Introdução: Climatério é definido como o período de tempo onde ocorre a mudança de vida reprodutiva para não reprodutiva, com extensão de duração variável. Durante esse período e após o estabelecimento da menopausa, é comum o surgimento de diversos sintomas que expressam o esgotamento dos folículos ovarianos. Dentre os sintomas, o mais comumente relatado pelas mulheres são os sintomas vasomotores ou fogachos. Além da Terapia de Reposição Hormonal (TRH), outras medicações como os Inibidores Seletivos da Recaptação da Serotonina (ISRS) têm sido empregadas na tentativa de melhorá-los. Justificativa: TRH não pode ser aplicado a todas as mulheres com sintomas. As medicações não hormonais, apesar de apresentarem melhores respostas que placebo, ainda demonstram pouco impacto clínico na redução dos sintomas vasomotores. Esta lacuna permite avaliar outras alternativas terapêuticas, como a Estimulação Transcraniana por Corrente Direta (ou tDCS, do inglês transcranial direct current stimulation). O racional para estudar o efeito desta técnica neste contexto, é o seu possível efeito modulatório autonômico. O que reforça a escolha desta técnica é o fato de ter eficácia demonstrada em outras patologias como depressão, dor, doença Parkinson dentre outras. A tDCS é um método de neuromodulação transcraniana não invasivo, que se baseia na aplicação de correntes contínuas de baixa intensidade, através de eletrodos colocados sobre o escalpo, de forma simples e indolor. Objetivo: Avaliar o efeito da tDCS (tratamento ativo) comparada ao tDCS-sham (placebo) nos sintomas vasomotores de mulheres na pós- menopausa como objetivo primário; e como objetivo secundário, seus efeitos na qualidade de vida. Método: Ensaio Clínico Randomizado realizado em 30 pacientes pós-menopáusicas com queixa de pelo menos 05 episódios de fogachos/dia. Participantes foram selecionadas no ambulatório de Climatério do Serviço de Ginecologia e Obstetrícia do Hospital de Clínicas de Porto Alegre e via chamamento de jornal. Estas foram randomizadas para um dos grupos: tDCS ou placebo-sham. A intervenção consistiu na aplicação de sessões diárias de estimulação com corrente elétrica de 02 mili Ampere, pelo período de 10 dias consecutivos, à exceção dos finais de semana. Por uma semana anterior à intervenção e por 30 dias após, as participantes registravam o número e intensidade dos fogachos ao dia. Responderam ao Women´s Health Questionaire (WHQ) antes e ao termino da intervenção. Resultados: A média de fogachos/dia se comportou de forma semelhante nos dois grupos havendo uma redução do número de fogachos nas três primeiras semanas após intervenção com retorno ao basal a partir da quarta semana pós-aplicação. No grupo tDCS, se observou uma tendência a uma transferência dos fogachos intensos para leves sugerindo uma melhora clínica. Os resultados, apesar de não apresentarem significância estatística, reforçam a ideia de ampliar a investigação, com maior número de pacientes e com maior tempo de duração além do caráter inovador da pesquisa. / Introduction: Menopause is defined as a period where there is a change from the reproductive stage to a nonreproductive phase, with variable duration. During this period and following the establishment of menopause, there is usually an onset of several symptoms indicating the depletion of ovarian follicles. Among the symptoms, the ones that are more frequently reported by women are vasomotor symptoms or hot flashes. In addition to Hormone Replacement Therapy (HRT), other medications such as Selective Serotonin Reuptake Inhibitors (SSRIs) have been employed to treat them. Justification: HRT may not be applied to all women with symptoms. Non-hormonal medications, despite having better responses than placebo, have still shown little clinical impact on the reduction of vasomotor symptoms. This gap allows other therapeutic alternatives to be considered, such as Transcranial Direct Current Stimulation (tDCS). The rationale for studying the effect of this technique in this context is its possible autonomic modulatory effect. What reinforces the choice of this technique is the efficacy which it has demonstrated in other disorders such as depression, pain, Parkinson's disease, among others. tDCS is a non-invasive transcranial neuromodulation method based on the application of continuous low-intensity currents through electrodes placed to the scalp, in a simple and painless way. Goal: To evaluate the effect of tDCS (active treatment) compared to tDCS-sham (placebo) on vasomotor symptoms in postmenopausal women as a primary endpoint and its effects on quality of life as a secondary endpoint. Method: Randomized Clinical Trial conducted in 30 postmenopausal patients complaining of at least five episodes of hot flashes per day. Participants were selected at the Gynecology and Obstetrics Service Menopause Outpatient Clinic, Hospital de Clínicas de Porto Alegre and via a newspaper call. These were randomized to one of the groups: tDCS or placebo-sham. The intervention consisted of daily sessions in which stimulation was applied with an electric current of 02 milliamperes for 10 consecutive days, except on weekends. Participants recorded the number and intensity of hot flashes per day for one week before and for 30 days after the intervention. They answered the Women’s Health Questionnaire (WHQ) before and after the intervention completion. Results: The mean of hot flashes/day behaved in a similar way in both groups, and there was a reduction in hot flashes in the first three weeks following the intervention with a return to baseline starting in the fourth week after the administration. In the tDCS group, a trend towards a conversion of intensive hot flashes into mild ones was noted, which suggested a clinical improvement. The results, despite not showing statistical significance, supported the idea of extending the investigation with a larger number of patients and longer duration, in addition to the innovating nature of the research.

Menopause transition is a natural process in a woman’s life associated with altered body fat distribution, increased cardiometabolic risk, and the presentation of vasomotor symptoms including hot flashes and night sweats. A 5-year observational, longitudinal study (MONET: Montreal Ottawa New Emerging Team), was performed to document the effect of menopause transition on body composition and cardiometabolic risk factors. Initially, the study included 102 healthy non-obese premenopausal women between the age of 47 and 55 years. By the end of year 5, 91 women completed the study, 4% were still premenopausal, 29% were perimenopausal and 67% became postmenopausal. The major finding of the first study was that the increases in body fat mass and visceral fat in our cohort of non-obese women followed through the menopause transition were independent of the increase in body weight. Furthermore, these changes in body composition and body fat distribution were not associated with cardiometabolic deteriorations. We further examined whether specific factors such as reporting vasomotor symptoms (hot flashes and/or night sweats), exaggerated exercise systolic blood pressure, physical activity levels and cardiorespiratory fitness, may be associated with adiposity, body fat distribution and cardiometabolic profile. Overall, women that experienced vasomotor symptoms (paper 2) or presented an exaggerated exercise systolic blood pressure (paper 3), did not present any alterations in their body composition, body fat distribution and cardiometabolic profile compared to asymptomatic women and participants with normal blood pressure response to exercise, respectively. Furthermore, exaggerated exercise systolic blood pressure was not predictive of future hypertension after a 5-year follow-up throughout menopause transition. On the other hand, total volume of physical activity was not linked with measures of a cardiometabolic profile, cardiorespiratory fitness appeared to have the greatest cardioprotective effect (paper 4). Therefore, in generally healthy physically active non-obese premenopausal women, the menopause transition does not generally alter cardiometabolic risk factors, and suggests that cardiorespiratory fitness may have greater cardiometabolic protective effects in this cohort.

Abstract Functional magnetic resonance imaging (fMRI) has become a leading tool in the evaluation of the human brain function. In fMRI the activation induced blood oxygenation changes in the brain can be detected with an inherent blood oxygen level dependent (BOLD) contrast. Even small blood oxygen fluctuations in a resting brain can be depicted with the BOLD contrast. This thesis focuses on characterizing spontaneous oxygenation fluctuations of the brain by using BOLD fMRI. The effects of anesthetics on blood oxygen fluctuations were assessed in 38 children and 12 adults. The spatial distribution, frequency, synchrony, and statistical independence of the spontaneous oxygenation changes were analyzed. The role of imaging artifacts in the generation of BOLD signal fluctuations was investigated. The study aimed to develop and compare methods of detecting the nondeterministic oxygenation fluctuations of the brain. VLF BOLD signal fluctuation in the brain cortex is induced by physiological oscillation instead of imaging artifacts. This study shows for the first time how the power and synchrony of very low frequency (VLF <  0.05 Hz) blood oxygen fluctuation significantly increases after sedation. In deeper anesthesia, the VLF fluctuation overpowers other sources of blood oxygen variation as a sign of reduced blood flow and altered hemodynamic control. Regional hemodynamic mechanisms induce non-Gaussian features on the VLF blood oxygen fluctuation that can be depicted effectively with independent component analysis. Combined use of frequency, time, and spatial domain analysis guarantees a more complete picture of brain oxygenation fluctuations. The results of this thesis have a dualistic impact on fMRI research. First of all, VLF fluctuation alters the BOLD activation and connectivity results after sedation. Thus it has to be accounted for in the fMRI of sedated subjects. Secondly, by using the methods developed in this thesis, VLF fluctuation and other physiological BOLD signal sources can now be used in characterizing physiological alterations and pathology of the brain.

The ability of an individual to withstand elevated head-to-toe gravitoinertial (+Gz) forces is determined by the capacity of their body to maintain sufficient head-level arterial pressure. Recent studies have shown a relationship between resting blood-vessel stiffness and an individual’s +Gz-tolerance, although the mechanisms behind this relationship are unclear. The aim of this project is to determine whether or not +Gz-tolerance is affected by a change inresting vasomotor tone. To evaluate this relationship, seven participants were asked to complete a +Gz-tolerance protocol using a human-use centrifugeon two different occasions. On both visits, gradual onset rate (0.1 G.s−1)and rapid onset rate (3.5 G.s−1) tests were done to evaluate the participants+Gz-tolerance. On one of the two visits, prior to the +Gz-tolerance testing,participants performed a 20-min cycle intervention to induce postexercisehypotension, with the aim of temporarily reducing participants’ resting bloodpressure and vasomotor tone. The cycling intervention was successful atinducing postexercise hypotension, as mean arterial pressure was significantlylower on the cycling visit (P<0.05). +Gz-tolerance was significantly lower(P<0.05) on the cycling visit compared with the non-cycling visit for both theGOR and ROR tests (absolute difference of 0.5 G and 0.25 G, respectively).The effect of the type of test on +Gz-tolerance was not influenced by the effectof the cycling intervention (P>0.05). Being the most documented mechanismlinked to postexercise hypotension, sustained vasodilation was assumed tohave occurred. This would have increased distensibility of the affected vessels,explaining the decrease in +Gz-tolerance. The decrease in +Gz-tolerance wassimilar for both tests, indicating that the baroreflex was not affected by thecycling intervention. Assuming that vasodilation occurred, this study showedthat a decrease in resting vasomotor tone decreased +Gz-tolerance, indicatingthe importance of this variable in the relationship between resting blood-vesselstiffness and an individual’s +Gz-tolerance.

This ex post facto correlational study seeks to identify if a relationship between blood glucose values and vasomotor instability intensity exists. The population consisted of a convenience sample of seven type 2 diabetic postmenopausal women experiencing vasomotor instability living in Southern Alberta. This study hypothesizes that a significant negative correlation would be identified between these two variables based on research done by Dormire and Reame (2003). The correlational results suggest that a small to moderate significant positive relationship exists between blood glucose and vasomotor instability: increased vasomotor instability was associated with increased blood glucose values. Overall, this study suggests a relationship exists between blood glucose and vasomotor instability but causality or direction of this relationship cannot be determined. Further research studies are recommended to clarify and validate this research. In particular, such a study should include type 1 diabetic postmenopausal women, a larger sample size, and sampling a wider geographical area. / ix, 109 leaves ; 29 cm.

Arteries respond to changes in global mechanical parameters (pressure, flow rate, and longitudinal stretching) by remodeling to restore local parameters (circumferential stress, shear stress, and axial strain) to baseline levels. Because a change in a single global parameter results in changes of multiple local parameters, the effects of individual local parameters on remodeling remain unknown. This study uses a novel approach to study remodeling in organ culture based on independent control of local mechanical parameters. The approach is illustrated by studying the effects of circumferential and shear stress on remodeling-related biological markers. Porcine carotid arteries were cultured for three days at a circumferential stress of 50 kPa or 150 kPa or, in separate experiments, a shear stress of 0.75 Pa or 2.25 Pa. At high circumferential stress, matrix synthesis, smooth muscle cell proliferation, and cell death are significantly greater, but matrix metalloproteinase-2 (MMP-2) and pro-MMP-2 activity are significantly less. In contrast, biological markers measured were unaffected by shear stress. Applications of the proposed approach for improved understanding of remodeling, optimizing mechanical conditioning of tissue engineered arteries, and selection of experimentally motivated growth laws are discussed.

[Truncated abstract] Cardiovascular reflex control of the vasculature is important in maintaining adequate tissue oxygenation in the face of disturbances in physiological homeostasis. Alterations in blood oxygen levels and blood distribution evoke integrated neural, mechanical and humoral responses which modulate peripheral vasomotor tone to maintain systemic cardiovascular integrity. The balance between the local effects of hypoxia and changes in chemoreflex control of vascular tone during hypoxia determine whether net vasoconstriction or vasodilatation is evident in the peripheral vasculature. The mechanisms contributing to hypoxic vasodilatation per se have not previously been defined in healthy humans. Study 1 of this thesis (Chapter 3) investigated the mechanisms contributing to vasomotor responses to chemoreflex activation in the human forearm ... Study 2 (Chapter 4a) investigated the mechanisms controlling vasomotor responses to isocapnic hypoxia in subjects with type 2 diabetes ... Study 3 (Chapter 5) compared the vascular responses to decreased venous return in individuals with and without right atrial afferent innervation ... The results of this thesis indicate that in healthy humans isocapnic hypoxia induces sympathetic vasoconstriction, which masks underlying β-adrenoceptor mediated vasodilatation. The normal vasomotor response to isocapnic hypoxia is impaired in subjects with type 2 diabetes. Despite intact vasoconstrictor responses, subjects with type 2 diabetes exhibited attenuated adrenaline-mediated vasodilatation compared to healthy control subjects, suggesting that the chemoreflex in these subjects is ill-equipped to respond to hypoxic stress. In clinical terms, impaired reflex vasomotor

<p>TCD apnea test kao neinvazivna i bezbedna neuroultrasonografska metoda pruža korisne informacije o vazomotornoj reaktivnosti (VMR) u procesu indirektnog sagledavanja funkcionisanja moždane autoregulacije. Vazomotorna reaktivnosti podrazumeva sposobnost dilatacije ili konstrikcije moždanih arteriola nastale kao odgovor na određeni vazoaktivni stimulus, najče&scaron;će ugljen dioksid. Cilj ove doktorske disertacije bio je ispitivanje i analiziranje promene karotidne hemodinamike kod bolesnika sa ishemijskim moždanim udarom (IMU) ili tranzitornim ishemijskim atakom (TIA) i simptomatskom karotidnom stenozom u preoperativnom i tromesečnom postoperativnom periodu, kao i procena revaskularizacionog efekta karotidne endarterektomije (KEA).U istraživanje je uključeno 60 hospitalizovanih bolesnika koji su doživeli prvi IMU i TIA u zoni vaskularizacije arterije cerebri anterior (ACA) i arterije cerebri medije (ACM), svi sa karotidnom stenozom, ACI &ge;70%. Bolesnici su bili hospitalizovani na Klinici za neurologiju, Kliničkog Centra Vojvodine, Klinici za kardiovaskularnu hirurgiju, Instituta za kardiovaskularne bolesti Vojvodine i Klinici za vaskularnu hirurgiju, u Novom Sadu. U odnosu na kliničke manifestacije bolesni i su podeljeni u tri grupe: bolesnici sa TIA i amaurosis fugax, sa parcijalnim infarktom u zoni ACA ili ACM i sa lakunarnim infarktom. Istraživanje je analiziralo uticaj promenljivih i nepromenljivih vaskularnih faktora rizika na pojavu IMU i TIA, ali i na VMR, procenjivanu kroz indeks zadržavanja daha (Breath Holding Index, BHI) ipsilateralno i kontralateralno u odnosu na karotidnu stenozu. Analizirana je povezanost stepena karotidne stenoze sa vrednostima BHI preoperativno, povezanost BHI sa težinom kliničke slike, uticaj kolateralnog krvotoka na VMR, distribucija BHI u pojedinim tipovima IMU i TIA kao i komparacija BHI u pre i u postoperativnom periodu od 30 i 90 dana. Na osnovu sprovedenog istraživanja, do&scaron;lo se do zaključaka da je redukovana VMR preoperativna karakteristika karotidne stenoze ipsilateralno kao i karakteristika različitih tipova IMU i TIA ipsilateralno; postoji negativna korela ija izmeĐu stepena karotidne stenoze i BHI vrednosti. Nije potvrđena hipoteza da veći roj razvijenih kolateralnih puteva uslovljava očuvanu VMR; utvrđena je pozitivna korelacija između BHI vrednosti u preoperativnom i postoperativnom periodu; redukovana VMR ima negativan uticaj na težinu kliničke slike. Prepoznavanje vrednosti TCD apnea testa, koji se može koristiti kao komplementarna metoda drugim vazoaktivnim testovima u praćenju karotidne hemodinamike, od posebne je važnosti neurologu i vaskularnom hirurgu. Time bi se doprinelo daljoj evaluaciji mehanizma nastanka IMU, planiranju terapijskog pristupa i determinisanju prognoze operisanih bolesnika. Činjenica da većina neurolo&scaron;kih odeljenja poseduje TCD aparat, apnea test postaje dostupan svakom neurologu u kliničkom radu, posebno u na&scaron;im uslovima, kada se do drugih drugih, skupljih metoda, te&scaron;ko stiže ili nam ostaju nedostižne.</p> / <p>TCD apnea test, as a noninvasive and safe neuroultrasonographic method, provides useful information about vasomotor reactivity (VMR) in the indirect evaluation of cerebral autoregulation. Vasomotor reactivity is the ability of cerebral arterioles to constrict or to dilate in response to a vasoactive stimulus, mainly carbon dioxide. The aim of this doctoral thesis was to investigate and analyze changes in carotid hemodynamics in patients with ischemic stroke (IS) or transient ischemic attack (TIA) and symptomatic carotid stenosis in the preoperative and three-month postoperative period as well as the assessment of revascularisation effect of carotid endarterectomy (CEA). The study included 60 hospitalized patients who experienced a first ischemic stroke or TIA in the vasularisation area of anterior cerebral artery (ACA) and middle cerebral artery (MCA), all with carotid stenosis &ge;70% ACI. Patients were hospitalized at the Clinic of Neurology, Clinical Center of Vojvodina, Department of Cardiovascular Surgery, Institute of Cardiovascular Diseases and the Department of Vascular Surgery in Novi Sad. Considering clinical manifestations of stroke, the patients were divided into three groups: patients with TIA and amaurosis fugax, with partial infarction in area ACA or ACM and with lacunar infarct. The study analyzed the impact of variabile and unvariable vascular risk factors on the incidence of ischemic stroke and TIA, but also on VMR, evaluated through Breath Holding Index (Breath Holding Index, BHI) on the ipsilateral and contralateral side from carotid stenosis. We analysed the correlation between the degree of carotid stenosis with preoperative values of BHI, BHI correlation to the severity of clinical findings, the impact of collateral circulation to the VMR, distribution of BHI in certain types of ischemic stroke and TIA as well as comparison of BHI in the pre and postoperative period of 30 and 90 days. On the basis of this research came the conclusion that reduced VMR is characteristic of ipsilateral carotid stenosis in preoperative period as well as number of developed collateral characteristics of different types of ipsilateral ischemic stroke and TIA; there is a negative correlation between the degree of carotid stenosis and BHI values. The hypothesis that the greater pathways causes preservation of VMR was not confirmed, while the positive correlation between BHI values in the preoperative and postoperative period was established. Reduced VMR has a negative impact on the degree of clinical picture severity. Recognizing the importance of TCD apnea test method, that can be used as a complementary method to other vasoactive tests in monitoring of carotid hemodynamics, is of special importance to the neurologists and vascular surgeons. This would contribute to the further evaluation of mechanism of ischemic stroke, planning of therapeutic approach and determining the prognosis of treated patients. The fact that most of neurological department has TCD device, apnea test becomes available to every neurologist in clinical work, specially in our conditions, when other methods remain unattainable.</p>

African Americans have increased risk for cardiovascular and cerebral vascular disease relative to Caucasian Americans. While it is generally accepted that arteries become stiffer at a younger age in African Americans; less is known regarding cerebral vascular function / reactivity (CVMR) to hypercapnia in African Americans. Furthermore, little is known regarding the relationship between arterial stiffness and CVMR, particularly in young healthy adults. We hypothesized that African Americans have stiffer arteries (i.e. arterial stiffness) and reduced CVMR during hypercapnia relative to Caucasian Americans. We also hypothesized that there would be a negative relationship between arterial stiffness and CVMR. Lastly, we hypothesized that these responses would be related to a decrease in Vitamin D status in this population and there would be correlation between Vitamin D status and CVMR. In 11 African American and 19 Caucasian American subjects central arterial stiffness was indexed from carotid-femoral pulse wave velocity (PWV). CVMR was assessed by the cerebral vascular conductance (CVC) response to rebreathing-induced hypercapnia. Vitamin D status was assessed from plasma 25(OH) Vitamin D. PWV was elevated in the African Americans (African American: 581.16 ± 27.7 cm/sec vs. Caucasian American: 502.98 ± 17.6 cm/sec; P < 0.01). CVMR was significantly reduced during hypercapnic rebreathing in the African Americans (African American: 3.05 ± 0.38% of baseline/mmHg vs. Caucasian American: 5.09 ± 0.29% of baseline/mmHg; P < 0.001). When data from all subjects was included there was a trend towards a negative relationship (R = 0.32, P = 0.10) between PWV and CVMR. Vitamin D status was significantly lower in African Americans (African American: 14.96 ± 0.97 ng/ml vs. Caucasian American: 32.73 ± 0.99 ng/ml; P < 0.001); however, there was no significant relationship between Vitamin D status and CVMR (R = 0.23 P = 0.23). In conclusion, these data indicate that African Americans have impaired cerebral vascular responses to hypercapnia, stiffer arteries, and lower Vitamin D status when compared with Caucasian Americans. In addition, there may be a negative relationship between CVMR and PWV; however, no significant correlation between Vitamin D status and vascular function including PWV or CVMR was observed in this study. / text

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 4 uppsatser.