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The potential of ketogenic approaches to regulate energy balance has recently gained attention since ketones may influence both energy expenditure and energy intake. In this narrative review, we summarized the most relevant evidence about the role of ketosis on energy expenditure, substrate utilization, and energy intake in humans. We considered different strategies to induce ketosis, such as fasting, dietary manipulation, and exogenous ketone sources. In general, ketosis does not have a major influence on energy expenditure but promotes a shift in substrate utilization towards ketone body oxidation. The strategies to induce ketosis by reduction of dietary carbohydrate availability (e.g., ketogenic diets) do not independently influence energy intake, being thus equally effective for weight loss as diets with higher carbohydrate content. In contrast, the intake of medium-chain triglycerides and ketone esters induces ketosis and appears to increase energy expenditure and reduce energy intake in the context of high carbohydrate availability. These latter strategies lead to slightly enhanced weight loss. Unfortunately, distinguishing the effects of the various ketogenic strategies per se from the effects of other physiological responses is not possible with the available human data. Highly controlled, inpatient studies using targeted strategies to isolate the independent effects of ketones are required to adequately address this knowledge gap.

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Ketogenic diet therapy (KDT) is a nonpharmacological treatment that has been demonstrated to be effective in reducing seizures in patients with drug-resistant epilepsy. As the majority of patients on KDT are also receiving anti-seizure medications (ASMs), questions about their combination often arise. KDT is typically implemented as an add-on, and not a substitute for ASMs. Drug monitoring and specific laboratory studies may be helpful in specific cases of cotherapy. Valproate, topiramate, zonisamide, and lamotrigine may be potentially problematic with KDT, but the evidence for this is not conclusive. ASM reduction is usually attempted after 1 month of KDT if a child is showing seizure reduction (but weaning ASMs does not require seizure freedom). Failure to wean an ASM does not mean KDT has failed and adding a new ASM may be beneficial in those cases after several months of KDT fine-tuning. The purpose of this review was to discuss the evidence for possible negative (or positive) pharmacodynamic interactions between KDT and ASMs. In addition, practical suggestions for the weaning or adding of ASMs in patients on KDT are provided.

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ABSTRACT: This study evaluated milk fat to protein ratio (FPR) in the first test-day after calving of dairy cows in Paraná State. Data from 257,847 first monthly test-days after calving of 114,162 cows were submitted to analysis after the data edition. Procedures MIXED, CORR and STEPWISE from SAS were used in the data analysis. In order to validate FPR, a herd with regular postpartum monitoring of blood β-hydroxybutyrate (BHB) was used to estimate the correlation with FPR. There was a strong positive correlation between FPR and fat content (r = 0.85; P < 0.01) and a weak negative correlation between FPR and protein content (r = - 0.23; P < 0.01). The regression equation that best fitted FPR was 1.1806 + 0.3304*%F - 0.3877*%P (R2 = 0.98), where the variable with the greatest influence was milk fat content (partial R2 = 0.72). Animals of 4th and 5th or more lactations had higher (P < 0.01) FPR, followed by animals of third, first, and second lactations. Jersey cows had higher (P < 0.01) FPR than Holsteins and Brown Swiss animals. Cows milked twice daily had higher (P < 0.01) FPR than animals milked three times daily. There were small positive correlations between milk FPR and blood BHB on days 4, 7 and 12 after calving (0.07, 0.13, and 0.14, respectively). In conclusion, milk fat content was reported to be the most important variable affecting FPR changes, but the milk FPR has limited value to evaluate hyperketonemia incidence during the transition period.

RESUMO: Este estudo teve como objetivo avaliar a relação gordura:proteína (RGP) no primeiro controle leiteiro no pós-parto de vacas no estado do Paraná. Dados de 257.847 controles de 114.162 vacas leiteiras, realizados no primeiro controle mensal após o parto foram submetidos à análise estatística após edição dos dados. Os procedimentos MIXED, CORR e STEPWISE do programa estatístico SAS 9.4 foram utilizados. A fim de validar a RGP, um rebanho com monitoramento regular de β-hidroxibutirato (BHB) no sangue foi utilizado para estimar a correlação com RGP. Observou-se uma correlação forte e positiva entre a RGP e teor de gordura no leite (r = 0,85; P < 0,01) e uma correlação fraca e negativa entre a RGP e o teor de proteína (r = -0,23; P < 0,01). A equação de regressão que melhor se ajusta à RGP foi 1,1806 + 0,3304*%G - 0,3877*%P (R2 = 0,98), na qual a variável com maior influência foi a porcentagem de gordura (R2 = 0,72). Animais de 4ª e 5ª lactações ou mais, apresentaram maior (P < 0,01) RGP, seguidos dos animais de terceira, primeira e segunda lactações, com menores RGP. Vacas da raça Jersey apresentaram maior (P < 0,01) RGP que vacas da raça Holandesa e Pardo-Suíça. Animais com duas ordenhas diárias apresentaram maior (P < 0,01) RGP que os animais ordenhados três vezes ao dia. Observaram-se correlações positivas, mas de pequena magnitude, entre a RGP do leite e BHB no sangue no quarto, sétimo e 12 dias pós-parto (0,07, 0,13 e 0,14; respectivamente). Concluindo, o teor de gordura é o fator que mais impacta as variações da RGP do leite, mas a RGP tem valor limitado na avaliação da incidência de hipercetonemia no período de transição.

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This study evaluated milk fat to protein ratio (FPR) in the first test-day after calving of dairy cows in Paraná State. Data from 257,847 first monthly test-days after calving of 114,162 cows were submitted to analysis after the data edition. Procedures MIXED, CORR and STEPWISE from SAS were used in the data analysis. In order to validate FPR, a herd with regular postpartum monitoring of blood ß-hydroxybutyrate (BHB) was used to estimate the correlation with FPR. There was a strong positive correlation between FPR and fat content (r = 0.85; P < 0.01) and a weak negative correlation between FPR and protein content (r = - 0.23; P < 0.01). The regression equation that best fitted FPR was 1.1806 + 0.3304*%F - 0.3877*%P (R2 = 0.98), where the variable with the greatest influence was milk fat content (partial R2 = 0.72). Animals of 4th and 5th or more lactations had higher (P < 0.01) FPR, followed by animals of third, first, and second lactations. Jersey cows had higher (P < 0.01) FPR than Holsteins and Brown Swiss animals. Cows milked twice daily had higher (P < 0.01) FPR than animals milked three times daily. There were small positive correlations between milk FPR and blood BHB on days 4, 7 and 12 after calving (0.07, 0.13, and 0.14, respectively). In conclusion, milk fat content was reported to be the most important variable affecting FPR changes, but the milk FPR has limited value to evaluate hyperketonemia incidence during the transition period.

Este estudo teve como objetivo avaliar a relação gordura:proteína (RGP) no primeiro controle leiteiro no pós-parto de vacas no estado do Paraná. Dados de 257.847 controles de 114.162 vacas leiteiras, realizados no primeiro controle mensal após o parto foram submetidos à análise estatística após edição dos dados. Os procedimentos MIXED, CORR e STEPWISE do programa estatístico SAS 9.4 foram utilizados. A fim de validar a RGP, um rebanho com monitoramento regular de ß-hidroxibutirato (BHB) no sangue foi utilizado para estimar a correlação com RGP. Observou-se uma correlação forte e positiva entre a RGP e teor de gordura no leite (r = 0,85; P < 0,01) e uma correlação fraca e negativa entre a RGP e o teor de proteína (r = -0,23; P < 0,01). A equação de regressão que melhor se ajusta à RGP foi 1,1806 + 0,3304*%G - 0,3877*%P (R2 = 0,98), na qual a variável com maior influência foi a porcentagem de gordura (R2 = 0,72). Animais de 4ª e 5ª lactações ou mais, apresentaram maior (P < 0,01) RGP, seguidos dos animais de terceira, primeira e segunda lactações, com menores RGP. Vacas da raça Jersey apresentaram maior (P < 0,01) RGP que vacas da raça Holandesa e Pardo-Suíça. Animais com duas ordenhas diárias apresentaram maior (P < 0,01) RGP que os animais ordenhados três vezes ao dia. Observaram-se correlações positivas, mas de pequena magnitude, entre a RGP do leite e BHB no sangue no quarto, sétimo e 12 dias pós-parto (0,07, 0,13 e 0,14; respectivamente). Concluindo, o teor de gordura é o fator que mais impacta as variações da RGP do leite, mas a RGP tem valor limitado na avaliação da incidência de hipercetonemia no período de transição.

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A cetose, conhecida também como acetonemia, é um distúrbio metabólico que afeta principalmente vacas leiteiras de alta produção. A elevação anormal de corpos cetônicos nos tecidos e fluidos corporais do animal ocorre devido a um déficit de energia. A quantidade de alimento/nutrientes ingeridos não é suficiente para suprir a demanda corporal do mesmo, assim como a eficiência reprodutiva que está diretamente ligada à saúde, condição corporal e sua capacidade de produção. Animais de alta produção possuem um desafio muito grande de aumentar a produção a cada lactação, com isso, estão susceptíveis a mudanças metabólicas, entre elas a cetose, clínica ou subclínica. Tal enfermidade ocorre devido a uma má adaptação metabólica do animal a sua nova condição de lactante. A elevada incidência de doenças uterinas no pós-parto de vacas leiteiras é responsável por inúmeros prejuízos para a atividade, principalmente pela redução da eficiência reprodutiva das vacas acometidas por infecções. Contudo, visto que a cetose subclínica prevalece nos rebanhos leiteiros de alta produção, o objetivo desta revisão de literatura é apresentar a patogenia e os efeitos que esse distúrbio metabólico têm sobre a reprodução das vacas de aptidão leiteira no após o parto, utilizando de indicadores como taxa de prenhez, taxa de concepção, retorno a ciclicidade, intervalo entre partos e intervalo entre parto e estro.(AU)

Ketosis, also known as acetonemia, is a metabolic disorder that primarily affects high-yielding dairy cows. The abnormal elevation of ketone bodies in the animal's tissues and body fluids occurs due to an energy deficit. The amount of food/nutrients ingested are not enough to supply the body's demand, as well as the reproductive efficiency that is directly linked to health, body condition and its production capacity. High production animals have a very big challenge to increase production with each lactation, therefore, they are susceptible to metabolic changes, including clinical or subclinical ketosis. Such a disease occurs due to a poor metabolic adaptation of the animal to its new lactating condition. The high incidence of uterine diseases in the postpartum period of dairy cows is responsible for numerous losses to the activity, mainly for the reduction of the reproductive efficiency of cows affected by infections. However, since subclinical ketosis prevails in high production dairy herds, the objective of this literature review is to present the pathogenesis and the effects that this metabolic disorder has on the reproduction of dairy cows in the postpartum period, using indicators such as pregnancy rate, conception rate, return to cyclicity, calving interval and calving-estrus interval.(AU)

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Metabolic stress conditions caused by negative energy balance (NEB) have been associated with reduced fertility in cows. ß-hydroxybutyrate (BHBA) is the main circulating ketone body, which accumulates within follicular fluid. The aim of this study was to evaluate the effects of BHBA on follicle growth and on ovulatory mechanisms in cattle. At 72 h after intrafollicular injection, there was a decrease in follicular diameter in BHBA group compared to control (P = 0.02). Furthermore, follicle growth rate was reduced post-treatment with BHBA in comparison to the control group (P < 0.03). The BHBA intrafollicular injection in follicles ≥ 12 mm, however, did not affect E2 and P4 concentrations in the follicular fluid. In addition, the relative abundance of genes involved in the ovulatory cascade (ADAM 17, AREG, EREG, PTGS2), steroidogenesis (CYP19A1, 3BHSD, STAR), cellular stress (SOD1, CAT, GPX1, HSPA5, XBP1s, XBP1u, ATF4, ATF6), monocarboxylic acid transporters (SLC16A1, SLC16A7) and apoptosis (XIAP) was similar between groups. In conclusion, the results of this study indicate that the increase in intrafollicular concentrations of BHBA affects follicular growth, but it does not compromise the ovulatory cascade and cellular homeostasis in bovine granulosa cells.

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BACKGROUND: Ischemic kidney injury is a common clinical condition resulting from transient interruption of the kidney's normal blood flow, leading to oxidative stress, inflammation, and kidney dysfunction. The ketogenic diet (KD), a low-carbohydrate, high-fat diet that stimulates endogenous ketone body production, has potent antioxidant and anti-inflammatory effects in distinct tissues and might thus protect the kidney against ischemia and reperfusion (IR) injury. MAIN METHODS: Male Wistar rats were fed a KD or a control diet (CD) for three days before analyzing metabolic parameters or testing nephroprotection. We used two different models of kidney IR injury and conducted biochemical, histological, and Western blot analyses at 24 h and two weeks after surgery. KEY FINDINGS: Acute KD feeding caused protein acetylation, liver AMPK activation, and increased resistance to IR-induced kidney injury. At 24 h after IR, rats on KD presented reduced tubular damage and improved kidney functioning compared to rats fed with a CD. KD attenuated oxidative damage (protein nitration, 4-HNE adducts, and 8-OHdG), increased antioxidant defenses (GPx and SOD activity), and reduced inflammatory intermediates (IL6, TNFα, MCP1), p50 NF-κB expression, and cellular infiltration. Also, KD prevented interstitial fibrosis development at two weeks, up-regulation of HSP70, and chronic Klotho deficiency. SIGNIFICANCE: Our findings demonstrate for the first time that short-term KD increases tolerance to experimental kidney ischemia, opening the opportunity for future therapeutic exploration of a dietary preconditioning strategy to convey kidney protection in the clinic.

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Background: Ketosis is the most important metabolic disease with prevalence from 15 to 45%. Ketosis is diagnosed using a metabolic profile. Due to the high prevalence, it is necessary to determine a large number of metabolic profiles within farm, which represents an additional cost, so the implementation of pooled serum in assessing the metabolic status of cows was examined. The aim of this study was to validate and evaluate the influence of the relative position (Z-score) of the value of pooled sample metabolic parameters within the known reference value of healthy cows in the detection of ketosis in herd during early lactation. Materials, Methods & Results: The experiment has been carried out using blood samples collected by puncture of coccygeal vein from 50 ketotic and 50 healthy cows. Laboratory analysis includes determination of beta-hydroxybutyrate-BHB, non-esterified fatty acids-NEFA, cholesterol-CHOL, triglycerides-TGC, glucose-GLU, albumin-ALB, total protein-TPROT, UREA, Ca, P, total bilirubin-TBIL and aspartat aminotransferase-AST. The pooled serum was made from 10 individual samples originating from 10 different cows. A serum aliquot of 0.1 mL was taken from each sample, and a 1 mL volume of pooled serum was finally formed. Three types of serum pools were made: 1) 30 pooled sample were from ketosis; 2) 30 pooled sample were from healthy cows and 3) 60 pooled samples containing mixed sera of healthy cows and cows with ketosis were made as follows: 10 pools contain 10% to 60% of ketotic cows (1/10 to 6/10 samples). Statistical analysis includes: a) difference in metabolite concentration and Z-score in pooled sample and arithmetic mean individual sample in healthy and ketotic cow, b) correlation between Z-score of pooled sample and arithmetic mean of individual sample, c) ability of Z-score of metabolite to divide ketotic from healthy cow, d) correlation between Z-score and % of ketotic cow in pooled sample; and e) calculation of 95%CI of pooled sample Z-scores for each % of ketotic cow in pools. Z-score and all analysis were calculated for each metabolic parameter. The results of the study show that the mean values and Zscores of the pool and the calculated average value of the individual samples participating in that pool differ significantly in healthy cows and cows in ketosis, except for TPROT and Ca. A higher value and a higher Z-score were found for BHB, NEFA, UREA, TBIL and AST, and a lower value and a lower Z-score for TGC, CHOL, GLU, ALB and P in ketotic cows compared to healthy cows. The value of the Z-score of the pooled sample and the calculated mean values of individual samples participating in the pool are highly correlated with each other (coefficient of determination over 99%). Z-score of metabolites in the pooled sample can be used to distinguish healthy from ketotic cows (ROC AUC= 0.711 to 0.989), except for TPROT and Ca. The Z-score value of the pooled sample shows a linear correlation with the percentage of ketotic cows in the pool and the reference ranges of Z-scores change significantly as a function of the percentage of ketosis cows. Discussion: Modern research on the metabolic profile in cows requires obtaining a large amount of information from as few samples as possible. The advantages of using the Z-score are reflected in the following: this score does not depend on the absolute value of the metabolite, but on the position within the known population reference value, Z-score of sample and the arithmetic mean of individual samples included in the same pool are almost identical, the Z-score of these 2 groups of results is ideally correlated, the Z-score significantly correlates with the % of ketosis samples in the pooled sample. The use of pooled sample Z-score can be a useful in a herd level assessment of metabolic status and detection of ketosis as most important metabolic disease in dairy cows.

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Postpartum cows, mainly with metabolic diseases, such as ketosis, usually experience an increased number of services per conception. During ketosis, high concentrations of ß-hydroxybutyrate (BHBA) in follicular, uterine and oviductal fluid have been considered to cause subfertility in cows. However, the effect of sperm exposure to an environment with high BHBA concentration is not known. This study investigated the influence of high levels of BHBA on kinetics, oxidative status and morphology of bovine spermatozoa. To assess the effect of BHBA after sperm selection, bovine spermatozoa were incubated (180 min) with different BHBA concentrations: 0 (Control), 0.8, 2.4 or 5 mM. Sperm kinetics was evaluated after 30, 60, 120 and 180 min, and oxidative status and morphology were analysed at 180 min. Oxidative status was evaluated through the production of reactive oxidative species (ROS), total antioxidant capacity and lipid peroxidation. High concentrations of BHBA decreased the curvilinear velocity, straight line velocity, mean path velocity, linearity, straightness and hyperactivity of spermatozoa. However, there was no effect of BHBA on oxidative and antioxidant capacity as well as on sperm morphology. In conclusion, exposure of bovine spermatozoa to high levels of BHBA impairs sperm kinetics without altering oxidative and antioxidant mechanisms.

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Tuberculosis remains a significant infectious disease of farm animals and humans worldwide. The objective of this study was to assess various risk factors associated with testing positive for bovine tuberculosis (bTB) in high-yielding Holstein cows in an intensive dry-lot dairy operation. In a retrospective observational study, 9312 records from Holstein cows from a large dairy herd in northern Mexico were used. The incidence rate of lactating cows reactor to bTB was 7.3 cases/100 cow years (95% CI = 6.7-7.9%). Multiple logistic regression models indicated that cows with total milk yield during the first lactation >10,200 kg were 1.3 times (95% confidence intervals (CI) for odds ratio (OR) = 1.2-1.6) more likely to be detected as bTB reactors than cows with total milk yield <10,200 kg (8.2 vs. 6.4%; P < 0.01). The risk of being reactor to bTB increased with x̅ total milk yield/lactation >11,500 kg (OR=2.7, 95% CI = 2.3-3.3; 10.4 vs. 4.2%) compared with cows with x̅ total milk yield/lactation <11,500 kg. Cows with >10,200 kg 305-day milk yield in the last lactation was associated (P < 0.01) with 1.3 times higher odds (95% CI for OR = 1.1-1.5) of being classed as reactors than cows with <10,200 kg. Cows with peak milk yield >48 kg were 1.9 times (95% CI for OR = 1.6-2.2) more likely to be reactor to bTB than cows with peak milk yield <48 kg (9.2 vs. 5.1%; P < 0.01). Cows with either puerperal metritis (OR = 0.07, 95% CI = 0.5-0.9) or carrying twins (OR = 0.05, 95% CI = 0.01-0.19) had a protective role for being reactor to bTB. This study showed that increased milk production was associated with a higher risk of becoming positive to tuberculin skin test in high-yielding Holstein cows.

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Ketosis can seriously impair cow performance. This study detected changes in prepartum blood metabolic parameters for predicting postpartum ketosis occurrence in dairy cows. Body condition score (BCS) was assessed before and after delivery. Blood samples of 63 cows were collected from 10 days before calving to 10 days after calving to measure metabolic parameters including ß-hydroxybutyric acid (BHBA), non-esterified fatty acid (NEFA), glucose (GLU), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total protein (TP), albumin (ALB), globulin (GLO), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). There was a postpartum subclinical ketosis incidence of 42.25%. Compared with prepartum, plasma, levels of BHBA, AST, and NEFA significantly increased postpartum, and prepartum AST (R=0.57) and NEFA (R=0.45) showed a significant positive correlation with ketosis postpartum. Plasma GLU level significantly decreased postpartum and was significantly negatively correlated with ketosis (R=-0.21). Receiver operating characteristic curve analysis revealed prepartum BSC < 2.88, and prepartum plasma AST > 68.0 U/L, GLU < 3.97mmol/L, NEFA > 0.27mmol/L, and BHBA > 0.43mmol/L, indicating a high risk of subclinical ketosis postpartum. These levels can be used as risk indicators to predict the occurrence of subclinical ketosis in postpartum cows.(AU)

A cetose pode trazer sérios prejuízos ao desempenho da vaca. Este estudo detectou alterações nos parâmetros metabólicos do sangue pré-parto para prever a cetose pós-parto que ocorre em vacas leiteiras. O escore de condição corporal (ECC) foi avaliado antes e após o parto. Foram coletadas amostras de sangue de 63 vacas entre 10 dias antes e 10 dias após o parto para medir os parâmetros metabólicos, incluindo ácido ß-hidroxibutírico (BHBA), ácido graxo não esterificado (NEFA), glicose (GLU), bilirrubina total (TBIL), bilirrubina direta (DBIL), bilirrubina indireta (IBIL), proteína total (TP), albumina (ALB), globulina (GLO), alanina aminotransferase (ALT) e aspartato aminotransferase (AST). Houve uma incidência de cetose subclínica pós-parto de 42,25%. Em comparação com o pré-parto, o plasma, os níveis de BHBA, AST e NEFA aumentaram significativamente no pós-parto, e AST no pré-parto (R = 0,57) e NEFA (R = 0,45) mostraram uma correlação significativa positiva com cetose pós-parto. O nível plasmático de GLU diminuiu significativamente no pós-parto e foi negativamente correlacionado com a cetose de forma significativa (R = -0,21). A análise da curva característica de operação do receptor revelou BSC pré-parto <2,88 e AST plasmático pré-parto> 68,0 U / L, GLU <3,97mmol / L, NEFA> 0,27mmol / L e BHBA> 0,43mmol / L, indicando um alto risco de cetose subclínica pós-parto. Esses níveis podem ser usados ​​como indicadores de risco para prever a ocorrência de cetose subclínica em vacas no pós-parto.(AU)

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RESUMEN Objetivo. Determinar la prevalencia de cetosis bovina según las concentraciones séricas (mmol/Lt) de beta-hidroxibutirato (βHB) y estimar su asociación con enfermedades del posparto temprano en vacas lecheras. Materiales y métodos. Se llevó a cabo un estudio epidemiológico de corte transversal con información individual de los niveles sanguíneos de βHB y presentación clínica de enfermedades puerperales de n=1149 animales; además se evaluó la eficiencia de la prueba como predictora de enfermedad posparto. Posteriormente, se realizó X 2 y un modelo de regresión logística final para explorar los factores asociados con hipercetonemia. La relación entre βHB sanguíneo, la presentación de cetosis y la ocurrencia de enfermedades puerperales se calculó analizando Característica Operativa del Receptor (Receiver Operating Characteristic -ROC). Resultados. Según los niveles de -3HB, la prevalencia de cetosis fue de 7.9%, cetosis clínica 0.6% y cetosis subclínica 7.3%. La prueba fue predictora de enfermedad puerperal (LR+ del 13.6). La condición corporal ≥3.5, número de partos igual a 2 y ≥3, la presentación de retención de placenta, fiebre de leche y la enfermedad posparto, son factores de riesgo de cetosis. El análisis de la curva ROC mostró que la medición de βHB (≥1.2 mmol/Lt) en sangre sirve para diagnosticar cetosis (p<0.0001). Conclusiones. La medición de niveles sanguíneos de βB permitió determinar que la presentación de cetosis es baja, es una alerta no solamente para esta enfermedad sino para las enfermedades del posparto temprano. Los resultados de este estudio confirman lo reportado en estudios previos sobre los factores de riesgo de cetosis.

ABSTRACT Objective. Determine the prevalence of bovine ketosis based on serum concentrations (mmol/Lt) of beta-hydroxybutyrate (βHB) and estimate its association with early postpartum diseases in dairy cows. Materials and methods. An epidemiological cross-sectional study was carried out with individual information on blood levels of βHB and clinical presentation of puerperal diseases in 1149 animals; In addition, the efficiency of the test was evaluated as a predictor of postpartum disease. Subsequently, univariate analysis and a final logistic regression model were performed to explore the factors associated with hyperketonemia. The association between blood βHB, the presentation of ketosis and the occurrence of puerperal diseases was calculated by analyzing the Receiver Operating Characteristic -ROC. Results. According to βHB levels, the prevalence of ketosis was 7.9%, clinical ketosis 0.6% and subclinical ketosis 7.3%. The test was a predictor of puerperal disease (LR+ of 13.6). Body condition score ≥3.5, number of births 2 and ≥3, presentation of retained fetal membranes, milk fever and postpartum disease, are risk factors for ketosis. The analysis of the ROC curve showed that the measurement of βHB (≥1.2 mmol/Lt) in blood serves to diagnose ketosis (p<0.0001). Conclusions. The measurement of βHB blood levels allowed to determine that ketosis presentation is low, it is an alert not only for this disease but for early postpartum diseases. The results of this study confirm risk factors observed in previous studies.

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The aims of this study were to characterize the biochemical profile, the reproductive performance and to identify potential predictive biomarkers of disease state of dairy cows with hyperketonemia, lipomobilization and hypocalcemia raised in tropical conditions in southeastern Brazil. Dairy cows (n = 50) were divided into a group of healthy cows (n = 14), cows with lipomobilization (n = 14), cows with hypocalcemia (n = 11), and a group of cows with hyperketonemia (n = 11). Evaluation of body condition score (BCS), body weight (BW) and blood samples was performed on 21, 14, 7, 4 and 2 days before calving, parturition, 1, 7, 14, 21, 30, 45 and 60 days post-partum and milk production was recorded on days 7, 14, 21, 30, 45 and 60 after parturition. Blood samples were assayed for aspartate aminotransferase (AST), gamma-glutammyltransferase (GGT), albumin, total protein, globulin, fibrinogen, total cholesterol, triglyceride, urea and creatinine concentrations. The biochemical profile, BCS, BW, milk production and reproductive performance differed (p < .05) among the groups. Our findings indicate changes in the biochemical profile of dairy cows with metabolic diseases and impaired production and fertility of dairy cows in this group. Variable importance in projection plots demonstrated that cholesterol, urea, total protein, albumin and fibrinogen in the serum were the strongest discriminators between cows with hypocalcemia and healthy cows; and AST, cholesterol, urea and triglycerides for cows with hyperketonemia and healthy cows; and cholesterol, urea, triglycerides, total protein and fibrinogen for lipomobilization and healthy cows, which might be useful as predictive biomarkers of the disease state.

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RESUMEN La hipercetonemia o cetosis bovina es un desorden metabólico, que se caracteriza por el incremento patológico de cuerpos cetónicos (beta-hidroxibutirato (βHB), Acetoacetato (AcAc) y acetona) y ocurre en el periparto de vacas de leche. El origen primario de la enfermedad es el balance energético negativo (BEN), que puede ser desencadenado por el incremento excesivo de los requerimientos energéticos o la presentación de enfermedades posparto, resultando en la presentación de signos clínicos o disminución de la producción de leche. El objetivo de esta revisión consiste en describir, mediante un modelo, los procesos bioquímicos del rumen y los mecanismos fisiopatológicos, involucrados con incremento excesivo de los cuerpos cetónicos. En resumen, se realizó un modelo fisiológico uniendo literatura fragmentada, sobre la relación entre la función ruminal, hepática y la inducción de lipolisis e incremento de la actividad de Carnitil-Palmitoil transferasa-1 (CPT-1), cuyo resultado puede ser la producción excesiva de Acetil-CoA que, junto con la falta de propionato y oxalacetato (precursores de gluconeogénesis y ciclo de Krebs), dan lugar a la producción patológica de acetoacetato y beta-hidroxibutirato.

ABSTRACT Bovine hyperketonemia or ketosis is a metabolic disorder characterized by high levels of ketone bodies (beta-hydroxybutyrate (βHB), Acetoacetate (AcAc), and acetone) in periparturient dairy cows. A Negative Energy Balance (NEB) is identified as the primary cause of the disease, which is triggered by the excessive increase of energy requirements or the presence of postpartum diseases, resulting in the appearance of clinical signs or decreased milk production. The purpose of this review is to describe the rumen's biochemical Process and the physiopathological mechanisms involved in the excessive production of ketone bodies. After conducting a literature review, a physiological model was carried out in order to understand the relationship between the rumen and liver functions with lipolysis induction and increased CPT-1 activity. The above may result in the overproduction of Acetyl-CoA, which together, with the lack of propionate and oxaloacetate (gluconeogenesis and Krebs cycle precursors), leads to the pathological production of acetoacetate and beta-hydroxybutyrate.

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Spinal muscular atrophy is an uncommon cause of ketoacidosis, where there is a decrease in muscle mass, an abnormal metabolism of glucose and fatty acids, and changes in neuroendocrine function. These conditions favor the accumulation of keto acids and the development of metabolic acidosis. We report a 26-year-old female, with a history of spinal muscular atrophy type III, consulting for abdominal pain and vomiting lasting one week. She was admitted to the emergency service somnolent and poorly perfused. She had a pH of 6.98, HCO3- of 3.8 mmol/L, pCO2 of 16.4 mmHg, BE of -26 mmol/L, delta ratio of 1.05, anion gap of 31 mEq/L, creatinine of 0.37 mg/dL, sodium of 147 mEq/L, potassium of 3.7 mEq/L, chloride of 112 mEq/L, lactate of 1.2 mmol/L, glucose of 108 mg/dL, albumin of 4.2 g/dL, ketonemia +++, ketonuria +, measured plasma osmolality of 322 mOsm/kg, estimated osmolality of 314 mOsm/kg, toxilab negative, salicylate levels < 3 µg/mL, acetaminophen levels < 1.2 µg/mL. Intravenous hydration and bicarbonate were started, without satisfactory response. Interpreting the clinical picture as a ketoacidosis induced by stress in a patient with spinal muscular atrophy, it was handled with glucose, amino acids, vitamins and trace elements, with a favorable response.

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BACKGROUND: The end of pregnancy is the period with the highest risk of occurrences of ketosis and pregnancy toxemia due to fat mobilization and increasing non-esterified fatty acids in the liver which are converted in ketone bodies, mainly ß-hydroxybutyrate acid (BHB). This ketone body may also become elevated in the bloodstream. The present study validates the use of a handheld meter for determining the blood concentration of BHB and ascertaining the predictive value and accuracy of BHB measurements in diagnosing hyperketonaemia in ewes. METHODS: A total of 19, non-pregnant, crossbred ewes were subjected to 2 h of intravenous infusion of a saturated BHB solution. Over 6 h of evaluation, 247 blood samples were obtained in 13 sampling moments. The BHB concentration was measured by an enzymatic colorimetric method in an automated biochemical analyzer (gold-standard) and by a handheld meter using an electrochemical enzyme technique. RESULTS: There was a high correlation between both methods (r = 0.98; P < 0.001). Considering the blood BHB concentrations range 0.8-1.6 mmol/L for moderate ketosis the handheld meter presented sensitivity and specificity of 0.98 and 0.81, respectively. For severe ketosis (BHB ≥ 1.6 mmol/L) sensitivity and specificity were 0.99 and 0.75, respectively. Thus, the handheld device can be useful for diagnoses of cases of mild or severe pregnancy toxemia at field conditions.

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Background: Cows in perinatal period are prone to ketosis, characterized by increased ketone bodies and decreased bloodsugar. Study found that cows with type II ketosis had higher blood glucose levels. This type of ketosis exhibits insulinresistance and impaired glucose tolerance that are similar to type 2 diabetes. The purpose of this study was to investigatethe role of insulin resistance(IR) in type II ketosis in dairy cows.Materials, Methods & Results: In one intensive cattle farm, eight cows with ketosis and eight healthy cows that were 14-21 days postpartum were selected. The plasma of experimental dairy cows was collected and tested for the concentrationof glucose concentration. Glucose tolerance of blood glucose levels in 120 min was used as the cut-off point to divide thedairy cows into three groups: the abnormal glucose tolerance ketosis group (TH), the normal glucose tolerance ketosis(TL), and the healthy control group. Simultaneously, the indexes of plasma liver function, oxidative stress, and insulinresistance were detected. The results showed that after intravenous glucose injection, there was no significant differencein blood glucose concentration between the TL and control group, while the blood glucose levels in the TH group werealways higher than in the other two groups. The insulin sensitivity index (RQUICKI) value was significantly lower in theTH group than in the other two groups. Liver function abnormalities in the TH group were more severe than in the TL andcontrol group. Oxidative stress was higher in the TH group than in the TL and control groups...(AU)

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Atualmente o uso de sensores portáteis para mensuração de corpos cetônicos está padronizado e difundido na rotina clínica, contudo estudos em ovinos são escassos. Assim, a presente pesquisa objetivou avaliar a acurácia dos sensores portáteis de uso humano e de uso veterinário para a determinação de beta-hidroxibutirato (BHB) em ovelhas no final da gestação e no pós-parto recente. Foram utilizadas 37 amostras de sangue provenientes de nove ovelhas mestiças Corriedale. A determinação bioquímica de BHB no soro, considerada como o padrão-ouro, foi realizada utilizando-se metodologia enzimática colorimétrica. A média obtida na bioquímica sérica foi de 0,497mmol/L; no sensor de uso humano, a média foi igual a 0,537mmol/L, enquanto no sensor de uso veterinário foi de 0,751mmol/L. Foi verificada alta correlação entre o dosímetro de uso humano e o padrão-ouro (r=0,93, P<0,001). A média do aparelho de uso veterinário diferiu das demais (51%; P<0,05), superestimando os resultados em ovelhas. As medições obtidas no aparelho veterinário também apresentaram menor precisão e veracidade. Concluiu-se que o sensor portátil de uso humano é mais acurado e mais preciso no diagnóstico precoce de toxemia da gestação em ovelhas.

Currently the use of portable sensors for measuring ketone bodies is standardized and diffused in the clinical routine, however, studies in sheep are scarce. Therefore, the present study aimed to evaluate the accuracy of the human portable sensor and the veterinary portable sensor for the determination of beta-hydroxybutyrate (BHB) in sheep at the end of gestation and postpartum. We used 37 samples of blood from nine crossbred Corriedale sheep. Biochemical determination of serum BHB, considered gold standard, was performed using colorimetric enzymatic methodology. The mean serum biochemistry was 0.497mmol/L, in the human sensor the mean was 0.537mmol/L, while in the veterinary sensor it was 0.751mmol/L. A high correlation was verified between the dosimeter for human use and the gold standard (r= 0.93, P< 0.001). The mean of the veterinary apparatus differed from the others, being 51% (P< 0,05), higher than the standard, that is, it was less accurate and had lower veracity, overestimating the results in sheep. It was concluded that the portable sensor for human use is more accurate and accurate in the early diagnosis of toxemia of pregnancy in sheep.

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Atualmente o uso de sensores portáteis para mensuração de corpos cetônicos está padronizado e difundido na rotina clínica, contudo estudos em ovinos são escassos. Assim, a presente pesquisa objetivou avaliar a acurácia dos sensores portáteis de uso humano e de uso veterinário para a determinação de beta-hidroxibutirato (BHB) em ovelhas no final da gestação e no pós-parto recente. Foram utilizadas 37 amostras de sangue provenientes de nove ovelhas mestiças Corriedale. A determinação bioquímica de BHB no soro, considerada como o padrão-ouro, foi realizada utilizando-se metodologia enzimática colorimétrica. A média obtida na bioquímica sérica foi de 0,497mmol/L; no sensor de uso humano, a média foi igual a 0,537mmol/L, enquanto no sensor de uso veterinário foi de 0,751mmol/L. Foi verificada alta correlação entre o dosímetro de uso humano e o padrão-ouro (r=0,93, P<0,001). A média do aparelho de uso veterinário diferiu das demais (51%; P<0,05), superestimando os resultados em ovelhas. As medições obtidas no aparelho veterinário também apresentaram menor precisão e veracidade. Concluiu-se que o sensor portátil de uso humano é mais acurado e mais preciso no diagnóstico precoce de toxemia da gestação em ovelhas.(AU)

Currently the use of portable sensors for measuring ketone bodies is standardized and diffused in the clinical routine, however, studies in sheep are scarce. Therefore, the present study aimed to evaluate the accuracy of the human portable sensor and the veterinary portable sensor for the determination of beta-hydroxybutyrate (BHB) in sheep at the end of gestation and postpartum. We used 37 samples of blood from nine crossbred Corriedale sheep. Biochemical determination of serum BHB, considered gold standard, was performed using colorimetric enzymatic methodology. The mean serum biochemistry was 0.497mmol/L, in the human sensor the mean was 0.537mmol/L, while in the veterinary sensor it was 0.751mmol/L. A high correlation was verified between the dosimeter for human use and the gold standard (r= 0.93, P< 0.001). The mean of the veterinary apparatus differed from the others, being 51% (P< 0,05), higher than the standard, that is, it was less accurate and had lower veracity, overestimating the results in sheep. It was concluded that the portable sensor for human use is more accurate and accurate in the early diagnosis of toxemia of pregnancy in sheep.(AU)

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Ketosis is a metabolic disorder that has an important impact on health and productivity in dairy cattle during early lactation. In Colombia, the incidence and risk factors for ketosis development have not been studied. The objectives of the present study were to determine the incidence of subclinical (SCK) and clinical ketosis (CK) and to determine the risk factors associated with ketosis within the first 6 weeks of lactation in dairy cattle in Colombia. A prospective cohort study was carried out. A convenience sample of 150 lactating dairy cows from ten commercial dairy farms in the Cundi-Boyacencian Andean plateau were tested weekly using a point of care device to measure ß-hydroxybutyrate during the first 6 weeks of lactation. Incidence of SCK and CK was calculated. Risk factors were evaluated using a survey for each animal and for each farm. Potential risk factors were evaluated using a X2 test, Relative Risk was calculated for significant variables by the X2 test (P ≤ 0.05) and these variables were included in the logistic regression model. Cumulative incidence of SCK was 25.33%, 3.33% for CK, and overall incidence of ketosis was 26%. In the logistic regression model, parity 3 or more, herd size > 150 animals, body condition score ≥ 3, retained placenta, and metritis were determined as risk factors for ketosis. The results of this study confirm previous reports in which a high body condition score, increased parity, herd size, retained placenta, and metritis are associated with an increased risk of ketosis in stabled and grazing cattle.

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