Novel perspectives on the subependymal zone complexity and modulation

Tese de doutoramento em Ciências da SaúdeIn the mammalian brain adult neurogenesis occurs in two restricted sites: the subependymal zone (SEZ) and the subgranular zone of the hippocampal dentate gyrus. The SEZ comprises neural stem and progenitor cells that lie adjacent to the ependyma layer of the lateral ventricles. SEZ born neuroblasts migrate anteriorly in the rostral migratory stream towards the olfactory bulbs where they differentiate and integrate into neuronal circuitries. Because cells in the SEZ niche sense alterations in brain homeostasis and are able to alter their proliferative, migratory and differentiation profiles in response to injury, it is of particular interest to completely understand this dynamics both in physiological and pathological conditions. In this context, the present thesis addresses three main aspects in regard to SEZ niche complexity and modulation. First, in regard to SEZ heterogeneity, we performed a topographic analysis of the rat SEZ niche along the anterior-posterior and dorsal-ventral axes. We found that the SEZ cell proliferation decreases along the anterior-posterior axis and varies considerably according to the position in the dorsal-ventral axis. Furthermore, these differences were associated with relevant gradients in the neuroblasts population and in the neural stem cell (NSC) population throughout the dorsalventral axis. Next, we performed the same analysis on the proliferative and progenitor population profile in the mouse adult neurogenic niche, and found relevant species-specific differences between rat and mouse models, two closely related species. The proliferation gradients and the neuroblasts distribution observed in rat were absent in mice. Finally, in regard to SEZ modulation/modulators in disease, we report the impact of a peripheral inflammatory stimulus, triggered by lipopolysaccharide (LPS), on the SEZ, choroid plexus (CP) and cerebrospinal fluid (CSF). The CP is the structure of the brain that produces and secretes most of the CSF that is in direct contact with the NSCs of the SEZ. In response to an acute peripheral inflammatory stimulus CP gene expression of modulators of the SEZ is altered and this is partially reflected on the CSF composition. The same inflammatory stimulus triggered a rapid and transient increase on SEZ cell proliferation. The peak of CP response to the inflammatory trigger was at 6h and 12h upon LPS administration and the induction of SEZ cell proliferation occurred specifically after 12h of LPS stimulus. In summary, the data presented here reveals relevant topographical specificities of the rat and mouse SEZ and highlights species-specific differences. Moreover, it gives further insights on the SEZ response to acute peripheral inflammatory stimulus and pinpoints relevant CP synthetized molecules that when secreted towards the CSF can modulate the SEZ dynamics.No cérebro adulto dos mamíferos existem dois locais onde ocorre neurogénese: a zona subependimal (SEZ) e a zona subgranular que constitui a circunvolução denteada do hipocampo. A SEZ compreende células estaminais neurais e células progenitoras que se encontram adjacentes à camada do epêndima dos ventrículos laterais. Os progenitores de neurónios (também designados por neuroblastos) provenientes da SEZ migram anteriormente na via rostral de migração para os bolbos olfativos onde se diferenciam e integram nos circuitos neuronais. Como as células da SEZ percecionam alterações na homeostasia do cérebro e são capazes de alterar os seus perfis de proliferação, migração e diferenciação, em resposta a uma lesão, tornase particularmente interessante entender completamente esta dinâmica, tanto em condições fisiológicas como patológicas. Neste contexto, esta tese aborda três aspetos principais em relação à complexidade e modulação da SEZ. Em primeiro lugar, no que diz respeito à heterogeneidade da SEZ, foi realizada uma análise topográfica deste nicho neurogénico no rato ao longo dos eixos anterior-posterior e dorsal-ventral. Os resultados obtidos demonstraram que a proliferação das células da SEZ diminui ao longo do eixo anterior-posterior e varia consideravelmente de acordo com a posição no eixo dorsal-ventral. Para além disso, estas diferenças estão associadas a uma distribuição diferencial na população dos neuroblastos e na população das células estaminais neurais (NSCs) ao longo do eixo dorsalventral. Em seguida, foi realizada a mesma análise na SEZ do murganho adulto. A análise destes resultados revelou diferenças relevantes entre estas duas espécies filogeneticamente muito próximas. A proliferação e a distribuição diferencial das NSCs e dos neuroblastos observada em ratos não ocorrem em murganhos. Finalmente, no que diz respeito à modulação da SEZ em resposta a insultos ao cérebro, foi estudado o impacto de um estímulo inflamatório periférico, desencadeada por um lipopolissacarídeo (LPS), componente da parede das bactérias gram negativas, sobre a SEZ, o plexus coroideus (CP) e o líquido cefalorraquidiano (CSF). O CP é a estrutura do cérebro que produz e segrega a maioria do CSF que por sua vez está em contacto direto com as NSCs da SEZ. Em resposta a um estímulo periférico inflamatório, a expressão genética no CP de moduladores da SEZ é alterada, sendo esta alteração parcialmente refletida na composição proteica do CSF. O mesmo estímulo inflamatório desencadeou um aumento rápido e transitório na proliferação celular na SEZ. O pico da resposta do CP ao estímulo inflamatório desencadeado pelo LPS foi às 6h e 12h após a administração de LPS e a indução da proliferação celular na SEZ ocorreu especificamente após 12h de estímulo com LPS. Em resumo, os resultados apresentados nesta tese revelam especificidades topográficas da SEZ no rato e no murganho, destacando ainda diferenças específicas entre estas duas espécies. Além disso, revela também a resposta da SEZ a um estímulo periférico inflamatório agudo e realça algumas moléculas sintetizadas no CP que quando segregadas para o CSF podem modular as células da SEZ

Height difference between the vestibular and palatal walls and palatal width: a cone beam computed tomography approach

Background: The objective of this study was to measure two parameters involved in tri-dimensional implant plan‑ ning: the position of the buccal and palatal bone wall and the palatal thickness. Methods: Cone beam computed tomography (CBCT) images (Planmeca ProMax 3D) of 403 teeth (208 upper teeth and 195 lower teeth) were obtained from 49 patients referred to the Dental School of Seville from January to Decem‑ ber 2014. The height diference between the palatal and buccal walls was measured on the most coronal point of both walls. The thickness of the palatal wall was measured 2 mm from the most coronal point of the palatal wall. Results: The mean values in the maxilla were 1.7±0.9 mm for central and lateral incisors, 2.2±1.7 mm for canines, 1.6±0.9 mm for premolars and 1.9±1.5 mm for molars. In the lower jaw, the mean values were 1.3±0.8 mm for inci‑ sors, 1.7±1.2 mm for canines, 2.3±1.3 mm for premolars, and 2.6±1.7 mm for molars. In the upper jaw, more than 55% of maxillary teeth (excluding second premolars and molars) presented mean height diferences greater than 1 mm. In the mandible, more than 60% of incisors showed a buccal bone thickness of 1 mm from the apical to lingual aspect. All teeth except the second premolar presented a buccal wall located more than 1 mm more apically than the lingual bone wall. Conclusions: The buccal bone wall is located more apically (greater than 1 mm) than the palatal or lingual table in most of the cases assessed. The thickness of the palatal or lingual table is also less than 2 mm in the maxilla and man‑ dible, except in the upper canines and premolars and the lower molars

Toxicological Study Employing Repeated Doses of Garcinielliptone FC, a Polyisoprenylated-Benzophenone Isolated from Seed of Platonia Insignis Mart

The major constituent from the hexane extract of the seeds of P. insignis is GFC (garcinielliptone FC). Doses of 25, 50and 75 mg/kg of GFC were aseptically suspended in 0.05% Tween 80 dissolved in 0.9% saline (vehicle) and orally administered for30, 90 and 120 consecutive days to adult Swiss mice. In this work, the repeated oral administration, in animals of both sexes,demonstrates that this compound is not able to induce mortality and/or behavioral changes in adult mice. In addition, body weightgain, feed intake and disposal of excreta were not altered by the administration of this compound with repeated doses. Furthermore,no differences in weight and macroscopic structure of the brain, liver, kidney, lung, heart and spleen between groups of male andfemale adult mice were observed after treatment. During the periods of treatment, GFC produced no significant changes onhaematological and biochemical parameters in male and female mice treated with all doses used. The aim of this study was toinvestigate the toxicological potential of GFC through behavioral, hematological, biochemical and morphological parameters inanimals in order to ensure the safe use of Platonia insignis in folk medicine.Fil: Silva, Ana P.. Federal University of Piauí; BrasilFil: Filho, José Carlos C. L. S.. North Union of Parana; BrasilFil: da Costa Júnior, Joaquim S.. Federal Institute of Piauí; BrasilFil: Peláez, Walter José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Faillace, Martín Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Falcão Ferraz, Alexandre de B.. Lutheran University of Brazil; BrasilFil: David, Jorge M.. Institute Of Chemistry, Federal University Of Bahia; Brasil. Universidade Federal da Bahia; BrasilFil: Freitas, Rivelilson M.. Federal University of Bahia; Brasi

Activated Carbon Post Treatment - Influence on Phenolic Compounds Removal

● AC preparation from different precursors and their modification / optimisation with sodium hydroxide and urea to improve the adsorption capacities for phenolic compounds from the liquid phase. ● Comparative study of the influence of textural and chemical parameters of AC on the liquid phase adsorption

Modification and Optimization of Activated Carbons for Phenolic Compounds removals

Phenols are generally considered to be one of the important organic pollutants discharged into the environment causing unpleasant taste and odour of drinking water. Development of inexpensive adsorbents from industrial wastes for the treatment of wastewaters is an important area in environmental sciences. For the phenolic compounds removal, it appears that the pH of the solution, the real surface area of the solid, and functional groups play a major role. The objective of this study was to screen various adsorbents for potential application for the removal of phenolic compounds for drinking water concentration range. The adsorbents used in this study were AC prepared from recycled PET and AC prepared from cork submitted to a reduction post treatment

Modification and Optimization of Activated Carbons for Phenolic

Phenolic compounds are generally considered to be one of the important organic pollutants discharged into the environment causing unpleasant taste and odour of drinking water [1,2]. So, removal of phenolics compounds from industrial effluents is required before sewage disposal. The development of inexpensive adsorbents from industrial wastes for the treatment of wastewaters is an important area in environmental sciences. For the phenolic compounds removal, it appears that the pH of the solution, the real surface area of the solid and functional groups play a major role. Adsorption onto activated carbons (AC) is often considered, amongst the methods currently employed to remove inorganic and organic pollutants, from aqueous or gaseous phases, as the most efficient and one of the most economical. A detailed characterization of physical and chemical surface properties of an AC has become one of the most important issues in adsorption technology because it ascertain its suitability for one or more of the application fields

The influence of the activated carbon post-treatment on the phenolic

The aim of this research was to investigate how post treatment modification, such as those with sodium hydroxide or urea, can influence the capacity of activated carbon (AC) for phenolic compounds removal from liquid media. The ACs modification was performed using urea impregnation followed by pyrolysis at high temperature. With all ACs used, this treatment induced a pore volume increase, a mean pore size broadening, an increase in the point of zero charge and also in the basic character. The modification with sodium hydroxide brings to light the influence of the precursor nature as the achievements are really diverse. With the ACs obtained from PET, a pore volume and mean pore size reduction occurred, with the AC-cloth no textural effect was observed and with the AC obtained from cork, an enlargement of the mean pore size and an increase of the pore volume were confirmed. The difference in the acidic/basic character exhibited by the modified ACs was in agreement with the presence of acidic/basic superficial groups identified by FTIR. The textural and chemical properties of the ACs affect in a direct way the phenolic compounds removal capacity. Particularly, those modified with urea, which exhibited a superior removal capacity for both phenolic compounds

A CFD study of a pMDI plume spray

Uncorrected proofAsthma is an inflammatory chronic disease characterized by airway obstructions disorders. The treatment is usually done by inhalation therapy, in which pressurized metered-dose inhalers (pMDIs) are preferred devices. The objective of this paper is to characterize and simulate a pMDI spray plume by introducing realistic factors through a computational fluid dynamics (CFD) study. Numerical simulations were performed with Fluent® software, by using a three-dimensional “testbox” for room environment representation. A salbutamol/HFA-134a formulation was used for characterization, whose properties taken as input for the CFD simulations. Spray droplets were considered to be composed by ethanol, salbutamol and HFA-134a. Propellant evaporation was taken into consideration, as well as, drag coefficient correction. Results showed an air temperature drop of 3.3 °C near the nozzle. Also, an increase in air velocity of 3.27 m/s was noticed. The CFD results seem to be in good agreement with Dunbar (1997) data on particle average velocity along the axial distance from the nozzle.National Funds-Portuguese Foundation for Science and Technology, under Strategic Project PEst-C/EME/UI4077/2011 and PEst-OE/EME/299UI0252/201

Altered iron metabolism is part of the choroid plexus response to peripheral inflammation.

Iron is essential for normal cellular homeostasis but in excess promotes free radical formation and is detrimental. Therefore, iron metabolism is tightly regulated. Here, we show that mechanisms regulating systemic iron metabolism may also control iron release into the brain at the blood-choroid plexus-cerebrospinal fluid (CSF) barrier. Intraperitoneal administration of lipopolysaccharide (LPS) in mice triggers a transient transcription of the gene encoding for hepcidin, a key regulator of iron homeostasis, in the choroid plexus, which correlated with increased detection of pro-hepcidin in the CSF. Similarly, the expression of several other iron-related genes is influenced in the choroid plexus by the inflammatory stimulus. Using primary cultures of rat choroid plexus epithelial cells, we show that this response is triggered not only directly by LPS but also by molecules whose expression increases in the blood in response to inflammation, such as IL-6. Intracellular conveyors of these signaling molecules include signal transducer and activator of transcription 3, which becomes phosphorylated, and SMAD family member 4, whose mRNA levels increase soon after LPS administration. This novel role for the choroid plexus-CSF barrier in regulating iron metabolism may be particularly relevant to restrict iron availability for microorganism growth, and in neurodegenerative diseases in which an inflammatory underlying component has been reported.This work was supported by Grant POCTI/SAU-NEU/56618/2004 from Fundacao para a Ciencia e Tecnologia (Portugal) and a grant from The Dana Foundation (USA). F. M. is the recipient of postdoctoral fellowship, and A. M. F. is the recipient of a Ph. D., fellowship from Fundacao para a Ciencia e Tecnologia (Portugal)

Influencia de la dinámica de estuarios sobre la variabilidad espacial de macrobentos a lo largo de la plataforma continental del sudeste de Brasil

Along the southeast continental shelf of Brazil, the Paraíba do Sul River (PSR) plays a fundamental role in sediment and nutrient transport. This study focuses on the contribution of the PSR and its effect on the benthic macrofauna. Physical and chemical analyses of the sediment were conducted, and the macrofauna were identified and counted. Multivariate analyses were used to compare the distribution patterns of the benthic assemblages related to the depth gradient over two sampling periods. The principal component analysis showed that shallow waters assemblages are mostly influenced by the environmental descriptors temperature, salinity and chlorophyll a, whereas pheophytin, degree of sediment sorting, total carbonate and organic carbon were correlated with benthic assemblages at greater depths. The high organic enrichment reflected an increase in surface and sub-surface deposit feeders such as the polychaetes Spiophanes sp. and Prionospio cristata and the crustacean Phtisica marinain the deeper stations, with a corresponding decrease in other trophic groups. This study provides evidence of differences in organic matter sources, from primary production in shallow waters to detritus in deep waters. These sources provide different niches for the corresponding macrofaunal assemblages along the continental shelf adjacent to the PSR, with species richness and abundance of benthic populations related to the river output.A lo largo de la plataforma continental del sudeste de Brasil, el río Paraíba do Sul (RPS) juega un papel fundamental en el transporte de sedimento y nutrientes. Este estudio se enfoca en la contribución del RPS y sus efectos sobre la macrofauna bentónica. Se condujeron análisis físicos y químicos del sedimento, y la macrofauna fue identificada y contada. Se realizaron análisis multivariados para comparar los patrones de distribución de los ensamblajes bentónicos relacionados al gradiente de profundidad en dos periodos de muestreo. El análisis de componentes principales (ACP) mostró que los ensamblajes de aguas poco profundas son influenciados principalmente por los descriptores ambientales de temperatura, salinidad, y clorofila a, mientras que la feofitina, grado de clasificación de sedimentos, carbonato total y el carbón orgánico estaban correlacionados a los ensamblajes bentónicos a mayores profundidades. El alto enriquecimiento orgánico se refleja en un incremento de detritívoros superficiales y sub-superficiales como los poliquetos Spiophanes sp. y Prionospio cristata y el crustáceo Phtisica marinaen las estaciones más profundas, con el decrecimiento correspondiente en otros grupos tróficos. Este estudio provee evidencia de diferencias entre fuentes de materia orgánica, desde la producción primaria en aguas poco profundas hasta detrito en aguas profundas, que proveen distintos nichos a los ensamblajes macrofaunales correspondientes a lo largo de la plataforma continental adyacente al RPS, con la riqueza de especies y abundancia de las poblaciones bentónicas relativas al flujo del rio