Pretreatment With Fluticasone Propionate Increases Antibiotic Efficacy During Treatment of Late-Stage Primary Pneumonic Plague

Severe and late-stage pneumonias are often difficult to treat with antibiotics alone due to overwhelming host inflammatory responses mounted to clear infection. These host responses contribute to pulmonary damage leading to acute lung injury, acute respiratory distress syndrome, and death. In order to effectively treat severe and late-stage pneumonias, use of adjunctive therapies must be considered to reduce pulmonary damage when antimicrobial agents can be administered. Pneumonic plague, a severe pneumonia caused by inhalation of Yersinia pestis , is a fatal disease that causes death within six days without antibiotic intervention. Late-stage pneumonic plague is difficult to treat, as antibiotics must be delivered within 24 hours after onset of symptoms to be effective. Here, we use a murine model of primary pneumonic plague to examine how host inflammatory responses impact antibiotic treatment of late-stage pneumonic plague. We developed a murine infection model demonstrating the poor outcomes associated with delayed delivery of antibiotics. We show that pretreatment of mice with intranasal fluticasone propionate increased efficacy of delayed antibiotic delivery and enhanced murine survival. Mice receiving fluticasone propionate also showed decreased bacterial burden and reduced inflammatory pathology in the lungs. Further, we show that treatment and survival correlated with decreased levels of IL-6 and reduced neutrophil infiltration to the lungs. This work demonstrates how host inflammatory responses complicate treatment of late-stage pneumonic plague, and suggests that targeting of host inflammatory responses may improve treatment of severe, late-stage pneumonia.

Haemoptysis as Complication of Wire-Guided Pulmonary Vein Orifice Cryoballoon Ablation in Complex Anatomy: a Clinical Case Series

Background. Cryoballoon ablation of pulmonary vein orifices is an effective measure in atrial fibrillation but associates with risks of interventional complications, including haemoptysis. The described clinical case series presents novel evidence to revisit the complication sources.Materials and methods. Four haemoptysis-complicated cryoballoon ablations of pulmonary vein orifice have been analysed retrospectively. Interventions completed in a common clinical protocol with no additional postoperative complications.Results. Fluoroscopy revealed a loop-formed balloon-supporting end of guidewire located in peripheral lower lobe of right lung. Postoperative chest computed tomography also depicted the main lung blood volume confined in right lower lobe, thus indicating pulmonary damage by the guidewire.Discussion. Pulmonary vein anatomy is diverse and can greatly sophisticate the cryoballoon ablation procedure with a peculiar balloon navigation in left atrium. An optimal pulmonary vein orifice occlusion can be attained with guidewire, albeit incurring complications in form of haemoptysis.Conclusions. The appliance advancement towards lung periphery associates with a higher risk of haemoptysis and bleeding. Perioperative haemoptysis and bleeding are most likely associated with mechanical injury to minor veins and require further investigation.

The nanocomposite fullerol reduces oxidative stress, pulmonary injury, and mortality in a rat model of acute lung injury

BACKGROUND AND PURPOSE Acute lung injury (ALI) is a critical disorder that has high mortality rates, and pharmacological therapies are so far ineffective. The pathophysiology of ALI involves pulmonary oxidative stress and inflammatory response. Fullerol is a carbon nanocomposite that possesses antioxidant and anti-inflammatory properties. Here, we evaluated the therapeutic potential of fullerol and its mechanisms in a model of paraquat-induced ALI. EXPERIMENTAL APPROACH Rats were divided into ALI (paraquat alone), fullerol (paraquat plus fullerol), and control groups. Survival curves were estimated using the Kaplan-Meier method. The myeloperoxidase assay, ELISA, and hematoxylin and eosin staining were used to determine neutrophils infiltration, cytokines production, and histopathological parameters in lung samples, respectively. The antioxidant effect of fullerol was evaluated in vitro and ex vivo. KEY RESULTS Fullerol (0.01 to 0.3 mg/kg) markedly reduced the severe lung injury and high mortality rates observed in ALI rats. Moreover, fullerol (0.03 mg/kg) inhibited the reactive oxygen species formation and lipid peroxidation seen in lungs from ALI rats, and exhibited a potent concentration-dependent (10 to 10 mg/ml) in vitro antioxidant activity. Importantly, fullerol (0.03 mg/kg) inhibited neutrophils accumulation in bronchoalveolar lavage and lungs, and the increase in pulmonary levels of TNF-α, IL-1β, IL-6, and CINC-1 in ALI rats. CONCLUSIONS AND IMPLICATIONS Fullerol treatment was effective in reducing pulmonary damage and ALI-induced mortality, highlighting its therapeutic potential in an ALI condition. Searching for new pharmacological therapies to treat ALI may be desirable especially in view of the new coronavirus disease 2019 that currently plagues the world.

EVALUATION OF THE POSSIBILITY OF USING CORYOLIS VITRATOMYER IN THE DIAGNOSIS OF PULMONARY DAMAGE IN VICTIMS WITH FIRE PENETRATION EARLY WOUNDS

Summary: The aim of the study was to determine the dependence of the volume of air discharge from the pleural cavity on the choice of surgical treatment in patients with penetrating chest injuries. Materials and methods. Of the 39 observations, video-assisted thoracoscopy (VATS) was performed in 24 patients due to existing hemothorax. Results and their discussion. Among patients with penetrating chest injuries and early complications in the form of isolated pneumothorax on the first day, VATS was performed in three cases, due to increased air discharge from the pleural cavity. On the second and third day, 3 and 1 patient needed PBX, respectively. The article presents the experience of using a Coriolis flowmeter to objectify the diagnosis of lung injuries in victims with gunshot wounds penetrating the chest. Depending on the speed and volume of air discharge from the pleural cavity, the dynamics can be determined by the tactics of treatment. Conclusions: 1. Observation in the dynamics of the rate (

Sex differences in cardio-pulmonary pathology of SARS-CoV2 infected and Trypanosoma cruzi co-infected mice

Coronavirus disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; CoV2) is a deadly contagious infectious disease. For those who survived COVID-19, post-COVID cardiac damage poses a major threat for the progression of cardiomyopathy and heart failure. Currently, the number of COVID-related cases and deaths is increasing in Latin America, where a major COVID comorbidity is Chagas heart disease (caused by the parasite Trypanosoma cruzi). Here, we investigated the effect of T. cruzi infection on the pathogenesis and severity of CoV2 infection and, conversely, the effect of CoV2 infection on heart pathology during coinfection. We used transgenic human angiotensin-converting enzyme 2 (huACE2) mice infected with CoV2, T. cruzi, or coinfected with both in this study. Our study shows for the first time that white adipose tissue (WAT) serves as a reservoir for CoV2 and the persistence of CoV2 in WAT alters adipose tissue morphology and adipocyte physiology. Our data demonstrate a correlation between the loss of fat cells and the pulmonary adipogenic signaling and pathology in CoV2 infection. The viral load in the lungs is inversely proportional to the viral load in WAT, which differs between male and female mice. Our findings also suggest that adiponectin-PPAR signaling may differently regulate Chagas cardiomyopathy in coinfected males and females. We conclude that adipogenic signaling may play important roles in cardio-pulmonary pathogenesis during CoV2 infection and T. cruzi coinfection. The levels of adiponectin isomers differ between male and female mice during CoV2 infection and coinfection with T. cruzi, which may differently regulate inflammation, viral load, and pathology in the lungs of both the sexes. Our findings are in line with other clinical observations that reported that males are more susceptible to COVID-19 than females and suffer greater pulmonary damage.

Effect of Hyaluronic Acid on the Differentiation of Mesenchymal Stem Cells into Mature Type II Pneumocytes

Hyaluronic acid (HA) is an essential component of the extracellular matrix (ECM) of the healthy lung, playing an important role in the structure of the alveolar surface stabilizing the surfactant proteins. Alveolar type II (ATII) cells are the fundamental element of the alveolus, specializing in surfactant production. ATII cells represent the main target of lung external lesion and a cornerstone in the repair process of pulmonary damage. In this context, knowledge of the factors influencing mesenchymal stem cell (MSC) differentiation in ATII cells is pivotal in fulfilling therapeutic strategies based on MSCs in lung regenerative medicine. To achieve this goal, the role of HA in promoting the differentiation of MSCs in mature Type II pneumocytes capable of secreting pulmonary surfactant was evaluated. Results demonstrated that HA, at a specific molecular weight can greatly increase the expression of lung surfactant protein, indicating the ability of HA to influence MSC differentiation in ATII cells.

Obesity-Induced Dysbiosis Exacerbates IFN-γ Production and Pulmonary Inflammation in the Mycobacterium tuberculosis Infection

The microbiota of the gut–lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4+IFN-γ+IL-17− cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut–lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology.

Dying of VOC-202012/01 — multimodal investigations in a death case of the SARS-CoV-2 variant

The current pandemic with Severe acute respiratory syndrome-coronavirus-2 has been taking on new dynamics since the emergence of new variants last fall, some of them spreading more rapidly. Many countries currently find themselves in a race to ramp up vaccination strategies that have been initiated and a possible third wave of the pandemic from new variants, such as the Variant of Concern-202012/01 from the B.1.1.7 lineage. Until today, many investigations in death cases of Coronavirus-disease-19 have been conducted, revealing pulmonary damage to be the predominant feature of the disease. Thereby, different degrees of macroscopic and microscopic lung damage have been reported, most of them resembling an Acute Respiratory Distress Syndrome. Far more, systemic complications of the disease such as pulmonary embolisms have been described. However, neither morphologic nor virologic findings of patients dying of the new variants have yet been reported. Here, we report on a comprehensive analysis of radiologic, morphologic, and virologic findings in a fatal case of this variant.