RESUMO
A study of Quantitative Structure Activity Relationship (QSAR) was performed to assess the possible adverse effects of 25 pharmaceuticals commonly found in the Brazilian water compartments and to establish a ranking of environmental concern. The occurrence (O), the persistence (P), the mobility (M), and the toxicity (T) of these compounds in the Brazilian drinking water reservoirs were evaluated. Moreover, to verify the predicted OPMT dataset outcomes, a quality index (QI) was also developed and applied. The main results showed that: (i) after in silico predictions through VEGA QSAR, 19 from 25 pharmaceuticals consumed in Brazil were classified as persistent; (ii) moreover, after in silico predictions through OPERA QSAR, 15 among those 19 compounds considered persistent, were also classified as mobile or very mobile. On the other hand, the results of toxicity indicate that only 9 pharmaceuticals were classified with the highest toxicity level. Ultimately, the QI of 7 from 25 pharmaceuticals were categorized as 'optimal'; 15 pharmaceuticals were categorized as 'good'; and only 3 pharmaceuticals were categorized as 'regular'. Therefore, based on the QI criteria used, it is possible to assume that this OPMT prediction dataset had a good reliability. Efforts to reduce emissions of OPMT-pharmaceuticals in Brazilian drinking water reservoirs are encouraged.
Assuntos
Água Potável , Poluentes Químicos da Água , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/química , Brasil , Reprodutibilidade dos Testes , Relação Quantitativa Estrutura-Atividade , Preparações Farmacêuticas , Medição de RiscoRESUMO
Sixty Centropomus parallelus juveniles were collected in March 2013 in two locations (Tromomó and Guaraguaçu) inside the Paranaguá estuarine complex, southern Brazil. The habitat residency and movement patterns of the individuals were inferred from Sr:Ca ratios and age recorded in the otoliths. Data suggest that the species spawns preferentially in brackish areas mainly from October to January, and that growth rate during the early juvenile stage could be influenced by environmental salinity. Furthermore, the data also show that C. parallelus can occupy diverse salinity habitats and migrate among marine, brackish and freshwater areas within the Paranaguá estuarine complex, showing a high environmental plasticity and adaptation.
Assuntos
Distribuição Animal , Ecossistema , Peixes/fisiologia , Animais , Brasil , Peixes/crescimento & desenvolvimento , Água Doce , Internato e Residência , SalinidadeRESUMO
Cystic fibrosis (CF) an autosomal recessive genetic disorder, affects many organs. The great majority of deaths occur due to respiratory failure after many years of chronic pulmonary infection. Despite recent progress in early detection by studies of genetic mutations and better understanding to treat nutritional and infectious states, lung transplantation is the CF treatment for most advanced cases. According to the International Society for Heart and Lung Transplantation (ISHLT) data, CF is the third most common reason for lung transplantation (16.8%) showing the best survival rate (60% at 5 years). We have described our experience in lung transplantation of CF patients between January 2000 and December 2011, reviewing medical charts of these patients were for gender, age, body mass index (BMI), comorbidities, disease duration, previous sputum gram stain, ischemic time, incidence of severe primary graft dysfunction (PGD Grade 3), intensive care unit (ICU) length of stay, and Kaplan-Meier survival. Among 150 lung transplantation, the 30 CF patients (20%) represented the second most common cause. The average age was 27.4 ± 9.2 years, with a slight predominance of males (n = 16; 53.3%). The average BMI was 18.9 ± 2.6. Most patients (60%) had pancreatic exocrine dysfunction. Also, 83.3% of patients showed a positive sputum culture for Pseudomonas, while Burkholderia cepacia was identified in only 4 patients (13.3%). The average time of the disease was 20.8 ± 9.7 years. All transplantation were bilateral with an average ischemic time of 472 ± 98.3 minutes and ICU length of stay of 9.9 ± 6.3 days. The survival rates at 1 and 5 years were 92% and 77%, respectively, corresponding to the best outcomes among underlying diseases, comparable with other worldwide series and better than the ISHLT reports. CF, the second most common cause for lung transplantation among our cases, showed the best survival rate among all causes. Our survival rate was comparable with other reports.
Assuntos
Fibrose Cística/cirurgia , Transplante de Pulmão , Adolescente , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Lung transplantation has become a standard procedure for some end-stage lung diseases, but primary graft dysfunction (PGD) is an inherent problem that impacts early and late outcomes. The aim of this study was to define the incidence, risk factors, and impact of mechanical ventilation time on mortality rates among a retrospective cohort of lung transplantations performed in a single institution. METHODS: We performed a retrospective study of 118 lung transplantations performed between January 2003 and July 2010. The most severe form of PGD (grade III) as defined at 48 and 72 hours was examined for risk factors by multivariable logistic regression models using donor, recipient, and transplant variables. RESULTS: The overall incidence of PGD at 48 hours was 19.8%, and 15.4% at 72 hours. According multivariate analysis, risk factors associated with PGD were donor smoking history for 48 hours (adjusted odds ratio [OR], 4.83; 95% confidence interval [CI], 1.236-18.896; P = .022) and older donors for 72 hours (adjusted OR, 1.046; 95% CI, 0.997-1.098; P = .022). The operative mortality was 52.9% among patients with PGD versus 20.3% at 48 hours (P = .012). At 72 hours, the mortality rate was 58.3% versus 21.2% (P = .013). The 90-days mortality was also higher among patients with PGD. The mechanical ventilation time was longer in patients with PGD III at 48 hours namely, a mean time of 72 versus 24 hours (P = .001). When PGD was defined at 72 hours, the mean ventilation time was even longer, namely 151 versus 24 hours (P < .001). The mean overall survival for patients who developed PGD at 48 hours was 490.9 versus 1665.5 days for subjects without PGD (P = .001). Considering PGD only at 72 hours, the mean survival was 177.7 days for the PGD group and 1628.9 days for the other patients (P < .001). CONCLUSION: PGD showed an important impacts on operative and 90-day mortality rates, mechanical ventilation time, and overall survival among lung transplant patients. PGD at 72 hours was a better predictor of lung transplant outcomes than at 48 hours. The use of donors with a smoking history or of advanced age were risk factors for the development of PGD.
Assuntos
Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/epidemiologia , Adulto , Fatores Etários , Brasil/epidemiologia , Seleção do Doador , Feminino , Humanos , Incidência , Modelos Logísticos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Disfunção Primária do Enxerto/mortalidade , Modelos de Riscos Proporcionais , Respiração Artificial/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Fatores de Tempo , Doadores de Tecidos/provisão & distribuição , Resultado do Tratamento , Adulto JovemRESUMO
All transplant patients are at increased risk of developing pulmonary infections, a significant cause of morbidity and mortality. Immunosuppressants increase the incidence of lung infection by acting not only directly on the inflammatory cells, but also on the native immune system. Experimental studies have shown corticosteroid therapy, which is used in most immunosuppressive protocols after transplantation, to suppress mucus production by inhibiting calceiform. The objective of this study was to evaluate the effects of prednisone on mucociliary clearance. A total of 120 male Wistar rats were distributed into 4 groups. Animals in P1, P2, and P3 groups received daily doses of prednisone (0.625, 1.25, and 2.5 mg/kg/d), and hosts in the Sal group underwent gavage with saline solution (2.5 mL/d). After 7, 15, and 30 days, treatment, animals were killed. We assessed ciliary beating frequency (CBF), mucociliary transport velocity (MCTV), and mucus transportability (MT). There was no significant difference for CBF regarding dose (P = .089) or treatment duration (P = .175). MCTV values of 0.60 ± 0.14 in group P1, 0.59 ± 0.13 in group P2, 0.51 ± 0.19 in group P3, and 0.61 ± 0.08 Group Sal, showed P3 to significantly differ from P1 (P = .048) and Sal (P = .007) groups. Regardless of the prednisone dose, all groups displayed impaired MT compared with the Sal group: P1 (P = .02); P2 (P = .02) P3 (P = .03). There was no interaction between the therapy and the treatment time for CBF (P = .10), MCTV (P = .71), and MT (P = .64). Prednisone reduced the transportability of mucus even when administered at low doses; however, this change was not sufficient to alter the mucociliary clearance. Only high doses of prednisone impaired mucociliary clearance.
Assuntos
Corticosteroides/farmacologia , Imunossupressores/farmacologia , Pulmão/efeitos dos fármacos , Depuração Mucociliar/efeitos dos fármacos , Muco/metabolismo , Prednisona/farmacologia , Corticosteroides/toxicidade , Animais , Relação Dose-Resposta a Droga , Imunossupressores/toxicidade , Pulmão/metabolismo , Masculino , Modelos Animais , Prednisona/toxicidade , Ratos , Ratos Wistar , Fatores de TempoRESUMO
INTRODUCTION: In lung transplantation, graft dysfunction is a frequent cause of mortality; the etiopathogenesis is related to ischemia-reperfusion injury. We sought to compare the lung performance of rats after reperfusion after presentation with 3 solutions at 2 ischemia times. METHODS: We randomized 60 male Wistar rats to undergo anterograde perfusion via the pulmonary artery with low-potassium dextran (LPD), histidine-tryptophan ketoglutarate (HTK), or saline. After extraction, the heart-lung blocks were preserved in a solution at hypothermia for 6 or 12 hours before perfusion with homologous blood for 60 minutes using ex vivo system Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus). Respiratory mechanics, pulmonary weight, pulmonary artery pressure (PAP), and relative lung oxygenation capacity (ROC) measurements were obtained every 10 minutes. RESULTS: Comparing tidal volume (TV), compliance, resistance, ROC, PAP, and pulmonary weight the LPD, HTK, and saline group did not differ at 6 and 12 hours. The TV was higher in the lungs with 6-hour ischemia in the LPD, HTK, and saline groups. Compliance was higher in the lungs with 6-hour ischemia in the LPD and saline groups. There were no differences in ROC values comparing lungs with 6- versus 12-hour ischemia in the LPD group. A significant difference was observed between lungs in the HTK and saline groups. Resistance was higher in the lungs with 12-hour ischemia among the LPD, HTK, and saline groups. There was a gradual weight increase in the lungs, particularly those undergoing 12-hour ischemia, despite the absence of a significant difference between groups. CONCLUSION: Rat lungs perfused with LPD and HTK preservation solutions showed similar reperfusion performances in this ex-vivo perfusion model.
Assuntos
Dextranos , Pulmão/fisiologia , Perfusão , Potássio/análise , Animais , Glucose , Cobaias , Técnicas In Vitro , Masculino , Manitol , Oxigênio/metabolismo , Cloreto de Potássio , Procaína , Ratos , Ratos WistarRESUMO
INTRODUCTION: Lung transplantation, a consolidated treatment for end-stage lung disease, utilizes preservation solutions, such as low potassium dextran (LPD), to mitigate ischemia-reperfusion injury. We sought the local development of LPD solutions in an attempt to facilitate access and enhance usage. We also sought to evaluate the effectiveness of a locally manufactured LPD solution in a rat model of ex vivo lung perfusion. METHODS: We randomized the following groups \?\adult of male Wistar rats (n = 25 each): Perfadex (LPD; Vitrolife, Sweden); locally manufactured LPD-glucose (LPDnac) (Farmoterapica, Brazil), and normal saline solution (SAL) with 3 ischemic times (6, 12, and 24 hours). The harvested heart-lung blocks were flushed with solution at 4°C. After storage, the blocks were connected to an IL-2 Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus) and reperfused with homologous blood for 60 minutes. Respiratory mechanics, pulmonary artery pressure, perfusate blood gas analysis, and lung weight were measured at 10-minute intervals. Comparisons between groups and among ischemic times were performed using analysis of variance with a 5% level of significance. RESULTS: Lungs preserved for 24 hours were nonviable and therefore excluded from the analysis. Those preserved for 6 hours showed better ventilatory mechanics when compared with 12 hours. The oxygenation capacity was not different between lungs flushed with LPD or LPDnac, regardless of the ischemic time. SAL lungs showed higher PCO(2) values than the other solutions. Lung weight increased over time during perfusion; however, there were no significant differences among the tested solutions (LPD, P = .23; LPDnac, P = .41; SAL, P = .26). We concluded that the LPDnac solution results in gas exchange were comparable to the original LPD (Perfadex); however ventilatory mechanics and edema formation were better with LPD, particularly among lungs undergoing 6 hours of cold ischemia.