Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Thesis (Ph. D.)--West Virginia University, 1999. / Title from document title page. Document formatted into pages; contains xii, 150 p. : ill. Includes abstract. Includes bibliographical references (p. 124-128).

Thesis (M. Sc.)--University of Toronto, 1996. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M. Sc.)--University of Toronto, 1996. / Includes bibliographical references.

Objetivo: revisar sistematicamente os efeitos da Spirulina platensis em marcadores inflamatórios em humanos. Métodos: foi realizada busca por ensaios clínicos randomizados, realizados em humanos adultos com o objetivo de verificar os efeitos da Spirulina Platensis sob marcadores inflamatórios. A busca foi efetuada até outubro de 2015 nas bases de dados Medline via Pubmed, Cochrane Central, Clinical Trials, Scielo, LILACS, banco de teses da CAPES, assim como em bancos de grey literature. Resultados: Identificados vinte e oito estudos dos quais foram elegíveis três ensaios clínicos randomizados. A amostra foi constituída de 34 a 78 participantes, de ambos os sexos, com idade variando de 18 a 87 anos. Os marcadores inflamatórios avaliados foram: IL-2, IL-6, e TNF- e a intervenção foi feita com cápsulas de Spirulina platensis versus placebo. A IL-2 foi avaliada em dois estudos porém, não foi possível realizar a metanálise, pois um dos artigos não descrevia os valores encontrados em seu grupo controle. A IL-6 ao ser analisada em conjunto, não demonstrou diferença significativa com o uso da Spirulina platensis [-0,36 (IC95%: -0,90 a 0,18), com I2=0%]. Quanto ao TNF- não houve diferença significativa com o uso da Spirulina platensis [-0,03 (IC95%: -0,42 a 0,37)] com teste de inconsistência mostrando moderada heterogeneidade e insignificância estatística [I2= 31%, P= 0,23]. Conclusão: A informação disponível sobre o tema proposto é escassa e o efeito da Spirulina platensis sobre os marcadores inflamatórios se mostrou inconsistente. Ensaios clínicos randomizados adicionais com maior número de participantes e melhores avaliações dos marcadores são necessários para verificar o real papel anti-inflamatório da Spirulina platensis. / Objective: Perform a systematic review on the anti-inflammatory effects of Spirulina platensis in humans. Methods: A search was conducted in Medline via PubMed, Cochrane Central and Clinical Trials until October 2015 and dissertations published in CAPES, and gray literature banks for randomized controlled trials performed in adults to assess the anti-inflammatory effects of Spirulina platensis. Results: The search identified twenty eight articles. Only three randomized clinical trials were elegible for this study. The sample ranged between 34 and 78 participants, both genders, with the age ranged from 18 to 78 years. The measurements of inflammatory outcome were assessed through IL-2, IL-6, and TNF-. The intervention was capsules of Spirulina platensis versus placebo. The IL-2 was evaluated in two studies but it was not possible to evaluate the results together through meta-analysis because one of the articles did not describe the values in the control group. IL-6, when analyzed together, showed no significant difference between Spirulina platensis and placebo [-0.36 (95% CI: -0.90 to 0.18), with I2 = 0%]. Regarding the TNF- no significant difference was found [-0.03 (95% CI: -0.42 to 0.37)]. The inconsistency test showed moderate heterogeneity and no statistical significance [I2 = 31%, P = 0.23]. Conclusion: The available information on anti-inflammatory effects of S. platensis is scarce. Spirulina platensis presented no significant effect on the inflammatory markers. Additional randomized clinical trials, with more participants and better markers assessments are needed to verify the real anti-inflammatory role of Spirulina platensis.

Objetivo: revisar sistematicamente os efeitos da Spirulina platensis em marcadores inflamatórios em humanos. Métodos: foi realizada busca por ensaios clínicos randomizados, realizados em humanos adultos com o objetivo de verificar os efeitos da Spirulina Platensis sob marcadores inflamatórios. A busca foi efetuada até outubro de 2015 nas bases de dados Medline via Pubmed, Cochrane Central, Clinical Trials, Scielo, LILACS, banco de teses da CAPES, assim como em bancos de grey literature. Resultados: Identificados vinte e oito estudos dos quais foram elegíveis três ensaios clínicos randomizados. A amostra foi constituída de 34 a 78 participantes, de ambos os sexos, com idade variando de 18 a 87 anos. Os marcadores inflamatórios avaliados foram: IL-2, IL-6, e TNF- e a intervenção foi feita com cápsulas de Spirulina platensis versus placebo. A IL-2 foi avaliada em dois estudos porém, não foi possível realizar a metanálise, pois um dos artigos não descrevia os valores encontrados em seu grupo controle. A IL-6 ao ser analisada em conjunto, não demonstrou diferença significativa com o uso da Spirulina platensis [-0,36 (IC95%: -0,90 a 0,18), com I2=0%]. Quanto ao TNF- não houve diferença significativa com o uso da Spirulina platensis [-0,03 (IC95%: -0,42 a 0,37)] com teste de inconsistência mostrando moderada heterogeneidade e insignificância estatística [I2= 31%, P= 0,23]. Conclusão: A informação disponível sobre o tema proposto é escassa e o efeito da Spirulina platensis sobre os marcadores inflamatórios se mostrou inconsistente. Ensaios clínicos randomizados adicionais com maior número de participantes e melhores avaliações dos marcadores são necessários para verificar o real papel anti-inflamatório da Spirulina platensis. / Objective: Perform a systematic review on the anti-inflammatory effects of Spirulina platensis in humans. Methods: A search was conducted in Medline via PubMed, Cochrane Central and Clinical Trials until October 2015 and dissertations published in CAPES, and gray literature banks for randomized controlled trials performed in adults to assess the anti-inflammatory effects of Spirulina platensis. Results: The search identified twenty eight articles. Only three randomized clinical trials were elegible for this study. The sample ranged between 34 and 78 participants, both genders, with the age ranged from 18 to 78 years. The measurements of inflammatory outcome were assessed through IL-2, IL-6, and TNF-. The intervention was capsules of Spirulina platensis versus placebo. The IL-2 was evaluated in two studies but it was not possible to evaluate the results together through meta-analysis because one of the articles did not describe the values in the control group. IL-6, when analyzed together, showed no significant difference between Spirulina platensis and placebo [-0.36 (95% CI: -0.90 to 0.18), with I2 = 0%]. Regarding the TNF- no significant difference was found [-0.03 (95% CI: -0.42 to 0.37)]. The inconsistency test showed moderate heterogeneity and no statistical significance [I2 = 31%, P = 0.23]. Conclusion: The available information on anti-inflammatory effects of S. platensis is scarce. Spirulina platensis presented no significant effect on the inflammatory markers. Additional randomized clinical trials, with more participants and better markers assessments are needed to verify the real anti-inflammatory role of Spirulina platensis.

Objetivo: revisar sistematicamente os efeitos da Spirulina platensis em marcadores inflamatórios em humanos. Métodos: foi realizada busca por ensaios clínicos randomizados, realizados em humanos adultos com o objetivo de verificar os efeitos da Spirulina Platensis sob marcadores inflamatórios. A busca foi efetuada até outubro de 2015 nas bases de dados Medline via Pubmed, Cochrane Central, Clinical Trials, Scielo, LILACS, banco de teses da CAPES, assim como em bancos de grey literature. Resultados: Identificados vinte e oito estudos dos quais foram elegíveis três ensaios clínicos randomizados. A amostra foi constituída de 34 a 78 participantes, de ambos os sexos, com idade variando de 18 a 87 anos. Os marcadores inflamatórios avaliados foram: IL-2, IL-6, e TNF- e a intervenção foi feita com cápsulas de Spirulina platensis versus placebo. A IL-2 foi avaliada em dois estudos porém, não foi possível realizar a metanálise, pois um dos artigos não descrevia os valores encontrados em seu grupo controle. A IL-6 ao ser analisada em conjunto, não demonstrou diferença significativa com o uso da Spirulina platensis [-0,36 (IC95%: -0,90 a 0,18), com I2=0%]. Quanto ao TNF- não houve diferença significativa com o uso da Spirulina platensis [-0,03 (IC95%: -0,42 a 0,37)] com teste de inconsistência mostrando moderada heterogeneidade e insignificância estatística [I2= 31%, P= 0,23]. Conclusão: A informação disponível sobre o tema proposto é escassa e o efeito da Spirulina platensis sobre os marcadores inflamatórios se mostrou inconsistente. Ensaios clínicos randomizados adicionais com maior número de participantes e melhores avaliações dos marcadores são necessários para verificar o real papel anti-inflamatório da Spirulina platensis. / Objective: Perform a systematic review on the anti-inflammatory effects of Spirulina platensis in humans. Methods: A search was conducted in Medline via PubMed, Cochrane Central and Clinical Trials until October 2015 and dissertations published in CAPES, and gray literature banks for randomized controlled trials performed in adults to assess the anti-inflammatory effects of Spirulina platensis. Results: The search identified twenty eight articles. Only three randomized clinical trials were elegible for this study. The sample ranged between 34 and 78 participants, both genders, with the age ranged from 18 to 78 years. The measurements of inflammatory outcome were assessed through IL-2, IL-6, and TNF-. The intervention was capsules of Spirulina platensis versus placebo. The IL-2 was evaluated in two studies but it was not possible to evaluate the results together through meta-analysis because one of the articles did not describe the values in the control group. IL-6, when analyzed together, showed no significant difference between Spirulina platensis and placebo [-0.36 (95% CI: -0.90 to 0.18), with I2 = 0%]. Regarding the TNF- no significant difference was found [-0.03 (95% CI: -0.42 to 0.37)]. The inconsistency test showed moderate heterogeneity and no statistical significance [I2 = 31%, P = 0.23]. Conclusion: The available information on anti-inflammatory effects of S. platensis is scarce. Spirulina platensis presented no significant effect on the inflammatory markers. Additional randomized clinical trials, with more participants and better markers assessments are needed to verify the real anti-inflammatory role of Spirulina platensis.

Introduction; The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), affect well over 100,000 people in the United Kingdom Health related quality of life (HRQOL) is influenced by many factors in IBD including; the nature and severity of the disease, socio-economic factors, age, psychological well-being as well as· the efficacy and complications of treatment. Pilot Studies; Quality of life was assessed in 140 IBD patients (70 CD/70 UC). Diarrhoea was, not surprisingly, the most commonly reported physical symptom in both CD and UC and impaired faecal continence caused great social disability, with 72% CD patients and 68% UC patients reporting urgency or incontinence. Over a third of all patients reported occupational problems associated with their disease. Anxiety, but not depression, was common in the CD group and a major source of anxiety in many cases was lack of information. Three-quarters of patients felt additional information would have enabled them to cope with their chronic illness. It is a common perception that the provision of psychological support, such as the use of counselling skills, may alleviate many of the psychosocial problems associated with IBD, but this has not yet been proven. Hypothesis: That a nurse led counselling service improves HRQOL in IB D patients. Study Group/Design: Fifty patients with CD (aged 16-64, 33 females), 50 UC patients (aged 17-60, 26 females), 50 healthy volunteers (HV, aged 17- 61, 27 females) and a disease control group comprising 28 psoriatic arthritis (PS) patients (aged 22-66, 16 females) undeiwent structured interviews and completed a range of questionnaires measuring several facets of quality of life and psychological well-being (Hospital Anxiety and Depression Score (HAD), Attitudes and Preferences (AP), Styles and Strategies (SS) and Short-form 36 (SF36)). Patients with IBD were then randomised to receive either a counselling package or routine clinical follow-up. The counselling package consisted of disease specific information and teaching of stress management techniques, based on the "Challenge to change" programme devised by Dr. Derek Roger at the University of York. HRQOL scores were compared on entry at 6 and 12 months. Results; At baseline the scores for all questionnaires were within the nonnal range in the UC, PS, and HV groups. However CD patients recorded significantly higher anxiety scores (p<O.O I) and demonstrated significantly higher maladaptive coping mechanism scores (p<0.05). At six months, the anxiety scores of the CD patients improved significantly (p<0.05) as did their maladaptive coping mechanism scores (P<0.05). There was no significant change in disease activity over this period. These improvements were maintained at twelve months. Summary/Conclusion; Psychological morbidity is common in CD and can be quantified using validated questionnaires. Psychological morbidity improves with basic psychological support and information provision but sophisticated stress management techniques are probably unnecessary.

The neutrophil is the first haemopoetic cell to arrive at the site of infection. In acute respiratory distress syndrome (ARDS), dense neutrophilic infiltrates are found in the lung in response to bacterial infection as well as generalised inflammatory stimuli, such as pancreatitis. At sites of infection, phagocytosis of bacteria by neutrophils enhances their subsequent apoptosis and clearance by macrophages however at inflammatory sites, the lifespan of the neutrophil is influenced by both pro- and antiapoptotic factors in the inflammatory milieu. Furthermore subsequent macrophage phagocytosis of apoptotic neutrophils induces the macrophage to switch to an antiinflammatory phenotype thereby hastening resolution of inflammation. The Fas death receptor pathway is important in T lymphocyte apoptosis but its role in neutrophil apoptosis is controversial. We have shown that neutrophils express the Fas receptor (CD95) on their surface but there is no evidence of expression of its natural ligand (FasL). An agonistic anti-Fas monoclonal antibody (CH-11) accelerated neutrophil apoptosis under certain culture conditions. Lipopolysaccharide (LPS) originating from Gram-negative bacteria is often found at sites of inflammation. We have shown that LPS attenuated CH-11 - induced neutrophil apoptosis unless the Fas/FasL death receptor pathway was activated prior to the LPS signalling pathway. This LPS-mediated attenuation did not involve the p42/44 ERK, protein kinase C or phosphatidylinositol 3-kinase signalling pathway however the p38 MAPK and NF-κB pathway appeared to be partially involved. We have shown that neutrophils express the protein cFLIPs and that CH-11 and inflammatory mediators altered its expression. Although macrophages are principally phagocytes, they are also important in determining the composition of the milieu at an inflammatory site. Macrophages have been shown to express FasL which can be shed and may contribute to the pools of sFasL found in the bronchoalveolar lavage fluid (BALF) in ARDS patients. We have shown that the conditioned supernatants from LPS-activated macrophages induced neutrophil apoptosis at early time points. The pro-apoptotic activity was mediated by TNF-α and was found in the fraction containing proteins with molecular weights greater than 50kD. Macrophage phagocytosis of apoptotic neutrophils suppressed TNF-α production by LPS-activated macrophages and this was associated with loss of the pro-apoptotic activity. In summary, our data suggest that Fas/FasL fratricide does not appear to be involved in spontaneous neutrophil apoptosis. However LPS attenuates Fas-induced apoptosis unless the Fas/FasL death receptor pathway is activated prior to LPS signalling pathways. The signalling pathways involved in this attenuation are not clear but may involve cellular FLIP. Furthermore, activated macrophages secrete inflammatory mediators and at early time points, TNF-α appears to be the most important in inducing neutrophil apoptosis.

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy