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

Treatment of winery wastewater by combined almond skin coagulant and sulfate radicals: assessment of HSO5− activators

The large production of wine and almonds leads to the generation of sub-products, such as winery wastewater (WW) and almond skin. WW is characterized by its high content of recalcitrant organic matter (biodegradability index < 0.30). Therefore, the aim of this work was to (1) apply the coagulation–flocculation–decantation (CFD) process with an organic coagulant based on almond skin extract (ASE), (2) treat the organic recalcitrant matter through sulfate radical advanced oxidation processes (SR-AOPs) and (3) evaluate the efficiency of combined CFD with UV-A, UV-C and ultrasound (US) reactors. The CFD process was applied with variation in the ASE concentration vs. pH, with results showing a chemical oxygen demand (COD) removal of 61.2% (0.5 g/L ASE, pH = 3.0). After CFD, the germination index (GI) of cucumber and corn seeds was ≥80%; thus, the sludge can be recycled as fertilizer. The SR-AOP initial conditions were achieved by the application of a Box–Behnken response surface methodology, which described the relationship between three independent variables (peroxymonosulfate (PMS) concentration, cobalt (Co2+) concentration and UV-A radiation intensity). Afterwards, the SR-AOPs were optimized by varying the pH, temperature, catalyst type and reagent addition manner. With the application of CFD as a pre-treatment followed by SR-AOP under optimal conditions (pH = 6.0, [PMS] = 5.88 mM, [Co2+] = 5 mM, T = 343 K, reaction time 240 min), the COD removal increased to 85.9, 82.6 and 80.2%, respectively, for UV-A, UV-C and US reactors. All treated wastewater met the Portuguese legislation for discharge in a municipal sewage network (COD ≤ 1000 mg O2/L). As a final remark, the combination of CFD with SR-AOPs is a sustainable, safe and clean strategy for WW treatment and subproduct valorization.Fundação para a Ciência e a Tecnologia | Ref. UIDB/00616/2020Fundação para a Ciência e a Tecnologia | Ref. UI/BD/150847/2020CCRN - Comissão de Coordenação da Região Norte | Ref. NORTE-01- 0145-FEDER-00004

Effectiveness of silver nitrate compared to talc slurry as pleural sclerosing agent in rabbits. Influence of concomitant intrapleural lidocaine

Não está ainda definido, qual o agente ideal para a produção de uma pleurodese efetiva. O talco é o agente mais freqüentemente utilizado apesar de suas manifestações colaterais. Outra possibilidade é o nitrato de prata, largamente usado no passado. OBJETIVOS: Determinar a influência da injeção intrapleural de lidocaina na produção de pleurodese com nitrato de prata, definir o efeito da lidocaina na maturação das fibras colágenas e confirmar que a pleurodese produzida pelo nitrato de prata é mais potente que a conseqüente à injeção intrapleural de talco. MÉTODOS: Foram estudados três grupos de 8 coelhos. Dois receberam nitrato de prata a 0,5%; em um deles, foi injetado previamente 0,5 ml de lidocaina a 2%. O terceiro grupo recebeu 2 ml de talco (400 mg/kg). Os animais foram sacrificados após 28 dias da injeção intrapleural e as cavidades pleurais examinadas macroscopicamente, analisando-se a presença de fusão entre os folhetos pleurais e microscopicamente avaliando-se a inflamação e a fibrose. Quantificou-se o total de colágeno na pleura e a distribuição de fibras finas e grossas, utilizando-se a coloração de pricrosirius. RESULTADOS: Nos dois grupos em que se injetou nitrato de prata (s/ lidocaina: 3.5 + 0.3 e com lidocaina: 3.2 + 0.3), a pleurodese macroscópica (scala 0 - 4) foi significantemente (p = 0.001) melhor do que a pleurodese resultante do talco (1.6 + 0.2). A média da fibrose pleural induzida pelo nitrato de prata (3.5 + 0.2) foi significantemente (p = 0.004) mais acentuada do que a produzida por talco (1.9 + 0.1). A instilação prévia de lidocaina determinou tendência a diminuir a quantidade de fibrose (3.1 + 0.4). A média (10³mm²) do colágeno pleural foi significantemente (p = 0.009) maior nos coelhos que receberam nitrato de prata (116.9 + 22.7) do que naqueles que receberam talco (10.7 + 3.4). A injeção de lidocaina reduziu discretamente o colágeno (80.1 + 30.3). A distribuição das fibras colágenas não foi diferente entre os grupos estudados. CONCLUSÃO: Este modelo animal confirma que, o nitrato de prata injetado no espaço pleural mais efetivo do que o talco na produção de pleurodese. A injeção intrapleural de lidocaina determina uma tendência a reduzir a quantidade de colágeno, mas não muda a efetividade da sínfise pleural ou modifica a maturação do colágeno.The ideal agent for producing pleurodesis has not been identified. Talc, the most commonly used, poses several problems. Another possibility is silver nitrate, which was widely used in the past. PURPOSE: To determine the influence of the intrapleural instillation of lidocaine in producing a pleurodesis with silver nitrate, to define the effect of lidocaine in the maturation of the collagen fibers, and to confirm that the pleurodesis after silver nitrate is stronger than after talc. METHODS: We studied three groups of 8 rabbits. Two groups received 0.5% silver nitrate; in one we had previously injected 0.5 ml of 2% lidocaine. The third group received 400 mg/kg talc (2 ml). The animals were sacrificed 28 days after the injection, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of inflammation and fibrosis. The total amount of pleural collagen and the distribution of thick and thin collagen fibers were quantified. Collagen was identified using picrosirius red stain. RESULTS: In the two groups that received silver nitrate (without lidocaine: 3.5 + 03 and with lidocaine: 3.2 + 0.3), the macroscopic pleurodesis (scale 0 -- 4) was significantly (p = 0.001) better than that resulting from talc (1.6 + 0.2). The mean degree of pleural fibrosis induced by silver nitrate (3.5 + 0.2) was significantly (p = 0.004) higher than that induced by talc (1.9 + 0.1). The previous instillation of lidocaine resulted in a tendency for decreased amounts of fibrosis (3.1 + 0.4). The mean amount (10³mm²) of pleural collagen was significantly (p = 0.009) greater in the rabbits that received silver nitrate (116.9 + 22.7) than in those that received talc (10.7 + 3.4). The injection of lidocaine slightly reduced the collagen (80.1 + 30.3). The distribution of collagen fibers did not differ among the groups. CONCLUSION: This rabbit model clearly confirms that intrapleural silver nitrate is more effective than talc for producing pleurodesis. The previous intrapleural instillation of lidocaine results in a decreasing trend in the amount of collagen, but does not change the effectiveness of the pleural fusion or modify the process of collagen maturation

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&#45;pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin&#45;8, tumor necrosis factor&#45;&#945;, and transforming growth factor&#45;&#946;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&#45;&#946;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&#45;&#945; levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin&#45;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&#45;&#945; 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

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

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. (C) 2008 Elsevier Ltd. All rights reserved.State of Sao Paulo Research woundation (FAPESP)National Board of Scientific and Technologic Development (CNPq), Brazil

Low doses of silver nitrate induce pleurodesis with a limited systemic response

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.Foundation to Support Research of the State of Sao Paulo[FAPESP 99/02777-3

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.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

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.Foundation to Support Research of the State of Sao Paulo (FAPESP)National Council of Research (CNPq), Brazi