Resumo: O objetivo deste estudo foi avaliar o papel do ácido retinóico na remodelação cardíaca induzida pela exposição à fumaça do cigarro. Os ratos foram divididos em três grupos: controle (C, n = 8); expostos animais expostos à fumaça do cigarro (EFC, n = 9); animais expostos à fumaça de cigarro e suplementados com ácido retinóico (EFC-AR, n = 9). Após dois meses, foram submetidos ao ecocardiograma e análise morfométrica. Os dados estão expressos em média ± desvio padrão ou medianas e intervalo interquartílico (Q1-Q3). Não houve diferença na pressão sistólica caudal entre os grupos (C = 116 ± 27 mmHg; EFC = 129 ± 17 mmHg; EFC-AR = 139 ± 19 mmHg; p = 0,102). O grupo EFC mostrou maior diâmetro diastólico do ventrículo esquerdo ajustado ao peso corporal (C = 18,42 ± 3,57 mm/kg; EFC = 23 ± 1,85 mm/kg; EFC-AR = 19,51 ± 0,99 mm/kg; p = 0,001) e sistólico ajustado ao peso corporal (C = 8,25 ± 2,16 mm/kg; EFC = 11,53 ± 1,31 mm/kg; EFC-AR = 8,25 ± 0,71 mm/kg; p = <0,001) quando comparado com C grupo e EFC-AR. Por outro lado, não houve diferença entre C e EFC-AR. A espessura da parede do ventrículo esquerdo ajustado ao diâmetro diastólico do ventrículo esquerdo foi maior no grupo C do que nos EFC (C = 0,20 (0,18-0,23); EFC = 0,15 (0,14-0,18); EFC-AR = 0,19 (0,17-0,22; p = 0,003). A fração de ejeção (C = 0,91 ± 0,02; EFC = 0,87 ± 0,03; EFC-AR = 0,92 ± 0,03; p = 0,003) e a fração de encurtamento (C = 55,77 ± 4,41%; EFC = 49,73 ± 4,43%; EFC-AR = 57,60 ± 5,15%; p = 0,005) foram mais elevados nos animais do grupo C e EFC-AR em relação aos animais do grupo EFC. Por outro lado, não houve diferenças entre C e EFC-AR. Além disso, o tabagismo está associado com um aumento significativo da área seccional do miócito (C = 294 ± 21 μm2; EFC = 347 ± 44 μm2; EFC-AR = 310 ± 37 μm2; p = 0,016). Por outro lado... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The objective of this study was to evaluate the role of retinoic acid in the myocardial remodeling induced by tobacco smoke exposure. Rats were allocated into three groups: control (C, n=8); exposed to tobacco smoke (ETS, n=9); exposed to tobacco smoke and all-transretinoic acid (ETS-AR, n = 9). After two months, were submitted to echocardiogram, and morphometric analyses. Data are expressed as mean ± SD or medians (including the lower quartile and upper quartile). There were no differences in the tail systolic pressure among the groups (C = 116 ± 27 mmHg, ETS = 129 ± 17 mmHg, ETS-AR = 139 ± 19 mmHg; p = 0,102). ETS showed higher normalized left ventricular diastolic (C = 18,42 ± 3,57 mm/kg, ETS = 23 ± 1,85 mm/kg, ETS-AR = 19,51 ± 0,99 mm/kg; p = 0,001) and systolic (C = 8,25 ± 2,16 mm/kg, ETS = 11,53 ± 1,31 mm/kg, ETS-AR = 8,25 ± 0,71mm/kg; p = <0,001) diameters than C and ETS-AR. On the other hand, there were no differences between C and ETS-RA. LVWT/LVEDD was higher in C than ETS (C = 0,20 (0,18-0,23), ETS = 0,15 (0,14-0,18), ETS-RA = 0,19 (0,17-0,22; p = 0,030). The ejection fraction (C = 0,91 ± 0,02, ETS = 0,87 ± 0,03, ETS-AR = 0,92 ± 0,03; p = 0,003) and fractional shortening (C = 55,77 ± 4,41 %, ETS = 49,73 ± 4,43 %, ETS-AR = 57,60 ± 5,15 %; p = 0,005) were higher in C and ETS-RA animals than ETS animals. On the other hand, there were no differences between C and ETS-RA. Also, smoking was associated with significantly increased myocyte cross-sectional area (C = 294 ± 21 μm2, ETS = 347 ± 44 μm2, ETS-RA = 310 ± 37 μm2; p = 0,016). On the other hand, there were no differences between C and ETS-RA. Retinoic acid did not affect other functional or morphological variables. In conclusion, ...(Complete abstract click electronic access below) / Orientador: Leonardo A. M. Zornoff / Coorientador: Sergio A. R. de Paiva / Banca: Paula Schmidt Azevedo Gaiolla / Banca: Wilson Nadruz Junior / Mestre

Introduction: In patients who present with ST-elevation myocardial infarction (STEMI), primary percutaneous coronary intervention and the administration of dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) are recommended. This thesis aimed to determine the extent to which oral P2Y12 inhibitors (clopidogrel/prasugrel/ticagrelor) exert their antiplatelet effect during the acute phase of a STEMI compared to non-ST elevation myocardial infarction (NSTEMI). Methods: The degree and time-course of platelet inhibition following oral administration of P2Y12 inhibitors was determined in 87 patients from their pharmacokinetic (plasma concentration) and pharmacodynamic (degree of platelet inhibition) profiles at 20 minutes, balloon inflation, 60 and 240 minutes using liquid chromatography/mass spectrometry, VerifyNow and VASP-phosphorylation assays. Results: In STEMI patients, oral P2Y12 inhibitors do not provide adequate levels of platelet inhibition at the time of angioplasty and have a limited effect at 240 minutes. The NSTEMI group displayed a marked and rapid antiplatelet effect at all time points. A significant difference in the acute efficacy of oral P2Y12 inhibitors in STEMI vs NSTEMI patients (p < 0.001) was seen. Conclusion: Oral P2Y12 inhibitors display delayed and attenuated antiplatelet effects in STEMI patients in the immediate period following administration of a loading dose when compared with NSTEMI patients.

Syfte: Syftet med studien var att jämföra korneala mätningar tagna med två olika topografiska mätinstrument (Sirius &amp; Wave Analyzer Medica 700) och att utvärdera om dessa två instrument kan användas utbytbart. Metod: Det var 23 stycken deltagare i denna studie som var indelade i två grupper. Det var 17 stycken deltagare i grupp A som hade en normal kornea och i grupp B var det 6 stycken deltagare som hade en onormal kornea. Tre upprepade mätningar utfördes på det högra ögat för alla deltagare med båda instrumenten. Förutom på en deltagare som hade keratokonus i hens vänstra öga. De simulerade K (Sim-K) parametrarna som innehåller ”Flattest” (Kf), ”Steepest” (Ks) och ”Average” K (Km) analyserades. Dessutom togs den centrala korneas tjocklek också med båda mätinstrumenten och utvärderades. Resultat: En skillnad mellan de uppmätta värdena för de två mätinstrumenten hittades. Mellan dessa två mätinstrument var medelvärdet av skillnaden i grupp A för parametrarna Kf, Ks och Km ungefär 0,1mm. I grupp B var medelvärdet av skillnaden för parametrarna Kf, Ks och Km ungefär 0,15mm. För pachymetri var medelvärdet av skillnaden för de två mätinstrumenten 23µm för grupp A och 31µm för grupp B. Slutsats: De två topografiska mätinstrumenten visade en statistiskt signifikant skillnad i mätning utav korneala parametrarna. Trots att det var en statistiskt signifikant skillnad när man jämförde Sim-K för båda mätinstrumenten var skillnaden kliniskt obetydlig för de deltagare som hade en frisk kornea. Därför kan båda utav dessa mätinstrument användas utbytbart för att mäta keratometri i friska ögon.

Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

Il lavoro di ricerca verte sull'analisi del rapporto tra medicina e pedagogia, in una prospettiva di intervento educativo finalizzato alla formazione dei futuri medici. La ricerca si è avvalsa di una letteratura straniera per il segmento relativo all'affermarsi della pedagogia medica, a livello nazionale ed internazionale, cui è seguita un'indagine empirica tendente a "dare voce" ai protagonisti della ricerca, gli studenti delle Facoltà di Medicina. / The research analyses the relation between education and medicine, in order to plan an educational intervention for future doctors. The research work is based on an international bibliography on Medical Education. There is also an empirical part in order to study the 'real voice' of students and professors.

Thesis (Ph. D.)--University of Hong Kong, 2001. / Includes bibliographical references.

Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in History." Includes bibliographical references (p. 209-250).

Habilitationsschrift--Mainz. / Includes indexes. Includes bibliographical references (p. [217]-226).

published_or_final_version / Medicine / Master / Master of Research in Medicine

Influenza epidemics have become a major public health concern worldwide. According to the World Health Organization, the annual epidemics results in about three to five million cases of severe illness, and about 250 to 500 thousand deaths. Recurring emergence of new influenza viruses and viruses that are resistant to currently approved antiviral medications pose a critical need to explore new or alternative medications. A classical Traditional Chinese Medicine (TCM) decoction consisting of nine herbs, named Yinqiaosan (YQS, 銀翹散), has a long history for treating respiratory diseases in China. However, the efficacy of YQS has not been investigated mechanistically. In the present study, the effectiveness of YQS in treating influenza virus infection was examined. The potential mechanisms of action of two active compounds present in one of the component herbs of YQS were also investigated. Results showed that YQS increased the survival rate of the mice in an in vivo influenza virus infection model with significant reduction in lung viral titers. In order to further delineate the mechanisms of action of YQS, compounds present in a principal ingredient of YQS were examined for antiviral and immunomodulatory effects. In screening a panel of fractions extracted from YQS, forsythoside A was demonstrated to suppress the viral titers of a wide range of influenza viruses including the oseltamivir-resistant and the 2009 pandemic H1N1 viruses. Through electron microscopy, slow or abnormal viral budding events were observed upon forsythoside A treatment during influenza virus infection. Western blot analysis revealed a reduced influenza virus M1 protein expression. As previous report showed that assembly of viral components into an infectious particle required a threshold level of M1 protein, reduced M1 expression in the cells treated with forsythoside A may contribute to the virus replication suppression. On the other hand, innate immune responses provide first line protection against influenza virus infections. However, excessive responses often result in tissue damage. Cyclooxygenase (COX)-2 is an immunomodulatory factor that has been shown to play a role in the pathogenesis of influenza viruses. A previous COX-2 knock-out mice model showed that COX-2 deficiency is beneficial to the host during influenza viral infection, in which mortality was significantly reduced. Furthermore, during H5N1 infection, it has been shown that COX-2 level significantly increased and it played an essential role in coordinating the productions of inflammatory cytokines, while in another study, pharmacological inhibition of COX-2 suppressed H5N1 virus replication in primary human macrophages. In view of the roles of COX-2 during influenza virus infection, the presence of compound in YQS that reduces the influenza virus-induced COX-2 level was examined. Present results showed that jacaranone not only reduced the influenza virus-induced cyclooxygenase (COX)-2 mRNA level, it also suppressed the subsequent production of prostaglandin E2 level in primary human macrophages. At the same time, jacaranone inhibited the virus induced-activations of ERK1/2 and Akt, which are involved in the COX-2 induction. Jacaranone also suppressed, at least in part, the COX-2 mRNA level at the transcriptional level by inhibiting the nuclear translocation of NF-κB. To conclude, TCM has been recognized as an important part in complementary and alternative medicine and it is an ample source of antimicrobial drugs. The use of a mixture of herbs is the major therapeutic approach of TCM in which, the principal ingredients provide the main therapeutic actions while the others enhance the effects or diminish the side effects of the principal ones. Some components act mainly for symptomatic control. The present study not only supports the efficacy of YQS, but also gives evidences to an active antiviral compound and an immunomodulatory compound found in YQS. They may act as either principle or supporting components depending on the purpose of application. This study provides new insights on future novel drug development from the existing wisdom of TCM. / published_or_final_version / Paediatrics and Adolescent Medicine / Doctoral / Doctor of Philosophy