Cardiac and vascular phenotypes in the apolipoprotein E-deficient mouse

Cardiovascular death is frequently associated with atherosclerosis, a chronic multifactorial disease and a leading cause of death worldwide. Genetically engineered mouse models have proven useful for the study of the mechanisms underlying cardiovascular diseases. The apolipoprotein E-deficient mouse has been the most widely used animal model of atherosclerosis because it rapidly develops severe hypercholesterolemia and spontaneous atherosclerotic lesions similar to those observed in humans. In this review, we provide an overview of the cardiac and vascular phenotypes and discuss the interplay among nitric oxide, reactive oxygen species, aging and diet in the impairment of cardiovascular function in this mouse model

A comparison between preterm and full-term infants\u2019 preference for faces [Uma compara\ue7\ue3o entre rec\ue9m-nascidos prematuros e a termo na prefer\ueancia por faces]

Objective: Visual preference for faces at birth is the product of a multimodal sensory experience experienced by the fetus even during the gestational period. The ability to recognize faces allows an ecologically advantageous interaction with the social environment. However, perinatal events such as premature birth, may adversely affect the adequate development of this capacity. In this study, we evaluated the preference for facial stimuli in preterm infants within the first few hours after birth. Methods: This is a cross-sectional observational study of 59 newborns, 28 preterm and 31 full-term infants. The babies were assessed in the first hours of life, with two white boards in the shape of a head and neck: one with the drawing of a face similar to the human face (natural face), and one with the drawing of misaligned eyes, mouth and nose (distorted face). After the newborn fixated the eyes on the presented stimulus, it was slowly moved along the visual field. The recognition of the stimulus was considered present when the baby had eye or head movements toward the stimulus. Results: The preterm infants, in addition to showing a lower occurrence of orientation movements for both stimuli, on average (1.8 ± 1.1 to natural faces and 2.0 ± 1.2 for distorted ones) also showed no preference for any of them (p = 0.35). Full-term newborns showed a different behavior, in which they showed a preference for natural faces (p = 0.002) and a higher number of orientations for the stimulus, for both natural (3.2 ± 0.8) and distorted faces (2.5 ± 0.9). Conclusion: Preterm newborns recognize facial stimuli and disclose no preference for natural faces, different from full-term newborns. Resumo: Objetivo: A preferência visual por faces ao nascimento é produto de uma experiência sensorial multimodal vivenciada pelo feto ainda no período gestacional. A habilidade de reconhecer faces possibilita uma interação ecologicamente vantajosa com o ambiente social. Entretanto, eventos perinatais, como o nascimento prematuro, podem prejudicar o desenvolvimento adequado dessa habilidade. Nesse trabalho, avaliamos a preferência por estímulos faciais de recém-nascidos prematuros nas primeiras horas após o nascimento. Métodos: Trata-se de um estudo observacional transversal realizado com 59 recém-nascidos, 28 prematuros e 31 nascidos termos. Os bebês foram avaliados, nas primeiras horas de vida, com duas pranchas brancas em formato de cabeça e pescoço: uma com o desenho de uma face similar ao rosto humano (face natural), e outra com o desenho de olhos, boca e nariz desalinhados (face distorcida). Após o recém-nascido fixar o olhar no estímulo apresentado o mesmo era lentamente movimentado ao longo do campo visual. O reconhecimento do estímulo foi considerado presente quando o bebê apresentou movimentos dos olhos ou cabeça em direção ao estímulo. Resultados: Os recém-nascidos prematuros além de apresentarem menor ocorrência de movimentos de orientação para ambos os estímulos, em média (1,8 ± 1,1 para faces naturais e 2,0 ± 1,2 para faces distorcidas), também não apresentaram preferência por qualquer um deles (p = 0,35). Diferente foi o comportamento dos recém-nascidos a termo que apresentaram preferência por faces naturais (p = 0,002) e um número maior de orientações para o estímulo, tanto para faces naturais (3,2 ± 0,8) quanto para faces distorcidas (2,5 ± 0,9). Conclusão: Recém-nascidos prematuros reconhecem os estímulos faciais e não apresentam preferência por faces naturais, diferente de recém-nascidos a termos. Keywords: Model of visual recognition, Visual perception, Newborn, Preterm infant, Full-term infant, Palavras-chave: Reconhecimento visual de modelos, Percepção visual, Recém-nascido, Prematuro, Nascimento a term

Comparative bioavailability of two digoxin formulations: determination in human plasma by microparticle enzyme immunoassay

The present study was performed to compare the bioavailability of two digoxin 0.25 mg tablet formulation in 30 volunteers of both sexes. The study was conducted open with randomized two period crossover design and a three-week washout period. Plasma samples were obtained over a 144 h interval. Digoxin concentrations were analyzed by a validated microparticle enzyme immunoassay with optical detection by fluorescence. Bioequivalence between the products was determined by calculating 90 % confidence intervals (90 % I.C) for the ratio of AUC0-72h and Cmax values for the test and reference products, using logarithmic transformed data. The 90 % confidence intervals were 86.98-118.33 %, and 84.52–98.76 %, respectively. Since the 90 % confidence intervals for Cmax and AUC0-72h were within the 80-125 % interval proposed by Food and Drug Administration, it was concluded that the two Digoxin formulations are bioequivalent in their rate and extent of absorption.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Comparative bioavailability of two digoxin formulations: determination in human plasma by microparticle enzyme immunoassay

The present study was performed to compare the bioavailability of two digoxin 0.25 mg tablet formulation in 30 volunteers of both sexes. The study was conducted open with randomized two period crossover design and a three-week washout period. Plasma samples were obtained over a 144 h interval. Digoxin concentrations were analyzed by a validated microparticle enzyme immunoassay with optical detection by fluorescence. Bioequivalence between the products was determined by calculating 90 % confidence intervals (90 % I.C) for the ratio of AUC0-72h and Cmax values for the test and reference products, using logarithmic transformed data. The 90 % confidence intervals were 86.98-118.33 %, and 84.52–98.76 %, respectively. Since the 90 % confidence intervals for Cmax and AUC0-72h were within the 80-125 % interval proposed by Food and Drug Administration, it was concluded that the two Digoxin formulations are bioequivalent in their rate and extent of absorption.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Cardiac and vascular changes in elderly atherosclerotic mice: the influence of gender

<p>Abstract</p> <p>Background</p> <p>Although advanced age is considered a risk factor for several diseases, the impact of gender on age-associated cardiovascular diseases, such as atherosclerotic processes and valvular diseases, remains not completely clarified. The present study was designed to assess aortic valve morphology and function and vascular damage in elderly using the apolipoprotein E knockout (ApoE KO) mouse. Our hypothesis was that advanced age-related cardiovascular changes are aggravated in atherosclerotic male mice.</p> <p>Methods</p> <p>The grade (0 to 4) of aortic regurgitation was evaluated through angiography. In addition, vascular lipid deposition and senescence were evaluated through histochemical analyses in aged male and female ApoE KO mice, and the results were compared to wild-type C57BL/6J (C57) mice.</p> <p>Results</p> <p>Aortic regurgitation was observed in 92% of the male ApoE KO mice and 100% of the male C57 mice. Comparatively, in age-matched female ApoE KO and C57 mice, aortic regurgitation was observed in a proportion of 58% and 53%, respectively. Histological analysis of the aorta showed an outward (positive) remodeling in ApoE KO mice (female: 1.86 ± 0.15; male: 1.89 ± 0.68) using C57 groups as reference values. Histochemical evaluation of the aorta showed lipid deposition and vascular senescence only in the ApoE KO group, which were more pronounced in male mice.</p> <p>Conclusion</p> <p>The data show that male gender contributes to the progression of aortic regurgitation and that hypercholesterolemia and male gender additively contribute to the occurrence of lipid deposition and vascular senescence in elderly mice.</p

Comparative bioavailability of two digoxin formulations: determination in human plasma by microparticle enzyme immunoassay

The present study was performed to compare the bioavailability of two digoxin 0.25 mg tablet formulation in 30 volunteers of both sexes. The study was conducted open with randomized two period crossover design and a three-week washout period. Plasma samples were obtained over a 144 h interval. Digoxin concentrations were analyzed by a validated microparticle enzyme immunoassay with optical detection by fluorescence. Bioequivalence between the products was determined by calculating 90 % confidence intervals (90 % I.C) for the ratio of AUC0-72h and Cmax values for the test and reference products, using logarithmic transformed data. The 90 % confidence intervals were 86.98-118.33 %, and 84.52–98.76 %, respectively. Since the 90 % confidence intervals for Cmax and AUC0-72h were within the 80-125 % interval proposed by Food and Drug Administration, it was concluded that the two Digoxin formulations are bioequivalent in their rate and extent of absorption.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Isogeometric analysis for fluid shear stress in cancer cells

Este trabalho foi financiado pelo Concurso Anual para Projetos de Investigação, Desenvolvimento, Inovação e Criação Artística (IDI&CA) 2018 do Instituto Politécnico de Lisboa. Código de referência IPL/2018/IGACFC_ISELThe microenvironment of the tumor is a key factor regulating tumor cell invasion and metastasis. The effects of physical factors in tumorigenesis is unclear. Shear stress, induced by liquid flow, plays a key role in proliferation, apoptosis, invasion, and metastasis of tumor cells. The mathematical models have the potential to elucidate the metastatic behavior of the cells’ membrane exposed to these microenvironment forces. Due to the shape configuration of the cancer cells, Non-uniform Rational B-splines (NURBS) lines are very adequate to define its geometric model. The Isogeometric Analysis allows a simplified transition of exact CAD models into the analysis avoiding the geometrical discontinuities of the traditional Galerkin traditional techniques. In this work, we use an isogeometric analysis to model the fluid-generated forces that tumor cells are exposed to in the vascular and tumor microenvironments, in the metastatic process. Using information provided by experimental tests in vitro, we present a suite of numerical experiments which indicate, for standard configurations, the metastatic behavior of cells exposed to such forces. The focus of this paper is strictly on geometrical sensitivities to the shear stress’ exhibition for the cell membrane, this being its innovation.info:eu-repo/semantics/publishedVersio

Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice

The objective of the present study was to assess the effects of the immunosuppressant rapamycin (Rapamune®, Sirolimus) on both resistance vessel responsiveness and atherosclerosis in apolipoprotein E-deficient 8-week-old male mice fed a normal rodent diet. Norepinephrine (NE)-induced vasoconstriction, acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced vasorelaxation of isolated mesenteric bed, and atherosclerotic lesions were evaluated. After 12 weeks of orally administered rapamycin (5 mg·kg-1·day-1, N = 9) and compared with untreated (control, N = 9) animals, rapamycin treatment did not modify either NE-induced vasoconstriction (maximal response: 114 ± 4 vs 124 ± 10 mmHg, respectively) or ACh- (maximal response: 51 ± 8 vs 53 ± 5%, respectively) and SNP-induced vasorelaxation (maximal response: 73 ± 6 vs 74 ± 6%, respectively) of the isolated vascular mesenteric bed. Despite increased total cholesterol in treated mice (982 ± 59 vs 722 ± 49 mg/dL, P < 0.01), lipid deposition on the aorta wall vessel was significantly less in rapamycin-treated animals (37 ± 12 vs 68 ± 8 µm2 x 103). These results indicate that orally administered rapamycin is effective in attenuating the progression of atherosclerotic plaque without affecting the responsiveness of resistance vessels, supporting the idea that this immunosuppressant agent might be of potential benefit against atherosclerosis in patients undergoing therapy