Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO). In these conditions, NO promotes proliferation of neural stem cells (NSC) in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA) induced seizuremouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons.Foundation for Science and Technology (FCT, Portugal); COMPETE; FEDER [PTDC/SAU-NEU/102612/2008, PTDC/NEU-OSD/0473/2012, PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014]; FCT, Portugal [SFRH/BPD/78901/2011, SFRH/BD/77903/2011

Recorded places, experienced places: some remarks about the Holocene Rock Art of the Iberian Atlantic Northwest

info:eu-repo/semantics/acceptedVersio

Antibodies Against M-Type Phospholipase A2 Receptor (PLA2R) in Patients with Primary Membranous Nephropathy and Lupus Nephritis Class V: A Review

Membranous nephropathy (MN) is a very common disease of male adults with nephrotic syndrome. The disease can be primary, when the cause is not known, or secondary associated with infections, drugs, neoplasias and autoimmune systemic diseases, such as systemic lupus erythematosus (SLE). The primary form accounts for 70–80% of the cases. SLE is a common cause of secondary MN affecting young women. The differential diagnosis from primary and lupus MN by clinical and morphological findings can be difficult. The search for autoantibodies against podocyte antigen M-type phospholipase A2 receptor (PLA2R) has demonstrated high positivity in the serum and renal biopsies in the primary MN and negativity in lupus MN (WHO class V). There is a large literature on the role of anti-PLA2R antibody in the diagnosis and follow-up of patients with membranous nephropathy. The aim of this review is to summarize the literature data on the etiopathogenesis of MN and the value of anti-PLA2R antibody screening for the diagnosis and management of patients

Optimization of the determination of tocopherols in Agaricus sp. edible mushrooms by a normal phase liquid chromatographic method

Individual tocopherol profile of five Agaricus mushroom species, widely consumed in Portugal, was obtained by a normal-phase high-performance liquid chromatography (NP-HPLC). It was used a simple solid–liquid extraction procedure without saponification step and the chromatographic separation was achieved using a YMC-Pack Polyamine II column using an isocratic elution with hexane/ethyl acetate (70:30, v/v) at a flow rate of 1.0 mL/min. The effluent was monitored by a fluorescence detector. All the compounds were separated in a period of time of 30 min. The method proved to be sensitive, reproducible and accurate, allowing the determination of tocopherols

Freshwater periphyton response to technical-grade and two commercial formulations of glyphosate

El glifosato es el herbicida más utilizado a nivel mundial. Puede llegar a los cuerpos de agua y afectar a las comunidades microbianas. Comparamos los efectos del glifosato grado técnico y dos formulados comerciales sobre una comunidad perifítica de agua dulce. Se llevó a cabo un experimento de laboratorio con cuatro tratamientos: glifosato ácido grado técnico, Glifosato II Atanor®, Roundup Max®, a una concentración de 3 mg de ingrediente activo/L, y un Control. A los 2, 5 y 9 días posteriores a la aplicación de los herbicidas se determinaron la concentración de pigmentos, peso seco, peso seco libre de cenizas y densidad algal del perifiton. Se registró un incremento de la abundancia de Cyanobacteria y una disminución de Chlorophyta y Bacillariophyta en todos los tratamientos con herbicida. Este efecto fue mayor con la adición de Roundup Max® y Glifosato II Atanor®, y fue menor con glifosato grado técnico, sugiriendo que los aditivos en los formulados comerciales pueden intensificar los efectos del glifosato.Glyphosate is the most widely used herbicide worldwide. It may reach water bodies and affect microbial communities. We compared the effects of two commercial formulations and technical-grade glyphosate on a freshwater periphytic community. A laboratory bioassay was carried out with four treatments: technicalgrade glyphosate acid, Glifosato II Atanor®, Roundup Max®, at a concentration of 3 mg active ingredient/L, and Control. At 2, 5 and 9 days after herbicide application, pigments concentration, dry weight, ash-free dry weight, and periphytic algal density were determined. An increase of Cyanobacteria and a decrease of Chlorophyta and Bacillariophyta abundances were registered in all treatments with the herbicide. This effect was greater when Roundup Max® and Glifosato II Atanor® were added, and was lower with technical-grade glyphosate, suggesting that additives in the commercial formulations may enhance glyphosate effects

New non-toxic biocompatible dianionic ionic liquids that enhance the solubility of oral drugs from BCS class II

The authors thank Fundação para a Ciência e Tecnologia, FCT/ MCTES (Portugal) for financial support through an Investigator contract (IF/00621/2015 – P.M. Reis), and through projects IF/00621/2015 and CryoDES (PTDC/EQU-EQU/29851/2017). This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme, under grant agreement No ERC-2016-CoG 725034. This work was also partially supported by the Associate Laboratory for Green Chemistry - LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020) The NMR spectrometers are part of The National NMR Facility, supported by FCT/MCTES (RECI/BBB-BQB/0230/2012). The authors are grateful for important discussions with PhD Wagner Silva about two-dimensional NOESY 1H-1H experiments.New dianionic ionic liquids (ILs) based on carboxylic anions and ammonium cations were prepared and characterized. They were used as excipients to increase the solubility of two model oral drugs of BCS class II, ibuprofen and piroxicam. With only 0.2 mol% (≈100 mM) of [N4 1 1 2OH]2[C4H4O4], the solubility increases over 40-fold and 2-fold for ibuprofen, when compared with the parent drug for water and phosphate buffer solution (PBS) 0.01M pH=7.4, respectively. With only 0.02 mol% of [N4 1 1 2OH]2[C4H4O4] it is possible to achieve a water solubility of ≈600 mg/L, in only 5 min at 37°C, corresponding to one dose of ibuprofen that an adult can take. Piroxicam also showed an increase of 20-fold and 1.5-fold for water and PBS respectively, with [N4 1 1 2OH]2[C4H4O4] and [N4 1 1 2OH]2[C5H6O4]. The lipophilicity (logP) of both drugs decreased in the presence of these compounds. The cytotoxicity profile of several of these ILs was determined, and all except [N4 1 1 2OH]2[C3H2O4] have an IC50 higher than 100 mM for fibroblasts L929 cells.publishersversionpublishe

Spontaneous B-cell lymphoma in hamster

Durante estudo anatomopatológico, incluindo imunoistoquímica, sobre pancreatite chagásica, experimentalmente induzida em hamsters machos, não-isogênicos, com quatro meses de idade, pesando 107,8 ± 10,9g, infiltração por linfoma foi observada em um animalcontrole normal, com 15 meses de idade. A neoplasia foi notada na ocasião da necropsia, 330 dias após o início do experimento. Lirifoma similar não foi achado nos demais controles normais (n=73), nem nos hamsters do grupo infectado, pareados para peso e idade (n=94). As alterações histopatológicas e imunoistoquímicas foram consistentes com linfoma difuso, não-Hodgkin, de grandes céiulas-B; porém, a hipótese de eventual origem leucêmica não foi inteiramente excluída. Linfomas experimentalmente induzidos têm sido relatados em animais de laboratório; entretanto, relatos de caso de linfoma, ocorrendo espontaneamente em hamsters, não têm sido freqüentes. No presente caso, o desenvolvimento da doença poderia ter alguma relação com o processo de envelhecimento.During anatomopathologic study, including immunohistochemistry, about chagasic pancreatitis experimentally induced in four month aged male non-isogenic hamsters, weighing 107.8 ± 10.9g, lymphoma infiltration was observed in a 15 month-aged normal control animal. The neoplasia was disclosed on the occasion of necropsy studies, 330 days after the beginning of experiment. Similar lymphoma was not found in the remainder normal controls (n=73), nor in the group of infected hamsters age and weight matched (n=94). The neoplasia histopathologic and immunohistochemical changes were consistent with non-Hodgkin diffuse large B-ceIl lymphoma; nevertheless, the hypothesis of eventual leukemic origin was not entirely excluded. Experimentally induced lymphomas have been related in laboratory animais; however, cases of spontaneously occurring lymphoma have been infrequently described in hamsters. In the present case, the development of the disease could have some relation with the animal aging process

Apoptosis-associated microRNAs are modulated in mouse, rat and human neural differentiation

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRs or miRNAs) regulate several biological processes in the cell. However, evidence for miRNAs that control the differentiation program of specific neural cell types has been elusive. Recently, we have shown that apoptosis-associated factors, such as p53 and caspases participate in the differentiation process of mouse neural stem (NS) cells. To identify apoptosis-associated miRNAs that might play a role in neuronal development, we performed global miRNA expression profiling experiments in NS cells. Next, we characterized the expression of proapoptotic miRNAs, including miR-16, let-7a and miR-34a in distinct models of neural differentiation, including mouse embryonic stem cells, PC12 and NT2N cells. In addition, the expression of antiapoptotic miR-19a and 20a was also evaluated.</p> <p>Results</p> <p>The expression of miR-16, let-7a and miR-34a was consistently upregulated in neural differentiation models. In contrast, expression of miR-19a and miR-20a was downregulated in mouse NS cell differentiation. Importantly, differential expression of specific apoptosis-related miRNAs was not associated with increased cell death. Overexpression of miR-34a increased the proportion of postmitotic neurons of mouse NS cells.</p> <p>Conclusions</p> <p>In conclusion, the identification of miR-16, let-7a and miR-34a, whose expression patterns are conserved in mouse, rat and human neural differentiation, implicates these specific miRNAs in mammalian neuronal development. The results provide new insights into the regulation of neuronal differentiation by apoptosis-associated miRNAs.</p