Mechanisms for the inhibition of amiloride-sensitive Na+ absorption by extracellular nucleotides in mouse trachea

Purinergic stimulation of airway epithelial cells induces Cl- secretion and modulates Na+ absorption by an unknown mechanism. To gain insight into this mechanism, we used a perfused micro-Ussing chamber to assess transepithelial voltage (V-te) and amiloride-sensitive short-circuit current (Isc-Amil) in mouse trachea. Exposure to apical ATP or UTP (each 100 mumol/l) caused a large initial increase in lumen negative V-te and I-sc corresponding to a transient Cl- secretion, while basolateral application of ATP/UTP induced only a small secretory response. Luminal, but not basolateral, application of nucleotides was followed by a sustained and reversible inhibition of Isc-Amil that was independent of extracellular Ca2+ or activation of protein kinase C and was not induced by carbachol (100 mumol/l) or the Ca2+ ionophore ionomycin (1 mumol/l). Removal of extracellular Cl- or exposure to 200 muM DIDS reduced UTP-mediated inhibition of Isc-Amil Substantially. The phospholipase inhibitor U73122 (10 mumol/l) and pertussis toxin (PTX 200 ng/ml) both attenuated UTP-induced Cl- secretion and inhibition of Isc-Amil. Taken together, these data imply a contribution of Cl- conductance and PTX-sensitive G proteins to nucleotide-dependent inhibition of the amiloride-sensitive Na+ current in the mouse trachea.

No evidence for inhibition of ENaC through CFTR-mediated release of ATP

Both purinergic stimulation and activation of cystic fibrosis transmembrane conductance regulator (CFTR) increases Cl- secretion and inhibit amiloride-sensitive Na+ transport. CFTR has been suggested to conduct adenosine 5'-triphosphate (ATP) or to control ATP release to the luminal side of epithelial tissues. Therefore, a possible mechanism on how CFTR controls the activity of epithelial Na+ channels (ENaC) could be by release of ATP or uridine 5'-triphosphate (UTP), which would then bind to P2Y receptors and inhibit ENaC. We examined this question in native tissues from airways and colon and in Xenopus oocytes. Inhibition of amiloride-sensitive transport by both CFTR and extracellular nucleotides was observed in colon and trachea. However, nucleotides did not inhibit ENaC in Xenopus oocytes, even after coexpression of P2Y(2) receptors. Using different tools such as hexokinase, the P2Y inhibitor suramin or the Cl- channel blocker 4,4'diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), we did not detect any role of a putative ATP secretion in activation of Cl- transport or inhibition of amiloride sensitive short circuit currents by CFTR. In addition, N-2,2'-O-dibutyrylguanosine 3',5-cyclic monophosphate (cGMP) and protein kinase G (PKG)-dependent phosphorylation or the nucleoside diphosphate kinase (NDPK) do not seem to play a role for the inhibition of ENaC by CFTR, which, however, requires the presence of extracellular Cl-. (C) 2002 Elsevier Science B.V. All rights reserved.

An overview of drugs and ancillary equipment for the dentist's emergency kit

The concept of a basic (i.e., essential) medical emergency kit suitable for a general dental practitioner varies somewhat between different authorities. A practitioner's choice is also dependant on the proximity of medical aid and the nature of the dental practice. Over recent years the trend has been to restrict the items to a minimum, in the interest of both common sense and safety, for example, just oxygen, adrenaline 1:1000, an oral carbohydrate source, glyceryl trinitrate and aspirin as first options. Ancillary equipment should include an oxygen therapy facemask, a pocket mask and a set of oral (Guedel) airways. Two further medication options for consideration are an aerosol bronchodilator and, in certain circumstances, an injectable antihypoglycaemic agent. This paper provides a selective overview of the subject. An absolute necessity is for dentists to be competent in Basic Life Support skills, and to maintain a complete and current medical history for all patients.

O papel da cidade de Viçosa-MG na rede urbana : a especialização funcional de uma cidade média mineira

Rede é o nome dado para se referenciar qualquer forma que seja composta por linhas interligadas por pontos, sendo assim essa denominação é utilizada para participar de nomes e conceitos em diversas área do conhecimento. Na geografia isso não ocorre de forma diferente. As redes geográficas são a denominação dada as ligações feitas no espaço articuladas por pontos, notadamente são usadas para se fazer referência a redes materiais, mas podem ser mais imateriais ou abstratas a depender do objeto de pesquisa e do adjetivo adotado. A noção de redes urbanas nasceu vinculada aos objetos materiais, entretanto com a evolução da técnica passou a abranger objetos cada vez mais virtuais. As redes urbanas são compostas pelo conjunto de cidades, cada qual com sua centralidade representadas por pontos ou nós na rede, e pelas ligações entre elas, rodovias, hidrovias, infovias etc. As cidades que compõem a rede, por mais semelhanças que possam ter entre si, tem diferentes tipos e graus de centralidade, de poder de atração de pessoas, de recursos; sendo uma região de influência singular, que muda de tempos em tempos, face a evolução do território onde se insere. Tanto as centralidades quanto as redes de urbanas estão em constante mudança, necessitando sempre de atualização tornando o estudo das redes e das centralidades uma questão sempre nova; em especial quando considerado um território tão vasto e complexo como o brasileiro. Neste trabalho relatamos os resultados do estudo das especificidades da centralidade da cidade de Viçosa, que está localizada no interior do estado de Minas Gerais, Brasil. Este estudo fez uso de dados numéricos, fotográficos e cartográficos coletados em diversos momentos da evolução do município e da região onde este se insere, que revelaram as mudanças de qualidade e de intensidade na centralidade dessa cidade, hoje tipificada como média ou intermediária, inserida na rede urbana mineira. No período compreendido entre os anos de 1850 e 1930, Viçosa passou de uma inexpressiva localidade rural, a importante centro de produção de café, galgando ganhos políticos nesse período. Seguiu-se um período de menor pujança, por cerca de setenta anos, para depois, na virada do século XX para XXI, ressurgi como uma localidade especializada em oferecer serviços, notadamente vinculados ao ensino superior e à produção de ciência e tecnologia. Essa nova centralidade, ao contrário do que muitas vezes ocorre, não foi fruto nem de um recurso natural inerente ao território e nem, tão pouco, pela atuação de grandes grupos capitalistas. Foi galgado principalmente pela atuação do Estado que construiu ali as bases de uma especialização funcional, através da implantação de uma universidade pública.

Fungi, bacteria and pollens seasonally quantified at 3 basic schools in Lisbon: evaluation of ventilation need

Nowadays, most individuals spend about 80% of their time indoor and, consequently, the exposure to the indoor environment becomes more relevant than to the outdoor one. Children spend most of their time at home and at school and evaluations of their indoor environment are important for the time-weighted exposure. Due to their airways still in development, children are a sensitive group with higher risk than adults. Larger impact in health and educational performance of children demand indoor air quality studies of schools. The aim of this study was to assess the children exposure to bioaerosols. A methodology based upon passive sampling was applied to evaluate fungi, bacteria and pollens; its procedures and applicability was optimized. An indoor air study by passive sampling represents an easier and cheaper method when comparing with the use of automatic active samplers. Furthermore, it is possible to achieve important quality information without interfering in the classroom activities. The study was conducted in three schools, representative of different environments in the Lisbon urban area, at three different periods of the year to obtain a seasonal variation, to estimate the variability through the city and to understand the underneath causes. Fungi and bacteria were collected indoor and outdoor of the classrooms to determine the indoor/outdoor ratios and to assess the level of outdoor contamination upon the indoor environment. The children's exposure to pollen grains inside the classrooms was also assessed.

Qualidade de vida relacionada com o exercício em indivíduos com asma: revisão sistemática

Background: A asma condiciona o dia-a-dia do indivíduo asmático do ponto de vista clínico e emocional demonstrando-se muitas vezes como um subtractivo da qualidade de vida (QV). Alguns estudos, com particular incidência nos últimos dez anos, para além de demonstrarem os benefícios da actividade física na componente clínica da doença, têm analisado o seu efeito na QV dos asmáticos. Objectivo: Analisar os efeitos da actividade física na QV de indivíduos com asma tendo por base uma revisão da literatura actual. Métodos: Foi conduzida uma pesquisa dos randomized controlled trials (RCT) compreendidos entre Janeiro de 2000 e Agosto de 2010, bem como as citações e as referências bibliográficas de cada estudo nas principais bases de dados de ciências da saúde (Academic Search Complete, DOAJ, Elsevier – Science Direct, Highwire Press, PubMed, Scielo Global, Scirus, Scopus, SpringerLink, Taylor & Francis e Wiley Interscience) com as palavras-chave: asthma, quality of life, QoL, physical activity, exercise, breathing, training e programme em todas as combinações possíveis. Os estudos foram analisados independentemente por dois revisores quanto aos critérios de inclusão e qualidade dos estudos. Resultados: Dos 1075 estudos identificados apenas onze foram incluídos. Destes, seis apresentaram um score 5/10, três 6/10 e dois 7/10 segundo a escala PEDro. Cinco destes estudos foram realizados em crianças entre os 7 e os 15 anos e os restantes em adultos. Os programas de intervenção dividiram-se em programas de treino aeróbio e programas de exercícios respiratórios. Todos programas de treino aeróbio apresentaram melhorias na QV demonstrando uma influência positiva do treino aeróbio na asma. Principais conclusões: Há uma tendência notória do benefício dos programas de treino aeróbio na QV dos indivíduos asmáticos. Os programas de exercícios respiratórios foram poucos e heterogéneos impossibilitando uma conclusão positiva quanto à sua recomendação para a melhoria da QV nesta patologia. Há uma grande necessidade de mais RCT com rigor metodológico.

Occupational exposure to Aspergillus by swine and poultry farm workers in Portugal

Aspergillus is among a growing list of allergens that aggravate asthmatic responses. Significant pulmonary pathology is associated with Aspergillus-induced allergic and asthmatic lung disease. Environments with high levels of exposure to fungi are found in animal production facilities such as for swine and poultry, and farmers working with these are at increased risk for occupational respiratory diseases. Seven Portuguese poultry and seven swine farms were analyzed in order to estimate the prevalence, amount, and distribution of Aspergillus species, as well as to determine the presence of clinical symptoms associated with asthma and other allergy diseases in these highly contaminated settings. From the collected fungal isolates (699), an average incidence of 22% Aspergillus was detected in poultry farms, while the prevalence at swine farms was 14%. The most frequently isolated Aspergillus species were A. versicolor, A. flavus, and A. fumigatus. In poultry farms, A. flavus presented the highest level of airborne spores (>2000 CFU/m3), whereas in swine farms the highest was A. versicolor, with an incidence fourfold greater higher than the other mentioned species. Eighty workers in these settings were analyzed, ranging in age from 17 to 93 yr. The potentially hazardous exposure of poultry workers to mold allergens using sensitization markers was evaluated. Although no significant positive association was found between fungal contamination and sensitization to fungal antigens, a high incidence of respiratory symptoms in professionals without asthma was observed, namely, wheezing associated with dyspnea (23.8%) and dyspnea after strenuous activities (12.3%), suggesting underdiagnosed respiratory disturbances. Further, 32.5% of all exposed workers noted an improvement of respiratory ability during resting and holidays. From all the analyzed workers, seven were previously diagnosed with asthma and four reported the first attack after the age of 40 yr, which may be associated with their occupational exposure. Some of the fungi, namely, the Aspergillus species detected in this study, are known to induce hypersensitivity reactions in humans. This study confirmed the presence and distribution of Aspergillus in Portuguese poultry and swine farms, suggesting a possible occupational health problem and raising the need for preventive and protective measures to apply to avoid exposure in both occupational settings.

Possible respiratory infection due to Aspergillus in workers from swineries and poultries

Recent epidemiologic studies clearly outline the link between fungal sensibilization and exarcebations of asthma, leading to increased morbidity and mortality. Amongst the filamentous fungi, Aspergillus scpecies have been strongly linked with exarcebations of asthma and other respiratory allergic diseases. Particles of approximately 1 to 4 pm are deposited in the lower respiratory tract. Therefore, conidia of A. fumigatus are small enough to traverse the terminal respiratory airways and reach the pulmonary alveoli, whereas the larger conidia of some other Aspergillus species, such as A. flavus and A. niger, tend to be deposited in the paranasal sinuses and upper airways. Exposute to environmental fungal spores has been associated with worsening asthma symptoms, lung function, hospital admissions and asthma-related deaths.

Evaluation of pharmaceutical assistance in public primary care in Brasília, Brazil

OBJECTIVE: Pharmaceutical assistance is essential in health care and a right of citizens according to Brazilian law and drug policies. The study purpose was to evaluate aspects of pharmaceutical assistance in public primary health care. METHODS: A cross-sectional study using WHO drug indicators was carried out in Brasília in 2001. From a random sample of 15 out of 62 centers thirty exiting patients per center were interviewed. RESULTS: Only 18.7% of the patients fully understood the prescription, 56.3% could read it, 61.2% of the prescribed drugs were actually dispensed, and mean duration of pharmaceutical dispensing was 53.2 seconds. Each visit lasted on average 9.4 minutes. Of prescribed and non-dispensed drugs, 85.3% and 60.6% were on the local essential drug list (EDL) respectively. On average 83.2% of 40 essential drugs were in stock, and only two centers had a pharmacist in charge of the pharmacy. The mean number of drugs per prescription was 2.3, 85.3% of prescribed drugs were on the EDL, 73.2% were prescribed using the generic denomination, 26.4% included antibiotics and 7.5% were injectables. The most prescribed groups were: cardiovascular drugs (26.8%), anti-infective drugs (13.1%), analgesics (8.9%), anti-asthmatic drugs (5.8%), anti-diabetic drugs (5.3%), psychoactive drugs (3.7%), and combination drugs (2.7%). CONCLUSIONS: Essential drugs were only moderately available almost 30 years after the first Brazilian EDL was formulated. While physician use of essential drugs and generic names was fairly high, efficiency was impaired by the poor quality of pharmaceutical care, resulting in very low patient understanding and insufficient guarantee of supply, particularly for chronic diseases.

Efeito de um programa de exercícios segundo Pilates em indivíduos com asma controlada – controlo motor vs. função ventilatória

Introdução: Embora existam estratégias para coordenar as funções postural e ventilatória numa situação normal, isto pode não ser verdade quando a necessidade para uma das funções está aumentada, como por exemplo em patologia respiratória (asma) ou no exercício físico, em que subsistem maiores necessidades ventilatórias. O método Pilates, que foca a relação entre o corpo e a disciplina mental, visa prosperar a saúde e o bem-estar pelo enfatizar da boa postura, do alinhamento corporal e da coordenação da ventilação com o movimento. Objectivo: Comparar características de controlo motor e parâmetros ventilatórios em asmáticos controlados e indivíduos sem patologia, e verificar o efeito de um programa de exercícios segundo Pilates nesses outcomes em indivíduos com asma controlada. Métodos: Estudo quasi-experimental, com uma amostra constituída por 21 estudantes voluntários, 7 pertencentes ao “grupo sem patologia”, 7 ao “grupo controlo asmático” e 7 ao “grupo experimental asmático”. Para avaliação do timing de ativação e do padrão de recrutamento muscular no movimento rápido do membro superior foi utilizada eletromiografia de superfície do Diafragma, Eretor da Coluna, Multífidos, Oblíquo Externo, Reto Anterior e Transverso Abdominal/Oblíquo Interno. Foram também avaliados parâmetros de função ventilatória: a percentagem de volume expiratório forçado no primeiro segundo do previsto, o débito expiratório máximo instantâneo, a ventilação máxima voluntária, a pressão inspiratória máxima e a pressão expiratória máxima. As avaliações decorreram antes e após 8 semanas da aplicação de um programa de exercícios segundo Pilates no grupo experimental asmático, com exceção do grupo sem patologia que realizou apenas o primeiro momento de avaliação. Resultados: O grupo controlo asmático apresentou um timing de ativação significativamente maior do Transverso Abdominal/Oblíquo Interno e do Diafragma, em relação ao grupo sem patologia. Nos parâmetros ventilatórios, o grupo controlo asmático apresentou menores valores de percentagem de volume expiratório no primeiro segundo do previsto, de débito expiratório máximo instantâneo e de pressão expiratória máxima. Após a realização do programa de exercícios segundo Pilates verificaram-se alterações significativas no timing de activação do Eretor da Coluna, do Multífidos, do Transverso/Oblíquo Interno e do Diafragma, tendo ambos diminuído no grupo experimental asmático. Ainda, o grupo experimental asmático, em relação aos parâmetros ventilatórios, apresentou diferenças significativas no débito expiratório máximo instantâneo, na ventilação máxima voluntária e na pressão expiratória máxima, tendo ambos aumentado estes valores. Conclusão: Os asmáticos controlados parecem possuir características de controlo motor, especificamente no timing de ativação, e valores de parâmetros ventilatórios diferentes em comparação aos indivíduos sem patologia. O programa de exercícios segundo Pilates, implementado no grupo experimental asmático, parece ter influenciado positivamente esses outcomes.

Molecular epidemiology of Aspergillus collected from cystic fibrosis patients

Background - Aspergillus respiratory infection is a common complication in cystic fibrosis (CF) and is associated with loss of pulmonary function and allergic disease. Methods - Fifty-three Aspergillus isolates recovered from CF patients were identified to species by Internal Transcribed Spacer Region (ITS), β-tubulin, and calmodulin sequencing. Results - Three species complexes (Terrei, Nigri, and Fumigati) were found. Identification to species level gave a single Aspergillus terreus sensu stricto, one Aspergillus niger sensu stricto and 51 Aspergillus fumigatus sensu stricto isolates. No cryptic species were found. Conclusions - To our knowledge, this is the first prospective study of Aspergillus species in CF using molecular methods. The paucity of non-A. fumigatus and of cryptic species of A. fumigatus suggests a special association of A. fumigatus sensu stricto with CF airways, indicating it likely displays unique characteristics making it suitable for chronic residence in that milieu. These findings could refine an epidemiologic and therapeutic approach geared to this pathogen.

Fisioterapia cardiorrespiratória em pacientes vítimas de queimaduras: projeto de intervenção precoce

Mestrado em Fisioterapia

Modeling of the lung impedance using a fractional order ladder network with constant phase elements

The self similar branching arrangement of the airways makes the respiratory system an ideal candidate for the application of fractional calculus theory. The fractal geometry is typically characterized by a recurrent structure. This study investigates the identification of a model for the respiratory tree by means of its electrical equivalent based on intrinsic morphology. Measurements were obtained from seven volunteers, in terms of their respiratory impedance by means of its complex representation for frequencies below 5 Hz. A parametric modeling is then applied to the complex valued data points. Since at low-frequency range the inertance is negligible, each airway branch is modeled by using gamma cell resistance and capacitance, the latter having a fractional-order constant phase element (CPE), which is identified from measurements. In addition, the complex impedance is also approximated by means of a model consisting of a lumped series resistance and a lumped fractional-order capacitance. The results reveal that both models characterize the data well, whereas the averaged CPE values are supraunitary and subunitary for the ladder network and the lumped model, respectively.

Inhibition of Aspergillus fumigatus and its biofilm by Pseudomonas aeruginosa is dependent on the source, phenotype and growth conditions of the bacterium

Aspergillus fumigatus (Af) and Pseudomonas aeruginosa (Pa) are leading fungal and bacterial pathogens, respectively, in many clinical situations. Relevant to this, their interface and co-existence has been studied. In some experiments in vitro, Pa products have been defined that are inhibitory to Af. In some clinical situations, both can be biofilm producers, and biofilm could alter their physiology and affect their interaction. That may be most relevant to airways in cystic fibrosis (CF), where both are often prominent residents. We have studied clinical Pa isolates from several sources for their effects on Af, including testing involving their biofilms. We show that the described inhibition of Af is related to the source and phenotype of the Pa isolate. Pa cells inhibited the growth and formation of Af biofilm from conidia, with CF isolates more inhibitory than non-CF isolates, and non-mucoid CF isolates most inhibitory. Inhibition did not require live Pa contact, as culture filtrates were also inhibitory, and again non-mucoid>mucoid CF>non-CF. Preformed Af biofilm was more resistant to Pa, and inhibition that occurred could be reproduced with filtrates. Inhibition of Af biofilm appears also dependent on bacterial growth conditions; filtrates from Pa grown as biofilm were more inhibitory than from Pa grown planktonically. The differences in Pa shown from these different sources are consistent with the extensive evolutionary Pa changes that have been described in association with chronic residence in CF airways, and may reflect adaptive changes to life in a polymicrobial environment.

Intrinsic fractal dynamics in the respiratory system by means of pressure-volume loops

This contribution presents novel concepts for analysis of pressure–volume curves, which offer information about the time domain dynamics of the respiratory system. The aim is to verify whether a mapping of the respiratory diseases can be obtained, allowing analysis of (dis)similarities between the dynamical pattern in the breathing in children. The groups investigated here are children, diagnosed as healthy, asthmatic, and cystic fibrosis. The pressure–volume curves have been measured by means of the noninvasive forced oscillation technique during breathing at rest. The geometrical fractal dimension is extracted from the pressure–volume curves and a power-law behavior is observed in the data. The power-law model coefficients are identified from the three sets and the results show that significant differences are present between the groups. This conclusion supports the idea that the respiratory system changes with disease in terms of airway geometry, tissue parameters, leading in turn to variations in the fractal dimension of the respiratory tree and its dynamics.