Thesis (Ph. D.)--Ohio State University, 2004. / Document formatted into pages; contains xiii, 73 p. Includes bibliographical references (p. 69-73). Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2006 Mar. 24.

Thesis--Catholic University of America. / Includes bibliographical references (p. 21-23).

Thesis (M. Phil.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves 96-114).

Thesis--Catholic Univ. of America.

Inaug.-diss.-Bern. / Lebenslauf.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1956. / Typescript. Abstracted in Dissertation abstracts, v. 16 (1956) no. 11, p. 2197. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 149-171).

Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / Wenjun Ma / Rift Valley fever virus (RVFV) is an enveloped, negative-sense, ssRNA virus with a tripartite genome that causes morbidity and mortality in both livestock and humans. Although RVFV is mainly circulating in mainland Africa, this arthropod-borne virus is a potential threat to the other parts of the world. No fully licensed vaccines for human or animal use in the U.S., and effective antiviral drugs have not been identified. As virulent RVFV strains are only handled in biosafety level (BSL) 3 or higher level facilities in the U.S., few laboratories have access to RVFV which limits antiviral development. However, it is crucial to develop effective antivirals to protect public and animal health. Animal models that reproduce Rift Valley fever are vital to identifying and developing antiviral compounds. The currently available attenuated RVFV strain, MP12, provides a BSL-2 challenge model virus for preliminary investigations of RVFV prior to using the virulent RVFV strains. All strains of RVFV have a highly conserved genome, indicating that antivirals or vaccines effective against any RVFV strain will most likely be effective for all RVFV strains. Therefore, we hypothesize that the MP12 is a suitable model virus that can be used for identification and evaluation of effective RVF antivirals. The first objective of this project was to establish a mouse model susceptible to MP12 infection. Based on the literature, we selected and screened six different strains of mice to test their susceptibilities to MP12. We found the STAT-1 knockout mice are the most susceptible to MP12 infection based on clinical symptoms, mortality, viremia, virus replication, histopathological, and immunochemical analyses. Importantly, these mice displayed acute-onset hepatitis and delayed-onset encephalitis similar to severe cases of human RVFV infection. Our second objective was to identify potential antiviral drugs in vitro. We developed and employed a cell-based assay using the recombinant MP12 virus expressing Renilla luciferase to screen a library of 727 small compounds purchased from National Institutes of Health. Of the compounds, 23 were identified and further tested for their inhibitory activities on the recombinant MP12 virus expressing green fluorescent protein. Further plaque reduction assays confirmed that two compounds inhibited replication of parental RVFV MP12 strain with limited cytotoxic effects. The 50% inhibitory concentrations using an MP12 multiplicity of infection (MOI) of 2 were 211.4 µM and 139.5 µM, respectively. Our third objective was to evaluate these two candidates, 6-azauridine and mitoxantrone, in vivo using our mouse model. After one-hour post MP12 infection via an intranasal route, treatment was given intranasally twice daily. Mice treated with placebo and 6-azauridine displayed severe weight loss and reached the threshold for euthanasia with obvious neurological signs, while mice treated with ribavirin (a known antiviral drug) or mitoxantrone showed delayed onset of disease. This result indicates that the mitoxantrone can improve the outcome of RVFV infection in our mouse model. The underlying mechanism of mitoxantrone to inhibit RVFV replication remains to be investigated. Our studies build the foundation for identification and development of antivirals against RVFV in a BSL-2 environment.

目的: 通過搜索有關天灸治療過敏性鼻炎的臨床研究文獻，以系統評價及數據挖掘技術提取其干預措施的細節，包括敷貼藥物的組成、選用的穴位、治療時間點、治療頻率, 敷貼時長及治療次數等，並且基於此研究，從循證醫學角度提供天灸治療過敏性鼻炎干預措施的建議性方案，為進一步的臨床實踐和研究提供循證醫學依據。 方法: 選取包括中國期刊全文數據庫（ CNKI ）、中國科技期刊數據庫（ VIP ）和萬方數據庫（ Wanfang Database ）在內的中文文獻數據庫及包括EMBASE 數據庫和MEDLINE數據庫在內的英文文獻數據庫進行文獻檢索，檢索範圍為各數據庫已知收錄時間至20 1 6 年2 月的全部期刊，檢索對象為所有有關天灸治療過敏性鼻炎的臨床研究文獻，制定文獻納人和排除標準進行篩選，對所納人的文獻進行數據挖掘，並通過計算比例、百分數、平均數、中位數等數據處理方法列出相應圖表進行報告。 結果：根據檢索以及對符合納入標準的文獻進行統計、最終符合納人標準的文獻為88篇。通過干預措施數據提取分析，可知目前臨床使用率最高的四種藥物分別是白芥子（ n=85, 93 . 41 % ），緬辛（ n=85, 93 . 41 % ），甘遂（ n=72, 79.12% ）和延胡索（ n = 7 0, 76.92% ），通過將上述藥物比例換算為百分數，再計算中位數之比，得出結果為白芥子（ 28. 60% ），延胡索（ 2 0.00 % ），名田辛（ 16. 70% ），甘遂（ 16.70%) , 即白芥子： 延胡索：細辛：甘遂三7:5:4:4 的組方比例。最常用的五個穴位分別為肺俞(n=85, 96 . 5 9% ） ，大椎（ n =67, 76 . 14% ） ， 腎俞（ n =64, 72.7 3% ），脾俞( n= 56, 63 . 64 % ）和風門（ n=56, 63. 6 4% ） 。治療時間點一般分為三伏天（ n 49，53. 26% ） 與常日（ n=32 , 34. 78% ） 兩類，治療頻次及次數多為10 天貼1 次， 共 貼3次為一療程。貼敷時間一般為成人3-4h ，小兒l. 5 -2 h ， 貼藥時間以皮膚可耐受為度。 結論：通過以上數據挖掘，得出天灸治療過敏性鼻炎的建議干預措施方案為： 將白芥子、延胡索、細辛、甘遂按7: 5 : 4 : 4 的比例研組末混合，以新鮮生薑汁調成糊狀, 保鮮備用。取大椎、風門、肺俞、脾俞和腎俞，將配制好的藥物取約2 g 藥量, 置於專用敷貼繆布中央， 貼在上述穴位上。除大惟穴外，其余穴位均取雙側。 預約患者於當年三伏天當天進行治療, 1 0 天貼l 次，共貼3 次為一療程。成人一般貼敷3-4h，小兒一般貼敷1. 5-2h ， 貼藥時間可視患者具體情況而定。如發癢、灼痛感不明顯者可貼敷較長時間，如發癢、灼痛戚非常明顯者宜適當縮短貼敷時間。

Made available in DSpace on 2014-06-11T19:23:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2003-02Bitstream added on 2014-06-13T19:50:50Z : No. of bitstreams: 1 souza_ah_me_jabo.pdf: 135909 bytes, checksum: 8630e91d950b872f828e910f5c4dd484 (MD5) / A endotoxemia é uma afecção importante nas diversas espécies animais decorrente da ação de lipopolissacarídeos liberados na circulação durante o choque séptico, os quais ativam a cascata inflamatória induzindo a síntese e liberação de citocinas (TNF, IL-1, IL-6), capazes de produzir febre. É bastante comum, em eqüinos, quadros de cólica gastrintestinal devido à intoxicação por amitraz (AMZ), um acaricida formamidínico. A compactação de cólon é uma das conseqüências dessa intoxicação principalmente, pela ação desta substância sobre receptores adrenérgicos a-2. Sabendo-se que as substâncias agonistas de receptores a-2 produzem um aumento do tônus vagal e que a estimulação das fibras vagais, aferentes e eferentes reduz a liberação de TNF-a, o objetivo deste estudo foi avaliar os efeitos do AMZ sobre a febre, quando administrado antes da indução experimental de endotoxemia com LPS ou da administração de IL-1ß. Foram utilizados, em duas fases experimentais, 40 coelhos machos, raça Branco da Nova Zelândia, com peso entre 2,5 e 3,5 kg. Na primeira fase, para determinação da dose hipnótica 50% do AMZ (DHA50%), os animais foram separados em 4 grupos iguais de cinco animais (G1, G2, G3, G4). Na segunda fase experimental os animais foram divididos em 8 grupos iguais (GI, GII, GIII, GIV, GV, GVI, GVII, GVIII), compostos de cinco animais cada, os quais foram pré-tratados com salina (NaCl 0,9%), AMZ (0,3 mg.kg-1) ou DMSO e desafiados com salina, LPS(1,5 æg.kg-1) ou IL-1ß (100 ng.kg-1). A DHA50% e DSHA, para coelhos, foi 0,55 mg.kg-1 e 0,3 mg.kg-1, respectivamente. A febre observada no grupo AMZ-LPS foi inferior àquela demonstrada pelo grupo sal-LPS e superior àquela anotada no grupo DMSO-LPS. Concluiu-se que o AMZ, na dose de 0,3 mg.kg-1, diminui a intensidade da resposta febril ao LPS, mas o DMSO demonstra maior efetividade sobre a febre induzida por LPS. O AMZ não bloqueia a febre causada pela IL-1ß. / Endotoxemia is an important condition in several species being induced by lipopolysaccharides. Released into the bloodstream during the septic shock, they activate the inflammatory cascade leading to syntheses and release of cytokines (TNF, IL-1, IL-6) which are able to produce fever. Colic in horses is frequently observed after treatment with amitraz, a formamidine pesticide. Large colon impactation is one of the consequences of intoxication, mainly by acting on a-2-adrenergic receptors. As a-2 agonists has been proven to produce an increase of the vagus tone, ant that the stimulation of afferent and efferent vagus has been shown to reduced TNF release, the main goal of this study was to evaluate the effects of amitraz over fever when administered before induction of experimental endotoxemia with LPS or IL-1ß administration. Forty male rabbits of the New Zealand white breed weighing 2.5-3.5 kg were used. The present study consisted of two experimental phases. In the first phase, to determine the 50% hypnotic dose of amitraz (DHA50%), the rabbits were divided into four groups (n=5). In the second phase, the rabbits were divided into eight groups (n=5). They were submited to treatment with saline (NaCl 0,9%), AMZ (0.3 mg.kg-1) or DMSO 10 minutes before intravenous injection of saline, LPS (1.5 mg.kg-1) or IL-1ß (100 ng.mg.kg-1). The DHA50% and DSHA for rabbits was 0.55 mg.kg-1 and 0.3 mg.kg-1, respectively. The results demonstrated that the fever observed in AMZ-LPS group was comparatively lower than the fever induced in the group sal-LPS and higher than the fever induced in the group DMSO-LPS. Therefore, It was concluded that amitraz, at the dose of 0,3 mg/kg, decreases the intensity of febrile response to LPS, despite the fact that DMSO is more effective over fever induced by LPS. On the other hand, amitraz does not interfere with the febrile response induced by intravenous administration of IL-1ß.

Made available in DSpace on 2014-06-11T19:29:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-09-02Bitstream added on 2014-06-13T19:38:45Z : No. of bitstreams: 1 carvalho_sm_me_botfm.pdf: 851185 bytes, checksum: eea10cd209e9c4f24efd8d9bd0d1f8fb (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A febre reumática (FR) é uma doença pós-infecciosa, causada pelo Streptococus β hemolítico do Grupo A de Lancefield, de mecanismo auto-imune. As suas manifestações clínicas principais são denominadas sinais maiores, incluindo a artrite, cardite, coréia, nódulos subcutâneos e eritema marginado. Entre as manifestações denominadas sinais menores estão o aumento do intervalo P-R no eletrocardiograma, febre, provas de fase aguda positivas, como a VHS e a proteína C reativa. A comprovação de infecção recente pelo estreptococo é considerada um critério essencial. A FR é ainda prevalente nos países em desenvolvimento e emergentes, tendo como complicações crônica o dano valvular causado pela cardite. A sua prevenção é realizada com a erradicação do estreptococo na orofaringe, por meio da profilaxia primária com penicilina benzatina e a profilaxia secundária com a manutenção da penicilina benzatina em intervalos de 21 dias, de acordo com a recomendação da OMS. Como a FR pode apresentar seqüelas, impacto social e na qualidade de vida, justifica-se a avaliação do desfecho clínico e as suas manifestações em longo prazo. Examinar a epidemiologia, as características clínicas e o desfecho da FR em uma série de casos, nos últimos 20 anos em uma unidade acadêmica dedicada à reumatologia pediátrica (HC-FMB-UNESP). 178 casos foram identificados no período de 1986 a 2007 e destes, 134 foram revisados de acordo com um protocolo listando as manifestações clínicas e laboratoriais, o uso de medicação, o período de acompanhamento e os episódios de recorrência durante o seguimento para vigilância da profilaxia secundária. Os dados demográficos, assim como as manifestações clínicas, laboratoriais e de desfecho são apresentados por meio de freqüência para os dados categóricos e pela estatística descritiva para variáveis contínuas. A probabilidade... / Rheumatic Fever (RF) is a post-infectious disease caused by group A Streptococcus, with autoimmune mechanism. The main clinical features are named major signs as arthritis, carditis, chorea, subcutaneous nodules and erythema marginatum. Among other features, there are the minor signs as increased P-R interval on electrocardiogram (ECG), fever and acute phase reaction measured by erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Evidence of previous streptococcal infection is considered a core criteria. RF is highly prevalent in developing countries, where the main complication is damaged heart valves due to carditis. Prophylaxis is called primary when long-acting benzyl penicilin is administered for the first time after diagnosis and it is called secondary prophylaxis for maintenance treatment with long-acting benzyl penicilin every 3 weeks, according to the WHO guidelines. As RF may result in heart damage with both quality of life and social impact, it is valuable to assess its long term outcome. To examine epidemiology , clinical features and outcome of RF in a paediatric case series, seen in an academic unit dedicated to paediatric rheumatology (HC-FMB-UNESP) during the last 20 years. 178 cases were identified from 1986 to 2007, of those 134 were fully revised according to a standardized protocol checking for clinical and laboratorial features, treatment, follow up and acute RF relapse during follow up for prophylaxis surveillance. Demographics, clinical and laboratorial features as well as outcome data are reported by frequency for categorical variables. Continuous variables are presented by descriptive statistics. The probability of carditis, valve damage and RF relapses were examined by survival analysis with actuarial survival plots. Of 134 revised cases, age at onset was from 4 to 13.8 years, follow up duration was from 1.1 to 16.9 years mean 6.8 SD (3.6) and median... (Complete abstract click electronic access below)