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Bleeding within the pleural space may result in persistent clot formation called retained hemothorax (RH). RH is prone to organization, which compromises effective drainage, leading to lung restriction and dyspnea. Intrapleural fibrinolytic therapy is used to clear the persistent organizing clot in lieu of surgery, but fibrinolysin selection, delivery strategies, and dosing have yet to be identified. We used a recently established rabbit model of RH to test whether intrapleural delivery of single-chain urokinase (scuPA) can most effectively clear RH. scuPA, or single-chain tissue plasminogen activator (sctPA), was delivered via thoracostomy tube on day 7 as either one or two doses 8 h apart. Pleural clot dissolution was assessed using transthoracic ultrasonography, chest computed tomography, two-dimensional and clot displacement measurements, and gross analysis. Two doses of scuPA (1 mg/kg) were more effective than a bolus dose of 2 mg/kg in resolving RH and facilitating drainage of pleural fluids (PF). Red blood cell counts in the PF of scuPA, or sctPA-treated rabbits were comparable, and no gross intrapleural hemorrhage was observed. Both fibrinolysins were equally effective in clearing clots and promoting pleural drainage. Biomarkers of inflammation and organization were likewise comparable in PF from both groups. The findings suggest that single-agent therapy may be effective in clearing RH; however, the clinical advantage of intrapleural scuPA remains to be established by future clinical trials. [ABSTRACT FROM AUTHOR]

Stressful events trigger a set of complex biological responses which follow a bell-shaped pattern. Low-stress conditions have been shown to elicit beneficial effects, notably on synaptic plasticity together with an increase in cognitive processes. In contrast, overly intense stress can have deleterious behavioral effects leading to several stress-related pathologies such as anxiety, depression, substance use, obsessive-compulsive and stressor- and trauma-related disorders (e.g., post-traumatic stress disorder or PTSD in the case of traumatic events). Over a number of years, we have demonstrated that in response to stress, glucocorticoid hormones (GCs) in the hippocampus mediate a molecular shift in the balance between the expression of the tissue plasminogen activator (tPA) and its own inhibitor plasminogen activator inhibitor-1 (PAI-1) proteins. Interestingly, a shift in favor of PAI-1 was responsible for PTSD-like memory induction. In this review, after describing the biological system involving GCs, we highlight the key role of tPA/PAI-1 imbalance observed in preclinical and clinical studies associated with the emergence of stress-related pathological conditions. Thus, tPA/PAI-1 protein levels could be predictive biomarkers of the subsequent onset of stress-related disorders, and pharmacological modulation of their activity could be a potential new therapeutic approach for these debilitating conditions. [ABSTRACT FROM AUTHOR]

Owing to advances in treatment modalities and supportive care, overall survival rates have reached up to 90% among children with acute lymphoblastic leukemia (ALL). However, due to the underlying illness and therapy, they are at a greater risk of developing lifestyle diseases. Hence, special attention is paid to early detection of the components of metabolic syndrome (MetS). This study aimed at investigating the association of plasma levels of nine diabetes markers with being overweight and components of MetS in ALL survivors. The study included 56 subjects with mean age of 12.36 ± 5.15 years. The commercially available Bio-Plex Pro Human Diabetes 10-Plex Panel kit was used to evaluate levels of diabetes biomarkers. ALL survivors presented statistically higher concentrations of GIP (p = 0.026), glucagon (p = 0.001), leptin (p = 0.022), and PAI-1 (p = 0.047), whereas the concentration of ghrelin was lower (p < 0.001) compared to the control group. Moreover, subjects within normal BMI range showed higher GIP (p = 0.005) and lower ghrelin concentration (p < 0.001) compared to healthy peers. At least one risk factor of MetS was present in 58.9% of participants, who showed significantly higher levels of C-peptide (p = 0.028), leptin (p = 0.003), and PAI-1 (p = 0.034) than survivors who did not meet any MetS criteria. In conclusion, ALL survivors are at greater risk of disturbances in carbohydrate metabolism. Understanding the pathogenesis and applicability of diabetes markers is crucial for developing strategies to prevent metabolic syndrome in ALL survivors. [ABSTRACT FROM AUTHOR]