No description available.

Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease involving both innate and adaptive immune responses. Abnormal numbers of inflammatory cells have been examined in COPD subjects, as well as the effects of cigarette smoking on immune cells and molecules. Killer cells, including CD8+ T cells, NKT-like cells and NK cells, are thought to play a role in the development of COPD through their cytotoxic functions. In this project, we report ex vivo, activation levels of these cell types in COPD patients, as well as effects induced by cigarette smoke extract in vitro. PBMCs were collected from healthy non-smokers (HNS), current healthy smokers (HS), current smokers with COPD (cuS-COPD) and ex-smokers with COPD (exS-COPD). Activation levels of interest and CSE effects on them were analysed by flow cytometry. Killer cells, including CD8+ T cells, NKT-like cells and NK cells, were significantly activated in current smokers with or without COPD compared to healthy non-smokers. Furthermore, KIR (CD158e1) expression was dramatically lower in smokers with or without COPD in comparison with healthy non-smokers. The cytotoxicity of CD8+ T cells from both current smokers and ex-smokers with COPD patients were significantly less than that in healthy volunteers. Also, in vitro, CSE markedly decreased IL-15 treated NK cell activation in current smokers with COPD compared to other three groups. The expression of granzyme B was also significantly inhibited on IL-15 stimulated NK cells when CSE was added. We conclude systemic ex vivo killer cell activation is smoking rather than disease related. Cigrette smoking has immunosuppressive effects on killer cell activation and granzyme B expression in PBMCs from current smokers with COPD.

A research report submitted tot the Faculty of Health Sciences, University of the Witwatersrand , Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the branch of Anaesthesia. Johannesburg, 2014 / Background: Post-operative pain is often undertreated, exposing patients to significant morbidity. The appropriate management of pain depends upon the accurate assessment thereof, however, this is difficult during general anaesthesia due to many confounders and thus intra-operative analgesia is administered according to multimodal “recipes” and changes in vital signs. Aim: To determine whether intra-operative respiratory rate in a patient under general anaesthesia is a valid indicator of post-operative analgesic adequacy. Method: The respiratory rates of 60 consenting adult female patients undergoing standardised general anaesthesia for elective breast surgery were measured. Post-operatively, each patient was assessed for the presence of pain using a Verbal Numeric Rating Scale (VNRS). Results: Spearman correlation coefficient of 0.62 was calculated between the intra-operative respiratory rates and post-operative VNRS scores. A ROC curve (with AUC equals 0.77) was plotted to test the validity of respiratory rate as a predictor for post-operative pain, with a VNRS score greater than three indicating unacceptable pain. The suggested cut-off point for respiratory rate to predict unacceptable pain is greater than or equal to 17 breaths per minute. Conclusion: The adequacy of post-operative analgesia may be predicted intra-operatively from the respiratory rate if patients are allowed to breathe spontaneously. This provides anaesthetists with a reliable, valid, affordable and easy method of titrating analgesia intra-operatively.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 5 uppsatser.

No description available.

Made available in DSpace on 2014-06-11T19:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-12-08Bitstream added on 2014-06-13T19:58:07Z : No. of bitstreams: 1 vicentini_al_me_guara.pdf: 755578 bytes, checksum: 83e65f05ef3fc87f102d91877cb24ae9 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A doença pulmonar obstrutiva crônica (DPOC) é um sério problema de Saúde Pública na maior parte do mundo, é uma patologia progressiva e incapacitante. No Brasil atinge de 6% a 15,8% da população com mais de 40 anos, entre 3 e 7 milhões de doentes. É responsável por 270 mil hospitalizações e cerca de 30 mil óbitos/ano. A ventilação mecânica se impõe como recurso necessário nos casos de descompensação da DPOC, porém, ainda hoje, apesar dos modernos ventiladores e do melhor conhecimento da fisiopatologia da doença, a ventilação mecânica é utilizada de 20% a 60% nos pacientes com DPOC internados, e a mortalidade hospitalar varia de 10% a 30%, o que aponta para a necessidade de mais estudos. Com base nesses dados, desenvolvemos e construímos um protótipo do sistema respiratório no laboratório de Biomecânica do Departamento de Mecânica da FEG/UNESP de Guaratinguetá, com o objetivo de simular a ventilação com pressão positiva. Esta simulação serviu como mediadora da aplicabilidade do ventilador mecânico de pressão positiva, modelo Bird Mark 7, frente a diferentes graus de obstrução do fluxo aéreo pulmonar. Utilizando o software de estatística SPSS, avaliamos a correlação entre as variáveis pesquisadas, o que constatou fortes índices de correlação entre as variáveis, todas acima de 0,9 e o nível de significância menores do que 1%, o que demonstra um alto grau de confiabilidade dos dados, permitindo-se constatar fortes indícios de essas variáveis serem correlacionadas. A contribuição maior desta pesquisa reside no que diz respeito ao aperfeiçoamento e desenvolvimento da técnica de ventilação mecânica e que possibilite a otimização no tratamento, prognóstico, sobrevida e melhoria da qualidade de vida dos pacientes portadores da doença pulmonar obstrutiva crônica. / A chronical obstructive pulmonary disease (DPOC) is a serious problem that occurs in public health around the world. It is an increasing and incapacitating pathology. In Brazil, it occurs in a range of 6% to 15,8% in a population above 40 years old, causing problems in around 3 to 7 million people. It is responsible to 270 thousand hospitalizations and around 30 thousand deaths a year. Mechanical ventilation becomes a necessary resource in DPOC arrhythmia, but, still today, despite all modern ventilators and the increase of knowledge on the physiopathology of the disease, mechanical ventilation is used in 20 to 60% of patients with DPOC and death rates in hospitals has varied from 10% to 30% what demonstrate the necessity of more studies. Based on these data, we developed and built a prototype of the respiratory system in the Biomechanics Laboratory at the Mechanical Department of FEG/UNESP located at Guaratinguetá, with the intent of simulating the ventilation with positive pressure. This stimulation was applied as a measure for the positive pressure mechanical ventilator, model Bird Mark 7, observing different stages of pulmonary air flow obstructions. Using the SPSS statistic software, we evaluate the co-relation among the variables that have been presented as “high variables”, all over 0,9%, and significant levels lower than 1%, what gives us a high level of confidence on the data, allowing us to focus on the high indications of these co-relations. The biggest contribution of this research is the development and the increase on the technics for mechanical ventilation with positive pressure, and also that it will improve the treatment of the disease, its prognosis, its forecoming and bring a better life quality for patients with chronically pulmonary obstruction disease.

Orientador: Araildo Lima da Silva / Banca: Araildo Lima da Silva / Banca: João Zangrandi Filho / Banca: Mauro Cesar Tavares de Souza / Resumo: A doença pulmonar obstrutiva crônica (DPOC) é um sério problema de Saúde Pública na maior parte do mundo, é uma patologia progressiva e incapacitante. No Brasil atinge de 6% a 15,8% da população com mais de 40 anos, entre 3 e 7 milhões de doentes. É responsável por 270 mil hospitalizações e cerca de 30 mil óbitos/ano. A ventilação mecânica se impõe como recurso necessário nos casos de descompensação da DPOC, porém, ainda hoje, apesar dos modernos ventiladores e do melhor conhecimento da fisiopatologia da doença, a ventilação mecânica é utilizada de 20% a 60% nos pacientes com DPOC internados, e a mortalidade hospitalar varia de 10% a 30%, o que aponta para a necessidade de mais estudos. Com base nesses dados, desenvolvemos e construímos um protótipo do sistema respiratório no laboratório de Biomecânica do Departamento de Mecânica da FEG/UNESP de Guaratinguetá, com o objetivo de simular a ventilação com pressão positiva. Esta simulação serviu como mediadora da aplicabilidade do ventilador mecânico de pressão positiva, modelo Bird Mark 7, frente a diferentes graus de obstrução do fluxo aéreo pulmonar. Utilizando o software de estatística SPSS, avaliamos a correlação entre as variáveis pesquisadas, o que constatou fortes índices de correlação entre as variáveis, todas acima de 0,9 e o nível de significância menores do que 1%, o que demonstra um alto grau de confiabilidade dos dados, permitindo-se constatar fortes indícios de essas variáveis serem correlacionadas. A contribuição maior desta pesquisa reside no que diz respeito ao aperfeiçoamento e desenvolvimento da técnica de ventilação mecânica e que possibilite a otimização no tratamento, prognóstico, sobrevida e melhoria da qualidade de vida dos pacientes portadores da doença pulmonar obstrutiva crônica. / Abstract: A chronical obstructive pulmonary disease (DPOC) is a serious problem that occurs in public health around the world. It is an increasing and incapacitating pathology. In Brazil, it occurs in a range of 6% to 15,8% in a population above 40 years old, causing problems in around 3 to 7 million people. It is responsible to 270 thousand hospitalizations and around 30 thousand deaths a year. Mechanical ventilation becomes a necessary resource in DPOC arrhythmia, but, still today, despite all modern ventilators and the increase of knowledge on the physiopathology of the disease, mechanical ventilation is used in 20 to 60% of patients with DPOC and death rates in hospitals has varied from 10% to 30% what demonstrate the necessity of more studies. Based on these data, we developed and built a prototype of the respiratory system in the Biomechanics Laboratory at the Mechanical Department of FEG/UNESP located at Guaratinguetá, with the intent of simulating the ventilation with positive pressure. This stimulation was applied as a measure for the positive pressure mechanical ventilator, model Bird Mark 7, observing different stages of pulmonary air flow obstructions. Using the SPSS statistic software, we evaluate the co-relation among the variables that have been presented as "high variables", all over 0,9%, and significant levels lower than 1%, what gives us a high level of confidence on the data, allowing us to focus on the high indications of these co-relations. The biggest contribution of this research is the development and the increase on the technics for mechanical ventilation with positive pressure, and also that it will improve the treatment of the disease, its prognosis, its forecoming and bring a better life quality for patients with chronically pulmonary obstruction disease. / Mestre

Colonisation and persistent lung infection by pathogens, mainly Pseudomonas aeruginosa (PA), is an important cause of morbidity and mortality in Cystic Fibrosis patients. PA persists inside the lungs by forming drug-resistant biofilms. Investigation into the behaviour of bacterial cells within these structures and their response to components of the innate immune response will give us an insight into novel approaches to combat infection. The main aim of this thesis was investigate the effect of inflammatory mediators such as cytokines and immune cells on the development of PA biofilms. For this the BioFlux system and PA expressing green fluorescent protein were used to generate biofilms. After incubation with serum, cytokines such as GM-CSF and IFN-γ, changes in the characteristic of the biofilms were analysed. No significant changes on PA biofilms were observed in the presence of the cytokines but human serum was shown to have an inhibitory effect. Incubation of PA biofilms with labelled purified human monocytes and macrophages indicate that macrophages, unlike monocytes attached to PA biofilms. Cell surface receptors expressed by monocytes and macrophages were compared and, as previously described, high mannose receptor (MR) expression was found in macrophages. MR is a carbohydrate binding receptor that plays a crucial role in innate immunity. MR binds mannose-rich carbohydrates through C-type lectin-like domains (CTLD) 4 to 7. Using a recombinant protein containing the mannose binding region of MR (CTLD 4-7-Fc) it was found that MR can directly interact with PA biofilms and that this binding is increased when Psl expression is increased. Furthermore CTLD 4-7-Fc was shown to bind crude extracts of carbohydrates from PA biofilm enriched for the extracellular polysaccharide Psl. We hypothesize that MR expressed by macrophages and dendritic cells might contribute to PA recognition through Psl. Future work will explore the capability of immune mammalian C-type lectins to recognise PA biofilms and purified Psl and elucidate the role of Psl in modulating the recognition of PA by immune cells using PA strains expressing different combinations of extracellular polysaccharides. Our results will shed light on the impact of Psl on the immune recognition of PA, and might open the avenues for the discovery of novel therapeutic targets. Dispersion is the final stage of the biofilm cycle and contributes to dispersal and transmission of pathogens to colonize new sites. Till now not many studies have focused on the role of dispersion in pathogenesis. Thus the present study also focused on the contribution of a dispersal molecule produced during PA biofilm formation termed cis-2-decenoic acid (CDA) and analyse its role in immunomodulation. Previous observations showed that addition of exogenous CDA is able to disperse mature biofilm and inhibit biofilm formation of different gram negative and gram positive bacteria such as PA, E. coli and S. aureus. The present study showed that exogenous addition of CDA is able to modify some aspects of the inflammatory response by modulating production of the pro-inflammatory cytokine TNF-α by human monocytes and macrophages. Thus the present study has identified the potential impact of CDA as an immune modulator which will offer many opportunities for development of drug with potential anti-inflammatory action.

Injury to the bronchial epithelium in respiratory diseases such as asthma and COPD results in the loss of barrier function and an elevated sensitivity to environmental insults. An increased release of the endogenous cannabinoid, anandamide in response to inhalation of allergen in asthmatic patients has been reported. In contrast, previous clinical trial findings suggest anti-inflammatory and broncho-relaxant properties of the phytocannabinoid, ∆9-tetrahydrocannabinol (THC). The aim of this study was, therefore, to determine the effects of endocannabinoids and phytocannabinoids on bronchial epithelial cell permeability and to investigate the mechanisms involved. Calu-3 human bronchial epithelial cells were cultured at air-liquid interface to allow development of tight junctions. Changes in transepithelial electrical resistance (TEER), a reflection of epithelial permeability, were measured at various time points post-treatment. The endogenous cannabinoid anandamide produced a significant reduction in TEER, which was unaffected by cannabinoid receptor antagonists, but attenuated by URB597, an inhibitor of fatty acid amide hydrolase, and by a combination of cyclooxygenase and lipooxygenase blockade. Subsequent immunoblotting data revealed that the expression of tight junction proteins, occludin and ZO-1, were also reduced by anandamide. Inhibition of ERK activation by MEK1/2 inhibitors, PD98059 and U0126, prevented the anandamide-induced reduction in TEER and prevented the reduction in occludin expression. Thus, ERK activation is likely to mediate these effects by altering the expression of tight junction proteins. Treatment with THC prevented TNFα-induced decrease in TEER and increased in paracellular permeability. CB1 and CB2 receptor-like immunoreactivity was found in Calu-3 cells. Subsequent pharmacological blockade of either cannabinoid receptor inhibited the THC effect. In comparison, stimulation of both or either CB1 or CB2 receptors displayed similar effect to that of THC. Western immunoblotting also revealed reproducible decreases in occludin and ZO-1 expression in TNFα-treated cells, whereas cells pre-incubated with THC alone or in combination with TNFα did not alter expression levels. Phosphorylation of myosin-phosphatase target protein at threonine 696 residue by TNFα was attenuated in the presence of THC, indicating the involvement of RhoA/ROCK cascade. Selective stimulation of either cannabinoid receptor in TNFα-treated cells suggests THC-induced inhibitory effect on RhoA/ROCK signalling was mediated through CB2 receptor, and not CB1. In summary, these data suggest that the reduction in transepithelial resistance by anandamide, indicative of increased epithelial permeability, is caused by its metabolites rather than anandamide itself. Inhibition of anandamide degradation might provide a novel approach to treat airway inflammation. Conversely, THC reverses the reduction in transepithelial resistance caused by TNFα, through an effect at CB1 and CB2 receptors. Hence, THC, or perhaps other cannabinoid receptor ligands may have potential therapeutic roles in inflammation-induced changes in airway epithelial cell permeability, such as asthma and COPD.

No description available.