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Hypoxia in preterm infants is a clinical condition that has been associated with cognitive and behavioral disturbances for which treatment strategies are strongly required. Melatonin administration following brain insults has been considered a promising therapeutic strategy due to its antioxidant and anti-inflammatory effects. Not surprisingly, it has been extensively studied for preventing disturbances following brain injury. This study evaluated the effects of melatonin on developmental disturbances, memory disruption, and hippocampal cell loss induced by neonatal anoxia in rats. Neonatal Wistar rats were subjected to anoxia and subsequently treated with melatonin. Later, maturation of physical characteristics, ontogeny of reflexes, learning and memory in the Morris water maze (MWM), and estimates of the number of hippocampal neurons, were evaluated. Melatonin treatment attenuated (1) female anoxia-induced delay in superior incisor eruption, (2) female anoxia-induced vibrissae placement reflexes, and (3) male and female anoxia-induced hippocampal neuronal loss. Melatonin also promoted an increase (5) in swimming speeds in the MWM. In addition, PCA analysis showed positive associations between the acoustic startle, auditory canal open, and free fall righting parameters and negative associations between the male vehicle anoxia group and the male melatonin anoxia group. Therefore, melatonin treatment attenuates both anoxia-induced developmental deficits and hippocampal neuronal loss.

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Elucidating the selective forces shaping the diversity of vertebrate brains continues to be a major area of inquiry, particularly as it relates to cognition. Historically brain evolution was interpreted through the lens of relative brain size; however, recent evidence has challenged this approach. Investigating neuroanatomy at a finer scale, such as neuron number, can provide new insights into the forces shaping brain evolution in the context of information processing capacity. Ecological factors, such as the complexity of a species' habitat, place demands on cognition that could shape neuroanatomy. In this study, we investigate the relationship between neuron number and habitat complexity in three brain regions across six closely related anole species from Puerto Rico. After controlling for brain mass, we found that the number of neurons increased with habitat complexity across species in the telencephalon and 'rest of the brain,' but not in the cerebellum. Our results demonstrate that habitat complexity has shaped neuroanatomy in the Puerto Rican anole radiation and provide further evidence of the role of habitat complexity in vertebrate brain evolution.

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Chronic social stress is a significant risk factor for several neuropsychiatric disorders, mainly major depressive disorder (MDD). In this way, patients with clinical depression may display many symptoms, including disrupted social behavior and anxiety. However, like many other psychiatric diseases, MDD has a very complex etiology and pathophysiology. Because social isolation is one of the multiple depression-inducing factors in humans, this study aims to understand better the link between social stress and MDD using an animal model based on social isolation after weaning, which is known to produce social stress in mice. We focused on cellular composition and white matter integrity to establish possible links with the abnormal social behavior that rodents isolated after weaning displayed in the three-chamber social approach and recognition tests. We used the isotropic fractionator method to assess brain cellularity, which allows us to robustly estimate the number of oligodendrocytes and neurons in dissected brain regions. In addition, diffusion tensor imaging (DTI) was employed to analyze white matter microstructure. Results have shown that post-weaning social isolation impairs social recognition and reduces the number of neurons and oligodendrocytes in important brain regions involved in social behavior, such as the anterior neocortex and the olfactory bulb. Despite the limitations of animal models of psychological traits, evidence suggests that behavioral impairments observed in patients might have similar biological underpinnings.

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The human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in women's frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has ~10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity.

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Obesity is defined as abnormal or excessive fat accumulation that may impair health and is a risk factor for developing other diseases, such as type 2 diabetes and cardiovascular disorder. Obesity is also associated with structural and functional alterations in the brain, and this condition has been shown to increase the risk of Alzheimer's disease. However, while obesity has been associated with neurodegenerative processes, its impact on brain cell composition remains to be determined. In the current study, we used the isotropic fractionator method to determine the absolute composition of neuronal and non-neuronal cells in different brain regions of the genetic mouse models of obesity Lepob/ob and LepRNull/Null . Our results show that 10- to 12-month-old female Lepob/ob and LepRNull/Null mice have reduced neuronal number and density in the hippocampus compared to C57BL/6 wild-type mice. Furthermore, LepRNull/Null mice have increased density of non-neuronal cells, mainly glial cells, in the hippocampus, frontal cortex and hypothalamus compared to wild-type or Lepob/ob mice, indicating enhanced inflammatory responses in different brain regions of the LepRNull/Null model. Collectively, our findings suggest that obesity might cause changes in brain cell composition that are associated with neurodegenerative and inflammatory processes in different brain regions of female mice.

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Chronic hypoxia during gestation and postnatal period induces pulmonary hypertension, aorta stiffening and vascular remodeling. In this study, we hypothesized that a postnatal treatment with Cinaciguat, a guanylate cyclase activator, may improve the vascular function by enhancing NO-sGC pathways that induce vasodilation. To assess this, we collected aortas from six lambs gestated, born and raised at 3600 masl. Half of these lambs received a Cinaciguat postnatal treatment, while the other half was used as control (vehicle). Uniaxial tension was applied on samples of each group of aortas (control and Cinaciguat-treated) through cyclic loading. The obtained stress-stretch curves were used to identify constitutive parameters of a hyperelastic damage model. These material constants allowed us to assess the softening/dissipation behavior and to characterize the treatment effects. Results showed that Cinaciguat has an effect on the damage behavior at large strains, altering the damage onset under uniaxial tension. We conclude that Cinaciguat, as a vasodilator, can prevent the very early effects of vascular remodeling caused by perinatal hypoxia, and improve the aortic-tissue damage properties of hypoxic lambs.

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BACKGROUND: Education is believed to contribute positively to brain structure and function, as well as to cognitive reserve. One of the brain regions most impacted by education is the medial temporal lobe (MTL), a region that houses the hippocampus, which has an important role in learning processes and in consolidation of memories, and is also known to undergo neurogenesis in adulthood. We aimed to investigate the influence of education on the absolute cell numbers of the MTL (comprised by the hippocampal formation, amygdala, and parahippocampal gyrus) of men without cognitive impairment. METHODS: The Isotropic Fractionator technique was used to allow the anisotropic brain tissue to be transformed into an isotropic suspension of nuclei, and therefore assess the absolute cell composition of the MTL. We dissected twenty-six brains from men aged 47 to 64 years, with either low or high education. RESULTS: A significant difference between groups was observed in brain mass, but not in MTL mass. No significant difference was found between groups in the number of total cells, number of neurons, and number of non-neuronal cells. Regression analysis showed that the total number of cells, number of neurons, and number of non-neuronal cells in MTL were not affected by education. CONCLUSIONS: The results indicate a resilience of the absolute cellular composition of the MTL of typical men to low schooling, suggesting that the cellularity of brain regions is not affected by formal education.

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The use of composite materials in several sectors, such as aeronautics and automotive, has been gaining distinction in recent years. However, due to their high costs, as well as unique characteristics, consequences of their heterogeneity, they present challenging gaps to be studied. As a result, the finite element method has been used as a way to analyze composite materials subjected to the most distinctive situations. Therefore, this work aims to approach the modeling of composite materials, focusing on material properties, failure criteria, types of elements and main application sectors. From the modeling point of view, different levels of modeling-micro, meso and macro, are presented. Regarding properties, different mechanical characteristics, theories and constitutive relationships involved to model these materials are presented. The text also discusses the types of elements most commonly used to simulate composites, which are solids, peel, plate and cohesive, as well as the various failure criteria developed and used for the simulation of these materials. In addition, the present article lists the main industrial sectors in which composite material simulation is used, and their gains from it, including aeronautics, aerospace, automotive, naval, energy, civil, sports, manufacturing and even electronics.

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Nutrition is one of the most influential environmental factors affecting the development of different tissues and organs. It is suggested that under nutrient restriction the growth of the brain is spared as a result of the differential allocation of resources from other organs. However, it is not clear whether this sparing occurs brain-wide. Here, we analyzed morphological changes and cell composition in different regions of the offspring mouse brain after maternal exposure to nutrient restriction during pregnancy and lactation. Using high-resolution magnetic resonance imaging, we found that brain regions were differentially sensitive to maternal protein restriction and exhibited particular patterns of volume reduction. The cerebellum was reduced in absolute and relative volume, while cortex volume was relatively preserved. Alterations in cell composition (examined by the isotropic fractionator method) and organization of white matter (measured by diffusor tensor images) were also region specific. These changes were not related to the metabolic rate of the regions and were only partially explained by their specific growth trajectories. This study is a first step towards understanding the mechanisms of regional brain sparing at microstructural and macrostructural levels resulting from undernutrition.

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The central nervous system is a highly complex network composed of various cell types, each one with different subpopulations. Each cell type has distinct roles for the functional operation of circuits, and ultimately, for brain physiology in general. Since the absolute number of each cell type is considered a proxy of its functional complexity, one approach to better understand how the brain works is to unravel its absolute cellularity and the quantitative relations between cell populations; in other words, how one population of cells is quantitatively structured, in relation to another. Oligodendrocytes are one of these cell types - mainly, they provide electric insulation to axons, optimizing action potential conduction. Their function has recently been revisited and their role extended, one example being their capability of providing trophic support to long axons. To determine the absolute cellularity of oligodendroglia, we have developed a protocol of oligodendrocyte quantification using the isotropic fractionator with a pan-marker for this cell type. We report a detailed assessment of specificity and universality of the oligodendrocyte transcription factor 2 (Olig2), through systematic confocal analyses of the C57BL/6 mouse brain. In addition, we have determined the absolute number (17.4 million) and proportion (about 20%) of this cell type in the brain (and in different brain regions), and tested if this population, at the intraspecific level, scales with the number of neurons in an allometric-based approach. Considering these numbers, oligodendrocytes proved to be the most numerous of glial cells in the mouse brain.

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Several constitutive models for fibrous soft tissues used in literature provide a completely isotropic response when fibers are compressed. However, recent experimental investigations confirm the expectation that tendons behave anisotropically during compression tests. Motivated by these facts, the present manuscript presents an appropriate choice of hyperelastic potentials able to predict the coupled mechanical behaviors of tendons under both tensile and compressive loads with a relatively small number of material parameters. The high stiffness of tendons under tensile tests is handled by a transversely isotropic model while the coupled compressive response is modeled by means of a Fung-type potential in terms of Seth-Hill's generalized strain tensors. In present study the logarithm strain measure is used instead of the usually employed Green-Lagrange strain. After a parameter identification procedure, the resulting model showed ability to satisfactorily reproduce the experimental data. Details on the analytical material tangent modulus are provided. Present results will then enhance further researches related to tendon dissipative effects and numerical multiscale investigations.

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What is the influence of sex and age on the quantitative cell composition of the human brain? By using the isotropic fractionator to estimate absolute cell numbers in selected brain regions, we looked for sex- and age-related differences in 32 medial temporal lobes (comprised basically by the hippocampal formation, amygdala and parahippocampal gyrus), sixteen male (29-92 years) and sixteen female (25-82); and 31 cerebella, seventeen male (29-92 years) and fourteen female (25-82). These regions were dissected from the brain, fixed and homogenized, and then labeled with a DNA-marker (to count all nuclei) and with a neuron-specific nuclear marker (to estimate neuron number). Total number of cells in the medial temporal lobe was found to be 1.91 billion in men, and 1.47 billion in women, a difference of 23 %. This region showed 34 % more neurons in men than in women: 525.1 million against 347.4 million. In contrast, no sex differences were found in the cerebellum. Regarding the influence of age, a quadratic correlation was found between neuronal numbers and age in the female medial temporal lobe, suggesting an early increase followed by slight decline after age 50. The cerebellum showed numerical stability along aging for both neurons and non-neuronal cells. In sum, results indicate a sex-related regional difference in total and neuronal cell numbers in the medial temporal lobe, but not in the cerebellum. On the other hand, aging was found to impact on cell numbers in the medial temporal lobe, while the cerebellum proved resilient to neuronal losses in the course of life.

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Durante muchos años se han utilizado los postes colados, considerados como un estándar en la odontología protésica, pero presentan limitantes técnicas y mecánicas, ya que exhiben altos módulos de elasticidad y, por lo mismo, imposibilitan la capacidad de disipar las fuerzas con efectividad, lo que significa concentrar tensiones dentro del conducto radicular. Literatura basada en evidencia científica describe a los postes de fibra de vidrio con módulos de elasticidad semejantes o próximos a la dentina, presentando propiedades anisotrópicas, en comparación con los postes tradicionales, que presentan propiedades isotrópicas. Se propone un concepto restaurador que involucra el poste, el cemento y la dentina, constituyendo un complejo homogéneo denominado ®monobloque¼ que permite un mejor comportamiento mecánico benéfico para el remanente dentario

For many years now, cast posts have been regarded as standard in prosthetics despite the technical and mechanical limitations caused by their high moduli of elasticity, which prevent the forces involved from being effectively dissipated and, therefore, concentrate stress within the root canal. Scientifi c evidence-based literature describes fi berglass posts with moduli of elasticity similar to or approaching that of dentin as having anisotropic properties, as opposed to the isotropic properties of traditional posts. We propose a restorative approach that involves the post, the cement, and the dentin, forming a homogeneous complex known as a ®monobloc¼ that enables enhanced mechanical behavior that benefits the remaining tooth structure.

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The identification and quantification of crystalline phases of antihypertensive drugs - Losartan potassium (LOS-K), Hydrochlorothiazide (HCTZ) and Chlorthalidone (CTD) were carried out by means of X-ray powder diffraction data and the Rietveld method. Quantitative phase analyses of Losartan potassium/Chlorthalidone (LOS-K/CTD) and Losartan potassium/Hydrochlorothiazide (LOS-K/HCTZ) combinations were also evaluated. The results indicated that for diuretics (HCTZ and CTD) only one crystalline phase was found in samples, and for LOS-K the crystal structure showed similarity between the Bragg peaks to the phase described as monoclinic and space group P21/c. After one year storage, the orthorhombic one was also observed in this sample.

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Alzheimer's disease is the commonest cause of dementia in the elderly, but its pathological determinants are still debated. Amyloid-ß plaques and neurofibrillary tangles have been implicated either directly as disruptors of neural function, or indirectly by precipitating neuronal death and thus causing a reduction in neuronal number. Alternatively, the initial cognitive decline has been attributed to subtle intracellular events caused by amyloid-ß oligomers, resulting in dementia after massive synaptic dysfunction followed by neuronal degeneration and death. To investigate whether Alzheimer's disease is associated with changes in the absolute cell numbers of ageing brains, we used the isotropic fractionator, a novel technique designed to determine the absolute cellular composition of brain regions. We investigated whether plaques and tangles are associated with neuronal loss, or whether it is dementia that relates to changes of absolute cell composition, by comparing cell numbers in brains of patients severely demented with those of asymptomatic individuals-both groups histopathologically diagnosed as Alzheimer's-and normal subjects with no pathological signs of the disease. We found a great reduction of neuronal numbers in the hippocampus and cerebral cortex of demented patients with Alzheimer's disease, but not in asymptomatic subjects with Alzheimer's disease. We concluded that neuronal loss is associated with dementia and not the presence of plaques and tangles, which may explain why subjects with histopathological features of Alzheimer's disease can be asymptomatic; and exclude amyloid-ß deposits as causes for the reduction of neuronal numbers in the brain. We found an increase of non-neuronal cell numbers in the cerebral cortex and subcortical white matter of demented patients with Alzheimer's disease when compared with asymptomatic subjects with Alzheimer's disease and control subjects, suggesting a reactive glial cell response in the former that may be related to the symptoms they present.

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Se presenta un modelo de endurecimiento isotrópico para biomateriales metálicos, el cual emplea un esquema de integración explícita bajo una formulación incremental. Para la implementación computacional se programó un elemento finito de usuario UEL en lenguaje FORTRAN para su ejecución en el software ABAQUS. Con el fin de validar el modelo se resuelven dos ejemplos tipo benchmark y sus resultados son comparados con ANSYS y el UMAT de Dunne y Petrinic para ABAQUS. Finalmente, el modelo es usado para simular la extensión de un stent coronario fabricado en acero inoxidable 316L. Se concluye que el modelo posee un error numérico aceptable teniendo en cuenta que el elemento finito fue programado por completo y no posee ninguna de las optimizaciones de los códigos comerciales. En trabajos futuros el UEL será acoplado con modelos de mecánica de daño continuo para la predicción de la falla por fatiga, cuyo análisis es un estándar básico en la manufactura de stents

A isotropic hardening model is presented for metallic biomaterials, which uses a explicit integration scheme under increasing formula. To computer implementation a finite element from UEL user was programmed in FORTRAN language for its execution in the ABAQUS software. To model validation two examples type benchmark were solved and results are compared with ANSYS and the UMAT of Dunne and Petrinic for ABAQUS. Finally, model is used to simulate the extension of a coronary stent manufactures in 316L stainless steel. We conclude that the model has an acceptable numerical error taking into account that finite element was programmed as a whole and has not any of the optimizations of commercial codes. In future papers the UEL will be coupled with continuous damage mechanics model to predict the failure due to fatigue, whose analysis is a basic standard in stent manufacturing

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The present investigation aims to evaluate an isotropic and thermodynamically stable nanoemulsion formulation for transdermal delivery of glycyrrhizin (GZ), with minimum surfactant and cosurfactant (Smix) concentrations that could improve its solubility, permeation enhancement, and stability. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared using soyabean oil as oil, Span 80, Brij 35 as a surfactant and isopropyl alcohol as a cosurfactant. Nanoemulsion formulations that passed the thermodynamic stability tests were characterized for pH, viscosity and droplet size using a transmission electron microscopy. The transdermal ability of glycyrrhizin through human cadaver skin was determined using Franz diffusion cells. The in vitro skin permeation profile of the optimized nanoemulsion formulation (NE2) was compared to that of conventional gel. A significant increase in permeability parameters such as steady-state flux (Jss) and permeability coefficient (Kp) was observed in the optimized nanoemulsion formulation (NE2), which consisted of 1 percent wt/wt of mono ammonium glycyrrhizinate (MAG), 32.4 percent Span 80, 3.7 percent Brij 35, 10 percent isopropyl alcohol, 46.5 percent soyabean oil and 6.4 percent distilled water. No obvious skin irritation was observed for the studied nanoemulsion formulation (NE2) or the gel. The results indicated that nanoemulsions are promising vehicles for transdermal delivery of glycyrrhizin through human cadaver skin, without the use of additional permeation enhancers, because excipients of nanoemulsions act as permeation enhancers themselves.

O objetivo da investigação é avaliar uma nanoemulsão isotrópica termodinamicamente estável para a administração transdérmica da glicirrizina (GZ), com concentrações mínimas de tensoativo e co-tensoativo (Smix), que poderiam melhorar a sua solubilidade, a permeação e a estabilidade. Os diagramas pseudo-ternários de fase foram desenvolvidos e diversas nanoemulsões foram preparadas com óleo de soja como óleo, Span 80, Brij 35 como tensoativos e álcool isopropílico como co-tensoativo. As nanoemulsões que passaram por testes de estabilidade termodinâmica foram caracterizadas por pH, viscosidade, tamanho de gota e microscopia eletrônica de transmissão. A capacidade transdérmica da glicirrizina em passar através da pele de cadáver humano foi determinada por células de difusão de Franz. O perfil in vitro de permeação cutânea da formulação otimizada (NE2) foi comparada com a de gel convencional. Observou-se aumento significativo nos parâmetros de permeabilidade, como fluxo de equilíbrio (JSS) e coeficiente de permeabilidade (Kp) na formulação otimizado (NE2), que consistiu de 1 por cento wt/wt de monoglicirrizinato de amônio (MAG), 32,4 por cento de Span 80, 3,7 por cento de Brij 35, 10 por cento de álcool isopropílico, 46,5 por cento de óleo de soja e 6,4 por cento de água destilada. Não se observou irritação óbvia da pele para as nanoemulsões estudadas (NE2) ou de gel. Os resultados indicaram que nanoemulsões são promissores veículos para a administração transdérmica de glicirrizina através da pele de cadáveres humanos, sem o uso adicional de promotor de permeação, porque excipientes de nanoemulsões atuam como promotores de permeação.

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Based on solvation studies of polymers, the sum (1:1) of the electron acceptor (AN) and electron donor (DN) values of solvents has been proposed as an alternative polarity scale. To test this, the electron paramagnetic resonance isotropic hyperfine splitting constant, a parameter known to be dependent on the polarity/proticity of the medium, was correlated with the (AN+DN) term using three paramagnetic probes. The linear regression coefficient calculated for 15 different solvents was approximately 0.9, quite similar to those of other well-known polarity parameters, attesting to the validity of the (AN+DN) term as a novel "two-parameter" solvent polarity scale.

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Apesar do titânio extensivamente usado como biomaterial, ainda existem dúvidas quanto à influência da rugosidade superficial, qualidade, composição e espessura da camada de óxido que recobre o implante na resposta biológica. Durante a cicatrização, que ocorre em alguns dias e a remodelação que necessita de semanas ou até anos, ocorrem mudanças biológicas na interface implante-hospedeiro, as quais dependem das propriedades da camada inicial de óxido titânio. Para acelerar os micromecanismos de ligação do implante aos tecidos os implantes são submetidos aos tratamentos da superfície, os quais são feitos por imersão em ácidos, jateamento, tratamento eletroquímico ou com laser. No presente trabalho implantes dentários osseointegráveis foram submetidos aos diferentes tratamentos citados. Os resultados obtidos mostraram que as superfícies dos implantes como usinada ou tratada com laser apresentaram morfologias anisotrópicas e, os implantes tratados com ácidos, jateados ou oxidados têm superfície mais homogênea e com características morfológicas isotrópicas. A vantagem da superfície isotrópica esta associada à melhor biodesão das células, crescimento celular em todas as direções da superfície e menor tempo de osseointegração

Commercial purê titanium (CP Ti) is used in dental implants because of its chemical stability and biocompatibility, which are attributed to a surface layer of titanium oxide. Several mechanical and chemical treatments have been proposed to increase this biocompatibility. One possibility is to increase the surface roughness and the thickness of the titanium oxide layer. In the present work, dental implants as machined, acid etched, sandblasted, oxidized and submitted to laser treatmente were analysed. The results showed that the surface morphology of dental implant as machined and the treated by laser were anisotropic. Surfaces dental implant as acid etched, sandblasted and oxidized are isotropic

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