9,287 research outputs found
Concurrent metaboreflex activation increases chronotropic and ventilatory responses to passive leg movement without sex-related differences
Previous studies in animal models showed that exercise-induced metabolites accumulation may sensitize the mechanoreflex-induced response. The aim of this study was to assess whether the magnitude of the central hemodynamic and ventilatory adjustments evoked by isolated stimulation of the mechanoreceptors in humans are influenced by the prior accumulation of metabolic byproducts in the muscle. 10 males and 10 females performed two exercise bouts consisting of 5-min of intermittent isometric knee-extensions performed 10% above the previously determined critical force. Post-exercise, the subjects recovered for 5 min either with a suprasystolic circulatory occlusion applied to the exercised quadriceps (PECO) or under freely-perfused conditions (CON). Afterwards, 1-min of continuous passive leg movement was performed. Central hemodynamics, pulmonary data, and electromyography from exercising/passively-moved leg were recorded throughout the trial. Root mean square of successive differences (RMSSD, index of vagal tone) was also calculated. Δpeak responses of heart rate (ΔHR) and ventilation ([Formula: see text]) to passive leg movement were higher in PECO compared to CON (ΔHR: 6 ± 5 vs 2 ± 4 bpm, p = 0.01; 3.9 ± 3.4 vs 1.9 ± 1.7 L min-1, p = 0.02). Δpeak of mean arterial pressure (ΔMAP) was significantly different between conditions (5 ± 3 vs - 3 ± 3 mmHg, p < 0.01). Changes in RMSSD with passive leg movement were different between PECO and CON (p < 0.01), with a decrease only in the former (39 ± 18 to 32 ± 15 ms, p = 0.04). No difference was found in all the other measured variables between conditions (p > 0.05). These findings suggest that mechanoreflex-mediated increases in HR and [Formula: see text] are sensitized by metabolites accumulation. These responses were not influenced by biological sex
Circadian variations in aortic stiffness, sympathetic vasoconstriction, and post-ischemic vasodilation in adults with and without type 2 diabetes.
The current literature reveals a lack of information on the circadian variations of some important cardiovascular risk factors related to the work of the heart or the capacity to provide blood and oxygen to various tissues. These factors include aortic stiffness, peripheral vasoconstrictor responsiveness, and post-ischemic vasodilation capacity. Furthermore, it is not clear whether the impact of an external stressor capable of activating the sympathetic nervous system could have greater repercussions on the cardiovascular system in the morning than in the evening. Given the higher incidence of acute cardiovascular events in the morning than in the evening, the studies undertaken in this thesis aim to investigate the circadian variations of these factors that are linked to cardiovascular risk, both at rest and during acute activation of the sympathetic nervous system. Type 2 diabetes (T2DM) is a condition that induces deleterious changes in cardiovascular function, impacting cardiovascular mortality and morbidity. Thus, the impact of diabetes will be evaluated. As a secondary purpose, considering the sex differences in the incidence and prognosis of cardiovascular disease, the effect of sex will be evaluated. Aortic stiffness proved not to be increased in the morning compared to the evening at specific times when the cardiovascular risk is significantly different, both at rest and during sympathetic activation. However, while healthy older women show similar aortic stiffness values compared to their male counterparts during acute stress, older women with T2DM reported greater aortic stiffness compared to men with T2DM. The post-ischemic forearm vasodilation is blunted in the morning compared to the evening in healthy elderly and such an attenuated vasodilation capacity impairs blood flow supply towards the ischemic area. The presence of T2DM does not affect vasodilation capacity and reactive hyperemia, but induces circadian variations in arterial pressure. The peripheral vasoconstriction triggered by a standardized sympathetic stressor is similar between morning and evening, regardless of the presence of T2DM and reduced baseline vascular conductance values in the morning. However, the peripheral vasoconstriction responsiveness is blunted in individuals with T2DM than in healthy ones as sympathetic activation induces vasodilation on the contralateral forearm in individuals with T2DM and vasoconstriction in healthy age-matched subjects. This finding highlights a neurovascular response to an external stressor altered by T2DM. Taken together, our findings suggest that the baseline state of constriction of the peripheral vascular tissue is greater in the morning than in the evening, but this fact is not due to greater sympathetic vasoconstriction responsiveness in the morning. Higher morning vasoconstriction at baseline however affects the capacity of a vascular tissue to dilate and, in turn, to supply blood to an ischemic tissue. Similar sympathetic vasoconstriction responsiveness between morning and evening is a likely factor explaining similar or lower values of central artery stiffness in the morning than in the evening, not only at rest but also during sympathetic excitation. Paradoxically, adults with T2DM report an increase in sympathetic-mediated dilatation capacity on the vascular tissue, which might be a defense mechanism that allows to reduce the central pressor response during sympathetic excitation
A proprietary black cumin oil extract (Nigella sativa) (BlaQmax®) modulates stress-sleep-immunity axis safely: Randomized double-blind placebo-controlled study
ObjectiveStress, sleep, and immunity are important interdependent factors that play critical roles in the maintenance of health. It has been established that stress can affect sleep, and the quality and duration of sleep significantly impact immunity. However, single drugs capable of targeting these factors are limited because of their multi-targeting mechanisms. The present study investigated the influence of a proprietary thymoquinone-rich black cumin oil extract (BCO-5) in modulating stress, sleep, and immunity.MethodsA randomized double-blinded placebo-controlled study was carried out on healthy volunteers with self-reported non-refreshing sleep issues (n = 72), followed by supplementation with BCO-5/placebo at 200 mg/day for 90 days. Validated questionnaires, PSQI and PSS, were employed for monitoring sleep and stress respectively, along with the measurement of cortisol and melatonin levels. Immunity markers were analyzed at the end of the study.ResultsIn the BCO-5 group, 70% of the participants reported satisfaction with their sleep pattern on day 7 and 79% on day 14. Additionally, both inter- and intra- group analyses of the total PSQI scores and component scores (sleep latency, duration, efficiency, quality, and daytime dysfunction) on days 45 and 90 showed the effectiveness of BCO-5 in the improvement of sleep (p < 0.05). PSS-14 analysis revealed a significant reduction in stress, upon both intra (p < 0.001) and inter-group (p < 0.001) comparisons. The observed reduction in stress among the BCO-5 group, with respect to the placebo, was significant with an effect size of 1.19 by the end of the study (p < 0.001). A significant correlation was also observed between improved sleep and reduced stress as evident from PSQI and PSS. Furthermore, there was a significant modulation in melatonin, cortisol, and orexin levels. Hematological/immunological parameters further revealed the immunomodulatory effects of BCO-5.ConclusionBCO-5 significantly modulated the stress-sleep-immunity axis with no side effects and restored restful sleep
Annual SHOT Report 2018
SHOT is affiliated to the Royal College of PathologistsAll NHS organisations must move away from a blame culture towards a just and learning culture. All clinical and laboratory staff should be encouraged to become familiar with human factors and ergonomics concepts. All transfusion decisions must be made after carefully assessing the risks and benefits of transfusion therapy. Collaboration and co-ordination among staff is vital
Anuário científico da Escola Superior de Tecnologia da Saúde de Lisboa - 2021
É com grande prazer que apresentamos a mais recente edição (a 11.ª) do Anuário Científico da Escola Superior de Tecnologia da Saúde de Lisboa. Como instituição de ensino superior, temos o compromisso de promover e incentivar a pesquisa científica em todas as áreas do conhecimento que contemplam a nossa missão. Esta publicação tem como objetivo divulgar toda a produção científica desenvolvida pelos Professores, Investigadores, Estudantes e Pessoal não Docente da ESTeSL durante 2021. Este Anuário é, assim, o reflexo do trabalho árduo e dedicado da nossa comunidade, que se empenhou na produção de conteúdo científico de elevada qualidade e partilhada com a Sociedade na forma de livros, capítulos de livros, artigos publicados em revistas nacionais e internacionais, resumos de comunicações orais e pósteres, bem como resultado dos trabalhos de 1º e 2º ciclo. Com isto, o conteúdo desta publicação abrange uma ampla variedade de tópicos, desde temas mais fundamentais até estudos de aplicação prática em contextos específicos de Saúde, refletindo desta forma a pluralidade e diversidade de áreas que definem, e tornam única, a ESTeSL. Acreditamos que a investigação e pesquisa científica é um eixo fundamental para o desenvolvimento da sociedade e é por isso que incentivamos os nossos estudantes a envolverem-se em atividades de pesquisa e prática baseada na evidência desde o início dos seus estudos na ESTeSL. Esta publicação é um exemplo do sucesso desses esforços, sendo a maior de sempre, o que faz com que estejamos muito orgulhosos em partilhar os resultados e descobertas dos nossos investigadores com a comunidade científica e o público em geral. Esperamos que este Anuário inspire e motive outros estudantes, profissionais de saúde, professores e outros colaboradores a continuarem a explorar novas ideias e contribuir para o avanço da ciência e da tecnologia no corpo de conhecimento próprio das áreas que compõe a ESTeSL. Agradecemos a todos os envolvidos na produção deste anuário e desejamos uma leitura inspiradora e agradável.info:eu-repo/semantics/publishedVersio
EVALUACIÓN ANALGÉSICA PERIOPERATORIA DEL ACETAMINOFÉN EN PERRAS SOMETIDAS A OVARIOHISTERECTOMÍA ELECTIVA
Tesis de doctorado que evalúa el efecto analgésico del acetaminofén en perras ovarihisterectomizadas.La administración de analgésicos antiinflamatorios no esteroidales (AINES) para el control del
dolor post-quirúrgico en perros es una práctica común, debido a sus efectos analgésicos,
antiinflamatorios y antipiréticos. En el presente trabajo se realizaron dos estudios. En el
experimento 1, el objetivo fue evaluar la analgesia post-operatoria del acetaminofén
(paracetamol) a través de la utilización de las escalas de reconocimiento clínico del dolor
DIVAS (Escala Dinámica e Interactiva Analógica Visual) y UMPS (Escala de la Universidad
de Melbourne), en perras sometidas a ovariohisterectomía electiva. Además de valorar la
seguridad y eficacia clínica del uso del acetaminofén en perros mediante pruebas de
funcionamiento hepático y renal en el post-operatorio inmediato. Para ello, se utilizaron 30
perras de diferentes razas que fueron asignadas aleatoriamente a uno de los tres grupos de
tratamiento: acetaminofén [GACET; n=10, 15 mg kg-1 intravenoso (IV)], carprofeno (GCARP;
n=10, 4 mg kg-1 IV) y meloxicam (GMELOX; n=10, 0.2 mg kg-1 IV). Todos los tratamientos se
administraron 30 minutos antes de la cirugía y posterior a esta durante 48 horas. En este período
el acetaminofén se administró por vía oral cada 8 horas (15 mg kg-1); el carprofeno (4 mg kg-1)
y el meloxicam (0.1 mg kg-1) se administraron por vía IV cada 24 horas. Durante el
postoperatorio, los sistemas de puntuación del dolor DIVAS y UMPS fueron medidos a las 1,
2, 4, 6, 8, 12, 16, 20, 24, 36 y 48 horas post-cirugía. Para evaluar la seguridad clínica de los
tratamientos, se recolectaron muestras de sangre de la vena yugular para realizar la medición de
enzimas ALT, AST, ALP, y los metabolitos bilirrubina directa, bilirrubina indirecta, bilirrubina
total, creatinina, urea, albúmina y glucosa. Esto fue realizado en T0 (pre-anestesia; TBASAL), 48
y 96 horas después de la cirugía (T48, T96). Los resultados indican que en la evaluación clínica
del dolor de todos los grupos de estudio, hubo una reducción gradual en la percepción del mismo
durante el postoperatorio en ambos sistemas de puntuación; no obstante, también fue observado
que ninguna escala difirió significativamente entre los tres grupos de tratamiento (P>0.05) en
cada momento de evaluación durante las 48 horas post-cirugía. En cuanto a los parámetros
bioquímico séricos, sólo la ALT aumentó significativamente en T96 en el GACET y GCARP con
respecto a los valores basales (P<0.01). El resto de los analitos séricos evaluados se mantuvo
en rangos normales. En el experimento 2 bajo el mismo diseño experimental de tratamientos
administrados, el objetivo fue evaluar el efecto analgésico perioperatorio del acetaminofén
2
administrado pre y post-quirúrgicamente en perras sometidas a ovariohisterectomía electiva a
través de la medición del índice de la actividad del tono parasimpático (PTA). Este parámetro
hemodinámico fue medido 60 minutos antes de la cirugía (TBASAL) y durante el transquirúrgico
en la aplicación de estímulos nociceptivos: colocación de las pinzas de campo backhouse
(TPINZ), incisión de piel y abordaje quirúrgico primario (TINC), ligadura y extracción de pedículo
ovárico izquierdo (TOVI) y derecho (TOVD), ligadura y transfixión del cuello uterino (TLIGUT),
sección quirúrgica del cuello uterino (TCUT), reconstrucción de peritoneo y planos anatómicos
musculares (TMUSC) y sutura de piel (TSUT). Durante el postoperatorio, el índice PTA fue
valorado a las 1, 2, 4, 6, 8, 12, 16, 20, 24, 36 y 48 horas, en los mismos tiempos en que fueron
evaluadas las escalas de reconocimiento de dolor DIVAS y UMPS. Los resultados obtenidos en
la medición del índice PTA basal para GACET fue 65 ± 8, para GCARP 65 ± 7 y para GMELOX 62 ±
5. Durante los diferentes tiempos transquirúrgicos, los valores promedio de índice PTA indican
que GACET (76 ± 14) y GMELOX (72 ± 18) muestran tendencia a manifestar mayores niveles en
comparación con GCARP (62 ± 13) desde el inicio del procedimiento quirúrgico sin que esto
pudiera comprobarse estadísticamente, ya que no hubo diferencias significativas entre grupos
de tratamiento ni entre los tiempos quirúrgicos evaluados (P>0.05). En el postoperatorio, el
índice PTA fue de 65 ± 9 en el GACET, 63 ± 8 en el GCARP y 65 ± 8 en el GMELOX. Los resultados
tampoco mostraron diferencias estadísticamente significativas con los valores basales o entre
los tratamientos (P>0.05). El índice PTA postoperatorio mostró una sensibilidad del 40%,
especificidad del 98.46% y valor predictivo negativo del 99.07% con respecto a la escala
validada de UMPS. En conclusión, el acetaminofén puede considerarse una herramienta para el
tratamiento efectivo del dolor perioperatorio agudo en perros, ya que mostró la misma eficacia
clínica que el meloxicam y el carprofeno para la analgesia postquirúrgica en perras sometidas a
ovariohisterectomía electiva. Además, la evidencia del uso de este medicamento no condujo a
reacciones adversas o cambios en los parámetros evaluados, lo que indica su seguridad clínica.
Finalmente, destacar que el índice PTA representa una medición objetiva del comfort y
analgesia postoperatoria, por lo que es una herramienta que podría ayudar a predecir las
respuestas hemodinámicas asociadas con el dolor
Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico
Valve replacement remains as the standard therapeutic option for aortic
stenosis patients, aiming at abolishing pressure overload and triggering
myocardial reverse remodeling. However, despite the instant hemodynamic
benefit, not all patients show complete regression of myocardial hypertrophy,
being at higher risk for adverse outcomes, such as heart failure. The current
comprehension of the biological mechanisms underlying an incomplete reverse
remodeling is far from complete. Furthermore, definitive prognostic tools and
ancillary therapies to improve the outcome of the patients undergoing valve
replacement are missing. To help abridge these gaps, a combined myocardial
(phospho)proteomics and pericardial fluid proteomics approach was followed,
taking advantage of human biopsies and pericardial fluid collected during
surgery and whose origin anticipated a wealth of molecular information
contained therein.
From over 1800 and 750 proteins identified, respectively, in the myocardium
and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated
proteins were detected. Gene annotation and pathway enrichment analyses,
together with discriminant analysis, are compatible with a scenario of increased
pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by
complement activity and other extrinsic factors, such as death receptor
activators), acute-phase response, immune system activation and fibrosis.
Specific validation of some targets through immunoblot techniques and
correlation with clinical data pointed to complement C3 β chain, Muscle Ring
Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation
regulated kinase 1A (DYRK1A) as potential markers of an incomplete
response. In addition, kinase prediction from phosphoproteome data suggests
that the modulation of casein kinase 2, the family of IκB kinases, glycogen
synthase kinase 3 and DYRK1A may help improve the outcome of patients
undergoing valve replacement. Particularly, functional studies with DYRK1A+/-
cardiomyocytes show that this kinase may be an important target to treat
cardiac dysfunction, provided that mutant cells presented a different response
to stretch and reduced ability to develop force (active tension).
This study opens many avenues in post-aortic valve replacement reverse
remodeling research. In the future, gain-of-function and/or loss-of-function
studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic
targets. Besides, clinical studies in larger cohorts will bring definitive proof of
complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de
referência para doentes com estenose aórtica e visa a eliminação da
sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica.
Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes
apresentam regressão completa da hipertrofia do miocárdio, ficando com maior
risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os
mecanismos biológicos subjacentes a uma remodelagem reversa incompleta
ainda não são claros. Além disso, não dispomos de ferramentas de
prognóstico definitivos nem de terapias auxiliares para melhorar a condição
dos pacientes indicados para substituição da válvula. Para ajudar a resolver
estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica
para a caracterização, respetivamente, do miocárdio e do líquido pericárdico
foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em
ambiente cirúrgico.
Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio
e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90
proteínas desreguladas foram detetadas. As análises de anotação de genes,
de enriquecimento de vias celulares e discriminativa corroboram um cenário de
aumento da expressão de genes pro-hipertróficos e de síntese proteica, um
sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular
(potencialmente acelerada pela atividade do complemento e por outros fatores
extrínsecos que ativam death receptors), com ativação da resposta de fase
aguda e do sistema imune, assim como da fibrose.
A validação de alguns alvos específicos através de immunoblot e correlação
com dados clínicos apontou para a cadeia β do complemento C3, a Muscle
Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation
regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta
incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma,
sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a
glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição
dos pacientes indicados para intervenção. Em particular, a avaliação funcional
de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo
importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes
responderam de forma diferente ao estiramento e mostraram uma menor
capacidade para desenvolver força (tensão ativa).
Este estudo levanta várias hipóteses na investigação da remodelagem reversa.
No futuro, estudos de ganho e/ou perda de função realizados em
cardiomiócitos isolados ou em modelos animais de banding-debanding da
aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos
encontrados. Além disso, estudos clínicos em coortes de maior dimensão
trarão conclusões definitivas quanto ao valor de prognóstico do complemento
C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin
Influence of local PO₂ on skeletal muscle microvascular blood flow during hyperinsulinemia
The goal of this thesis was to test the hypothesis that insulin mediated hyperemia is partially dependent on local muscle oxygen concentration. To do so, microvascular blood flow was measured in response to varying imposed concentrations of oxygen in rat skeletal muscle. Sprague-Dawley rats were anesthetized, and the extensor digitorum longus (EDL) was reflected onto an inverted microscope. Intravital video microscopy sequences were recorded during baseline and hyperinsulinemic euglycemia. The muscle was reflected over a glass stage insert (Experiment 1a and 1b), or over a gas exchange chamber (Experiment 2), and microvascular capillary blood flow was recorded during sequential changes (7%-12%-2%-7%) of oxygen (O₂) concentration. Blood flow was measured by the red blood cell supply rate (SR) in number of cells per second. In Experiment 1a, supply rate (SR) increased from 8.0 to 14 cells/s at baseline to euglycemia (p = 0.01), while no significant SR variation was detected after performing a sham hyperinsulinemic euglycemic clamp (Experiment 1b). In Experiment 2, SR decreased at 12% O₂ and increased at 2% O₂, compared to 7% O₂, under both experimental conditions. SR responses to oxygen square wave oscillations during euglycemia were not different to those at baseline at each O₂ concentration (p > 0.9). Our results suggest the increase in blood flow observed in response to insulin is eliminated if tissue oxygen microenvironment is clamped at given oxygen concentrations.
All animal protocols were approved by Memorial University’s Institutional Animal Care Committee
Recommended from our members
European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.
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