Thesis (Ph. D.)--University of Oregon, 2005. / Includes bibliographical references (leaves 195-207). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (Ph. D.)--University of Oregon, 2005. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 195-207). Also available for download via the World Wide Web; free to University of Oregon users.

Th.--Méd.--Nancy 1, 1984. N°: 278.

xvii, 168 p. : ill. A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / An acute bout of moderate-intensity dynamic exercise results in a sustained rise in skeletal muscle blood flow from that of pre-exercise levels. This postexercise skeletal muscle hyperemia is mediated by two histamine receptors (subtypes, H 1 and H 2 ). Skeletal muscle glucose uptake is also enhanced, in an insulin-independent manner, following moderate-intensity dynamic exercise. The impact of skeletal muscle hyperemia on glucose regulation following exercise has yet to be examined. Therefore, the purpose of this dissertation was to determine if postexercise skeletal muscle hyperemia plays a substantial role in glucose regulation in humans. In Chapter III I tested my ability to block local H 1 - and H 2 -receptors located in the vastus lateralis muscle in humans. The results demonstrate that I was able to successfully block the increase in local blood flow evoked by compound 48-80 with the combination of the H 1 -receptor antagonist pyrilamine and the H 2 -receptor antagonist cimetidine, administered via skeletal muscle microdialysis. In Chapter IV I sought to determine the effect of local combined H 1 - and H 2 -receptor blockade, administered via skeletal muscle microdialysis, on postexercise interstitial glucose concentrations. My findings indicate postexercise delivery of glucose to the interstitial space of the previously active skeletal muscle is mediated, in part, by local H 1 - and H 2 -receptors. In Chapter V I examined the effect of oral administration of H 1 - and H 2 -receptor antagonists on glucose regulation following a postexercise oral glucose load. The results showed that the glycemic and insulin responses to postexercise oral glucose load were more sustained with H 1 - and H 2 -receptor blockade versus control, suggesting a histaminergic effect on postexercise glucose regulation. / Adviser: John Halliwill

No Brasil, o consumo de pescado in natura cresce a cada ano e sua ingestão tem sido associada a problemas de saúde, principalmente, surtos de intoxicação alimentar causado pela histamina, podendo representar risco à saúde do consumidor. A histamina pode provocar erupções na pele, náuseas, dor de cabeça, palpitações, vômitos, dores abdominais, distúrbios respiratórios e taquicardia. O Brasil exporta pescado para os principais mercados consumidores e tem enfrentado barreiras comerciais pela exigência de análises de histamina, com a finalidade de assegurar a qualidade do pescado exportado. Assim sendo, foi desenvolvido e validado um método por cromatografia líquida de ultra eficiência (CLUE) para a determinação dos teores de histamina em peixes. O método desenvolvido mostrou ter boa linearidade, seletividade, exatidão e precisão, ser robusto e com os limites de detecção e quantificação determinados de 0,03 µg mL-1 e 0,10 µg mL-1, respectivamente. A metodologia foi aplicada a amostras de pescados (atum e sardinha) in natura e em conservas. Das 12 amostras analisadas de atum in natura somente uma apresentou teor de histamina de 1,07 mg.kg-1, 05 amostras de sardinha in natura apresentaram teores de 26,81, 0,35, 37,25, 9,97 e 0,94 mg kg-1, respectivamente. Nas amostras de atum em conserva, 02 apresentaram teores de 1,30 e 0,13 mg kg-1. Enquanto que, 04 amostras de sardinha em conserva continham teores de histamina de 2,49, 68,96 e 11,66 mg kg-1, e uma das amostras de sardinha em conserva estava com o teor muito acima, cerca de 17 vezes do limite máximo estabelecido pelo MAPA, de 100 mg kg-1 para conservas de sardinha. Essa quantidade de histamina encontrada pode sugerir a ocorrência de uma intoxicação, representando risco à saúde humana. Além disso, foi calculada a incerteza de medição, pois garante uma maior confiabilidade dos resultados analíticos para tomadas de decisões importantes em Vigilância Sanitária e Saúde Pública. / In Brazil, the consumption of fish in nature grows every year and its intake has been linked to health problems, especially food poisoning outbreaks caused by histamine, which may pose a risk to consumer health. Histamine can cause skin rashes, nausea, headache, palpitations, vomiting, abdominal pain, respiratory disorders and tachycardia. Brazil exports fish to the main consumer markets and has faced trade barriers by requiring histamine analysis, in order to ensure the quality of exported fish. Thus, it was a method developed and validated liquid chromatography ultra efficiency (CLUE) for determining histamine levels in fish. The method was proven to have good linearity, selectivity, accuracy and precision and be robust with the limits of detection and quantification of certain 0,03 ug mL-1 and 0.10 ug mL-1, respectively. The methodology was applied to fish samples (tuna and sardines) in fresh and canned. Of the 12 samples analyzed tuna in fresh only one showed histamine content of 1.07 mg.kg-1, 05 sardine in fresh samples showed levels of 26.81, 0.35, 37.25, 9.97 and 0.94 mg kg-1, respectively. In the samples of canned tuna, 02 showed levels of 1.30 and 0.13 mg kg-1. While 04 canned sardines containing histamine concentrations of 2.49, 68.96 and 11.66 mg kg-1, and one sample canned sardine content was much higher, about 17 times higher than the maximum limit established by MAPA, 100 mg kg-1 for canned sardine. This amount of histamine found may suggest the occurrence of intoxication, representing a risk to human health. In addition, the measurement uncertainty was calculated as it ensures a higher reliability of the analytical results for taking important decisions on Health Surveillance and Public Health.

Orientador: Ricardo de Lima Zollner / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T13:48:19Z (GMT). No. of bitstreams: 1 Trevizan_Giovanna_M.pdf: 992041 bytes, checksum: 788bad7f2b885488c459d8cc22f66468 (MD5) Previous issue date: 2010 / Resumo: As reações alérgicas à ferroada de inseto resultam de resposta exacerbada do sistema imune, com produção de elevados níveis de anticorpos IgE alérgeno-específicos e padrão de citocinas Th2. A diferenciação de linfócitos Th2 e a secreção de citocinas por estas células são reguladas pelo fator de transcrição GATA-3. A ligação da IgE ao seu receptor de alta afinidade (Fc?RI) em mastócitos e basófilos, promove a liberação de mediadores inflamatórios. Muitos estudos demonstram a eficácia da imunoterapia específica na dessensibilização e no desenvolvimento de tolerância em indivíduos com quadros graves de hipersensibilidade à ferroada de insetos, sobretudo da classe Hymenoptera. A histamina é o principal mediador liberado durante a resposta alérgica; através da ativação de diferentes receptores (HR1, HR2, HR3 ou HR4) as células do sistema imune podem ser tanto inibidas como estimuladas. Via HR1, a histamina estimula principalmente linfócitos Th1, enquanto inibe linfócitos Th2 via HR2. O receptor 4 desempenha papel central na diferenciação de linfócitos Th2 e também é capaz de modular a produção de citocinas. A liberação de histamina é regulada por fatores de liberação de histamina (HRF), sendo que os HRF dependentes de IgE induzem a liberação de histamina na fase tardia das reações alérgicas. Considerando-se todas essas informações, o objetivo do presente trabalho foi avaliar os efeitos modulatórios da imunoterapia na expressão gênica dos receptores de histamina (HR1, HR2 e HR4), fatores de liberação de histamina (HRF) e cadeia ? do receptor de alta afinidade de IgE, além da expressão protéica do fator de transcrição GATA-3, em células linfomononucleares de pacientes alérgicos ao veneno de abelha. As células foram isoladas de pacientes submetidos à imunoterapia, em diferentes períodos do tratamento (Pré, 1, 3, 6, 12, 18 e 24 meses), após injeção subcutânea, e submetidas à cultura por 72 horas, com estimulo de veneno de abelha a 1 ng/ml. Indivíduos não alérgicos foram estudados como grupo controle. Com objetivo de avaliar a expressão gênica foram realizadas extração de RNA, seguida de síntese de cDNA e PCR, para avaliação da expressão protéica, utilizou-se a técnica de imunofluorescência. A expressão gênica de HR1 e HR4, assim como de HRF e da cadeia gama do Fc?RI foi significativamente reduzida ao final do período analisado. O receptor 2 de histamina não apresentou alterações bem definidas após 24 meses de imunoterapia. O fator de transcrição GATA-3 apresentou diminuição significativa na expressão a nível protéico. Nossos resultados demonstram que a imunoterapia específica ao veneno de abelha foi capaz de modular elementos envolvidos na resposta imune / Abstract: Allergic disease is an abnormal response from the immune system, with high levels of allergen specific IgE antibodies and Th2 pattern of cytokines. Development of Th2 cells and the production of cytokines are regulated by transcription factor GATA-3. Binding of IgE to its high affinity receptor (Fc?RI) in mast cells and basophils induces inflammatory mediators' release. Many studies have shown the efficacy of specific immunotherapy. Histamine is an important mediator in allergy, through activation of distinct histamine receptors (HR1, HR2, HR3 or HR4) in the immune system; cells can be either stimulated or inhibited. Histamine can stimulate, by HR1 receptor, especially Th1 response, and inhibit particularly Th2 cells through HR2 activation. HR4 plays a central role in Th2 polarization and also modulates cytokine profile production. IgE-dependent histamine releasing factors (IgE-HRF) induce histamine release in late phase reaction. In regard of this information, the aim of this study was to evaluate the modulating effects of specific immunotherapy in gene expression of histamine receptors (HR1, HR2 and HR4), histamine releasing factor (HRF), in patients with allergy and the gama chain of Fc?RI, and also GATA-3 protein levels. Bee venom allergic subjects underwent specific bee venom immunotherapy (VIT) in different stages of treatment (Pre, 3, 6, 12, 18 and 24 months) were studied. Peripheral blood mononuclear cells were isolated after subcutaneous venom injection and submitted to culture for 24, 48 and 72 hours stimulated with 1ng/ml of bee venom. In parallel healthy subjects were studied as well. Total RNA extraction, followed by cDNA synthesis and PCR were used to evaluate gene expression; GATA-3 protein expression was analyzed by immunofluorescence assay. Data from all time of cell culture - 24, 48 and 72 hours - were grouped and analyzed. Gene expression from HR1 and HR4 and also HRF and ? chain of Fc?RI were significantly reduced at the end of 24 months of immunotherapy. Histamine receptor 2 didn't show well established alterations. For transcription factor GATA-3 significant decrease at protein level was observed. Together, our results indicate that bee venom specific immunotherapy was able to modulate some of the elements involved in the immune response / Mestrado / Ciencias Basicas / Mestre em Clinica Medica

Rats lesioned shortly after birth with 6-hydroxydopamine (6-OHDA; 134 μg icv) represent a near-ideal model of severe Parkinson's disease because of the near-total destruction of nigrostriatal dopaminergic fibers. There are scarce data that in Parkinson's disease, activity of the central histaminergic system is increased. The element manganese, an essential cofactor for many enzymatic reactions, itself in toxic amount, replicates some clinical features similar to those of Parkinson's disease. The aim of this study was to examine the effect of neonatal manganese exposure on 6-OHDA modeling of Parkinson's disease in rats, and to determine effects on histamine content in the brain of these rats in adulthood. Manganese (MnCl 2•4H 2O; 10,000 ppm) was included in the drinking water of pregnant Wistar rats from the time of conception until the 21st day after delivery, the age when neonatal rats were weaned. Control rats consumed tap water. Other groups of neonatal rat pups, on the 3rd day after birth, were pretreated with desipramine (20 mg/kg ip 1 h) prior to bilateral icv administration of 6-OHDA (60 or 134 μg) or its vehicle saline-ascorbic (0.1%) (control). At 2 months after birth, in rats lesioned with 60 or 134 μg 6-OHDA, endogenous striatal dopamine (DA) content was reduced, respectively, by 92 and 98% (HPLC/ED), while co-exposure of these groups to perinatal manganese did not magnify the DA depletion. However, there was prominent enhancement of histamine content in frontal cortex, hippocampus, hypothalamus, and medulla oblongata of adult rat brain after 6-OHDA (60 and 134 μg) injection on the day 3rd postnatal day. These findings indicate that histamine and the central histaminergic system are altered in the brain of rats lesioned to model Parkinson's disease, and that manganese enhances effects of 6-OHDA on histamine in brain.

京都大学 / 0048 / 新制・論文博士 / 博士(農学) / 乙第13019号 / 論農博第2829号 / 新制||農||1042(附属図書館) / 学位論文||H28||N4965(農学部図書室) / 32947 / (主査)教授 久米 新一, 教授 松井 徹, 教授 祝前 博明 / 学位規則第4条第2項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

The role of histamine in chronic gastrointestinal diseases has been increasingly recognized in humans, but the role of histamine in the canine gastrointestinal tract has not been thoroughly investigated. The presence and distribution of all 4 histamine receptors (H1, H2, H3, and H4) in the stomach, duodenum, ileum, jejunum, and colon of healthy dogs were evaluated with a commonly employed immunohistochemistry technique using antibodies predicted to cross react with canine histamine receptors. All 4 histamine receptors were identified in the canine gastrointestinal tract, and differed in location and density within sections of the canine gastrointestinal tract. Antibody specificity was evaluated with Western blot. With the establishment of a method to study histamine receptors in the canine gastrointestinal tract, additional research to evaluate histamine receptors in dogs is warranted to further understand the pathophysiology and treatment of chronic canine enteropathies.

<p> Treatment of canine colonic tissue with some O-alkyl and O-benzyl hydroxylamines potentiated the response of the tissue to histamine in different experimental environments.</p> <p> Sixteen O-substituted hydroxylamine compounds were synthesized using a modification of the Gabriel synthesis. These compounds were tested for their ability to potentiate histamine in canine colonic tissue through diamine oxidase inhibition.</p> <p> Three procedures were used to determine their activity: (1) secondary rise -hydroxylamine derivatives were added to epithelial tissue preparations in Ussing chambers after an initial dose of histamine. Active compounds caused a secondary increase in the short circuit current across the tissue, (2) dose-response profiles were constructed for several hydroxylamine compounds to determine whether they caused a significant shift to the left of the normal histamine curve (potentiated response), and (3) diamine oxidase enzyme assays were performed to examine the ability of the hydroxylamine derivatives to inhibit partially purified diamine oxidase. This aided in determining if inactive compounds could not potentiate histamine due to an inability to access the enzyme in the epithelial preparation.</p> <p> The structure-activity relation observed indicates that: (1) active compounds are oxygen and not nitrogen substituted hydroxylamines, (2) branched compounds are less active than their straight chain analogues, (3) greater steric bulk of the alkyl substituent can decrease the activity of the compound, (4) the presence of a carbon-carbon double (allyl) or triple (4-pentynyl) bond does not affect the activity of the compound, (5) longer straight chain O-alkyl hydroxylamines are less active than shorter chain derivatives, (6) steric bulk of the benzyl compounds is not likely to be the cause of its inability to inhibit diamine oxidase since the cinnamyl derivative is active, and (7) meta- and para-oxygen substituents (-OH, -OCH3) on O-benzyl hydroxylamines increase their diamine oxidase inhibiting properties.</p> / Thesis / Master of Science (MSc)