Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 4 uppsatser.

No description available.

A polinose é uma rinite alérgica sazonal que acontece pela sensibilização por pólens. Possui periodicidade anual, repetindo-se os sintomas sempre na mesma época do ano. Clinicamente, é caracterizada por rinoconjuntivite e/ou asma brônquica. A imunoterapia alérgeno-específica é o único tratamento capaz de modificar a evolução natural da doença, porém, depende fundamentalmente da correta identificação do alérgeno responsável. Diante disso e do número de pacientes que procuram o Ambulatório de Alergia da Universidade de Fortaleza com manifestações alérgicas exacerbadas na época de floração do cajueiro, o objetivo deste estudo foi produzir um extrato protéico a partir do pólen do cajueiro e identificar os alérgenos ainda não estudados presentes neste pólen. Doze pacientes residentes em Fortaleza, Nordeste do país, foram selecionados com base na história de rinite alérgica persistente e agravamento dos sintomas no momento da floração do cajueiro. Foi selecionado outro grupo com rinite alérgica que vive na mesma região, entretanto não apresenta relação clínica com a época de floração. Além disso, foram incluídos 5 indivíduos não-atópicos e expostos ao cajueiro como grupo controle. O soro desses pacientes foi testado em Western Blot 1D e 2D (WB) e as proteínas selecionadas foram submetidas à espectrometria de massas para identificação. Os epitopos foram preditos in silico pesquisando sequências detectadas por massa contra bases de dados de epítopos já conhecidos. Foi possível identificar alguns homólogos de alérgenos de outros pólens, como isoflavona redutase (Bet v 6), beta-1,3-glucanase (Ole e 9), proteína de choque térmico 70kDa (Cor a 10), além de outras proteínas que podem representar novos alergénios, tais como aminociclase, glutamina sintetase, fosfoglucomutase, ?-1,4-glucano-proteína-sintase, factor de alongamento 2 e biotina carboxilase, entre outros. A predição de epítopos revelou a possibilidade de reatividade cruzada com outros alérgenos de pólen conhecidos, tais como Phl p 4, Mal d 1, além de outros aeroalérgenos que também apareceram. Esta é a primeira descrição da alergia ao pólen do caju mostrando a reatividade específica de IgE no soros dos pacientes. A caracterização imunológica e estrutural de novos alérgenos, além de auxiliar no diagnóstico e tratamento de alergias não descritas, oferece ferramentas para prever epítopos e produzir moléculas hipoalergênicas nesta era da medicina de precisão / Pollinosis is a seasonal allergic rhinitis that develops due to pollens sensitization. Symptoms are manifested always in the same period of the year. Clinically, it is characterized by rhinoconjunctivitis and/or asthma. Allergen-specific immunotherapy is the only available treatment that can modify the natural course of the disease, however, it relies on the correct identification of the triggering allergen. Considering this and the number of patients attending the Allergy Clinic at University of Fortaleza with exacerbation of allergic symptoms during cashew flowering period, the aim of this study was to produce a protein extract from cashew tree pollen and identify the allergens not yet studied. Twelve patients living in Fortaleza, Northeast of country, were selected based on history of persistent allergic rhinitis and aggravation of symptoms at the time of cashew tree flowering. Another group living in the same region with allergic rhinitis without clinical relation with the flowering season was selected. Also 5 non-atopic subjects exposed to cashew tree were selected as a control group. The serum of these patients was tested for 1D and 2D Western Blotting (WB) and selected proteins were submitted to mass spectrometry for identification. Epitopes were predicted by in silico search comparing detected sequences against epitope databases. It was possible to identify some homologs of allergens from other pollens such as isoflavone reductase (Bet v 6), beta-1,3-glucanase (Ole e 9), heat shock protein 70kDa (Cor a 10), besides other proteins that might represent novel allergens, such aminociclase, glutamina sintetase, phosphoglucomutase, alpha-1,4-glucan-protein-synthase, elongation factor 2 and biotin carboxylase among others. The epitope prediction revealed the possibility of cross-reactivity with other known pollen allergens such as Phl p 4, Mal d 1 and other aeroallergens also appeared. This is the first description of cashew pollen allergy showing specific IgE reactivity of patients\' sera. The immunological and structural characterization of new allergens, besides aiding the diagnosis and treatment of non-described allergies, offers tools for predicting epitopes and producing hypoallergenic molecules in this era of precision medicine

Abstract Antioxidants function as blockers of radical processes and eliminate harmful reactive oxygen species (ROS) produced during normal cellular metabolism. A complex antioxidant defence system has evolved to protect the cellular homeostasis. This system includes antioxidant enzymes (AOEs), such as superoxide dismutases (SODs), which are intracellular MnSOD and CuZnSOD and extracellular ECSOD, H2O2 scavenging enzymes catalase and glutathione peroxidase, and hemeoxygenase-1 (HO-1), an important enzyme in heme metabolism, which has also been suggested to have antioxidant capacities. ROS play an important role in the pathogenesis of interstitial lung diseases. These diseases represent a group of disorders with different etiology, histopathology, treatment and prognosis. Sarcoidosis, extrinsic allergic alveolitis and two different forms of idiopathic pulmonary fibrosis, usual interstitial pneumonia (UIP) and desquamative interstitial pneumonia (DIP) were included in this study. The purpose of this research was to evaluate the expressions of inducible nitric oxide synthase (i-NOS), endothelial nitric oxide synthase (e-NOS) and xanthine oxidase (XAO), oxidant generating enzymes commonly associated with tissue injury, and, on the other hand, the expressions of AOEs suggested to be involved in the defence of lung tissue against oxidant stress. The methods included immunohistochemistry on lung biopsies (n=48) and Western blotting, Northern blotting or reverse polymerase chain reaction (RT-PCR) on human inflammatory cells and cells obtained from bronchoalveolar lavage. I-NOS was intensively expressed in inflammatory, but not in fibrotic lesions, similar e-NOS expression was found in control lung and in all interstitial lung diseases, while XAO was mainly negative. MnSOD and HO-1 were highly expressed in the granulomas of sarcoidosis. In contrast the expressions of MnSOD and HO-1 in late fibrotic lesions of UIP were low or undetectable by immunohistochemistry. CuZnSOD and catalase showed similar immunoreactivity in healthy and diseased lung. A cell specific expression and regulation of various enzymes may play an important role during acute inflammatory diseases and also in the progression of lung fibrogenesis.

The objective was to establish the safety and therapeutic efficacy of oral potassium humate in reducing the signs and symptoms of hayfever. Potassium humate was randomly assigned to 40 atopic patients with acute symptoms of hayfever. Blood and nasal samples were used to determine the safety and the effects of potassium humate on basophil activation, cytokine levels and eosinophil migration. A skin prick test was used to determine its anti-allergic effects. An in vitro neutrophil adhesion was also used. A significant decrease in the skin prick test results and eosinophil counts was observed. No significant differences were observed with regard to neutrophil adhesion nor were any differences observed with regard to the stimulation of basophils. Decreases were observed in the expression of IL-4, IL-5, IL-8 and IL-1â after treatment, although not reaching significance. This study confirmed that this product possesses anti-inflammatory and anti-allergic properties possibly due to a decreased recruitment of eosinopils to the inflammatory site the recruitment and activation of eosinophils by decreasing the expression of IL-4, IL-5, IL-8 and IL-1â, although not reaching statistical significance. / Dissertation (MSc (Pharmacology))--University of Pretoria, 2008. / Pharmacology / unrestricted

The lung was recently identified to consist of a complex microenvironment made up of microorganisms that interact with one another and the host cells via direct and indirect interactions. As a result, understanding the dynamic of the microbiome in chronic respiratory diseases has become the focus of pulmonary researches. In cystic fibrosis (CF), chronic infections are a comorbidity associated with the genetic disorder. Recently, it was noted that the interactions of the fungus, Aspergillus fumigatus, and the bacterium, Pseudomonas aeruginosa together contribute to more severe disease outcomes in CF patients. In vitro co-cultures show that P. aeruginosa and A. fumigatus can affect one another’s growth and pathogenicity, but very few studies have attempted to model interactions of these microorganisms in vivo. Based on clinical and basic research, we developed a co-exposure model in which we could compare non-allergic and allergic animals co-exposed to Pseudomonas aeruginosa and Aspergillus fumigatus. While both groups had significant neutrophilia and production of acute phase response cytokines and chemokines, the allergic co-exposed group had a greater mortality with 34.8% of the animals expiring by 24h in comparison to 12.5% for the non-allergic co-exposed animals and 100% survival in the controls. A contributing factor to the more severe disease outcomes in the allergic co-exposed group is the increase in eosinophilic inflammation and IL-17A production, which only occurs when both microorganisms are viable. In addition, it was found that viable P. aeruginosa but not A. fumigatus causes interstitial inflammation, significant neutrophilia, and even death during co-exposures. The decline in health of animals co-exposed to the fungus and bacteria could be attributed not only to the host’s inflammatory response, but also to the spatial and temporal co-localization in the lung. To address this, we performed in vitro studies finding an aggregation of the microorganisms that could also be identified in vivo. This current research emphasizes the need for in vivo studies on polymicrobial interactions. / ND Agricultural Experiment Station; National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R155AI137886

Pulmonary tuberculosis (TB) remains one of the most infectious causes of death worldwide. Mycobacterium tuberculosis (M.tb), the causative agent of TB is transmitted via infectious aerosols, and in the majority of cases the bacteria is effectively controlled, by the host, resulting in a chronic latent infection. Currently, the only available vaccine is the Bacillus Calmette-Guérin (BCG), which despite being successful in preventing childhood disseminated forms of TB, has failed to control the adult pulmonary TB epidemic. One of the major contributing factors in the failure of the BCG is that although antigen-specific T cells are present at the time of M.tb infection, the recruitment of such T cells into the site of infection is significantly delayed. This delay, while reduced compared to non-vaccinated hosts, allows the bacteria to replicate unchecked within the lung and establish a “foothold” prior to the arrival of protective T cells and subsequent immune control. Thus, novel initiatives seek to close this “immunological gap” through increasing the level of protective T cell responses within the airway mucosa immediately following M.tb infection. We therefore investigated the impact of deliberate modulation of T cell geography following BCG vaccination on the outcome of pulmonary M.tb infection. In addition, a number of environmental factors are also thought to affect the site of M.tb infection: the respiratory mucosa. However, little is currently known about the effects of environmental exposure to allergens and other substances such as cigarette smoke on the outcome of pulmonary TB. Throughout this thesis we have investigated the mechanisms of immune protection and failure of protection against pulmonary M.tb infection within the respiratory mucosa. / Thesis / Doctor of Philosophy (Medical Science)

Thymic stromal lymphopoietin (TSLP) is a pleotropic cytokine highly implicated in the pathophysiology of asthma and allergic diseases. Although there are robust data regarding the associations of TSLP polymorphisms with the development of allergy and asthma, there is very little information on how these TSLP variants functionally affect downstream effector pathways and disease phenotype. The overall objective of this thesis was to investigate how TSLP polymorphisms are linked to alterations in TSLP secretion and subsequent downstream cellular events. Initially, we investigated the influence of innate and adaptive stimuli on epithelial-derived TSLP expression and secretion, including effects on dendritic cells (DC). We show that polyinosinic:polycytidylic acid (polyI:C) and allergen-specific T cells induced enhanced TSLP secretion from asthmatic bronchial epithelial cells (BEC) compared to non-asthmatic BEC. Furthermore, activated-BEC culture supernatants induced TSLP-dependent CCL17 production from monocyte-derived DC in relation to clinical asthmatic status (Chapter 2). Next, we examined effects of TSLP on hemopoietic progenitor eosinophil-basophil (Eo/B) differentiation, demonstrating enhanced TSLP-mediated hemopoiesis ex vivo in relation to clinical atopic status. We further demonstrated p38MAPK-dependent autocrine signaling by TNFα in TSLP-mediated human Eo/B differentiation ex vivo (Chapter 3). Lastly, to explore the potential functional consequences of a key variant of the TSLP gene, we investigated associations between the rs1837253 TSLP variant and ex vivo production of TSLP in nasal epithelial cells (NEC). We showed that NEC derived from individuals with the “protective” minor allele have diminished TSLP secretion, which suggests that this rs1837253 polymorphism may be directly involved in the regulation of TSLP secretion (Chapter 4). The novel work presented herein provides further evidence for TSLP regulation of distinct immunological pathways in allergic immune inflammatory airway responses initiated at the epithelial surface, and thus (by implication) of allergic disease. These observations support the concept that TSLP is potentially an important biomarker and therapeutic target for allergic diseases characterized by increased Th2 and/or eosinophilic-basophilic inflammation. Continued investigations into the functional mechanisms linking TSLP variants to allergic disease phenotype are of critical importance. / Dissertation / Doctor of Science (PhD)