Nos últimos anos, vários estudos têm demonstrado que durante o desenvolvimento da insuficiência cardíaca (IC) ocorre uma ativação no sistema imunológico, notadamente através de alterações nos níveis plasmático de citocinas pro e antiinflamatórias. Desta forma, estratégias terapêuticas têm sido utilizadas com o intuito de modular a ação destas citocinas e neste caso, o treinamento físico aeróbio parece promissor. Em nosso estudo, avaliamos o efeito de oito semanas de um programa de treinamento aeróbio em esteira para ratos com IC secundária a infarto do miocárdio (IM). Apesar da produção e expressão dos genes (TNF-<font face=\"symbol\">a, IL-6 e IL10) estarem aumentados nos músculo sóleo dos animais com IC, o programa de treinamento aeróbio foi capaz de reverter este quadro, demonstrando valores próximos aos animais normais (sem IC). Desta forma, nos estudo sugere que o treinamento aeróbio moderado demonstrou efeito antiinflamatório em animais com IC secundária a (IM), podendo exercer um importante papel como terapêutica em programas de reabilitação de doenças cardiovasculares. / Recently, several studies has demonstrated immune activation during heart failure (HF) development, notably through changes in plasmatic levels pro and anti-inflammatory cytokines. For this reason, therapeutic interventions have been used with targeting to modulate this cytokine action and in this way, endurance training may be promising. In our study, we evaluated the effect of 8 weeks of endurance training program in a treadmill for post-myocardial (MI) HF rats. Despite increased of levels and gene expression (TNF-<font face=\"symbol\">a, IL-6 e IL10) in soleus muscle of post-MI HF rats, endurance training was able to reverse this change, showing similar values that as founded in control group (without HF). In this way, our study suggests that moderate endurance training demonstrated anti-inflammatory effect in post-MI HF rats, and it may play an important role as therapeutic in rehabilitation programs of cardiovascular disease.

Orientador: Luís Guilherme de Oliveira / Abstract: Mycoplasma hyopneumoniae é o agente etiológico da Pneumonia Enzoótica Suína (PES), enfermidade de distribuição mundial, e responsável por prejuízos como queda no ganho de peso diário e aumento da susceptibilidade dos animais acometidos a infecções respiratórias secundárias mais graves. Os principais fatores envolvidos na formação de lesão de consolidação crânio-ventral em suínos infectados ainda não são bem elucidados. Sendo assim, este estudo teve como objetivo esclarecer os principais fatores imunológicos e de carga bacteriana envolvidos na formação de lesões macroscópicas, bem como a dinâmica do agente em quatro pontos no tempo da fase aguda da enfermidade em suínos experimentalmente infectados. Para este fim, 24 suínos provenientes de fazenda livre de M. hyopneumoniae foram divididos em dois grupos: controle (n=8) e infectados (n=16). No dia 0 pós-infecção (dpi) os animais do grupo infectado foram inoculados com inóculo de pulmão contendo 106 CCU∕mL de M.hyopneumoniae, pela via intratraqueal, enquanto os animais do grupo controle foram inoculados com 5 mL de meio esterilizado. Semanalmente, os animais foram examinados, pesados e amostras de sangue e suabes nasais foram colhidas. Nos dias 14, 28, 42 e 56 pós-infecção quatro animais infectados e dois controles foram eutanasiados e necropsiados. Durante as necropsias realizou-se o escore de lesão pulmonar macroscópica e foram colhidas amostras biológicas de lesão pulmonar (qPCR e histopatologia), lavado traqueobrônquico (LTB... (Complete abstract click electronic access below) / Doutor

Diese Arbeit beschreibt Ergebnisse einer in-vitro Untersuchung der Antipsychotika Chlorpromazin, Haloperidol, Clozapin, N-Desmethylclozapin und Quetiapin bezüglich ihrer Wirkung auf die Zytokinproduktion. Dafür wurde Vollblut von gesunden Probandinnen invitro mit dem Immunmodulator Toxic-Shock-Syndrome-Toxin-1 (TSST-1) stimuliert. Dabei wurden die Konzentrationen der Zytokine Interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-17 und Tumornekrosefaktor-α (TNF-α) im unstimulierten Blut und im stimulierten Blut, jeweils mit und ohne Zusatz der Antipsychotika gemessen. Es zeigte sich, dass TSST-1 eine signifikante Stimulation der Produktion aller getesteten Zytokine bewirkte und dass es über diese Stimulation mit TSST-1 hinaus zu einer Erhöhung von IL-17 unter allen getesteten Antipsychotika kam. Aufgrund dieser Ergebnisse ist es denkbar, dass Antipsychotika, in Ergänzung zu ihrer Wirkung an Dopaminrezeptoren, auch über diese immunologische Eigenschaft Wirkungen und Nebenwirkungen entfalten können. Weiterhin könnte die IL-17-Produktion ein Biomarker in der Behandlung mit Antipsychotika sein, der wiederum zur individuellen Vorhersage von Wirkungen und Nebenwirkungen beitragen könnte.

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Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Hematopoiesis is a precisely regulated process, dependent on the activity of hematopoietic cytokines and their receptors. Due to an extra round of whole genome duplication in teleost fish, two paralogs of many important genes, including some hematopoietic cytokines and their receptors, are present in the zebrafish (Danio rerio) genome. In this project, we have been investigating the role of zebrafish Kit ligands in hematopoiesis. Kit ligand is a pleiotropic cytokine, which is essential for vertebrate erythropoiesis; however, in zebrafish, no such role has been reported so far. To determine the function of zebrafish paralogs of Kit ligand (Kitlga and Kitlgb) in hematopoiesis, we performed in vivo and ex vivo gain- and loss-of-function experiments. Strikingly, we were the first to report the synergistic cooperation of zebrafish Kitlga with erythropoietin and dexamethasone, enabling the growth of kidney marrow-derived suspension cells and providing optimal conditions for the expansion of adult erythroid progenitors. We assume that by using different cytokine combinations, optimal conditions for the growth of other hematopoietic cell types can be established, and therefore, this new approach now available for the...

Wir untersuchten Liquor- und Serumproben von 40 an einem shuntversorgten Hydrocephalus erkrankten Kindern auf die Konzentration der Zytokine bFGF, TGF-β1, VEGF, IL-6, IGF-1 und Leptin sowie deren Korrelation mit dem Risiko von Shuntinsuffizienzen. Dabei konnten wir die Hypothese bestätigen, dass erhöhte Konzentration der fibrogenen Zytokine bFGF und TGF-β1 im Serum bzw. Liquor mit einem erhöhten Risiko für operationspflichtige Shuntinsuffizienzen durch Obstruktion des Schlauchsystems einhergehen, und dass diese Komplikationen mit steigenden Zytokinkonzentrationen umso eher eintreten. Außerdem war bFGF im Liquor von Kindern, die zum Abnahmezeitpunkt an einer Shuntdysfunktion durch Obstruktion oder Einwachsen des Shunts litten, signifikant höher als bei Kindern, die zum Zeitpunkt der Abnahme keine Shuntdysfunktion aus eben genannten Gründen hatten. Des Weiteren fanden wir Konzentrationsunterschiede für IL-6 im Liquor zwischen den einzelnen Ursachen der Erkrankung, wobei das Zytokin am höchsten bei Tumorpatienten war, gefolgt von posthämorrhagischem und postmeningitischem Hydrocephalus, und am niedrigsten bei Kindern mit kongenitaler ZNS-Fehlbildung.

Alcohol represents the third leading cause of preventable death in the United States. Yet, despite its prevalent role in impeding human health, there is much to understand about how it elicits its effects on the body and how the body and brain change when an individual becomes physiologically dependent upon alcohol. The work presented herein represents an effort to elucidate the acute and chronic effects of alcohol on the nervous system. We investigate two specific protein pathways and their role in alcohol's effects on the body. The first begins with brain-derived neurotrophic factor (BDNF), which acts on TrkB, and ends with KCC2. We demonstrate that BDNF expression is increased in the VTA during withdrawal from chronic but not acute alcohol exposure and that this increase persists for at least seven days. Concomitantly, we demonstrate that the activation of GABAA channels on produces less inhibition of VTA GABA neurons in mice treated with chronic intermittent ethanol exposure than in alcohol naïve mice. This effect likewise persisted for at least seven days. We illustrate that BDNF has no apparent direct effect on VTA GABA neuron firing rate. The second pathway begins with the T cell marker CD5 and ends with the anti-inflammatory cytokine, IL-10. We demonstrate that in a genetic CD5 knockout (CD5 KO) mouse model both alcohol consumption as well as the sedative properties of alcohol are reduced. Since CD+ B cells secrete more IL-10 than CD5- B cells, we also demonstrate the effects of IL-10 on VTA neurons. We show that IL-10 has direct effects on VTA dopamine (DA) neurons by increasing their firing activity. We relatedly illustrate that IL-10 produces an increase in DA release in the nucleus accumbens (NAc). However, contrary to our hypotheses, we show that IL-10 produces conditioned place aversion rather than conditioned place preference in a place conditioning paradigm, suggesting that IL-10 might mediate pain-induced secretions of DA. Collectively, these results suggest two potential therapeutic targets to reduce alcohol consumption that need further validation. They also suggest a novel mechanism for the sedative effects of alcohol at moderate and high doses.

Alcohol represents the third leading cause of preventable death in the United States. Yet, despite its prevalent role in impeding human health, there is much to understand about how it elicits its effects on the body and how the body and brain change when an individual becomes physiologically dependent upon alcohol. The work presented herein represents an effort to elucidate the acute and chronic effects of alcohol on the nervous system. We investigate two specific protein pathways and their role in alcohol’s effects on the body. The first begins with brain-derived neurotrophic factor (BDNF), which acts on TrkB, and ends with KCC2. We demonstrate that BDNF expression is increased in the VTA during withdrawal from chronic but not acute alcohol exposure and that this increase persists for at least seven days. Concomitantly, we demonstrate that the activation of GABAA channels on produces less inhibition of VTA GABA neurons in mice treated with chronic intermittent ethanol exposure than in alcohol naïve mice. This effect likewise persisted for at least seven days. We illustrate that BDNF has no apparent direct effect on VTA GABA neuron firing rate. The second pathway begins with the T cell marker CD5 and ends with the anti-inflammatory cytokine, IL-10. We demonstrate that in a genetic CD5 knockout (CD5 KO) mouse model both alcohol consumption as well as the sedative properties of alcohol are reduced. Since CD+ B cells secrete more IL-10 than CD5- B cells, we also demonstrate the effects of IL-10 on VTA neurons. We show that IL-10 has direct effects on VTA dopamine (DA) neurons by increasing their firing activity. We relatedly illustrate that IL-10 produces an increase in DA release in the nucleus accumbens (NAc). However, contrary to our hypotheses, we show that IL-10 produces conditioned place aversion rather than conditioned place preference in a place conditioning paradigm, suggesting that IL-10 might mediate pain-induced secretions of DA. Collectively, these results suggest two potential therapeutic targets to reduce alcohol consumption that need further validation. They also suggest a novel mechanism for the sedative effects of alcohol at moderate and high doses.

No description available.