Development and characterization of nanostructured lipid carrier-based gels for the transdermal delivery of donepezil.

Donepezil is one of the main compounds used in the therapy of Alzheimer's disease. Oral administration of this drug presents many drawbacks, resulting in treatment non-adherence among patients. Thus, the development of transdermal formulations for donepezil delivery is important. The aim of this study was to prepare and to evaluate nanostructured lipid carrier-based gels (NLC gel) able to improve the skin delivery of donepezil free base (DPB). The components of nanostructured lipid carriers (NLCs) were selected after evaluating their enhancing effects using in vitro DPB skin delivery assays. DPB-loaded NLC were prepared by a microemulsion technique, by employing stearic acid as a solid lipid, oleic acid as a liquid lipid, lecithin as a surfactant, and sodium taurodeoxycholate as a co-surfactant. The DPB-NLC dispersions were characterized morphologically using atomic force microscopy and physicochemically using dynamic light scattering and surface charge measurements. These data along, with the encapsulation studies, indicated that uniformly nano-sized particles with high drug encapsulation were fabricated. In vitro skin permeation assays were performed, and the results indicated that drug skin permeation from DPB-NLC gel was increased, not only by the enhancing effect of their components, but the lipid nanocarriers also presented an additional enhancing effect to increase drug flux across the skin. Therefore, DPB-NLC gel is an interesting formulation for the enhanced treatment of Alzheimer's disease.

Desempenho produtivo e características de carcaça de cordeiros Rabo Largo puro e cruzados com Santa Inês / Performance and carcass traits of Rabo Largo lambs and crossbreeding with Santa Inês

Objetivou-se avaliar o efeito do cruzamento entre ovinos nativos no desempenho e características da carcaça. Foram utilizados vinte cordeiros, machos, inteiros, com idade inicial de quatro meses, e peso médio inicial 19,0±5,11, distribuídos em dois grupos genéticos: Rabo Largo (RL) e Santa Inês x Rabo Largo (F1SI x RL), em um delineamento inteiramente ao acaso. Os animais foram terminados em regime de confinamento durante 70 dias. Os cordeiros F1SI x RL apresentaram maiores pesos ao desmame, ao abate, do corpo vazio, das carcaças quente e fria, e maior rendimento biológico. Verificaram maiores valores para os parâmetros de morfometria da carcaça para animais F1SI x RL comparados aos animais Rabo Largo (P<0,05). Os pesos da hemi-carcaça e dos cortes comerciais foram superiores para cordeiros F1SI x RL. Nas medidas obtidas no músculo Longissimus dorsi, os cordeiros Rabo Largo apresentaram valores superiores para espessura de gordura subcutânea. A utilização da raça Santa Inês como base paterna acarreta em melhorias nas características de carcaça de cordeiros Rabo Largo podendo ser indicado em sistemas de produção de carne ovina.(AU)

The aim of study was to evaluate the effect of crossbreeding among native sheep on performance and traits carcass. Twenty intact lambs, male, at four months of age, with an initial weight of 19.0±5.11kg, were distributed in two groups genetics: Rabo Largo (RL) e Santa Inês x Rabo Largo (F1SI x RL), in a completely randomized design. The animals were finished in feedlot by 70 days. The lambs F1SI x RL showed higher weight at weaning, to slaughter, of the empty body, and hot and cold carcass, and increased biological yield. Higher values for carcass morphometry in F1SI x RL animals were found in comparison to Rabo Largo animals (P<0.05). The weight of half-carcass and the commercial cuts were higher for lambs. On the measurements obtained in muscle Longissimus dorsi, Rabo Largo lambs showed higher values for subcutaneous fat thickness. The use of the breed Santa Inês like base paternal may bring in improvements in lambs's carcass characteristics Rabo Largo and may be recommended in sheep meat production systems.(AU)

Glycan microarray analysis of the carbohydrate-recognition specificity of native and recombinant forms of the lectin ArtinM.

This article contains data related to the researc.h article entitled "Yeast-derived ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM" by Cecílio et al. (2015) [1]. ArtinM, a D-mannose-binding lectin isolated from the seeds of Artocarpus heterophyllus, exerts immunomodulatory and regenerative activities through its Carbohydrate Recognition Domain (CRD) (Souza et al., 2013; Mariano et al., 2014 [2], [3]). The limited availability of the native lectin (n-ArtinM) led us to characterize a recombinant form of the protein, obtained by expression in Saccharomyces cerevisiae (y-ArtinM). We compared the carbohydrate-binding specificities of y-ArtinM and n-ArtinM by analyzing the binding of biotinylated preparations of the two lectin forms using a neoglycolipid (NGL)-based glycan microarray. Data showed that y-ArtinM mirrored the specificity exhibited by n-ArtinM.

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women.

The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9% and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15%), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3% and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3%) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women

The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9 percent and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15 percent), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3 percent and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3 percent) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.

Desempenho produtivo de ovinos em confinamento alimentados com diferentes dietas / Performance of confined sheep fed different diets

Avaliaram-se o desempenho produtivo e a viabilidade econômica da utilização de diferentes dietas na terminação de ovinos. Foram utilizados 20 ovinos machos inteiros com sete meses de idade e peso vivo inicial de 25kg. O experimento teve duração de 60 dias, sendo que os animais tiveram sete dias de adaptação às dietas e 53 para o período de pesagens, coletas das sobras e dietas oferecidas. Utilizou-se o delineamento inteiramente ao acaso com quatro tratamentos e cinco repetições: milho + soja + feno de Tifton 85 (DR); milho + soja + caju + feno de Tifton 850 (DC); milho + soja + maracujá + feno de Tifton 85 (DM); milho desintegrado com palha e sabugo (MDPS) + feno de leucena + feno de Tifton 85 (DL). Observou-se efeito do tratamento (P<0,05) sobre consumo de matéria seca (CMS), consumo de proteína bruta (CPB) e consumo de fibra em detergente neutro (CFDN). Os ganhos médios diários de peso, em gramas, foram 171,60, 218,80, 217,20, 187,00 para os tratamentos DR, DC, DM e DL, respectivamente. Registrou-se menor CMS, CPB e CFDN para o tratamento DL. Não foi observada influência das dietas sobre o rendimento de carcaça quente e fria. A análise econômica revelou valores de benefício líquido de R$-20,40; R$44,77; R$31,41; 39,10 e taxa de retorno de -12,4 por cento; 31,8 por cento; 20,6 por cento; 32,8 por cento para os tratamentos DR, DC, DM e DL, respectivamente.

The performance and economical viability of using different diets in sheep termination were evaluated. Twenty rams aging seven-month old and averaging initial live body weight of 25kg were used. The experimental period lasted 60 days, with seven adaptation and 53 for body weight evaluation, and feed and leftover sampling. A completely randomized design with four treatments and five repetitions was used. The treatments included: corn + soybean + Tifton 85 hay (DR), corn + soybean + cashew + Tifton 85 hay (DC), corn + soybean + passion fruit + Tifton 85 hay (DM), and corn and cob meal (MDPS) + Tifton 85 hay + leucaena hay (DL). Treatment affected (P<0.05) intakes of dry matter (CMS), crude protein (CPB), and neutral detergent fiber (CFDN). Average body weight gains (g) were 171.60, 218.80, 217.20, and 187.00 for the treatments DR, DC, DM, and DL, respectively. Lower CMS, CPB, and CFDN were observed for DL. There was no effect of diets on the hot and cold carcass yields. Economical analysis indicated liquid profits of R$ -20.40, R$ 44.77, R$ 31.41, and 39.10 and return ratios of 12.4 percent, 31.8 percent, 20.6 percent, and 32.8 percent for DR, DC, DM, and DL, respectively.

Valor nutritivo do resíduo da indústria processadora de abacaxi (Ananas comosus L.) em dietas para ovinos. 1. Consumo, digestibilidade aparente e balanços energético e nitrogenado / Nutritive value of pineapple by-product (Ananas comosus L.) in diets for sheep. 1. Intake, apparent digestibility, energetic and nitrogenous balance

O presente estudo foi conduzido para avaliar a influência da inclusão do resíduo do processamento de abacaxi (Ananas comosus L.) nas dietas sobre os consumos (por unidade de tamanho metabólico - UTM) e coeficientes de digestibilidade da matéria seca (MS), matéria orgânica (MO), proteína bruta (PB), extrato etéreo (EE), fibra detergente neutro (FDN), fibra detergente ácido (FDA), hemiceluloses (HCEL), celulose (CEL) e energia de dietas experimentais isofibrosas e isoprotéicas. Avaliaram-se também os balanços nitrogenados e de energia dos animais. Vinte ovinos machos, inteiros receberam rações com quatro níveis de inclusão do resíduo (0; 11 por cento; 16 por cento; 27 por cento) em base de matéria seca, em delineamento inteiramente ao acaso, com cinco repetições por tratamento. Maiores consumos de matéria seca foram evidenciados quando as rações continham 11 por cento do resíduo. Maiores consumos de proteína bruta, fibra detergente neutro, fibra detergente ácido e celulose (g/UTM) e energia metabolizável (kcal/UTM) foram apresentados por animais alimentados com dietas contendo 11 por cento de resíduo em relação ao das dietas com 27 por cento de inclusão (P<0,05). Maior coeficiente de digestibilidade da FDA ocorreu para dietas que não continham o resíduo de abacaxi. Os coeficientes de digestibilidade da CEL foram semelhantes. Os balanços energéticos e protéicos foram positivos. Melhores resultados para os parâmetros analisados foram observados para dietas que incluíam até 16 por cento do resíduo de abacaxi na base da matéria seca.

The influence of increasing levels of pineapple by-product (Ananas comosus L.) on intake (unit metabolic size - UMS) and apparent digestibility ( percent) of dry matter (DM), organic matter (OM), crude protein (CP), ether extract (EE), neutral detergent fiber (NDF), acid detergent fiber (ADF), hemicelluloses (HCEL) and cellulose (CEL) and energy of isofibrous and isoproteic experimental diets of sheep were evaluated. Energetic and nitrogenous balance were also measured. Twenty rams were randomly allotted to four treatments in a completely randomized design with five replications. The treatments were formulated to contain zero; 11, 16 and 27 percent of pineapple by-product on DM basis. Higher dry matter intake was observed on 11 percent pineapple by-product diet. CP, NDF, ADF, CEL intake (g/UMS) and metabolizable energy intake (kcal/UMS) of 11 percent pineapple by-product diet were higher than 27 percent pineapple by-product diet (P<0.05). ADF digestibility was higher for 0 percent pineapple by-product diet. Energy and nitrogenous balances were positives. Diets formulated to contain up to 16 percent of pineapple by-product presented the best results.

Scalar-field-dominated cosmology with a transient acceleration phase.

A new cosmological scenario driven by a slow rolling homogeneous scalar field whose exponential potential V(Phi) has a quadratic dependence on the field Phi in addition to the standard linear term is discussed. The derived equation of state for the field predicts a transient accelerating phase, in which the Universe was decelerated in the past, began to accelerate at redshift z approximately 1, is currently accelerated, but, finally, will return to a decelerating phase in the future. This overall dynamic behavior is profoundly different from the standard evolution of the cold dark matter model with a cosmological constant, and may alleviate some conflicts in reconciling the idea of a dark-energy-dominated universe with observables in String or M theory. Some theoretical predictions for the present scalar field plus dark matter dominated stage are confronted with cosmological observations in order to test the viability of the scenario.

Short term maintenance of sheep preantral follicles in situ in 0.9% saline and Braun-Collins solution.

The present study has investigated the efficiency of 0.9% saline solution and Braun-Collins solution in the preservation of sheep preantral follicles in situ, at different temperatures and different incubation periods. The ovaries were divided into 19 fragments for each animal. One ovarian fragment was taken randomly and immediately fixed for histology (control-time zero). The other 18 ovarian fragments were randomly distributed in tubes containing 2ml of 0.9% saline solution or Braun-Collins solution at 4, 20 or 39 degrees C for 4, 12 or 24h. A total of 1629, 208 and 63 primordial, primary and secondary follicles were examined, respectively. Histological analysis showed that the storage of ovarian fragments in both solutions at 20 or 39 degrees C significantly reduced the percentage of morphologically normal preantral follicles (MNPF) when compared with the control, except after preservation in 0.9% saline solution at 20 degrees C for 4h. In contrast, the preservation at 4 degrees C, in both solutions, kept the percentage of MNPF similar to control values. In conclusion, this study shows for the first time that sheep preantral follicles can be preserved in situ successfully at 4 degrees C in 0.9% saline solution or Braun-Collins solution for up to 24h.

Effect of Braun-Collins and saline solutions at different temperatures and incubation times on the quality of goat preantral follicles preserved in situ.

The present work has investigated the efficiency of Braun-Collins and saline (0.9%) solutions in the conservation of goat preantral follicles in situ, at different temperatures and incubation times. For each animal the ovarian pair was divided into 19 fragments. One ovarian fragment was taken randomly and immediately fixed (control). The other 18 ovarian fragments were randomly distributed in tubes containing Braun-Collins or saline (0.9%) solutions at 4, 20 or 39 degrees C for 4, 12 or 24h. A total of 3385, 372 and 191 primordial, primary and secondary follicles were examined, respectively. The quality of preantral follicles was evaluated by histology and transmission electron microscopy. The storage of ovarian fragments in saline (0.9%) or Braun-Collins solutions at 4 degrees C did not reduce significantly the percentage of morphologically normal follicles when compared with the control. The histological analysis revealed a morphological integrity of goat preantral follicles stored at 4 degrees C for up to 24h in both solutions, but these results were not confirmed by ultrastructural analysis. The transmission electron microscopy revealed that only preantral follicles stored at 4 degrees C for a maximum of 12h in both solutions were ultrastructurally normal. In conclusion, this study shows for the first time that goat preantral follicles can be stored in situ successfully at 4 degrees C in saline (0.9%) or Braun-Collins solution for up to 12h.

Morphological and ultrastructural changes occurring during degeneration of goat preantral follicles preserved in vitro.

The present work has investigated the morphological and ultrastructural changes occurring during degeneration of goat preantral follicles preserved in vitro and showed quantitative data about the distribution of follicular degeneration types in the control and after preservation in coconut water solution or Braun-Collins solution at different temperatures (4, 20 or 39 degrees C) and incubation times (4, 12 or 24h). At the slaughterhouse, the pair of ovaries of each animal was divided into 19 fragments. One ovarian fragment was immediately fixed (control: Time 0). The other 18 fragments were randomly distributed in tubes containing 2ml of coconut water or Braun-Collins solution at 4, 20 or 39 degrees C and stored for 4, 12 or 24h. Normal preantral follicles exhibited a healthy oocyte surrounded by one or more well-organized layers of granulosa cells. The ooplasm contained numerous rounded or elongated mitochondria with continuous mitochondrial membranes. Golgi complexes were rare. Both smooth and rough endoplasmic reticulum were observed, either as isolated aggregations or complex associations with mitochondria and vesicles. Degenerated preantral follicles in the control tissue exhibited pycnotic nuclei of the oocyte, vacuolated ooplasm and normal granulosa cells. This kind of degeneration also predominated significantly (P<0.05) after preservation at 4 degrees C. In contrast, after preservation at 20 or 39 degrees C a significant predominance (P<0.05) of preantral follicles showing a retracted oocyte and swollen granulosa cells was observed. These follicles showed large irregularity of the oocyte and nuclear outlines. The ooplasm exhibited moderate proliferation of the endoplasmic reticulum and mitochondria showed disappearance of most of the cristae and damage to the mitochondrial membrane. Some follicles had numerous vacuoles in the ooplasm. Granulosa cells were spread and a low density of organelles was observed. The alterations in follicular structure progressed with an increase of temperature from 20 to 39 degrees C as well as with an increase of the incubation time from 4 to 12, or 24h. In conclusion, the present study shows for the first time that initial proliferation of the endoplasmic reticulum and damage to mitochondria are the first signs of degeneration in goat preantral follicles during storage in vitro.

Effect of coconut water and Braun-Collins solutions at different temperatures and incubation times on the morphology of goat preantral follicles preserved in vitro.

Preservation of preantral follicles becomes very important to ensure follicle quality at the onset of cryopreservation or in vitro culture. However, for domestic animals, the ovarian donor of preantral follicles for in vitro studies is commonly encountered far away from reproduction laboratories. We investigated the effectiveness of coconut water and Braun-Collins solutions on the preservation of goat preantral follicles. At the slaughterhouse, the ovarian pair of each animal was divided into 19 fragments. One ovarian fragment was immediately fixed (Control - Time 0). The other 18 fragments were randomly distributed into tubes containing 2 mL of coconut water or Braun-Collins solution at 4 degrees, 20 degrees or 39 degrees C and then stored for 4, 12 or 24 h. Histological analysis showed that the storage of ovarian fragments in coconut water and Braun-Collins solutions at 20 degrees or 39 degrees C for 12 or 24 h significantly reduced (P < 0.05) the percentage of morphologically normal preantral follicles when compared with the control. However, storage in coconut water at 20 degrees C for 4 h and in both solutions at 4 degrees C kept the percentage at control values. Ultrastructural analysis of follicles exposed to the stated conditions confirmed the integrity of preantral follicles stored at 4 degrees C in Braun-Collins and coconut water solutions for up to 12 and 24 h, respectively. Reduced cellular metabolism at 4 degrees C may explain why the best preservation of preantral follicles was at 4 degrees C, which may suggest a useful method for ovary transport in the future.

Quantitative and qualitative analysis of the effectiveness of a mechanical method for the isolation of preantral follicles from ovine ovaries.

The preantral follicles are the major source of oocytes and its utilization has been investigated as an important tool to store large numbers of female gametes for further utilization in reproductive programs. The aim of the present study was to perform quantitative and qualitative analyses of the efficacy of a mechanical method for isolating of preantral follicles from the ovaries of fetuses and from nonpregnant and pregnant ewes, using as reference the population of preantral follicles in situ. In the isolation method the ovaries were cut into fragments in the tissue chopper. Then, the suspension was filtered through nylon mesh filters. The number of isolated follicles per ovary was 1655, 4735 and 4770, respectively, for the fetus, nonpregnant ewe and pregnant ewe. The number of in situ preantral follicles per ovary was 32961, 16627 and 17794, respectively, for the fetus, nonpregnant ewe and pregnant ewe. The follicle recovery rate (number of isolated preantral follicles/number of in situ preantral follicles x 100) was higher in adult ewes (26 and 28%, respectively, for nonpregnant and pregnant ewes) than in fetuses (5%). Histological analysis showed that very few preantral follicles (less than 0.26% in situ and 0.46% after the isolation procedure) were degenerated. In conclusion, this study showed that a mechanical method could be used effectively to isolate a large number of intact ovine preantral follicles. In the future, with improvements in culture systems, the isolation of a great number of oocytes enclosed in preantral follicles will make a valuable contribution to the rare breeds and endangered species, agricultural efficiency and basic research in folliculogenesis.