RESUMO
Bovine anaplasmosis causes considerable economic losses in dairy cattle production systems worldwide, ranging from $300 million to $900 million annually. It is commonly detected through rectal temperature, blood smear microscopy, and packed cell volume (PCV). Such methodologies are laborious, costly, and difficult to systematically implement in large-scale operations. The objectives of this study were to evaluate (1) rumination and activity data collected by Hr-Tag sensors (SCR Engineers Ltd.) in heifer calves exposed to anaplasmosis; and (2) the predictive ability of recurrent neural networks in early identification of anaplasmosis. Additionally, we aimed to investigate the effect of time series length before disease diagnosis (5, 7, 10, or 12 consecutive days) on the predictive performance of recurrent neural networks, and how early anaplasmosis disease can be detected in dairy calves (5, 3, and 1 d in advance). Twenty-three heifer calves aged 119 ± 15 (mean ± SD) d and weighing 148 ± 20 kg of body weight were challenged with 2 × 107 erythrocytes infected with UFMG1 strain (GenBank no. EU676176) isolated from Anaplasma marginale. After inoculation, animals were monitored daily by assessing PCV. The lowest PCV value (14 ± 1.8%) and the finding of rickettsia on blood smears were used as a criterion to classify an animal as sick (d 0). Rumination and activity data were collected continuously and automatically at 2-h intervals, using SCR Heatime Hr-Tag collars. Two time series were built including last sequence of -5, -7, -10, or -12 d preceding d 0 or a sequence of 5, 7, 10, or 12 d randomly selected in a window from -50 to -15 d before d 0 to ensure a sequence of days in which PCV was considered normal (32 ± 2.4%). Long short-term memory was used as a predictive approach, and a leave-one-animal-out cross-validation (LOAOCV) was used to assess prediction quality. Anaplasmosis disease reduced 34 and 11% of rumination and activity, respectively. The accuracy, sensitivity, and specificity of long short-term memory in detecting anaplasmosis ranged from 87 to 98%, 83 to 100%, and 83 to 100%, respectively, using rumination data. For activity data, the accuracy, sensitivity, and specificity varied from 70 to 98%, 61 to 100%, and 74 to 100%, respectively. Predictive performance did not improve when combining rumination and activity. The use of longer time-series did not improve the performance of models to predict anaplasmosis. The accuracy and sensitivity in predicting anaplasmosis up to 3 d before clinical diagnosis (d 0) were greater than 80%, confirming the possibility for early identification of anaplasmosis disease. These findings indicate the great potential of wearable sensors in early identification of anaplasmosis diseases. This could positively affect the profitability of dairy farmers and animal welfare.
Assuntos
Anaplasma marginale , Anaplasmose , Doenças dos Bovinos , Anaplasmose/diagnóstico , Anaplasmose/microbiologia , Animais , Bovinos , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/microbiologia , Eritrócitos , Feminino , Vacinação/veterináriaRESUMO
This study aimed to assess the predictive ability of different machine learning (ML) methods for genomic prediction of reproductive traits in Nellore cattle. The studied traits were age at first calving (AFC), scrotal circumference (SC), early pregnancy (EP) and stayability (STAY). The numbers of genotyped animals and SNP markers available were 2342 and 321 419 (AFC), 4671 and 309 486 (SC), 2681 and 319 619 (STAY) and 3356 and 319 108 (EP). Predictive ability of support vector regression (SVR), Bayesian regularized artificial neural network (BRANN) and random forest (RF) were compared with results obtained using parametric models (genomic best linear unbiased predictor, GBLUP, and Bayesian least absolute shrinkage and selection operator, BLASSO). A 5-fold cross-validation strategy was performed and the average prediction accuracy (ACC) and mean squared errors (MSE) were computed. The ACC was defined as the linear correlation between predicted and observed breeding values for categorical traits (EP and STAY) and as the correlation between predicted and observed adjusted phenotypes divided by the square root of the estimated heritability for continuous traits (AFC and SC). The average ACC varied from low to moderate depending on the trait and model under consideration, ranging between 0.56 and 0.63 (AFC), 0.27 and 0.36 (SC), 0.57 and 0.67 (EP), and 0.52 and 0.62 (STAY). SVR provided slightly better accuracies than the parametric models for all traits, increasing the prediction accuracy for AFC to around 6.3 and 4.8% compared with GBLUP and BLASSO respectively. Likewise, there was an increase of 8.3% for SC, 4.5% for EP and 4.8% for STAY, comparing SVR with both GBLUP and BLASSO. In contrast, the RF and BRANN did not present competitive predictive ability compared with the parametric models. The results indicate that SVR is a suitable method for genome-enabled prediction of reproductive traits in Nellore cattle. Further, the optimal kernel bandwidth parameter in the SVR model was trait-dependent, thus, a fine-tuning for this hyper-parameter in the training phase is crucial.
Assuntos
Bovinos/genética , Aprendizado de Máquina , Modelos Genéticos , Reprodução/genética , Animais , Brasil , Feminino , Genômica , Fenótipo , Polimorfismo de Nucleotídeo Único , GravidezRESUMO
Taxifolin possesses gastroprotective property but is characterized by low water solubility, is instabile in alkaline medium, and is degraded by the intestinal bacteria flora. The purpose of the work was therefore to produce a gastroadhesive formulation to prolong taxifolin residence time and release in the stomach. We first demonstrated that taxifolin is stable in simulated gastric fluid with or without pepsin and mucus, and is able to cross pig gastric mucus layer and stomach mucosa. Next, gastromucoadhesive microparticles composed of Syloid® AL-1 mesoporous silica, chitosan and HPMC were produced using spray-drying. Microparticles were characterized by a spherical shape and a mean volume-equivalent diameter around 12 µm. The optimized microparticles were able to release taxifolin and to adhere to pig stomach mucosa for 5 h.
Assuntos
Quitosana/química , Portadores de Fármacos/química , Fármacos Gastrointestinais/química , Quercetina/análogos & derivados , Adesividade , Animais , Liberação Controlada de Fármacos , Excipientes/química , Mucosa Gástrica/metabolismo , Microtecnologia , Mimusops/química , Tamanho da Partícula , Permeabilidade , Quercetina/química , Sementes/química , Dióxido de Silício/química , SuínosRESUMO
The increase in fructose consumption in the last decades has an important correlation with the growth of overweight population. Fructose is a monosaccharide found in fruits, vegetables and honey, however, it is widely used in processed food and beverages such as sweeteners. This monosaccharide is metabolized in the liver, so it can produce glucose, lactate, triglycerides, free fatty acids and uric acid, which are responsible for negative effects on the liver and extrahepatic tissues. One effect of the high consumption of fructose is the resistance to Insulin, which appears to be an important issue in the development of metabolic abnormalities observed in animals that were subjected to a high fructose diet. The population and, consequently, the market search for natural sources to manage metabolic abnormalities is increasing, but, adequate scientific proof still is necessary. The Passiflora edulis peel flour (PEPF) is a byproduct of the juice industry, and, represents an important source of fiber and bioactive compounds. The present study investigates the PEPF supplementation (30%) effects on insulin sensitivity, adiposity and metabolic parameters in young rats that were given beverages enriched with 10% of fructose for 8 weeks. Fructose intake induced insulin resistance, increased serum triglycerides levels, growth of fat deposits in the liver and widening of the diameter of adipocytes. In contrast, the group that received PEPF did not present such abnormalities, which could be related to the presence of fiber or bioactive compounds (phenolics compounds, e.g., caffeic acid and isoorientin) in its composition, as identified by analytical methods. Thus, for the first time, it has been demonstrated that PEPF supplementation prevents insulin resistance and hepatic steatosis induced by low-fructose-diet in young rats.
Assuntos
Dieta , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/prevenção & controle , Farinha , Resistência à Insulina , Passiflora/química , Extratos Vegetais/uso terapêutico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Envelhecimento/patologia , Animais , Antioxidantes/farmacologia , Fígado Gorduroso/sangue , Fígado Gorduroso/patologia , Frutose , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Extratos Vegetais/farmacologia , Ratos Wistar , Aumento de Peso/efeitos dos fármacosRESUMO
The objective of this study was to investigate the association of single nucleotide polymorphisms (SNPs) with birth weight, weight gain from birth to weaning and from weaning to yearling, yearling height and cow weight in Nelore cattle. Data from 5064 animals participating in the DeltaGen and PAINT breeding programs were used. The animals were genotyped with a panel of 777 962 SNPs (Illumina BovineHD BeadChip) and 412 993 SNPs remained after quality control analysis of the genomic data. A genome-wide association study was performed using a single-step methodology. The analyses were processed with the BLUPF90 family of programs. When applied to a genome-wide association studies, the single-step GBLUP methodology is an iterative process that estimates weights for the SNPs. The weights of SNPs were included in all analyses by iteratively applying the single-step GBLUP methodology and repeated twice so that the effect of the SNP and the effect of the animal were recalculated in order to increase the weight of SNPs with large effects and to reduce the weight of those with small effects. The genome-wide association results are reported based on the proportion of variance explained by windows of 50 adjacent SNPs. Considering the two iterations, only windows with an additive genetic variance >1.5% were presented in the results. Associations were observed with birth weight on BTA 14, with weight gain from birth to weaning on BTA 5 and 29, with weight gain from weaning to yearling on BTA 11, and with yearling height on BTA 8, showing the genes TMEM68 (transmembrane protein 8B) associated with birth weight and yearling height, XKR4 (XK, Kell blood group complex subunit-related family, member 4) associated with birth weight, NPR2 (natriuretic peptide receptor B) associated with yearling height, and REG3G (regenerating islet-derived 3-gamma) associated with weight gain from weaning to yearling. These genes play an important role in feed intake, weight gain and the regulation of skeletal growth.
Assuntos
Cruzamento , Bovinos , Estudo de Associação Genômica Ampla , Animais , Peso Corporal , Bovinos/genética , Bovinos/crescimento & desenvolvimento , Feminino , Fenótipo , Polimorfismo de Nucleotídeo Único , Desmame , Aumento de PesoRESUMO
Finishing precocity visual score selection was adopted to estimate the time from birth to reach slaughter age. This study estimated (co)variance components and genetic correlations for the finishing precocity score at weaning (WP) and yearling (YP) stages by using daily weight gain (BWG = from birth to weaning; WYG = from weaning to yearling) and speed of weight gain (BWR = from birth to weaning; WYR = from weaning to yearling) as support for a genetic evaluation program for Angus beef cattle. Genetic parameters were estimated using Bayesian inference, considering multi-trait analysis and assuming a nonlinear model for WP and YP and linear model for all other traits. Direct heritability estimates were 0.17 (WP), 0.19 (YP), 0.15 (BWG), 0.16 (WYG), 0.15 (BWR), and 0.16 (WYR). The genetic correlation between the finishing precocity score at two ages (weaning and yearling) was 0.61. Positive and moderate genetic correlations were obtained between WP and BWG (0.47) and WP and BWR (0.46). In contrast, negative and low genetic associations were estimated between WP and yearling growth traits (-0.16, WYG; -0.15, WYR). Genetic correlations between YP and other traits were positive 0.29 (BWG), 0.28 (BWR), 0.48 (WYG), and 0.47 (WYR). The selection response for the finishing precocity score at weaning and yearling ages would be low. Selection to increase WP and YP should result in favorable genetic changes in daily weight gains as a correlated response. Therefore, to obtain animals suited for beef cattle production systems, finishing precocity score and growth traits should be considered as selection criteria.
Assuntos
Bovinos/crescimento & desenvolvimento , Animais , Bovinos/genética , Método de Monte CarloRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Aleurites moluccana L. (Willd) Euforbiaceae is a native tree of Indonesia and India that has become acclimatized and well-adapted to the South and Southwest of Brazil. It is commonly used in traditional medicine to treat pain, fever, inflammation, asthma, hepatitis, headache, gastric ulcer, cuts, skin sores and other ailments. The oral antinociceptive effects of standardized 70:30 (v/v) ethanol:water spray dried extract of A. moluccana leaf, as well as its flavonoids 2"-O-rhamnosylswertisin (I) and swertisin (II), have previously been reported. AIM: The aim of this study was to develop a stable and effective semisolid herbal medicine for topical use in the treatment of pain, inflammation and wound healing, containing 0.5 and 1.0% of standardized dried extract of A. moluccana. MATERIALS AND METHODS: The chemical markers I and II were assayed by HPLC-UV analysis after extraction by matrix solid dispersion phase (MSDP) followed analytical validation as ICH Guidelines. The semisolid preparations of Hostacerin CG(®) vehicle containing 0.5 and 1.0% of dried extract of A. moluccana were submitted to stability studies (180 day of accelerated and long-term studies). The phytomedicine semisolid was analysed in croton oil-induced ear oedema model in mice, in the healing process, using the excisional wound model in rats, and to prevent mechanical sensitization following plantar incision in rats in the postoperative model of pain. RESULTS: The MSDP method showed average recovery of 101.6 and 105.7% for I and II, respectively, with good precision (RSD<2.0%) and selectivity, without interference of the excipients. The formulations were approved in the stability studies, maintaining conformity after 180 day of accelerated and long-term studies, with variation<10% in the analytical parameters. The phytomedicine reduced the ear oedema in 37.6±5.7% and 64.8±6.2%, for 0.5 and 1.0% of dried extract, respectively. The formulation also accelerated the healing process by up to 50.8±4.1% and 46.0±4.0% at 0.5 and 1.0% of extract, respectively, and both amounts were capable of preventing the development of mechanical sensitization following plantar incision in rats. CONCLUSIONS: The MSDP followed by HPLC-UV analytical method was appropriate for the quality control of the topical phytomedicine based on A. moluccana. The formulation developed at 0.5 and 1.0% of A. moluccana dried extract proved to be effective as an analgesic, anti-inflammatory and wound healing in the pre-clinical studies, which is in agreement with the ethnopharmacological data.
Assuntos
Aleurites/química , Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Flavonoides/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Cicatrização/efeitos dos fármacos , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Apigenina/farmacologia , Apigenina/uso terapêutico , Modelos Animais de Doenças , Orelha , Edema/induzido quimicamente , Edema/tratamento farmacológico , Flavonas/farmacologia , Flavonas/uso terapêutico , Flavonoides/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/normas , Folhas de Planta , Ratos , Ratos Wistar , Ramnose/análogos & derivados , Ramnose/farmacologia , Ramnose/uso terapêutico , Ferimentos e Lesões/tratamento farmacológicoRESUMO
Metformin hydrochloride (MH) is an oral hypoglycemic agent and a high-dose drug that has poor flow and compression properties. In this study, the feasibility of developing adequate, low cost 500mg tablets of metformin hydrochloride by wet granulation was tested with several binders (Starch / PVP K30®; Starch1500® /PVP K30®, PVP K30® and PVP K90®) in a simple tablet press of the type used in small pharmaceutical laboratories. The drug powder was tested for ability to flow, by determining Carr?s Index (CI) and the Hausner ratio (HR). Differential scanning calorimetry and thermogravimetric analysis were carried out on isolated MH and 1:1 (w/w) binary mixtures with the excipients. The size distribution, friability, flow properties and drug content of the granules were analyzed, as were the hardness, friability, disintegration, dissolution and uniformity of the dosage form. The drug powder showed CI > 22% and HR > 1.25, characteristic of a poor flow powder, and no significant incompatibilities with the excipients. All the granules showed adequate flow properties and were suitable for pressing into tablets, all of which complied with pharmacopeial specifications. The starch /PVP K30® and starch 1500®/PVP K30® mixtures were best for producing 500 mg MH tablets.
Cloridrato de metformina é um fármaco hipoglicemiante oral que apresenta propriedades pobres de fluxo e compressibilidade. Este trabalho teve como objetivo o desenvolvimento de comprimidos de baixo custo,após granulação por via úmida, contendo 500 mg de cloridrato de metformina e diferentes aglutinantes (F1-amido / PVP K30®; F2- Starch 1500® / PVP K30®, F3-PVP K30®, F4- PVP K90®) em máquinas de compressão de baixo desempenho usadas em laboratórios farmacêuticos de pequeno porte. As propriedades defluxo do fármaco foram analisadas através do índice de Carr (IC) e fator de Hausner (FH). Cloridrato de metformina e suas misturas binárias com os excipientes na relação 1:1 (m/m) foram analisadas por calorimetria diferencial por varredura e análise termogravimétrica. Os granulados foram analisados quanto a distribuição granulométrica, friabilidade, propriedades de fluxo e teor e os comprimidos em relação à dureza, friabilidade, desintegração, dissolução e uniformidade de conteúdo.O cloridrato de metformina apresentou IC > 22% e FH> 1,25, característicos de fluxo pobre e não apresentou incompatibilidades com os outros excipientes. Todos os granulados demonstraram adequadas propriedades de fluxo e facilidade no processo de compressão. Os comprimidos apresentaram conformidade com as especificações farmacopeicas. As misturas amido / PVPK30® e Starch 1500® / PVP K30® foram mais adequadas para produzir comprimidos de cloridrato de metformina 500 mg.
Assuntos
Composição de Medicamentos , Avaliação de Medicamentos , Metformina/farmacocinética , Preparações Farmacêuticas , ComprimidosRESUMO
Metformin hydrochloride is a high-dose drug widely used as an oral anti-hyperglycemic agent. As it is highly crystalline and has poor compaction properties, it is difficult to form tablets by direct compression. The aim of this study was to develop adequate metformin tablets, pharmaceutically equivalent to the reference product, Glucophage® (marketed as Glifage® in Brazil). Metformin 500mg tablets were produced by wet granulation with various binders (A equal starch, B equal starch 1500®, C equal PVP K30®, D equal PVP K90®). The tablets were analyzed for their hardness, friability, disintegration, dissolution, content uniformity and dissolution profile (basket apparatus at 50 rpm, pH 6.8 phosphate buffer). The 4 formulations, F1 (5% A and 5% C), F2 (5% Band 5% C), F3 (10% C) and F4 (5% D), demonstratedadequate uniformity of content, hardness, friability, disintegration and total drug dissolution after 30minutes (F1, F2 and F4), and after 60 minutes (F3). The drug release time profiles fitted a Higuchi model (F1, F2and F3), similarly to the pharmaceutical reference, or a zero order model (F4). The dissolution efficiency for all the formulations was 75%, except for F3 (45%). F1 andF2 were thus equivalent to Glifage®.
Assuntos
Comprimidos/farmacocinética , Metformina , Testes de Aglutinação , Equivalência TerapêuticaRESUMO
Directly compressed theophylline tablets, containing commercial xanthan (X) (Keltrol) and a highly hydrophilic galactomannan (G) from the seeds of Mimosa scabrella (a brazilian leguminous tree called bracatinga) as release-controlling agents, were obtained. Gums were used at 4, 8, 12.5 and 25% (w/w), either alone or in mixture (X:G 1:1). During galactomannan extraction process, the biopolymer was dried in a scale up, by vacuum oven (VO) or spray dryer (SD). The in vitro drug release was evaluated at different time intervals during 8 h using apparatus 1 (USP 26) at 100 rpm. The pH of the dissolution medium (1.4) was changed to 4.0 and 6.8 after 2 and 3 h, respectively. Tablets containing G(SD) resulted in more uniform drug release than G(VO) ones, due to their smaller particle size. The drug release decreased with the increase of polymer concentration and all formulations at 25% w/w of gums showed excessive sustained release effect. The matrices made with alone X showed higher drug retention for all concentrations, compared with G matrices that released the drug too fast. The XG matrices were able to produce near zero-order drug release. The XG(SD) 8% tablets provided the required release rate (about 90% at the end of 8 h), with zero-order release kinetics. Tablets containing G(VO) in low concentration showed a complete erosion, while the others demonstrated fast hydration and swelling in contact with the dissolution medium. The release mechanism was a combination of diffusion and relaxation. The relative importance of these two processes varied with matrix composition. The XG(SD) 8% matrix showed higher contribution of polymer relaxation.