Cardiovascular diseases (CVD) are the number one cause of death worldwide. About one fifth of those who survived a myocardial infarction will suffer a recurrent cardiovascular event (CVE). Given the low participation in recommended cardiac rehabilitation, there is interest in early risk stratification after a primary CVE. This dissertation evaluates leisure time physical activity (LTPA), N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) and cystatin C as predictors of a secondary CVE in a German cohort of cardiac rehabilitation patients with stable coronary heart disease followed from 1999 to 2008. Study 1 evaluated self-reported LTPA at one-year follow-up. Those reporting seldom/never practice of LTPA showed a higher risk (Hazard Ratio (HR) 1.30 [95% Confidence Interval (CI) 0.62, 2.69]), while those reporting LTPA at least 5-6 times/week had a reduced risk (HR 0.88 [95% CI 0.54, 1.43]) for a subsequent CVE, when compared to the reference group (1-4 times/month). Study 2 examined LTPA trajectories during the age period 20-49 years. Compared to those with a gradual decline of LTPA, the highest risk was observed among those with a steeper decrease of LTPA (HR 1.59 [95% CI 0.97, 2.62]). A continuous increase of LTPA was associated with a risk reduction (HR 0.71 [95% CI 0.41, 1.22]) with respect to a recurrent CVE. Studies 3 and 4 evaluated the prognostic value of two novel biomarkers, when added to a model containing well-established CVD risk factors. In Study 3, NT-proBNP levels at one-year follow-up and a 10% increase in the slope of a NT-proBNP three-year trajectory were associated with a subsequent CVE ,with HRs of 1.63 [95% CI 1.17, 2.27] and 1.24 [95% CI 1.12, 1.37], respectively. One-year, but not baseline, levels of NT-proBNP showed an improvement in risk reclassification. Study 4 examined cystatin C versus creatinine. Although both were associated with a recurrent CVE, only the addition of cystatin C improved model performance, discrimination and reclassification. In conclusion, in patients with stable coronary heart disease, LTPA, NT-proBNP, and cystatin C might help to identify individuals at high risk for a recurrent CVE. Further research is needed to evaluate treatment modalities for secondary prevention in this group.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20275号 / 医博第4234号 / 新制||医||1021(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 横出 正之, 教授 小西 靖彦, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21658号 / 医博第4464号 / 新制||医||1035(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 福田 和彦, 教授 湊谷 謙司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21660号 / 医博第4466号 / 新制||医||1035(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 柳田 素子, 教授 滝田 順子, 教授 妻木 範行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21673号 / 医博第4479号 / 新制||医||1036(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 道行, 教授 滝田 順子, 教授 戸口田 淳也 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21678号 / 医博第4484号 / 新制||医||1036(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 柳田 素子, 教授 福原 俊一, 教授 今中 雄一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24787号 / 医博第4979号 / 新制||医||1066(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 秀一, 教授 森本 尚樹, 教授 安達 泰治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Atrial Naturietic Peptide (ANP) is a neuropeptide that regulates function of the hypothalamic-pituitary-adrenal (HPA) axis, immune and neuroimmune system, and epigenetic factors. Research has indicated that ANP may mediate alcohol intake, withdrawal, and craving like behaviors. ANP receptors are present in the mesocorticolimbic (MCL) reward pathway of the brain, which includes the nucleus accumbens (Acb) and the ventral tegmental area (VTA). The objectives of the present study were to examine the effects of ANP microinjected into Acb subregions (Shell (Sh), Core (Co), ventral to AcbSh) on operant ethanol (EtOH) self-administration and into posterior VTA (pVTA) on EtOH-seeking behavior of female alcohol-preferring (P) rats. In the first experiment, ANP (0, 10 μg, or 100 μg) was microinjected into subregions of the Acb to determine its effects on EtOH self-administration. In the second experiment, ANP was microinjected into pVTA to determine its effects on Pavlovian Spontaneous Recovery (PSR) of responding, a measure of context-induced EtOH-seeking behavior. Administration of ANP directly into the AcbSh significantly reduced EtOH self-administration compared to vehicle, whereas ANP into the AcbCo or areas directly ventral to the AcbSh did not alter responding for EtOH. Microinjection of ANP into the pVTA significantly reduced responding on the EtOH-associated lever during the PSR test. The data indicate that activation of ANP systems in the (a) AcbSh can inhibit EtOH intake, and (b) in the pVTA can inhibit EtOH-seeking behavior. The results suggest that manipulations of the ANP system could be a potential target for pharmacotherapeutic intervention to treat alcohol use disorder. Supported in part by AA07462, AA07611, AA10717, AA10721, AA013522, AA019366, AA020908, AA022287, and AA024612.

No description available.

The production of embryos has been described as a revolutionary process with the ability to make cattle systems more successful. However, despite constant research done in the field of embryology, there remains a discrepancy between the quality of in vitro produced (IVP) and in vivo derived (IVD) embryos. This difference is potentially associated with the lack of synchronization between nuclear and cytoplasmic maturation events within the oocyte, which is carefully mediated in the ovarian environment and the cumulus oocyte complex (COC). The purpose of this thesis was to utilize a pre-maturation culture system to keep oocytes in an arrested germinal vesicle (GV) state before subjecting them to maturation. In the first half of the experiment, oocytes were pre-matured in C-type natriuretic peptide (CNP) supplemented medium for 12 hours. Following pre-maturation, oocytes were transferred to amphiregulin (AREG) for another 12 hours to develop. This procedure is known as CAPA-AREG. After fertilization and a 7- day culture, embryos were assessed for cleavage rate and blastocyst rate. Embryos were also subjected to staining in order to evaluate lipid content and mitochondrial activity via confocal microscopy and ImageJ software. Hurdles in acquiring data also encouraged an assessment on the IVF laboratory and how procedures can be optimized. Overall, embryology lab procedures must be strictly followed, and the laboratory environment must be maintained to the best of the staff’s ability to increase success rates. Due to mishaps in the laboratory, the effectiveness of CNP and AREG on improving bovine oocyte maturation and embryo development is still inconclusive. Further research is required to determine if CNP and AREG can be utilized in future bovine IVF procedures.