One countermeasure to cardiovascular spaceflight deconditioning being tested is the application of intermittent artificial gravity provided by centripetal acceleration of a human via centrifuge. However, artificial gravity protocols have not been optimized for the cardiovascular system, or any other physiological system for that matter. Before artificial gravity protocols can be optimized for the cardiovascular system, cardiovascular responses to the variables of artificial gravity need to be quantified. The research presented in this document is intended to determine how the artificial gravity variables, radius (gravity gradient) and lower limb exercise, affect cardiovascular responses during centrifugation. Net fluid (blood) shifts between body segments (thorax, abdomen, upper leg, lower leg) will be analyzed to assess the cardiovascular responses to these variables of artificial gravity, as well as to begin to understand potential mechanism(s) underlying the beneficial orthostatic tolerance response resulting from artificial gravity training. Methods: Twelve healthy males experienced the following centrifuge protocols. Protocol A: After 10 minutes of supine control, the subjects were exposed to rotational 1 Gz at radius of rotation 8.36 ft (2.54 m) for 2 minutes followed by 20 minutes alternating between 1 and 1.25 Gz. Protocol B: Same as A, but lower limb exercise (70% V02max) preceded ramps to 1.25 Gz. Protocol C: Same as A but radius of rotation 27.36 ft (8.33 m). Results: While long radius without exercise presented an increased challenge for the cardiovascular system compared to short radius without exercise, it is likely at the expense of more blood “pooling” in the abdominal region. Whereas short radius with exercise provided a significant response compared to short radius without exercise. More fluid loss occurred from the thorax and with the increased fluid loss from the thorax blood did not “pool” in the abdominal region but instead was essentially “mobilized” to the upper and lower leg. The exercise fluid shift profile presented in this document is applicable to not only artificial gravity protocol design but also proposes a mechanistic reason as to why certain artificial gravity protocols are more effective than others in increasing orthostatic tolerance.

Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro / O Chá Verde, derivado das folhas da planta Camellia sinensis, rico em flavonóides, cuja maior concentração é de Epigalocatequina gallato (EGCG), possui efeito termogênico, além de promover a oxidação da gordura corporal, tendo potencial interesse para o tratamento da obesidade, que atinge prevalência alarmante em diversos países no mundo. O objetivo deste estudo foi a avaliação de parâmetros bioquímicos e investigação da função endotelial em mulheres com Índice de Massa Corporal (IMC) entre 30kg/m2 e 40kg/m2, na faixa de 30 e 50 anos, antes e após 03 meses de consumo de chá verde (600mL/dia, equivalente a 114,42mg de EGCG). Todas as 60 pacientes voluntárias foram submetidas à análise das medidas antropométricas (Peso, Altura, Índice de Massa Corporal, Circunferência de Cintura, Circunferência de Quadril, Relação Cintura-Quadril, Pressão Arterial, à análise da bioquímica de rotina (Glicemia e Insulina de jejum, Triglicerídeos, Colesterol Total, HDL-Colesterol, LDL-Colesterol, Teste Oral de Tolerância à Glicose, Hemograma Completo, Proteína C-Reativa), à análise da bioquímica específica para estresse oxidativo e inflamação (Interleucinas 1 e 6, Fator de Necrose Tumoral Alfa, LDL-Oxidado, VCAM Vascular Cell Adhesion Molecule, ICAM Intercellular Adhesion Molecule, e E-Selectina) e à Pletismografia de Oclusão Venosa (variação de fluxo médio máximo durante a Hiperemia Reativa/Fluxo Basal 1 (VQ Hiper) e fluxo após administração de 0,4mg de Nitroglicerina Sublingual/Fluxo Basal 2 (VQ Nitro)). Após os 3 meses (3M) de tratamento houve redução no peso corporal (86,35[83,00-94,25] vs 3M = 86,00[81,50-92,00] Kg, P < 0,05); no IMC (34,02[32,05-35,62] vs 3M = 33,13[32,28-35,05] kg/m2, P < 0,05); na circunferência de cintura (99[93-107] vs 3M = 98[91-105]cm, P < 0,001); na circunferência de quadril (115[110-119] vs 3M = 114[110-117] cm, P < 0,001); na relação cintura-quadril (0,89[0,84-0,93] vs 3M = 0,88[0,83-0,93], P < 0,001); e, na pressão arterial diastólica (75[73-82] vs 3M = 69[67-72] mmHg, P < 0,001); e, melhora significativa no fluxo sanguíneo da VQ Hiper (4,57[3,54-5,01] vs 3M = 5,83[4,46-6,56], P < 0,001); e da VQ Nitro (1,26[1,13-1,38] vs 3M = 1,41[1,25-1,50], P < 0,001). Com o uso do chá verde, 600mL/dia, contendo 114,42mg de EGCG, durante 3 meses observamos a redução de 3% no IMC e a redução da circunferência de cintura e de circunferência de quadril em 1cm; a não modificação do padrão bioquímico, incluindo os marcadores de inflamação e de estresse oxidativo; e, o aumento das vasodilatações endotélio-dependente e endotélio-independente, visualizadas por Pletismografia de Oclusão Venosa Não-Invasiva. / Green tea, derived from the leaves of the plant Camellia sinensis, rich in flavonoids, whose greatest concentration is Epigallocatechin gallato (EGCG), has termogenic effect, and promote fat oxidation, with potential interest for the treatment of obesity, which is reaching alarming prevalence in many countries worldwide. The aim of this study was to evaluate biochemical parameters and endothelial function in women with Body Mass Index (BMI) between 30kg/m2 and 40kg/m2, 30 and 50 years old, before and after 03 months of consumption of green tea (600mL/day, equivalent to 114.42mg of EGCG). All the 60 voluntary patients were submitted to the analyses of anthropometric measures (weight, height, body mass index, waist circumference, hip circumference, waist-hip ratio, blood pressure), to the biochemicalanalysis of routine (fasting glucose and insulin, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, oral glucose tolerance, hemogram, C-Reactive protein), to the biochemical analysis of specific oxidative stress and inflammation (interleukins 1 and 6, tumor necrosis factor alpha, oxidized LDL, VCAM - Vascular Cell Adhesion Molecule, ICAM - Intercellular Adhesion Molecule and E-selectin) and to venous occlusion plethysmography (variation of maximum average flux during Reactive Hyperemia/Basal 1 Flow (VQ Hiper) and flow after administration of 0,4mg Sublingual Nitroglycerin/Basl 2 Flow (VQ Nitro)).After 03 months (3M) of treatment there was a reduction in body weight (86.35[83.00-94.25] vs 3M = 86.00[81.50-92.00] Kg, P < 0.05); in BMI (34.02[32.05-35.62] vs 3M = 33.13[32.28-35.05] kg/m2, P < 0.05); in waist circumference (99[93-107] vs 3M = 98[91-105]cm, P < 0.001); in hip circumference (115[110-119] vs 3M = 114[110-117] cm, P < 0.001); in waist-hip ration (0.89[0.84-0.93] vs 3M = 0.88[0.83-0.93], P < 0.001); and in diastolic blood pressure (75[73-82] vs 3M = 69[67-72] mmHg, P < 0.001); and, a significant improvement in blood flow of VQ Hiper (4.57[3.54-5.01] vs 3M = 5.83[4.46-6.56], P < 0.001); and in blood flow of VQ Nitro (1.26[1.13-1.38] vs 3M = 1.41[1.25-1.50], P < 0.001). With the use of green tea, 600mL/day, containing 114.42mg of EGCG for 3 months we saw a reduction of 3% in BMI and in the waist and hip circumferences of 1cm. There were no modification of standard biochemical parameters, including markers of inflammation and oxidative stress. There was increased endothelium-dependent and endothelium-independent vasodilation, viewed by noninvasive venous occlusion plethysmography.

Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro / O Chá Verde, derivado das folhas da planta Camellia sinensis, rico em flavonóides, cuja maior concentração é de Epigalocatequina gallato (EGCG), possui efeito termogênico, além de promover a oxidação da gordura corporal, tendo potencial interesse para o tratamento da obesidade, que atinge prevalência alarmante em diversos países no mundo. O objetivo deste estudo foi a avaliação de parâmetros bioquímicos e investigação da função endotelial em mulheres com Índice de Massa Corporal (IMC) entre 30kg/m2 e 40kg/m2, na faixa de 30 e 50 anos, antes e após 03 meses de consumo de chá verde (600mL/dia, equivalente a 114,42mg de EGCG). Todas as 60 pacientes voluntárias foram submetidas à análise das medidas antropométricas (Peso, Altura, Índice de Massa Corporal, Circunferência de Cintura, Circunferência de Quadril, Relação Cintura-Quadril, Pressão Arterial, à análise da bioquímica de rotina (Glicemia e Insulina de jejum, Triglicerídeos, Colesterol Total, HDL-Colesterol, LDL-Colesterol, Teste Oral de Tolerância à Glicose, Hemograma Completo, Proteína C-Reativa), à análise da bioquímica específica para estresse oxidativo e inflamação (Interleucinas 1 e 6, Fator de Necrose Tumoral Alfa, LDL-Oxidado, VCAM Vascular Cell Adhesion Molecule, ICAM Intercellular Adhesion Molecule, e E-Selectina) e à Pletismografia de Oclusão Venosa (variação de fluxo médio máximo durante a Hiperemia Reativa/Fluxo Basal 1 (VQ Hiper) e fluxo após administração de 0,4mg de Nitroglicerina Sublingual/Fluxo Basal 2 (VQ Nitro)). Após os 3 meses (3M) de tratamento houve redução no peso corporal (86,35[83,00-94,25] vs 3M = 86,00[81,50-92,00] Kg, P < 0,05); no IMC (34,02[32,05-35,62] vs 3M = 33,13[32,28-35,05] kg/m2, P < 0,05); na circunferência de cintura (99[93-107] vs 3M = 98[91-105]cm, P < 0,001); na circunferência de quadril (115[110-119] vs 3M = 114[110-117] cm, P < 0,001); na relação cintura-quadril (0,89[0,84-0,93] vs 3M = 0,88[0,83-0,93], P < 0,001); e, na pressão arterial diastólica (75[73-82] vs 3M = 69[67-72] mmHg, P < 0,001); e, melhora significativa no fluxo sanguíneo da VQ Hiper (4,57[3,54-5,01] vs 3M = 5,83[4,46-6,56], P < 0,001); e da VQ Nitro (1,26[1,13-1,38] vs 3M = 1,41[1,25-1,50], P < 0,001). Com o uso do chá verde, 600mL/dia, contendo 114,42mg de EGCG, durante 3 meses observamos a redução de 3% no IMC e a redução da circunferência de cintura e de circunferência de quadril em 1cm; a não modificação do padrão bioquímico, incluindo os marcadores de inflamação e de estresse oxidativo; e, o aumento das vasodilatações endotélio-dependente e endotélio-independente, visualizadas por Pletismografia de Oclusão Venosa Não-Invasiva. / Green tea, derived from the leaves of the plant Camellia sinensis, rich in flavonoids, whose greatest concentration is Epigallocatechin gallato (EGCG), has termogenic effect, and promote fat oxidation, with potential interest for the treatment of obesity, which is reaching alarming prevalence in many countries worldwide. The aim of this study was to evaluate biochemical parameters and endothelial function in women with Body Mass Index (BMI) between 30kg/m2 and 40kg/m2, 30 and 50 years old, before and after 03 months of consumption of green tea (600mL/day, equivalent to 114.42mg of EGCG). All the 60 voluntary patients were submitted to the analyses of anthropometric measures (weight, height, body mass index, waist circumference, hip circumference, waist-hip ratio, blood pressure), to the biochemicalanalysis of routine (fasting glucose and insulin, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, oral glucose tolerance, hemogram, C-Reactive protein), to the biochemical analysis of specific oxidative stress and inflammation (interleukins 1 and 6, tumor necrosis factor alpha, oxidized LDL, VCAM - Vascular Cell Adhesion Molecule, ICAM - Intercellular Adhesion Molecule and E-selectin) and to venous occlusion plethysmography (variation of maximum average flux during Reactive Hyperemia/Basal 1 Flow (VQ Hiper) and flow after administration of 0,4mg Sublingual Nitroglycerin/Basl 2 Flow (VQ Nitro)).After 03 months (3M) of treatment there was a reduction in body weight (86.35[83.00-94.25] vs 3M = 86.00[81.50-92.00] Kg, P < 0.05); in BMI (34.02[32.05-35.62] vs 3M = 33.13[32.28-35.05] kg/m2, P < 0.05); in waist circumference (99[93-107] vs 3M = 98[91-105]cm, P < 0.001); in hip circumference (115[110-119] vs 3M = 114[110-117] cm, P < 0.001); in waist-hip ration (0.89[0.84-0.93] vs 3M = 0.88[0.83-0.93], P < 0.001); and in diastolic blood pressure (75[73-82] vs 3M = 69[67-72] mmHg, P < 0.001); and, a significant improvement in blood flow of VQ Hiper (4.57[3.54-5.01] vs 3M = 5.83[4.46-6.56], P < 0.001); and in blood flow of VQ Nitro (1.26[1.13-1.38] vs 3M = 1.41[1.25-1.50], P < 0.001). With the use of green tea, 600mL/day, containing 114.42mg of EGCG for 3 months we saw a reduction of 3% in BMI and in the waist and hip circumferences of 1cm. There were no modification of standard biochemical parameters, including markers of inflammation and oxidative stress. There was increased endothelium-dependent and endothelium-independent vasodilation, viewed by noninvasive venous occlusion plethysmography.

Made available in DSpace on 2014-12-17T15:16:19Z (GMT). No. of bitstreams: 1 MurilloFLC_DISSERT.pdf: 1116563 bytes, checksum: 0ce3679bea0b52e58c079903ac1afc85 (MD5) Previous issue date: 2013-03-28 / Objetivo: Determinar os efeitos agudos de diferentes intensidades de press?o expirat?ria positiva sobre o padr?o respirat?rio e volumes operacionais de pacientes com doen?a de Parkinson. M?todos: Foram eleitos para o estudo 23 pacientes em est?gios II ou III da doen?a, estando na condi??o ON , sendo 8 exclu?dos, e 15 controles saud?veis. Os indiv?duos foram submetidos a uma avalia??o inicial, constando de dados gerais, avalia??o antropom?trica, fun??o pulmonar e for?a muscular respirat?ria. Ap?s esta etapa inicial, realizou-se a avalia??o dos volumes pulmonares com pletismografia optoeletr?nica associado a utiliza??o de press?o expirat?ria positiva (PEP) em tr?s intensidades de press?o positiva, 10 cmH2O, 15 cmH2O e 20 cmH2O em ordem aleat?ria. Resultados: O grupo Parkinson apresentou valores espirom?tricos e de for?a muscular respirat?ria significativamente menores que o grupo controle (p<0.01). Houve diferen?a nos valores de volume corrente (Vt) do grupo Parkinson em rela??o ao grupo controle na respira??o tranq?ila (p<0.001) e aumento no Vt do grupo Parkinson com uso das tr?s intensidades de PEP (p<0.001), sem diferen?as estatisticamente significativas entre as intensidades e com diferen?a na distribui??o compartimental do Vt entre os grupos (p<0.001). O fluxo inspirat?rio m?dio e o volume minuto do grupo Parkinson foram menores em rela??o ao grupo controle na respira??o tranq?ila (p<0.001) e aumentaram com o uso das tr?s intensidades de PEP (p<0.001), sem diferen?as estatisticamente significativas entre as intensidades. Houve diferen?a na varia??o dos volumes operacionais entre os grupos em todas as intensidades de PEP (p < 0.001). O volume pulmonar expirat?rio final n?o aumentou no grupo Parkinson com uso de PEP. O volume pulmonar inspirat?rio final aumentou no grupo Parkinson em todas intensidades de PEP (p < 0.001), n?o havendo diferen?as entre as intensidades. Conclus?o: Os pacientes com doen?a de Parkinson apresentam altera??es em diferentes componentes do padr?o respirat?rio e a terapia com PEP determina modifica??es clinicamente importantes nos volumes pulmonares, considerando a intensidade de 10 cmH2O suficientes para este objetivo terap?utico

Dietas ricas em gordura ou carboidrato têm sido difundidas e consumidas nas últimas décadas, entretanto pouco é conhecido sobre as consequências metabólicas destas em longo prazo. Neste estudo, foram analisados a quantidade de gordura intramiocelular (IMCL), a função endotelial, além da lipemia, glicemia, insulinemia e resistência à insulina após semanas de dieta rica em gordura ou carboidrato, perdendo ou mantendo peso. De 43 mulheres triadas com sobrepeso (25< BMI <29.9 Kg/m2), 22 foram randomizadas para duas diferentes sequências de dietas. O IMCL foi medido através de espectroscopia por ressonância magnética 1H e a função endotelial pela pletismografia. Após 4 semanas de dieta rica em carboidrato, mantendo peso, foi observado aumento no IMCL do músculo tibial anterior (2.06 ± 1.27 vs. 3.52 ± 1.92, p=0.04) e na insulinemia em jejum (11.55 ± 4.43 vs. 14.03 ± 5.23, p=0.04), enquanto a dieta rica em gordura, no mesmo período, ocasionou aumento no HDL-C (37.06 ± 8.42 vs. 42.5 ± 9.32, p=0.003) e redução nos níveis de triglicerídeos em jejum (102,83 ± 34,10 vs. 75,83 ± 20,91, p=0,02). A função endotelial, colesterol total, LDL-C e resistência à insulina não mudaram durante esta fase. A perda de peso (média de 5%, por 8 semanas), não promoveu modificações nos parâmetros metabólicos vistos com a dieta de manutenção de peso. A partir destes resultados, concluiu-se que a ingestão de dieta rica em carboidrato, por 4 semanas de manutenção de peso, aumenta a insulinemia em jejum e o IMCL do músculo tibial anterior, enquanto a dieta rica em gordura pelo mesmo período aumenta o HDL-C e reduz triglicerídeos em mulheres saudáveis com sobrepeso. / High fat or high carbohydrate (cab) diet have been widely difunded and consumed during last decades; however it is not clear their metabolic effects in long term. In the present study we analyzed intramyocellular lipids (IMCL), endothelial function, plasma lipids, glucose, insulin and insulin resistance after high fat or high cab diet during weeks, maintaining or losing weight. 43 overweight women (25< BMI <29.9 Kg/m2) were screened, 22 of them were randomized to two different diet sequence. IMCL was measured by using 1H magnetic resonance spectroscopy and endothelial function by using plethysmography method. Tibialis anterior IMCL (2.06 ± 1.27 vs. 3.52 ± 1.92, p=0.04) and fasting insulinemia increased (11.55 ± 4.43 vs. 14.03 ± 5.23, p=0.04) after four weeks of high cab diet after maintenance phase, while fasting HDL-C increased (37.06 ± 8.42 vs. 42.5 ± 9.32, p=0.003) and triglycerides levels decreased (102.83 ± 34.10 vs. 75.83 ± 20.91, p=0.02) after maintenance phase of high fat diet. Endothelial function, total cholesterol, LDL-C and insulin resistance did not alter during maintenance phase. A weight loss of 5%, after eight weeks, did not promote changes in the metabolic parameters, as seen during maintenance phase. Based on these results, it was concluded that high cab diet, four weeks with no weight change, increases tibialis anterior IMCL and fasting insulinemia, while high fat diet during same period increases HDL-C and decreases triglycerides in a healthy overweight women population.

La buprénorphine (BUP) peut être responsable d’une dépression respiratoire à l’origine d’intoxications graves parfois mortels. Cependant, les mécanismes exacts de ces effets respiratoires délétères ne sont pas encore clairement établis. Les objectifs de cette thèse étaient d’analyser la variabilité des effets respiratoires de la BUP en y intégrant : 1) le rôle exact de la P-glycoprotéine (P-gp) 2) le rôle de l’acquisition d’une tolérance aux opioïdes, tout en précisant les différences potentielles entre tolérance aux effets analgésiques et respiratoires et les mécanismes moléculaires mis en jeu. Pour cela, nous avons étudié en pléthysmographie les effets respiratoires de la BUP et de son métabolite actif la norbuprénorphine (NBUP) chez la souris Fvb femelle. Nous avons mesuré leur transport par la P-gp à la barrière hémato-encéphalique (BHE) en perfusion cérébrale in situ, après inhibition pharmacologique ou suppression du gène codant pour la P-gp. Nous avons étudié la part de variabilité dans ces effets, attribuable au sexe et à la souche de souris. Nous avons ainsi démontré que la P-gp exprimée à la BHE joue un rôle-clé dans la protection contre les effets respiratoires délétères induits par la BUP, en empêchant l’entrée dans le compartiment encéphalique de son métabolite, la NBUP. Nous avons observé que les souris Fvb femelles sont plus sensibles à la toxicité respiratoire de la BUP que les souris Fvb mâles qui sont, eux-mêmes plus sensibles à ces effets que les souris Swiss mâles, sans que la P-gp ne soit à aucun moment impliquée dans cette variabilité. Enfin, nous avons montré qu’une tolérance aux effets analgésiques et respiratoires de la BUP se développe de façon significativement plus réduite chez les souris Fvb déficientes en P-gp, suggérant un rôle crucial pour ce transporteur dans l’acquisition et l’expression de la tolérance à la BUP. Par ailleurs, nous avons montré qu’après administration répétée de morphine, apparait une tolérance plus faible à ses effets respiratoires qu’à ses effets analgésiques. La mise en évidence d’une superactivation de l’adénylate cyclase dans la région périaqueducale impliquée dans les effets antinociceptifs des opioïdes, et non dans le tronc cérébral qui contient les centres de régulation de la ventilation, pourrait au moins en partie, expliquer cette différence d’intensité de tolérance observée. Enfin, pour compléter nos travaux expérimentaux, nous avons réalisé deux mini-revues bibliographiques pour, d’une part faire la synthèse des mécanismes de la tolérance aux opioïdes et de leur rôle dans la dépression respiratoire et d’autre part, analyser les situations déjà rapportées d’effets cliniques nés d’interactions médicamenteuses médiées par la P-gp. / Buprenorphine (BUP) may be responsible for respiratory depression resulting in serious andsometimes fatal poisonings. However, the exact mechanisms leading to these deleterious respiratoryeffects still remain unclear. The objectives of this thesis were to study the variability of BUP-inducedrespiratory effects by focusing on: 1) the involvement of P-glycoprotein 2) the role of tolerance to opioids in addition to investigating possible differences among tolerance to opioid-related antinociceptive and respiratory effects as well as the involved molecular mechanisms. We studied the respiratory effects of BUP and its active metabolite, norbuprenorphine (NBUP) using plethysmography in female Fvb mice. We measured P-gp-related transport of BUP and NBUP at the blood-brain barrier (BBB) using in situ brain perfusion after pharmacological P-gp inhibition as well as in P-gp knock-out mice. We also studied the role of gender and mice strain in the variability of BUP-related respiratory effects. We showed that P-gp at the BBB plays a key-protective role against BUP-related respiratory effects by limiting NBUP distribution into the brain. We observed that female Fvb mice are more sensitive to BUP-induced deleterious respiratory effects than male Fvb mice thatare more sensitive than male Swiss mice. Furthermore, we assessed that gender- and strain-attributedvariability is not related to P-gp. Finally, we demonstrated that tolerance to BUP-induced antinociceptive and respiratory effects is significantly reduced in P-gp knockout mice in comparison to controls, suggesting a critical role for P-gp in tolerance to BUP. In parallel, we showed that repeated administration of morphine results in reduced tolerance to its respiratory effects in comparison to its antinociceptive effects. Adenylate cyclase super-activation that we evidenced in the periaqueductal grey matter, the area involved in opioid-related analgesia control, but not in the brainstem, the area that contains centres of ventilation regulation, may at least in part be responsible for these observed differences in tolerance. Finally, to complete our experimental researches, we performed two mini-reviews, aiming at summarizing the various mechanisms of tolerance and their involvement in respiratory depression in addition to highlighting the importance of drug-drug interactions leading to P-glycoprotein inhibition in the occurrence of deleterious clinical effects.

Le syndrome d'ondine est une maladie génétique rare caractérisée par une hypoventilation pendant le sommeil, des apnées et une absence de réponse au CO2. La majorité des patients ont une mutation hétérozygote à expansion d'alanine du gène PHOX2B, important dans le développement du système nerveux autonome. Notre objectif est d'étudier le rôle de Phox2b dans le contrôle de la ventilation et de valider un modèle murin du syndrome d'Ondine. Grâce à une plateforme d'exploration fonctionnelle originale permettant les mesures non invasives dans un environnement contrôlé en température et en gaz des variables cardiorespiratoires chez le souriceau, nous avons analysé in vivo deux modèles de souris hétérozygotes pour Phox2b. Les souriceaux hétérozygotes Phox2b+/-, issus d'une invalidation d'un allèle Phox2b, présentent une instabilité ventilatoire associée à une activité tonique anormalement élevée de leurs chémorécepteurs périphériques. Leur phénotype ventilatoire dépend fortement de la température ambiante. La reproduction de la mutation humaine majoritaire, une insertion de 7 alanines (souriceaux Phox2b27Ala/+) chez le souriceau, produit un phénotype similaire au syndrome d'Ondine. Ces souriceaux meurent rapidement d'apnée centrale à la naissance. Ils ont une perte spécifique de neurones exprimant de neurones du noyau rétrotrapézoïde/groupe respiratoire parafacial (RTN/pFRG) impliqués dans la chémoréception centrale et la rythmogenèse, ce qui montre le rôle important du RTN/pFRG dans la chémosensibilité au CO2, et dans la rythmogénèse respiratoire néonatale / Ondine syndrome is a rare genetic disease characterized by hypoventilation during sleep, apneas and the absence of ventilatory response to CO2. The majority of patients carry a heterozygous mutation with polyalanine expansion of PHOX2B gene, which is important in the development of autonomous nervous system. We aim to study the role of Phox2b in ventilatory control and to validate a mouse model of Ondine syndrome. We used a platform that allows in vivo, non-invasive measurements of cardiorespiratory variables in newborn mice in controlled temperature and gas conditions. Heterozygous Phox2b+/- pups, which were obtained by invalidation of one allele of Phox2b, show ventilatory instability with augmented tonic activity of peripheral chemoreceptor. Their ventilatory phenotype strongly depends on ambient temperature. Reproducing in mice Phox2b mutation, which is frequently observed in patients, an insertion of 7 alanines (mutant pups Phox2b27Ala/+) produces a similar phenotype to Ondine syndrome. These newborn mice rapidly die of central apnea after birth. Phox2b27Ala/+ pups have a specific loss of neurons expressing Phox2b in retrotrapezoïd nucleus/parafacial respiratory group (RTN/pFRG) involved in central chemoreception and in rhythmogenesis, showing the important role of RTN/pFRG in CO2 chemosensitivity, and in respiratory rhythmogenesis at birth

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Charles University Prague, Czech Rep. Raculty of Philosophy Department of Psychology Doctoral Theses Comparison of Accuracy and Precision of Sexodiagnostic Methods of Penile Plethysmography and Viewing Time Ondřej Trojan, 2017 Abstract The diagnosis of pedophilia denotes (according to ICL 10) the erotic preference for prepubescent or early pubescent children. Penile plethysmography (PPG) measures the reaction of these men in respon- se to either visual stimuli or to erotic narrative stories including child objects. Penile plethysmography is quite an intrusive assessment method, so viewing time (VT) might be a good alternative if it is shown to be compapratively accurate. Several studies in the past have shown inconsistent data, therefore more research is needed to confirm its validity in distinguishing responses to the preferred age category of pedophilic men. Method: Participants were 30 self-referred admitting paedophiles aged between 18 and 55 in the experimental group and 30 heterosexual gynephile men in the comparison group. A set of photographs depicting naked adults in addition to male and female children across 6 age categories ranging from young infants to adolescents was used; the same set of 38 stimuli were used to measure PPG (first) and VT(after). PPG apparatus was used to measure penile...

This critical synopsis of prior work by Clive Beggs is submitted in support of a PhD by published work. The work focuses on venous and cerebrospinal fluid (CSF) anomalies associated with multiple sclerosis (MS) and other neurological diseases. MS is characterized by focal inflammatory lesions, which are often venocentric. Recently a vascular syndrome, chronic cerebrospinal venous insufficiency (CCSVI) has been linked with MS. This syndrome, which is characterized by constricted cerebral venous outflow, has become mired in controversy, with various studies producing conflicting findings, with the result that the science associated with CCSVI has become obscured. Clive Beggs work seeks to bring clarity to the debate surrounding CCSVI by characterizing physiological changes associated with constricted cerebral venous outflow. The work submitted here involves collaborative studies with Robert Zivadinov (University of Buffalo), Paolo Zamboni (University of Ferrara), and Chih- Ping Chung (National Yang Ming University of Medicine). The key findings of these studies are: (i) MS patients, diagnosed with CCSVI, exhibit greatly increased hydraulic resistance of the cerebral venous drainage system; (ii) MS patients experience loss of the small cerebral veins; (iii) MS patients exhibit reduced CSF bulk flow, consistent with mild venous hypertension; (iv) MS patients exhibit increased CSF pulsatility in the Aqueduct of Sylvius, which appears to be linked with mild venous hypertension associated with CCSVI; and (v) jugular venous reflux is associated with white matter and parenchymal volumetric changes in Alzheimer’s patients. Collectively, these findings suggest that extracranial venous anomalies are associated with changes in the intracranial physiology.