Evaluation of Information Theoretic Network Meta-analysis to Rank First-Line Anticancer Regimens for Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer.

Importance: Hormone receptor-positive, ERBB2 (formerly HER2/neu)-negative metastatic breast cancer (HR-positive, ERBB2-negative MBC) is treated with targeted therapy, endocrine therapy, chemotherapy, or combinations of these modalities; however, evaluating the increasing number of treatment options is challenging because few regimens have been directly compared in randomized clinical trials (RCTs), and evidence has evolved over decades. Information theoretic network meta-analysis (IT-NMA) is a graph theory-based approach for regimen ranking that takes effect sizes and temporality of evidence into account. Objective: To examine the performance of an IT-NMA approach to rank HR-positive, ERBB2-negative MBC treatment regimens. Data Sources: HemOnc.org, a freely available medical online resource of interventions, regimens, and general information relevant to the fields of hematology and oncology, was used to identify relevant RCTs. Study Selection: All primary and subsequent reports of RCTs of first-line systemic treatments for HR-positive, ERBB2-negative MBC that were referenced on HemOnc.org and published between 1974 and 2019 were included. Additional RCTs that were evaluated by a prior traditional network meta-analysis on HR-positive, ERBB2-negative MBC were also included. Data Extraction and Synthesis: RCTs were independently extracted from HemOnc.org and a traditional NMA by separate observers. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for NMA with several exceptions: the risk of bias within individual studies and inconsistency in the treatment network were not assessed. Main Outcomes and Measures: Regimen rankings generated by IT-NMA based on clinical trial variables, including primary end point, enrollment number per trial arm, P value, effect size, years of enrollment, and year of publication. Results: A total of 203 RCTs with 63 629 patients encompassing 252 distinct regimens were compared by IT-NMA, which resulted in 151 rankings as of 2019. Combinations of targeted and endocrine therapy were highly ranked, especially the combination of endocrine therapy with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. For example, letrozole plus palbociclib was ranked first and letrozole plus ribociclib, third. Older monotherapies that continue to be used in RCTs in comparator groups, such as anastrozole (251 of 252) and letrozole (252), fell to the bottom of the rankings. Many regimens gravitated toward indeterminacy by 2019. Conclusions and Relevance: In this network meta-analysis study, combination therapies appeared to be associated with better outcomes than monotherapies in the treatment of HR-positive, ERBB2-negative MBC. These findings suggest that IT-NMA is a promising method for longitudinal ranking of anticancer regimens from RCTs with different end points, sparse interconnectivity, and decades-long timeframes.

Morfogênese de braquiárias sob estresse hídrico / Morphogenesis of Brachiarias species under water stress

Objetivou-se avaliar Urochloa spp. submetida a duas situações de estresse hídrico: déficit e alagamento. As forrageiras estudadas foram: U. humidicola cv. Tully, U. humidicola cv. Llanero, U. brizantha cv. BRS Piatã, U. brizantha cv. Xaraés, U. decumbens cv. Basilisk e U. ruziziensis cv. Kenedy, e os parâmetros avaliados foram relacionados às características estruturais e morfogênicas. O trabalho foi desenvolvido em casa de vegetação pertencente à Unidade Universitária de Aquidauana. Os tratamentos consistiram em diferentes condições de umidade do solo: 50 e 80% da capacidade de retenção de umidade do solo, e lâminas de 0cm, 1cm e 5cm de água acima do solo, com quatro repetições, em delineamento inteiramente ao acaso. O modelo considerou o efeito de umidade do solo para cada espécie forrageira a 5% de significância. As características estruturais e morfogênicas do capim-tully não foram afetadas pelas diferentes condições hídricas aqui avaliadas. O capim-llanero não reagiu ao alagamento. O capim-piatã foi tolerante às condições de déficit hídrico e apresentou mecanismos de adaptação ao alagamento. A U. decumbens cv. Basilisk apresentou respostas adaptativas que melhoram sua tolerância ao alagamento. A U. ruziziensis cv. Kenedy apresentou-se inapta às condições de alagamento e de déficit hídrico.(AU)

The aim of this study was to evaluate braquiarias submitted to two situations of water stress: deficit and flood. The studied forages were: U. humidicola cv. Tully, U. humidicola cv. Llanero, U. brizantha cv. BRS Piatã, U. brizantha cv. Xaraés, U. decumbens cv. Basilisk and U. ruziziensis cv. Kenedy, and the parameters evaluated were related to the structural and morphogenic characteristics. The work was carried out in a greenhouse at the University Unit of Aquidauana. The treatments consisted of different soil moisture conditions: 50 and 80% of the moisture retention capacity of the soil, and slides of 0cm, 1cm and 5cm of water above the soil, with four replications, in a completely randomized design. The model considered the effect of soil moisture for each forage species at 5% of significance. The structural and morphogenic characteristics of grass-tully were not affected by the different water conditions evaluated here. The grass-llanero did not react to flooding. The grass-piatã was tolerant to water deficit conditions and presented adaptation to flooding. The U. decumbens cv. Basilisk presented adaptive responses that improved its tolerance to flooding. The U. ruziziensis cv. Kenedy was unfit for flood and water deficit conditions.(AU)

Bioglass implant-coating interactions in synthetic physiological fluids with varying degrees of biomimicry.

Synthetic physiological fluids are currently used as a first in vitro bioactivity assessment for bone grafts. Our understanding about the interactions taking place at the fluid-implant interface has evolved remarkably during the last decade, and does not comply with the traditional International Organization for Standardization/final draft International Standard 23317 protocol in purely inorganic simulated body fluid. The advances in our knowledge point to the need of a true paradigm shift toward testing physiological fluids with enhanced biomimicry and a better understanding of the materials' structure-dissolution behavior. This will contribute to "upgrade" our vision of entire cascades of events taking place at the implant surfaces upon immersion in the testing media or after implantation. Starting from an osteoinductive bioglass composition with the ability to alleviate the oxidative stress, thin bioglass films with different degrees of polymerization were deposited onto titanium substrates. Their biomineralization activity in simulated body fluid and in a series of new inorganic-organic media with increasing biomimicry that more closely simulated the human intercellular environment was compared. A comprehensive range of advanced characterization tools (scanning electron microscopy; grazing-incidence X-ray diffraction; Fourier-transform infrared, micro-Raman, energy-dispersive, X-ray photoelectron, and surface-enhanced laser desorption/ionization time-of-flight mass spectroscopies; and cytocompatibility assays using mesenchymal stem cells) were used. The information gathered is very useful to biologists, biophysicists, clinicians, and material scientists with special interest in teaching and research. By combining all the analyses, we propose herein a step forward toward establishing an improved unified protocol for testing the bioactivity of implant materials.

Amino acid deprivation using enzymes as a targeted therapy for cancer and viral infections.

INTRODUCTION: Amino acid depletion in the blood serum is currently being exploited and explored for therapies in tumors or viral infections that are auxotrophic for a certain amino acid or have a metabolic defect and cannot produce it. The success of these treatments is because normal cells remain unaltered since they are less demanding and/or can synthesize these compounds in sufficient amounts for their needs by other mechanisms. Areas covered: This review is focused on amino acid depriving enzymes and their formulations that have been successfully used in the treatment of several types of cancer and viral infections. Particular attention will be given to the enzymes L-asparaginase, L-arginase, L-arginine deiminase, and L-methionine-γ-lyase. Expert opinion: The immunogenicity and other toxic effects are perhaps the major limitations of these therapies, but they have been successfully decreased either through the expression of these enzymes from other organisms, recombination processes, pegylation of the selected enzymes or by specific mutations in the proteins. In 2006, FDA has already approved the use of L-asparaginase in the treatment of acute lymphoblastic leukemia. Other enzymes and in particular L-arginase, L-arginine deiminase, and L-methioninase have been showing promising results in vitro and in vivo studies.

Exigências de energia de borregas mestiças alimentadas com níveis crescentes de concentrado na dieta / Energy requirements of crossbreed ewe lambs fed with increasing dietary levels of concentrate

Objetivou-se estimar as exigências energéticas de borregas mestiças confinadas, alimentadas com níveis crescentes de concentrado na dieta. Foram avaliadas 36 borregas, com peso corporal inicial de 23,7±3,67kg. Seis animais foram abatidos no início do experimento para obtenção dos valores do grupo referência. Os demais (30 animais) foram distribuídos em cinco tratamentos: mantença (alimentação restrita com feno de capim Tifton) e suplementados com níveis crescentes de concentrado (20, 40, 60 e 80%) em base de matéria seca (seis animais por tratamento). As borregas foram abatidas quando atingiram 37,70±9,89kg. Os níveis de concentrado influenciaram a eficiência de utilização da energia metabolizável para mantença (km) e consequentemente as exigências diárias de energia metabolizável para mantença. A exigência de energia líquida para mantença de borregas mestiças em crescimento é 57 kcal/PCJ0,75/dia, em que PCJ é o peso corporal em jejum. As borregas com 20kg apresentaram exigência de energia líquida para 100g de ganho de peso diário de 465kcal/dia. As borregas com 40kg de peso corporal exigiram 930kcal/dia de energia líquida para o mesmo ganho. A exigência líquida para mantença de borregas pode ser estimada pela equação: ELm (Mcal/dia) = 0,057* PCJ0,75. A exigência líquida de energia para ganho de borregas mestiças (Mcal/dia) pode ser estimada a partir da equação: ELg = 0,524 x PVJ0,75 x GPCVZ1,21, em que GPCVZ é o ganho de peso do corpo vazio. As dietas influenciam as eficiências de usos da energia metabolizável para mantença (km) e ganho (kg).(AU)

The aim of this study was to estimate the energy requirements of crossbreed ewe lambs in a feedlot fed with increasing levels of concentrate in the diet. 36 ewe lambs were evaluated with initial body weight of 23.7±3.67kg. Six animals were slaughtered at the beginning of the experiment to obtain the reference group values. Animals (30) were distributed in five treatments: maintenance (feed restricted with Tifton grass hay) and those supplemented with increasing dietary levels of concentrate (20, 40, 60 and 80%) on a dry matter basis (six animals per treatment). The ewe lambs were slaughtered when they reached 37.70±9.89kg. The concentrate levels influenced the utilization efficiency of metabolizable energy for maintenance (km) and consequently the daily requirements of metabolizable energy for maintenance. The net energy requirements for maintenance of crossbred lambs in growth is 57kcal/FCW 0.75/day, where FCW is body weight on fasting. The ewe lambs with 20kg presented net energy requirement for 100g daily weight gain of 465kcal/day. The ewe lambs with 40kg of body weight required 930 kcal/day of net energy for the same gain. The net energy requirement for maintenance of ewe lambs can be estimated by the equation: NEm (Mcal/day) = 0.057 * FCW0.75. The net energy requirement for crossbred ewe lambs gain (Mcal/day) can be estimated from the equation: NEg (Mcal/day) = 0.524*FCW 0.75*GEBW1.21, where GEBW represented gain empty body weight. Diets affect the efficiencies of uses of metabolizable energy for maintenance (km) and gain (kg).(AU)

Antimitotic and antimutagenic action of the Hymenaea stigonocarpa bark on dividing cells / Ação antimitótica e antimutagênica do ritidoma de Hymenaea stigonocarpa Mart ex Hayne na divisão celular

Abstract The objective of this study was to evaluate the action of Hymenaea stigonocarpa bark hydroalcoholic extract against a mutagenic compound using A. cepa meristematic root cells as a test system. The treatment groups were: Negative Control (NC) – distilled water; Positive Control (PC) – paracetamol at a concentration of 0.008 mg/mL, Jatoba Control (JC) – aqueous fraction jatobá-do-cerrado at 0.5 or 1.0 or 1.5 mg/mL, and Simultaneous Treatment (ST) - jatobá-do-cerrado aqueous fraction at a concentration of 0.5 or 1.0 or 1.5 mg/mL associated with paracetamol solution at a concentration of 0.008 mg/mL. All groups were analyzed at 24 and 48 h. Five onion bulbs (five replications) were used for each treatment group. The root tips were fixed in Carnoy and slides prepared by the crush technique. Cells were analyzed throughout the cell cycle, totaling 5,000 for each treatment group at each exposure time. Mitotic indices were subjected to statistical analysis using the chi-square test (p<0.05). From the results it was found that the ST group, at the three concentrations, significantly potentiated the antiproliferative effect of the test system cells when compared to PC, NC and TJ at the three concentrations. Furthermore, the three ST concentrations significantly reduced the number of cell aberrations when compared to the number of aberrant cells obtained for the PC, demonstrating antimutagenic action on the A. cepa test system cells.

Resumo O objetivo do presente trabalho foi avaliar a ação do extrato hidroalcólico do ritidoma de Hymenaea stigonocarpa frente a um composto mutagênico, utilizando como sistema teste as células meristemáticas de raízes de A. cepa. Os grupos tratamentos avaliados foram: Controle Negativo (CN) – água destilada; Controle Positivo (CP) – paracetamol na concentração de 0,008 mg/mL, Controle Jatobá (CJ) – fração aquosa de jatobá-do-cerrado na concentração de 0,5 ou 1,0 ou 1,5 mg/mL, e Tratamento Simultâneo (TS) – fração aquosa de jatobá-do-cerrado na concentração de 0,5 ou 1,0 ou 1,5 mg/mL associada a solução de paracetamol na concentração de 0,008 mg/mL. Todos os grupos foram analisados nos tempos de 24 e 48 h. Para cada grupo tratamento cinco bulbos de cebolas (cinco repetições) foram utilizados. As radículas foram fixadas em Carnoy e as lâminas preparadas pela técnica de esmagamento. Analisaram-se células em todo ciclo celular, totalizando 5.000 para cada grupo tratamento em cada tempo de exposição. Os índices mitóticos obtidos foram submetidos à análise estatística do Qui-quadrado (p<0,05). A partir dos resultados verificou-se que o grupo TS, nas três concentrações, potencializou o efeito antiproliferativo significativo as células do sistema teste quando comparado ao CP, CN e TJ nas três concentrações. Ainda, o TS nas três concentrações reduziu de forma significativa o número de aberrações celulares quando comparado com o número de células aberrantes obtidas para o CP, demonstrando ação antimutagênica as células do sistema teste A. cepa.

Predicting difficult laryngoscopy using ultrasound measurement of distance from skin to epiglottis.

BACKGROUND: Unpredicted difficult intubation can have severe consequences, and it is a significant source of morbidity and mortality. Although recent studies indicate that specific ultrasonography (US) measurements may be predictors of difficult laryngoscopy, their use is still limited, and its quantification is missing. The purpose of this prospective observational study is to evaluate the use of US-measured distance from skin to epiglottis (DSE) for difficult laryngoscopy prediction. METHODS: In a double-blind study, standard preintubation, screening tests, and DSE were obtained from 74 adult patients requiring endotracheal intubation. The relationship between difficult laryngoscopy and DSE was evaluated using a t test. A comparative analysis of its predictive performance with common clinical preintubation screening tests was performed using bootstrapping. RESULTS: We found that increasing DSE is strongly associated with difficult laryngoscopy (P < .001, 2-sided t test). We showed that a cutoff value of 27.5 mm was able to predict difficult laryngoscopy with an accuracy of 74.3%, a sensitivity of 64.7%, and a specificity of 77.1%. CONCLUSIONS: Our work demonstrates that the DSE can be effectively used to predict difficult laryngoscopy. Moreover, combining DSE with the modified Mallampati score in a decision tree significantly improves the predictive power over either test alone.

Eficiência produtiva ao desmame de vacas Nelore criadas no pantanal / Productive efficiency to weaning of Nellore cows raised in the pantanal

O trabalho objetivou avaliar a eficiência produtiva de vacas ao desmame de acordo com seu tamanho (peso) e estimar correlação fenotípica entre as características peso do bezerro ao desmame (PBD), peso da vaca ao desmame do bezerro (PVD) e relação desmame (RD = PBD/ PVD) de animais da raça Nelore criados no Pantanal de Mato Grosso do Sul. Foram utilizadas 706 observações para pares de dados de pesos de vacas e de bezerros da raça Nelore ao desmame criados em regime de pastejo. Foram formados seis grupos com base no peso de vaca ao desmame (GPVD) a partir dos desvios (40,73kg) de peso em relação à média geral do rebanho (420,56kg). Os grupos de vacas com menores pesos obtiveram maiores RD. As correlações fenotípicas entre PVD e PBD variaram de 0,05 a 0,26, enquanto para PVD e RD as correlações foram negativas e com variação de 0,11 a 0,25. As correlações fenotípicas entre PBD e RD apresentaram-se positivas e de alta magnitude (0,91 a 0,98). As maiores eficiências produtivas foram determinadas para vacas de pequeno a médio porte (327,20 a 438,62kg), além de estas serem menos exigentes quanto a nutrientes digestíveis totais (NDT). A seleção de vacas de tamanho médio (379, 83 a 461,29kg) apresenta-se mais vantajosa por gerar menor custo de mantença que as vacas maiores e produzir bezerros mais pesados que as vacas menores.

The study aimed to evaluate the productive efficiency of cow at weaning according to their size (weight) and estimated phenotypic correlation between the characteristics of weaning weight of calf and cow and weaning ratio of Nellore cattle raised in the Pantanal of Mato Grosso do Sul. 706 observations were used to weight data pairs of cow and calves at weaning. Six groups were formed based on the weight of cow at weaning from deviations (40.73kg) of weight in relation to the overall mean of the herd (420.56kg). The groups of cows with lower weaning weight have the highest weaning ratio. Phenotypic correlations of cow weight at weaning and weaning of calf weight ranged from 0.05 to 0.26, cow weight at weaning and weaning ratio were negative correlations ranging from -0.11 to -0.25. Phenotypic correlations between weaning of calf and weaning ratio were positive and of high magnitude (0.91 to 0.98). The highest efficiencies were determined for cows between 327.20 and 438.62kg, and are less demanding on total digestible nutrients (TDN). A selection of medium sized cows (379, 83 to 461.29kg) appears more interesting because it has lower maintenance costs than larger cows, and produces heavier calves than the smaller cows.

Capim-piatã adubado com fontes de fósforo de diferente solubilidade em água / Piata palisadegrass fertilized with different sources of phosphorus for solubility in water

The development of piatã grass fertilized with phosphorus sources with different solubilities in water was evaluated. The experiment was developed in the unit of Aquidauana of UEMS, MS, from February to August, 2012. Four treatments were evaluated: control (without phosphorus fertilization), slow solubility, fast solubility (readily available), and mixed solubility sources of phosphorus (FH Pasture(r)). It was adopted a randomized blocks design with four blocks and four replicates in a total of 16 pastures (0.5 ha each one). Measurements were performed weekly to evaluate structural characteristics and morphogenic variables of the plants. Data were submitted to a variance analysis according to the model. When necessary, the means of treatments with different phosphorus fertilizer sources were compared with the control using the Dunnett test and with other treatments by using student's t test. The significance level of 5% was adopted in all analysis. No significant effect was observed (P 0.05) in the evaluated traits in the first year of the experiment.

Colonic patch and colonic SILT development are independent and differentially regulated events.

Intestinal lymphoid tissues have to simultaneously ensure protection against pathogens and tolerance toward commensals. Despite such vital functions, their development in the colon is poorly understood. Here, we show that the two distinct lymphoid tissues of the colon-colonic patches and colonic solitary intestinal lymphoid tissues (SILTs)-can easily be distinguished based on anatomical location, developmental timeframe, and cellular organization. Furthermore, whereas colonic patch development depended on CXCL13-mediated lymphoid tissue inducer (LTi) cell clustering followed by LTα-mediated consolidation, early LTi clustering at SILT anlagen did not require CXCL13, CCR6, or CXCR3. Subsequent dendritic cell recruitment to and gp38(+)VCAM-1(+) lymphoid stromal cell differentiation within SILTs required LTα; B-cell recruitment and follicular dendritic cell differentiation depended on MyD88-mediated signaling, but not the microflora. In conclusion, our data demonstrate that different mechanisms, mediated mainly by programmed stimuli, induce the formation of distinct colonic lymphoid tissues, therefore suggesting that these tissues may have different functions.

Nutritional diversity of agricultural and agro-industrial by-products for ruminant feeding / Diversidade nutricional de subprodutos agrícola e agro-industrial para alimentação de ruminantes

Fifty-seven by-products were collected from regions throughout Brazil. Chemical composition, in vitro neutral detergent fiber digestibility (IVNDFD), and total digestible nutrients (TDN) were determined with the objective of grouping by-products with similar nutritional characteristics. The by-products belonging to group one (G1) presented the highest content of neutral detergent fiber exclusive of ash and nitrogenous compounds [aNDFom(n)] and lowest energy content, with 42.5% and 38.8% of IVNDFD and TDN, respectively. A new cluster analysis was carried in order to better characterize G2 by-products, six subgroups (SGs) were established (SG1 to SG6). SG1 by-products had the highest and the lowest values for lignin and TDN, respectively. SG2 by-products had the highest aNDFom(n) value, with TDN and IVNDFD values greater than 600 and 700g/kg, respectively, and crude protein (CP) value below 200g/kg in dry matter (DM). Among all the subgroups, SG3 had the highest TDN (772g/kg) and IVNDFD (934g/kg) values and the lowest lignin (23g/kg in DM) value. The ether extract was what most influenced the hierarchical establishment of residual grouping in SG4. SG5 by-products had the highest concentration of non-fibrous carbohydrate. Different from the other subgroups, SG6 by-products had the highest value of available CP.

Cinquenta e sete subprodutos foram coletados de diferentes regiões do Brasil. Foram determinados a composição química, a digestibilidade in vitro da fibra em detergente neutro (DIVFDN) e os nutrientes digestíveis totais (NDT), com o objetivo de agrupar os subprodutos com características nutricionais semelhantes. Os subprodutos pertencentes a um grupo (G1) apresentaram maior conteúdo de fibra em detergente neutro corrida para cinzas e compostos nitrogenados (FDNcp) e menor teor energético, e tinham 42,5% e 38,8% de DIVFDN e NDT, respectivamente. Uma nova análise de cluster foi realizada no intuito de melhor caracterizar os subprodutos do G2; seis subgrupos (SG) foram estabelecidos (SG1 a SG6). Os subprodutos SG1 tiveram os maiores e os menores valores de lignina e NDT, respectivamente. Os subprodutos SG2 tiveram o maior valor de FDNcp, com valores de NDT e DIVFDN acima de 600 e 700g/kg, respectivamente, e de proteína bruta (PB) abaixo de 200g/kg de matéria seca (MS). Entre todos os subgrupos, SG3 tiveram os maiores valores de NDT (772g/kg) e DIVFDN (934g/kg) e o menor valor de lignina (23g/kg de MS). O extrato etéreo foi o que mais influenciou no estabelecimento hierárquico de agrupamento em SG4. Os subprodutos SG5 tinham maior concentração de carboidratos não fibriosos. Diferentemente dos demais subgrupos, subprodutos SG6 tinham o valor mais elevado de PB disponível.

Systemic in vivo lentiviral delivery of miR-15a/16 reduces malignancy in the NZB de novo mouse model of chronic lymphocytic leukemia.

Similar to human chronic lymphocytic leukemia (CLL), the de novo New Zealand Black (NZB) mouse model has a genetically determined age-associated increase in malignant B-1 clones and decreased expression of microRNAs miR-15a and miR-16 in B-1 cells. In the present study, lentiviral vectors were employed in vivo to restore miR-15a/16, and both the short-term single injection and long-term multiple injection effects of this delivery were observed in NZB. Control lentivirus without the mir-15a/16 sequence was used for comparison. We found that in vivo lentiviral delivery of mir-15a/16 increased miR-15a/16 expression in cells that were transduced (detected by GFP expression) and in sera when compared with control lentivirus treatment. More importantly, mice treated with the miR-expressing lentivirus had decreased disease. The lentivirus had little systemic toxicity while preferentially targeting B-1 cells. Short-term effects on B-1 cells were direct effects, and only malignant B-1 cells transduced with miR-15a/16 lentivirus had decreased viability. In contrast, long-term studies suggested both direct and indirect effects resulting from miR-15a/16 lentivirus treatment. A decrease in B-1 cells was found in both the transduced and non-transduced populations. Our data support the potential use of systemic lentiviral delivery of miR-15a/16 to ameliorate disease manifestations of CLL.

Gastroprotective activity of Zanthoxylum rhoifolium Lam. in animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: The stem barks of Zanthoxylum rhoifolium Lam. (Rutaceae), locally known as "mamica de cadela", are popularly used in dyspepsies, stomachic, tonic, antitumoral, antipyretic and are used in treating flatulence and colic. The objective of this study was to evaluate the gastroprotective effect of the ethanolic extract of Zanthoxylum rhoifolium (EEZR) stem barks in acute gastric lesion models, investigating their possible mechanisms. MATERIALS AND METHODS: Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The gastroprotective action of EEZR was analyzed in the absolute ethanol, HCl/ethanol and indomethacin-induced gastric lesion models in mice, hypothermic-restraint stress, and ischemia/reperfusion in rats. In the investigation of the gastroprotective mechanisms of EEZR, the participation of the NO-synthase pathway, ATP-sensitive potassium channels (K(ATP)), the levels of the non-protein sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced gastric mucosa lesion model and the quantification of the gastric mucus and the antisecretory activity through pylorus ligature model in rats were analyzed. RESULTS: The animals did not present any signs of acute toxicity for the EEZR (up to the 4 g/kg dose, po), and it was not possible to calculate the DL(50). EEZR (125-500 mg/kg) exhibited a significant gastroprotective effect in absolute ethanol, HCl/ethanol, hypothermic-restraint stress, and ischemia/reperfusion-induced gastric lesion models. EEZR (250 and 500 mg/kg) exhibited still a gastroprotective activity in the indomethacin-induced ulcer model. Gastroprotection of EEZR was significantly decreased in pre-treated mice with l-NAME or glibenclamide, the respective nitric oxide synthase and K(ATP) channels inhibitors. Our studies revealed that EEZR (500 mg/kg) prevented the decrease of the non-protein sulfhydril groups (NP-SH) and increased the catalase levels in ethanol-treated animals. Furthermore, the extract (500 mg/kg) significantly increased the mucus production, however, the gastric secretion parameters (volume, [H(+)], pH) did not show any alteration. CONCLUSIONS: Our results indicate that the ethanolic extract of Zanthoxylum rhoifolium exhibits a significant gastroprotection, because it inhibits the formation of gastric lesions using different models. The release of the nitric oxide, the opening of the K(ATP) channels, the participation of the non-protein sulfhydril groups (NP-SH), catalase and the increase of mucous secretion seem to be involved in the gastroprotection activity of the EEZR. Nevertheless, this activity does not seem to be related to antisecretory mechanisms.

Consumo, digestibilidade total, produção de proteína microbiana e balanço de nitrogênio em dietas para ruminantes de subprodutos / Intake, total digestibility, microbial protein production, and the nitrogen balance in ruminant diets based on agricultural and agro-industrial by-products

Avaliaram-se os efeitos da inclusão da fonte - subproduto do cacau, mandioca-casca, mandioca-caule e farelo de glúten de milho - e da proporção - 10 e 30 por cento - de subprodutos, em substituição parcial à silagem de milho sobre consumo, digestibilidade dos nutrientes, produção de proteína microbiana, balanço de nitrogênio, predição das frações digestíveis e nutrientes digestíveis totais. Os consumos de matéria seca e de fibra em detergente neutro foram influenciados pela fonte de subproduto. A fonte de subproduto influiu na digestibilidade do extrato etéreo e dos carboidratos não fibrosos. O subproduto farelo de glúten de milho apresentou valor energético 17 por cento maior do que a da silagem de milho, enquanto os da mandioca-casca, da mandioca-caule e do cacau apresentaram valores energéticos 10, 19 e 38 por cento menores do que o valor observado para silagem de milho. A fonte e o nível de subproduto não influíram na excreção urinária de derivados de purinas totais, de purinas absorvidas e de nitrogênio microbiano, e na eficiência microbiana. A fonte do subproduto influenciou a ingestão, a excreção nas fezes e na urina dos compostos nitrogenados e o balanço de nitrogênio. O farelo de glúten de milho e a mandioca-casca podem substituir, parcialmente, os concentrados energéticos, sem prejuízos para consumo, digestibilidade, eficiência microbiana e retenção de nitrogênio.

The effects of inclusion of by-products (cocoa, cassava peel, cassava stalk, and corn gluten meal) and their levels (10 and 30 percent), replacing part of corn silage on intake, digestibility of nutrients, microbial protein production, nitrogen balance, prediction of digestible fractions, and total digestible nutrients were evaluated. The intakes of dry matter and neutral detergent fiber were affected by source of by-product, which affected the digestibility of ether extract and non-fibrous carbohydrates. The energy corn gluten meal was 17 percent higher than that of corn silage, while the values for cassava peel, cocoa, and cassava stalk were 10, 19, and 38 percent lower than the value for corn silage. The source and the level of by-product did not affect the urinary excretion of total purine, purine absorbed, microbial nitrogen, and microbial efficiency. The source of by-product affected intake, nitrogen compounds, excretion in feces and urine, and nitrogen balance. The corn gluten meal and cassava peel are by-products with potential to partly replace the energhetic concentrates, with no influence on the intake, digestibility, microbial efficiency, and nitrogen retention.

Colloid cyst of the third cerebral ventricle with an embryological remnant consistent with paraphysis cerebri in an adult human.

The histogenesis of colloid cysts of the third ventricle remains unsettled. Initial theories favored a neuroepithelial (paraphysis, ependyma, choroid plexus) origin and some investigators based on morphologic analysis have offered an alternative endodermal source. We report a case of colloid cyst of the third ventricle arising in association with a remnant which we believe corresponds to the paraphysis cerebri in man.

In vivo evaluation of highly macroporous ceramic scaffolds for bone tissue engineering.

During the last decades, different materials of both natural and synthetic origin have been developed with the aim of inducing and controlling osteogenic differentiation of mesenchymal stem cells (MSCs). In order for that to happen, it is necessary that the material to be implanted obey a series of requirements, namely: osteoconduction, biocompatibility, and biodegradability. Additionally, they must be low-priced, easy to produce, shape, and store. Hydroxyapatite (HA) is a well known ceramic with a composition similar to the mineral component of bone and is highly biocompatible and easy to obtain and/or process. On the other hand, collagen is the main structural protein present in the human body and bone. In this study, a polymer replication method was applied and a highly porous HA scaffold was produced. Collagen was later incorporated to improve the biological properties of the scaffold while resembling the bone composition. The scaffolds were characterized by means of scanning electron microscopy, Fourier transform infrared spectroscopy and energy dispersive spectroscopy. In vitro and in vivo testing was performed in all scaffolds produced. The goal of this study was to evaluate the in vivo osteogenic potential of MSCs from two different species seeded on the different HA basedporous scaffolds with collagen type I. The resultsindicate that all scaffolds exhibit relevant bone formation, being more prominent in the case of the HA scaffolds.

Uso de pinças ópticas para avaliação do potencial zeta de hemácias em EDTA, CPD-SAGM e estocadas / Use of optical tweezers for evaluation of szeta potential of red blood cells in EDTA, CPD-SAGM and stored in blood banks

A hemácia é carregada negativamente, principalmente devido ao ácido siálico que gera um potencial elétrico denominado Potencial Zeta que impede a aglutinação intravascular. Os testes de hemaglutinação na rotina transfusional, necessitam de substâncias potencializadoras, das quais muitas agem diminuindo o Potencial Zeta para se ter maior sensibilidade. Através da pinça óptica, ferramenta capaz de capturar células utilizando a luz, foi proposta uma metodologia para quantificar o potencial zeta e aplicar em hemácias coletadas com EDTA e estocadas em CPD-SAGM (visando avaliar alterações de cargas da membrana relacionadas a lesões de armazenamento. Os potenciais zeta em CPD-CAGM foram superiores (-14,8 mV) aos em EDTA (-7,9 mV) e decrescentes a partir do primeiro dia de armazenamento, estabilizando-se a partir da terceira semana com potencial zeta -7,6 mV. Hemácias com CPD-SAGM apresentaram potencial zeta maior, pois possivelmente este conservante evitou lesões mais significativas da membrana que poderiam alterar as cargas. A redução do potencial zeta no armazenamento pode ser consequência de enzimas liberadas de leucócitos lisados que tenham alterado as glicoforinas da membrana. A metodologia permitiu avaliar o potencial zeta em diferentes condições e poderá contribuir na padronização de técnicas de hemaglutinação com diferentes meios potencializadores e no melhor conhecimento das lesões de estocagem para fins transfusionais.

BNDb - Biomolecules Nucleus Database: an integrated proteomics and transcriptomics database

Proteomics correspond to the identification and quantitative analysis of proteins expressed in different conditions or life stages of a cell or organism. Methods used in proteomics analysis include mainly chromatography, two-dimensional electrophoresis and mass spectrometry. Data generated in proteomics analysis vary significantly, and to identify a protein it is often necessary to perform a series of experiments, comparing its results to those found in proteomics databases. Existing proteomics databases are usually related to only one type of experiment or represent processed results, not raw data. Therefore, proteomics researchers frequently have to resort to several data repositories in order to be able to perform the identification. In this paper, we propose an integrated proteomics and transcriptomics database that stores raw and processed data, which are indexed allowing them to be retrieved together or individually. The proposed database, dubbed BNDb for Biomolecules Nucleus Database, is implemented using an MySQL server and is being used to store data from the parasite Schistosoma mansoni, the scorpion Tittyus serrulatus and the spider Phoneutria nigriventer. The database construction uses a relational approach and data indexes. The data model proposed uses groups of tables for each data subtype, which store details regarding the experimental procedure as well as raw data, analysis results and associated publications. BNDb also stores transcriptomics data publicly available which are associated with identifications performed on new samples. By using BNDb, we expect not only to contribute to proteomics research but also to provide a useful service for the scientific community.

Ligand binding and signalling pathways of PTH receptors in sea bream (Sparus auratus) enterocytes.

Whole animal studies have indicated that Ca(2+) uptake by the gastrointestinal tract is regulated by the action of parathyroid hormone-related peptide (PTHrP) in teleost fish. We have characterised PTH receptors (PTHR) in piscine enterocytes and established, by using amino-terminal PTHrP peptides, the amino acid residues important for receptor activation and for stabilising the ligand/receptor complex. Ligand binding of (125)I-(1-35(tyr)) PTHrP to the membrane fraction of isolated sea bream enterocytes revealed the existence of a single saturable high-affinity receptor (K (D)=2.59 nM; B (max)=71 fmol/mg protein). Reverse transcription/polymerase chain reaction with specific primers for sea bream PTH1R and PTH3R confirmed the mRNA expression of only the later receptor. Fugu (1-34)PTHrP increased cAMP levels in enterocytes but had no effect on total inositol phosphate accumulation. The amino-terminal peptides (2-34)PTHrP, (3-34)PTHrP and (7-34)PTHrP bound efficiently to the receptor but were severely defective in stimulating cAMP in enterocyte cells indicating that the first six residues of piscine (1-34)PTHrP, although not important for receptor binding, are essential for activation of the adenylate cyclase/phosphokinase A (AC-PKA)-receptor-coupled intracellular signalling pathway. Therefore, PTHrP in teleosts acts on the gastrointestinal tract through PTH3R and the AC-PKA intracellular signalling pathway and might regulate Ca(2+) uptake at this site. Ligand-receptor binding and activity throughout the vertebrates appears to be allocated to the same amino acid residues of the amino-terminal domain of the PTHrP molecule.