H1-antihistamines as antischistosomal drugs: in vitro and in vivo studies.

BACKGROUND: Schistosomiasis is a socioeconomically devastating parasitic infection afflicting hundreds of millions of people and animals worldwide. It is the most important helminth infection, and its treatment relies solely on the drug praziquantel. Oral H1-antihistamines are available worldwide, and these agents are among the most widely used of all medications in children and adults. Given the importance of the drug repositioning strategy, we evaluated the antischistosomal properties of the H1-antihistamine drugs commonly used in clinical practices. METHODS: Twenty-one antihistamine drugs were initially screened against adult schistosomes ex vivo. Subsequently, we investigated the anthelmintic properties of these antihistamines in a murine model of schistosomiasis for both early and chronic S. mansoni infections at oral dosages of 400 mg/kg single dose or 100 mg/kg daily for five consecutive days. We also demonstrated and described the ability of three antihistamines to induce tegumental damage in schistosomes through the use of scanning electron microscopy. RESULTS: From phenotypic screening, we found that desloratadine, rupatadine, promethazine, and cinnarizine kill adult S. mansoni in vitro at low concentrations (5-15 µM). These results were further supported by scanning electron microscopy analysis. In an animal model, rupatadine and cinnarizine revealed moderate worm burden reductions in mice harboring either early or chronic S. mansoni infection. Egg production, a key mechanism for both transmission and pathogenesis, was also markedly inhibited by rupatadine and cinnarizine, and a significant reduction in hepatomegaly and splenomegaly was recorded. Although less effective, desloratadine also revealed significant activity against the adult and juvenile parasites. CONCLUSIONS: Although the worm burden reductions achieved are all only moderate, comparatively, treatment with any of the three antihistamines is more effective in early infection than praziquantel. On the other hand, the clinical use of H1-antihistamines for the treatment of schistosomiasis is highly unlikely.

Promethazine exhibits antiparasitic properties in vitro and reduces worm burden, egg production, hepato-, and splenomegaly in a schistosomiasis animal model.

The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoni ex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility, viability, and it induced severe tegumental damage in schistosomes. The LC50 of the drug was 5.84 µM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg for five successive days at different intervals from the time of infection, for the evaluation of the stage-specific susceptibility (pre-patent and patent infections). Various parasitological criteria indicated the in vivo antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, and hepato- and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (> 90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an antischistosomal agent.

Polydimethylsiloxane/nano calcium phosphate composite tracheal stents: Mechanical and physiological properties.

In this study, we report the production and characterization of tracheal stents composed of polydimethylsiloxane/nanostructured calcium phosphate composites obtained by reactive synthesis. Tracheal stents were produced by transfer molding, and in vivo tests were carried out. PDMS was combined with H3 PO4 and Ca(OH)2 via an in situ reaction to obtain nanoparticles of calcium phosphate dispersed within the polymeric matrix. The incorporation of bioactive inorganic substances, such as calcium phosphates, improved biological properties, and the in situ reaction allowed tight coupling of particles to the matrix. Results showed the presence of the nanoparticles of DCPA and CDHA. The porosity generated during mixing decreased the tensile strength and tear properties. Composites presented higher values of cell viability compared with those for PDMS. In vivo tests indicated the presence of inflammatory tissue 30 days after implantation in both cases. Thus, the present biomaterial shows potential for application in tracheal disease, however further evaluation is needed. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 545-553, 2019.

Antiparasitic, structural, pharmacokinetic, and toxicological properties of riparin derivatives.

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is one of the most important parasitic diseases in the world, affecting over 200 million people in developing countries. Riparins are natural alkamides found in Aniba riparia (Lauraceae) fruits that possess several pharmacological properties. In this study, we reported the synthesis, characterization and structural analysis of six riparin derivatives (A-F), as well as their schistosomicidal activity against S. mansoni worms together with a biological, pharmacokinetic and toxicological in silico evaluation. Firstly, these compounds were synthesized, purified and characterized by elemental analysis, FT-IR spectroscopy, X-ray diffraction and theoretical calculations to evaluate their stability and conformation. Next, the schistosomicidal activity of the riparins was tested against S. mansoni worms. Bioassays revealed that Riparins E and F were the most active compounds, showing half-maximum inhibitory concentration at low micromolar ranges (IC50 values ~10 µM). Also, confocal laser scanning microscopy studies revealed tegumental damage in parasites after exposition with Riparins B, E and F. Additionally, based on MTT assay, all tested riparins showed no cytotoxic potential toward mammalian cells. Finally, in silico analyses were used to predict the absorption, distribution, metabolism, elimination and toxicity (ADMET) of the compounds. Taken together, the results revealed a promising ADMET profile and suggested that riparins could be starting points for lead optimization programs for natural products with antischistosomal properties.

Antischistosomal agents: state of art and perspectives.

Praziquantel has remained the drug of choice for schistosomiasis chemotherapy for almost 40 years. The pressing need to develop a new antischistosomal drug may necessitate exploring and filtering chemotherapeutic history to search for the most promising ones. In this context, this review attempts to summarize all progress made in schistosomiasis chemotherapy from the early 20th century (mid-1910s) to 2016. We gathered almost 100 compounds providing information on therapeutic action, specifically covering at least first in vivo studies in animal model and in vitro. Pharmacokinetic and toxicity profiles of antischistosomal agents were also described. Preclinical studies indicate a handful of promising future candidates.

Fiber-reinforced silicone for tracheobronchial stents: An experimental study.

A trachea is a tubular structure composed of smooth muscle that is reinforced with cartilage rings. Some diseases can cause sagging in smooth muscle and cartilaginous tissue. The end result is reduction (narrowing) of the trachea diameter. A solution to this problem is the use of tracheal stents, which are small tubular devices made of silicone. One is inserted into the trachea to prevent or correct its constriction. The purpose of tracheal stent use is to maintain cartilage support that would otherwise be lost in the airway. Current tracheal stent models present limitations in terms of shape and characteristics of the silicone used in their production. One of the most important is the large thickness of the wall, which makes its placement difficult; this mainly applies to pediatric patients. The wall thickness of the stent is closely related to the mechanical properties of the material. This study aims to test the reinforcement of silicone with three kinds of fibers, and then stents that were produced using fiber with the best compressive strength characteristics. Silicone samples were reinforced with polypropylene (PP), polyamide (PA), and carbon fiber (CF) at concentrations of 2% and 4% (vol%), which then underwent tensile strength and Shore A hardness testing. Samples with fiber showed good characteristics; surface analyses were carried out and they were used to produce stents with an internal diameter of 11 or 13mm and a length of 50mm. Stents underwent compression tests for qualitative evaluation. Samples with 2% and 4% CF blends showed the best mechanical performance, and they were used to produce stents. These samples presented similar compressive strengths at low deformation, but stents with a 4% CF blend exhibited improved compressive strength at deformations greater than 30-50% of their diameter (P ≤ 0.05). The addition of 2% and 4% CF blends conferred greater mechanical strength and resistance to the silicone matrix. This is particularly true at low deformation, which is the condition where the stent is used when implanted. In the finite element compression strength tests, the stent composite showed greater compression strength with the addition of fiber, and the results were in accordance with mechanical compression tests performed on the stents. In vivo tests showed that, after 30 days of post-implantation in sheep trachea, an inflammatory process occurred in the region of the trachea in contact with the stent composite and with the stent without fiber (WF). This response is a common process during the first few days of implantation.

Changes in respiratory mechanics during respiratory physiotherapy in mechanically ventilated patients.

OBJECTIVE: To evaluate the changes in ventilatory mechanics and hemodynamics that occur in patients dependent on mechanical ventilation who are subjected to a standard respiratory therapy protocol. METHODS: This experimental and prospective study was performed in two intensive care units, in which patients dependent on mechanical ventilation for more than 48 hours were consecutively enrolled and subjected to an established respiratory physiotherapy protocol. Ventilatory variables (dynamic lung compliance, respiratory system resistance, tidal volume, peak inspiratory pressure, respiratory rate, and oxygen saturation) and hemodynamic variables (heart rate) were measured one hour before (T-1), immediately after (T0) and one hour after (T+1) applying the respiratory physiotherapy protocol. RESULTS: During the period of data collection, 104 patients were included in the study. Regarding the ventilatory variables, an increase in dynamic lung compliance (T-1 = 52.3 ± 16.1mL/cmH2O versus T0 = 65.1 ± 19.1mL/cmH2O; p < 0.001), tidal volume (T-1 = 550 ± 134mL versus T0 = 698 ± 155mL; p < 0.001), and peripheral oxygen saturation (T-1 = 96.5 ± 2.29% versus T0 = 98.2 ± 1.62%; p < 0.001) were observed, in addition to a reduction of respiratory system resistance (T-1 = 14.2 ± 4.63cmH2O/L/s versus T0 = 11.0 ± 3.43cmH2O/L/s; p < 0.001), after applying the respiratory physiotherapy protocol. All changes were present in the assessment performed one hour (T+1) after the application of the respiratory physiotherapy protocol. Regarding the hemodynamic variables, an immediate increase in the heart rate after application of the protocol was observed, but that increase was not maintained (T-1 = 88.9 ± 18.7 bpm versus T0 = 93.7 ± 19.2bpm versus T+1 = 88.5 ± 17.1bpm; p < 0.001). CONCLUSION: Respiratory therapy leads to immediate changes in the lung mechanics and hemodynamics of mechanical ventilation-dependent patients, and ventilatory changes are likely to remain for at least one hour.

Alterações da mecânica ventilatória durante a fisioterapia respiratória em pacientes ventilados mecanicamente / Changes in respiratory mechanics during respiratory physiotherapy in mechanically ventilated patients

RESUMO Objetivo: Avaliar as alterações da mecânica ventilatória e da hemodinâmica que ocorrem em pacientes dependentes de ventilação mecânica submetidos a um protocolo padrão de fisioterapia respiratória. Métodos: Estudo experimental e prospectivo realizado em duas unidades de tratamento intensivo, nas quais pacientes dependentes de ventilação mecânica por mais de 48 horas foram alocados, de forma consecutiva, e submetidos a um protocolo estabelecido de manobras de fisioterapia respiratória. Variáveis ventilatórias (complacência pulmonar dinâmica, resistência do sistema respiratório, volume corrente, pressão de pico inspiratório, frequência respiratória e saturação periférica de oxigênio) e hemodinâmicas (frequência cardíaca) foram mensuradas 1 hora antes (T-1), imediatamente (T0) e após 1 hora (T+1) da realização do protocolo de manobras de fisioterapia respiratória. Resultados: Durante o período de coleta dos dados, 104 pacientes foram incluídos no estudo. Quanto às variáveis ventilatórias, houve aumento da complacência pulmonar dinâmica (T-1 = 52,3 ± 16,1mL/cmH2O versus T0 = 65,1 ± 19,1mL/cmH2O; p < 0,001), do volume corrente (T-1 = 550 ± 134mL versus T0 = 698 ± 155mL; p < 0,001) e da saturação periférica de oxigênio (T-1 = 96,5 ± 2,29% versus T0 = 98,2 ± 1,62%; p < 0,001), além de redução da resistência do sistema respiratório (T-1 = 14,2 ± 4,63cmH2O/L/s versus T0 = 11,0 ± 3,43cmH2O/L/s; p < 0,001) logo após a realização das manobras de fisioterapia respiratória. Todas as alterações se mantiveram na avaliação realizada 1 hora (T+1) após as manobras de fisioterapia respiratória. Já com relação às variáveis hemodinâmicas, houve elevação imediata, porém não sustentada da frequência cardíaca (T-1 = 88,9 ± 18,7bpm versus T0 = 93,7 ± 19,2bpm versus T+1 = 88,5 ± 17,1bpm; p < 0,001). Conclusão: Manobras de fisioterapia respiratória geram mudanças imediatas na mecânica pulmonar e na hemodinâmica dos pacientes dependentes da ...

ABSTRACT Objective: To evaluate the changes in ventilatory mechanics and hemodynamics that occur in patients dependent on mechanical ventilation who are subjected to a standard respiratory therapy protocol. Methods: This experimental and prospective study was performed in two intensive care units, in which patients dependent on mechanical ventilation for more than 48 hours were consecutively enrolled and subjected to an established respiratory physiotherapy protocol. Ventilatory variables (dynamic lung compliance, respiratory system resistance, tidal volume, peak inspiratory pressure, respiratory rate, and oxygen saturation) and hemodynamic variables (heart rate) were measured one hour before (T-1), immediately after (T0) and one hour after (T+1) applying the respiratory physiotherapy protocol. Results: During the period of data collection, 104 patients were included in the study. Regarding the ventilatory variables, an increase in dynamic lung compliance (T-1 = 52.3 ± 16.1mL/cmH2O versus T0 = 65.1 ± 19.1mL/cmH2O; p < 0.001), tidal volume (T-1 = 550 ± 134mL versus T0 = 698 ± 155mL; p < 0.001), and peripheral oxygen saturation (T-1 = 96.5 ± 2.29% versus T0 = 98.2 ± 1.62%; p < 0.001) were observed, in addition to a reduction of respiratory system resistance (T-1 = 14.2 ± 4.63cmH2O/L/s versus T0 = 11.0 ± 3.43cmH2O/L/s; p < 0.001), after applying the respiratory physiotherapy protocol. All changes were present in the assessment performed one hour (T+1) after the application of the respiratory physiotherapy protocol. Regarding the hemodynamic variables, an immediate increase in the heart rate after application of the protocol was observed, but that increase was not maintained (T-1 = 88.9 ± 18.7 bpm versus T0 = 93.7 ± 19.2bpm versus T+1 = 88.5 ± 17.1bpm; p < 0.001). Conclusion: Respiratory therapy leads to immediate changes in the lung mechanics and hemodynamics of mechanical ventilation-dependent patients, and ventilatory changes ...

Avaliação da qualidade de vida e função pulmonar em pacientes com câncer de pulmão / Assessing quality of life and lung function in patients with lung cancer

Introdução: O câncer de pulmão é uma doença muito prevalente e altamente fatal. O objetivo deste estudo foi avaliar a qualidade de vida (QV) e função pulmonar de pacientes com câncer de pulmão do Hospital de Clínicas de Porto Alegre que receberam tratamento cirúrgico e/ou quimio-radioterapia. Métodos: Foi realizado um estudo de coorte, prospectivo, observacional incluindo 92 pacientes ambulatoriais/internações com diagnóstico recente de câncer de pulmão e que ainda não tinham iniciado tratamento, os quais foram submetidos a uma avaliação da QV através do Medical Outcomes Study 36-item Short-Form Health Survey (SF- 36), além de espirometria e teste da caminhada de seis minutos, antes de iniciar o tratamento, após 60 dias e 120 dias do início do mesmo. Resultados: Foram analisados 27 pacientes cirúrgicos, 60 não cirúrgicos, e 5 que não realizaram tratamentos específicos. Predominou o tipo adenocarcinoma e o estádio avançado da doença. Não houve diferença na QV entre os três momentos, mas observou-se um aumento significativo do porcentual de capacidade vital forçada previsto nos primeiros 60 dias no grupo não cirúrgico (p=0,023). Nesse grupo, houve correlação significativa entre as seguintes variáveis: volume expiratório forçado (VEF1 ) e aspectos físicos (r=0,471), distância e dor (r=0,471), distância e vitalidade (r=0,460). No grupo cirúrgico, foi encontrada correlação entre VEF1 e capacidade funcional (r=0,600). Sobrevida foi de 50% nos primeiros 160 dias. Conclusões: Houve correlação positiva entre VEF1 e QV em pacientes com câncer de pulmão, tanto cirúrgicos quanto não cirúrgicos, e entre distância da caminhada e vitalidade em pacientes não cirúrgicos.

Introduction: Lung cancer is a very prevalent and highly fatal disease. The aim of this study was to evaluate quality of life (QL) and lung function in patients with lung cancer from the Hospital de Clinicas de Porto Alegre who underwent surgery and/or chemoradiotherapy. Methods: A prospective, observational cohort study was conducted including 92 outpatients/inpatients with newly diagnosed lung cancer and who had not started treatment yet. They underwent an assessment of QL using the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), spirometry, and the six-minute walk test before treatment, and 60 and 120 days after treatment. Results: A total of 27 surgical and 60 nonsurgical patients was analyzed, together with 5 patients who did not undergo specific treatments. The predominant cancer typewas adenocarcinoma and the predominant stage was advanced disease. There was no difference in QL among the three time points, but a significant increase in percent predicted forced vital capacity was observed in the first 60 days in the nonsurgical group (p=0.023). In this group, there was a significant correlation between the following variables: forced respiratory volume in one second (FEV1 ) and physical aspects (r=0.471), walked distance and pain (r=0.471), and walked distance and vitality (r=0.460). A correlation between FEV1 and functional capacity was found in the surgical group (r=0.600). Survival rates were 50% in the first 160 days. Conclusions: There was a positive correlation between FEV1 and QL in surgical and non-surgical patients with lung cancer, and between walked distance and vitality in nonsurgical patients.

Correlação dos escores de risco com a anatomia coronária na síndrome coronária aguda sem supra-ST / Correlation of risk scores with coronary anatomy in non-ST-elevation acute coronary syndrome

FUNDAMENTO:Há poucas publicações sobre a correlação entre escores de risco e anatomia coronária na síndrome coronária aguda (SCA). OBJETIVO: Correlacionar os escores de risco com a gravidade da lesão coronária na SCA sem supra-ST. MÉTODOS: Foram analisados 582 pacientes entre julho de 2004 e outubro de 2006. Avaliou-se a correlação entre os escores de risco TIMI, GRACE hospitalar e em seis meses com lesão coronária > 50%, por método não paramétrico de Spearman. Modelo de regressão logística múltipla foi realizado para determinar a habilidade preditiva dos escores em discriminar quem terá ou não lesão coronária > 50%. RESULTADOS: Foram 319 (54,8%) homens e a média de idade era 59,9 (± 10,6) anos. Correlação positiva foi observada entre a pontuação dos escores de risco e lesão coronária > 50% (escore de risco TIMI r = 0,363 [p < 0,0001]; escore GRACE hospitalar r = 0,255 [p < 0,0001]; escore GRACE em seis meses r = 0,209 [< 0,0001]). A área sob a curva ROC de cada escore para discriminar quem terá ou não lesão coronária > 50% foi: TIMI = 0,704 [IC95% 0,656-0,752; p <0,0001]; GRACE hospitalar = 0,623 [IC 95% 0,573-0,673; p < 0,0001]; GRACE em seis meses = 0,562 [IC95% 0,510-0,613; p = 0,0255]. Na comparação entre as áreas sob a curva ROC, tem-se: TIMI versus GRACE hospitalar: p = 0,01; TIMI versus GRACE em seis meses: p < 0,0001; GRACE hospitalar versus GRACE em seis meses: p = 0,0461. CONCLUSÃO: Os escores de risco se correlacionam com a gravidade das lesões coronárias, sendo o escore de risco TIMI o que demonstrou melhor habilidade preditiva.

BACKGROUND: The literature lacks studies regarding the correlation between risk scores and coronary anatomy in acute coronary syndrome (ACS) OBJECTIVE: Correlate risk scores with the severity of the coronary lesion in ACS with non-ST elevation. METHODS: A total of 582 patients were analyzed between July 2004 and October 2006. The correlation between TIMI risk scores and GRACE (hospital and six months) scores was performed for patients with coronary lesion > 50%, using Spearman´s non-parametric method. Multiple regression logistics was used to determine the predictive ability of the scores to discriminate to discriminate who will have a coronary lesion > 50%. RESULTS: Most subjects were male (319 or 54.8%), mean age of 59.9 (± 10.6) years. A positive correlation was observed between risk scores and >coronary lesion > 50% (TIMI r = 0.363 [p < 0.0001]; hospital GRACE r = 0.255 [p < 0.0001]; GRACE at six months r = 0.209 [< 0.0001]). The area under the ROC curve for each score to determine to discriminate who will have a coronary lesion > 50% was: TIMI = 0.704 [CI95% 0.656-0.752; p <0.0001]; hospital GRACE = 0.623 [CI95% 0.573-0.673; p < 0.0001]; GRACE at six months= 0.562 [CI95% 0.510-0.613; p ;= 0.0255]. Comparing the areas under the ROC curve, it was found: TIMI versus hospital GRACE: p = 0.01; TIMI versus GRACE at six months:p < 0.0001; hospital GRACE versus GRACE at six months: p = 0.0461. CONCLUSION: Risk scores correlate with the severity of coronary lesions, and the TIMI risk score showed the best predictive ability.

Correlation of risk scores with coronary anatomy in non-ST-elevation acute coronary syndrome.

BACKGROUND: The literature lacks studies regarding the correlation between risk scores and coronary anatomy in acute coronary syndrome (ACS) OBJECTIVE: Correlate risk scores with the severity of the coronary lesion in ACS with non-ST elevation. METHODS: A total of 582 patients were analyzed between July 2004 and October 2006. The correlation between TIMI risk scores and GRACE (hospital and six months) scores was performed for patients with coronary lesion ≥ 50%, using Spearman's non-parametric method. Multiple regression logistics was used to determine the predictive ability of the scores to discriminate to discriminate who will have a coronary lesion ≥ 50%. RESULTS: Most subjects were male (319 or 54.8%), mean age of 59.9 (± 10.6) years. A positive correlation was observed between risk scores and coronary lesion ≥ 50% (TIMI r = 0.363 [p < 0.0001]; hospital GRACE r = 0.255 [p < 0.0001]; GRACE at six months r = 0.209 [< 0.0001]). The area under the ROC curve for each score to determine to discriminate who will have a coronary lesion > 50% was: TIMI = 0.704 [CI95% 0.656-0.752; p <0.0001]; hospital GRACE = 0.623 [CI95% 0.573-0.673; p < 0.0001]; GRACE at six months= 0.562 [CI95% 0.510-0.613; p ;= 0.0255]. Comparing the areas under the ROC curve, it was found: TIMI versus hospital GRACE: p = 0.01; TIMI versus GRACE at six months:p < 0.0001; hospital GRACE versus GRACE at six months: p = 0.0461. CONCLUSION: Risk scores correlate with the severity of coronary lesions, and the TIMI risk score showed the best predictive ability.

Modelo experimental de estenose traqueal mediante ressecção cirúrgica submucosa de anéis traqueais combinada com instilações de hidróxido de sódio / Experimental model of tracheal stenosis with submucosal resection of cartilaginous rings combined with sodium hydroxide instillations

OBJETIVO: Desenvolver, experimentalmente, malácia e estenose traqueal para testar novos modelos de órteses traqueais. MÉTODOS: Ressecamos três anéis cartilaginosos da traqueia cervical de cães no grupo A (n=5) e seis anéis no grupo B (n=4) para produzir malácia. Logo após, a mucosa da região com malácia recebeu aplicações de uma solução de hidróxido de sódio (NaOH) a 23 por cento, e os animais eram acompanhados com exames broncoscópicos para observar o desenvolvimento de estreitamento da luz da via aérea. Quando a estenose era de mais de 50 por cento da luz, ou havia sinais mínimos de insuficiência ventilatória, os animais eram sacrificados. O segmento de via aérea estreitada foi então coletado para análise histológica e era calculada a área de luz residual do segmento traqueal com estenose e malácia. RESULTADOS: Na análise histológica, foi constatada fibrose na submucosa e adventícia, associada a granulomas na mucosa. A luz residual média dos segmentos com estenose foi de 9 por cento e 12 por cento nos grupos A e B, respectivamente, (p>0,05). CONCLUSÃO: A combinação da ressecção de anéis cartilaginosos e da aplicação de NaOH 23 por cento na mucosa respiratória promoveu uma estenose traqueal intensa, porém esteve associada à perda de animais. Novos estudos são necessários para verificar se o emprego isolado de uma das técnicas seria mais seguro e eficaz para desenvolver estenose traqueal.

OBJECTIVE: To experimentally develop tracheal stenosis and malacia to test new models of tracheal stents. METHODS: We resected three cartilaginous rings from the cervical trachea of dogs in group A (n = 5) and six rings in group B (n = 4) to produce malacia. The mucosa of the region with malacia then received applications of a solution of sodium hydroxide (NaOH) at 23 percent, and the animals were accompanied with bronchoscopic examinations to observe the development of luminal narrowing of the airway. When the stenosis was of more than 50 percent or there were minimal signs of ventilatory failure, the animals were sacrificed. The segment of narrowed airway was then collected for histological analysis and calculation of the area of residual lumen in the tracheal segment with stenosis and malacia. RESULTS: In histological analysis, fibrosis was found in the submucosa and adventitia, associated with granulomas in the mucosa. The average residual lumen of the segments with stenosis was 9 percent and 12 percent in groups A and B, respectively (p> 0.05). CONCLUSION: The combination of resection of the cartilaginous rings and the application of 23 percent NaOH in the respiratory mucosa promoted severe tracheal stenosis, but was associated with loss of animals. Further studies are needed to verify that the isolated use of one of the techniques would be safer and more effective to develop tracheal stenosis.

Microbiological quality of drinking rainwater in the inland region of Pajeú, Pernambuco, Northeast Brazil.

Despite all efforts to store and reduce its consumption, water is becoming less inexhaustible and its quality is falling faster. Considering that water is essential to animal life, it is necessary to adopt measures to ensure its sanitary conditions in order to be fit for consumption. The aim of this study was to analyze the microbiological quality of drinking rainwater used by rural communities of Tuparetama, a small town located in Northeast Brazil. The study covered seven rural communities, totaling 66 households. In each household two samples were collected, one from a tank and the other from a clay pot located inside the home, resulting in 132 samples (tank plus clay pot). Approximately 90% of samples were below the standard recommended by the current legislation, being considered unfit for human consumption. Part of this high microbiological contamination of drinking rainwater could be related to the lack of sanitary education and of an adequate sewerage sanitation system.

Microbiological quality of drinking rainwater in the inland region of Pajeú, Pernambuco, Northeast Brazil / Qualidade microbiológica da água potável no interior, região de Pajeú, Pernambuco, nordeste do Brasil

Despite all efforts to store and reduce its consumption, water is becoming less inexhaustible and its quality is falling faster. Considering that water is essential to animal life, it is necessary to adopt measures to ensure its sanitary conditions in order to be fit for consumption. The aim of this study was to analyze the microbiological quality of drinking rainwater used by rural communities of Tuparetama, a small town located in Northeast Brazil. The study covered seven rural communities, totaling 66 households. In each household two samples were collected, one from a tank and the other from a clay pot located inside the home, resulting in 132 samples (tank plus clay pot). Approximately 90 percent of samples were below the standard recommended by the current legislation, being considered unfit for human consumption. Part of this high microbiological contamination of drinking rainwater could be related to the lack of sanitary education and of an adequate sewerage sanitation system.

Apesar de todos os esforços para armazenar e diminuir o seu consumo, a água está se tornando, cada vez menos, inesgotável e sua qualidade vem se reduzindo cada vez mais rápido. Sendo a água imprescindível à vida animal, é necessário que se adotem medidas para garantir sua qualidade higiênico-sanitária a fim de que seja própria para o consumo. O objetivo desse trabalho foi analisar a qualidade microbiológica da água da chuva utilizada pelas comunidades rurais da cidade de Tuparetama, localizada no nordeste do Brasil. O estudo envolveu sete comunidades rurais, totalizando 66 residências. Em cada residência foram coletadas duas amostras, uma da água armazenada na cisterna e outra da água armazenada no pote de barro localizado no interior da residência, resultando em 132 amostras (cisterna mais pote de barro). Aproximadamente, 90 por cento das amostras estavam em desacordo com a Legislação vigente, sendo consideradas impróprias para o consumo humano. Parte dessa elevada contaminação microbiológica da água da chuva armazenada para consumo pode dever-se à falta de educação sanitária e de um sistema de esgotamento sanitário adequado.

Experimental model of tracheal stenosis with submucosal resection of cartilaginous rings combined with sodium hydroxide instillations.

OBJECTIVE: To experimentally develop tracheal stenosis and malacia to test new models of tracheal stents. METHODS: We resected three cartilaginous rings from the cervical trachea of dogs in group A (n = 5) and six rings in group B (n = 4) to produce malacia. The mucosa of the region with malacia then received applications of a solution of sodium hydroxide (NaOH) at 23%, and the animals were accompanied with bronchoscopic examinations to observe the development of luminal narrowing of the airway. When the stenosis was of more than 50% or there were minimal signs of ventilatory failure, the animals were sacrificed. The segment of narrowed airway was then collected for histological analysis and calculation of the area of residual lumen in the tracheal segment with stenosis and malacia. RESULTS: In histological analysis, fibrosis was found in the submucosa and adventitia, associated with granulomas in the mucosa. The average residual lumen of the segments with stenosis was 9% and 12% in groups A and B, respectively (p> 0.05). CONCLUSION: The combination of resection of the cartilaginous rings and the application of 23% NaOH in the respiratory mucosa promoted severe tracheal stenosis, but was associated with loss of animals. Further studies are needed to verify that the isolated use of one of the techniques would be safer and more effective to develop tracheal stenosis.

Development of a new experimental model of intramuscular electrical stimulation of the diaphragm in rabbits.

PURPOSE: To develop an animal model of diaphragmatic electrical stimulation able to generate an appropriate ventilatory support through the direct implantation of electrodes in the diaphragm (electroventilation). METHODS: Six New Zealand female rabbits (2-3 kg) were placed on mechanical ventilation. Then, a laparotomy was performed in order to identify the motor points in each hemidiaphragm, followed by the implantation of the electrodes for diaphragmatic stimulation. We tested two types of electrodes according to the conduction of electrical stimulation: unipolar and bipolar. The electrodes were placed on different occasions in the same animals and tested with current intensities of 20, 26 and 32 mA. Each current intensity was repeated three times for 10 respiratory cycles with 1 minute interval between each cycle, and 5 minutes for new current intensity. We recorded the relationship between current intensity and inspiratory volume. RESULTS: The electrodes adequately stimulate the diaphragm and obtain inspired volumes using different intensity currents. The bipolar electrode generated inspiratory volumes as high as 4.5 times of baseline while the unipolar electrode reached up to 3.5 times of baseline. CONCLUSION: This model has proved to be effective for studying the performance of the diaphragm under different electrical stimulations using different set of electrodes.

Novel silicone stent to treat tracheobronchial lesions: results of 35 patients.

We describe a case series of 35 patients with either benign (14) or malignant (21) tracheal stenosis who were treated using a novel silicone stent, the HCPA-1, designed to prevent migration. Between March 2001 and September 2008, 13 women and 22 men received 41 HCPA-1 stents. The median duration of stenting in benign cases was 457 days (range, 4-2,961 days). Successful stent removal with curative results was accomplished in 2 patients with tracheomalacia and 1 with post-intubation stenosis. In malignant cases, the median duration of stenting was 162 days (range, 1-1,279 days). Five patients had tumor progression with obstruction requiring repeated laser resection, dilatation, or additional stents. Two patients died due to airway obstruction despite bronchoscopic intervention. Twelve patients with malignant lesions died with the stent in place. At the end of the study, 3 patients with malignant disease remained alive; 2 were lost to follow-up. The HCPA-1 stent proved to be safe, with no severe complications during the study period, and effective in improving quality of life with relief of dyspnea.

Development of a new experimental model of intramuscular electrical stimulation of the diaphragm in rabbits / Desenvolvimento de um novo modelo experimental de estimulação elétrica intramuscular do diafragma em coelhos

PURPOSE: To develop an animal model of diaphragmatic electrical stimulation able to generate an appropriate ventilatory support through the direct implantation of electrodes in the diaphragm (electroventilation). METHODS: Six New Zealand female rabbits (2-3 kg) were placed on mechanical ventilation. Then, a laparotomy was performed in order to identify the motor points in each hemidiaphragm, followed by the implantation of the electrodes for diaphragmatic stimulation. We tested two types of electrodes according to the conduction of electrical stimulation: unipolar and bipolar. The electrodes were placed on different occasions in the same animals and tested with current intensities of 20, 26 and 32 mA. Each current intensity was repeated three times for 10 respiratory cycles with 1 minute interval between each cycle, and 5 minutes for new current intensity. We recorded the relationship between current intensity and inspiratory volume. RESULTS: The electrodes adequately stimulate the diaphragm and obtain inspired volumes using different intensity currents. The bipolar electrode generated inspiratory volumes as high as 4.5 times of baseline while the unipolar electrode reached up to 3.5 times of baseline. CONCLUSION: This model has proved to be effective for studying the performance of the diaphragm under different electrical stimulations using different set of electrodes.

OBJETIVO: Desenvolver um modelo animal de estimulação elétrica diafragmática capaz de gerar um suporte ventilatório adequado através da implantação direta de eletrodos no diafragma (eletroventilação). MÉTODOS: Seis coelhas da raça Nova Zelândia (2-3 kg) foram colocadas em ventilação mecânica. Através de uma laparotomia foram identificados os pontos motores em ambas as cúpulas diafragmáticas, seguido pela implantação dos eletrodos para estimulação diafragmática. Foram testados dois tipos de eletrodos de acordo com a condução do estímulo elétrico: unipolar e bipolar. Os eletrodos foram posicionados em diferentes ocasiões nos mesmos animais e testados com intensidades de corrente de 20, 26 e 32 mA, sendo cada uma delas repetidas três vezes durante 10 ciclos respiratórios com intervalo de 1 minuto entre cada ciclo e repouso de 5 minutos para nova intensidade de corrente. Foram registradas a relação entre a intensidade de corrente e o volume de ar inspirado. RESULTADOS: Os eletrodos estimularam adequadamente o diafragma com um volume de ar inspirado até 4,5 vezes maior no modo bipolar e de 3,5 vezes no modo unipolar em relação à linha de base. CONCLUSÃO: Este modelo demonstrou ser efetivo para o estudo do desempenho do diafragma sob diferentes estimulações elétricas e diferentes tipos de eletrodos.

Tomografia computadorizada e Dor Torácica. A contribuição da tomografia computadorizada na avaliação na avaliação da dor torácica aguda / Tomografia computadorizada e Dor Torácica. A contribuição da tomografia computadorizada na avaliação na avaliação da dor torácica aguda

A doença cardíaca isquêmica é uma das principais causas de morte no mundo. Segundo os dados de 2010 do Heart Disease and Stroke Statistics aproximadamente uma morte a cada segundo mais de 151.000 americanos com menos de 65 anos já morreram este ano de doenças cardiovasculares. Os custos diretos e indiretos com doenças cardiovasculares , acidente vascular cerebral e condições relacionadas nos Estados Unidos da América são estimados em torno de 503,2 bilhões de dólares por ano. Isso inclui custos médicos, cuidados hospitalares, antendimento residencial, medicações, além de custos indiretos relacionados à perda de produtividade...

Using the Cusum curve to evaluate the training of orotracheal intubation with the Truview EVO2 laryngoscope.

BACKGROUND AND OBJECTIVES: Learning curves have proved to be useful tools to monitor the performance of a worker on a new assignment. Those curves have been used to evaluate several medical procedures. The objective of this study was to evaluate the learning of orotracheal intubation (OTI) with the Truview EVO2 laryngoscope with the CUSUM learning curve. METHODS: Four trainees underwent OTI training with the Truview EVO2 laryngoscope in a mannequin. They received orientation on the successful and failure criteria of OTI and alternated during the attempts, for a total of 300 OTI for each one. Four learning curves were plotted using the CUSUM cumulative addition method. RESULTS: It was calculated that the 105 OTIs were necessary to achieve proficiency. The four trainees crossed the line of acceptable failure rate of 5% before completing 105 OTIs; the first trainee reached proficiency after 42 OTIs, the second and third after 56 OTIs, and the fourth after 97 OTIs, and from then on their performance remained constant. Differences in the success rate between residents and experienced anesthesiologists were not observed. CONCLUSIONS: The CUSUM learning curve is a useful instrument to demonstrate objectively the ability when performing a new task. Laryngoscopy with the Truview EVO2 in a mannequin proved to be an easy procedure for physicians with prior experience in OTI; however, one should be cautious when transposing those results to clinical practice.