Both sympathoneural and sympathoadrenal systems are involved in the regulation of arterial blood pressure and in the pathogenesis of hypertension. Spontaneously hypertensive rats (SHR), the mostly used animal model of genetic hypertension, is characterized by multiple molecular, morphological and functional alterations at different levels of sympathoneural and sympathoadrenal systems. The study of young prehypertensive SHR allows to reveal the abnormalities preceding hypertension development, whereas adult SHR with established hypertension offers a better model for the treatment of human essential hypertension. The aim of my PhD Thesis was to describe abnormalities in sympathoneural and sympathoadrenal systems in SHR under different conditions. Firstly, ontogenetic differences which might contribute to hypertension development were determined. Secondly, the effect of chemical sympathectomy induced by guanethidine in adulthood on cardiovascular parameters and on the compensatory mechanisms counteracting the reduction of blood pressure were studied. Thirdly, stress-induced cardiovascular response and stress-induced changes of sympathoneural and sympathoadrenal systems were described in adult SHR. My Thesis brought several important results. The increased adrenal catecholamine content and the...

Maintaining of homeostasis is essential for the survival of the organism. Stress disturbs the homeostasis and prepares the organism for mental or physical stress. During the stress situation, the endogenous stress factors are released. Through these factors stress affects tissue regeneration, the immune system and other metabolic processes. Chronic stress impacts many parts of body and mind and has a negative effect on these processes. Acute stress has the opposite effect. Mesenchymal stem cells (MSCs) participate in regenerative processes and modulate the immune system. Therefore, it can be assumed that stress will affect on MSCs. The aim of this study was to investigate the effect of stress factors, norepinephrine and corticosterone on the properties and function of MSCs in acute and chronic stress model. In our study, stress factors did not affect the morphology, vitality and differentiation of MSCs. However, the metabolic activity of MSCs was reduced regardless of the duration of their action. The action of stress factors also affected the production of some immunologically relevant molecules and proteins. Unfortunately, the results did not show a clear effect of stress factors on the lymphocyte modulation by MSCs. Key words: mesenchymal stem cells, catecholamines, adrenergic receptors,...

Nutrient restriction is a relatively common production insult to pregnancy in cattle. Recently, melatonin supplementation has been investigated as a possible therapeutic to rescue the negative effects of nutrient restriction. Neurotransmitters have been implicated as having negative programming effects in mouse and human pregnancies, manifested as metabolic and neurologic disorders. The role of neurotransmitters in fetal development has only begun to be understood in mice and humans. Neurotransmitters have not been analyzed in cattle, much less within the context of a compromised pregnancy. Brangus heifers were allotted to one of four treatments (ADQ-CON, RES-CON, ADQ-MEL, RES-MEL) in either Fall 2019 or Summer 2020. Cesarian sections, at day 240 of gestation, allowed for fetal and placental tissues to be collected for neurotransmitter and gene expression analysis. Alterations to neurotransmitter pathways were observed in a seasonally dependent manner. Future investigation is needed into the implications of altered neurotransmitters on post-natal life.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

INTRODUÇÃO: Não são conhecidos os mecanismos que determinam o comportamento da pressão arterial durante o sono. OBJETIVO: Investigar o papel do sistema nervoso simpático, do sistema renina-angiotensinaaldosterona e da excreção de sódio urinário no descenso da pressão arterial durante o sono. MÉTODOS: Hipertensos e normotensos foram submetidos a duas monitorizações ambulatoriais de pressão arterial (MAPA)/24h com SpaceLabs 90207, medidas de 15/15 minutos durante a vigília e de 20/20 minutos no período de sono. Na ocasião da MAPA 1 foram submetidos às dosagens laboratoriais de atividade de renina (ARP), aldosterona e catecolaminas plasmáticas e excreção em diurese de 24h de sódio (Na+u), potássio (K+u) e creatinina. Após o período médio de 50 ± 20 (média ± DP) dias a MAPA e as dosagens foram repetidas. RESULTADOS: Foram incluídos 35 hipertensos e 24 normotensos, com idade 56 ± 12 anos, 45 mulheres e 42 com cor da pele branca. Não houve diferença nos parâmetros laboratoriais na ocasião da MAPA 1 e da MAPA 2 nos normotensos e hipertensos. Mantiveram o mesmo comportamento de descenso da pressão sistólica e diastólica durante o sono nas duas MAPAs (>= 10% ou < 10%) 29 (49%) indivíduos, denominado grupo manteve (hipertensos n = 18). Mudaram o comportamento do descenso durante o sono da pressão sistólica ou diastólica (de >= 10% para < 10% ou de < 10% para >= 10%) 30 (51%) indivíduos, denominado grupo mudou (hipertensos n = 17). O grupo \"mudou\" apresentou menor Na+u na ocasião da MAPA 2 (145 ± 65 mEq/24 h vs 120 ± 46 mEq/24 h, p = 0,04). Houve correlação positiva entre: a) a diferença do descenso da pressão sistólica e a diferença dos resultados das dosagens de Na+u (r = 0,41; p = 0,01) realizadas nas MAPAs 1 e 2 em todos os indivíduos dos grupos \"manteve\" e \"mudou\"; b) a diferença do descenso da pressão sistólica e a diferença de Na+u/creatinina urinária (r = 0,67; p = 0,03) e de L dopa plasmática (r = 0,75; p = 0,003) realizadas nas MAPAs 1 e 2 no grupo \"manteve\" (>= 10%); e c) a diferença do descenso da pressão sistólica e a diferença do resultado das dosagens de ARP/Na+u realizadas nas MAPAs 1 e 2 (r = 0,81; p = 0,03) no grupo \"manteve\" (< 10%). CONCLUSÃO: Em hipertensos e normotensos, sem intervenção medicamentosa ou dietética, a diferença do descenso da pressão sistólica durante o sono entre duas MAPAs apresenta correlação positiva com a diferença da excreção de sódio urinário / INTRODUCTION: The mechanisms which determine the pattern of blood pressure during sleep are unknown. OBJECTIVE: To investigate the role of the sympathetic nervous system, renin-angiotensin-aldosterone system and urinary sodium excretion in the nocturnal blood pressure fall. METHODS: Hypertensive and normotensive subjects were submitted to two ambulatorial blood pressure monitorings (ABPM)/24h with a SpaceLabs 90207 equipment programmed to obtain measurements 15/15 minutes while awake and 20/20 minutes during sleep. Upon the ABPM 1, they were submitted to laboratory measurements of plasma renin activity (PRA), plasma aldosterone and catecholamines, as well as of the excretion of sodium (UNa+), potassium (UK+) and creatinine in 24-h-diuresis. After a mean period of 50 ± 20 days, the ABPM and the laboratory measurements were repeated. RESULTS: Included in the study were 35 hypertensive and 24 normotensive subjects, aged 56 ± 12 years, of which 45 were females and 42 Caucasian. There was no difference in the laboratory parameters measured upon ABPM 1 or 2, in either normotensive or hypertensive subjects. The same pattern of nocturnal systolic and diastolic pressure fall was maintained in both ABPMs (>=10% or <10%) by 29 (49%) subjects, named the \"maintained\" group (hypertensive n = 18). The nocturnal systolic or diastolic pressure fall changed (from >=10% to <10% or from <10% to >=10%) in 30 (51%) subjects, named the \"changed\" group (hypertensive n = 17). The \"changed\" group showed a smaller UNa+ upon the ABPM 2 (145 ± 65 mEq/24 h vs 120 ± 46 mEq/24 h; p = 0.04). There was a positive correlation between the difference in the nocturnal systolic pressure fall and the difference in the results of the UNa+ (r = 0,41; p = 0,01) measurements performed upon ABPM 1 and 2 in the normotensive or hypertensive subjects of the \"maintained\" and \"changed\" groups; b) the difference in the nocturnal systolic pressure fall and the difference in the measurements of UNa+/creatinine excretion (r = 0.67; p = 0.025) and plasma L dopa (r = 0.75; p = 0.003) carried out upon ABPM 1 and 2 in the \"maintained\" group (>=10%); and c) the difference in the nocturnal systolic pressure fall and the difference in the results of the PRA/UNa+ measurements performed upon ABPM 1 and 2 (r = 0.81; p = 0.03) in the \"maintained\" group (<10%). CONCLUSION: In hypertensive and normotensive individuals, without any pharmacological or dietary intervention, the difference in the nocturnal systolic pressure fall between the two ABPMs shows a positive correlation with the difference in urinary sodium excretion

O núcleo pré-mamilar dorsal (PMd), de crucial importância para expressão do comportamento de defesa exibido por roedores durante o confronto com predador natural, odor ou contexto associado, representa o sítio hipotalâmico com maior aumento no número de células imunorreativas a proteína Fos após o confronto predatório. Estudos mostram que a mediação noradrenérgica central é crítica para a expressão das respostas de medo e que tanto as respostas incondicionadas como as contextuais ao odor do gato dependem de sua ação central, mediada pelo PMd. Dada a importância da modulação noradrenérgica no PMd para a expressão das respostas anti-predatórias, investigamos quais grupamentos catecolaminérgicos aferentam o núcleo empregando técnicas de rastreamento retrógrado somado a técnica de imunofluorescência (dupla-marcação). Nossos resultados revelaram que a única fonte de aferência catecolaminérgica para o PMd é oriunda do locus ceruleus, onde encontramos um número conspícuo de células duplamente marcadas, indicando ser este o responsável pelo suporte noradrenérgico ao PMd. / Evidence suggests the medial hypothalamic defensive system plays a pivotal role in processing of predator-derived and contextual-related cues. Fear responses to predatory threats rely heavily on the PMd beta adrenergic neurotransmission. Thus, it has been shown that propranolol significantly reduced PMdFos expression in response to cat odor, and that beta adrenoceptor blockade, in the PMd, reduced defensive responses to both cat odor exposure and cat odor-related context. Given the importance of the noradrenergic innervation of the PMd to the expression of unconditioned and learned fear responses, we have presently investigated the putative noradrenergic source of inputs to the nucleus. To this end, we have combined Fluoro-Gold retrograde tract-tracing and catecholamine immunostaining, and found that the locus ceruleus is seemingly the only source of catecholaminergic source of inputs to the PMd. In addition, the present findings are particularly interesting given the well-documented roles of the locus ceruleus roles in attentional processes.

A sepse grave e o choque séptico são complicações decorrentes de um processo infeccioso, associados à alta mortalidade em UTI e caracterizados por disfunção cardiovascular, renal e metabólica. A terapia farmacológica (TF) visa oferecer suporte hemodinâmico e reduzir níveis glicêmicos. Nesse cenário, o presente estudo objetivou analisar o impacto da TF e da alteração glicêmica na evolução clinica do paciente em sepse grave e choque séptico nas primeiras 72 horas.Trata-se de um ensaio clínico controlado randomizado em que os pacientes (n=46) foram alocados em grupos glicêmicos intensivo (manutenção da glicemia entre 80-110mg/dl) e convencional (manutenção da glicemia entre180-220mg/dl). Os dados foram coletados no período de 2004-2006 em um Hospital Universitário do Município de São Paulo. Na análise estatística foram usados os testes t-student, Qui-Quadrado, sendo considerados significativo p<0,05. Os resultados mostraram que a amostra foi constituída por pacientes do sexo masculino (58,7%), clínicos (78,3%) que apresentaram choque séptico (78,3%) decorrente de infecções no sistema respiratório (39,1%), com disfunção cardíaca (36,9%) e que apresentaram lesão renal aguda (56,5%). A média de idade foi de 51,6 anos. Os medicamentos de suporte mais prescritos foram noradrenalina (69,6%; 56,5%), hidrocortisona (56,5%;67,4%) e insulina (67,4%;73,9%), nas 24 e 48 h. Na comparação entre os grupos, observou-se diferença estatisticamente significante (p=0,00) na média glicêmica; não houve diferença estatisticamente significantes para as variáveis FC mínima (p= 0,68), máxima (p=0,11), PAM mínima (p=0,06) e máxima (p=0,11), no DU (p=0,23), Cr (p=0,33), volume infundido de cristalóides (p=0,10) e na mortalidade (p=0,11). A instabilidade hemodinâmica no grupo convencional foi mais duradoura e os óbitos ocorreram, apenas, entre os pacientes alocados no grupo convencional. Dessa forma, os dados sugerem que o controle glicêmico intensivo favorece o restabelecimento hemodinâmico de pacientes em choque séptico e, de certo modo, os protege do desfecho mortalidade / Severe sepsis and septic shock are complications that develop from an inflammatory process leading to high mortality in the intensive care unit (ICU) and characterized by cardiovascular, renal and metabolic dysfunction. The pharmacological therapy (PT) aims at offering hemodynamic support and at reducing glycemic levels. In this scenario, the present study had the objective of analyzing the impact of PT and of the glycemic alteration in the clinical evolution of severe sepsis and septic shock patients in the first 72 hours. This is a randomized control trial in which the patients (n=46) were divided into intensive glycemic group (maintenance of glycemia between 80-110mg/dl) and conventional glycemic group (maintenance of glycemia between 180-220 mg/dl). The data were collected in the 2004-2006 period in a University Hospital in the city of São Paulo. In the statistical analysis, the tests used were t-student, Qui-Quadrado, being considered meaningful p<0,05. The results showed that the sample was formed by male patients (58.7%), clinical patients (78.3%) that presented septic shock (78.3%) as a result of infection in the respiratory system (39.1%), with cardiac dysfunction (36.9%) and those that presented acute renal lesion (56.5%). The average age was 51.6 years. The most commonly prescribed support drugs were noradrenaline (69.6%, 56.5%) and hydrocortisone (56.5%, 67.4%) in the first 24 and 48 hours. In the comparison between groups, statistically significant difference was observed (p=0,00) in the glycemic average, there was no statistically significant difference for the variables: minimal FC (p=0,68), maximum (p=0,11), minimum PAM (p=0,06) and maximum (p=0,11), DU (p=0,23), CR (p=0,33), volume infundido de cristalóides (p=0,10) and mortality (p=0,11). The hemodynamic instability in the conventional group lasted longer and deaths occurred only among the conventional group patients. Therefore, the data suggest that the intensive glycemic control favors the hemodynamic recovery of septic shock patients and, in a way, protects them from death

Les troubles du sommeil, tels que la somnolence diurne excessive et les attaques narcoleptiques, sont fréquemment observés chez les patients Parkinsoniens. Malgré de nombreux efforts cliniques à l’échelle mondiale, il reste à déterminer si ces troubles sont causés par les lésions neuronales dopaminergiques (DAergiques) ou non DAergiques, par les troubles moteurs ou par les effets délétères des médicaments anti-parkinsoniens. Par une approche pluridisciplinaire (analyse EEG; mesure de l’activité locomotrice; tests pharmacologiques; immunohistochimie) chez le félin traité au MPTP, nous avons étudié la corrélation possible entre perte DAergique et troubles du cycle veille-sommeil (V/S). Le MPTP (5mg/kg/jour x5, i.p.) induit en période aiguë, une hypersomnie en sommeil lent (SL), une suppression du sommeil paradoxal (SP), ainsi qu’une diminution de la locomotion et une difficulté à l’initiation des mouvements. Les agonistes DAergiques (L-dopa; ropinirole) empêchent l’hypersomnie en SL de façon transitoire. Durant la période chronique, les taux d’éveil et de SL reviennent à la normale. Le SP augmente transitoirement et s’associe à des épisodes narcoleptiques. Les analyses ex-vivo révèlent une diminution du marquage TH (corps cellulaire de la substance noire ; fibres du striatum). Le marquage des neurones cholinergiques (cerveau antérieur basal et tegmentum mésopontique) semblent inchangée. Nos résultats montrent donc que le MPTP induit chez le félin des symptômes moteurs et des troubles du sommeil proches de ceux observés chez les patients parkinsoniens. Cette étude suggère également une corrélation possible entre les troubles du cycle V/S et la perte des cellules DAergiques / Motors disorders are not the only symptoms of Parkinson disease (PD), and sleep disorders such as somnolence and narcolepsy are frequently reported in PD patients. Despite much investigation worldwide, it remains unknown whether these disorders are caused by dopaminergic (DArgic), non-DArgic neural lesions, nocturnal motor disability or deleterious effect of anti-PD drugs. Using multiple experimental approaches (EEG and sleep-wake recordings/pharmacological dosing / immunohistochemistry) in cats treated with MPTP, which causes DArgic neuronal loss, we have studied the possible correlation between the induced effects on the sleep-wake (S/W) cycle and those on DArgic neurons. MPTP (5mg/kg/day x 5, i.p.) caused, during the acute period, a slow wave sleep hypersomnia (SWS, up to 80% of recorded time) and a suppression of paradoxical sleep (PS), accompanied with pronounced behavioural somnolence, marked decrease in locomotion and difficulty to initiate movements. DArgic agonists L-dopa and ropinirole transiently prevented hypersomnia in SWS. During the chronic period, whereas the amount of W and SWS returned to control, PS transiently increased, associated with narcolepsy-like episodes. Ex-vivo analyses revealed marked decrease in TH labelling (cell bodies in the substantia nigra and terminal-like dots in the striatum) whereas cholinergic neurons in the basal forebrain and mesopontine-tegmentum seemed unchanged. Thus, MPTP treated cats showed major signs of motor and S/W disorders similar to those seen in PD patients and so could serve as useful animal model. Our results also suggest a possible correlation/causality between the MPTP-induced S/W disorders and DArgic cell loss.

Includes bibliographical references (leaves 183-207) A local intradermal technique using colchicine to estimate cell division rate in wool follicles is refined and used throughout the thesis. Statistical methods used to analyse data obtained with this method are described and discussed. The implications of the findings are of great significance to research into the influence of physiological changes on wool production, and suggest experiments should be conducted under controlled environmental conditions, with a minimum of stress imposed on the animals.