Activation of GPR40 induces hypothalamic neurogenesis through p38- and BDNF-dependent mechanisms.

Hypothalamic adult neurogenesis provides the basis for renewal of neurons involved in the regulation of whole-body energy status. In addition to hormones, cytokines and growth factors, components of the diet, particularly fatty acids, have been shown to stimulate hypothalamic neurogenesis; however, the mechanisms behind this action are unknown. Here, we hypothesized that GPR40 (FFAR1), the receptor for medium and long chain unsaturated fatty acids, could mediate at least part of the neurogenic activity in the hypothalamus. We show that a GPR40 ligand increased hypothalamic cell proliferation and survival in adult mice. In postnatal generated neurospheres, acting in synergy with brain-derived neurotrophic factor (BDNF) and interleukin 6, GPR40 activation increased the expression of doublecortin during the early differentiation phase and of the mature neuronal marker, microtubule-associated protein 2 (MAP2), during the late differentiation phase. In Neuro-2a proliferative cell-line GPR40 activation increased BDNF expression and p38 activation. The chemical inhibition of p38 abolished GPR40 effect in inducing neurogenesis markers in neurospheres, whereas BDNF immunoneutralization inhibited GPR40-induced cell proliferation in the hypothalamus of adult mice. Thus, GPR40 acts through p38 and BDNF to induce hypothalamic neurogenesis. This study provides mechanistic advance in the understating of how a fatty acid receptor regulates adult hypothalamic neurogenesis.

Effect of sirolimus on carotid atherosclerosis in kidney transplant recipients: data derived from a prospective randomized controlled trial.

BACKGROUND: In animal models, the mammalian target of rapamycin inhibitors (mTORIs) may prevent atherogenesis by the regulation of homeostasis of cholesterol and by a reduced inflammatory response. The aim of this study is to compare the carotid intima-media thickness (cIMT) between de novo tacrolimus/mycophenolate and tacrolimus/sirolimus at low doses. The cIMT is considered a surrogate marker of atherosclerosis. METHODS: We evaluated cIMT at baseline and at 6 and 12 months after kidney transplantation in a database derived from a previously published trial. That trial had prospectively randomly assigned kidney transplant recipients older than 60 years of age to one of two groups: tacrolimus/sirolimus (n = 21) or tacrolimus/mycophenolate (n = 23). The cIMT was evaluated by using ultrasound in the common carotid artery wall on both sides. RESULTS: The total and high-density lipoprotein cholesterol levels were higher in the sirolimus group at 6 and 12 months. The cIMT decreased over time at 6 and 12 months in the sirolimus group (P = 0.012); this decrease continued to be significant in a model adjusted for age, sex, presence of diabetes, statin use and smoking. CONCLUSIONS: The use of sirolimus plus tacrolimus de novo in kidney transplantation is associated with a reduction in cIMT after 12 months, a decrease more significant than seen with the combination of mycophenolate plus tacrolimus. This suggests a class effect of mTORI in the prevention of atherosclerosis.

Non-thermal combined treatments in the processing of açai (Euterpe oleracea) juice.

Quality parameters of açai juice processed with ultrasound-assisted, ozone and the combined methods were analyzed in this work. Two ultrasound energy densities (350 and 700 J·mL-1) and two ozonization times (5 and 10 min with 1.5 ppm) were analyzed for pure açai juice and 8 different treatments (22 complete factorial). To evaluate the quality parameters of the juice, physical-chemical analyzes such as pH, titratable acidity, cloud value, non-enzymatic browning, rheology, antioxidant activity (DPPH and ABTS), phenolic compounds, anthocyanins, enzymatic activity (peroxidase and polyphenol oxidase) and microbial counts (mesophilic bacteria, molds and yeasts) were conducted. The treatments with ozone were better for microbial inactivation and the ultrasound for enzymatic inactivation. In general, the use of non-thermal methods can be a good alternative for the processing of açai juice.

[Comparison of operative and oncologic results between partial nephrectomy and radiofrequency ablation for treatment of renal tumors in patients older than 75]. / Comparaison des résultats opératoires et oncologiques de la néphrectomie partielle et de l'ablation par radiofréquence pour traitement des tumeurs rénales chez les patients de plus de 75 ans.

INTRODUCTION: Elderly patients represent a growing part of our society for who treatment strategy for localized renal tumors has to be chosen knowing iatrogen effects and renal function morbidity. The aim was to analyze oncological and functional results of nephron sparing surgery (PN) versus radiofrequency ablation (RFA). MATERIALS AND METHODS: All patients aged more than 75 treated by partial nephrectomy or radiofrequency ablation between 2007 and 2014 in our centre were included. Patient and tumors data were compared and these criteria were analyzed: survival (overall and without recurrence) and loss of renal function (pre- and postoperative MDRD). RESULTS: In total, 100 patients were included (26 partial nephrectomies, group 1 and 74 radiofrequency ablation, group 2) with a 32-months medium follow-up. Medium age and tumor size were significantly different (respectively, 78 versus 81 years old, P=0.001, 38mm versus 29mm, P=0.003). Perioperative results showed no differences in complications. Transfusion rate and duration of hospital stay were significantly higher in the PN group. Median overall survival were 45 vs. 27 months (P=0.23) for PN and RFA and median recurrence-free survival were 28 vs. 10 months (P=0.34). On a multivariate analysis, operative technique (PN or RFA) were not significantly linked to survival (HR 2.37 [95% CI: 0.66-8.5]), P=0.19. Loss of renal function were 1.5±14mL/min/1.73m2 for PN and 3±14mL/min/1.73m2 for RFA (P=0.69). CONCLUSION: Our study showed better perioperative results for RFA than for PN, without significant different survival. Loss of renal function were little and similar. LEVEL OF EVIDENCE: 4.

Mechanistic model for the firefly luciferin regeneration in biomimetic conditions: a model for the in vivo process?

The emission of light by fireflies involves the enzymatic oxidation of firefly luciferin and ends up in the formation of 2-cyano-6-hydroxybenzothiazole, and this is recycled back to luciferin by condensation with cysteine. In this work, we suggest a mechanism for this transformation that operates under mild conditions that are similar to in vivo environments (i.e. biomimetic); the rate-determining step consists of an intermolecular nucleophilic attack from the cysteine thiolate on the nitrile, catalysed by a specific base, followed by a complex sequence of intramolecular reactions which are highly dependent on the medium pH.

Synthesis of the Peptide Ac-Wahx-KTTKS and Evaluation of the Ability to Induce In Vitro Collagen Synthesis.

In this work, we report the synthesis of a peptide analogue of the KTTKS, termed Ac- Wahx-KTTKS and evaluate its cytotoxicity and role in biosynthesis of collagen for future application in skin aging. The peptide was obtained with purity higher than 97.5%. In the cytotoxicity assay, we observed non-toxic effects for Ac-WAhx-KTTKS at concentrations below 600 µM for HaCaT and 500 µM for HepG2 cells, respectively. After 24 and 48 h it was possible to observe significant changes in collagen synthesis in the groups treated with various concentrations of the peptide. In conclusion, the Ac-Wahx- KTTKS peptide increased collagen synthesis in fibroblasts by 80% and it is a promising candidate for improving skin aging.

[Up-to-date on the treatment of benign prostatic hyperplasia. Which adenoma to treat and how to do it?]. / Actualités sur la prise en charge de l'hyperplasie bénigne de la prostate. Quel adénome traiter et comment ?

Benign prostatic hyperplasia is a state of the nature rather than a disease. It affects mainly men over 50 years and represents a public health problem. A literature review on the therapeutic management of benign prostatic hyperplasia was carried out from a selection of publications with the highest level of evidence. Medical treatment is based on herbal medicine, alpha-blockers and 5-alpha-reductase inhibitors. Surgical treatment is used in case of complications or failure of medical management. Surgical options are numerous. Transurethral prostate resection and prostate adenomectomy are the most usual procedures. Due to their significant morbidity, other less invasive procedures have recently been developed. The choice of treatment will depend on prostate volume and anatomy and patient's comorbidities.

Avaliações fonológicas: análise das palavras de maior ocorrênciaconsiderando o vocabulário e a classe de sons / Phonological assessments: analysis of the most frequent words considering the vocabulary and sound class / Evaluaciones fonológicas: análisis de las palabras más frecuentes teniendo en cuenta el vocabulario y la clase de sonido

O objetivo do estudo foi analisar as palavras selecionadas como mais frequentes entre quatro avaliações fonológicas disponíveis no Português Brasileiro e, destas, verificar quais fazem parte do vocabulário básico das crianças e as classes de sons de maior ocorrência. Analisou-se as palavras que compõem os testes AFC, ABFW, REALFA e AVALIE, sendo consideradas como mais frequentes as que ocorreram em, no mínimo, três dos quatro testes. Das palavras analisadas, a maioria faz parte do vocabulário básico das crianças; já com relação às classes de sons, estas, no geral, seguiram a ordem de aquisição fonológica. Assim, os avaliadores devem estar atentos para que seja possível verificar naavaliação todos os fonemas em todas as suas posições. Além disso, o terapeuta tem uma essencial função na seleção das palavras-estímulos visando o posterior sucesso no tratamento fonoaudiológico...

The aim of this study was to analyze the selected words as more frequent among four phonological assessments available in Brazilian Portuguese, and of these, check which words do part of the basicvocabulary of children and the sound classes of greater occurrence. We analyzed the words that make up the AFC tests, ABFW, REALFA and AVALIE, being considered as the most frequent occurring in atleast three of the four tests. Of the words analyzed, most part belongs to basic vocabulary of children, as with respect to classes of sounds, they, in general, followed the order of phonological acquisition. Thus, the evaluators should be aware that you can verify in evaluating all the phonemes in all positions. In addition, the therapist has a key role in the selection of stimulus words targeting the later success in speech therapy...

El objetivo de este estudio fue analizar las palabras seleccionadas como más frecuente entre cuatro evaluaciones fonológicas disponibles en portugués de Brasil, y de éstas, ver, las que forman parte delvocabulario básico de los niños y las clases de sonido de mayor ocurrencia. Se analizaron las palabras que componen las pruebas AFC, ABFW, REALFA y AVALIE, siendo consideradas como más frecuenteslas que ocurrieron en al menos tres de las cuatro pruebas. De las palabras analizadas, la mayoría es parte del vocabulario básico de los niños. Con respecto a la clase de sonidos, estas, en general, siguieronla orden de adquisición fonológica. Por lo tanto, los evaluadores deben estar atentos para que se pueda verificar, en la evaluación, todos los fonemas en todas las posiciones. Además, el terapeuta tiene un papelclave en la selección de las palabras-estímulo para el posterior éxito en el tratamiento fonoaudiológico...

Accelerated dendritic cell differentiation from migrating Ly6C(lo) bone marrow monocytes in early dermal West Nile virus infection.

No study has investigated the participation of Ly6C(+) monocytes in the earliest phase of skin infection with the mosquito-borne West Nile virus. In a novel murine model mimicking natural dermal infection, CCL2-dependent bone marrow (BM)-derived monocyte migration, differentiation into Ly6C(+) dendritic cells (DC), and accumulation around dermal deposits of infected fibroblasts by day 1 postinfection were associated with increasing numbers of monocyte-derived TNF/inducible NO synthase-producing DC by day 2 postinfection in draining auricular lymph nodes (ALN). Adoptive transfer demonstrated simultaneous migration of bone marrow-derived Ly6C(lo) monocytes to virus-infected dermis and ALN, where they first become Ly6C(hi) DC within 24 h and then Ly6C(lo) DC by 72 h. DC migration from the infected dermis to the ALN derived exclusively from Ly6C(lo) BM monocytes. This demonstrates that Ly6C(hi) and Ly6C(lo) BM-derived monocytes have different fates in vivo and suggests that BM may be a reservoir of preinflammatory monocytes for rapid deployment as inflammatory DC during virus infection.

Anatomia do plexo braquial de macaco-barrigudo (Lagothrix lagothricha) / Anatomy of the brachial plexus of the Woolly-Monkey (Lagothrix lagothricha

The woolly-monkey (Lagothrix lagothricha) is an antropoid belonging to the Atelidae Family which includes the largest neotropical primates. A female cadaver woolly-monkey was fixed in a 10 percent formaldehyde solution and dissected using a stereoscopic magnifying glass and photodocumented. The brachial plexus originated from the spinal nerves C5 to C8 and T1, forming the cranial, medium, and caudal stems, from which derived the peripheral nerves; those nerves had similar origin and innervation area when compared to plexuses from other primates, with the exception of the musculocutaneous nerve that crossed the coracobraquial muscle. Data from studies with brachial plexus from primates allow the access to valuable information regarding the morphology of those animals, and could also assist in the establishment of anatomical parameters among species, which could then contribute to anesthetic procedures and injury treatments.

O macaco-barrigudo (Lagothrix lagothricha) é um antropóide pertencente à Família Atelidae que possui os maiores primatas neotropicais. Um cadáver fêmea de macaco-barrigudo foi fixado com solução de formaldeído a 10 por cento, posteriormente dissecado com o auxílio de lupa estereoscópica e fotodocumentado. O plexo braquial originou-se dos nervos espinhais C5 a C8 e T1, formando os troncos cranial, médio e caudal, dos quais derivaram os nervos periféricos que se assemelharam na origem e no território de inervação com os plexos de outros primatas, com exceção do nervo musculocutâneo que atravessou o músculo coracobraquial. Pesquisas sobre o plexo braquial de primatas fornecem dados que disponibilizam o acesso a informações valiosas sobre a morfologia destes animais e auxiliam no estabelecimento de parâmetros anatômicos entre as espécies, contribuindo também no tratamento de injúrias e procedimentos anestésicos.

Solution phase synthesis of a combinatorial library of chalcones and flavones as potent cathepsin V inhibitors.

Cathepsin V is a papain-like cysteine protease. It is involved in the control of human T cells (responsible for cell immunity), and presents the largest elastolytic activity among the proteolytic enzymes. Therefore, cathepsin V is a potential molecular target for the treatment of atherosclerosis. In the present work, natural flavonoids were screened against cathepsin V, and two flavones were identified as potent inhibitors of cathepsin V. On the basis of this result, a combinatorial library of chalcones and flavones was prepared, in solution phase employing a scavenger reagent, and fully evaluated.

Selenium and aflatoxin levels in raw Brazil nuts from the Amazon basin.

Whereas selenium (Se) is an important antioxidant in human metabolism to prevent cancer, aflatoxins are highly carcinogenic. Brazil nuts from Eastern and Western Amazon regions were evaluated to find any relationship between Se and aflatoxins levels. A total of 80 (in-shell and shelled) nuts samples were collected directly from different forest sites and analyzed for Se by atomic emission spectrometry and aflatoxins by liquid chromatography tandem mass spectrometry. The limit of quantitation (LOQ) for Se was 2.0 mg/kg, and LOQ for total aflatoxins was 0.390 microg/kg. Nut Se levels from the Eastern region were higher than the Western, in addition to the aflatoxins. The moisture content (mc) and water activity (aw) of the raw nuts from the two regions did not present a significant difference, for either in-shell or shelled. The mc was 24.5% (minimum of 20.1% and maximum of 30.4%) and 22.1% (minimum of 14.6% and maximum of 28.9%) and a w of 0.85 for both regions. Further studies need to be carried out to discover the role of Se on fungi growth stress and aflatoxin production mechanisms.