Pulmonary Capillary Permeability Research Articles

Case Report: Scrub Typhus manifesting as Acute Respiratory Distress Syndrome (ARDS) with corresponding radiological findings

Background Scrub typhus is a life-threatening infectious disease endemic in the Asia-Pacific region. It typically presents with nonspecific symptoms such as fever, headache, and myalgia, making early diagnosis challenging. Acute Respiratory Distress Syndrome (ARDS) is a severe pulmonary condition characterized by acute-onset hypoxemia, bilateral lung infiltrates on radiology, and increased pulmonary capillary permeability. Case Presentation An 18-year-old female student in central India presented with a seven-day history of recurrent fever, chills, dry cough, and severe shortness of breath, escalating to Modified Medical Research Council dyspnea grade III-IV. After unsuccessful local clinic treatment, a chest radiograph revealed bilateral pneumonia. On admission, she displayed tachycardia, tachypnea, hypotension, and hypoxia requiring non-invasive ventilation (NIV). Computed tomography confirmed scrub typhus-associated pneumonia, and serological testing was positive for scrub typhus. She was diagnosed with moderate ARDS and began treatment. Symptomatic improvement was seen in the ICU, and she was discharged on day 10 with radiological and clinical resolution. Management and Outcomes She received intravenous doxycycline and oral azithromycin for scrub typhus and any potential concurrent lung infection. In the ICU, she required continuous NIV and supplemental oxygen, with significant symptomatic improvement, evidenced by reduced tachypnoea and oxygen requirements after 72 hours. She was weaned off NIV and monitored for an additional four days. After satisfactory oxygen saturation on room air, she was discharged on the tenth day. High-resolution CT scan demonstrated resolution of ground glass opacities and consolidation. Sequential chest radiographs exhibited gradual reduction in bilateral alveolar infiltrates over time, in parallel with clinical improvement. Laboratory findings, including reduced CRP and D-dimer values, and a normal hemogram on discharge indicated a resolution of leukopenia. Conclusion This case underscores the importance of early recognition and intervention in scrub typhus-associated ARDS and highlights the utility of timely diagnostic imaging in monitoring the progress of the disease.

High-intensity intermittent training ameliorates methotrexate-induced acute lung injury

Inflammation and oxidative stress are recognized as two primary causes of lung damage induced by methotrexate, a drug used in the treatment of cancer and immunological diseases. This drug triggers the generation of oxidants, leading to lung injury. Given the antioxidant and anti-inflammatory effects of high-intensity intermittent training (HIIT), our aim was to evaluate the therapeutic potential of HIIT in mitigating methotrexate-induced lung damage in rats. Seventy male Wistar rats were randomly divided into five groups: CTL (Control), HIIT (High-intensity intermittent training), ALI (Acute Lung Injury), HIIT+ALI (pretreated with HIIT), and ALI + HIIT (treated with HIIT).HIIT sessions were conducted for 8 weeks. At the end of the study, assessments were made on malondialdehyde, total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (Gpx), myeloperoxidase (MPO), interleukin 10 (IL-10), tumor necrosis factor-alpha (TNF-α), gene expression of T-bet, GATA3, FOXP3, lung wet/dry weight ratio, pulmonary capillary permeability, apoptosis (Caspase-3), and histopathological indices.Methotrexate administration resulted in increased levels of TNF-α, MPO, GATA3, caspase-3, and pulmonary edema indices, while reducing the levels of TAC, SOD, Gpx, IL-10, T-bet, and FOXP3. Pretreatment and treatment with HIIT reduced the levels of oxidant and inflammatory factors, pulmonary edema, and other histopathological indicators. Concurrently, HIIT increased the levels of antioxidant and anti-inflammatory factors.

Fe-Capsaicin Nanozymes Attenuate Sepsis-Induced Acute Lung Injury via NF-κB Signaling.

In sepsis, the lungs are one of the most severely affected organs, usually resulting in acute lung injury (ALI). Capsaicin (CAP) is a natural compound found in chili peppers that has pain-relieving and anti-inflammatory properties. Here, we report that nanoparticles containing capsaicin and iron (Fe-CAP NPs) exhibited anti-inflammatory effects in the treatment of ALI. The morphological characteristics of nanozymes were detected. RAW 264.7 cells were divided into four groups: control, lipopolysaccharide (LPS), CAP+LPS and Fe-CAP+LPS groups. The expression of inducible nitric oxide synthase (iNOS), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) was assessed by immunofluorescence, Western blot, and enzyme-linked immunosorbent assay (ELISA). Nuclear factor kappa-B (NF-κB) expression was determined by Western blot. C57 mice were divided into control, LPS, CAP+LPS and Fe-CAP+LPS groups. Interleukin-6 (IL-6) and iNOS expression in the lung was detected by Western Blot. IL-6 and TNF-α expression in serum was detected by ELISA. Extravasated Evans blue, histopathological evaluation and wet-to-dry (W/D) weight ratio were used to assess pulmonary capillary permeability. The blood and major organs (heart, liver, spleen, lung and kidney) of mice were tested for the toxicity of Fe-CAP NPs. In the LPS group, TNF-α, iNOS, p-NF-κB and p-IKBα expression increased. However, their expression was significantly decreased in the Fe-CAP+LPS group. TGF-β expression showed the opposite trend. In vivo, IL-6 and iNOS expression was notably increased in the lungs of LPS group of mice but decreased with Fe-CAP pretreatment. Fe-CAP significantly ameliorated lung EB leakage, improved the histopathology of lung tissue and reduced the W/D weight ratio. The nanoparticles showed non-cytotoxicity, when studying these biological activities. Fe-CAP NPs could alleviated inflammation by inhibiting the expression of pro-inflammatory factors in macrophages, increasing the expression of anti-inflammatory factors, and alleviating lung tissue damage.

Case Report: Scrub Typhus manifesting as Acute Respiratory Distress Syndrome (ARDS) with corresponding radiological findings

Background Scrub typhus is a life-threatening infectious disease endemic in the Asia-Pacific region. It typically presents with nonspecific symptoms such as fever, headache, and myalgia, making early diagnosis challenging. Acute Respiratory Distress Syndrome (ARDS) is a severe pulmonary condition characterized by acute-onset hypoxemia, bilateral lung infiltrates on radiology, and increased pulmonary capillary permeability. Case Presentation An 18-year-old female student in central India presented with a seven-day history of recurrent fever, chills, dry cough, and severe shortness of breath, escalating to Modified Medical Research Council dyspnea grade III-IV. After unsuccessful local clinic treatment, a chest radiograph revealed bilateral pneumonia. On admission, she displayed tachycardia, tachypnea, hypotension, and hypoxia requiring non-invasive ventilation (NIV). Computed tomography confirmed scrub typhus-associated pneumonia, and serological testing was positive for scrub typhus. She was diagnosed with moderate ARDS and began treatment. Symptomatic improvement was seen in the ICU, and she was discharged on day 10 with radiological and clinical resolution. Management and Outcomes She received intravenous doxycycline and oral azithromycin for scrub typhus and any potential concurrent lung infection. In the ICU, she required continuous NIV and supplemental oxygen, with significant symptomatic improvement, evidenced by reduced tachypnoea and oxygen requirements after 72 hours. She was weaned off NIV and monitored for an additional four days. After satisfactory oxygen saturation on room air, she was discharged on the tenth day. High-resolution CT scan demonstrated resolution of ground glass opacities and consolidation. Sequential chest radiographs exhibited gradual reduction in bilateral alveolar infiltrates over time, in parallel with clinical improvement. Laboratory findings, including reduced CRP and D-dimer values, and a normal hemogram on discharge indicated a resolution of leukopenia. Conclusion This case underscores the importance of early recognition and intervention in scrub typhus-associated ARDS and highlights the utility of timely diagnostic imaging in monitoring the progress of the disease.

Acute brain injury increases pulmonary capillary permeability via sympathetic activation-mediated high fluid shear stress and destruction of the endothelial glycocalyx layer

Neurogenic pulmonary edema secondary to acute brain injury (ABI) is a common and fatal disease condition. However, the pathophysiology of brain-lung interactions is incompletely understood. This study aims to investigate whether sympathetic activation-mediated high fluid shear stress after ABI would damage pulmonary endothelial glycocalyx thus leading to increased pulmonary capillary permeability. The tricuspid annular plane systolic excursion (TAPSE) was detected in a rat model of controlled cortical impact (CCI) and CCI + transection of the cervical sympathetic trunk (TCST). Changes in pulmonary capillary permeability were assessed by analyzing the Evans blue, measuring the dry/wet weight ratio of the lungs and altering protein levels in the bronchoalveolar lavage fluid (BALF). The parallel-plate flow chamber system was used to simulate the fluid shear stress in vitro. Western blotting and immunofluorescence staining were used to determine the expression levels of hyaluronan-binding protein (CEMIP), syndecan-1 and tight junction proteins (TJPs, including claudin-5 and occludin). TCST could restrain cardiac overdrive and sympathetic activation in a rat model of CCI. Compared to the CCI group, the CCI + TCST group showed a reduction of CEMPI (which degrades hyaluronic acid), along with an increase of syndecan-1 and TJPs. CCI + TCST group presented decreasing pulmonary capillary permeability. In vitro, high shear stress (HSS) increased the expression of CEMIP and reduced syndecan-1 and TJPs, which was coordinated with the results in vivo. Our findings show that sympathetic activation-mediated high fluid shear stress after ABI would damage pulmonary endothelial glycocalyx thus leading to increased pulmonary capillary permeability.

Dual Delivery of Tetramethylpyrazine and miR-194-5p Using Soft Mesoporous Organosilica Nanoparticles for Acute Lung Injury Therapy.

The respiratory system is intensely damaged by acute lung injury (ALI). The anti-inflammatory effects of tetramethylpyrazine (TMP) against ALI have been confirmed, but it exhibits a short half-life. miR-194-5p could directly target Rac1, but the internalization rate of miRNA cells was low. To explore the potential of the soft mesoporous organic silica nanoplatform (NPs) as carriers for delivery of TMP and miR-194-5p through the tail vein. NPs@TMP and NPs@PEI@miR-194-5p were added to the HUVEC cell-lines, in vitro, to observe the cell uptake and cytotoxic effects. In vivo experiments were conducted by injecting fluorescently labeled NPs through the tail vein and tracking distribution. Therapeutic and toxic side-effects were analyzed systemically. In vitro study exhibited that NPs have no toxic effect on HUVECs within the experimental parameters and have excellent cellular uptake. The IVIS Spectrum Imaging System shows that NPs accumulate mainly in the lungs. NPs@TMP treatment can improved oxidative stress and inflammation levels in ALI mice and inhibited the TLR4/NLRP3/caspase 1 pathway. NPs@PEI@miR-194-5p can inhibit the Rac1/ZO-1/occludin pathway and improved endothelial cell permeability in ALI mice. The co-treatment of NPs@TMP and NPs@PEI@miR-194-5p can significantly improved the survival rates of the mice, reduced pulmonary capillary permeability and improved pathological injury in ALI mice. This study combined traditional Chinese medicine, bioinformatics, cellular molecular biology and nanobiomedicine to study the pathogenesis and treatment of ALI. The rate of cellular internalization was improved by changing the shape and hardness of nanoparticles. NPs@TMP and NPs@PEI@miR-194-5p combined application can significantly improve the survival condition and pathological injury of mice. NPs loaded with TMP and miR-194-5p showed a greater therapeutic effect in ALI mice.

Pulmonary, circulatory and renal considerations in the early postoperative management of the lung transplant recipient.

Lung transplantation volumes and survival rates continue to increase worldwide. Primary graft dysfunction (PGD) and acute kidney injury (AKI) are common early postoperative complications that significantly affect short-term mortality and long-term outcomes. These conditions share overlapping risk factors and are driven, in part, by circulatory derangements. The prevalence of severe PGD is up to 20% and is the leading cause of early death. Patients with pulmonary hypertension are at a higher risk. Prevention and management are based on principles learned from acute lung injury of other causes. Targeting the lowest effective cardiac filling pressure will reduce alveolar edema formation in the setting of increased pulmonary capillary permeability. AKI is reported in up to one-half of lung transplant recipients and is strongly associated with one-year mortality as well as long-term chronic kidney disease. Optimization of renal perfusion is critical to reduce the incidence and severity of AKI. In this review, we highlight key early post-transplant pulmonary, circulatory, and renal perturbations and our center's management approach.

Schisandrin A ameliorates increased pulmonary capillary endothelial permeability accompanied with sepsis through inhibition of RhoA/ROCK1/MLC pathways.

Sepsis is a systemic inflammatory response, and vascular leakage associated with acute lung injury (ALI) is an important pathophysiological process during sepsis. Schisandrin A (SchA) is a bioactive lignan which has been reported to have the anti-inflammatory effects in many studies, while whether SchA can ameliorate ALI-related vascular leakage caused by sepsis is unknown. To evaluate the role and the underlying mechanism of SchA in increase of pulmonary vascular permeability induced by sepsis. The effect of SchA on pulmonary vascular permeability was examined in rat acute lung injury model. The effect of SchA on skin vascular permeability of mice was investigated through Miles assay. MTT assay was performed to detect the cell activity, and transwell assay was used to detect the effect of SchA on cell permeability. The effects of SchA on junction proteins and RhoA/ROCK1/MLC signaling pathway were manifested by immunofluorescence staining and western blot. The administration of SchA alleviated rat pulmonary endothelial dysfunction, relieved increased permeability in the mouse skin and HUVECs induced by lipopolysaccharide (LPS). Meanwhile, SchA inhibited the formation of stress fibers, reversed the decrease of expression of ZO-1 and VE-cadherin. Subsequent experiments confirmed that SchA inhibited RhoA/ROCK1/MLC canonical pathway in rat lungs and HUVECs induced by LPS. Moreover, overexpression of RhoA reversed the inhibitory effect of SchA in HUVECs, which suggested that SchA protected the pulmonary endothelial barrier by inhibiting RhoA/ROCK1/MLC pathway. In summary, our results indicate that SchA ameliorates the increase of pulmonary endothelial permeability induced by sepsis through inhibition of RhoA/ROCK1/MLC pathway, providing a potentially effective therapeutic strategy for sepsis.

Protective effect of barium chloride pretreatment on lung in mice with acute respiratory distress syndrome

To explore whether barium chloride (BaCl2) preconditioning has the protective effect on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) model in mice and the possible mechanism. Sixty 8-12 week old healthy C57BL/6 male mice were randomly divided into control group, ARDS model group and BaCl2 pretreatment group, with 20 mice in each group. The BaCl2 pretreatment group was continuously injected with BaCl2 (4 mg/kg through the tail vein) for 3 days before ARDS model establishment. ARDS model was established by intratracheally injecting (3 mg/kg) LPS. The control group was intratracheally given the same volume of 0.9% normal saline. On 24th hour after ARDS model establishment, some mice were sacrificed for obtaining fresh lung tissue. And the right lower lobe of the lung was separated for observing the pathological changes of lung tissue while the left lung tissue was used to measure the wet/dry weight ratio (W/D) of the lung. Some mice were sacrificed for observing pulmonary microvascular permeability at 2nd hours after injecting Evans blue (EB) through tail vein. The left mice were killed for alveolar lavage to measure the levels of tumor necrosis factor-α (TNF-α) via enzyme linked immunosorbent assay (ELISA). Comparing with the control group, ARDS model group showed typical ARDS pathological changes, which included the increased W/D ratio (4.951±0.161 vs. 3.449±0.299, P < 0.01) and the content of EB in the lung tissue (μg/g: 0.130±0.027 vs. 0.085±0.011, P < 0.01), the damaged alveolar wall structure, lung congestion and exudates in the alveoli, as well as amounts of inflammatory cells. The pathological score of lung injury (10.33±1.15 vs. 1.67±0.58) and the level of TNF-α in BALF (ng/L: 900.85±247.80 vs. 68.21±5.79) were significantly increased in the ARDS model group (both P < 0.01). Comparing with the ARDS model group, the lung W/D ratio (4.620±0.125 vs. 4.951±0.161) and the EB content in the lung tissue (μg/g: 0.108±0.011 vs. 0.130±0.027) of BaCl2 pretreatment group were significantly reduced (both P < 0.01). And the damaged pulmonary structural BaCl2 pretreatment group were significantly alleviated. In addition, the pulmonary pathological score (5.00±1.00 vs. 10.33±1.15) and the level of TNF-α in BALF (ng/L: 169.16±73.33 vs. 900.85±247.80) were significantly decreased (both P < 0.01). Barium chloride pretreatment can improve the lung histopathological changes of ARDS model mice induced by LPS by reducing the permeability of pulmonary capillaries and local inflammatory reaction.Barium chloride has the protective effect against LPS attack in mice model of ARDS.

Bone mesenchymal stromal cell-derived small extracellular vesicles inhibit inflammation and ameliorate sepsis via delivery of microRNA-21a-5p

Background aimsSepsis is a potentially life-threatening disease that results from a severe systemic inflammatory response due to infection. Mesenchymal stromal cell-derived small extracellular vesicles (MSC sEVs) are able to transfer bioactive molecules and have been demonstrated to play an important role in the pathophysiological process of sepsis. Herein the authors aimed to investigate the potential role and downstream molecular mechanism of MSC sEVs in sepsis. MethodsMSC sEVs were acquired by ultracentrifugation and then injected into a cecal ligation and puncture mouse model. The efficacy of MSC sEVs in both in vitro and in vivo models of sepsis was evaluated. ResultsMSC sEV therapy improved survival, reduced sepsis-induced inflammation, attenuated pulmonary capillary permeability and improved liver and kidney function in septic mice. In addition, the authors found that microRNA-21a-5p (miR-21a-5p) was highly enriched in MSC sEVs, could be transferred to recipient cells, inhibited inflammation and increased survival in septic mice. Furthermore, the authors demonstrated that MSC sEV miR-21a-5p suppressed inflammation by targeting toll-like receptor 4 and programmed cell death 4. The therapeutic efficacy of MSC sEVs was partially abrogated by transfection with miR-21a-5p inhibitors. ConclusionsCollectively, the authors’ data suggest that miR-21a-5p-bearing MSC sEVs may be a prospective and effective sepsis therapeutic strategy.

Integrated Proteomics and Metabolomics Analysis to Explore the Amelioration Mechanisms of Rosa roxburghii Tratt Fruit Polyphenols on Lipopolysaccharide-Induced Acute Lung Injury Mice

Acute lung injury (ALI) is the main cause of death for the elderly and children due to its high morbidity and mortality rates. Plant-derived functional foods are becoming increasingly important to the healthcare and food industries for adjunctive and alternative treatments of ALI. Polyphenols have been regarded to be beneficial to the prevention and amelioration of ALI. Rosa roxburghii Tratt fruit polyphenols (RRTP) has potential to prevent ALI, but mechanism remains unclear. This study was set up to systematically analyze the RRTP extract active ingredients, comprehensively evaluate its protective effects via lung histopathological examination, protein concentration, and cytokines production in ALI mice induced by lipopolysaccharide (LPS), and finally revealed alleviation mechanisms of the regulatory effects of RRTP by proteomics and metabolomics approach. The results demonstrated RRTP could synergistically exert significant preventive effects against ALI by notably ameliorating lung histopathological damage and pulmonary capillary permeability in ALI mice, inhibiting lung tissue inflammatory response and acute phase proteins and S-100 calcium binding proteins, suppressing excessive activation of complement and coagulation cascades, and regulating disordered lipids metabolism and amino acid metabolism. This study illustrated that RRTP has obvious advantages in ALI adjunctive therapy and revealed the complicated amelioration mechanisms, which provides a breakthrough for the development and demonstration of RRTP as a nutritional compound additive for complementary therapy of ALI.

Analysis of protective effects of Rosa Roxburghii Tratt fruit polyphenols on lipopolysaccharide-induced acute lung injury through network pharmacology and metabolomics.

Acute lung injury (ALI) is a respiratory disease with high morbidity and mortality rates and is the primary cause of death in children and the elderly around the world. The use of Chinese foods in the complementary and alternative treatment of ALI has attracted more and more attention. This study aimed to explore the anti-ALI activity of Chinese functional foods Rosa roxburghii Tratt fruit polyphenols (RRTP). RRTP was administered to lipopolysaccharide-induced ALI mice, and its protective effects were comprehensively evaluated by lung histopathological examination, wet/dry (W/D) ratio, and cytokine production. Metabolomics analysis was used to identify the differential metabolites and metabolic pathways in plasma, and molecular docking and systemic biology-based network pharmacology assay were performed to explore the active components and potential therapeutic targets. The results indicated that RRTP significantly attenuated the severity of pathological changes and pulmonary capillary permeability. Furthermore, RRTP limited the increase in tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6) levels and the decrease in interleukin 10 (IL-10) levels in ALI mice. Metabolomics studies revealed that RRTP markedly affected 19 different metabolites, three amino acid metabolism pathways, and sphingolipid metabolism. Moreover, network pharmacology identified AKT1 (AKT serine/threonine kinase 1), TP53, IL-6, VEGFA (vascular endothelial growth factor A), and TNF (tumor necrosis factor) as the most promising target proteins, while quercetin, luteolin, and kaempferol were the core active components of RRTP. This study investigated the complex mechanisms of RRTP against ALI for the first time, and provided a foundation for the application of RRTP as a functional food, facilitating the research of nutritional food additives for the adjuvant treatment of ALI.

Macromolecules in polysorbate 80 for injection: an important cause of anaphylactoid reactions

Polysorbate 80 for injection (TW80) is a common excipient used for injection whose macromolecular impurities, including those that cause anaphylactoid reactions, are frequently ignored. The main aim of this study was to prove that the macromolecular impurities in the excipient are an important cause of anaphylactoid reactions. Component A (containing macromolecules > 100 kDa), Component B (containing macromolecules from 10 to 100 kDa), and Component C (containing substances < 10 kDa) were prepaired from the original TW80 using ultrafilters. The original TW80 contained numerous substances with molecular weights > 10kD. The original TW80 and Components A and B caused strong anaphylactoid reactions in both guinea pigs and rabbits by intravenous administration. Moreover, the original TW80 and Components A and B even caused strong passive cutaneous anaphylactoid (PCA) reactions and pulmonary capillary permeability. The PCA reaction and increased permeability were partly prevented by cromolyn sodium. Additionally, the original TW80 and Components A and B caused vasodilation and severe hemolysis in vitro. The anaphylactoid reactions were associated with histamine release but not with mast cell degranulation. Nevertheless, Component C almost caused no anaphylactoid reactions or hemolysis and was weaker in the few reactions that ocurred. Taken together, these results suggest that macromolecular substances are one of the main risk factors responsible for anaphylactoid reactions and hemolysis caused by TW80.

Protective effect of breviscapine on acute lung injury in rats with infectious shock

Acute lung injury (ALI), during the progression of infectious shock, leads to systemic inflammatory response syndromewith increased pulmonary capillary membrane permeability due to pulmonary inflammation and uncontrolled inflammatoryresponses. It may cause fatality in patients. Here, we evaluated the protective effect of breviscapine on ALI in rats withinfectious shock. Sprague-Dawley (SD) rats were assigned into Sham, model [lipopolysaccharide (LPS) group], andbreviscapine treatment groups (LPS + breviscapine group) and weighed. The lung coefficient, and the wet-to-dry weightratio (W/D) and moisture content of lung tissues were calculated. The pathological changes of the lung tissues were detectedusing hematoxylin-eosin (HE) staining, and the protein expressions of interleukin-1 beta (IL-1β), IL-6, and tumor necrosisfactor-alpha (TNF-α) were determined by enzyme-linked immunosorbent assay. Western blotting was conducted to measurethe protein expressions of toll-like receptor-9 (TLR-9) and nuclear factor-kappa B (NF-κB) (p65). Compared with LPSgroup, breviscapine significantly lowered the lung coefficient and the W/D and moisture content of lung tissues, relieved thepathological changes of lung tissues, reduced the protein expression levels of IL-1β, IL-6, and TNF-α, weakened theactivation of NF-κB (p65) in lung tissues, and repressed the protein expressions of TLR-9 and NF-κB (p65).

Targeting Procalcitonin Protects Vascular Barrier Integrity.

Rationale: Capillary leakage frequently occurs during sepsis and after major surgery and is associated with microvascular dysfunction and adverse outcome. Procalcitonin is a well-established biomarker in inflammation without known impact on vascular integrity. Objectives: We determined how procalcitonin induces endothelial hyperpermeability and how targeting procalcitonin protects vascular barrier integrity. Methods: In a prospective observational clinical study, procalcitonin levels were assessed in 50 patients who underwent cardiac surgery and correlated to postoperative fluid and vasopressor requirements along with sublingual microvascular functionality. Effects of the procalcitonin signaling pathway on endothelial barrier and adherens junctional integrity were characterized invitro and verified in mice. Inhibition of procalcitonin activation by dipeptidyl-peptidase 4 (DPP4) was evaluated in murine polymicrobial sepsis and clinically verified in cardiac surgery patients chronically taking the DPP4 inhibitor sitagliptin. Measurements and Main Results: Elevated postoperative procalcitonin levels identified patients with 2-fold increased fluid requirements (P < 0.01), 1.8-fold higher vasopressor demand (P < 0.05), and compromised microcirculation (reduction to 63.5 ± 2.8% of perfused vessels, P < 0.05). Procalcitonin induced 1.4-fold endothelial and 2.3-fold pulmonary capillary permeability (both Ps < 0.001) by destabilizing VE-cadherin. Procalcitonin effects were dependent on activation by DPP4, and targeting the procalcitonin receptor or DPP4 during sepsis-induced hyperprocalcitonemia reduced capillary leakage by 54 ± 10.1% and 60.4 ± 6.9% (both Ps < 0.01), respectively. Sitagliptin before cardiac surgery was associated with augmented microcirculation (74.1 ± 1.7% vs. 68.6 ± 1.9% perfused vessels in non-sitagliptin-medicated patients, P < 0.05) and with 2.3-fold decreased fluid (P < 0.05) and 1.8-fold reduced vasopressor demand postoperatively (P < 0.05). Conclusions: Targeting procalcitonin's action on the endothelium is a feasible means to preserve vascular integrity during systemic inflammation associated with hyperprocalcitonemia.

Pulmonary perfusion imaging and delayed imaging to measure pulmonary capillary permeability in pulmonary contusion.

Explore the application value of pulmonary perfusion imaging and delayed imaging for evaluating pulmonary capillary permeability. After establishing a rat model of pulmonary contusion, changes in the metabolic index of technetium-99m macroaggregated albumin (99mTC-MAA) in the lungs of model rats were evaluated for two consecutive days. 99mTC-MAA metabolic indices of rat lungs with pulmonary contusion of varying severity (mild, moderate, and severe) were correlated with lung wet/dry weight ratio (W/D) and Evans blue extravasation. Finally, the method was validated in patients with pulmonary contusion and one healthy volunteer. The 99mTC-MAA metabolic index was 23.56% ± 2.44% in healthy control (HC) rat lung, 8.56% ± 3.42% immediately after lung contusion (d0), 8.35% ± 3.20% after 1 day (d1), and 17.45% ± 6.44% after 2 days (d2); indices at d0 and d1 were significantly higher than those at HC (P < 0.05). The metabolic index of 99mTC-MAA in lung had significant negative correlations with W/D (r = -0.8025; P = 0.0092) and Evans blue extravasation (r = -0.9356; P = 0.0002). Metabolic and oxygenation indices of 99mTC-MAA exhibited a significant positive linear correlation in patients with pulmonary contusion (r = 0.8925; P = 0.0416). Pulmonary perfusion and delayed imaging of 99mTC-MAA have potential value for evaluating pulmonary capillary permeability.

Mechanism of SMND-309 against lung injury induced by chronic intermittent hypoxia

IntroductionObstructive sleep apnea–hypopnea syndrome (OSAHS) is a common sleep disorder that causes severe physiological disturbance. Evidence showed that OSAHS is an important associated comorbidity that can affect the survival of patients with pulmonary fibrosis. Until now, the potential mechanisms by which OSAHS accelerates the progression of lung fibrosis remain unclear. By constructing a pathological model of chronic intermittent hypoxia (CIH), the present study aimed to explore the pathological progress and potential mechanism of lung injury caused by OSAHS. Meanwhile, SMND-309 was given for treatment to evaluate its potential therapeutic role in CIH-induced lung injury. MethodsMice were randomly divided into (C57BL/6 wild-type) WT+(room air) RA, WT + CIH, SMND-309 + RA, and SMND-309 + CIH groups. The WT + CIH and SMND-309 + CIH groups were exposed to CIH condition for 12 weeks, while the other groups were processed in normal oxygen at the same time. The SMND-309 + RA and SMND-309 + CIH groups were intraperitoneally injected with SMND-309 at the last week of the modeling period. After 12 weeks of treatment, three mice from each group were perfused through the heart. Lung tissues were isolated, fixed, sectioned, and stained with H&E, Masson, and immunofluorescence stain. The rest of the lung tissues were harvested for Western blot and ELISA assays. ResultsCIH treatment increased the expression of pro-inflammatory factors (TNF-α and IL-6), resulting in lung tissue structure disorder, inflammatory cell infiltration, increased pulmonary capillary permeability, and pulmonary edema. The activation of the NF-κB signaling pathway played a crucial role in the process of inflammation. Noticeably, we observed M2 macrophage accumulation in the lung after CIH exposure, which promoted epithelial–mesenchymal transition (EMT) and pulmonary tissue fibrosis. ELISA assays showed the increased expression of TGF-β, IL-10, and IL-4 in the CIH group. SMND-309 inhibited pulmonary inflammation, reduced the accumulation of M2 macrophage, alleviated collagen deposition andlung damage. ConclusionCIH could induce chronic lung inflammation, promote the activation of M2 macrophages, trigger the occurrence of EMT, and accelerate the deposition of lung collagen, eventually leading to lung tissue damage. This study presents a possible explanation by which interstitial lung diseases, particularly idiopathic pulmonary fibrosis (IPF) with OSAHS, are usually associated with fast progress and poor prognosis. SMND-309 showed a good protective effect on CIH-induced lung damage.

Vascular hyperpermeable molecules potentially contributing to the development of pulmonary edema in sepsis-associated ARDS

The acute respiratory distress syndrome (ARDS) is an important cause of respiratory failure in critically ill patients and may become a life-threatening condition where inflammation of the lungs may begin in one lung but eventually affects both, leading to damage to the alveoli and surrounding small blood vessels. ARDS is particularly characterized by noncardiogenic pulmonary edema caused by an increase in pulmonary capillary permeability. Several clinical disorders can precipitate in ARDS, including pneumonia, sepsis, aspiration of gastric contents, and major trauma. The most common cause of ARDS is sepsis, which is a serious and widespread infection of the bloodstream and is now defined as life-threatening organ dysfunction due to a dysregulated reponse of the host to infection. In sepsis, a number of vascular hyperpermeable factors, such as histamine, nitric oxide, thromboxane A2, and vascular endothelial growth factor, can be overproducted and contribute to the development of pulmonary edema. Given that sepsis can be regarded as a gene-related disorder, the nucleic-acid based gene therapeutic strategy to regulate some transcription factors involved in expression of vascular hyperpermeable genes may be considered to be a promising novel approach for treatment of ARDS in sepsis.

TO STUDY PROFILE OF PATIENTS WITH PLEURAL EFFUSION AT TERTIARY CARE CENTRE.

Pleural effusion is the condition characterized by an abnormal collection of uid in pleural space resulting from excess uid production or decreased absorption(1–3). It is due to pleural uid accumulation inside pleural space. The major mechanism include: increased interstitial uid in the lungssecondary to increased pulmonary capillary pressure (i.e., heart failure) or permeability (i.e., pneumonia); decreased intrapleural pressure (i.e., atelectasis); decreased plasma oncotic pressure (i.e., hypoalbuminemia); increased pleural membrane permeability and obstructed lymphatic ow (e.g., pleural malignancy or infection); diaphragmatic defects (i.e., hepatic hydrothorax); and thoracic duct rupture (i.e., chylothorax)(4).

PREGNANCY MANAGEMENT AND OUTCOME IN A WOMAN WITH CONGENITAL UNILATERAL LUNG AGENESIS: A CASE REPORT

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Congenital unilateral lung agenesis is a rare condition characterized by the complete absence of a lung and the bronchovascular tree. It is often associated with cardiac and bronchopulmonary malformations, resulting in significant morbidity and mortality. Pregnancy, due to the physiologic changes during gestation and childbirth, poses additional risks to these patients. We report a case of a woman with congenital right lung agenesis (CRLA) whose successful pregnancy could offer guidance to clinicians in the interdisciplinary management of a high-risk condition (1). CASE PRESENTATION: A 26-year-old G1P0 was referred to our Maternal Fetal Medicine (MFM) clinic for her CRLA with resultant dextrocardia and left lung hyperinflation. She was asymptomatic and was able to tolerate daily activities without concerns. Pre-conceptional imaging studies showed results consistent with her medical history.There were no obstetric concerns with normal prenatal labs and normal fetal anatomy ultrasound. She was recommended to undergo cardiopulmonary evaluation and follow up with the relevant specialists.The patient remained clinically stable throughout the gestation. Delivery and postpartum planning was done in the early third trimester at a multidisciplinary conference with the MFM, Anesthesia, Cardiology, Pulmonology, Obstetrics, and Critical Care teams.The patient was electively induced at 39 weeks resulting in an uncomplicated vaginal delivery. Careful monitoring of the patient's hemodynamic status was performed during the intra- and postpartum periods due to the concern of volume overload from intravenous fluid infusions during and autotransfusion following delivery. Her postpartum course was uncomplicated. DISCUSSION: Several cardiopulmonary physiological changes occur in pregnancy to accommodate the growing fetus. An increase in cardiac output with a decrease in pulmonary and systemic vascular resistance leads to an increase in pre-load and increased pulmonary capillary permeability. The risk of pulmonary edema is highest in the second stage of labor due to the autotransfusion into the systemic circulation and the relief of pressure on the inferior vena cava (2). During pregnancy, there is a 40% increased oxygen requirement by the growing fetus, placenta, and maternal organs with a decreased reserve secondary to the increased consumption and decreased functional residual capacity. These changes are often the source of significant morbidity and mortality in women with compromised systems (3). For these reasons, a multidisciplinary care approach was of utmost importance for this patient. CONCLUSIONS: We advocate for the utility of a multidisciplinary approach with frequent follow-up and testing with each specialty to ensure the best care for a successful pregnancy outcome in this patient with CRLA. REFERENCE #1: Wert S. E. (2016). Normal and Abnormal Structural Development of the Lung. In Polin R. A., Abman S. H., Rowitch D. H., Benitz W. E., & Fox W. W., Fetal and Neonatal Physiology (pp. 627-641). Elsevier. https://doi.org/10.1016/B978-0-323-35214-7.00061-5 REFERENCE #2: Silversides C. K. & Colman J. M. (2007). Physiological changes in pregnancy. Oakley, C. & Warnes C. A. (2007). Heart Disease in Pregnancy (pp. 6-16). Blackwell Publishing Limited. REFERENCE #3: Gabbe, S. G., Niebyl, J. R., Simpson, J. L., Landon, M. B., Galan, H. L., Jauniaux, E. R., ... & Grobman, W. A. (2016). Obstetrics: normal and problem pregnancies e-book. Elsevier Health Sciences. DISCLOSURES: No relevant relationships by Kajal Angras, source=Web Response No relevant relationships by Kelly Ca, source=Web Response No relevant relationships by Cherise Hatch, source=Web Response No relevant relationships by VANI MOVVA, source=Web Response