Interstitial Pulmonary Edema Research Articles

Pulmonary hypertension in patients carrying FLNA loss-of-function variants.

Pulmonary hypertension (PH) is an unusual complication of X-linked disease caused by loss-of-function (LOF) variants in the filamin A (FLNA) gene. Patients with FLNA LOF may also present dysmorphic facial features, aortic dilation, thrombopenia, and periventricular nodular heterotopia (PVNH). We reported clinical, functional, radiologic, and hemodynamic characteristics of patients with FLNA LOF variants and PH from the French PH Network. Nine patients were identified with a female to male ratio of 8:1. PH was diagnosed at a median age of 36 [0-69] years. Associated conditions included epilepsy (n=5), PVNH (n=7), valvular heart disease (n=8), congenital heart diseases (n=4), thrombocytopenia (n=4), and hyperlaxity (n=4). Right heart catheterisation confirmed moderate-to-severe precapillary PH with a median mPAP of 33 [22-49] mmHg and PVR of 4.7 [2.4-8.0] WU. The DLCO was markedly decreased (48 [22-64] %pred) and five patients had obstructive ventilatory disorder. High-resolution CT showed heterogeneous parenchyma (n=8), emphysema (n=3), presence of a peripheral hyperclear band (n=3) and aortic ectasia (n=4). Pathologic assessment available in one patient revealed significant remodelling of small pulmonary arteries, interstitial edema, and irregular alveoli shapes. During follow-up, three patients died, including two from right heart failure. No patient died from aortic rupture. Precapillary PH, likely due to multiple mechanisms, may complicate the course of patients with LOF FLNA variants and may be the presenting symptom leading to diagnosis. The combination of PH with parenchymal involvement and extrapulmonary symptoms (epilepsy, congenital heart diseases, valvular and aortic involvement, thrombocytopenia) should prompt genetic screening for FLNA.

Nosological Pattern of Diseases Accompanied by Chronic Cough in Dogs

Introduction. A practicing veterinarian usually faces difficulties in both diagnosing and treating coughing in dogs. The unsolved problem in diagnosing entails doubts in the efficacy of the prescribed therapy. This is especially relevant for small dog breeds of middle and old age that often suffer from the chronic respiratory diseases and mitral insufficiency due to endocardiosis, and each of these diseases can lead to chronic cough. The aim of the research is to reveal the nosological pattern of the diseases accompanied by chronic cough in dogs.Materials and Methods. The research was based on the analysis of the medical records of 145 dogs with chronic cough that have attended to the network of veterinary clinics “Vita” (Rostov region) in the period from September 1, 2021 to July 31, 2024. The research was carried out using the following equipment: Karl Storz video bronchoscope (PAL colour system, working channel 2.3 mm, gaze direction 0°, aperture angle 120°, up/down deviation 180°/100°, depth of field 3–50 mm, working length 61 cm, outer diameter 6.2 mm); premium ultrasound scanner with improved image quality on the ZST+Mindray Vetus 9 platform; Maxivet 400 veterinary X-ray digital DR system; Poli-Spectrum–8/B computerassisted electrocardiograph; automatic hematology analyzer Idexx ProCyte Dx; automatic biochemistry analyzer Idexx Catalyst One; digital microscope Celestron.Results. The conducted research allowed us to find out the main causes of coughing in dogs. The most common cause of chronic cough found in these animals was chronic bronchitis, including that occurring simultaneously with the collapse of the upper respiratory tract. The rarest revealed cause of chronic cough was endocardiosis.Discussion and Conclusion. Coughing in dogs is not a characteristic sign of endocardiosis: even when the disease was clinically evident, coughing was observed only in the cases of lung congestion and interstitial pulmonary edema. As a rule, dogs with endocardiosis that have a pronounced loud cough intensifying after exertion, have a concomitant disease of the upper respiratory tract. Coughing in dogs with endocardiosis and upper respiratory tract lesion does not go away upon getting merely a specific endocardiosis treatment.

NUPR1 modulates pulmonary embolism progression via smooth muscle cells phenotypic transformation

ObjectiveThis study aimed to investigate the role of Nuclear Protein 1 (NUPR1) in pulmonary embolism (PE) and its impact on the phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs). MethodsA PE model was established via autologous pulmonary emboli infusion into the jugular vein. Partial Pressure of Oxygen (PaO2), Oxygenation Index (OI), Brain Natriuretic Peptide (BNP), and Troponin I (TnI) were measured, and lung tissue was subjected to hematoxylin-eosin (HE) staining. NUPR1 expression was assessed through Immunofluorescence and Western blot analyses. To investigate role of NUPR1, PE rats were treated with lentiviral vectors for NUPR1 knockdown (si-NUPR1) or overexpression (ov-NUPR1), and the effects on lung pathology were examined. NUPR1 expression was evaluated in human PASMCs. Additionally, PASMCs from SD rats were cultured under normoxic and hypoxic conditions to evaluate NUPR1 expression. Transfection of NUPR1 expression vectors into PASMCs allowed monitoring of phenotypic transformation-associated protein changes and PASMCs activity. ResultsIncreased NURP1 was observed in human-derived PASMCs. In PE rats, histological examination revealed ruptured pulmonary alveoli, exudate accumulation, interstitial edema, and infiltration of inflammatory cells, concomitant with elevated NUPR1 expression levels. Knockdown of NUPR1 in PE rats significantly improved lung tissue structure, reducing alveolar rupture and interstitial edema. Conversely, NUPR1 overexpression exacerbated lung damage, leading to increased inflammatory infiltration. NUPR1 expression in rat PASMCs remained stable under normoxic conditions; however, under hypoxic conditions, NUPR1 protein expression increased progressively over time. Subsequent upregulation of NUPR1 expression led to a decrease in the levels of contractile phenotype markers α-SMA and SM22α in PASMCs, accompanied by increased expression of synthetic phenotype markers Vimentin and OPN. This phenotypic shift was associated with enhanced cellular proliferation, invasion, and migration. ConclusionsElevated NUPR1 expression in PE exacerbates abnormal PASMCs proliferation by promoting their phenotypic transformation, thereby fostering the pathological progression of PE.

Curcumin-mediated enhancement of lung barrier function in rats with high-altitude-associated acute lung injury via inhibition of inflammatory response

BackgroundExposure to a hypobaric hypoxic environment at high altitudes can lead to lung injury. In this study, we aimed to determine whether curcumin (Cur) could improve lung barrier function and protect against high-altitude-associated acute lung injury.MethodsTwo hundred healthy rats were randomly divided into standard control, high-altitude control (HC), salidroside (40 mg/kg, positive control), and Cur (200 mg/kg) groups. Each group was further divided into five subgroups. Basic vital signs, lung injury histopathology, routine blood parameters, plasma lactate level, and arterial blood gas indicators were evaluated. Protein and inflammatory factor (tumor necrosis factor α (TNF-α), interleukin [IL]-1β, IL-6, and IL-10) concentrations in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method and enzyme-linked immunosorbent assay, respectively. Inflammation-related and lung barrier function-related proteins were analyzed using immunoblotting.ResultsCur improved blood routine indicators such as hemoglobin and hematocrit and reduced the BALF protein content and TNF-α, IL-1β, and IL-6 levels compared with those in the HC group. It increased IL-10 levels and reduced pulmonary capillary congestion, alveolar hemorrhage, and the degree of pulmonary interstitial edema. It increased oxygen partial pressure, oxygen saturation, carbonic acid hydrogen radical, and base excess levels, and the expression of zonula occludens 1, occludin, claudin-4, and reduced carbon dioxide partial pressure, plasma lactic acid, and the expression of phospho-nuclear factor kappa.ConclusionsExposure to a high-altitude environment for 48 h resulted in severe lung injury in rats. Cur improved lung barrier function and alleviated acute lung injury in rats at high altitudes.

Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in mice

Acute lung injury (ALI) is the result of damage to the capillary endothelia and the alveolar epithelial cell caused by various direct and indirect factors, leading to significant pulmonary interstitial and alveolar edema and acute hypoxic respiratory insufficiency. A subset of ALI cases progresses to irreversible pulmonary fibrosis, a condition with fatal implications. Zafirlukast is a leukotriene receptor antagonist licensed for asthma prevention and long-term treatment. This study demonstrated a significant improvement in lung tissue pathology and a reduction in inflammatory cell infiltration in models of lipopolysaccharide (LPS)-induced ALI and bleomycin (BLM)-induced lung inflammation following zafirlukast administration, both in vivo and in vitro. Moreover, zafirlukast was found to suppress the inflammatory response of alveolar epithelial cells in vitro and lung inflammation in vivo by reducing the activation of the TLR4/NF-κB/NLRP3 inflammasome pathway. In conclusion, zafirlukast relieved lung injury and the infiltration of inflammatory cells in the lung by regulating the TLR4/NF-κB/NLRP3 pathway.

A retrospective analysis of transudative pleural effusion due to fibrosing mediastinitis

BackgroundPleural effusion caused by fibrosing mediastinitis is rarely reported. This study aimed to summarize the clinical manifestations, diagnosis and treatment of transudative pleural effusion due to fibrosing mediastinitis.MethodsMedical records and follow-up data of 7 patients with transudative pleural effusion due to fibrosing mediastinitis in Beijing Chaoyang Hospital between May 2014 and Feb 2018 were retrospectively analyzed.ResultsThese patients included 4 males and 3 females, with an average age of (64 ± 9) years. There were 3 left-sided effusions, 2 right-sided effusions and 2 bilateral effusions. Previous or latent tuberculosis was found in 6 patients. Pulmonary hypertension was indicated by echocardiography in all the 7 patients. Computed tomography pulmonary angiography (CTPA) of all the 7 cases showed increased soft tissue images visible in the mediastinum and bilateral hilus, different degrees of stenosis or occlusion in the pulmonary artery and pulmonary vein. In addition, 4 cases were found of right middle lobe atelectasis with a mediastinal window setting. There was interstitial pulmonary edema on the side of pleural effusion with a lung window setting. All the 7 patients were treated with intermittent drainage of pleural effusion combined with diuretic therapy. Five patients were treated with antituberculosis therapy. Up to now, two patients died of right heart failure and respiratory failure after 2 and 16 months respectively; The remaining 5 patients were still in follow up.ConclusionFibrosing mediastinitis can lead to pulmonary vein stenosis or occlusion, and thus cause transudative pleural effusion, which can be detected by CTPA. Pulmonary hypertension, long time of cough, and a history of tuberculosis are common in these patients. The common therapy is intermittent drainage of pleural effusion combined with diuretic therapy.

Impact of fluid balance and opioid-sparing anesthesia within enchanced recovery pathway on postoperative morbidity after transthoracic esophagectomy for cancer.

BackgroundEnhanced Recovery After Surgery (ERAS) protocol for esophagectomy may reduce the high incidence of postoperative morbidity and mortality. The aim of this study was to assess the impact of properly conducted ERAS protocol with specific emphasis on fluid balance and opioid-sparing anesthesia (OSA) on postoperative major morbidity and mortality after esophagectomy.MethodsPatients undergoing elective esophagectomy for esophageal cancer at the Hospital for Digestive Surgery, University Clinical Center of Serbia, from December 2017 to March 2021, were included in this retrospective observational study. Patients were divided into two groups: the ERAS group (OSA, intraoperative goal-directed therapy, and postoperative “near-zero” fluid balance) and the control group (opioid-based anesthesia, maintenance mean blood pressure ≥ 65 mmHg, and liberal postoperative fluid management). The primary outcome was major morbidity within 30 days from surgery and 30-day and 90-day mortality. Multivariable analysis was used to examine the effect of the ERAS protocol.ResultsA total of 121 patients were divided into the ERAS group (69 patients) and the control group (52 patients). Patients in the ERAS group was received less fentanyl, median 300 (interquartile range (IQR), 200–1,550) mcg than in control group, median 1,100 (IQR, 650–1750) mcg, p < 0.001. Median intraoperative total infusion was lower in the ERAS group, 2000 (IQR, 1000–3,750) mL compared to control group, 3,500 (IQR, 2000–5,500) mL, p < 0.001. However, intraoperative norepinephrine infusion was more administered in the ERAS group (52.2% vs. 7.7%, p < 0.001). On postoperative day 1, median cumulative fluid balance was 2,215 (IQR, −150-5880) mL in the ERAS group vs. 4692.5 (IQR, 1770–10,060) mL in the control group, p = 0.002. After the implementation of the ERAS protocol, major morbidity was less frequent in the ERAS group than in the control group (18.8% vs. 75%, p < 0.001). There was no statistical significant difference in 30-day and 90-day mortality (p = 0.07 and p = 0.119, respectively). The probability of postoperative major morbidity and interstitial pulmonary edema were higher in control group (OR 5.637; CI95%:1.178–10.98; p = 0.030 and OR 5.955; CI95% 1.702–9.084; p < 0.001, respectively).ConclusionA major morbidity and interstitial pulmonary edema after esophagectomy were decreased after the implementation of the ERAS protocol, without impact on overall mortality.

Elevated left ventricular end diastolic pressure, chronic pulmonary oedema and valve disease

As part of ageing and with increased longevity of older people, there has been a rise of those with increased left ventricular end diastolic pressure (LVEDP) and left ventricular diastolic dysfunction (LVDD). Comorbidities like hypertension, diabetes, chronic kidney disease, coronary artery disease and others appear to be contributing to this. Chronic interstitial pulmonary edema may be a part of the presentation of those with elevated LVEDP/LVDD. Progressive valvular heart disease may also complicate the picture and make clinical decision-making difficult. This case report discusses these issues.

Hantavirus infection in a child: clinical case

Hantavirus infection is a rare zoonotic viral disease characterized by fever, interstitial pneumonia, acute respiratory failure, respiratory distress syndrome, acute heart failure, renal failure and digestive tract disorders. The aim of the work is to acquaint practitioners with the case of hantavirus infection in a child. Materials and methods. The child was treated at Zaporizhzhia City Pediatric Hospital No. 5. He underwent clinical and biochemical blood tests, microbiological, radiological and ultrasound examinations using hospital equipment. Determination of immunoglobulins M and G to hantavirus by immunofluorescence analysis was conducted in a reference laboratory. Results. The child was admitted with complaints of headache, fever, epigastric pain, vomiting and stools with blood, shortness of breath, cough, blood in sputum, muscle pain, decreased diuresis. Laboratory findings included leukocytosis, anemia, thrombocytopenia, elevated ESR, elevated procalcitonin and creatinine levels, and hypercoagulability. Instrumentally, right-sided interstitial pneumonia and duodenal ulcer were diagnosed. The positive result for hantavirus infection was confirmed by the levels of immunoglobulins M and G to hantavirus and the increase in their titers in the dynamics. Comprehensive intensive care resulted in relatively rapid recovery of the child. Conclusions. The criteria for the diagnosis of hantavirus infection with pulmonary and renal syndromes are: the presence of interstitial pulmonary edema, fever with myalgias, arthralgias, cephalgia, nausea, vomiting and headache, followed by oliguria. Neutrophilic leukocytosis, anemia, thrombocytopenia, increased hematocrit, proteinuria, and microhematuria are characteristic. Determination of IgM and G to hantavirus and their dynamics is effective for confirming the diagnosis. Hantavirus infection is rather rare in Ukraine. Clinical discussions of diseases that are rarely occurring in practice are useful for physicians and will facilitate a faster diagnostic search.

UNVEILING THE PROTECTIVE MECHANISMS OF PUERARIN AGAINST ACUTE LUNG INJURY: A COMPREHENSIVE EXPLORATION OF THE ROLES AND MECHANISMS OF MST1/ERS SIGNALING.

Objectives: Puerarin, the principal active constituent extracted from Pueraria, is believed to confer protection against sepsis-induced lung injury. The study aimed to elucidate the role and mechanism of Mst1/ERS in puerarin-mediated protection against acute lung injury (ALI). Methods: Monolayer vascular endothelial cell permeability was assessed by gauging the paracellular flow of FITC-dextran 40,000 (FD40). ELISA was employed for the quantification of inflammatory cytokines. Identification of target proteins was conducted through western blotting. Histological alterations and apoptosis were scrutinized using hematoxylin-eosin staining and TUNEL staining, respectively. The ultrastructure of the endoplasmic reticulum was observed via transmission electron microscopy. Results: Puerarin significantly protected mice from LPS-induced ALI, reducing lung interstitial width, neutrophil and lymphocyte infiltration, pulmonary interstitial and alveolar edema, and lung apoptosis. Puerarin treatment also markedly attenuated levels of TNF-α and IL-1β in both alveolar lavage fluid and serum. Furthermore, puerarin significantly attenuated LPS-induced increases in Mst1, GRP78, CHOP, and Caspase12 protein expression and blunted LPS-induced decrease in ZO-1 protein expression in lung tissues. Puerarin obviously reduced endoplasmic reticulum expansion and vesiculation. Similarly, puerarin significantly mitigated the LPS-induced reduction in HUVEC cell viability and ZO-1 expression. Puerarin also attenuated LPS-induced increase in apoptosis, TNF-α and IL-1β, FD40 flux, and Mst1, GRP78, CHOP, and Caspase12 expression in HUVEC cells. Nevertheless, the inhibitory impact of puerarin on vascular endothelial cell injury, lung injury, and endoplasmic reticulum stress (ERS) was diminished by Mst1 overexpression. Conclusion: These findings demonstrated that the Mst1/ERS signaling pathway played a pivotal role in the development of LPS-induced vascular endothelial cell dysfunction and ALI. Puerarin exhibited the ability to attenuate LPS-induced vascular endothelial cell dysfunction and ALI by inhibiting the Mst1/ERS signaling pathway.

Lung Ultrasonography Does Not Distinguish between Interstitial and Alveolar Pulmonary Edema

For a long time, lung diseases have been considered the “forbidden zone” for ultrasound diagnosis because the lung is filled with gas, and the ultrasound waves are totally reflected when they encounter gas [...]

High Respiratory and Cardiac Drive Exacerbate Secondary Lung Injury in Patients With Critical Illness.

The high respiratory and cardiac drive is essential to the host-organ unregulated response. When a primary disease and an unregulated secondary response are uncontrolled, the patient may present in a high respiratory and cardiac drive state. High respiratory drive can cause damage to the lungs, pulmonary circulation, and diaphragm, while high cardiac drive can lead to fluid leakage and infiltration as well as pulmonary interstitial edema. A "respiratory and cardiac dual high drive" state may be a sign of an unregulated response and can lead to secondary lung injury through the increase of transvascular pressure and pulmonary microcirculation injury. Ultrasound examination of the lung, heart, and diaphragm is important when evaluating the phenotype of high respiratory drive in critically ill patients. Ultrasound assessment can guide sedation, analgesia, and antistress treatment and reduce the risk of high respiratory and cardiac drive-induced lung injury in these patients.

Acute Lung Injury and the NLRP3 Inflammasome.

Acute lung injury (ALI) manifests through harm to the capillary endothelium and alveolar epithelial cells, arising from a multitude of factors, leading to scattered interstitial alterations, pulmonary edema, and subsequent acute hypoxic respiratory insufficiency. Acute lung injury (ALI), along with its more serious counterpart, acute respiratory distress syndrome (ARDS), carry a fatality rate that hovers around 30-40%. Its principal pathological characteristic lies in the unchecked inflammatory reaction. Currently, the main strategies for treating ALI are alleviation of inflammation and prevention of respiratory failure. Concerning the etiology of ALI, NLRP3 Inflammasome is essential to the body's innate immune response. The composition of this inflammasome complex includes NLRP3, the pyroptosis mediator ASC, and pro-caspase-1. Recent research has reported that the inflammatory response centered on NLRP3 inflammasomes plays a key part in inflammation in ALI, and may hence be a prospective candidate for therapeutic intervention. In the review, we present an overview of the ailment characteristics of acute lung injury along with the constitution and operation of the NLRP3 inflammasome within this framework. We also explore therapeutic strategies targeting the NLRP3 inflammasome to combat acute lung injury.

Naked Gene Delivery Induces Autophagy for Effective Treatment of Acute Lung Injury in a Mouse Model.

Acute lung injury (ALI) leads to diffuse pulmonary interstitial and alveolar edema, further developing into acute respiratory distress syndrome (ARDS). The present therapeutic approaches showed limited effects with poor clinical efficacy or severe side effects. This study aims to develop novel pharmaceutical agents to reduce lung damage with acceptable side effects for ALI. Naked gene delivery system based on epigallocatechin 3-gallate (EGCG) was synthesized to deliver plasmid expressing DNA damage regulated autophagy modulator 1 (DRAM1), designated as EGCG/DRAM1 (ED). ED was characterized by dynamic light scattering analysis and transmission electron microscope. The biodistribution of ED in mice was measured by an in vivo small animal imaging system. The therapeutic potentials of ED were evaluated in MLE12 cells and LPS-induced ALI mice. Our results showed that ED was nearly spherical with a diameter of ~100 nm and increased the stability of DRAM1 plasmid that encapsulated. The synthesized ED showed negligible toxicity at the selected experimental concentration in MLE12 cells. ED could be taken up by MLE12 cells with high efficiency and escape from the lysosome. In ALI mice, ED facilitated the accumulation and retention of DRAM1 plasmid in lung, and attenuated pulmonary edema and pulmonary vascular permeability. The therapeutic effects of ED on ALI were associated with increased autophagy and reduced oxidative stress in lung. In summary, ED attenuated pulmonary edema and pulmonary vascular permeability, and improved pulmonary dysfunction in ALI mice. This naked gene delivery system for autophagy enhancement may serve as a potential therapeutic strategy to attenuate ALI.

The use of furosemide during Intravenous Immunoglobulin therapy should not always be considered contraindicated

AimsEndothelial damage in acute respiratory distress syndrome (ARDS) increases capillary permeability, resulting in an increase in free lung fluid, interstitial pulmonary edema, and ventilation-perfusion imbalance. Due to their high osmolarity, Intravenous Immunoglobulin (IVIG) treatment may deepen hypoxemia by increasing lung fluid leakage. Adding furosemide to IVIG treatment in ARDS secondary to COVID-19 (CARDS) cases may increase treatment tolerance and success. Materials and methodsIn our study, we aimed to measure the effectiveness of this treatment combination in CARDS cases and to report the observed complications. Patients who were followed up in the 34-bed adult COVID intensive care unit between March 2020/2021 and who received IVIG, high-dose corticosteroid, and furosemide combination therapy were included in the study. Patients' age, gender, comorbidities, Acute Physiology, and Chronic Health Assessment II (APACHE-II), and Sequential Organ Failure Assessment (SOFA) scores were recorded. The day IVIG duration of treatment, additional medical treatments, respiratory support treatments, laboratory examinations, the percentage of involvement of lung lesions (Covid Visual Assessment Scale), clinical outcomes, and treatment complications were recorded. ResultsCombination therapy with found to improve respiratory failure in 50 % of patients. Troponin elevation was found in two patients, femoral artery embolism in one patient, and thrombosis in the femoral vein in one patient. In addition to IVIG treatment, the administration of two doses of immune plasma increased the chance of discharge (P = 0.037) ConclusionIn severe viral ARDS refractory to standard therapy, using furosemide in addition to IVIG therapy has an acceptable side-effect profile and may increase treatment success. Furosemide given during IVIG therapy should not be considered a contraindication in every patient.

A Case Report of Pneumoretroperitoneum from Blunt Trauma in a Patient with Chronic Obstructive Pulmonary Disease.

Pneumomediastinum is a rare complication of blunt traumatic injury and is thought to be due to the Macklin effect, a pathophysiologic process comprised of three steps: alveolar rupture secondary to blunt injury; air dissecting along bronchovascular sheaths; and spread of pulmonary interstitial edema into the mediastinal space. Pneumomediastinum is rarely associated with pneumoretroperitoneum. We present a case of a patient who suffered a cardiac arrest after a fall during a chronic obstructive pulmonary disease exacerbation, leading to pneumoretroperitoneum. This case highlights the complications that can arise from blunt trauma and how underlying lung pathology can worsen these complications.

Effects of the PI3K/Akt/HO-1 pathway on autophagy in a sepsis-induced acute lung injury mouse model

Sepsis-induced lung injury is an acute hypoxic respiratory insufficiency caused by systemic infectious factors that results in alveolar epithelial cell and capillary endothelial cell injury, diffuse pulmonary interstitial edema, and alveolar edema. Heme oxygenase (HO)-1 is usually associated with inflammation and has anti-inflammatory effects. Autophagy is a degradation pathway that eliminates cellular metabolic waste and plays an important protective role during stress. The phosphatidylinositol 3-kinase/ protein kinase B (PI3K/Akt) signaling pathway plays a key role in mediating cellular responses to inflammatory reactions. Therefore, we hypothesized that HO-1 is associated with autophagy and regulated by the PI3K/Akt signaling pathway in mice with sepsis-induced lung injury. Sepsis-induced lung injury was induced in mice using cecal ligation and puncture (CLP). Hemin or Sn-protoporphyrin IX (SnPP) was administered via intraperitoneal injection before surgery. Survival rates were observed during days 1–7 after the surgery; lung histology was discerned 24 h after the surgery; pro-inflammatory and anti-inflammatory factors in plasma and lung tissue were measured using enzyme-linked immunosorbent assay (ELISA); HO-1, Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B)-II, p62 and lysosome associated membrane protein (LAMP)2 protein expression levels were measured 24 h after the surgery; HO-1 and LC3B-II protein expression levels were observed using immunofluorescence 24 h after the surgery; and autophagosomes were detected using electron microscopy 24 h after the surgery. Furthermore, when PI3K inhibitors LY294002, PI3K activators Recilisib and hemin were administered before the surgery, Akt, p-Akt, HO-1, and LC3-II levels were measured 24 h post-surgery. We found that HO-1 overexpression increased the survival rate and inhibited sepsis-induced lung injury. HO-1 overexpression attenuated the levels of proinflammatory cytokines (TNF-α, IL-1β) and increased the anti-inflammatory cytokine (IL-10, HO-1) overexpression. Moreover, HO-1 overexpression was also associated with increased expression of Beclin-1, LC3B-II and LAMP2 protein expression; decreased p62 protein expression; and significantly increased autophagosome formation. The results for HO-1-downregulated mice contrasted with those mentioned above. LY294002 inhibited p-Akt/Akt, HO-1, and LC3B-II protein expression; and hemin reversed the inhibitory effect of LY294002. The protective effect of HO-1 was involved in the mediation of autophagy, which may be regulated by the PI3K/Akt signaling pathway during sepsis-induced lung injury in mice.

A clinical case of SARS-CoV-2 infection complicated by viral interstitial pneumonia and pulmonary edema in a patient with dilated cardiomyopathy

COVID-19 is especially severe in patients with a premorbid background.Aim: To describe a clinical case of SARS-CoV-2 infection complicated by bilateral viral pneumonia, cardiogenic pulmonary edema, and dilated сardiomyopathy.Clinical case. Patient M.V., 76 years old, from 02.11.2022 to 03.11.2022 was hospitalized at the Republican Cardiological Dispensary with a diagnosis of Bilateral viral pneumonia, the percentage of damage was 75%. Acute respiratory distress syndrome, severe. Complaints at admission: lack of air in a horizontal position, fever up to 38,0 °С, dry cough. Computed tomography of the chest was performed; bilateral viral pneumonia was determined (75% of lesions). PCR smear for coronavirus infection was positive. Determination of troponin T from 02.11.2022: 0.022 ng/ml. History: hypertension for many years with maximum blood pressure of 190/100 mm Hg, acute myocardial infarction of the anterior wall of the left ventricle with ST segment elevation (November 20, 2021), percutaneous coronary intervention (November 20, 2021). The above complaints were noted within a week. On the second day of inpatient treatment, a lethal outcome occurred. She was sent for a post-mortem examination. In the lungs, histological examination revealed a violation of microcirculation in the form of erythrocyte sludge, stasis. Widespread atelectasis/dystelectasis. There was intraalveolar edema. On macroscopic examination, the cavities of the heart are enlarged.Histological examination revealed large-focal cardiosclerosis, areas of wave-like deformation of myocardial muscle fibers. Virological examination of sectional material in the lungs and heart revealed SARS-CoV-2 RNA.Conclusion. Viral infection with COVID-19 contributed to the development of decompensation of chronic heart failure in the form of arrhythmia and cardiogenic pulmonary edema in a patient with dilated cardiomyopathy.

Damage effects of bisphenol A against sepsis induced acute lung injury

In addition to oxidative damage, sepsis can cause multiple organ dysfunction and poses a life-threatening threat. In addition to severe tissue damage, hypotension, and multiple organ failure, sepsis can cause high morbidity and mortality. It is the lungs that are most vulnerable in abdominal sepsis, with impaired oxygen and nutrient exchange occurring in the pulmonary microcirculation. However, the etiology of sepsis and the link between sepsis and lung injury has not been elucidated. In this work, by exploring the data from the GEO and CTD database, a gene association study was conducted to determine whether sepsis-induced lung injury is caused by BPA. Further analysis demonstrated that MMP9, CEBPA, CYP1B1, CTSD, FKBP5, DGAT2, HP, TIMP2, ARG1 and MGST1 may play an important role in sepsis-induced lung injury. Finally, the single-cell RNA sequence demonstrated that CEBPA is mainly enriched in lung epithelial cells and epithelial cells, whereas CYP1B1 is closely related to basal cells, macrophages, and interstitial cells. In order to maintain lung function, epithelial and alveolar macrophages as well as other lung cells are important. When the lung epithelium is activated for a prolonged period of time, barrier function may be compromised and tissue damage may result, aggravating the lung injury. By using the animal model, we successfully simulated the model of sepsis lung injury. The HE staining demonstrated the rats with BPA-treated septic lung injury showed more alveolar structure to be disordered, pulmonary interstitial edema to be evident, and red blood cells as well as inflammatory cells. For PCR assay, the results demonstrated that the expression level of CEBPA is higher in the lung samples with sepsis compared with the normal samples of the lung. In order to evaluate the expression level of CEBPA and CYP1B1 in lung tissue, we then performed the PCR assay. For CYP1B1, the results demonstrated that the expression level of CYP1B1 in lung samples with sepsis is lower than in normal lung samples. In total, BPA may be a potential contributing factor to sepsis-induced lung injury.

Stuve-wiedemann syndrome in a child: a case report

Introduction: Stüve-Wiedemann Syndrome was first described in 1971. However, this disease was considered a single entity only a few years later. The syndrome is now known to be an autosomal recessive disorder in which the patient has dysautonomia, bone dysplasia and respiratory distress and eating disorder. Objective: To report the case of a girl with Stuve-Wiedemann Syndrome. Case Description: A 7-year-old female SSG patient presented, at birth, with early neonatal sepsis, septic shock, pneumonia, respiratory acidosis, jaundice without the need for phototherapy, food intolerance, anemia, seizures, interstitial pulmonary edema, myositis and osteomyelitis of the right humerus. After 11 months of follow-up, she was referred to a maternal-fetal clinic for genetic testing to investigate the symptoms. The patient was diagnosed with Stüve-Wiedemann Syndrome. Final Considerations: This disease is considered a primary congenital bone dysplasia, characterized by skeletal and joint changes, bowing of the long bones, episodic hyperthermia, periodic respiratory infections, eating disorders and high mortality. These were facts found in the case of the child presented here. On the other hand, this disease can manifest other symptoms such as fissured tongue and episodes of hyperhidrosis, but it was not found in our patient's case. Rare diseases of genetic origin have a high negative impact on patients' quality of life. However, with the practice of physical activity, patients can have a healthy diet. Swimming practice by SSG presents itself as an extremely important activity for the physical and psychological development of this child, contributing to the improvement of her quality of life.