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Author(s): Monica Lapa[sup.1] , Milena M. P. Acencio[sup.1] , Alberto Q. Farias[sup.1] , Lisete R. Teixeira[sup.1] , Caio J. C. Fernandes[sup.1] , Carlos P. Jardim[sup.1] , Mario Terra-Filho[sup.1] Author Affiliations: [...], Purpose The aim of this study was to evaluate the expression profiles of the relevant selectins and PDGF in schistosomiasis-associated pulmonary hypertension. Methodology Patients with three distinct clinical profiles were enrolled in the study: IPAH(n = 11), schistosomiasis-associated PH (Sch-PH))(n = 13), and schistosomiasis without PH (Sch) (n = 13). Healthy volunteers, were recruited as a control group(n = 13). Echocardiography was performed in all groups, and the PH patients underwent right heart catheterization. Plasma soluble adhesion molecules E- and P-Selectin, PDGF-AB, PDGF-BB were determined by ELISA. Results E-selectin was significantly increased in the IPAH group compared with the other groups [the control, Sch + PH and Sch groups) (p < 0.001) (Fig. 2)]. P-selectin was lower in Sch (20.2 + 8.9 × 103 pg/mL) as compared to the control, (43 16.8 × 103 pg/mL), IPAH (35.8 7.8 × 103 pg/mL), and Sch + PH (36.8 ± 15.7 × 103 pg/mL) (p = 0.005) groups. Serum PDGF-BB levels were higher in the control group (8.9 ± 4.8 × 103 pg/mL) compared with the IPAH (3.7 ± 2.17 × 103 pg/mL), Sch + PH (5.2 ± 3.7 × 103 pg/mL) and Sch (2.4 ± 1.7 × 103 pg/mL) groups (p < 0.05). PDGF-AB levels were also higher in the control group (25.6 ± 8.6 × 103 pg/mL), compared with the other three groups, being the Sch group the one with lower serum levels of this marker (11.4 ± 8.6 × 103 pg/mL) (p = 0.006). Conclusions In conclusion, vascular inflammation in schistosomiasis, with or without PH, is different from IPAH suggesting distinct pathophysiological mechanisms associated with the development of pulmonary hypertension.

Background and objective: The experimental model of pleurodesis in rabbits has been useful in understanding the pathophysiology of the pleural inflammatory injury induced by several sclerosing agents. However, restrictions on the use of rabbits in laboratory investigation are making this model less accessible. The aim of this study was to present a new experimental model of pleurodesis in mice using talc or silver nitrate. Methods: Four groups of 10 C57BL/6 mice received talc 2 or 4 mg/g in 0.5 mL saline, or 0.025% or 0.05% silver nitrate in 0.5 mL H2O. After 28 days the animals were sacrificed, and the pleural cavity was opened and evaluated for evidence of macroscopic pleural adhesions and haemothorax (scores 0–4), atelectasis (scores 0–2), and microscopic pleural and alveolar inflammation and fibrosis (scores 0–4). Statistical analysis usedanova. Results: Silver nitrate 0.05% produced a more effective pleurodesis in mice than did 0.025% silver nitrate or talc 4 mg/g, with significant higher scores for pleural adhesions, microscopic pleural inflammation and fibrosis. Haemothorax, atelectasis, and microscopic alveolar inflammation and fibrosis were negligible in both groups. Conclusions: Both talc 4 mg/g and 0.05% silver nitrate produced an efficient pleurodesis in this experimental model in mice. This new model may overcome the restrictions on the use of large- and medium-sized animals in laboratory investigation and may open new fields of investigation with knockout mice. [ABSTRACT FROM AUTHOR]

Background: In clinical practice, pleural and peritoneal effusions are usual diagnosis. We evaluated the performance of a hybrid panel of biomarkers in the diagnosis of the main diseases affecting pleura and/or peritoneum., Methods: Samples of pleural/ peritoneal fluid from 120 patients were evaluated for: CEA (carcinoembryonic antigen), VEGF-A (vascular endothelial growth factor A), PD-L1/B7-H1 (programmed death-ligand 1), NGAL (neutrophil gelatinase-associated lipocalin), TREM-1 (triggering receptor expressed in myeloid cells type-1) and IFNγ (gamma-interferon) by Luminex®; CALP (Calprotectin) by ELISA, and ADA (adenosine deaminase) by enzymatic deamination., Results: For malignant effusion (ME) diagnosis, CEA and NGAL presented superior performance than VEGF-A, PD-L1 and CALP. A CEA-NGAL association showed good sensitivity (86.6%) and accuracy (79.2%). For non-tuberculous infectious effusion (NTBIE), NGAL presented the best performance with sensitivity (75.0%), specificity (62.0%) and accuracy (65.0%) higher than TREM-1 and CALP; however, when associated, although with good sensitivity, there was important decrease in specificity. For tuberculous pleural effusion (TPE), IFNy-ADA presented excellent sensitivity (100%), specificity (87.6%), NPV (100%) and accuracies (~90%)., Conclusions: CEA, NGAL, ADA and IFNy were useful in discriminating ME and TPE. However, for NTBIE diagnosis, the hybrid panel did not demonstrate advantages over the classic parameters., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Tissue adhesives can be used to prevent pulmonary air leaks, which frequently occur after lung interventions. The objective of this study is to evaluate local and systemic effects of fibrin and cyanoacrylate tissue adhesives on lung lesions in rabbits., Methods: Eighteen rabbits were submitted to videothoracoscopy + lung incision alone (control) or videothoracoscopy + lung incision + local application of fibrin or cyanoacrylate adhesive. Blood samples were collected and assessed for leukocyte, neutrophil and lymphocyte counts and interleukin-8 levels preoperatively and at 48 hours and 28 days post-operatively. After 28 days, the animals were euthanized for gross examination of the lung surface, and lung fragments were excised for histopathological analysis., Results: Fibrin and cyanoacrylate produced similar adhesion scores of the lung to the parietal pleura. Microscopic analysis revealed uniform low-cellular tissue infiltration in the fibrin group and an intense tissue reaction characterized by dense inflammatory infiltration of granulocytes, giant cells and necrosis in the cyanoacrylate group. No changes were detected in the leukocyte, neutrophil or lymphocyte count at any time-point, while the interleukin-8 levels were increased in the fibrin and cyanoacrylate groups after 48 hours compared with the pre-operative control levels (p<0.01)., Conclusion: Both adhesive agents promoted normal tissue healing, with a more pronounced local inflammatory reaction observed for cyanoacrylate. Among the serum markers of inflammation, only the interleukin-8 levels changed post-operatively, increasing after 48 hours and decreasing after 28 days to levels similar to those of the control group in both the fibrin and cyanoacrylate groups.

Background: Pleurodesis performed either by pleurectomy or pleural abrasion is recommended in the approach to primary spontaneous pneumothorax to avoid recurrence. However, the efficacy of parietal pleural abrasion in producing pleurodesis is questioned. This study aims to determine the efficacy of apical abrasion alone, abrasion plus fibrin sealant application, and pleurectomy in producing pleurodesis in rabbits., Methods: Rabbits were subjected to video-assisted thoracic surgery alone (control) or to video-assisted thoracic surgery with apical gauze abrasion, abrasion plus fibrin sealant instillation, or apical pleurectomy. Blood samples were collected preoperatively and 48 h and 28 days postoperatively to measure total leukocytes (white blood cell count), neutrophil counts, and serum interleukin (IL)-8 levels. After 28 days the animals were sacrificed for macroscopic evaluation of the degree of apical pleurodesis and microscopic evaluation of local pleural fibrosis and collagen deposition., Results: White blood cell and neutrophil counts were similar in all groups, whereas the serum IL-8 level peaked at 48 h in all groups and decreased after 28 days, except in the pleurectomy group. After 28 days the abrasion plus fibrin sealant and pleurectomy groups had significantly more pleural adhesions, pleural fibrosis, and collagen deposition than the abrasion alone group, mainly due to thick mature fibers., Conclusions: Abrasion with local fibrin sealant instillation is as effective as pleurectomy in producing pleurodesis in rabbits. Apical pleurectomy elicits a more persistent elevation of serum IL-8 levels than apical abrasion alone or abrasion plus fibrin adhesive instillation., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: Chemical pleurodesis is an important therapeutic tool to control recurrent malignant pleural effusion. Among the various sclerosing agents, iodopovidone is considered effective and safe. However, in a recent study, ocular changes were described after iodopovidone was used in recurrent pneumothorax. The aim of the study was to evaluate the efficacy and morbidity of iodopovidone pleurodesis in an experimental model., Methods: New Zealand rabbits were submitted to intrapleural injection of iodopovidone at concentrations of 2%, 4% and 10%. Biochemical (lactic dehydrogenase, proteins, triiodothyronine, free thyroxine, urea and creatinine) and immunological (Interleukin-8 [IL-8], VEGF and TGFβ) parameters were measured in the pleural fluid and blood. After 1, 3, 7, 14 and 28 days, groups of animals were euthanized, and macro- (pleura) and microscopic (pleura and retina) analyses were performed., Results: An early pleural inflammatory response with low systemic repercussion was observed without corresponding changes in thyroid or renal function. The higher concentrations (4% and 10%) correlated with greater initial exudation, and maximum pleural thickening was observed after 28 days. No changes were observed in the retinal pigment epithelium of the rabbits., Conclusion: Iodopovidone is considered to be an effective and safe sclerosing agent in this animal model. However, its efficacy, tolerance and safety in humans should be further evaluated.

Background and Objective: Chemical pleurodesis controls recurrent malignant pleural effusion. The mechanism that determines pleural symphysis involves the action of vascular endothelial growth factor (VEGF). We assessed the influence of the anti-VEGF antibody (bevacizumab) on pleurodesis induced by talc or silver nitrate and analyzed the temporal development of pleural angiogenesis., Methods: Sixty New Zealand rabbits received intrapleural injection (2mL) of talc (400mg/kg) or 0.5% silver nitrate. In each group, half of the animals received an intravenous injection of bevacizumab 30min before the sclerosing agent. Five animals from each group were euthanized 7, 14, or 28 days after the procedure. Adhesions and inflammation (scores: 0-4), thickness (μm), vascular density (vessels/field), and collagen fibers (μm(2)) were evaluated in the visceral pleura., Results: Antibody anti-VEGF interferes in pleurodesis induced by talc or silver nitrate. Pleural inflammation was discreet with no difference between the groups, regardless the anti-VEGF treatment. Concerning the vascular density of the visceral pleura, a smaller number of neoformed vessels was noted in the animals that received bevacizumab. In the animals receiving silver nitrate, the decrement in adhesions and vascular density was associated with reduced thick and thin collagen fibers, resulting in less pleural thickness., Conclusion: The anti-VEGF antibody inhibits adhesions between pleural layers. Despite being an experimental study in animals with normal pleura, the results call attention to a likely lack of success in pleurodesis when VEGF blockers are used., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background and Objective: Light's criteria are frequently used to evaluate the exudative or transudative nature of pleural effusions. However, misclassification resulting from the use of Light's criteria has been reported, especially in the setting of diuretic use in patients with heart failure (HF). The objective of this study was to evaluate the utility of B-type natriuretic peptide (BNP) measurements as a diagnostic tool for determining the cardiac aetiology of pleural effusions., Methods: Patients with pleural effusions attributable to HF (n = 34), hepatic hydrothorax (n = 10), pleural effusions due to cancer (n = 21) and pleural effusions due to tuberculosis (n = 12) were studied. Diagnostic thoracentesis was performed for all 77 patients. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic accuracy of plasma BNP and pleural fluid BNP for the prediction of HF., Results: The areas under the ROC curves were 0.987 (95% CI 0.93-0.998) for plasma BNP and 0.949 (95% CI 0.874-0.986) for pleural fluid BNP, for distinguishing between patients with pleural effusions caused by HF (n = 34) and those with pleural effusions attributable to other causes (n = 43). The cut-off concentrations with the highest diagnostic accuracy for the diagnosis of HF as the cause of pleural effusion were 132 pg/mL for plasma BNP (sensitivity 97.1%, specificity 97.4%) and 127 pg/mL for pleural fluid BNP (sensitivity 97.1%, specificity 87.8%)., Conclusions: In patients with pleural effusions of suspected cardiac origin, measurements of BNP in plasma and pleural fluid may be useful for the diagnosis of HF as the underlying cause., (© 2011 The Authors. Respirology © 2011 Asian Pacific Society of Respirology.)

Background: Biochemical analysis of fluid is the primary laboratory approach in pleural effusion diagnosis. Standardization of the steps between collection and laboratorial analyses are fundamental to maintain the quality of the results. We evaluated the influence of temperature and storage time on sample stability., Methods: Pleural fluid from 30 patients was submitted to analyses of proteins, albumin, lactic dehydrogenase (LDH), cholesterol, triglycerides, and glucose. Aliquots were stored at 21 degrees , 4 degrees , and-20 degrees C, and concentrations were determined after 1, 2, 3, 4, 7, and 14 days. LDH isoenzymes were quantified in 7 random samples., Results: Due to the instability of isoenzymes 4 and 5, a decrease in LDH was observed in the first 24h in samples maintained at -20 degrees C and after 2 days when maintained at 4 degrees C. Aside from glucose, all parameters were stable for up to at least day 4 when stored at room temperature or 4 degrees C., Conclusions: Temperature and storage time are potential preanalytical errors in pleural fluid analyses, mainly if we consider the instability of glucose and LDH. The ideal procedure is to execute all the tests immediately after collection. However, most of the tests can be done in refrigerated samples, excepting LDH analysis., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background and Objective: Vascular endothelial growth factor (VEGF) is known to increase vascular permeability and promote angiogenesis. It is expressed in most types of pleural effusions. However, the exact role of VEGF in the development of pleural effusions has yet to be determined. The anti-VEGF mAb, bevacizumab, has been used in the treatment of cancer to reduce local angiogenesis and tumour progression. This study describes the acute effects of VEGF blockade on the expression of inflammatory cytokines and pleural fluid accumulation., Methods: One hundred and twelve New Zealand rabbits received intrapleural injections of either talc or silver nitrate. In each group, half the animals received an intravenous injection of bevacizumab, 30 min before the intrapleural agent was administered. Five animals from each subgroup were sacrificed 1, 2, 3, 4 or 7 days after the procedure. Twelve rabbits were used to evaluate vascular permeability using Evans's blue dye. Pleural fluid volume and cytokines were quantified., Results: Animals pretreated with anti-VEGF antibody showed significant reductions in pleural fluid volumes after talc or silver nitrate injection. IL-8 levels, vascular permeability and macroscopic pleural adhesion scores were also reduced in the groups that received bevacizumab., Conclusions: This study showed that bevacizumab interferes in the acute phase of pleural inflammation induced by silver nitrate or talc, reinforcing the role of VEGF as a key mediator in the production of pleural effusions. The results also suggest that bevacizumab should probably be avoided in patients requiring pleurodesis.

Background and Objective: Both talc and 0.5% silver nitrate have been shown to induce effective pleurodesis. However, acute adverse systemic inflammatory effects have been described with both agents. The aim of this study was to assess in rabbits the systemic effects associated with a new technique of pleurodesis using repeated low doses of 0.1% silver nitrate., Methods: Rabbits were injected intrapleurally through a chest tube with 0.1% silver nitrate at 0, 24 and 48 h. Other groups received a single injection of 0.5% silver nitrate or 400 mg/kg of talc. Blood samples were collected at 24, 48 and 72 h, and at 7 days, and cytological and biochemical measurements were performed. After 28 days, the presence of macroscopic pleural adhesions and microscopic pleural fibrosis in the pleural cavity were evaluated., Results: Both talc and 0.5% silver nitrate caused significant increases in blood neutrophils, serum LDH, IL-8, transforming growth factor-beta and CRP in comparison with control at almost all time points, whereas sequential doses of 0.1% silver nitrate only increased LDH and CRP in the first 24 h and transforming growth factor-beta at all time points. All groups showed efficient pleurodesis, with no differences in pleural adhesions or fibrosis., Conclusions: Sequential doses of 0.1% silver nitrate produced efficient pleurodesis in rabbits, with a low systemic inflammatory response in comparison with 400 mg/kg of talc or 0.5% silver nitrate.

Background: The intrapleural instillation of a sclerosing agent produces an inflammatory process frequently followed by pain. The treatment can include the use of analgesics or anti-inflammatory drugs. Previously, it was demonstrated (experimental studies) that corticoids and nonsteroidal anti-inflammatory drugs (diclofenac) reduce the inflammation and fibrosis produced by talc but not by transforming growth factor-beta or silver nitrate. The objective of this study was to determine whether parecoxib (COX-2 inhibitor) affects pleurodesis induced by talc or silver nitrate., Methods: 140 rabbits received intrapleural injection (2mL) of 400mg/kg of talc or 0.5% silver nitrate. A subgroup of 70 animals received additional daily intramuscular parecoxib (1mg/kg). They were sacrificed at 4, 24, 48, 72h or 7, 14, or 28 days after the procedure. The pleural fluid was quantified; biochemical examinations (glucose, lactic dehydrogenase, and proteins) and immunologic dosages (interleukin-8, vascular endothelial growth factor, and transforming growth factor-beta(1)) were analyzed in pleural fluid and blood. Finally, macro- and microscopic pleura and lung studies were performed., Results: Evaluation after 28 days demonstrated that parecoxib reduced pleural and pulmonary inflammation but not pleural adhesions. The changes were observed precociously (congruent with 72h) and were more evident after silver nitrate injection., Conclusion: Systemic parecoxib injection does not interfere with talc or silver nitrate pleurodesis. These results suggest that use of COX-2 inhibitors can be considered and depending of the results of other studies, recommended in human pleurodesis.

The mechanisms of the systemic response associated with talc-induced pleurodesis are poorly understood. The aim of this study was to assess the acute inflammatory response and migration of talc of small size particles injected in the pleural space. Rabbits were injected intrapleurally with talc solution containing small or mixed particles and blood and pleural fluid samples were collected after 6, 24 or 48 h and assayed for leukocytes, neutrophils, lactate dehydrogenase, IL-8, VEGF, and TGF-beta. The lungs, spleen, liver and kidneys were assessed to study deposit of talc particles. Both types of talc produced an acute serum inflammatory response, more pronounced in the small particles group. Pleural fluid IL-8 and VEGF levels were higher in the small particle talc group. Correlation between pleural VEFG and TGF-beta levels was observed for both groups. Although talc particles were demonstrated in the organs of both groups, they were more pronounced in the small talc group. In conclusion, intrapleural injection of talc of small size particles produced a more pronounced acute systemic response and a greater deposition in organs than talc of mixed particles.

Background and Objective: To clarify the influence of transforming growth factor beta-1 (TGF-beta(1)) in the development of pleural thickening in tuberculosis (TB), the levels of TGF-beta(1) in pleural fluid and in serum of patients with pleural TB and transudative effusions were determined., Methods: TGF-beta(1) was quantified in 58 pleural fluid and serum samples of patients with TB (n = 50) or transudative effusions (n = 8). Pleural thickening evaluated by high-resolution CT was scored as 0 (<3 mm); 1 (>or=3 and <10 mm) or 2 (>or=10 mm)., Results: The highest pleural fluid TGF-beta(1) levels before treatment for TB were observed in patients with a pleural thickness score of 2. Of the 14 patients with score 1, five regressed to 0, five progressed to 2, and four maintained 1. All 17 patients with score 2 maintained this evaluation. Patients who presented score 1 and progressed to 2 had higher TGF-beta(1) levels than those who maintained the same score or regressed (score 1 or 0). Patients with score 2 (before or after treatment) had higher TGF-beta(1) levels than those with score 0 or 1., Conclusion: Pleural fluid and serum TGF-beta(1) levels were higher in patients with TB, with a correlation between pleural fluid TGF-beta(1) levels before treatment and the degree of pleural thickening. This finding suggests that TGF-beta(1) might be considered as a predictor of pleural thickening in pleural tuberculosis.

Purpose: Chemical pleurodesis is a therapeutic tool for the treatment of recurrent pleural effusions, mainly those of neoplastic etiology. In the past, tetracycline was the sclerosant agent of choice in clinical practice, but presently, there is no consensus about an ideal agent. The aim of this study was to evaluate the effectiveness of macrolides (azithromycin and clarithromycin) or quinolones (levofloxacin and gatifloxacin) in inducing experimental pleurodesis in rabbits., Method: Forty New Zealand rabbits randomized into groups of 10 received (at a total volume of 2 mL for each animal) 1 of the 4 drugs by intrapleural injection. After 28 days, the animals were euthanized and the pleural cavity was evaluated macroscopically and microscopically., Results: The intensity of the macroscopic adhesions was mild in all groups. On microscopic analysis, minimal pleural fibrosis and inflammation were observed in all animals., Conclusion: The macrolides (azithromycin or clarithromycin) and the quinolones (levofloxacin or gatifloxacin) when injected into the normal pleural space of rabbits are not effective in promoting pleurodesis. Additional research is required to identify sclerosing agents capable of inducing pleurodesis.

Study Objective: s: To determine whether talc (TL) and silver nitrate (SN), two effective pleurodesis agents, induce a systemic inflammatory response in the acute phase of experimental pleurodesis in rabbits., Design: Samples of blood and pleural fluid were collected after 6, 24, and 48 h from rabbits injected intrapleurally with 3 mL saline solution, TL (400 mg/kg), or 0.5% SN, and were assayed for WBC count, percentage of neutrophils, and levels of lactate dehydrogenase (LDH), interleukin (IL)-8, and vascular endothelial growth factor (VEGF). The pleural liquid production was compared in the three different groups. A sample of blood collected from animals preinjection was used as the control., Results: At 6 h after pleural injection, the mean blood WBC count and percentage of neutrophils were significantly elevated in the TL group, whereas the mean LDH and IL-8 levels were significantly increased in the SN group. VEGF was undetectable in the preinjection serum and saline solution-injected animals, but was increased in the serum after the pleural injection of both TL and SN to a comparable degree. SN elicited a more intense acute pleural inflammation reaction than did TL, with higher WBC count and IL-8 levels found in the pleural fluid, mainly within the first 6 h. LDH and VEGF levels, and pleural liquid production were also higher for SN, and they increased with time., Conclusions: In the acute phase of pleural injection, TL induced a transient increase in blood WBC count and percentage of neutrophils, while SN induced increases in blood LDH and IL-8 levels. Both TL and SN induced significant increases in blood VEGF levels. SN induced an earlier and more intense acute pleural inflammation than TL. Pleural liquid VEGF levels were higher after SN injection and increased, as did pleural liquid production. These findings suggest that the intrapleural injection of TL and SN produce a systemic inflammatory response that may have a role in the pathogenesis of fever and ARDS, which occur with pleurodesis.