Abstract Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the latest class of drugs approved to treat type 2 DM (T2DM). Although adverse effects are often caused by a metabolite rather than the drug itself, only the safety assessment of disproportionate drug metabolites is usually performed, which is of particular concern for drugs of chronic use, such as SGLT2i. Bearing this in mind, in silico tools are efficient strategies to reveal the risk assessment of metabolites, being endorsed by many regulatory agencies. Thereby, the goal of this study was to apply in silico methods to provide the metabolites toxicity assessment of the SGLT2i. Toxicological assessment from SGLT2i metabolites retrieved from the literature was estimated using the structure and/or statistical-based alert implemented in DataWarrior and ADMET predictorTM softwares. The drugs and their metabolites displayed no mutagenic, tumorigenic or cardiotoxic risks. Still, M1-2 and M3-1 were recognized as potential hepatotoxic compounds and M1-2, M1-3, M3-1, M3-2, M3-3 and M4-3, were estimated to have very toxic LD50 values in rats. All SGLT2i and the metabolites M3-4, M4-1 and M4-2, were predicted to have reproductive toxicity. These results support the awareness that metabolites may be potential mediators of drug-induced toxicities of the therapeutic agents.

RESUMO A parvovirose canina é uma doença de alta mortalidade e de quadro clínico agudo. No entanto, existem poucos recursos para se estabelecer prognóstico de maneira precisa. Este estudo objetivou analisar os valores prognósticos de parâmetros físicos e hematológicos de cães naturalmente infectados pelo Carnivore protoparvovirus 1 (CPV). Um estudo retrospectivo de 103 casos de parvovirose canina foi realizado. Desses, 27% dos animais (28/103) foram a óbito, sendo 96% (27/28) com ocorrência nos primeiros quatro dias de internamento. Os cães que foram a óbito apresentaram medianas das frequências cardíaca (FC) e respiratória (f) significativamente maiores e pressão arterial sistólica (PAS) consideravelmente menor que a dos sobreviventes. Entre os animais mais intensamente leucopênicos (<1.000 células/(L), a taxa de mortalidade (68%, n=13) foi expressivamente maior que a dos demais pacientes (P<0,0007). Os animais com hipotensão grave (PAS<90mmHg), taquicardia (FC>150bpm) e leucopenia intensa (leucometria<1.000 células/µL), ou duas dessas alterações clínicas, representaram 34% (34/101) dos casos e tiveram taxa de sobrevida de 29% (10/34), enquanto os animais com, no máximo, um desses parâmetros alterados representaram 66% (67/101) dos animais, com taxa de sobrevida de 94% (63/67). A presença de dois ou três parâmetros alterados esteve significativamente relacionada ao maior risco de óbito de cães com parvovirose (P<0,0001).

ABSTRACT Canine parvovirosis is a high mortality disease with acute clinical picture. However, there are few available resources to help stablish prognosis accurately. This study aimed to determine the prognostic threshold values for vital and hematological parameters of dogs naturally infected by the Carnivore protoparvovirus 1 (CPV). A retrospective study of 103 canine parvovirosis cases was carried out. Twenty seven percent of these (28/103) died, 96% (27/28) of which within the first four days of hospitalization. Deceased animals had significantly higher median values for heart (HR) and respiratory (f) rates, as well as significantly lower systolic blood pressure (SBP) than survivors. Severely leukopenic animals (<1,000 cells/μL), had a significantly higher mortality rate (68%, n=13) compared to that of other patients (P<0.0007). Animals with at least two of the following findings: severe hypotension (SBP< 90mmHg), tachycardia (HR > 150 bpm) and leukopenia, represented 34% (34/101) of the cases and had a survival rate of 29% (10/34), while animals with at most one of these parameters represented 66% (67/101) and had a survival rate of 94% (63/67). The presence of two or three abnormal parameters was significantly related to the higher death risk among dogs with parvovirosis (P<0.0001).

Avaliou-se o desempenho produtivo e econômico de três grupos genéticos de bovinos em sistema com recria a pasto e terminação em confinamento, com ciclo de produção de um ano. Foram utilizados 36 bovinos não castrados, com média de 270±50 dias de idade e peso médio inicial de 241,3±34kg, sendo 12 Guzolandos (1/2 Guzerá x 1/2 Holandês), 12 Guzonel (1/2 Guzerá x 1/2 Nelore) e 12 Tricross (1/2 Simental x 1/2 Guzonel). O delineamento estatístico foi inteiramente ao acaso. Os animais permaneceram em pastejo rotacionado de Brachiaria brizantha cv. Marandu, com suplementação comercial; na terminação, receberam dieta composta por silagem de sorgo e concentrado (50:50) durante 61 dias. Os índices de desempenho avaliados foram o ganho médio de peso diário (GMD), ganho médio de peso no período, peso corporal final e, como indicadores econômicos, a receita total, custo operacional total por arroba (COT/@), margem bruta e margem líquida. O GMD na recria foi semelhante (P>0,05) entre os grupos que apresentaram média de 746 e 456 gramas, respectivamente, para os períodos águas/transição águas-seca e seca. O COT/@ da recria do grupo Tricross (R$69,44) foi superior aos dos grupos Guzonel (R$66,75) e Guzolando (R$ 64,86). No período de terminação, o GMD foi semelhante entre os grupamentos, apresentanto o valor médio de 1,55kg. O COT/@ da terminação em confinamento foi R$ 91,48, R$114,15 e R$122,78, para Tricross, Guzonel e Guzolando, respectivamente. Considerando-se o sistema de ciclo curto completo, obteve-se COT/@ menor para o grupamento Tricross (R$77,92), seguido pelo grupamento Guzonel (R$ 74,89) e Guzolando (R$ 78,43). Nas condições de produção avaliadas, o grupo Tricross foi o mais eficiente economicamente.

The productive and economic performance of different beef genetic groups in a pasture-based growing system and feedlot finishing with one year cycle was evaluated. Thirty-six bulls from three groups F1Guzerat x Nellore F1 (GN); F1 Guzerá x Hosltein (GH) and F1 1/2 Simmental + 1/4 Guzerá + 1/4 Nellore (SG), with average age of 270 (± 30) days and average body weight of 241.3 (± 34.0) kg were utilized. The experimental design utilized was completely randomized (3 x 12). During the growing phase, bulls were kept in rotational Brachiaria brizantha cv Marandu pastures, receiving commercial supplement; in the finishing phase, they received a diet containing sorghum silage and concentrate (50:50) for 61 days. The performance indices evaluated were average daily weight gain (ADG), average daily gain during the period (ADP), final body weight. Economic performance indicators were total revenue, total operating expenses per bushel (COT / @), gross margin and net margin. Average daily gain during the growing phase was similar (P> 0.05) among groups with an average of 746 and 456 grams, respectively, for the period's transitional rainy / dry season. The TOE/bushel recreates the grouping of SD (R$ 69.44) was higher than that of groups GN (R$ 66.75) and GH (R$ 64.86). In the finishing period, ADG was similar (P> 0.05) among groups with an average of 1.55kg. The TOE/bushel of the feedlot finishing were R$ 91.48, R$ 114.15 and R$ 122.78 respectively for SD, GN and GH groups. Considering the analysis of the short-cycle system, we obtained the lowest TOE/bushel for grouping SD (R$77.92) followed by grouping GN (R$ 74.89) and GH (R$ 78.43). These results provided higher profitability for the crosses SD (21.99%) compared to other intersections (18.92% and 18.31% respectively, and for GN and GH). In the conditions evaluated the SD group was the most economically efficient.

Este trabalho teve como objetivo descrever as características ultrassonográficas uterinas e ovarianas, e dopplervelocimétricas das suas artérias nos dias periovulatórios em cadelas. Quinze ciclos estrais em 10 animais foram avaliados. As características ultrassonográficas, índices de resistência (IR) e índices de pulsatilidade (IP) do útero e dos ovários em cada animal foram registrados 5 dias antes e depois da ovulação (D0). Os dados foram analisados estatisticamente e os resultados foram expressos em média ± erro padrão da média (P<0,05). Como resultados as características ultrassonográficas uterinas foram semelhantes em todos os ciclos e dias avaliados, tendo o corpo uterino um diâmetro médio de 0,85±0,02cm. Foi observado um aumento no volume dos ovários e nos diâmetros dos folículos, tendo os ovários um volume de 0,64±0,06cm³, e a cavidade dos folículos um diâmetro de 0,46±0,01cm no dia da ovulação. Após a ovulação, foi observado colapso dos folículos somente em alguns ciclos. A perfusão sanguínea uterina diminuiu dois dias antes da ovulação e permaneceu inalterada até a ovulação. Após a ovulação, houve um aumento gradual na perfusão das artérias uterinas e ovarianas, direcionando o fluxo de sangue para os ovários e aumentando a perfusão da artéria intra-ovariana um dia após a ovulação. Conclui-se que características específicas são observadas na imagem ultrassonográfica uterina e ovariana, e dopplervelocimétricas de suas artérias nos dias periovulatórios, e quando associadas permitem estimar com mais precisão o dia da ovulação.

This paper aims to describe the uterine and ovarian ultrasonographic characteristics and Doppler velocimetric features of their arteries in bitches during the periovulatory period. Fifteen estrous cycles in 10 animals were evaluated. The ultrasonographic characteristics, resistance indices (RI) and pulsatility indices (PI) of the uterus and ovaries in each animal were recorded 5 days before and after ovulation (D0). The data were statistically analyzed, and the results were expressed as the mean ± standard error of mean (P<0.05). In results the ultrasonographic features of the uterus were the same on all of the cycles and evaluated days. The uterus had an average diameter of 0.85±0.02cm. An increase in the volume of the ovaries and the diameter of the ovarian follicles were measured. Ovaries had a volume of 0.64±0.06cm³, and the follicles cavities had a diameter of 0.46 ± 0.01 cm on the day of ovulation. After ovulation, it was observed that some follicles not collapse in some cycles. Two days prior to ovulation, the uterine blood perfusion decreased. This decrease remained unchanged until ovulation. Following ovulation, we measured a gradual increase in the uterine perfusion and in the ovarian artery. This artery directed blood flow to the ovaries and increased the intra-ovarian perfusion on the day after ovulation. In conclusion, specific features are observed in the uterus and ovarian ultrasound image and Doppler values of their arteries presented on the periovulatory days and when associated allow to estimate more accurately the date of ovulation.

O objetivo deste trabalho foi avaliar o efeito inseticida de extratos aquosos, alcoólicos e oleosos de folhas de oito plantas medicinais contra Diabrotica speciosa preparadas em cinco concentrações. Os extratos que utilizaram óleo de soja comercial como solvente apresentaram as maiores mortalidades de D. speciosa em função do próprio óleo, independentemente das plantas utilizadas em suas concentrações. Sendo assim, o óleo de soja comercial foi descartado como solvente, pois nestes volumes acarretaria sérios problemas de fitotoxidade. Após 24 horas de exposição da praga aos extratos, os maiores valores de mortalidade de D. speciosa foram observados nos extratos de Copaifera Langsdorfii e de Chenopodium ambrosioides, ambos em álcool 5%, e de Artemisia verlotorum, em água 10%. Entretanto, na última avaliação de mortalidade (48 h), o extrato de C. langsdorfii em álcool a 5% apresentou maior mortalidade dessa praga, seguida pelo extrato alcoólico a 5% de C. ambrosioides comparada às demais plantas.

The aim of this study was to evaluate the insecticidal effect of aqueous, alcoholic, and oil extracts from leaves of eight medicinal plants against Diabrotica speciosa prepared at five concentrations. The extracts that used commercial soybean oil as solvent showed the highest D. speciosa mortality due to the solvent itself, regardless of the used plants and their concentrations. Thus, commercial soybean oil was discarded as solvent since at these volumes it would cause serious phytotoxicity problems. After 24 hours of exposure of the pest to the extracts, the highest D. speciosa mortality values were observed for Copaifera langsdorfii and Chenopodium ambrosioides extracts, both in 5% alcohol, and Artemisia verlotorum, in 10% water. However, in the last mortality assessment (48 h), C. langsdorfii extract in 5% alcohol showed higher mortality of this pest, followed by C. ambrosioides extract in 5% alcohol, compared to the remaining plants.

O objetivo deste trabalho foi determinar o melhor método de extração e concentração para Ruta graveolens L. (Rutaceae), Artemisia verlotorum Lamotte (Asteraceae) e Petiveria alliacea L. (Phytolaccaceae) quanto ao efeito inseticida a Diabrotica speciosa Germar (Coleoptera: Chrysomelidae). Os extratos que utilizaram óleo de soja comercial, pelo menos como um dos solventes, apresentaram maior mortalidade de D. speciosa em suas testemunhas (solvente = óleo), nas três plantas estudadas, em relação às suas concentrações. O extrato aquoso de R. graveolens, a 5% de concentração, apresentou maior mortalidade corrigida de D. speciosa (32,5%) que os extratos de A. verlotorum em água (10% de concentração) (20,3%) e P. alliacea em álcool etílico (2% de concentração) (12,5%). O método de extração com água é simples, sendo passível de utilização por pequenos agricultores. A R. graveolens é planta facilmente cultivada, sendo, portanto, boa alternativa de controle dessa praga.

The aim of this work was to determine the best extraction method and concentration for Ruta graveolens L. (Rutaceae), Artemisia verlotorum Lamotte (Asteraceae) and Petiveria alliacea L. (Phytolaccaceae) concerning their insecticidal effect against Diabrotica speciosa Germar (Coleoptera: Chrysomelidae). Extracts using commercial soybean oil as at least one of the solvents resulted in higher D. speciosa mortality in controls (solvent = oil) of the three studied plants, relative to their treatment concentrations. R. graveolens extract in water, at 5% concentration, showed higher D. speciosa corrected mortality (32.5%) than A. verlotiorum extracts in water (10% concentration) (20.3%) and P. alliacea in ethanol (2% concentration) (12.5%). The extraction method with water is simple and can be used by small farmers. R. graveolens is an easily cultivated plant and constitutes, therefore, a good alternative to control this plague.

Studies have shown a time-of-day of training effect on long-term explicit memory with a greater effect being shown in the afternoon than in the morning. However, these studies did not control the chronotype variable. Therefore, the purpose of this study was to assess if the time-of-day effect on explicit memory would continue if this variable were controlled, in addition to identifying the occurrence of a possible synchronic effect. A total of 68 undergraduates were classified as morning, intermediate, or afternoon types. The subjects listened to a list of 10 words during the training phase and immediately performed a recognition task, a procedure which they repeated twice. One week later, they underwent an unannounced recognition test. The target list and the distractor words were the same in all series. The subjects were allocated to two groups according to acquisition time: a morning group (N = 32), and an afternoon group (N = 36). One week later, some of the subjects in each of these groups were subjected to a test in the morning (N = 35) or in the afternoon (N = 33). The groups had similar chronotypes. Long-term explicit memory performance was not affected by test time-of-day or by chronotype. However, there was a training time-of-day effect [F (1,56) = 53.667; P = 0.009] with better performance for those who trained in the afternoon. Our data indicated that the advantage of training in the afternoon for long-term memory performance does not depend on chronotype and also that this performance is not affected by the synchronic effect.

This work proposes the application of the thermogravimetry (TG) in the control of quality of Cissampelos sympodialis, known popularly as 'milona'. After the extraction process, the alkaloids became the majority substances and the extracts showed the kinetic behavior of the bisbenzylisoquinoline alkaloids. This seems to be an important and useful parameter for the quality control of the 'milona' extracts.