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Objective: This study aims to evaluate the efficiencies and effects of different sclerosing agents. Materials and Methods: Thirty-five female Wistar-albino rats were included in this study and divided into five groups randomly. Isotonic saline (group 1), iodopovidone (group 2), rifamycin (group 3), autologous blood (group 4), talc (group 5) were given into intrapleural space. On postoperative 28th day, ipsilateral and contralateral pleural and parenchymal fibrosis and inflammation were evaluated. Results: There were statistically differences between control and other groups on macroscopically pleural fibrosis examination (p=0.004, p=0.001, p=0.001, p=0.000, respectively). Microscopically pleural fibrosis were determined in all groups when compared to control group (p=0.023, p=0.023, p=0.035, p=0.001, respectively). There were no significant differences between sclerosing agent groups (p>0.05). Significant differences were observed according to microscopic pleural inflammation evaluation between talc group and other groups. There was superiority in talc group according to intraparenchymal inflammation grade compared to other groups (p=0.010, p=0.042, p=0.030, respectively). Macroscopically, fibrosis and microscopically, inflammation were significantly observed between talc and other groups in the contralateral pleura (p = 0.037and p=0.009, respectively). Conclusion: Iodopovidone, autologous blood, talc, and rifamycin can be used as effective pleurodesis agents. However, we found that rifamycin and autologous blood are safer as effective pleurodesis agents. We think that these two agents can be used in patients with secondary lung diseases due to their less intraparenchymal inflammation rates. It may be advantageous to prefer other sclerosing agents which has lower costs and less side effects comparing to talc. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) are speculated to cause mesothelioma by persistent inflammation, oxidative stress, tissue injury, and genotoxicity. To investigate the pleural response to CNTs, we exposed C57BL/6 mice by intrapleural injection of 0.2 or 5 µg multiwalled CNTs (MWCNT-7, NM-401, and NM-403) or single-walled CNTs (NM-411). Inflammatory response, cellular reactive oxygen species (ROS) production of pleural lavage cells, and genotoxicity in cells from the mesothelial surface were assessed at days 1 and 90 after the exposure. Long and rigid types of MWCNTs (MWCNT-7 and NM-401) caused acute inflammation, characterized by influx of macrophages, neutrophils, and eosinophils into the pleural cavity. The inflammation was still evident at 90 days after the exposure, although it had reduced dramatically. The cellular ROS production was increased at day 90 after the exposure to MWCNT-7 and NM-401. The short and tangled type of MWCNT (ie NM-403) did not cause pleural inflammation or ROS production in pleural fluid cells. The exposure to NM-411 did not cause consistent inflammation responses or cellular ROS production. Levels of DNA strand breaks and DNA oxidation damage were unaltered, except for NM-411-exposed mice that had increased levels of DNA strand breaks at 90 days after the exposure. In conclusion, the long and rigid CNTs caused prolonged inflammatory response and increased ROS production in pleural lavage cells, yet it was not reflected in higher levels of DNA damage in pleural tissue. [ABSTRACT FROM AUTHOR]

Background. Pulmonary diseases associated with inflammation are largely found in humans. The lungs are continuously exposed to oxidative stress, a process that, through the release of reactive oxygen species, leads to tissue damage and to an increase in the initial inflammatory reaction. Therefore, it is necessary to find a therapy that is able to counteract the noxious effects of reactive species and of inflammation. Resveratrol is a natural polyphenol with anti-inflammatory effects, having the capacity to limit the production of pro-inflammatory factors such as interleukins and prostaglandins. Quercetin, a flavonoid with known anti-inflammatory and antioxidant effects, inhibits phospholipase A2 and the enzymes of lipid peroxidation, reducing the synthesis of leukotrienes. Aims. The antioxidant effects of resveratrol and quercetin were studied in an experimental model of carrageenan-induced pleural inflammation. Methods. The study was performed using male rats, divided into 2 groups, each group containing a further 4 groups (control, administration of carrageenan, resveratrol and carrageenan, and quercetin and carrageenan, respectively). The oxidant/antioxidant balance was evaluated in the serum and in the lung tissue at 4 hours (groups I-IV) and at 24 hours (groups V-VIII). Results. In serum, at 4 and at 24 hours after carrageenan administration, the malondialdehyde levels were decreased significantly by resveratrol and quercetin, and the ceruloplasmin concentration in the rats that were pre-treated with these chemicals was increased significantly, in comparison with the control and carrageenan groups. In lung homogenate, at 4 and at 24 hours, significant decreases of malondialdehyde in the groups that received antioxidants were recorded, compared to unprotected groups; increases of glutathione levels were recorded at 24 hours only in the resveratrol group. Conclusions. In serum, both compounds, resveratrol and quercetin, presented antioxidant effects. In the lungs, at 24 hours, resveratrol had superior antioxidant effects. [ABSTRACT FROM AUTHOR]

This study investigated the antiinflammatory properties of betulinic acid (BA) and xylopic acid (XA) extracted from Margaritaria discoidea and Xylopia aethiopica, respectively. M. discoidea and X. aethiopica are plants native in Ghana and the West-African region and used traditionally to treat different pathologies including inflammatory conditions. The antiinflammatory effect of BA and XA was established by an in vivo assay using the carrageenan-induced pleural inflammation model in mice. Also, the ability of BA and XA to increase catalase, superoxide dismutase, glutathione levels and decrease lipid peroxidation level in reactive oxidative assays was assessed. In addition, the ability of XA and BA to prevent potential lung tissue damage was quantified. Pretreatment with BA and XA reduced significantly, signs of inflammation: neutrophil infiltration, oedema, and alveoli septal thickening in carrageenan-treated lung tissue. Additionally, BA or XA pretreatment lowered the degree of lipid peroxidation in the lung tissue while increasing the levels of catalase, superoxide dismutase, and glutathione in vivo. Comparatively, XA was more efficacious than BA in the prevention of lung tissue damage. BA and XA derived from X. aethiopica and M. discoidea possess antiinflammatory and in vivo antioxidant activities in mice pleurisy model. The effect of these compounds gives credence to the traditional use in the management of inflammatory conditions of the airway. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective Exudative pleural effusions affect over 1500 patients per million population each year. The pathobiology of pleural exudate formation remains unclear. Our recent study revealed monocyte chemotactic protein-1 ( MCP-1) as a key driver of fibrinolytic-induced exudate effusion while another study found a role for MCP-1 in malignant effusion formation. In the present study, we further evaluated the role of MCP-1 in the development of pleural effusion in a mouse model of acute pleural inflammation. Methods λ-Carrageenan ( CAR) was injected into the pleural cavity of CD1 mice and pleural effusion volume measured up to 16 h post-injection. Pleural effusion and serum protein and MCP-1 concentrations were measured and differential cell counts performed in fluids. Mice were also treated with either intraperitoneal (i) anti- MCP-1 antibody or isotype control or (ii) an MCP-1 receptor ( CCR2) antagonist or vehicle control 12 h prior to and at the time of CAR injection. Results Intrapleural CAR induced significant pleural fluid accumulation (300.0 ± 49.9 μL) in mice after 4 h. Pleural fluid MCP-1 concentrations were significantly higher than corresponding serum MCP-1 (144 603 ± 23 204 pg/ mL vs 3703 ± 801 pg/ mL, P < 0.0001). A significant decrease in pleural fluid formation was seen both with anti- MCP-1 antibody (median (interquartile range, IQR): 36 (0-168) μL vs controls 290 (70-436) μL; P = 0.02) or CCR2 antagonist (153 (30-222) μL vs controls 240 (151-331) μL, P = 0.0049). Conclusions Blockade of MCP-1 activity significantly reduced inflammatory pleural effusion formation in a CAR model. Together with recent successes in MCP-1 blockade in other effusion formation models, our data strongly support clinical evaluation of MCP-1 antagonists as a novel approach to pleural fluid management. [ABSTRACT FROM AUTHOR]

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 Aim. Hyaluronic acid (HA) is a component of extracellular matrix and may play a role in the pleural inflammation which is implicated in parapneumonic effusions.The aim of the current study was to investigate HA levels in serum and pleura in patients with parapneumonic effusions. Methods. We prospectively studied pleural and serum levels of HA in 58 patients with pleural effusions due to infection (complicated and uncomplicated parapneumonic effusions), malignant effusions and transudative effusions due to congestive heart failure. In addition to HA, TNF-α and IL-1β levels were determined in pleural fluid and serum by ELISA. Results. The median±SD HA levels (pg/ml) in pleural fluid of patients with complicated effusions (39.058±11.208) were significantly increased (p

Relationships between the physical properties of carbon nanotubes (CNTs) and their toxicities have been studied. However, little research has been conducted to investigate the pulmonary and pleural inflammation caused by short-fiber single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs). This study was performed to characterize differences in rat pulmonary and pleural inflammation caused by intratracheal instillation with doses of 0.15 or 1.5 mg/kg of either short-sized SWCNTs or MWCNTs. Data from bronchoalveolar lavage fluid analysis, histopathological findings, and transcriptional profiling of rat lungs obtained over a 90-day period indicated that short SWCNTs caused persistent pulmonary inflammation. In addition, the short MWCNTs markedly impacted alveoli immediately after instillation, with the levels of pulmonary inflammation following MWCNT instillation being reduced in a time-dependent manner. MWCNT instillation induced greater levels of pleural inflammation than did short SWCNTs. SWCNTs and MWCNTs translocated in mediastinal lymph nodes were observed, suggesting that SWCNTs and MWCNTs underwent lymphatic drainage to the mediastinal lymph nodes after pleural penetration. Our results suggest that short SWCNTs and MWCNTs induced pulmonary and pleural inflammation and that they might be transported throughout the body after intratracheal instillation. The extent of changes in inflammation differed following SWCNT and MWCNT instillation in a time-dependent manner. [ABSTRACT FROM AUTHOR]

Pleural chronic inflammation (PP) and mesothelial hyperplasia (HP) may be critical to the development of malignant pleural mesothelioma (MPM). Nonetheless, studies searching for mechanistic links involving microRNA (miRNA) regulation among these interrelated processes have not been reported. Using PCR-Array, we identified the miRNAs expressed in pleural tissues diagnosed with MPM (n = 5), PP (n = 4) and HP (n = 5), as well as in non-cancerous/non-inflammatory tissue as the normal control (n = 5). We performed bioinformatics and network analysis of differentially expressed miRNAs to identify tumorigenesis-related miRNAs and their biological networks. The targets of four down-regulated miRNAs in MPM (mir-181a-5p, miR-101-3p, miR-145-5p and miR-212-3p), one in PP (mir-101-3p) and one in HP (mir-494) were significantly enriched in “pathways in cancer”. Interactome networks revealed that > 50% of down-regulated miRNAs in MPM targeted the signaling-activation molecule MAPK1, the transcription factor ETS1 and the mesenchymal transition-associated molecule FZDA, which have been associated with oncogenic function. Comparative analysis revealed that FZD4 was an overlapping gene target of down-regulated miRNAs that were associated with “pathways in cancer” in MPM, PP and HP. Moreover, MAPK1, ETS1 and Cox-2, a pro-inflammatory enzyme associated with over-expression in cancers, were among the 25 overlapping target genes in MPM and PP. This network analysis revealed a potential combinatory effect of deregulated miRNAs in MPM pathogenesis and indicated potential molecular links between pleural inflammation and hyperplasia with tumorigenesis mechanisms in pleura. [ABSTRACT FROM AUTHOR]

Multiwalled carbon nanotubes ( MWCNT) have a fibrous structure similar to asbestos, raising concern that MWCNT exposure may lead to asbestos-like diseases. Previously we showed that MWCNT translocated from the lung alveoli into the pleural cavity and caused mesothelial proliferation and fibrosis in the visceral pleura. Multiwalled carbon nanotubes were not found in the parietal pleura, the initial site of development of asbestos-caused pleural diseases in humans, probably due to the short exposure period of the study. In the present study, we extended the exposure period to 24 weeks to determine whether the size and shape of MWCNT impact on deposition and lesion development in the pleura and lung. Two different MWCNTs were chosen for this study: a larger sized needle-like MWCNT ( MWCNT- L; l = 8 μm, d = 150 nm), and a smaller sized MWCNT ( MWCNT- S; l = 3 μm, d = 15 nm), which forms cotton candy-like aggregates. Both MWCNT- L and MWCNT- S suspensions were administered to the rat lung once every 2 weeks for 24 weeks by transtracheal intrapulmonary spraying. It was found that MWCNT- L, but not MWCNT- S, translocated into the pleural cavity, deposited in the parietal pleura, and induced fibrosis and patchy parietal mesothelial proliferation lesions. In addition, MWCNT- L induced stronger inflammatory reactions including increased inflammatory cell number and cytokine/chemokine levels in the pleural cavity lavage than MWCNT- S. In contrast, MWCNT- S induced stronger inflammation and higher 8-hydroxydeoxyguanosine level in the lung tissue than MWCNT- L. These results suggest that MWCNT- L has higher risk of causing asbestos-like pleural lesions relevant to mesothelioma development. [ABSTRACT FROM AUTHOR]

The FDG-PET (fluorine-18 fluorodeoxyglucose positron emission tomography) scan is used with increasing frequency to investigate pleural abnormalities and to determine the possibility of neoplastic invasion. However, false-positive findings are not uncommon and talc pleurodesis has been reported to cause hypermetabolic pleural thickenings up to 5 years after the procedure. We report the cases of 3 patients (2 of whom had a history of asbestos exposure) requiring talc pleurodesis for recurrent pneumothoraces between 1988 and 1990, who were investigated in 2011 for pleural abnormalities. Avid pleural thickening on FDG-PET scan mimicking pleural cancer was found, but this was deemed secondary to the pleurodesis. Talc pleurodesis generates inflammation which promotes pleural adhesions. This inflammatory reaction could decrease with time, as in other inflammatory processes. Since talc is not metabolized by the body, the FDG-PET scan can remain positive, most likely because of a foreign-body granulomatous reaction, even 20 years later. It is important to be aware of this possibility and to question patients with pleural abnormalities about past procedures and mention such procedures to the colleagues who are responsible for interpreting metabolic imaging. Follow-up of hypermetabolic pleural lesions attributed to talc pleurodesis is important for the detection of new pleural lesions or neoplastic evolution. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Suspicion has been raised that high aspect ratio nanoparticles or nanofibers might possess asbestos-like pathogenicity. The pleural space is a specific target for disease in individuals exposed to asbestos and by implication of nanofibers. Pleural effects of fibers depends on fiber length, but the key threshold length beyond which adverse effects occur has never been identified till now because all asbestos and vitreous fiber samples are heterogeneously distributed in their length. Nanotechnology advantageously allows for highly defined length distribution of synthetically engineered fibers that enable for in-depth investigation of this threshold length. We utilized the ability to prepare silver nanofibers of five defined length classes to demonstrate a threshold fiber length for acute pleural inflammation. Nickel nanofibers and carbon nanotubes were then used to strengthen the relationship between fiber length and pleural inflammation. A method of intrapleural injection of nanofibers in female C57Bl/6 strain mice was used to deliver the fiber dose, and we then assessed the acute pleural inflammatory response. Chest wall sections were examined by light and scanning electron microscopy to identify areas of lesion; furthermore, cell- nanowires interaction on the mesothelial surface of the parietal pleura in vivo was investigated. Our results showed a clear threshold effect, demonstrating that fibers beyond 4 µm in length are pathogenic to the pleura. The identification of the threshold length for nanofiber-induced pathogenicity in the pleura has important implications for understanding the structure-toxicity relationship for asbestos-induced mesothelioma and consequent risk assessment with the aim to contribute to the engineering of synthetic nanofibers by the adoption of a benign-by-design approach. [ABSTRACT FROM AUTHOR]

Pleurodesis, from the Greek pleura and desis (binding together), is intended to achieve a symphysis between parietal and visceral pleura, in order to prevent accumulation of either air (pneumothrax) or fluid (pleural effusion) in the pleural space. The search for the ideal agent for pleurodesis continues. The aim of this research was to assess the chronic gross and microscopic pleural findings, after intrapleural administration of iodpovidone as a sclerosing agent. 12 New Zealand White rabbits were used for the study. After instillation of 2 ml 10% iodpovidone into the right pleural cavity, the animals were sacrificed in groups of three on day 5, 7, 10, 14. Gross pathology and histology analysis were performed. It was established, that jodpovidone has caused pleural inflammation whit mononuclear cells infiltration and formation of new blood vessels on day 5. It was also established expressive proliferation of fibroblasts within visceral pleura and collagen production. The final result was fibrotic transformation of the visceral pleura, which was established on day 14. As a result of pleural fibrotic transformation, complete obliteration of the pleural space occurred, which means effective pleurodesis. The study had shown that intrapleural instillation of iodpovidone has caused effective pleurodesis until the period of 14 days. The safeness of iodpovidone as an agent for chemical pleurodesis has also been proven in the study. [ABSTRACT FROM AUTHOR]

Summary: Background: Vascular endothelial growth factor (VEGF) participates in the pathogenesis of exudative pleural effusions (PEs). In the present study, we determined the pleural fluid (PF) and serum VEGF levels in patients with post-coronary artery by-pass grafting (post-CABG) PEs. Methods: Thirty-eight patients with post-CABG (two with bilateral) PEs were studied. PEs were divided into “early” (occurring earlier than 30 days after surgery) and “late” ones. VEGF levels were measured using ELISA. Results: (i) Serum and PF VEGF levels did not differ significantly when all the patients (P=0.053) or those with late effusions (P=0.6) were analyzed; serum VEGF levels were significantly elevated in comparison to PF VEGF levels in patients with early (P=0.007) effusions. (ii) Serum VEGF levels were significantly higher in patients with early than in those with late effusions (P=0.033), while PF VEGF levels were not significantly different between the two groups (P=0.77). (iii) PF VEGF levels were higher than corresponding serum levels in 4/24 patients with early and in 10/16 patients with late post-CABG PEs (P=0.006). (iv) In PEs VEGF levels significantly correlated with red blood cells (P=0.015), nucleated cells (P=0.003), protein levels (P=0.002) and lactate dehydrogenase (LDH) levels (P=0.04). Conclusion: In post-CABG PEs, preferential local production of VEGF in the pleural cavity is most commonly observed a month or later after surgery. The fact that in PEs VEGF levels correlate with markers of pleural inflammation (inflammatory cells and LDH levels) and vascular hyperpermeability (protein levels) suggests that VEGF may be involved in the pathogenesis of post-CABG PEs. [Copyright &y& Elsevier]