Die vorliegende Arbeit beschreibt Untersuchungen über die Auswirkungen des P2Y12-Rezeptor-Antagonisten AZD6140 (Ticagrelor) auf die Plättchenfunktionen diabetischer Ratten. AZD6140 ist ein reversibler, direkter, potenter und oraler Inhibitor des P2Y12-Rezeptors. AZD6140 reduziert als Einzeldosis von 5 mg/ kg Körpergewicht verabreicht die Empfindlichkeit der Plättchen hinsichtlich ADP schnell und reversibel. Zudem konnte bereits nach 30 Minuten eine signifikante Hemmung der Plättchenaggregation beobachtet werden. Auch die P-Selektin-Oberflächenexpression und die Plättchenadhäsion wurden nach Einmalgabe von AZD6140 signifikant reduziert. Eine chronische Behandlung diabetischer Ratten mit AZD6140 reduzierte die Plättchenaktivierung in vivo und die Plättchenempfindlichkeit in vitro. Zudem verminderte der P2Y12-Rezeptor-Antagonist nach zweiwöchiger Verabreichung signifikant die Sekretion des pro-inflammatorischen Zytokins RANTES. Der schnelle antithrombozytäre Effekt ist besonders bei Patienten, die für eine PCI vorgesehen sind, von Vorteil, da in solchen Situationen eine effektive, maximale, rasche und vorhersehbare Hemmung der ADP-induzierten Plättchenaggregation notwendig ist, um bessere klinische Ergebnisse erzielen zu können. Die reversible Wirkung von AZD6140 auf die thrombozytären Funktionen ist insbesondere bei vorbehandelten Patienten, die beispielsweise einen koronaren Bypass erhalten sollen, vorteilhaft, da in der Bypasschirurgie über exzessive Blutungsereignisse nach irreversibler antithrombozytärer Therapie berichtet wurde. Im Vergleich zu Clopidogrel ist die Behandlung mit diesem neuen P2Y12-Antagonisten mit einer stärkeren Plättchenhemmung und einer geringeren Variabilität in der Antwort auf die Therapie verbunden. Eine interindividuelle Variabilität in der Wirksamkeit, wie sie bei Clopidogrel zu finden ist, korreliert mit einem erhöhten Risiko unerwünschter kardiovaskulärer Ereignisse, eine Tatsache, die sich besonders gravierend in kardiovaskulären Risikogruppen auswirkt. AZD6140 zeigt eine bessere Wirksamkeit, einen schnelleren Beginn und ein rascheres Ende seiner Wirkung auf die Plättchenfunktionen sowie eine geringere Verlängerung der Blutungszeit im Vergleich zu Clopidogrel. In klinischen Studien wurde das Wirkungsprofil von AZD6140 mit dem von Clopidogrel verglichen. Zuletzt wurde in der Phase III-Studie PLATO die signifikante Überlegenheit in der Wirksamkeit von AZD6140 gegenüber Clopidogrel bestätigt. / The present work describes studies of the effects of the P2Y12 receptor antagonist AZD6140 (ticagrelor) on platelet functions of diabetic rats. AZD6140 is a reversible, direct, and potent oral inhibitor of the P2Y12 receptor. As a single dose of 5 mg / kg body weight AZD6140 reduced the sensitivity of platelets according to ADP quickly and reversibly. Moreover, after 30 minutes, a significant inhibition of platelet aggregation could be observed. The P-selectin surface expression and platelet adhesion were significantly reduced after a single dose of AZD6140. Chronic treatment of diabetic rats with AZD6140 reduced the platelet activation in vivo and the platelet sensitivity in vitro. In addition, after two weeks of administration the P2Y12 receptor antagonist significantly decreased the secretion of pro-inflammatory cytokine RANTES. The rapid antiplatelet effect is particularly beneficial in patients scheduled for PCI, as in such situations as an effective, maximum, rapid and predictable inhibition of ADP-induced platelet aggregation is necessary to achieve better clinical results. The reversible effect of AZD6140 on the platelet functions is especially advantageous in pre-treated patients receiving coronary bypass surgery. In bypass surgery, excessive bleeding after irreversible antiplatelet therapy has been reported. Compared with clopidogrel treatment with this new P2Y12 antagonists is connected with greater platelet inhibition and lower variability in the response to the therapy. An inter-individual variability in the effectiveness, as can be found at clopidogrel, correlates with an increased risk of adverse cardiovascular events, a fact that affects particularly serious in cardiovascular risk groups. AZD6140 shows better efficacy, a faster start and a quick end to its effects on platelet functions and a reduced increase in bleeding time compared to clopidogrel. In clinical trials, the effectivity profile of AZD6140 was compared with clopidogrel. In the phase III PLATO study the significant superiority in efficacy of AZD6140 was confirmed compared with clopidogrel.

The association between diabetes and coronary artery disease (CAD) has been recognized as a major public health problem in the developed world. While there is an increased prevalence of silent myocardial ischaemia among asymptomatic individuals with diabetes, diabetic individuals with CAD in their larger number are usually asymptomatic, and when they present with signs of disease, there is extensive and severe CAD. It should be noted that amongst black South African, ischemic heart disease (IHD) remains rare, and there is little data linking diabetes mellitus with IHD. However, contrary to early reports that have suggested a low prevalence of CAD in black population in Africa, many studies have indicated a rapid change on the spectrum of CAD in numerous parts of the African continent. Despite the emerging report of high prevalence of risk factors there are only limited data investigating prevalence of CAD in black African with diabetes. The purpose of this thesis was to use myocardial perfusion imaging (MPI) at rest and after stress testing to detect CAD in a group of asymptomatic black patients suffering from diabetes and therefore assess the prevalence of CAD; to assess the changes in myocardial perfusion in asymptomatic diabetic black individuals and compare the differences seen in myocardial perfusion changes between the asymptomatic diabetic black and, the asymptomatic diabetic white and Indian individuals; to include data from symptomatic diabetic patients who were referred for MPI as part of their routine clinical management for possible comparison Consecutive 94 asymptomatic diabetic black patients and 50 asymptomatic diabetic white and Indian patients were recruited from the outpatient diabetic clinic of the Johannesburg hospital. Data from 90 subjects forming a group of symptomatic diabetic patients, 45 blacks and 45 whites and Indians referred for MPI as part of their clinical management were also analyzed. A two-day protocol for SPECT MPI was used in all participants: on the first day the stress testing MPI while the rest MPI was consistently done on the second day. Both exercise and pharmacologic stress testing were used. Technetium-99m methoxy-isobutylisonitrile (MIBI) was used as the myocardial perfusion radiopharmaceutical. Myocardial perfusion was assessed by means of semi-quantitative scoring system to measure the extent and severity of perfusion abnormality. Visual inspection of the reconstructed SPECT MPI images was carried out to assess perfusion deficit where there was a doubt on the extent and severity of perfusion abnormality. The QPS/QGS software allows obtaining resting and post stress left ventricular ejection fraction (LVEF). The means and percentages on study variables were obtained. The Spearmen correlation coefficient was used to calculate correlations between variables. The Kruskal-Wallis test was used to assess differences between black diabetic and white or Indian diabetic patients and Wilcoxon scores (rank sum) two-sided were used to measure differences within these racial groups. There were 123 females (52.6%) and 111 males (47.4%) in total. From the recruited participants, 53 (56.4%) asymptomatic females and 41 (43.6%) asymptomatic males were blacks whereas 24 (48%) asymptomatic females and 26 (52%) asymptomatic males were whites or Indians. The symptomatic group was comprised of 26 (57.8%) female and 19 (42.2%) male black patients and 20 (44.5%) female and 25 (55.5%) male white or Indian patients. Asymptomatic diabetic black participants were younger than the participants from the asymptomatic diabetic white and Indian group with a mean age of 60 (SD±7.2) years Vs 64 (SD±7.7) [p=0.003]. Fourteen percent of asymptomatic black participants had evidence of ischaemia by showing improvement of perfusion on stress testing versus twenty eight percent of white and Indian asymptomatic participants (p=0.62). Perfusion defects that did not change from rest to post stress testing MPI (fixed defects) were also noted in 20% of asymptomatic black and 26% of asymptomatic white and Indian diabetic participants. These fixed perfusion defects are indicative of previous myocardial infarctions and therefore suggestive of CAD. No significant difference was noted on the changes of perfusion that could account either for ischaemia or infract between asymptomatic diabetic black participants and their white and Indian counterparts (p=0.47). The difference on the improvement of perfusion from rest to post-stress MPIs or reversibility of perfusion to suggest only the presence of ischaemia did not also show a significant difference between these two racial groups (p=0.62). Our data demonstrated a high prevalence of CAD in asymptomatic diabetic black participants similar to other racial groups. Our study has demonstrated evidence to recommend screening of asymptomatic diabetic black individuals in equal manner than other races for the detection of CAD. More importantly, stress MPI should be routinely used as a noninvasive investigation in our environment and be utilized more actively in the management of all asymptomatic diabetic patients.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Medicine in the branch of Internal Medicine, Johannesburg, 2014 / Objective: To evaluate and compare any differences in control, i.e. HbA1C, total cholesterol, BP and BMI in a single group of Type-2 diabetes patients during two time periods, i.e. before and after specialist-supervised care. In addition, to describe differences in the use of anti-platelet and statin therapy for primary cardiovascular prophylaxis. Methods: Patients were recruited from the Diabetes Clinic at Chris Hani Baragwanath Academic Hospital (CHBAH) and the audits of two separate time periods were conducted. The first audit recorded standard of care delivered by registrars from January 2005 to December 2007. The second audit recorded care after the introduction of specialist-supervised care from September 2009 to September 2012. The patients were all insulin-requiring and were required to be seen for at least 24 months during both audit periods. The first recorded HbA1C in (i) 2005 and (ii) from September 2009 triggered the inception of a patient’s assessment periods. Data for at least 80% of parameters had to be available for a patient to be included in the audit. Results: This study showed significant differences using ANCOVA comparing final values for each audit after adjustment for their respective baseline values in respect of HbA1C (p<0.000), SBP (p<0.012) and BMI (p<0.001) after the implementation of an endocrinologist-supervised clinic. The percentage of patients reaching guideline targets, and the use of aspirin and statins, improved as well. Conclusion: This study showed a difference in the level of care delivered by the endocrinologist-supervised clinic as opposed to one which was led by registrars. However, other factors may have contributed to the outcomes, most notably that the consultation time with each patient was longer after the introduction of expert supervision in 2009.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the branch of Internal Medicine Johannesburg, 2014 / Background Diabetes is a global epidemic. The International Diabetes Federation estimates that there are at least 285 million diabetics worldwide and this is estimated to grow to over 440 million by 2030 1 . A study was conducted at the Helen Joseph Hospital Diabetic clinic in an attempt to identify predictors of glycaemic control and to compare the level of care to the 2012 Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) guidelines. Methods Patients were recruited from the Helen Joseph Hospital Diabetic clinic. To be included the patient had to be part of the coloured (mixed race) community, be willing to give informed consent, be older than 18 years, have an HBA1C taken within 6 months, have a diagnosis of Type 2 diabetes mellitus and be a clinic attendee for at least 1 year. Pregnant patients, Type 1 diabetic patients, patients with a psychotic disorder or aphasia were excluded. Data collection consisted of face-to-face interviews, review of treatment, medication knowledge evaluation, a short examination and collection of recent blood results. Statistical analysis was done by stratifying patients into two groups by using the mean HBA1C. Variables with a p < 0.1 from this analysis were used in a logistic regression model. In addition, the correlation between continuous variables were tested. A comparison was made between the level of care and the 2012 SEMDSA guidelines. v Results A total of 100 patients were recruited into the study. The mean age was 62.8 years with mean duration of diabetes of 15.8 and clinic attendance of 10.9 years. The group had very poor education level and the median income of R1200 per month was also low. The mean HBA1C was found to be 9.74%, well above the target recommended by SEMDSA. Knowledge of diabetes with respect to management and complications was very poor. Age > 50 years (OR 0.372 CI 0.06-2.26), estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 (OR 0.90 CI 0.25-3.27), experiencing a microvascular complication (OR 0.73 CI 0.11-5.07) or any other diabetic complication (OR 0.56 CI 0.07-4.38) and having experienced a hypoglycaemic episode (OR 0.31 CI 0.09-1.10) predicted better glycaemic control. Duration of diabetes < 10 years (OR 1.36 CI 0.37-5.02), diastolic blood pressure ≥ 70 mmHg (OR 2.80 CI 0.80-9.78), aspirin dosage ≥ 150 mg daily (OR 6.47 CI 1.60-26.05), simvastatin dosage = 40 mg daily (OR 2.35 CI 0.31-18.10) and body mass index > 25 kg/m2 (OR 1.09 CI 0.49-2.41) all predicted a poorer glycaemic result. HBA1C was found to positively correlate with diastolic blood pressure (p = 0.0024, r = 0.31). Systolic blood pressure positively correlated with diastolic blood pressure (p < 0.0001, r = 0.56). Apart from correlating with systolic blood pressure and HBA1C, diastolic blood pressure also positively correlated with the triglyceride level (p = 0.0003, r = 0.36). Positive correlations between total cholesterol, triglycerides, HDL-C and LDL-C were found. As expected, body mass index and waist circumference correlated positively (p < 0.0001, r = 0.82). Level of care was not at the level recommended by the 2012 SEMDSA guidelines. Only 6% of patients met the waist circumference goal. Only 15% of patients achieved blood v i pressure goal. Most of the patients (86%) who qualified for aspirin did not receive it. In the group of patients receiving aspirin 33% did not qualify. According to the SEMDSA guidelines, most of the patients not receiving a statin (90%) should have been on statin therapy. Only 23.5% of patients on statins were at lipid goal. The frequency of laboratory testing did not meet SEMDSA guidelines. There were 31 (31%) patients without a urea, creatinine and electrolyte test for the previous year and 37 (37%) patients without a lipogram for the previous year. Only 21 patients had a listed urine albumin/creatinine ratio and only 33% of these had been done in the previous year. Conclusions Various new variables were identified in the search for predictors of glycaemic control. It was surprising to find that education level, monthly income, smoking status and knowledge of diabetes did not have a statistical impact on glycaemic control. Increased age, duration of diabetes, glomerular filtration rate, hypoglycaemic frequency and diabetic complications experienced were associated with improved glycaemic control. Increased diastolic blood pressure, aspirin dosage, statin dosage and body mass index were associated with worse glycaemic control. The standard of care in the clinic was found on the whole to be inferior to the level of care recommended by SEMDSA.

Thesis (M.S.)--Boston University

Made available in DSpace on 2019-03-29T23:16:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-12-21 / Diabetes mellitus (DM) is a progressive illness, currently accepted as a world-wide epidemic. Diabetic foot is one of the most serious complications with a high socio -economic impact. It is characterized by wounds resulting from neuropathy, ischemia and infection. The objective of this study is to evaluate the barapodometric parameters in patients with type 2 DM (DM2), through a force platform - Footwork. The study was carried out between August and November 2007, in the adult DM outpatients of the Endocrinology and Diabetes Service of the Walter Candido University Hospital, Faculty of Medicine, of the Federal University of Ceará. 138 individuals with DM2 were evaluated, selected sequentially a t the aforementioned outpatients during the period determined for the study s recruitment, of which 101 were females, with an average age of 57,9±10,5, average body mass index of 29,3±4,8kg/m2 , average glycemia of 180,5±77,9mg/dl. The data was tabulated and analyzed with the Statistical Package for Social Science program. The results showed that on the statistical examination the average load of the forefoot was 48,7±9,1%, for the hindfoot it was 51,4±9,1%, for the right foot 49,9±6,5% and the left foot 50,1±6,5%. The average peak foot pressure for the right foot was 2,3±0,9 kgf/cm2 and 2,2±0,8 kgf/cm2. for the left foot. In the dynamic test, the average peak foot pressure was 2,7±0,8kgf/cm2 2,7±0,8kgf/cm2 for the left foot. The study showed that the patients evaluated have an increased load on the hindfoot and raised peak foot pressure in the statistical test. There was no association between the alteration in vibratory sensitivity and changes in the distribution of load in the hindfoot/forefoot, neither between the right and left foot nor with changes to the static foot pressure peaks for both feet. The reproducibility of the results found in the analysis of the distribution of the load of the foot between forefoot/hindfoot and between the right/left f oot was only considered adequate for the forefoot/hind foot. There was a difficulty in comparing this data with that of previous authors, due to the variety of equipment and methods used to obtain data in the literature. In conclusion, this study was the first to use baropodometrics with the diabetic population in our midst. Considering the limitations of this exploratory study, further evaluations are required in more specific populations to standardize its technique, taking into consideration our regiona l characteristics, which would probably clearly define its benefits in the treatment and prevention of diabetic foot. / Diabetes mellitus (DM) é uma doença progressiva, atualmente aceita como uma epidemia mundial. O pé diabético é uma das complicações mais sérias de alto impacto sócio-econômico, caracterizada por lesões decorrentes de neuropatia, isquemia e infecção. Este estudo teve por objetivo avaliar os parâmetros baropodométricos em pacientes com DM tipo 2 (DM2), através de uma plataforma de força Footwork. O estudo foi realizado entre agosto a novembro de 2007, no ambulatório de DM do adulto do Serviço de Endocrinologia e Diabetes do Hospital Universitário Walter Cantídio, da Faculdade de Medicina, da Universidade Federal do Ceará. Foram avaliados 138 indivíduos com DM2, selecionados de forma seqüenciada no referido ambulatório durante o período determinado para o recrutamento do estudo, sendo 101 do sexo feminino, com idade média de 57,9±10,5 anos, índice de massa corpórea médio de 29,3±4,8kg/m 2, glicemia média de 180,5±77,9mg/dl. Os dados foram tabulados e analisados com o programa Statistical Package for Social Science. Os resultados mostraram que ao exame estático a média da carga plantar de antepé foi de 48,7±9,1%, a de retropé de 51,4±9,1%, a do pé direito de 49,9±6,5% e a do pé esquerdo de 50,1±6,5%. A média do pico de pressão plantar do pé direito foi de 2,3±0,9 kgf/cm2 e do pé esquerdo de 2,2±0,8 kgf/cm2. Ao exame dinâmico, a média do pico de pressão plantar do pé direito foi de 2,7±0,8kgf/cm2 e do pé esquerdo de 2,7±0,8kgf/cm2. O estudo revelou que os pacientes avaliados estão com a carga plantar aumentada em antepé e com elevação do pico de pressão plantar ao exame estático. Não houve associação entre alteração de sensibilidade vibratória e a presença de alteração na distribuição das cargas plantares de antepé/retrop é, nem entre pé direito e pé esquerdo e nem com alteração dos picos de pressão plantar estática em ambos os pés. A reprodutibilidade dos resultados encontrados na análise da distribuição da carga plantar entre antepé/retropé e entre pé direito/pé esquerdo foi considerada adequada apenas entre antepé/retropé. Verificou -se a dificuldade na comparação destes com dados prévios de outros autores, dado a diversidade de equipamentos e metodologias utilizadas nos dados de literatura. Em conclusão, no presente trabalho foi realizado o primeiro estudo utilizando a baropodometria em população diabética no nosso meio. Considerando as limitações deste estudo exploratório, serão necessárias avaliações futuras em populações mais específicas para uma melhor padronização desta técnica, considerando as nossas características regionais, que provavelmente definiriam de forma clara os seus benefícios no tratamento e na prevenção do pé diabético.

Made available in DSpace on 2019-03-29T23:27:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-12-18 / BACKGROUND: Diabetes mellitus is a chronic metabolic syndrome, characterized by hyperglycemia with potential to injure different organs, including eyes, kidneys, heart, blood vase, nerves and brain. If the anatomic and physiological changes resulting from the process of hyperglycemia has the potential to injure blood vase and nerves, it is believed that the organs responsible for hearing may also, be affected by diabetes, causing audio variations in these patients. OBJECTIVES: To evaluate the hearing of the type 2 diabetic patients, analyzing the audio threshold and cochlear function and to investigate the association between audiological findings, chronic complications and comorbidities. METHODS: The crosssectional analytical study was conducted at the Integrated Center of Hypertension and Diabetes of the State of Ceará. The sample was consisted of patients with diabetes mellitus type 2, regardless of sex, aged between 30 and 60 years, from April to July 2009. Was performed pure tone audiometry, transient evoked (TEOAE) and distortion product (DPOAE) from otoacoustic emissions. RESULTS: Of the study with 152 diabetic patients, 62.5% were female. The medium age was 53.4 ± 6.02 years. The average time in diagnosis of diabetes was 11.2 ± 6.3 years. The findings related to hearing showed audio loss in 63.2% of the patients, all of which were sensorineural with a predominance of bilateral and symmetric hearing losses, mild and flat configuration. The otoacoustic emissions analysis showed 114 (75%) patients with abnormal TEOAEs and 120 (78.9%) DPOAEs. The hearing thresholds average by frequency assumed values above 25dB from the frequency of 4 kHz, showing greater commitment to high frequencies. The association of hearing loss with the studied variables have shown a greater risk for males, aged over 50 and overweight (obesity). For TEOAEs was found more risk in men and in patients with obesity, and for the DPOAEs in men and in older age. CONCLUSION: The evaluation of hearing results showed a predominance of bilateral symmetrical sensorineural hearing loss, with more pronounced in high frequencies and greater involvement of the left side. The otoacoustic emissions analysis revealed a high percentage of changes, which have shown more injury in high frequencies and on the left side. The correlation between the results of audiometry and otoacoustic emissions have shown that the part of the sample had presented an absence of otoacoustic emissions before normal audibility thresholds, suggesting that the outer hair cells of the cochlea are damaged in this population. Sex, age and overweight/obesity were associated with hearing loss. Regarding to emissions, sex and overweight/obesity were associated with the absence of TEOAE; and sex and age with absence of DPOAE. The other variables have shown no statistically significant association for hearing disorders studied. / INTRODUÇÃO: O Diabetes mellitus é uma síndrome metabólica crônica, caracterizada por hiperglicemia, com potencial para lesionar diversos órgãos, entre eles: olhos, rins, coração, vasos sanguíneos, nervos e cérebro. Se as alterações anatomofisiológicas decorrentes do processo de hiperglicemia têm potencial para lesionar vasos sanguíneos e nervos, acredita-se que os órgãos responsáveis pela audição também possam ser afetados pela doença, causando alterações auditivas nos pacientes. OBJETIVOS: Caracterizar a audição do paciente diabético tipo 2, analisando o limiar de audibilidade e a função coclear e investigar a associação entre os achados audiológicos e as complicações crônicas e co-morbidades. METODOLOGIA: O estudo transversal e analítico foi realizado no Centro Integrado de Diabetes e Hipertensão do Estado do Ceará. A amostra foi composta por pacientes portadores de diabetes mellitus tipo 2, independente do sexo, com idades variando entre 36 e 60 anos, no período de abril a julho de 2009. Foram realizadas audiometria tonal liminar, emissões otoacústicas evocadas transientes (EOAT) e produto de distorção (EOAPD). RESULTADOS: Foram avaliados 152 pacientes diabéticos, 62,5% do sexo feminino. A média de idade foi de 53,4 ± 6,02 anos. O tempo médio de diagnóstico foi de 11,2 ± 6,3 anos. Os achados relacionados à audição mostraram perda auditiva em 63,2% dos pacientes, sendo todas do tipo sensorioneural, com predomínio das perdas bilaterais e simétricas, de grau leve e configuração plana. A análise das emissões otoacústicas mostrou 114 (75%) pacientes com alteração nas EOAT e 120 (78,9%) nas EOAPD. A média dos limiares de audibilidade por frequência assumiu valores acima de 25dB a partir da frequência de 4KHz, mostrando maior comprometimento de frequências agudas. A associação da perda auditiva com as variáveis estudadas mostrou mais risco para o sexo masculino, na faixa etária acima de 50 anos, e com sobrepeso, obesidade. Para as EOAT encontrou-se mais risco no sexo masculino e nos pacientes com sobrepeso ou obesidade; e para as EOAPD houve mais risco no sexo masculino e na faixa etária mais elevada. CONCLUSÃO: A avaliação da audição mostrou predomínio de perda auditiva sensorioneural bilateral simétrica, com prejuízo mais acentuado nas frequências agudas e maior comprometimento do lado esquerdo. A análise das emissões otoacústicas revelou elevada porcentagem de alterações, mostrando comprometimento maior nas frequências agudas e no lado esquerdo. A correlação entre os resultados da audiometria e das emissões otoacústicas mostrou que parte da amostra apresentou ausência de resposta das emissões otoacústicas diante de limiares de audibilidade normais, sugerindo que as células ciliadas externas da cóclea estão prejudicadas nesta população. O sexo, a faixa etária e o sobrepeso/obesidade apresentaram associação com a perda auditiva. Em relação às emissões otoacústicas, o sexo e o sobrepeso/obesidade apresentaram associação com a ausência de EOAT; e o sexo e a faixa etária com a ausência de EOAPD. As demais variáveis não apresentaram associação estatisticamente significante para as alterações auditivas estudadas.

Made available in DSpace on 2019-03-29T23:38:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-12-01 / The aging population brings about many chronic degenerative diseases such as type 2 diabetes, which leads the elderly to disabilities it is a challenge specially for the public health system. The type 2 diabetes significantly affects individuals, causing a need to modify lifestyle and adhere to stringent therapeutic guidelines therefore influencing the elderly s quality of life. Based on these assumptions, we opted for this study aimed at investigating adherence to non-pharmacological treatment in elderly patients with type 2 diabetes mellitus. The research results encouraged us to produce two articles: the first "A therapeutic proposal to unite the non-pharmacological treatment for elderly patients with type 2 diabetes," This article, with a quantitative approach, describes the factors that can influence the adhesion of elderly diabetic patient to a non-medication treatment. The elderly participated in a treatment plan of physical activity and health education. Adherence to non-pharmacological treatment was considered when the patient participated in the triad program of body activity, dietary control and participation in the health education program. We found in this study that low income, the longer pathology (years) and better quality of life are factors that influence adhere to non-pharmacological treatment in the elderly diabetic. The second, entitled "Medical conditions and quality of life in a group of elderly patients with type 2 mellitus diabetes," aimed to evaluate the clinical conditions and quality of life in a group of elderly patients with type 2 mellitus diabetes. It was an epidemiological, cross-sectional, descriptive, quantitative study of elderly in type 2 diabetic care as outpatients at the Center for Integrated Medical Care. Questionnaires were given out regarding demographic, socioeconomic, clinical and therapeutic information along with a questionnaire on quality of life. We conclude that elderly diabetic patients are mostly female, overweight, low income, low educational history and low level of quality of life. In general, non-adherence of individuals to programs offered by public services can be related to the lack of knowledge of elderly diabetic patients regarding the health-disease process and the importance of prevention and health promotion for the benefits of a better quality of life. / O envelhecimento populacional acarreta uma carga de doenças crônico-degenerativas, como o diabetes tipo 2, que leva o idoso a incapacidades, destacando-se como um desafio para a saúde pública. O Diabetes tipo 2 atinge de forma significativa os indivíduos, necessitando modificar hábitos de vida e aderir a orientações terapêuticas restritivas influenciando, assim, na qualidade de vida do idoso. Com base nestes pressupostos, optou-se por este estudo com o objetivo de investigar a adesão ao tratamento não farmacológico em idosos com diabetes mellitus tipo 2. Os resultados da pesquisa nos incentivaram a construir dois artigos: o primeiro Proposta terapêutica de adesão ao tratamento não farmacológico para idosos com Diabetes Mellitus tipo 2 , de abordagem quantitativa, descreve quais são os fatores que podem influenciar na adesão de idosos diabéticos a um tratamento não medicamentoso. Os idosos participaram de uma proposta terapêutica de atividade física e educação em saúde. A adesão ao tratamento não farmacológico foi considerada quando o paciente participou da tríade: programa de atividade corporal, controle na dieta e participação no programa de educação em saúde. Verificamos neste estudo que a baixa renda mensal, o maior tempo de patologia (anos) e a melhor qualidade de vida são fatores que influenciam na adesão ao tratamento não farmacológico no idoso diabético. O segundo, intitulado Condições clínicas e qualidade de vida em um grupo de idosos com Diabetes Mellitus tipo 2 , teve como objetivo avaliar as condições clínicas e a qualidade de vida em um grupo de idosos com diabetes mellitus tipo 2. Tratou-se de um estudo epidemiológico descritivo, transversal, de natureza quantitativa em idosos diabéticos tipo 2 em atendimento no serviço ambulatorial do Núcleo de Atenção Médica Integrada. Foram aplicados questionários com informações sobre o perfil demográfico, socioeconômico, clínico e terapêutico e um questionário de qualidade de vida. Concluímos que os idosos diabéticos na maioria são do gênero feminino, com sobrepeso, com baixa renda econômica, baixa escolaridade e baixos níveis de qualidade de vida. De uma forma geral, a não adesão dos indivíduos a programas ofertados pelos serviços públicos pode estar relacionado ao não conhecimento dos idosos diabéticos sobre o processo saúde-doença e sobre a importância da prevenção e promoção da saúde em benefício de uma melhor qualidade de vida.

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / As dislipidemias e o diabetes apresentam-se como importantes fatores de risco nas doenÃas cardiovasculares. Quando se associa ao estresse oxidativo podem acelerar a progressÃo das lesÃes aterosclerÃticas. Estudos com produtos naturais fornecem dados interessantes no controle dessas doenÃas. No presente estudo foram utilizados dois compostos derivados da canela, o Ãcido cinÃmico (AC) e cinamato de metila (CM), semelhantes estruturalmente e com atividades biolÃgicas e farmacolÃgicas jà descritas. O presente estudo tem por objetivo avaliar os possÃveis efeitos hipolipidÃmico e hipoglicÃmico, bem como o potencial antioxidante do Ãcido cinÃmico e do cinamato de metila em protocolos experimentais de dislipidemias e diabetes induzidas farmacologicamente. A hiperlipidemia foi induzida em camundongos machos atravÃs de dois protocolos agudos, mediante uma Ãnica administraÃÃo intraperitoneal de 400mg/Kg de Triton WR-1339 e 400mg/Kg de Poloxamer-407 em todos os animais, exceto no controle negativo. Os grupos foram tratados via oral por gavagem, onde o controle negativo e o controle positivo receberam Ãgua potÃvel de acordo com o peso, o grupo fenofibrato recebeu a dose de 200mg/Kg, enquanto que os grupos Ãcido cinÃmico e cinamato de metila receberam a mesma dose de 20mg/Kg. O sangue desses animais foi coletado em 24 e 48 horas apÃs as induÃÃes e foram verificados os nÃveis plamÃticos de colesterol total, triglicerÃdeos, glicose, AST e ALT. ApÃs a coleta de 48 horas retirou-se o tecido hepÃtico, em ambos os protocolos, para analisar a peroxidaÃÃo lipÃdica, atravÃs da determinaÃÃo dos grupos sulfidrÃlicos nÃo-proteÃcos (NP-SH), malondialdeÃdo (MDA) e das enzimas antioxidantes: superÃxido dismutase (SOD) e catalase (CAT). Para determinar o potencial hipoglicemiante do Ãcido cinÃmico e do cinamato de metila utilizou-se o protocolo de diabetes induzida por aloxano atravÃs de uma Ãnica injeÃÃo intraperitoneal na dose de 200mg/Kg. Os grupos foram tratados por sete dias com Ãgua potÃvel de acordo com o peso (grupo controle positivo), metformina 50mg/Kg (grupo metformina), Ãcido cinÃmico 20mg/Kg (grupo Ãcido cinÃmico) e cinamato de metila 20mg/Kg (grupo cinamato de metila). Observou-se que, apÃs a induÃÃo, tanto com o Triton quanto Poloxamer, o AC e o CM foram capazes de reduzir o colesterol e os triglicerÃdeos apÃs 24 e 48 horas, sem, no entanto alterar as enzimas hepÃticas AST e ALT. Somado a esse fator observou-se que as substÃncias em estudo apresentaram certa atividade sobre o estresse oxidativo tendo em vista a reduÃÃo do MDA e NP-SH no protocolo do Triton e da NP-SH no protocolo do poloxamer. Tendo o cinamato de metila apresentado uma maior atividade em comparaÃÃo ao Ãcido cinÃmico na anÃlise de 48 horas apÃs a induÃÃo em ambos os protocolos. Observando a resposta do AC e o CM em protocolo de induÃÃo de diabetes por aloxano, constatou-se que as referidas substÃncias foram capazes de reduzir de forma semelhante, a glicemia dos animais. Os resultados obtidos mostraram o potencial terapÃutico do AC e CM no tratamento das dislipidemias e do diabetes, no entanto faz necessÃrios novos estudos em protocolos crÃnicos que possam garantir a seguranÃa e eficÃcia de sua utilizaÃÃo. / Dyslipidemia and diabetes are presented as important risk factors in cardiovascular disease. When is associated with oxidative stress may accelerate the progression of atherosclerotic lesions. Studies with natural products provide interesting data in the control of these diseases. In the present study two compounds cinnamon derivatives, cinnamic acid (CA) and methyl cinnamate (MC) and structurally similar biological and pharmacological activities already described above were used. The present study aims to evaluate the possible hypolipidemic and hypoglycemic effects as well as the antioxidant potential of cinnamic acid and methyl cinnamate in experimental protocols pharmacologically induced dyslipidemia and diabetes. Hyperlipidemia was induced in male mice by two acute protocols through a single intraperitoneal administration of 400mg/kg Triton WR -1339 and 400mg/kg Poloxamer -407 in all animals except the negative control. The groups were treated orally by gavage, where the positive control and the negative control received drinking water according to the weight of fenofibrate group received 200mg/kg, whereas the cinnamic acid, methyl cinnamate groups and received the same dose 20mg/kg. The blood of these animals was collected at 24 and 48 hours after induction and was plamÃticos checked the levels of total cholesterol, triglycerides, glucose, AST and ALT. After collecting 48 hours we removed the liver tissue , in both protocols , to analyze lipid peroxidation , through the determination of non-protein sulfhydryl groups ( NP -SH ) , malondialdehyde ( MDA ) and antioxidant enzyme : superoxide dismutase (SOD ), and catalase (CAT). To determine the hypoglycemic potential of cinnamic acid and methyl cinnamate was used protocol alloxan induced diabetic by a single intraperitoneal injection at 200mg/kg. Both groups were treated for 7 days with drinking water according to the weight (positive control group), 50mg/Kg metformin (metformin group), cinnamic acid 20mg/kg (cinnamic acid group) and methyl cinnamate 20mg/kg (group cinamto methyl). It was observed that after induction with either Poloxamer as Triton, AC and BC were able to reduce cholesterol and triglycerides after 24 and 48 hours, without changing the liver enzymes AST and ALT. Added to this factor was observed that the substance under study showed some activity on oxidative stress in order to reduce the MDA and NP -SH in the protocol of the Triton and NP -SH in the poloxamer protocol. Having methyl cinnamate presented higher activity compared to cinnamic acid analysis 48 hours after the induction of both protocols. Observing the response of the CM and the AC induction protocol in alloxan diabetes, it was found that these compounds were able to similarly reduce the glucose levels. The results showed the therapeutic potential of CA and CM in the treatment of dyslipidemia and diabetes, however does require new studies in chronic protocols that can ensure the safety and efficacy of its use.

Xenotransplantation of neonatal porcine islets have been demonstrated to be a viable alternative to exogenous insulin therapy for diabetes mellitus. The use of liberase has gained much success in islet isolation but factors such as batch-to-batch variation and deterioration of a batch with storage time have hampered the quality and reproducibility of tissue dissociation. Islet culture aims to optimise islet survival and insulin release in response to glucose challenge. However, it is difficult to recover and preserve islets in vitro. Mitochondria play a key role in the secretion of insulin from pancreatic islet cells in response to glucose stimulation. Mitochondrial dysfunction results in the induction (at mRNA and protein levels) of a molecular stress protein/heat chock protein called Cpn60. Since mitochondrial impairment will have a significant effect on the ability of in vitro cultured islet cells to function properly (i.e. release insulin in response to glucose stimulation), the expression of Cpn60 was investigated as a function of exposing neonatal porcine islet cells to various growth conditions. The best choice of media to culture neonatal porcine islet cells was found to be not heated activated serum which showed the least levels of Cpn60 expression at mRNA levels suggesting that the cells had low levels of mitochondrial stress. Neonatal porcine islet cells would be best digested in cells digested with new liberase (QC 1050) while in 2% not heat inactivated porcine serum (NPS) as this gave the lowest levels of Cpn60 expression suggesting low levels of mitochondrial stress. Although expression of Cpn60 at mRNA levels seems to be modulated during the growth of the porcine islet cells in media supplemented with different serum, heat treatment of serum and liberase content, no firm conclusion can be made with regard to the effect of the different treatments on mitochondrial health status until the porcine Cpn60 protein can be unequivocally identified.