The specificity of frutalin lectin using biomembrane models

Frutalin is a homotetrameric alpha-D-galactose (D-Gal)-binding lectin that activates natural killer cells in vitro and promotes leukocyte migration in vivo. Because lectins are potent lymphocyte stimulators, understanding the interactions that occur between them and cell surfaces can help to the action mechanisms involved in this process. In this paper, we present a detailed investigation of the interactions of frutalin with phospho- and glycolipids using Langmuir monolayers as biomembrane models. The results confirm the specificity of frutalin for D-Gal attached to a biomembrane. Adsorption of frutalin was more efficient for the galactose polar head lipids, in contrast to the one for sulfated galactose, in which a lag time is observed, indicating a rearrangement of the monolayer to incorporate the protein. Regarding ganglioside GM1 monolayers, lower quantities of the protein were adsorbed, probably due to the farther apart position of D-galactose from the interface. Binary mixtures containing galactocerebroside revealed small domains formed at high lipid packing in the presence of frutalin, suggesting that lectin induces the clusterization and the forming of domains in vitro, which may be a form of receptor internalization. This is the first experimental evidence of such lectin effect, and it may be useful to understand the mechanism of action of lectins at the molecular level. (C) 2010 Elsevier B.V. All rights reserved.

A pharmacokinetic-pharmacodynamic model for duodenal levodopa infusion

Objective Levodopa in presence of decarboxylase inhibitors is following two-compartment kinetics and its effect is typically modelled using sigmoid Emax models. Pharmacokinetic modelling of the absorption phase of oral distributions is problematic because of irregular gastric emptying. The purpose of this work was to identify and estimate a population pharmacokinetic- pharmacodynamic model for duodenal infusion of levodopa/carbidopa (Duodopa®) that can be used for in numero simulation of treatment strategies. Methods The modelling involved pooling data from two studies and fixing some parameters to values found in literature (Chan et al. J Pharmacokinet Pharmacodyn. 2005 Aug;32(3-4):307-31). The first study involved 12 patients on 3 occasions and is described in Nyholm et al. Clinical Neuropharmacology 2003:26:156-63. The second study, PEDAL, involved 3 patients on 2 occasions. A bolus dose (normal morning dose plus 50%) was given after a washout during night. Plasma samples and motor ratings (clinical assessment of motor function from video recordings on a treatment response scale between -3 and 3, where -3 represents severe parkinsonism and 3 represents severe dyskinesia.) were repeatedly collected until the clinical effect was back at baseline. At this point, the usual infusion rate was started and sampling continued for another two hours. Different structural absorption models and effect models were evaluated using the value of the objective function in the NONMEM package. Population mean parameter values, standard error of estimates (SE) and if possible, interindividual/interoccasion variability (IIV/IOV) were estimated. Results Our results indicate that Duodopa absorption can be modelled with an absorption compartment with an added bioavailability fraction and a lag time. The most successful effect model was of sigmoid Emax type with a steep Hill coefficient and an effect compartment delay. Estimated parameter values are presented in the table. Conclusions The absorption and effect models were reasonably successful in fitting observed data and can be used in simulation experiments.

Revisão por pares na Revista Brasileira de Educação Especial

O artigo discute algumas questões relativas ao procedimento de revisão por pares na avaliação de originais submetidos a um periódico. Essa avaliação é aceita como necessária para assegurar a qualidade científica de artigos publicados, já que a integridade da literatura especializada é considerada essencial para o desenvolvimento da ciência. Entretanto, há críticas à revisão por pares, incluindo o longo tempo decorrido entre a entrega dos originais e a publicação, o tempo e a energia despendidos pelos autores e revisores, a subjetividade na avaliação e outros problemas que podem introduzir vieses na área. A Revista Brasileira de Educação Especial, que adota a avaliação cega por pares, tem-se mostrado relativamente versátil. O tempo médio entre o recebimento dos originais e o aceite final, depois de passar pela revisão por pares e conseqüente ajuste por parte dos autores, é de cerca de cinco meses e meio. Na literatura especializada, encontram-se sugestões como a eliminação de avaliação e publicação de todos os textos submetidos, em meios eletrônicos, menos onerosos e mais versáteis, deixando que os próprios leitores façam a sua avaliação. A análise procedida conclui que a revisão por pares é necessária. Aponta a necessidade de se realizarem discussões sobre a própria avaliação, para que se desenvolvam procedimentos mais eficientes de controle de qualidade das publicações. Sugere que a avaliação efetiva é feita pela própria comunidade acadêmica, após a publicação, mediante reconhecimento coletivo do valor científico da publicação, na forma de impacto que pode causar sobre novas investigações e construção do conhecimento na área.

Avaliação das Sub-Frações dos Carboidratos e das Proteinas, Usando as Metodologias do Cncps e In situ com Bovinos da Raça Nelore. 1. Silagem de Milho

To validate the use of the Cornell Net Carbohydrate and Protein System (CNCPS) under Brazilian conditions, the chemical composition, the potential and the effective degradabilities of the carbohydrate and protein subfractions, and the solid phase passage rate were determined for corn silage in diets with forage:concentrate ratios of 80:20 (DI) and 60:40 (D2) using Nellore cattle. The chromium mordant technique was used to determine the particulate passage rate of solids. For diet 2, there was a reduction in the potentially degradable dry matter (DM), and however not significant, a reduction in the degradation rates of neutral detergent Fiber (NDF, 49%) and neutral detergent insoluble nitrogen (NDIN, 32%), and an increase in the degradation rare of starch (ST, 25%). The use of lag time increased the effective DM degradation (EDDM) of corn silage in both diets (23% and 53% for D1 and D2, respectively). The concentrate ratios did not influence the particulate passage rate of the diets. The higher values related ro the availability of the protein subfractions may indicate a underestimation by CNCPS, Rnd(or) could be attributed to the Zebu animals used in this study.

Influence of growth rate and length on fluoride detection in human nails

This study aimed to determine the lag time between increased fluoride (F) intake and F detection in human nails, as well as the influence of nails growth rate and length on this. Ten 20- to 35-year-old volunteers received 1.8 mg F daily, for 30 days. Nail growth rate and length were determined for all fingernails and toenails. Nail samples were collected at the beginning of the study and every 2 weeks (15 collections in all) and F concentrations were determined. The growth rate was statistically higher in fingernails than in toenails. No statistically significant differences were observed between right and left sides. Growth rate was significantly greater for big toenails than for the other toenails, but this pattern was not found for fingernails. The estimated mean lag times for F detection in fingernails and toenails were 101 and 123 days, respectively. An apparent increase in fingernail F concentrations was observed 84 days after the beginning of the study, although this was not statistically different from baseline. For toenails, statistically significant increases in F concentration in relation to baseline were observed 112 and 140 days after increased F ingestion. These increases occurred within the 95% confidence intervals for the calculated mean lag time for fluoride detection in nails. Considering the large amount of sample provided by the big toenails, together with their faster growth rate, as well as the fact that toenails are less prone to environmental contamination, our data suggest that big toenails are more suitable biomarkers of fluoride intake.

Avaliação das Sub-Frações dos Carboidratos e das Proteínas, Usando as Metodologias do Cncps e In situ com Bovinos da Raça Nelore. 2. Milho e Farelo de Algodão

The chemical composition of corn and cottonseed meal was determined in accordance with the Cornell Net Carbohydrate and Protein System (CNCPS) in diets with forage:concentrate ratios of 80:20 (D1) and 60:40(D2) using Nellore cattle. The potential and effective degradabilities of the carbohydrate and protein subfractions were also determined. For corn. diet 2 resulted in an increase for potentially degradable dry matter (DM). An increase was observed in the effective degradation of DM (EDDM) when lag time was not considered, however, the use of Eng time increased the EDDM for both diets, 23 and 18% for DI and D2. respectively. For cottonseed meal, diet 2 determined a reduction in the potentially degradable DM: therefore, the use of lag time increased the EDDM for bath diets, 14% for D1 and 15% for D2. The availability of corn starch (fraction B1) was lower than that determined by CNCPS. The higher values for the degradability of corn and cottonseed meal protein subfractions may indicate an underestimation by the model, and, or, could be attributed to the Zebu animals used in this study.

Degradabilidade ruminal do amido de silagem de milho, farelo de soja e sorgo grão, em bovinos da raça Nelore

Four Bos indicus (Nellore) ruminally-fistulated animals, averaging 36 months of age and 520 kg, were used in a randomized block design to study the ruminal degradability of starch in corn silage, soybean meal, and sorghum grain. The experimental diets consisted of two levels of concentrate (18 and 39%) plus corn silage. The concentrate ingredients used were soybean meal, cottonseed meal, corn grain, and sorghum grain. The degradation rate of sorghum grain increased 40.2% in diet 2 . The potential degradability of starch (PDS) was similar in the two diets. There was no difference between the two diets in the effective degradability of starch (EDS) in corn silage. There was a significant increase of 26.5% in the EDS of starch in sorghum grain with the increase of level of concentrate in the diet, and considering the lag time in the calculation. The starch level estimated in this study was lower than the values cited in the literature, probably due to different laboratory methods for determining the starch content in feedstuffs. Previous studies suggested using a minimum of 6 incubation intervals between 2 and 24 hours.

Degradabilidade ruminal da matéria seca e da fração protéica da silagem de milho, do farelo de soja e do sorgo grão, em bovinos da raça nelore. Comparação com os dados obtidos pelo CNCPS

The nylon bag in situ degradation thecnique was employed to compare the data of the CNCPS to the ruminal degradability of the dry matter and crude protein in corn silage, soybean meal and sorghum grain, in four rumen fistulated Nellore steers, averaging 36 months of age and 520 kg of liveweight. A randomized complete block experimental design was used, where animals constituted the blocks. Two levels of concentrate, 18 and 39 %, were used in the diets. The forage used in the diets was corn silage and the concentrate ingredients were: soybean meal, cottonseed meal, corn grain and sorghum grain. There was a reduction in the potentially by degradable fraction (B) of the dry matter(DM) of the corn silage and sorghum grain with an increase in the concentrate level of the diet; however, the degradation rate(c) of the silage was similar for the two diets and the sorghum grain showed an increase of 28.4 %. The B fraction of the DM from the soybean meal was not affected by the diet, but its rate (c) was reduced by 18.1 %. The same effect was observed for the rate(c) of crude protein(CP) of the soybean meal, with a reduction of 38.1 %. The values for the effective degradability of the two fractions were not affected by the diet when the lag time was not considered. When lag time was considered, the degradability values of the studied feeds were superior in both fractions.

Degradabilidade ruminai da fibra em detergente neutro e do nitrogênio insolúvel em detergente neutro da silagem de milho e do farelo de soja, em bovinos da raça nelore

The nylon bag in situ degradation thecnique was employed to study the ruminai degradability of the neutral detergent fiber and neutral detergent insoluble nitrogen of the corn silage and soybean meal in four rumen fistulated Nellore steers, averaging 36 months of age and 520 kg of liveweight. A randomized completelcs block experimental design was used, where the animals constituted the blocks. It was used diets with two levels of concentrate: 20 and 40%.The forage used in the diets was corn silage, and the concentrate ingredients were: soybean meal, cottonseed meal, corn grain and sorghum grain. The NIDN degradation rate of the corn silage and the soybean meal showed a decrease of 32,1% and of 46,0 % as a function of the higher concentrate level of the diet, but the effective and potential degradability of this fraction were not affected. Concerning to the NDF, the soluble fraction, potentially degradable and undegrable , were not affected by the increase on the diet concentrate level, but for the corn silage, there were 21,8% of reduction on the effective degradability of NDF. The use of lag time promoted higher degradability values for the studied fraction. The obtained values for some evaluated parameters, different from that assumed by CNCPS, showed the necessity of more data about brazilian used feeds, for model adjustments.

Degradabilidade in situ e consumo voluntário de capim Tanzânia (Panicum maximu, J. cv. Tanzânia), sob pastejo, por vacas em lactação

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

In vitro fermentation parameters and biohydrogenation of vegetable oils without glycerol

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A novel automated alternating current biosusceptometry method to characterization of controlled-release magnetic floating tablets of metronidazole

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Glycerol combined with oils did not limit biohydrogenation of unsaturated fatty acid but reduced methane production in vitro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of dipyrone, meloxicam, or the combination on hemostasis in conscious dogs

To compare the effects of dipyrone, meloxicam, and of the combination of these drugs on hemostasis in dogs. Prospective, blinded, randomized crossover study. Research laboratory at a veterinary teaching hospital. Six adult dogs. Animals received 4 intravenous treatments with 15-day washout intervals: control (physiological saline, 0.1 mL/kg), meloxicam (0.2 mg/kg), dipyrone (25 mg/kg), and dipyrone-meloxicam (25 and 0.2 mg/kg, respectively). A jugular catheter was placed for drug injection and for collecting samples for whole blood platelet aggregation (WBPA) and thromboelastometry assays at baseline, 1, 2, 3, 5, and 8 hours after treatment administration. The percent change from baseline of lag time and of the area under the curve (AUC) of impedance changes in response to collagen-induced platelet activation were recorded during WBPA. Thromboelastometry-derived parameters included clotting time, clot formation time, alpha-angle, and maximum clot firmness. The buccal mucosal bleeding time was evaluated by a blinded observer at baseline, 1, 3, and 5 hours after treatment injection. No significant changes in WBPA and thromboelastometry were recorded in the control treatment. Dipyrone significantly (P < 0.05) increased the lag time for 2 hours and decreased the AUC for 3 hours after injection. Meloxicam did not alter WBPA. Dipyrone-meloxicam significantly increased lag time for 2 hours and decreased the AUC for 5 hours after treatment injection. Experimental treatments did not differ from the control treatment for thromboelastometry and buccal mucosal bleeding time. While meloxicam does not alter hemostasis by the methods evaluated, dipyrone inhibits platelet aggregation for up to 3 hours. Meloxicam-dipyrone combination causes more prolonged inhibition of platelet function than dipyrone alone. Decreased platelet aggregation induced by dipyrone and dipyrone-meloxicam does not appear to impact the viscoelastic properties of the blood clot nor increase the risk of bleeding in dogs without preexisting hemostatic disorders.

A novel gastroretentive floating system for zidovudine, based on calcium-silicate beads

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)