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Frontiers in Immunology 2024The pulmonary endothelium is the primary target of lung ischemia-reperfusion injury leading to primary graft dysfunction after lung transplantation. We hypothesized that...
INTRODUCTION
The pulmonary endothelium is the primary target of lung ischemia-reperfusion injury leading to primary graft dysfunction after lung transplantation. We hypothesized that treating damaged rat lungs by a transient heat stress during ex-vivo lung perfusion (EVLP) to elicit a pulmonary heat shock response could protect the endothelium from severe reperfusion injury.
METHODS
Rat lungs damaged by 1h warm ischemia were reperfused on an EVLP platform for up to 6h at a constant temperature (T°) of 37°C (EVLP group), or following a transient heat stress (HS) at 41.5°C from 1 to 1.5h of EVLP (EVLP group). A group of lungs exposed to 1h EVLP only (pre-heating conditions) was added as control (Baseline group). In a first protocol, we measured lung heat sock protein expression (HSP70, HSP27 and Hsc70) at selected time-points (n=5/group at each time). In a second protocol, we determined (n=5/group) lung weight gain (edema), pulmonary compliance, oxygenation capacity, pulmonary artery pressure (PAP) and vascular resistance (PVR), the expression of PECAM-1 (CD31) and phosphorylation status of Src-kinase and VE-cadherin in lung tissue, as well as the release in perfusate of cytokines (TNFα, IL-1β) and endothelial biomarkers (sPECAM, von Willebrand Factor -vWF-, sE-selectin and sICAM-1). Histological and immunofluorescent studies assessed perivascular edema and formation of 3-nitrotyrosine (a marker of peroxinitrite) in CD31 lung endothelium.
RESULTS
HS induced an early (3h) and persisting expression of HSP70 and HSP27, without influencing Hsc70. Lungs from the EVLP group developed massive edema, low compliance and oxygenation, elevated PAP and PVR, substantial release of TNFα, IL-1β, s-PECAM, vWF, E-selectin and s-ICAM, as well as significant Src-kinase activation, VE-cadherin phosphorylation, endothelial 3-NT formation and reduced CD31 expression. In marked contrast, all these alterations were either abrogated or significantly attenuated by HS treatment.
CONCLUSION
The therapeutic application of a transient heat stress during EVLP of damaged rat lungs reduces endothelial permeability, attenuates pulmonary vasoconstriction, prevents src-kinase activation and VE-cadherin phosphorylation, while reducing endothelial peroxinitrite generation and the release of cytokines and endothelial biomarkers. Collectively, these data demonstrate that therapeutic heat stress may represent a promising strategy to protect the lung endothelium from severe reperfusion injury.
Topics: Animals; Lung; Rats; Heat-Shock Response; Male; Perfusion; Reperfusion Injury; Lung Transplantation; Endothelium, Vascular; Platelet Endothelial Cell Adhesion Molecule-1
PubMed: 38807604
DOI: 10.3389/fimmu.2024.1390026 -
Critical Care (London, England) May 2024Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have...
BACKGROUND
Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The primary objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in a mouse model. A secondary objective was to identify shared transcriptomic features of pneumococcal pneumonia and steroid treatment in the mouse model and clinical samples.
METHODS
We carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. We also studied lower respiratory tract gene expression from a cohort of 15 mechanically ventilated patients (10 with Streptococcus pneumoniae and 5 controls) to compare with the transcriptional studies in the mice.
RESULTS
In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Transcriptomic analyses identified effects of steroid therapy in mice that were also observed in the clinical samples.
CONCLUSIONS
In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The transcriptional studies in patients suggest that the mouse model replicates some of the features of pneumonia in patients with Streptococcus pneumoniae and steroid treatment. Overall, these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.
Topics: Animals; Pneumonia, Pneumococcal; Mice; Disease Models, Animal; Adrenal Cortex Hormones; Humans; Dexamethasone; Female; Male; Streptococcus pneumoniae
PubMed: 38807178
DOI: 10.1186/s13054-024-04956-6 -
Journal of the American Heart... May 2024Pregnancy in patients with pulmonary hypertension (PH) is associated with a heightened risk of medical complications including right heart failure, pulmonary edema, and...
BACKGROUND
Pregnancy in patients with pulmonary hypertension (PH) is associated with a heightened risk of medical complications including right heart failure, pulmonary edema, and arrhythmias. Our study investigated the association between PH and these complications during delivery.
METHODS AND RESULTS
The National Inpatient Sample was used to identify delivery hospitalizations from 2011 to 2020. Multivariable logistic regression was performed to study the association of PH with the primary outcomes of in-hospital medical and obstetric complications. A total of 37 482 207 delivery hospitalizations in women ≥18 years of age were identified, of which 9593 patients had PH. Pregnant patients with PH had higher incidence of complications during delivery including preeclampsia/eclampsia, arrhythmias, and pulmonary edema among others, compared with those without PH. Pregnant patients with PH also had a higher incidence of in-hospital mortality compared with those without PH (0.51% versus 0.007%). In propensity-matched analyses, PH was still significantly associated with a higher risk of in-hospital mortality (odds ratio [OR], 5.02 [95% CI, 1.82-13.90]; =0.001), pulmonary edema (OR, 9.11 [95% CI, 6.34-13.10]; <0.001), peripartum cardiomyopathy (OR, 1.85 [95% CI, 1.37-2.50]; <0.001), venous thromboembolism (OR, 12.60 [95% CI, 6.04-26.10]; <0.001), cardiac arrhythmias (OR, 6.11 [95% CI, 4.97-7.53]; <0.001), acute kidney injury (OR, 3.72 [95% CI, 2.86-4.84]; <0.001), preeclampsia/eclampsia (OR, 2.24 [95% CI, 1.95-2.58]; <0.001), and acute coronary syndrome (OR, 2.01 [95% CI, 1.06-3.80]; =0.03), compared with pregnant patients without PH.
CONCLUSIONS
Delivery hospitalizations in patients with PH are associated with a high risk of mortality, pulmonary edema, peripartum cardiomyopathy, venous thromboembolism, arrhythmias, acute kidney injury, preeclampsia/eclampsia, and acute coronary syndrome.
PubMed: 38804208
DOI: 10.1161/JAHA.123.031632 -
Critical Care (London, England) May 2024Acute respiratory distress syndrome (ARDS) represents a life-threatening inflammatory reaction marked by refractory hypoxaemia and pulmonary oedema. Despite advancements... (Review)
Review
Acute respiratory distress syndrome (ARDS) represents a life-threatening inflammatory reaction marked by refractory hypoxaemia and pulmonary oedema. Despite advancements in treatment perspectives, ARDS still carries a high mortality rate, often due to systemic inflammatory responses leading to multiple organ dysfunction syndrome (MODS). Indeed, the deterioration and associated mortality in patients with acute lung injury (LI)/ARDS is believed to originate alongside respiratory failure mainly from the involvement of extrapulmonary organs, a consequence of the complex interaction between initial inflammatory cascades related to the primary event and ongoing mechanical ventilation-induced injury resulting in multiple organ failure (MOF) and potentially death. Even though recent research has increasingly highlighted the role of the gastrointestinal tract in this process, the pathophysiology of gut dysfunction in patients with ARDS remains mainly underexplored. This review aims to elucidate the complex interplay between lung and gut in patients with LI/ARDS. We will examine various factors, including systemic inflammation, epithelial barrier dysfunction, the effects of mechanical ventilation (MV), hypercapnia, and gut dysbiosis. Understanding these factors and their interaction may provide valuable insights into the pathophysiology of ARDS and potential therapeutic strategies to improve patient outcomes.
Topics: Humans; Respiratory Distress Syndrome; Lung; Respiration, Artificial; Gastrointestinal Tract
PubMed: 38802959
DOI: 10.1186/s13054-024-04966-4 -
Cureus Apr 2024Tuberculosis (TB), caused by the bacteria , is a highly infectious and prevalent disease. It is the leading cause of death among communicable diseases and the fifth...
Tuberculosis (TB), caused by the bacteria , is a highly infectious and prevalent disease. It is the leading cause of death among communicable diseases and the fifth leading cause of all diseases in India. The diagnosis can be challenging due to the disease's unique appearance and various presentations. Disseminated TB is characterized by the involvement of two or more non-contiguous sites resulting from hematogenous extension of the disease. Clinical confirmation of the diagnosis of disseminated TB is based on bacteriological or histological evidence. Based on various studies, there is evidence that satisfactory results are obtained from treatment with first-line anti-tubercular drugs. When there is a delay in diagnosis and treatment, it can become a life-threatening condition. We present a case of a 38-year-old alcoholic male who presented with generalized edema, pain, and distension of the abdomen. According to the initial presentation, the provisional diagnosis made was alcoholic liver disease, but it was later diagnosed as disseminated TB with sputum-positive pulmonary TB with abdominal involvement in the form of ascites and hepatosplenomegaly along with hematological involvement as pancytopenia. The patient started showing drastic improvement after the initiation of anti-tubercular therapy.
PubMed: 38800156
DOI: 10.7759/cureus.58902 -
Iranian Journal of Basic Medical... 2024Paraquat (PQ), a potent environmental herbicide, is recognized for inducing irreparable toxic damage to biological systems. This study aimed to evaluate the...
Evaluation of the influence of N-acetylcysteine and broccoli extract on systemic paraquat poisoning: Implications for biochemical, physiological, and histopathological parameters in rats.
OBJECTIVES
Paraquat (PQ), a potent environmental herbicide, is recognized for inducing irreparable toxic damage to biological systems. This study aimed to evaluate the effectiveness of N-acetylcysteine (NAC) and broccoli extract, individually and in combination, in alleviating PQ poisoning in rats, leveraging the exceptional anti-oxidant, anti-inflammatory, and anti-apoptotic properties of broccoli.
MATERIALS AND METHODS
Seventy Wistar rats were categorized into seven groups: C (control, vehicle), PQ (paraquat at 40 mg/kg), BC (broccoli extract at 300 mg/kg), NC (N-acetylcysteine at the same dose of 300 mg/kg), and combined groups PQ+BC, PQ+NC, and NC+PQ+BC, all administered equivalent doses. After 42 days, blood samples were collected to evaluate liver and kidney parameters, proinflammatory biomarkers, caspase-3, and caspase-9. Lung tissues were excised, with one part preserved for hydroxyproline and oxidative stress parameter measurement and another sectioned and stained for histopathological analysis.
RESULTS
The PQ group exhibited the highest lung-to-body weight (LW/BW) ratio, while the PQ+BC+NC group demonstrated the lowest ratio. Results indicated an elevated lung hydroxyproline concentration and a significant reduction in anti-oxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase, and total anti-oxidant capacity) (<0.001). The PQ+BC group showed modified malondialdehyde levels, reaching a peak in the PQ group. Additionally, a significant decrease in tumor necrosis factor, interleukin-1, caspase-3, and caspase-9 was observed in the PQ+BC+NC group (<0.01). Pulmonary edema, hyperemia, and severe hemorrhage observed in the PQ group were notably reduced in the PQ+BC+NC group.
CONCLUSION
The combination of active compounds from broccoli and NAC demonstrated significant systemic and pulmonary effects in mitigating PQ-induced toxicity.
PubMed: 38800031
DOI: 10.22038/IJBMS.2024.75258.16311 -
Narra J Apr 2024Radiological examinations such as chest X-rays (CXR) play a crucial role in the early diagnosis and determining disease severity in coronavirus disease 2019 (COVID-19)....
Radiological examinations such as chest X-rays (CXR) play a crucial role in the early diagnosis and determining disease severity in coronavirus disease 2019 (COVID-19). Various CXR scoring systems have been developed to quantitively assess lung abnormalities in COVID-19 patients, including CXR modified radiographic assessment of lung edema (mRALE). The aim of this study was to determine the relationship between mRALE scores and clinical outcome (mortality), as well as to identify the correlation between mRALE score and the severity of hypoxia (PaO2/FiO2 ratio). A retrospective cohort study was conducted among hospitalized COVID-19 patients at Dr. Soetomo General Academic Hospital Surabaya, Indonesia, from February to April 2022. All CXR data at initial admission were scored using the mRALE scoring system, and the clinical outcomes at the end of hospitalization were recorded. Of the total 178 COVID-19 patients, 62.9% survived after completing the treatment. Patients within non-survived had significantly higher quick sequential organ failure assessment (qSOFA) score (<0.001), lower PaO2/FiO2 ratio (=0.004), and higher blood urea nitrogen (<0.001), serum creatinine (<0.008) and serum glutamic oxaloacetic transaminase (=0.001) levels. There was a significant relationship between mRALE score and clinical outcome (survived vs deceased) (=0.024; contingency coefficient of 0.184); and mRALE score of ≥2.5 served as a risk factor for mortality among COVID-19 patients (relative risk of 1.624). There was a significant negative correlation between the mRALE score and PaO/FiO ratio based on the Spearman correlation test (=-0.346; <0.001). The findings highlight that the initial mRALE score may serve as an independent predictor of mortality among hospitalized COVID-19 patients as well as proves its potential prognostic role in the management of COVID-19.
Topics: Humans; COVID-19; Indonesia; Male; Female; Retrospective Studies; Middle Aged; Severity of Illness Index; Radiography, Thoracic; Adult; Pulmonary Edema; SARS-CoV-2; Aged; Prognosis
PubMed: 38798849
DOI: 10.52225/narra.v4i1.691 -
Journal of Pharmacological Sciences Jul 2024Interleukin (IL-19) belongs to the IL-10 family of cytokines and plays diverse roles in inflammation, cell development, viral responses, and lipid metabolism. Acute lung...
Interleukin (IL-19) belongs to the IL-10 family of cytokines and plays diverse roles in inflammation, cell development, viral responses, and lipid metabolism. Acute lung injury (ALI) is a severe respiratory condition associated with various diseases, including severe pneumonia, sepsis, and trauma, lacking established treatments. However, the role of IL-19 in acute inflammation of the lungs is unknown. We reported the impact of IL-19 functional deficiency in mice crossed with an ALI model using HCl. Lungs damages, neutrophil infiltration, and pulmonary edema induced by HCl were significantly worse in IL-19 knockout (KO) mice than in wild-type (WT) mice. mRNA expression levels of C-X-C motif chemokine ligand 1 (CXCL1) and IL-6 in the lungs were significantly higher in IL-19 KO mice than in WT mice. Little apoptosis was detected in lung injury in WT mice, whereas apoptosis was observed in exacerbated area of lung injury in IL-19 KO mice. These results are the first to show that IL-19 is involved in acute inflammation of the lungs, suggesting a novel molecular mechanism in acute respiratory failures. If it can be shown that neutrophils have IL-19 receptors and that IL-19 acts directly on them, it would be a novel drug target.
Topics: Animals; Acute Lung Injury; Interleukins; Hydrochloric Acid; Mice, Knockout; Mice, Inbred C57BL; Interleukin-6; Disease Models, Animal; Neutrophil Infiltration; Chemokine CXCL1; Male; Lung; Apoptosis; Mice; Neutrophils; Pulmonary Edema; Gene Expression
PubMed: 38797538
DOI: 10.1016/j.jphs.2024.04.003 -
Journal of Pharmacological Sciences Jul 2024Pulmonary inflammation may lead to neuroinflammation resulting in neurological dysfunction, and it is associated with a variety of acute and chronic lung diseases....
Pulmonary inflammation may lead to neuroinflammation resulting in neurological dysfunction, and it is associated with a variety of acute and chronic lung diseases. Paeonol is a herbal phenolic compound with anti-inflammatory and anti-oxidative properties. The aim of this study is to understand the beneficial effects of paeonol on cognitive impairment, pulmonary inflammation and its underlying mechanisms. Pulmonary inflammation-associated cognitive deficit was observed in TNFα-stimulated mice, and paeonol mitigated the cognitive impairment by reducing the expressions of interleukin (IL)-1β, IL-6, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) in hippocampus. Moreover, elevated plasma miR-34c-5p in lung-inflamed mice was also reduced by paeonol. Pulmonary inflammation induced by intratracheal instillation of TNFα in mice resulted in immune cells infiltration in bronchoalveolar lavage fluid, pulmonary edema, and acute fibrosis, and these inflammatory responses were alleviated by paeonol orally. In MH-S alveolar macrophages, tumor necrosis factor (TNF) α- and phorbol myristate acetate (PMA)-induced inflammasome activation was ameliorated by paeonol. In addition, the expressions of antioxidants were elevated by paeonol, and reactive oxygen species production was reduced. In this study, paeonol demonstrates protective effects against cognitive deficits and pulmonary inflammation by exerting anti-inflammatory and anti-oxidative properties, suggesting a powerful benefit as a potential therapeutic agent.
Topics: Lung Diseases; Acetophenones; Cognitive Dysfunction; Macrophages; Oxidative Stress; Mice, Inbred C57BL; Male; Animals; Mice; Tumor Necrosis Factor-alpha; Inflammation; Acute Lung Injury; MicroRNAs; Reactive Oxygen Species
PubMed: 38797534
DOI: 10.1016/j.jphs.2024.04.006 -
Sensors (Basel, Switzerland) May 2024Providing employees with proper work conditions should be one of the main concerns of any employer. Even so, in many cases, work shifts chronically expose the workers to... (Review)
Review
Providing employees with proper work conditions should be one of the main concerns of any employer. Even so, in many cases, work shifts chronically expose the workers to a wide range of potentially harmful compounds, such as ammonia. Ammonia has been present in the composition of products commonly used in a wide range of industries, namely production in lines, and also laboratories, schools, hospitals, and others. Chronic exposure to ammonia can yield several diseases, such as irritation and pruritus, as well as inflammation of ocular, cutaneous, and respiratory tissues. In more extreme cases, exposure to ammonia is also related to dyspnea, progressive cyanosis, and pulmonary edema. As such, the use of ammonia needs to be properly regulated and monitored to ensure safer work environments. The Occupational Safety and Health Administration and the European Agency for Safety and Health at Work have already commissioned regulations on the acceptable limits of exposure to ammonia. Nevertheless, the monitoring of ammonia gas is still not normalized because appropriate sensors can be difficult to find as commercially available products. To help promote promising methods of developing ammonia sensors, this work will compile and compare the results published so far.
Topics: Ammonia; Humans; Electronic Nose; Occupational Exposure; Workplace; Occupational Health; Environmental Monitoring; Working Conditions
PubMed: 38794006
DOI: 10.3390/s24103152