Shear stress-exposed pulmonary artery endothelial cells fail to upregulate HSP70 in chronic thromboembolic pulmonary hypertension.

The pathophysiological mechanisms underlying chronic thromboembolic pulmonary hypertension (CTEPH) are still unclear. Endothelial cell (EC) remodeling is believed to contribute to this pulmonary disease triggered by thrombus and hemodynamic forces disbalance. Recently, we showed that HSP70 levels decrease by proatherogenic shear stress. Molecular chaperones play a major role in proteostasis in neurological, cancer and inflammatory/ infectious diseases. To shed light on microvascular responses in CTEPH, we characterized the expression of molecular chaperones and annexin A2, a component of the fibrinolytic system. There is no animal model that reproduces microvascular changes in CTEPH, and this fact led us to isolated endothelial cells from patients with CTEPH undergoing pulmonary endarterectomy (PEA). We exposed CTEPH-EC and control human pulmonary endothelial cells (HPAEC) to high- (15 dynes/cm2) or low- (5 dynes/cm2) shear stress. After high-magnitude shear stress HPAEC upregulated heat shock protein 70kDa (HSP70) and the HSP ER paralogs 78 and 94kDa glucose-regulated protein (GRP78 and 94), whereas CTEPH-ECs failed to exhibit this response. At static conditions, both HSP70 and HSP90 families in CTEPH-EC are decreased. Importantly, immunohistochemistry analysis showed that HSP70 expression was downregulated in vivo, and annexin A2 was upregulated. Interestingly, wound healing and angiogenesis assays revealed that HSP70 inhibition with VER-155008 further impaired CTEPH-EC migratory responses. These results implicate HSP70 as a novel master regulator of endothelial dysfunction in type 4 PH. Overall, we first show that global failure of HSP upregulation is a hallmark of CTEPH pathogenesis and propose HSP70 as a potential biomarker of this condition.

Hybrid panel of biomarkers can be useful in the diagnosis of pleural and peritoneal effusions.

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.

Local and systemic effects of fibrin and cyanoacrylate adhesives on lung lesions in rabbits.

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.

Abrasion Plus Local Fibrin Sealant Instillation Produces Pleurodesis Similar to Pleurectomy in Rabbits.

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.

Effects of low-level laser therapy on the serum TGF-ß1 concentrations in individuals with autoimmune thyroiditis.

OBJECTIVE: The objective of this study was to evaluate the serum concentration of transforming growth factor-ß1 (TGF-ß1) after low-level laser therapy (LLLT) in patients with hypothyroidism resulting from chronic autoimmune thyroiditis (CAT). BACKGROUND DATA: Certain data indicate that LLLT is effective in patients with hypothyroidism caused by CAT; however, the mechanisms of action of LLLT in thyroid tissue are unknown. Cytokines could play a role in the response to LLLT. METHODS: A randomized, placebo-controlled trial included 43 patients with a history of levothyroxine therapy for CAT-induced hypothyroidism. The patients were randomly assigned to receive either 10 sessions of LLLT (830 nm, 50 mW output power, and 707 J/cm(2) fluence; L group, n=23) or 10 sessions of a placebo treatment (P group, n=20) twice a week. Levothyroxine was maintained at the same dose during the entire study period. TGF-ß1 was measured both pre-intervention and 30 days post-intervention in both groups. The differences were calculated between the TGF-ß1 values observed 30 days post-intervention and the pre-intervention TGF-ß1 values for each group (intragroup). RESULTS: Comparing the differences in TGF-ß1 levels between the L group (874.9±541.7 pg/mL) and the P group (-128.4±832.8 pg/mL) revealed that there was a statistically significant increase in TGF-ß1 levels 30 days post-intervention in group L compared with the placebo group (p=0.0379). CONCLUSIONS: This finding suggested that the significant increase in serum TGF-ß1 levels in patients with CAT-induced hypothyroidism was associated with the thyroid LLLT procedure. Future studies of the effect of LLLT on TGF-ß1 gene expression in thyroid tissue are necessary to confirm these findings.

Effectiveness and safety of iodopovidone in an experimental pleurodesis model.

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 TGFß) 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.

Effectiveness and safety of iodopovidone in an experimental pleurodesis model

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. .

Pleural tuberculosis: is radiological evidence of pulmonary-associated disease related to the exacerbation of the inflammatory response?

OBJECTIVE: Pleural tuberculosis is the most frequently occurring form of extra pulmonary disease in adults. In up to 40% of cases, the lung parenchyma is concomitantly involved, which can have an epidemiological impact. This study aims to evaluate the pleural and systemic inflammatory response of patients with pleural or pleuropulmonary tuberculosis. METHODS: A prospective study of 39 patients with confirmed pleural tuberculosis. After thoracentesis, a high resolution chest tomography was performed to evaluate the pulmonary involvement. Of the 39 patients, 20 exhibited only pleural effusion, and high resolution chest tomography revealed active associated-pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin-8, tumor necrosis factor-α, and transforming growth factor-ß(1) levels were quantified in the patient serum and pleural fluid. RESULTS: All of the effusions were exudates with high levels of adenosine deaminase. The levels of vascular endothelial growth factor and transforming growth factor-ß(1) were increased in the blood and pleural fluid of all of the patients with pleural tuberculosis, with no differences between the two forms of tuberculosis. The tumor necrosis factor-α levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin-8 levels were high in the pleural fluid of all of the patients, without any differences between the forms of tuberculosis. CONCLUSION: Tumor necrosis factor-α was the single cytokine that significantly increased in the pleural fluid of the patients with pulmonary involvement. However, an overlap in the results does not permit us to suggest that cytokine is a biological marker of concomitant parenchymal involvement. Although high resolution chest tomography can be useful in identifying these patients, the investigation of fast acid bacilli and cultures for M. tuberculosis in the sputum is recommended for all patients who are diagnosed with pleural tuberculosis.

Pleural tuberculosis: is radiological evidence of pulmonary-associated disease related to the exacerbation of the inflammatory response?

OBJECTIVE: Pleural tuberculosis is the most frequently occurring form of extra pulmonary disease in adults. In up to 40% of cases, the lung parenchyma is concomitantly involved, which can have an epidemiological impact. This study aims to evaluate the pleural and systemic inflammatory response of patients with pleural or pleuropulmonary tuberculosis. METHODS: A prospective study of 39 patients with confirmed pleural tuberculosis. After thoracentesis, a high resolution chest tomography was performed to evaluate the pulmonary involvement. Of the 39 patients, 20 exhibited only pleural effusion, and high resolution chest tomography revealed active associated-pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin-8, tumor necrosis factor-α, and transforming growth factor-β1 levels were quantified in the patient serum and pleural fluid. RESULTS: All of the effusions were exudates with high levels of adenosine deaminase. The levels of vascular endothelial growth factor and transforming growth factor-β1 were increased in the blood and pleural fluid of all of the patients with pleural tuberculosis, with no differences between the two forms of tuberculosis. The tumor necrosis factor-α levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin-8 levels were high in the pleural fluid of all of the patients, without any differences between the forms of tuberculosis. CONCLUSION: Tumor necrosis factor-α was the single cytokine that significantly increased in the pleural fluid of the patients with pulmonary involvement. However, an overlap in the results does not permit us to suggest that cytokine is a biological marker of concomitant parenchymal involvement. Although high resolution chest tomography can be useful in identifying these patients, the investigation of fast acid bacilli and cultures for M. tuberculosis in the sputum is recommended for all patients who are diagnosed with pleural tuberculosis.

Blockage of vascular endothelial growth factor (VEGF) reduces experimental pleurodesis.

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.

Clinical usefulness of B-type natriuretic peptide in the diagnosis of pleural effusions due to heart failure.

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.

Monoclonal anti-vascular endothelial growth factor antibody reduces fluid volume in an experimental model of inflammatory pleural effusion.

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.

Eosinophilic pneumonitis induced by aerosol-administered diesel oil and pyrethrum to mice.

OBJECTIVE: To confirm the episode of eosinophilic pneumonitis that occurred in March 2001 in Manaus, Amazon, northern Brazil, as secondary to home aerosolization with 2% cypermethrin diluted in diesel compared with the more conventional 1% cypermethrin and soybean solution used in prophylaxis of dengue. METHODS: Four groups of Swiss mice were kept in polycarbonate cages aerosolized with one of the following solutions: diesel, diesel and cypermethrin, soy oil and cypermethrin, and saline. Three and 6 days after exposure, resistance and compliance of the respiratory system and white cell kinetics in peripheral blood and lung tissue were analyzed. RESULTS: The group exposed to diesel and cypermethrin showed higher respiratory system resistance (p < 0.001), lower compliance (p = 0.03), and increased eosinophils in blood (p = 0.03) and lung tissue (p = 0.005) compared with the other groups. There was an increase of neutrophils in the blood of all experimental groups on the third day after exposure (p < 0.001). CONCLUSIONS: We concluded that diesel associated with cypermethrin induced lung hyperresponsiveness in this experimental model and was associated with increased polymorphonuclear cells (eosinophils and neutrophils) in blood and lungs. This effect is strongest on the third day after exposure. These results are similar to the episode that occurred in Manaus in 2001 and suggest that diesel plus cypermethrin home aerosolization for arbovirosis prophylaxis should be revised.

Eosinophilic pneumonitis induced by aerosol-administered diesel oil and pyrethrum to mice / Neumonía eosinofílica inducida por aerosol de aceite diésel y piretroide en ratones

OBJECTIVE: To confirm the episode of eosinophilic pneumonitis that occurred in March 2001 in Manaus, Amazon, northern Brazil, as secondary to home aerosolization with 2 percent cypermethrin diluted in diesel compared with the more conventional 1 percent cypermethrin and soybean solution used in prophylaxis of dengue. METHODS: Four groups of Swiss mice were kept in polycarbonate cages aerosolized with one of the following solutions: diesel, diesel and cypermethrin, soy oil and cypermethrin, and saline. Three and 6 days after exposure, resistance and compliance of the respiratory system and white cell kinetics in peripheral blood and lung tissue were analyzed. RESULTS: The group exposed to diesel and cypermethrin showed higher respiratory system resistance (p < 0.001), lower compliance (p = 0.03), and increased eosinophils in blood (p = 0.03) and lung tissue (p = 0.005) compared with the other groups. There was an increase of neutrophils in the blood of all experimental groups on the third day after exposure (p < 0.001). CONCLUSIONS: We concluded that diesel associated with cypermethrin induced lung hyperresponsiveness in this experimental model and was associated with increased polymorphonuclear cells (eosinophils and neutrophils) in blood and lungs. This effect is strongest on the third day after exposure. These results are similar to the episode that occurred in Manaus in 2001 and suggest that diesel plus cypermethrin home aerosolization for arbovirosis prophylaxis should be revised.

OBJETIVO: Confirmar el episodio de neumonía eosinofílica ocurrido en marzo de 2001 en Manaus, Amazonas, en el norte de Brasil, secundario al uso de aerosol de cipermetrina diluida al 2 por ciento en aceite diésel en las viviendas en comparación con la profilaxis más convencional contra el dengue, basada en cipermetrina al 1 por ciento con aceite de soya. MÉTODOS: Se mantuvieron cuatro grupos de ratones suizos en jaulas de policarbonato y se aplicó aerosol con una de las siguientes soluciones: aceite diésel, aceite diésel y cipermetrina, aceite de soya y cipermetrina, y solución salina. Se analizaron la resistencia y el funcionamiento del sistema respiratorio y la cinética de leucocitos en sangre periférica y tejido pulmonar a los tres y seis días después de la exposición. RESULTADOS: El grupo expuesto a aceite diésel y cipermetrina mostró mayor resistencia del sistema respiratorio (P < 0,001), peor funcionamiento (P = 0,03) y más eosinófilos en sangre (P = 0,03) y tejido pulmonar (P = 0,005) que los otros grupos. Se observó un aumento de neutrófilos en sangre en todos los grupos experimentales al tercer día después de la exposición (P < 0,001). CONCLUSIONES: El aceite diésel con cipermetrina indujo una hiperrespuesta pulmonar en este modelo experimental y se asoció con un aumento en las células polimorfonucleares (eosinófilos y neutrófilos) en sangre y tejido pulmonar. Este efecto es mayor al tercer día después de la exposición. Estos efectos son similares a los observados en el episodio ocurrido en Manaus en 2001 e indican que se debe reevaluar el uso de aerosol de aceite diésel con cipermetrina para la profilaxis de arbovirus en las viviendas.

Talc pleurodesis: evidence of systemic inflammatory response to small size talc particles.

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.

Experimental pleurodesis induced by antibiotics (macrolides or quinolones).

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.

Influence of storage time and temperature on pleural fluid adenosine deaminase determination.

OBJECTIVES AND BACKGROUND: The determination of adenosine deaminase (ADA) activity in pleural fluid is important for differentiation of pleural effusions and diagnosing pleural tuberculosis. Although measurement of ADA is simple and inexpensive, controversies exist regarding potential errors caused by time elapsed between sample collection and analysis, storage temperature and the use of anticoagulants. The objective of this study was to evaluate the influence of storage time (1, 3, 7, 10 and 28 days) and temperature (4 degrees C and -20 degrees C) on the determination of ADA in pleural fluid samples collected in EDTA and sent at ambient temperature to the laboratory for initial processing within 1 h of collection. METHODOLOGY: Twenty-seven pleural exudates obtained from 20 patients with neoplastic disease and seven with tuberculosis were analysed. The ADA activity obtained within 1 h of collection was considered the gold standard and was compared with the other measurements. RESULTS: The correlation between the initial measurement and all others was >or=0.90 for both temperatures up to the 10th day after thoracocentesis and tended to decrease by 28 days after collection, but this difference was not significant. CONCLUSIONS: Pleural fluid samples collected in EDTA and sent for analysis within 1 h after collection can be used to determine ADA up to 28 days after collection if stored at 4 degrees C or -20 degrees C, with no evidence of significant increases or decrease in enzyme activity that might distort the results.

Pleurodesis induced by talc or silver nitrate: evaluation of collagen and elastic fibers in pleural remodeling.

This study evaluated the extracellular matrix (collagen and elastic fibers) in pleurodesis induced by intrapleural talc (TL) or silver nitrate (SN). Study subjects were 420 rabbits divided into two groups and sacrificed from 15 min to 12 months after the injection of the sclerosing agents at intervals previously defined. Pleural adhesions and fibrosis were graded (0-4), and the collagen and elastin were quantified. The maximum score of the pleural adhesions was observed two months after TL (2.80 +/- 0.99) and 15 days after SN (3.75 +/- 0.25). More intense pleural adhesions were observed in the SN group from day 5 (p < 0.05). Pleural thickness and pleural fibrosis were, in general, significantly higher after SN (p < 0.05). Increased deposition of collagen and elastin was observed in both groups but was more evident in the SN group. In the TL group, a linear correlation was observed between pleural adhesions and fibrosis (r = 0.775), between pleural adhesions and collagen (r = 0.779), and between fibrosis and collagen (r = 0.709). In the SN group, these correlations were acceptable (r = 0.605, 0.665, and 0.663). The elastin presented a correlation of 0.707 (p < 0.001) in the TL group and of 0.564 (p < 0.001) in the SN group. In conclusion, intrapleural 0.5% silver nitrate and talc (400 mg/kg) are effective in the induction of pleurodesis. However, the intensity of adhesions and the richness of collagen after SN, in combination with the early onset of tissue remodeling, demonstrate the local superiority of this agent. Considering the easy availability and instillation, the low cost, and the absence of important side effects, silver nitrate might be considered as a sclerosing agent to induce pleurodesis in humans.

Experimental pleurodesis induced by antibiotics (macrolides or quinolones) / Pleurodese experimental induzida por antibióticos (macrolídeos e quinolonas)

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.

OBJETIVO: A pleurodese química representa uma ferramenta terapêutica utilizada no tratamento dos processos pleurais recidivantes, principalmente nos derrames neoplásicos. A escolha do melhor esclerosante pleural é ainda motivo de controvérsia, não havendo consenso com relação ao agente considerado ideal. O objetivo deste estudo é avaliar a efetividade dos macrolídeos (azitromicina e claritromicina) e das quinolonas (levofloxacina e gatifloxacina) na indução de pleurodese experimental em coelhos. MÉTODOS: Quarenta animais randomizados em grupos de 10, receberam, em volume total de 2 mL, estas drogas através de injeção intrapleural. RESULTADOS: Após 28 dias, os animais foram sacrificados sendo avaliada a cavidade pleural. A intensidade das aderências macroscópicas assim como da fibrose e da inflamação observadas à microscopia foi discreta tanto no grupo que recebeu macrolídeos quanto naquele que recebeu quinolonas. CONCLUSÃO: Azitromicina, Claritromicina, Levofloxacina e Gatifloxacina quando injetados na cavidade pleural de coelhos, não são eficazes na indução de pleurodese. Novas pesquisas devem ser realizadas com o intuito de identificar agentes esclerosantes capazes de produzir sínfise pleural.

Influence of antiinflammatory drugs (methylprednisolone and diclofenac sodium) on experimental pleurodesis induced by silver nitrate or talc.

STUDY OBJECTIVE: To determine whether the administration of antiinflammatory drugs interferes with experimental pleurodesis induced by silver nitrate or talc. STUDY DESIGN: Two groups of 30 white New Zealand rabbits were scheduled to receive an intrapleural injection of 0.5% silver nitrate or 400 mg/kg of talc. Each group was further classified into three subgroups (10 animals each), which received the following: (subgroup 1) the sclerosing agent only, (subgroup 2) the sclerosing agent plus 1 mg/kg of methylprednisolone, and (subgroup 3) the sclerosing agent plus 1.1 mg/kg of diclofenac sodium. The antiinflammatory agents were administered IM 24 h before the sclerosing agent and daily during the first week, followed by once-weekly injections until death at 28 days. At this time, the pleural cavity was macroscopically evaluated, and samples of pleura and lungs were collected for further microscopic examination. MEASUREMENTS AND RESULTS: The degree of pleural adhesions was higher after silver nitrate administration (p = 0.019). No reduction in the adhesions was observed after administering antiinflammatory drugs to this group (p > 0.05). Conversely, the adhesion score was significantly reduced after administration of both prednisolone (p = 0.028) and diclofenac (p = 0.032) to the animals that received talc. Administration of the antiinflammatory agents did not influence microscopic pleural or lung changes induced by silver nitrate or talc. CONCLUSION: These results show that the sustained systemic administration of antiinflammatory agents (steroidal or nonsteroidal) reduces the degree of pleural adhesions in animals with talc-induced pleurodesis but does not affect silver nitrate-induced pleurodesis. Extrapolation of these results to humans suggests that the use of antiinflammatory drugs should be avoided in patients with talc-induced pleurodesis and that appropriate clinical studies with silver nitrate should be conducted in patients chronically treated with these antiinflammatory agents.