Este estudo objetivou avaliar a: a) eficiência da antibioticoterapia associada à vacinação, de infecções intramamárias (IIM) causadas por Staphylococcus aureus (S. aureus) durante a lactação e secagem; b) variabilidade genética de S. aureus de acordo com a resposta ao tratamento, antibiograma e técnica de Polimorfismo do Comprimento de Fragmentos Amplificados (AFLP). Para a avaliação da eficiência da terapia durante a lactação, foram selecionadas 117 vacas com mastite subclínica causada por S. aureus, a partir de 5 rebanhos leiteiros, as quais foram distribuídas aleatoriamente em três tratamentos: a) controle (sem tratamento), b) antibioticoterapia intramamária + injetável, c) antibioticoterapia intramamária + injetável + vacinação contra S. aureus. Para avaliar a eficiência da antibioticoterapia associada à vacinação contra S. aureus na secagem, foram selecionadas 136 vacas com mastite subclínica causada por S. aureus, as quais foram distribuídas aleatoriamnte em quatro tratamentos: a) antibioticoterapia intramamária, b) antibioticoterapia intramamária + injetável, c) antibioticoterapia intramamária + vacina, d) antibioticoterapia intramamária + injetável + vacina. Para os protocolos de tratamento (lactação e secagem), foi utilizada a vacina antimastítica TopVac (Hipra, Espanha). O antibiótico injetável foi a enrofloxacina (Kinetomax®, Bayer, Brasil), dose única (7,5 mg/kg). A antibioticoterapia intramamária durante a lactação foi realizada com ampicilina 75 mg + cloxacilina 250 mg (Bovigam L, Bayer, Irlanda do Norte), e na secagem, com ampicilina 200 mg + cloxacilina 500 mg (Bovigam ®VS, Bayer, Irlanda do Norte). Um total de 117 isolados de S. aureus foram submetidos à técnica de AFLP. A taxa de cura dos quartos tratados com antibioticoterapia, durante a lactação e na secagem, foi de 80,5% (n = 82) e 91,5% (n = 106), respectivamente. A vacinação contra S. aureus não aumentou a taxa de cura do tratamento durante a lactação, porém reduziu a CCS das vacas vacinada em comparação com as vacas do tratamento controle. No tratamento durante a lactação, primíparas e vacas com apenas um quarto infectado apresentaram maior taxa de cura (79 e 70%, respectivamente) do que pluríparas e vacas com dois ou mais quartos infectados (11 e 17%, respectivamente), respectivamente. A resistência à penicilina não afetou a taxa de cura dos isolados de S. aureus. A probabilidade de um isolado não adaptado à glândula mamária ser multirresistente e resistente à oxacilina foi maior do que a de um isolado adaptado, porém a taxa de cura dos isolados não adaptados foi maior do que a de isolados adaptados. Em conclusão, a antibioticoterapia foi eficiente para tratamento de mastite subclínica causada por S. aureus durante a lactação e secagem, e o resultado de antibiograma foi associado à classificação dos isolados em adaptados e não adaptados, porém não foi associado à resposta a antibioticoterapia / The objectives of this study were to evaluate: a) treatment effectiveness, using antibiotics and vaccination, in cows with intramammary infections caused by S. aureus during lactation and dry period; b) the genetic variability of S. aureus strains according to treatment responses, antibiogram and the AFLP technique. To evaluate the effectiveness of the lactation therapy, 117 icows with S. aureus subclinical mastitis, from 5 herds, were randomly distributed into 3 treatments: a) control; b) Intramammary + Injectable; c) Intramammary + injectable + Vaccine. To evaluate the effectiveness of the dry off therapy, 136 cows with S. aureus subclinical mastitis were randomly distributed into 4 treatments: a) Intramammary; b) Intramammary + Injectable (INT + INJ); c) Intramammary + Vaccine (INT + VAC); d) Intramammary + Injectable + Vaccine (INT + INJ + VAC). For both therapies (lactation and dry off), the antimastitis vaccine was the TopVac (Hipra, Spain). The injetable antibiotic was enrofloxacin (Kinetomax®, Bayer S. A., Brasil) single dose (7,5 mg/kg). The intramammary therapy was, during lactation, with ampicillin 75 mg + cloxacilin 200 mg (Bovigam L, Bayer, North Ireland) and at dry off with ampicillin 250 mg + cloxacilin 500 mg (Bovigam ®VS, Bayer, North Ireland). S. aureus isolates (117) were submitted to the AFLP technique. The cure rate of quarters treated with antibiotics during lactation and dry period was 80,5% (n = 82) e 91,5% (n = 106), respectively. Vaccination against S. aureus didn't raise the cure rate during lactation, but lowered the SCC of vaccinated cows compared to control cows. In the lactation therapy, primiparous and cows with one infected quarter had higher cure rates (79 and 70%, respectively) than pluriparous and cows with more than one infected quarter (11 and 17%, respectively), respectively. Resistence to penicillin did not affect S. aureus isolates cure rate. The probability of a non adapted S. aureus isolate to be multiresistant and resistant to oxacilin was higher than an adapted isolate, but cure rates of non adapted isolates was higher than adapted isolates. In conclusion, antibiotic therapy was efficient to treat S. aureus subclinical mastitis during lactation and dry period, and the antibiogram result was associated with the isolates classification in adapted and non adapted, but was not associated with the response to therapy

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-06-22T15:01:31Z No. of bitstreams: 1 rafaelapinheirolacerda.pdf: 2532354 bytes, checksum: a9f84d4aefdf273756887ac76d89cfa7 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-08-07T19:22:32Z (GMT) No. of bitstreams: 1 rafaelapinheirolacerda.pdf: 2532354 bytes, checksum: a9f84d4aefdf273756887ac76d89cfa7 (MD5) / Made available in DSpace on 2017-08-07T19:22:32Z (GMT). No. of bitstreams: 1 rafaelapinheirolacerda.pdf: 2532354 bytes, checksum: a9f84d4aefdf273756887ac76d89cfa7 (MD5) Previous issue date: 2014-01-28 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / INTRODUÇÃO: Pacientes com hipotireoidismo subclínico (HSC) podem apresentar alterações no sistema cardiovascular. Dessa forma, o objetivo desse estudo foi avaliar a integridade do reflexo pressor do exercício físico em mulheres com HSC. MÉTODOS: Foram avaliadas dezoito mulheres com HSC (Grupo HSC) e vinte mulheres eutiroidianas (Grupo Controle), pareadas por idade (37 ± 11 vs. 38 ± 11 anos, p=0,907, respectivamente), índice de massa corporal (26 ± 5 vs. 24 ± 4 kg/m2, p=0,221, respectivamente) e nível de atividade física (6,93 ± 0,81 vs. 7,66 ± 1,14, p=0,063, respectivamente). A pressão arterial foi medida minuto a minuto pelo método oscilométrico (DIXTAL2023®), a frequência cardíaca medida continuamente pelo eletrocardiograma (DIXTAL2023®) e o fluxo sanguíneo do antebraço pela técnica de pletismografia de oclusão venosa (Hokanson®). A condutância vascular do antebraço foi calculada pela divisão do fluxo sanguíneo do antebraço pela pressão arterial média, multiplicada por 100. Registrando essas variáveis por 3 minutos de basal seguidos de 3 minutos de exercício físico, foram realizados os protocolos de exercício físico passivo, exercício físico isométrico a 10% da contração voluntária máxima do antebraço, exercício físico a 30% da contração voluntária máxima do antebraço e por 2 minutos oclusão circulatória pós-exercício físico isométrico a 30%. ANOVA de dois fatores foi utilizada para testar as diferenças, adotando significativo p<0,05. RESULTADOS: Durante o exercício físico passivo, a pressão arterial sistólica, diastólica e média sofreram diminuição significativa, porém semelhante entre os grupos HSC e Controle. A frequência cardíaca, o fluxo sanguíneo do antebraço e a condutância vascular do antebraço não apresentaram modificações ao longo do protocolo de exercício físico passivo. Durante o exercício físico de leve intensidade a pressão arterial sistólica não sofreu nenhuma alteração, a pressão arterial diastólica foi significativamente diferente entre os grupos HSC e Controle. Os valores da pressão arterial média, frequência cardíaca, fluxo sanguíneo do antebraço e condutância vascular do antebraço apresentaram aumento significativo e se comportaram similarmente. Durante o exercício físico de moderada intensidade os valores de pressão arterial sistólica, diastólica, média, fluxo sanguíneo do antebraço e condutância vascular do antebraço aumentaram significativamente e similarmente entre os grupos HSC e Controle. Entretanto a frequência cardíaca apresentou comportamento significativamente diferente entre os grupos HSC e Controle, porém, ambos os grupos apresentaram aumento significativo da frequência cardíaca em relação aos valores basais. Para a oclusão circulatória, os grupos sofreram aumento da pressão arterial sistólica, diastólica e média, porém com comportamento similar. CONCLUSÃO: Mulheres com HSC apresentam reflexo pressor do exercício físico íntegro. / INTRODUCTION: Patients with subclinical hypothyroidism (SCH) may show changes in the cardiovascular system. Thus, the aim of this study was to evaluate the integrity of the pressor reflex exercise in women with SCH. METHODS: Were evaluated eighteen women with SCH (Group SCH) and twenty euthyroid women (Group Control), matched for age (37 ± 11 vs. 38 ± 11 years; p=0.907, respectively), body mass index (26 ± 5 vs. 24 ± 4 kg/m2; p=0.221, respectively) and level of physical activity (6,93 ± 0,81 vs. 7,66 ± 1,14, p=0,063, respectively). Blood pressure was measured every minute by oscillometry (DIXTAL2023®), heart rate measured continuously by electrocardiogram (DIXTAL2023®) and forearm blood flow by the technique of venous occlusion plethysmography (Hokanson®). In forearm vascular conductance was calculated by dividing the forearm blood flow by the mean arterial pressure multiplied by 100. Registering these variables from baseline for 3 minutes followed by 3 minutes of exercise, the protocols of passive exercise, isometric exercise at 10% of maximal voluntary contraction of forearm exercise at 30% maximal voluntary contraction of the forearm were performed and circulatory occlusion for 2 minutes post-isometric physical exercise to 30%. Two-factor ANOVA was used to test differences, significant considering p< 0.05. RESULTS: During the passive exercise, systolic blood pressure, diastolic and mean suffered significant decline, but similar between SCH and Control groups. The heart rate, forearm blood flow and vascular conductance of the forearm showed no change during the protocol of passive exercise. During mild exercise systolic blood pressure did not undergo any changes, diastolic blood pressure was significantly different between the SCH and Control groups. The values of mean arterial pressure, heart rate, forearm blood flow and vascular conductance of the forearm showed a significant increase and behaved similarly. During exercise of moderate intensity values of systolic, diastolic, mean, forearm blood flow and vascular conductance of the forearm increased significantly and similarly between SCH and Control groups. However, the heart rate behavior was significantly different between the SCH and Control groups, however, both groups showed a significant increase in heart rate from baseline. To circulatory occlusion groups had an increase in systolic blood pressure, diastolic and mean, but with similar behavior. CONCLUSION: Women with SCH have pressor reflex upright exercise.

Psychopathy is a severe personality disorder that results in antisocial, manipulative, and callous behavior. The main diagnostic instrument for assessing psychopathy is the Psychopathy Checklist-Revised. This thesis will introduce the psychopathy construct, including what is known as subclinical psychopathy. Subclinical psychopathy refers to individuals who exhibit many of the characteristics of psychopathy, except for some of the more severe antisocial behaviors. This constellation of traits allows the subclinical psychopath to avoid incarceration. The fundamental difference between clinical and subclinical psychopaths is a major question in the field of psychopathy and is the main theme of this thesis. Impaired empathy is one of the key aspects of psychopathy and it may be a significant factor in both clinical and subclinical psychopaths. Subclinical psychopathy may be related to a moderated or altered expression of empathy. Hence, the empathy construct is a secondary concern in this thesis. This thesis has two aims: (a) to argue that the conceptualization of subclinical psychopathy is flawed and needs revision in accordance with less ambiguous criteria; and (b) to present data in support of the hypothesis that subclinical psychopaths have intact, or even enhanced, cognitive capacities in contrast to clinical psychopaths.

Elevated Thyroid-Stimulating Hormone (TSH) is associated with an increased risk of cardiovascular disease (CVD). We hypothesized that TSH-stimulated FA release from adipocytes contributes to macrophage inflammation. 3T3-L1 and human subcutaneous differentiated adipocytes were treated with TSH for 4 hours under various conditions and lipolysis assessed via glycerol secretion. Optimal conditions were determined and protein expression of ATGL, HSL and perilipin remained stable. TSH-stimulated 3T3-L1 or human adipocyte-conditioned medium (T-ACM) was placed on murine J774 or human THP-1 macrophages, respectively, and macrophage cytokine mRNA levels (IL-1β, IL-6, MCP-1, and TNFα) were measured by real-time RT-PCR. T-ACM did not change cytokine mRNA expression in J774 macrophages or THP-1 macrophages when compared to ACM. Absence of BSA in the medium may have hindered release of FA from differentiated adipocytes into the medium, BSA may be required to permit adequate FA accumulation in the medium to then evaluate the effect of T-ACM on macrophages. Further investigation is required to determine the effect of FA on J774 and THP-1 inflammatory response.

In subclinical hypothyroidism (SH), high levels of circulating thyroid stimulating hormone (TSH) maintain normal thyroid hormone levels, despite mild thyroid failure. SH is associated with cardiovascular disease and insulin resistance, although the underlying pathophysiology is not fully understood. We hypothesized that TSH may inhibit insulin action in adipocytes. To investigate this relationship, we studied primary human differentiated adipocytes. Abdominal subcutaneous adipose tissue samples were obtained (approved by OHSN-REB) from 16 weight-stable patients undergoing elective abdominal surgery. We stimulated adipocytes differentiated from stromal preadipocytes with 5 mU/ml TSH and/or 100 nM insulin, and assessed acute insulin signaling, lipogenesis and glucose uptake. Immunoblot analysis revealed that TSH suppressed insulin-stimulated Akt phosphorylation by 45% (n=5; p = 0.01). When adipocytes were pre-incubated with conventional protein kinase C (cPKC) inhibitor Gö6976, TSH inhibition was blocked. Our data indicate that TSH inhibits insulin-stimulated lipogenesis (up to 37%), but depends on BMI. Insulin-stimulated glucose uptake was enhanced by 36% and also correlated with BMI. This data suggests that TSH can modulate adipocyte insulin signaling.

Several psychological processes motivate the use of Facebook. The correlation between subclinical narcissistic traits and Facebook use has been examined, but the results have been inconsistent. The purpose of this study was to examine the relationship between Facebook use and the exhibition of subclinical narcissistic traits. The method for this study was meant to improve upon previous studies that used self-reported data by providing researchers with a technique to collect Facebook data from the personal pages of participants, with informed consent. Social learning theory provided the theoretical foundation for this study. This theory posits that new patterns of behavior can be acquired through direct experience or by observing the behavior of others. This theory could explain why a billion people choose to post pictures, share news articles, add friends, and engage in other Facebook activities. Using a quantitative approach, approximately 3 months of Facebook activity from 93 participants were analyzed and correlated with Narcissistic Personality Inventory (NPI) scores. A multiple regression analysis was then used to examine the data in relation to the research questions and hypotheses. There were no statistically significant findings for Facebook activity and NPI scores. These findings may challenge the popular notion that Facebook and other social media represent a platform for narcissistic self-promotion. This study has potential to promote social change, in that the negative connotation may be removed from social media use, allowing more people to communicate openly without the fear of being perceived as narcissistic.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20245号 / 医博第4204号 / 新制||医||1020(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 羽賀 博典, 教授 鈴木 茂彦 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

With the high mortality rate of cardiovascular disease, it is important to study the early signs. The early detection of cardiovascular disease can lead to saved lives. Currently the most prevalent detection methods are the Framingham Risk Score and the carotid intima media thickness, both of which are insufficient. The necessary tool for early detection requires a uniform quantification system. The stimulus leading to endothelial dysfunction, the most significant predictor of a major adverse cardiovascular event (MACE)—and subsequently subclinical atherosclerosis—is reduced shear stress. Increased surface relative roughness affects the flow profile transition from laminar to turbulent resulting in reduced shear rate. The relationship between the shear stress and the relative roughness was studied using a computer model for fluid flow. A model of the brachial artery was generated to study its hemodynamics. Roughness values for both laminar and turbulent flow were calculated to use with the governing equations programmed in COMSOL Multiphysics. With all other factors remaining constant in the model, the roughness values were changed. From the model profile plots, line graphs, and numeral data are generated. This data provides information about how the shear stress and the shear rate change with respect to the relative roughness value. The models with different wall boundary conditions—slip versus Navier slip—were unable to be directly compared due to the differences in value magnitude. When the flow profile transitions from laminar to turbulent, there is a corresponding drop in both the shear stress and the shear rate values. Additional testing is required to determine a critical relative roughness value for this change in cumulative shear.

Background: The human gut microbiota is the complex microbial community that lives in our gut. The gut microbiota has a key role in health and disease and its disruption has been linked to several chronic diseases such as cardiovascular diseases. As antibiotics are well known disruptors of gut microbiota, the aim of this thesis work was to identify associations between previous antibiotic consumption and the abundance of seven gut microbiota species previously linked to subclinical coronary atherosclerosis in the large population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort. Materials and Methods: Faecal samples of 9,794 individuals from the SCAPIS Uppsala and Malmö cohorts were analysed by deep shotgun metagenomics sequencing in a cross-sectional study. Previous antibiotic use was retrieved using the Swedish Drug Prescribed Register and divided into three periods: one year, between one and five years, and between five and nine years before faecal sampling. Associations between antibiotic consumption and the gut microbiota species were evaluated using linear regression adjusted for covariates and corrected for multiple testing. Results: Our results showed that antibiotic consumption was associated with an increased abundance of Ligilactobacillus salivarius, Bifidobacterium dentium, Rothia mucilaginosa, Streptococcus parasanguinis and Streptococcus oralis subsp. oralis. Often these positive associations were present for antibiotic consumed between one and five years before sampling.  The strongest associations were for broad-spectrum antibiotics and lincosamides with L. salivarius, B. dentium, R. mucilaginosa and S. parasanguinis; and for nitrofurantoin with S. oralis subsp. oralis.   Conclusions: This study provides insights on how antibiotic consumption is associated with enrichment and higher abundance of species previously linked with subclinical coronary atherosclerosis in the gut. Hence, this study provides insights on unintended effects of using antibiotics for managing infections, which underscores antibiotic use as not only a concern for development of antibiotic resistance but also for disrupting the gut microbiota, which may contribute to disease development. Knowledge about effect of antibiotics in gut microbiota may help to adequate this therapy according to comorbidities of individual profiles and to design better diagnostic tools for the risk population with the goal of preventing cardiovascular events in the general population.

Cardiovascular disease is the leading cause of death globally and is responsible for taking 17.9 million lives per year. Despite the use of clinical treatments and detection methods, there remains a large population of individuals that suffer from CVD whose symptoms are left undetected and untreated prior to a life-threatening cardiac event. This highlights a need for an early detection method that can prevent the manifestation and worsening of the disease as well as address limitations of current early detection methods. An area of interest for early detection of CVD is subclinical atherosclerosis, which is the long, early, asymptomatic stage of plaque formation. Subclinical atherosclerosis has been namely associated with endothelial dysfunction and is the result of the pathological state of the endothelium due to its impact on vascular homeostasis, thrombosis, and vascular tone. Endothelial dysfunction is a result of several factors contributing to and promoting inflammation and results in changes in biological pathways that can alter the surface of the endothelium. This surface modification or added roughness changes the flow profile from laminar to turbulent flow due to the decreased shear stress on the vascular wall. Current detection methods such as carotid intima media thickness (CIMT) and flow-mediated dilation (FMD) targeted at identifying the early stages of atherosclerosis present limitations such as identifying late-stage effects of plaque formation and subjective readings highlight the need for a different approach to early detection. This experimental study aims to present a possible method of detecting the morphological changes of the endothelium due to inflammation through acoustic analysis of flow. Three silicone artery phantom groups were created with different degrees of inner diameter surface roughness to explore the relationship between relative roughness and sound associated with fluid flow. The results of this study are power spectral density graphs (PSD) which show frequency peaks associated with each of the phantoms at a theoretical laminar and turbulent Reynolds number. The PSD graphs show that there is a difference in frequency response between a smooth and rough artery phantom at the same flow rate providing preliminary support that sound analysis of fluid flow could provide information regarding early-stage cardiovascular disease.