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Modelagem farmacocinética para otimização de doses de gentamicina em cães
(Universidade Federal de Lavras, 2025-03-25) Martins, Kevellyn Silveira Gomes; Ferrante, Marcos; Pereira, Aline Carvalho; Pinto, Juliana Tensol; Ferrante, Marcos; Marchetti, Maria Laura
Gentamicin is an aminoglycoside used to treat bacterial infections and is mainly used intravenously in hospitals. High concentrations of this drug can cause nephrotoxicity and ototoxicity. The aim of this study was to build pharmacokinetic models to predict the efficacy and risk of adverse effects of gentamicin doses in dogs. The first part of the study aimed to carry out this evaluation using a population pharmacokinetic model (popPK), which was built with Monolix software (Lixoft SAS, Simulations Plus Company), using raw data from a pharmacokinetic study carried out by Widerhon et al. In the second part of the study, efficacy and the risk of adverse effects were estimated by constructing a physiology-based pharmacokinetic model (PBPK), built with PK-Sim® software (Open Systems Pharmacology), using plasma concentration versus time data obtained from literature. Using the popPK model, it was possible to evaluate the efficacy of gentamicin for different minimum inhibitory concentrations and toxicity according to the dose administered. The PBPK model showed a high predictive performance, with a GMFE value of 1,13 for Cmax and 1,18 for AUC, meeting the double error criterion and was considered effective for predicting concentrations at different doses. Using this model, it was possible to simulate the concentration of gentamicin over a long period of time. The work thus proposed an approach aimed at optimizing dosages, according to the patient's clinical condition and bacterial infection, guaranteeing treatment efficacy and patient safety.
Qualidade e status antioxidante de oócitos recuperados de doadoras bos Taurus x Bos Indicus com alta e baixa contagem de folículos antrais
(Universidade Federal de Lavras, 2025-06-24) Martins, Clara Emmanuelly Mota; Alves, Nadja Gomes; Lima, Renato Ribeiro de; Torres, Barbara Azevedo Pereira; Siqueira, Luiz Gustavo Bruno; Carvalho,Bruno Campos de
Antral follicle count (AFC) has been associated with female fertility and oocyte quality, possibly related to oxidative status. However, the relationship between AFC and oocyte oxidative status is poorly understood. This study aimed to evaluate the oocyte quality of crossbred cows with high and low AFC, with emphasis on antioxidant status. Twenty-six lactating Holstein-Gir cows (1/2, 3/4, 5/8 and 7/8), primiparous and multiparous, with a milk production of 17.39 ± 8.38 kg/day and 108 ± 36 days in lactation, were used. Within the genetic groups, the cows were classified as low (first and second quartiles) or high AFC (fourth quartile), excluding the third quartile. Subsequently, they were grouped into G1 (1/2 and 5/8 HG: high CFA, n=3; low CFA, n=6) and G2 (3/4 and 7/8 HG: high CFA, n=5; low CFA, n=8). Cumulus-oocyte complexes (COCs) and follicular fluid were obtained by ovum pick-up after synchronization of follicular wave emergence. Viable COCs (grades I and II) were matured in vitro for 22 to 24 h and denuded for analyses of nuclear maturation, apoptosis, mitochondrial activity, and accumulation of reactive oxygen species (ROS). In the follicular fluid, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were evaluated. As expected, animals with high AFC presented more antral follicles compared to those with low: G1 (26.80 ± 3.61 vs. 15.54 ± 1.53; P<0.01) and G2 (24.60 ± 2.53 vs. 11.40 ± 1.04; P<0.001). The number of COCs recovered was higher in G1 compared to G2 (7.56 ± 1.19 vs. 4.62 ± 0.62; P<0.05). There was no difference (P > 0.05) between G1 and G2 regarding the percentage of viable COCs (65.33 ± 5.56 vs. 69.63 ± 7.26), nuclear maturation rates (51.84 ± 6.97 vs. 52.51 ± 7.08) and apoptosis (48.36 ± 10.26 vs. 1.75 ± 156.43). However, the percentage of degenerated COCs was lower in G1 (24.69 ± 3.50 vs. 36.80 ± 4.55%, P < 0.05). Mitochondrial activity was higher in oocytes from cows with low AFC compared to those with high AFC in G1 (19.55 ± 6.17 vs. 7.11 ± 2.76; P<0.05), but did not differ in G2 (16.92 ± 5.44 vs. 13.00 ± 4.07; P>0.05). ROS production was higher in cows with low AFC, both in G1 (38.98 ± 10.59 vs. 5.03 ± 1.67) and G2 (26.52 ± 8.19 vs. 9.00 ± 2.36; P<0.001). In follicular fluid, GPx activity was lower (0.0185 ± 0.0016 vs. 0.0258 ± 0.0018 U/mg protein/mL; P<0.05) and SOD activity tended to be lower (0.2001 ± 0.01598 vs. 0.2427 ± 0.01582 IU/mg protein/mL; P<0.07) in G1 compared to G2, but there was no difference (P>0.05) between cows with high or low AFC. Catalase activity did not differ (P>0.05) between genetic groups or AFC categories. It is concluded that AFC was not associated with the morphological quality of COCs. However, increased mitochondrial activity and/or ROS production without a concomitant increase in the antioxidant activity of the follicular fluid suggests oxidative stress in oocytes from cows with low AFC.
Perfil metagenômico durante a maturação de queijo elaborado com "pingo" e a influência da sua microbiota sobre Staphylococcus aureus
(Universidade Federal de Lavras, 2025-02-28) Sousa, Nathan Felipe Morais de; Piccoli, Roberta Hilsdorf; Arantes, Daniel; Boari, Cleube Andrade; Dorneles, Elaine Maria Seles; Schwan, Rosane Freitas; Pereira, Daniel Arantes
Artisanal Minas Cheese (QMA) is a traditional product from Minas Gerais, produced with raw milk and endogenous starter culture ("pingo"), whose microbiota directly influences its ripening, sensory quality, and microbiological safety. This study characterized the metataxonomic profile of a cheese analogous to QMA (QAQMA), produced from the "pingo" of a farm in the Campo das Vertentes region, under controlled conditions, throughout 22 days of ripening. Sixteen cheeses were produced, control (n=8) and inoculated (n=8). The control cheese was prepared in the traditional way, while the inoculated cheese was prepared with raw milk inoculated with 108 CFU/g of S. aureus. The influence of the autochthonous microbiota from the ―pingo‖ on Staphylococcus aureus was evaluated at four ripening times (0, 7, 14, and 22 days) by culture-dependent microbiological, physicochemical, and metataxonomic methods, from the sequencing of the V3-V4 region of the 16S rRNA. The physicochemical analyses showed a significant reduction in moisture (45.96% to 19.35%), and a pH variation between 6.79 and 6.86. The chloride content did not vary significantly during the ripening of the cheeses. The extension and depth of proteolysis indexes increased throughout ripening, indicating greater protein degradation and evolution of the ripening process. The milk microbiota was dominated by Pseudomonas, Serratia, and Lactococcus, while the "pingo" and the control cheese contained predominantly Lactococcus lactis (>92%). Some genera, such as Weissella, were observed only in the cheese, while others, such as Lactobacillus, were identified only in the "pingo" and cheese. The alpha diversity analysis pointed to the dominance of a few species, with L. lactis being predominant in the control cheese and L. lactis + S. aureus in the inoculated cheese. Beta diversity pointed to structural changes in the microbiota throughout ripening. The UniFrac distance evaluation pointed to milk as the most distinct sample, while the control cheese presented a community with low variation over time, unlike the inoculated group, which showed a gradual reduction of Staphylococcus and an increase of L. lactis. An increase in the similarity between the microbiotas of the inoculated and control cheese was observed, possibly due to the progressive replacement of S. aureus by Lactococcus. The PCoA (Bray-Curtis) indicated greater dispersion of the microbial community in the inoculated cheese, suggesting variations in the microbiota throughout ripening. The "pingo" microbiota showed moderate similarity with the microbiotas of the control and inoculated cheese, while the milk maintained a unique profile. The results suggest that ripening acts as a selective factor, reducing diversity and favoring the selection of L. lactis. The high presence of L. lactis in the cheese indicates a bioprotective effect, favoring the inhibition of S. aureus. The increase in proteolysis indexes associated with the selection of lactic acid bacteria reinforces the influence of the autochthonous microbiota on the ripening of QAQMA.
Nanopartículas na fisiologia e bioquímica de girassol sob estresse hídrico
(Universidade Federal de Lavras, 2025-09-16) Amoda, Deniasse Bernardo; Nery, Fernanda Carlota; Nascimento, Vitor de Laia; Guimarães, Luiz Gustavo de Lima; Reis, Michele Valquíria; Cunha Neto, António Rodrigues; Nery, Fernanda Carlota
Water deficit is one of the main environmental factors that affects plant growth and development. This study evaluated the effects of nanoparticles on ornamental sunflower Smiley under water stress. The experiment was conducted in a greenhouse and consist of two factors: the first factor consisted of four different molecule sources (copper sulfate, chitosan nanoparticles, and chitosan nanoparticles incorporated with copper sulfate), the second factor involved two water conditions (no water deficit at 90% of water retention capacity and water deficit at 60% of water retention capacity for a period of four consecutive days) which were factorially combined and laid out in a Completely Randomize Design (CRD) and replicated fifteen (15) times. The molecules were applied via foliar spray in the morning, between 8 and 9 a.m., with two applications before imposing water deficit during the vegetative phase V6 and the reproductive phase R1, respectively while water deficit was imposed at the beginning of the reproductive period, during the R1 phase. Growth, eco-physiological, and biochemical parameters were evaluated during the reproductive phase, at stages R4 and R5. Plant durability was assessed during the reproductive period, at stage R6. Results showed higher average values in the treatment with chitosan nanoparticles incorporated with copper sulfate. This treatment resulted to a higher mean values for variables such as plant height, stem diameter, midday water potential, stomatal conductance, photosynthetic pigments (chlorophylls a, b, and carotenoid content), reducing sugars, total soluble sugars, proteins, and amino acids. However, reductions in the mean values were observed for proline, malondialdehyde, and hydrogen peroxide levels. Additionally, higher averages were found in the activities of antioxidant enzymes superoxide dismutase, ascorbate peroxidase, and catalase. Greater mean values were also observed on the variables analyzed at the end of the experiment, such as relative water content, fresh biomass (roots, stems, leaves, and inflorescences), dry biomass (roots, leaves, inflorescences), and stem diameter. It can be concluded that chitosan nanoparticles, especially when incorporated with copper sulfate, have the potential to mitigate the effects of water stress in potted ornamental sunflower plants.
Um RPG eletrônico como recurso para o ensino de números reais no 9° ano do Ensino Fundamental em uma perspectiva histórica
(Universidade Federal de Lavras, 2025-09-30) Silva, Karina de Fátima Mesquita; Teodoro, Graziane Sales; Costa, Maria do Carmo Pacheco de Toledo; Fargnoli Filho, Helvécio Geovani; Vasconcelos, Lívia de Oliveira
This dissertation presents an investigation into the teaching of real numbers in the 9th grade of Elementary School through the integration of the History of Mathematics and the use of a RPG (Role-Playing Game). The study stems from the recognition that real numbers still represent an important challenge in the learning process of the students, especially when introduced in an exclusively formal manner. The main objective was to investigate the possible contributions that the relationship between historical narrative and interactive digital games can offer to the conceptual understanding of real numbers, particularly regarding the distinction between ratio- nal and irrational numbers. To achieve this purpose, a qualitative research study was conducted, involving the development of a teaching sequence based on the game titled The Guardian of the History of Mathematics: The Legacy of Numbers, authored by the researcher, and developed for pedagogical purposes. The teaching sequence was implemented in a public school in the south of Minas Gerais, with data collected through questionnaires, observations, and student productions. The analysis considered categories such as conceptual understanding, perception of the History of Mathematics, and evaluation of the game as a pedagogical resource. The re- sults revealed progress in the ability of the students to classify and distinguish between rational and irrational numbers, overcome recurring conceptual misconceptions, and relate real numbers to concrete situations. Greater engagement and motivation during the activities were also ob- served, fostered by the narrative and interactivity of the digital environment. Furthermore, the students recognized the History of Mathematics as an important element for understanding the origin and function of numerical concepts, attributing more meaning to the study of the content. Simultaneously, the proposal proved to be adaptable to other content areas, constituting a viable and innovative alternative for teaching Mathematics.