ST 36 group (N + ST 36 group) and a nicotine-GB 34 group (N+GB 34 group), 6 rats in each one. Starting at the 6th day of pregnancy, 0.9% sodium chloride solution was injected subcutaneously in the S group, 1 mg/kg; and in the rest 3 groups, nicotine of the same dose was injected through to the 21st postnatal day to establish the perinatal nicotine-exposure model. Simultaneously, during model preparation, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) in the N+ST 36 group and the N+GB 34 group respectively, once a day, through to the 21st postnatal day. The lung function analytic system for small animal was adopted to observe the changes in lung function indicators in newborn rats, such as peak inspiratory flow (PIF), peak expiratory flow (PEF), expiratory resistance (RE), inspiratory resistance (RI) and dynamic compliance (Cdyn). HE staining was used to observe the morphological changes of lung, such as alveolar fusion and rupture. Compared with the S group, PEF and Cdyn were lower and PIF, RI and RE higher in the N group (all P<0.01), additionally, alveoli were fused and ruptured, alveolar wall thickened, the numbers of alveoli reduced, the interspace of alveoli enlarged and the diameter increased (P<0.01). Compared with the N group, in the N+ST 36 group, PEF and Cdyn were increased, PIF, RI and RE reduced (P<0.05, P<0.01), the alveolar fusion and rupture relieved, the numbers of alveoli increased, alveolar wall thinner, the interpsace of alveoli became normal and the diameter was reduced significantly (P<0.01). In the N+GB 34 group, the changes of lung function and morphological indicators were not significant (P>0.05). Electroacupuncture at "Zusanli" (ST 36) in the pregnant rats significantly improves the perinatal nicotine-exposure-induced lung function and morphology of newborn rats than electroacupuncture at "Yanglingquan" (GB 34).

Outcome measures to be considered on asthma in elderly.

Asthma is a chronic heterogeneous respiratory disease which is characterized by airflow limitation and variable respiratory symptoms. Asthma in patients more than 65 years of age has an important negative impact on quality of life. The pathophysiology and treatment of asthma in older patients are not as well identified as in younger groups of ages. In this review we intend to outline characteristics found in elderly adults which distinguish them from other age groups of patients with asthma. With increasing age, there are alterations in the innate and adaptive immune responses, known as 'immunosenescence.' These age-associated modifications include an altered response after a pathogenic exposure or tissue injury, moderately mediated through an irreversible loss of cellular replication and defective tissue repair. Asthma is a consequence of complex gene-environment interactions, with diversity in clinical presentation and the type and intensity of airway inflammation and remodeling. Age-associated changes in lung physiology and morphology may occur and contribute to asthma. Aging is correlated with a notable decrease in elastic recoil, greater chest wall rigidity, and poor respiratory muscle strength. Underreporting of symptoms by elderly patients is common because of multiple underlying causes. VIDEO ABSTRACT: http://links.lww.com/COAI/A17.

(Pro)renin receptor regulates lung development via the Wnt/β-catenin signaling pathway.

The (pro)renin receptor [(P)RR] binds to prorenin to activate the renin-angiotensin system and is essential for the development of many different organ systems. Whether the (P)RR also plays a role in lung development is unknown. Immunostaining was used to determine the spatial-temporal distribution of (P)RR in the embryonic, postnatal, and adult lungs. We created a lung-specific (P)RR knockout mouse [Foxd1cre/+-(P)RRflox/flox] and assessed changes in lung morphology, cell proliferation, and apoptosis using immunohistochemistry and TUNEL staining. (P)RR function was confirmed by using siRNA to knock down (P)RR in human bronchial epithelial cells (HBECs) and then using the CCK-8 assay and flow cytometry to assess cell proliferation and apoptosis. Gene expression changes after knockdown were assessed by RT-PCR and Western blotting. (P)RR is expressed in the club cells of the bronchial epithelium, and expression increases throughout development. Lung-specific (P)RR knockout disrupted branching morphogenesis, leading to lung hypoplasia and neonatal mortality. These defects were associated with increased apoptosis and decreased proliferation of the pulmonary epithelial and mesenchymal cells and may be mediated by downregulation of Wnt11, β-catenin, and Axin2. (P)RR regulates lung development through canonical Wnt/β-catenin signaling and may present a new target for strategies to treat lung hypoplasia.

Electroacupuncture at "Zusanli" (ST36) and "Chize" (LU5) of mother rats exposed to nicotine during pregnancy and lactation has a protective effect on development of lung function and morphology in neonatal rats

To compare the different effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Chize" (LU5) of mother rats exposed to Nicotine during pregnancy and lactation on lung function and morphological changes in offspring rats, so as to explore the most effective acupoint for improving the development of lung in neonatal rats. A total of 24 female pregnancy SD rats were randomly divided into 4 groups: normal control, model, EA-ST36 and EA-LU5 (n＝6 rats in each group). Rats of the normal group were treated by subcutaneous injection of normal saline, and those of the other 3 groups treated by subcutaneous injection of nicotine (1 mg•kg－1•d－1) beginning from the 6th day to about the 21st day of pregnancy (childbirth day) for nicotine exposure during pregnancy and lactation. The daily EA treatment (2 Hz /15 Hz，1 mA) was applied to bilateral ST36 and LU5 for 20 min, beginning from the 6th day of pregnancy to the 21st day (childbirth day). The lung function of the offspring rats including the peak inspiratory flow (PIF), peak expiratory flow (PEF), lung resistance (RL), exhalation resistance (RE)and lung dynamic compliance (Cdyn) was detected by using a lung function analysis system. Histopathological changes (severity of alveolarization) of the offspring rats' lung tissue were observed under microscope after H．E. stain. Compared with the normal group, the PIF, RL and RE values were significantly increased (P<0.01), and PEF and Cdyn values significantly decreased in the model group (P<0.01). The alveolar diameter in the model group was evidently increased relevant to the normal group (P<0.01). Following the intervention, modeling induced increase of PIF, RL, RE and alveolar diameter and decrease of PEF and Cdyn values in the EA-ST36 group, and the increased PIF, RL and RE levels in the EA-LU5 group were obviously suppressed relevant to the model group (P<0.01, P<0.05). Additionally, modeling induced obvious congestion and edema of the alveolar wall, alveolar deformation, rupture and fusion, and reduction of the number of the pulmonary alveoli were evidently milder in both EA-ST36 and EA-LU5 groups. No significant differences were found between the EA-ST36 and EA-LU5 groups in the abovementioned 5 indexes of pulmonary function and alveolar diameter (P>0.05)．. EA of ST36 and LU5 of mother rats experiencing nicotine exposure during pregnancy and lactation can improve the lung function and morphological changes in neonatal rats, and the effect of ST36 is relatively better.

Therapeutic effects of Bianyanning decoction on acute pharyngitis in rats and its mechanism

To investigate the therapeutic effects and mechanisms of Bianyanning on acute pharyngitis in rats, and to provide evidence and experimental data for its clinical application. The acute pharyngitis of rats was induced by spraying ammonia directly to their throat. The model rats were randomly divided into model control group, the high-, medium- and low-dose group of Bianyanning, while normal rats were used as control group, 10 in each group. After the corresponding drug treatment, the symptoms and manifestations of each group were observed and recorded; 24 hours after last gavaging, blood samples of each group were collected from the abdominal aorta. The serum contents of interleukin 1-beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE method was used to observe the characteristic of the lung tissues and the transmission electron microscopy method was used to observe the trachea cilia. After the treatment, compared with the model control group, the high-, medium- and low-dose group of Bianyanning, the symptoms of acute pharyngitis such as inflamed and congestive throat were relieved obviously. The morphological changes of lung and bronchus tissues were apparently improved. The contents of IL-1β and TNF-α in serum were decreased significantly. Compound Bianyanning can promote the recovering process of acute pharyngitis, improve the morphology of lungs and bronchus, which may be related to inhibiting the releasing of the IL-1β and TNF-α in serum.

The role of PI3K/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion1.

PurposeTo investigate the role of PI3k/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion(I/R). MethodsMale Sprague-Dawley rats were subjected to 45 min of ischemia by occluding the superior mesenteric artery and to 2h of reperfusion to establish the model of I/R. Twenty four rats were randomly divided into four groups: Sham, intestinal I/R (II/R), propofol (P), wortmannin (W). In groups P, W, propofol was injected intravenously and continuously at the onset of reperfusion via infusion pump. PI3K inhibitor (wortmannin) was administered intravenously in group W 25 min before ischemia. Intestinal tissues and lung tissues were obtained for determination of histologic injury, wet/dry weight ratio, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. Meanwhile, the expressions of caspase-3 and phosphorylated Akt (p-Akt) in intestines and lungs were detected by western blot. ResultsPropofol treatment alleviated intestinal and lung morphological changes which were observed in II/R group , Moreover, wet/dry weight ratio, the MDA level, MPO activity and expression of caspase-3 were significantly decreased whereas the SOD activity and p-Akt expression were significantly increased. Notably, the protections were significantly reversed by pretreatment of wortmannin. Conclusion: PI3K/Akt pathway activation play a critical role in the protective effects of propofol on intestinal and lung injury induced by ischemia/reperfusion.

Probing Changes in Lung Physiology in COPD Using CT, Perfusion MRI, and Hyperpolarized Xenon-129 MRI

Chronic obstructive pulmonary disease (COPD) is highly heterogeneous and not well understood. Hyperpolarized xenon-129 (Xe129) magnetic resonance imaging (MRI) provides a unique way to assess important lung functions such as gas uptake. In this pilot study, we exploited multiple imaging modalities, including computed tomography (CT), gadolinium-enhanced perfusion MRI, and Xe129 MRI, to perform a detailed investigation of changes in lung morphology and functions in COPD. Utility and strengths of Xe129 MRI in assessing COPD were also evaluated against the other imaging modalities. Four COPD patients and four age-matched normal subjects participated in this study. Lung tissue density measured by CT, perfusion measures from gadolinium-enhanced MRI, and ventilation and gas uptake measures from Xe129 MRI were calculated for individual lung lobes to assess regional changes in lung morphology and function, and to investigate correlations among the different imaging modalities. No significant differences were found for all measures among the five lobes in either the COPD or age-matched normal group. Strong correlations (R > 0.5 or < -0.5, p < 0.001) were found between ventilation and perfusion measures. Also gas uptake by blood as measured by Xe129 MRI showed strong correlations with CT tissue density and ventilation measures (R > 0.5 or < -0.5, p < 0.001) and moderate to strong correlations with perfusion measures (R > 0.4 or < -0.5, p < 0.01). Four distinctive patterns of functional abnormalities were found in patients with COPD. Xe129 MRI has high potential to uniquely identify multiple changes in lung physiology in COPD using a single breath-hold acquisition.

Ozone protects the rat lung from ischemia-reperfusion injury by attenuating NLRP3-mediated inflammation, enhancing Nrf2 antioxidant activity and inhibiting apoptosis

Ischemia-reperfusion injury (IRI) is a major cause of lung dysfunction during cardiovascular surgery, heart transplantation and cardiopulmonary bypass procedures, and the inflammatory response, oxidative stress, and apoptosis play key and allegedly maladaptive roles in its pathogenesis. The aim of this study was to initially elucidate whether ozone induces oxidative preconditioning by activating nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and secondly to determine whether ozone oxidative preconditioning (OzoneOP) protects the lung from IRI by attenuating nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3)-mediated inflammation, enhancing the antioxidant activity of Nrf2 and inhibiting apoptosis. Rats treated with or without OzoneOP (2 ml containing 100 µg/kg/day) were subjected to 1 h of lung ischemia followed by 2 h of reperfusion for 10 days. Lung damage, antioxidant capacity, inflammation and apoptosis were evaluated and compared among different groups after reperfusion. OzoneOP significantly ameliorated changes in lung morphology and protected the lung from IRI by attenuating oxidative stress, inflammation-induced injury and lung apoptosis. Moreover, OzoneOP increased the expression of Nrf2 and decreased the levels of NLRP3, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), un-cleavable cysteine-requiring aspartate protease-1 (procaspase-1), cysteine-requiring aspartate protease-1 (caspase-1) and interleukin-1β (IL-1β) in the rat lungs. In summary, these results provide new insights into the molecular events modulated by ozone and suggest that ozone therapy may be an integrative support for patients with lung IRI.

Effect of Fructus schisandrae syrup on bronchial asthma mice model.

PurposeTo investigate the effect of Fructus schisandrae syrup on bronchial asthma mice model.MethodsSixty Kunming mice were randomly divided into normal control group, bronchial asthma model group, low-, middle-, and high-dose Fructus schisandrae syrup groups. Bronchial asthma was induced by injection of ovalbumin combined smoking. Two hours after the last administration, the change of lung function were observed, the contents of NO, IL-6 in serum were detected, the morphological changes of lung and bronchial were also observed, so as to explore the effect of Fructus schisandrae syrup on bronchial asthma mice.ResultsCompared with model group, the Schisandrae Fructus syrup groups can significantly increase the tidal volume of mice and decrease the respiratory frequency and the degree of bronchial stenosis (P < 0.01); The Schisandrae Fructus syrup groups can decrease the levels of NO and IL-6 in serum and improve the pathological changes of lung and bronchus in different degrees.ConclusionFructus schisandrae syrup can significantly improve the biochemical indexes and pathological status of mice with bronchial asthma.

Oropharyngeal administration of silica in Swiss mice: A robust and reproducible model of occupational pulmonary fibrosis

Pulmonary fibrosis (PF) is a lethal end stage of interstitial lung disease with increasing prevalence. The disease burden of PF has seen a sharp surge in the past two decades owing to entry of heavy amount of particulate matter due to industrialization and urbanization. In this work, we developed an oropharyngeal aspiration model of silica (1.5 mg/mice) induced pulmonary fibrosis as a homogeneous, reproducible, simple and alternative strategy in Swiss albino mice. Various BALF (protein, albumin, cell count), biochemical parameters (MDA, GSH, hydroxyproline), cytokines (IL-1β, IL-6, TNF-α and TGF-β1), histological (H&E and PSR staining) and protein expression (N-cadherin, vimentin, α-SMA, CTGF, collagen-1) studies were conducted to validate the model. Oropharyngeal administration of silica in Swiss mice produced significantly changes in lung morphology with statistically higher lung weights compared to normal control animals. The silica treated mice showed profoundly elevated BALF soluble and cytological parameters and enhanced oxidative and nitrosative stress in lungs. The levels of hydroxyproline were increased by 2.6 fold in the silica treated mice. The expression of pro-inflammatory cytokines were profoundly increased in silica treated mice. The histology and PSR staining indicated increased inflammatory infiltration and staggering fibrosis in silica treated group. In addition, the expression of EMT markers (N-cadherin, vimentin, α-SMA and CTGF) were significantly increased indicating their role in silica induced pulmonary fibrosis. Our work clearly demonstrates the superiority of stress free oropharyngeal instillation of silica with dose reduction over the conventional invasive and non-homogeneous intratracheal route.

TRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia.

Transient receptor potential A1 (TRPA1) channels were originally characterized in neuronal tissues but also identified in lung epithelium by staining with fluorescently coupled TRPA1 antibodies. Its exact function in non-neuronal tissues, however, is elusive. TRPA1 is activated in vitro by hypoxia and hyperoxia and is therefore a promising TRP candidate for sensing hyperoxia in pulmonary epithelial cells and for inducing alveolar epithelial hyperplasia. Here, we isolated tracheal, bronchial, and alveolar epithelial cells and show low but detectable TRPA1 mRNA levels in all these cells as well as TRPA1 protein by Western blotting in alveolar type II (AT II) cells. We quantified changes in intracellular Ca2+ ([Ca2+]i) levels induced by application of hyperoxic solutions in primary tracheal epithelial, bronchial epithelial, and AT II cells isolated from wild-type (WT) and TRPA1-deficient (TRPA1-/-) mouse lungs. In all cell types, we detected hyperoxia-induced rises in [Ca2+]i levels, which were not significantly different in TRPA1-deficient cells compared to WT cells. We also tested TRPA1 function in a mouse model for hyperoxia-induced alveolar epithelial hyperplasia. A characteristic significant increase in thickening of alveolar tissues was detected in mouse lungs after exposure to hyperoxia, but not in normoxic WT and TRPA1-/- controls. Quantification of changes in lung morphology in hyperoxic WT and TRPA1-/- mice, however, again revealed no significant changes. Therefore, TRPA1 expression does neither appear to be a key player for hyperoxia-induced changes in [Ca2+]i levels in primary lung epithelial cells, nor being essential for the development of hyperoxia-induced alveolar epithelial hyperplasia.

Amifostine Analog, DRDE-30, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice.

Bleomycin (BLM) is an effective curative option in the management of several malignancies including pleural effusions; but pulmonary toxicity, comprising of pneumonitis and fibrosis, poses challenge in its use as a front-line chemotherapeutic. Although Amifostine has been found to protect lungs from the toxic effects of radiation and BLM, its application is limited due to associated toxicity and unfavorable route of administration. Therefore, there is a need for selective, potent, and safe anti-fibrotic drugs. The current study was undertaken to assess the protective effects of DRDE-30, an analog of Amifostine, on BLM-induced lung injury in C57BL/6 mice. Whole body micro- computed tomography (CT) was used to non-invasively observe tissue damage, while broncheo-alveolar lavage fluid (BALF) and lung tissues were assessed for oxidative damage, inflammation and fibrosis. Changes in the lung density revealed by micro-CT suggested protection against BLM-induced lung injury by DRDE-30, which correlated well with changes in lung morphology and histopathology. DRDE-30 significantly blunted BLM-induced oxidative stress, inflammation and fibrosis in the lungs evidenced by reduced oxidative damage, endothelial barrier dysfunction, Myeloperoxidase (MPO) activity, pro-inflammatory cytokine release and protection of tissue architecture, that could be linked to enhanced anti-oxidant defense system and suppression of redox-sensitive pro-inflammatory signaling cascades. DRDE-30 decreased the BLM-induced augmentation in BALF TGF-β and lung hydroxyproline levels, as well as reduced the expression of the mesenchymal marker α-smooth muscle actin (α-SMA), suggesting the suppression of epithelial to mesenchymal transition (EMT) as one of its anti-fibrotic effects. The results demonstrate that the Amifostine analog, DRDE-30, ameliorates the oxidative injury and lung fibrosis induced by BLM and strengthen its potential use as an adjuvant in alleviating the side effects of BLM.

Effects of propofol pretreatment on lung morphology and heme oxygenase-1 expression in oleic acid-induced acute lung injury in rats.

To investigate the effects of propofol pretreatment on lung morphology and heme oxygenase-1 expression in oleic acid -induced acute lung injury in rats. A total of 32 male Sprague-Dawley rats (250-300g) were randomly divided into the following four groups (n=8/group): group C, group OA, group OA+PR, and group OA+IX to compare related parameter changes. PaO2, PCO2, and PaO2/FiO2 were significantly different among the four treatment groups (P<0.05 or P<0.01). Lung wet/dry weight ratio and HO-1 protein expression also significantly differed among the groups (P<0.01). Immunohistochemistry showed that the expression of HO-1 in group OA+PR was stronger than those in groups OA, OA+IX, and C. Light microscopy revealed that pathological changes in lung tissues in group OA+PR were milder than those in group OA and group OA+IX. Electron microscopy showed that alveolar type II epithelial cell ultrastructure in group OA was relatively irregular with cell degeneration and disintegration and cytoplasmic lamellar bodies were vacuolized. Changes in group OA+PR were milder than those in group OA; however, they were more severe in group OA+IX than in group OA. Propofol significantly increases the expression of HO-1 in the lung tissueand prevents changes in lung morphology due to ALI in rats.

Mouse Models of COPD.

Elastase and chronic cigarette smoke exposure animal models are commonly used to study lung morphologic and functional changes associated with emphysema-like airspace enlargement in various animal species. This chapter describes the rationale for using these two models to study mechanisms of COPD pathogenesis and provides protocols for their implementation. E-cigarettes are an emerging health concern and may also contribute to lung disease. Accordingly, approaches to study e-cigarette vapors are provided. This chapter also includes methods and tools necessary to assess lung morphologic and functional changes in animals with emphysema-like airspace enlargement.