Relationship between rumen microbiota and pregnancy toxemia in ewes.

Introduction: Pregnancy toxemia (PT) is a nutritional metabolic disease of ewes in late pregnancy. This study aimed to reveal the relationship between rumen microbiota and PT. Methods: We selected 10 healthy ewes (CON) and 10 pregnancy toxemia ewes (PT) at 135 days of gestation according to the blood ß-hydroxybutyrate (BHBA), glucose (Glu) concentrations and clinical symptoms. Blood and rumen fluid were collected before morning feeding to determine serum biochemical indices and rumen fermentation parameters. Total DNA of rumen fluid was extracted and the V3-V4 regions of 16S rRNA were amplified by PCR for high-throughput sequencing. Results: The results showed that the serum concentrations of Glu, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), uric acid (UA), creatinine (Cr), acetate, propionate, butyrate, and microbial crude protein (MCP) were decreased (p < 0.05) and the concentrations of BHBA, aspartate aminotransferase (AST), acetate to propionate ratio (A/P), and ammonia nitrogen (NH3-N)were higher (p < 0.05) in PT ewes than those in CON ewes. 16S rRNA analysis showed the differences of ß-diversity were observed in rumen microbiota between CON and PT ewes. At the phylum level, the relative abundance of Bacteroidota and Proteobacteria were higher (p < 0.01), while Firmicutes was lower (p < 0.01) in PT ewes. At the genus level, the relative Prevotella, Butyrivibrio, Ruminococcus, Lachnospiraceae_AC2044_group, Lachnospiraceae_XPB1014_group, Lachnospiraceae_ND3007_group, and Oribacterium were lower (p < 0.01) in PT ewes. Meanwhile, the relative abundance of Oribacterium, Butyrivibrio, Ruminococcus, and Lachnospiraceae_AC2044_group were positively correlated (p < 0.01) with Glu, INS, acetate, propionate, and butyrate, and negatively correlated (p < 0.01) with BHBA, P, GC, AST, and A/P. Discussion: In conclusion, the decrease of Oribacterium, Butyrivibrio, Ruminococcus, and Lachnospiraceae_AC2044_group in the rumen of PT ewes reduced the concentrations of volatile fatty acids (acetate, propionate, and butyrate) and serum Glu, and increased BHBA concentration, indicating that the differences in rumen bacteria genera were related to pregnancy toxemia of ewes.

Conventional and Doppler ultrasonographic diagnosis of subclinical pregnancy toxemia with altered serum cortisol and biochemical parameters in pregnant does.

The pathogenesis and diagnosis of subclinical pregnancy toxemia (SCPT) remain elusive and need further investigation in pregnant does. Therefore, the aim of our study was to describe the typical properties of hepatic venous hemodynamics by Doppler ultrasonography. A total of 70 pregnant does were classified based on the blood serum concentrations of ß-hydroxybutyric acid (ßHBA), pregnant does were categorized into control group (ßHBA concentrations <0.8 mmol/L; n = 40) and SCPT group (ßHBA concentrations >0.8 mmol/L; n = 30). DRAMISKI 4vet slim diagnostic ultrasound scanner with B, M, and Doppler (color, power, pulsing wave) modes was used for diagnosis of SCPT. Total serum cortisol level was quantitative using chemiluminescent immunoassay. Serum glucose, triglycerides, cholesterol, HDL and LDL- cholesterol and LDH- cholesterol were measured by colorimetric and kinetic methods. Liver ultrasonography of does with SCPT had been shown mild fatty infiltration with rounded margin, which was characterized by hyperechoic area. There was a significant decrease in the values of portal vein diameter (PVD), portal vein area (PVA), portal mean velocity (PMV) and portal blood flow (PBF) in SCPT does compared to control pregnant does. PVD, PVA and PBF were negatively correlated with ßHBA concentrations in does with SCPT (P < 0.05). PVD was inversely associated with serum cholesterol and triglycerides concentrations (P < 0.05). In conclusions, Doppler ultrasonography examinations of pregnant does with SCPT indicate abnormal hepatic variation. Reduced PVD, PVA, PMV and PBF together with increased ßHBA concentrations could predict SCPT in does with fair sensitivity and specificity.

Analysis of fecal microbiome and metabolome changes in goats with pregnant toxemia.

BACKGROUND: Pregnancy toxemia is a common disease, which occurs in older does that are pregnant with multiple lambs in the third trimester. Most of the sick goats die within a few days, which can seriously impact the economic benefits of goat breeding enterprises. The disease is believed to be caused by malnutrition, stress, and other factors, that lead to the disorder of lipid metabolism, resulting in increased ketone content, ketosis, ketonuria, and neurological symptoms. However, the changes in gut microbes and their metabolism in this disease are still unclear. The objective of this experiment was to evaluate the effect of toxemia of pregnancy on the fecal microbiome and metabolomics of does. RESULTS: Eight pregnant does suspected of having toxemia of pregnancy (PT group) and eight healthy does during the same pregnancy (NC group) were selected. Clinical symptoms and pathological changes at necropsy were observed, and liver tissue samples were collected for pathological sections. Jugular venous blood was collected before morning feeding to detect biochemical indexes. Autopsy revealed that the liver of the pregnancy toxemia goat was enlarged and earthy yellow, and the biochemical results showed that the serum levels of aspartate aminotransferase (AST) and ß-hydroxybutyric acid (B-HB) in the PT group were significantly increased, while calcium (Ca) levels were significantly reduced. Sections showed extensive vacuoles in liver tissue sections. The microbiome analysis found that the richness and diversity of the PT microbiota were significantly reduced. Metabolomic analysis showed that 125 differential metabolites were screened in positive ion mode and enriched in 12 metabolic pathways. In negative ion mode, 100 differential metabolites were screened and enriched in 7 metabolic pathways. CONCLUSIONS: Evidence has shown that the occurrence of pregnancy toxemia is related to gut microbiota, and further studies are needed to investigate its pathogenesis and provide research basis for future preventive measures of this disease.

Changes in free amino acid profile in goats with pregnancy toxemia.

Pregnancy toxemia is a metabolic disorder that afflicts goats when the heightened energy requirements preceding parturition are not sufficiently satisfied. At present, the potential association between pregnancy toxemia and the free amino acid composition in hair goats remains uncharted territory. The purpose of this study is to investigate the free amino acid profile in goats during the pivotal three weeks preceding delivery, distinguishing among those with subclinical pregnancy toxemia (SPT), clinical pregnancy toxemia (CPT), and those in the control group (CG). Additionally, the study aims to investigate any potential relationship between the amino acid profile and beta hydroxy butyric acid (BHBA) levels. The researchers analyzed a total of 50 goats, comprising 20 goats with SPT, 20 with CPT, and 10 in the CG. The serum free amino acid profile was determined using a gas chromatography flame ionization detector (GC-FID) device. BHBA concentration in goats with CPT and SPT was significantly higher than KG (p < 0.001). Furthermore, in goats with CPT, the glucose concentration was significantly lower than in CG (p < 0.012). In goats with CPT and SPT, the concentration of valine, one of the gluconeogenic amino acids, was significantly higher than in control group (p < 0.001), while histidine concentration was significantly lower (p < 0.020) than in control group. Specifically in goats with CPT, the concentrations of alanine (p < 0.002), serine (p < 0.001), and threonine (p < 0.043) were significantly lower than in control group. Moreover, the concentration of phenylalanine, which is both a glycogenic and ketogenic amino acid, was significantly lower (p < 0.028) in goats with SPT compared to the control group. The Fisher ratio (p < 0.010) and Glycine/Alanine ratio (p < 0.001) were significantly higher in pregnancy toxemia goats with than in control group goats, indicating a poor nutritional and energy status of the goats during the prepartum period. In summation, the findings of this study underscore that amino acids exhibiting marked concentration variations hold considerable promise in the diagnosis, prognosis, and therapeutic management of pregnancy toxemia.

Association of vitamin D status with redox balance and insulin resistance and its predicting ability for subclinical pregnancy toxemia in pregnant sheep.

The study aimed to evaluate the role of vitamin D on redox balance, insulin resistance and its predicting value for subclinical pregnancy toxemia (SPT) in pregnant ewes. At four weeks pre-lambing, fifteen healthy pregnant ewes were divided into two groups, ewes with sufficient vitamin D (25-hydroxy-vitamin D (25VitD) (SVD, n = 9) and ewes with insufficient 25VitD (ISVD, n = 6). Blood samples were collected at 4 weeks pre-lambing using modified frequently sampled intravenous glucose tolerance test for the estimation of various metabolites. The baseline glucose, insulin, non-esterified fatty acid (NEFA), fructosamine, beta-hydroxy butyric acid (ß-BHA), calcium, phosphorus concentration and total oxidant status (TOS) did not differ significantly between the two groups, however, total antioxidant capacity (TAC) was significantly (p = 0.031) low in ISVD ewes. Area under the curve for glucose, insulin, elimination rate of glucose and peak insulin also did not differ significantly between the two groups. Correlation analysis revealed, positive association of 25VitD with fructosamine, calcium and TAC, and negative correlation with NEFA and TOS. Subsequent blood sampling at 2 weeks pre-lambing and at lambing showed significant difference in NEFA (p = 0.001), ß-HBA (p = 0.001), and fructosamine(p = 0.012) between the two groups. A significant time x group interaction was observed in NEFA (p = 0.019), ß-HBA (p = 0.031), and fructosamine (p = 0.026) concentration. The NEFA concentrations were increased and fructosamine decreased at 2 weeks pre-lambing and at lambing along with significantly increased ß-HBA at 2 weeks pre-lambing in ISVD compared to SVD. Taking 0.8 mmol/L ß-HBA as the cut off limit for SPT, ISVD ewes had higher odds of developing SPT two weeks prior to lambing (OD 16.00; p = 0.042) and at lambing (OD 10; p = 0.077). This study concludes that 25VitD significantly influence redox balance and energy profile and serves as a valuable predictor for SPT in pregnant sheep.

Clinical and Biochemical Study of Pregnancy Toxemia in Iraqi Ewes.

Pregnancy toxemia (PT), also known as ketosis or twin lamb disease, is a group of in-sequence metabolic disorders usually observed in the last pregnancy period of ewes. Blood samples from 60 Awassi ewes were collected, including 50 ewes suffering from PT and 10 healthy ewes (2-8 years old) as a control group. All of them were in their final month of pregnancy from different regions of Salah Aldin Governorate, Iraq. The samples were collected between October 2021 and February 2022. Biochemical analysis of serum concentrations of all parameters was performed using the atomic absorption spectrophotometer, except for the beta-hydroxybutyrate and non-esterified fatty acids that were analyzed by enzyme-linked immunosorbent assay method. The results of the clinical criteria tests for temperature, respiration, and pulse showed nonsignificant differences (P<0.05) in the infected animals, compared to the healthy group. Clinical signs included depression, loss of appetite, weight loss, lying down, odor of ketogenic bodies through breathing, inability to walk, neurological signs, dental grinding, jaundice, blindness, bloat, dystocia, animal death, and fetal death. Based on the results of the biochemical parameters tests of the blood, a significant increase (P<0. 05) was observed in the parameters of the results of beta-hydroxybutyrate, non-esterified fatty acids, triglycerides, total bilirubin, and liver enzymes (ALT, AST, ALP, and GGT) in the animals affected by PT, compared to the control group. However, a significant decrease (P<0.05) was observed in the parameters of glucose, cholesterol, total protein, albumin, and globulin in the affected animals, compared to the healthy group. Concerning the association between disease and oxidative stress criteria, the infected animals showed a substantial (P<0.05) increase in malondialdehyde concentration and a significant (P<0.05) drop in glutathione and superoxide dismutase levels.

Pulse wave Doppler ultrasound of umbilical cord in experimentally induced pregnancy toxemia in sheep.

Contrary to its widespread use in human cases, the use of Doppler ultrasonography is only recently becoming prevalent in farm animals. This study aimed to determine the effects of maternal metabolic and clinical changes on fetal hemodynamics during pregnancy toxemia with the doppler examination of umbilical cord. In the study twenty ewes with a single healthy fetus were included in the study. At the end of the 120th day of pregnancy, 20 single-bearing pregnant ewes were randomly categorized into two groups. Ewes in the control group were fed to meet all nutritional requirements. On the other contrary, the experimental ewes were fed to meet equivalent to 50 % of the daily needs and then fasted for 96 h. Doppler ultrasonographic examinations of umbilical cord were performed once every two days and once a day during fasting. Beta hydroxybutyric acid (BHBA) concentration was measured by taking blood from sheep on examination days. Pulse systolic velocity (PSV), end diastolic velocity (EDV), PSV/EDV, pulsatility index (PI), resistance index (RI), and fetal heart rate (FHR) as well as BHBA values and how those parameters has changed over time (time by treatment effect) due to energy deprivation during pregnancy were evaluated using repeated measure analysis of variance. No clinical signs were observed in both toxemia and control groups during restricted feeding. BHBA concentration increased and there was a significant time, time by treatment and main effect of treatment effect between groups. No significant main effect of treatment and time by treatment interaction was observed in the changes of PI, RI, FHR, and systolic/diastolic velocity values over time in both groups. FHR was reduced over time, and there was a significant time effect in FHR in both groups. Although doppler indices didn't increase, both PSV and EDV values increased significantly in the pregnancy toxemia group compared with the controls (Time P = 0.03, time by treatment interaction P < 0.05) and the main effect of treatment P < 0.05). The marked increase in blood velocities (PSV and EDV) in the umbilical cord is probably due to the compensatory functioning for excessive energy deprivation of the fetus. Therefore, PSV and EDV might be a valuable indicator for evaluating the fetus's health status during the management of the PT.

Pregnancy Toxemia Therapeutic Options.

This review covers the treatment options for pregnancy toxemia in small ruminants. Clinical assessment and detection of underlying metabolic and electrolyte derangements direct resuscitation efforts and provide prognostic indications. Treatment programs are dependent on producer goals and case specifics. Options include oral glucogenic precursors (eg, propylene glycol, glycerol), intravenous glucose solutions, insulin, and other supportive care measures. Induction of parturition or C-section is often carried out to minimize ongoing energy deficits, with variable survival rates. Prolonging gestation to maximize fetal viability often requires intensive care in a hospital setting and carries significant risk to both dam and offspring.

Pregnancy Toxemia in Sheep and Goats.

Pregnancy toxemia is a common metabolic disease of late pregnant ewes and does, which potentially has devastating impacts on health and performance. This metabolic syndrome is not only one of over conditioned animals but is more typically associated with inadequate energy intake to support pregnancy requirements leading to body protein and fat mobilization. Blood chemistries provide insight into diagnosis and possibly may predict responsiveness to treatment and outcome. Early recognition of the disease with appropriate intervention is the best approach to minimizing the impact of this disease in the sheep flock or goat herd.

Evaluation of Freestyle Optium Neo H and TaiDoc-TD4235 point-of-care meters for measuring blood ß-hydroxybutyrate concentration in sheep.

BACKGROUND: Accurate and rapid measurement of blood ß-hydroxybutyrate (ß-OHB) concentrations is critical to identify hyperketonemia in sheep. OBJECTIVE: The objective of this study was to test the performance of Freestyle Optium Neo H and TaiDoc-TD4235 point-of-care (POC) devices for measuring blood ß-OHB concentrations in sheep. METHODS: Venous blood samples from 105 sheep were evaluated with Freestyle Optium Neo H and TaiDoc-TD4235 meters. A reference approach was the laboratory measurement of serum BHB concentrations using the Randox D-3 Hydroxybutyrate reagent kit. Data were analyzed using Passing- Bablok regression and Bland-Altman analysis. The diagnostic accuracy was assessed using serum ß-OHB concentration at a cut-off value of 0.8 mmol/L. RESULTS: Passing-Bablok regression analysis revealed an intercept of 0.066 (CI95 : 0.018-0.125) and slope of 1.242 (CI95 : 1.136-1.342) for Freestyle Optium Neo H. Intercept and slope values for the TaiDoc-TD4235 meter were 0.625 (CI95 : 0.539-0.724) and 1.265 (CI95 : 1.044-1.497), respectively. The Bland-Altman plot revealed a bias of 0.224 mmol/L and 0.737 mmol/L for Freestyle Optium Neo H and TaiDoc-TD4235 meters, respectively, compared with the reference method. Observed Total Error (TEobs ) was 56.7% for the Freestyle Optium Neo H and 168.7% for the Taidoc-TD4235. The sensitivity and specificity for the Freestyle Optium Neo H were 100% and 80.9%, respectively, at the threshold of 0.8 mmol/L. The Taidoc-TD4235 demonstrated a sensitivity of 93.3% and specificity of 8.9% at the threshold of 0.8 mmol/L. CONCLUSIONS: Because of the large TEobs , the Freestyle Optium Neo H and TaiDoc-TD4235 meters should not be used to quantify blood ß-OHB concentrations in sheep.

Pregnancy Toxemia in Ewes: A Review of Molecular Metabolic Mechanisms and Management Strategies.

Pregnancy toxemia is a nutritional metabolic disease during late gestation in small ruminants. The condition is characterized by disorders in carbohydrate and fat metabolism. Obese and multiparous ewes are particularly susceptible to pregnancy toxemia, which may lead to maternal death, abortion, or premature birth. Highly productive multiparous meat ewes are major breeding animals, which has led to an increased incidence of the disease. However, the pathogenesis of pregnancy toxemia remains unclear and adequate disease prevention and treatment strategies are absent. Investigating the pathogenesis of pregnancy toxemia, especially the metabolic pathways of hepatic lipids, is key to an improved understanding of the condition. This review provides a snapshot of the genes that are associated with lipid metabolism in the ovine liver, including genes involved in fatty acid oxidation, acetyl coenzyme metabolism, and triglyceride synthesis; describes the interrelationships between these genes; and summarizes the diagnosis, prevention, and treatment of pregnancy toxemia.

Serum concentrations of folic acid and cobalamin and energy metabolism of ewes as a function of the energy density of the diet, peripartum period, and pregnancy toxemia.

The aim of this study was to determine the serum levels of folic acid, cobalamin, and indicators of energy metabolism during the peripartum period of ewes submitted to different diets and with or without pregnancy toxemia. Forty Santa Inês ewes were divided into three groups, a group of 20 animals fed only roughage-diet with low energy density (G1), a group of 10 ewes submitted to diet containing roughage and concentrate-diet with high energy density (G2), and a group of 10 ewes with diagnosis of pregnancy toxemia (PT) (G3). In the ewes of groups G1 and G2, blood samples were collected -30, -15, -7 days pre-partum, on the day of partum, and 7, 15, and 30 days postpartum; blood samples from G3 animals were collected during the veterinary clinic care. Significant variations were observed in the plasma concentration of glucose and serum folic acid, cobalamin, fructosamine, NEFA, and ß-hydroxybutyrate in the groups fed diets with different energy levels, with and without PT (P < 0.05). A positive correlation of folic acid and cobalamin was observed with plasma glucose and serum NEFA concentrations, in addition to negative correlation of glucose with NEFA and ß-hydroxybutyrate and positive correlation between the latter biomarkers of energy metabolism. The ewes diagnosed with PT showed higher levels of folic acid, NEFA, and ß-hydroxybutyrate (P < 0.05). Ewes fed diet containing roughage and concentrate present higher serum levels of folic acid, cobalamin, and glucose, in the pre-partum period and in the lactation period. The results obtained contribute to better understanding of the application of blood concentration tests for folic acid and cobalamin in the energy metabolism and in PT in ewes.

Evaluation of metabolic and oxidative profile in ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of disease.

This study was conducted on ewes with pregnancy toxemia (PT) with an attempt to evaluate metabolic and oxidative profile in subclinical and clinical ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of the disease. A total of 20 ewes having beta-hydroxy butyric acid (ß-HBA) > 2.5 mmol/L and proven clinical sings of PT, categorized as clinical PT (CPT); 12 ewes having ß-HBA 0.8-2.5 mmol/L and no clinical signs of PT, categorized at subclinical PT (SPT); and 10 ewes having ß-HBA ≤ 0.8 mmol/L, categorized as healthy control (CON) were enrolled. Among 20 CPT ewes, 11 had negative outcomes (non-survivors), six ewes had positive outcomes (survivors), and three were lost during follow-up. A significant increase in non-esterified fatty acid, ß-HBA, triglycerides, gamma-glutamyl transferase, lactate dehydrogenase, and malondialdehyde levels and a significant decrease in fructosamine were observed in CPT and SPT compared to CON. A significant increase in cholesterol, aspartate amino transferase, and creatinine kinase and a significant decrease in albumin, potassium, calcium, superoxide dismutase, and catalase were observed in CPT only. Glucose was significantly decreased in SPT only. The highest area under the curve (AUC) was observed for fructosamine (89.7% and 87.5% for CPT and SPT, respectively) with the optimum cutoff point calculated on the basis of maximum sensitivity (SE) and specificity (SP) being 0.607 mmol/L (SE: 89.3% and SP: 72.2%) and 1.005 mmol/L (SE: 90.0% and SP: 75.3%) for CPT and SPT, respectively. At the cutoff limit of 0.607 mmol/L and 1.005 mmol/L, the odds ratio was 10.8 and 8.0 for CPT and SPT, respectively. A significant decrease in fructosamine and potassium and a significant increase in creatinine, lactate dehydrogenase, and malondialdehyde were observed in non-survivors compared to survivors. It was thus concluded that fructosamine was the best diagnostic indicator of both CPT and SPT followed by non-esterified fatty acid. Fructosamine, creatinine, potassium, lactate dehydrogenase, and malondialdehyde were the best prognostic indicators of PT.

BHBA regulates the expressions of lipid synthesis and oxidation genes in sheep hepatocytes through the AMPK pathway.

Pregnancy toxemia (PT) is the most frequent metabolic disease of sheep during late pregnancy, which can lead to enormous economic losses in sheep farm industry. However, the underlying mechanism of PT in sheep has not been fully elucidated. High levels of ß-hydroxy butyric acid (BHBA) exist in PT sheep. The AMP-activated protein kinase (AMPK) pathway plays a major role in regulating liver function. The aim of this study was to explore the effects of gradient concentrations of BHBA on lipid metabolism of sheep hepatocytes and the underlying molecular mechanism in vitro. The results showed that 0.6, 1.2 mmol/L BHBA could activate AMPKα, promoted the expressions of peroxisome proliferator-activated receptor alpha (PPARα) and its target genes, and inhibited the expressions of sterol regulatory element binding protein-1c (SREBP-1c) as well as its downstream genes. When the concentration of BHBA was beyond 1.2 mmol/L, the expressions of the above-mentioned proteins and genes were just the opposite. However, the expressions of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) did not change significantly. The levels of very low density lipoprotein (VLDL), triglyceride (TG) and cholesterol (T-CHOL) showed a gradually increasing trend with the increase of BHBA concentration. According to the results above, it demonstrates that high levels of BHBA can inhibit the expression of the AMPK pathway and cause lipid metabolism disorders in sheep hepatocytes, which may lead to the occurrence of PT.

Acid-base disorders in sick goats and their association with mortality: A simplified strong ion difference approach.

OBJECTIVES: To investigate the acid-base status of sick goats using the simplified strong ion difference (sSID) approach, to establish the quantitative contribution of sSID variables to changes in blood pH and HCO3 - and to determine whether clinical, acid-base, and biochemical variables on admission are associated with the mortality of sick goats. ANIMALS: One hundred forty-three sick goats. METHODS: Retrospective study. Calculated sSID variables included SID using 6 electrolytes unmeasured strong ions (USI) and the total nonvolatile buffer ion concentration in plasma (Atot ). The relationship between measured blood pH and HCO3 - , and the sSID variables was examined using forward stepwise linear regression. Cox proportional hazard models were constructed to assess associations between potential predictor variables and mortality of goats during hospitalization. RESULTS: Hypocapnia, hypokalemia, hyperchloremia, hyperlactatemia, and hyperproteinemia were common abnormalities identified in sick goats. Respiratory alkalosis, strong ion acidosis, and Atot acidosis were acid-base disorders frequently encountered in sick goats. In sick goats, the sSID variables explained 97% and 100% of the changes in blood pH and HCO3 - , respectively. The results indicated that changes in the respiratory rate (<16 respirations per minute), USI, and pH at admission were associated with increased hazard of hospital mortality in sick goats. CONCLUSIONS AND CLINICAL IMPORTANCE: The sSID approach is a useful methodology to quantify acid-base disorders in goats and to determine the mechanisms of their development. Clinicians should consider calculation of USI in sick goats as part of the battery of information required to establish prognosis.

The distinctive short-term response of late-pregnant prolific ewes to propylene glycol or glycerol drenching.

Pregnancy toxemia is the most frequent metabolic disorder of ewes in late pregnancy. Although propylene glycol (PG) and glycerol (GLY) are common glucogenic supplements for treating pregnancy toxemia in ewes, the relative benefit of these 2 supplements is not entirely clear. Therefore, the objectives of the present study were to determine the changes during 24 h in key blood metabolites and insulin in response to PG or GLY drenching in prolific ewes. To this end, 36 multiparous late-pregnant Afec-Assaf ewes (∼132.4 d pregnant) bearing 2 to 4 fetuses, divided into 2 blocks (18 ewes in each block), with a blood ß-hydroxybutyrate (BHB) concentration of 0.5 to 1.6 mmol/L were included. Ewes were divided into 3 groups (12 ewes each; 6 ewes in each experimental day), according to their BHB levels, expected litter size, body weight, and body condition score, and were drenched with the following: (1) control group (CTL), 55 mL of water; (2) PG, 106 mL of PG (100% PG, 448 calories); or (3) GLY, 108 mL of Koforin 80 (80% GL; 448 calories). Blood samples were taken before drenching and every hour after drenching for 24 h. Plasma concentration of glucose, BHB, nonesterified fatty acids, lactate, glycerol, and insulin were determined. Because there were no effects of treatments after 12 h in the first block, the data were analyzed for 12 h after drenching rather than 24 h. The plasma glucose concentration during the first 5 h after drenching was the highest in the GLY, BHB concentration was the lowest in the PG, and the nonesterified fatty acid levels were lower in the PG compared with the CTL ewes during the first 5 h after drenching. However, glucose concentration was higher in the PG ewes at 9, 11, and 12 h after drenching than in CTL or GLY ewes. The mean lactate concentration in plasma for 12 h was 2.5- and 1.9-fold higher in the PG compared with the CTL and GLY ewes, respectively, and except at 11 h after drenching, it was significantly higher at each time point. The insulin concentration was higher in the GLY than in both other groups at 2 to 5 h after drenching. These results suggest that during the first few hours after drenching the effect of PG was more effective in reducing the BHB concentration, whereas the GLY effect was more effective in enhancing glucose concentration. The increased concentration in lactate following PG treatment suggests that the PG contribution to gluconeogenesis is mediated through its metabolism to lactate. In contrast, the lack of an effect on lactate, and the faster increase in blood glucose in response to GLY suggest that GLY has a more advanced entry point to gluconeogenesis, which influences the immediate response in enhancing the glucose blood concentration.

Validation of a handheld ß-hydroxybutyrate acid meter to identify hyperketonaemia in ewes.

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.

Changes in cardiac biomarkers in goats naturally affected by pregnancy toxemia.

Pregnancy toxemia (PT) is considered one of the most common metabolic diseases with high impact on the production of small ruminants. The objective of this study was investigate possible myocardial damage in goats affected with PT by the determination of serum myocardial biomarkers CK-MB and cTnI. A total of 44 goats affected with PT, and 10 apparently healthy goats (control group or CG) were used in the study. In goats with PT, the serum concentrations of cTnI (0.43 ng/mL) were significantly higher than that in CG goats (0.06 ng/mL). Although CK-MB showed no significant difference, it was approximately three times higher in animals with PT. The serum concentrations of insulin were significantly lower in PT goats (5.03 ppmol/L) compared to CG goats (10.66 pmol/L). The serum concentrations of cortisol in PT goats (155.41 nmol/L) were significantly higher than that in CG goats (36.58 nmol/L). Results of this study indicate that a clinically significant myocardial damage might occur in goats affected with PT leading to significant elevations in values of cTnI and CK-MB. Therefore, these parameters could be used as a potential prognostic indicator in goats affected with this important disease.

Factors effective in the prevention of Preeclampsia:A systematic review.

Due to the morbidity and mortality of mothers and fetuses developed by preeclampsia, preventive approaches have always been taken into account in high risk individuals. Systematic review studies contribute to make a better decision about the results of such studies. Accordingly, this study strived to systematically study the factors effective in the prevention of preeclampsia. The MEDLINE, ISI Web of Science, PubMed, Scopus, Google Scholar, and Proquest databases were systematically reviewed between January 2000 and May 2019. The quality of the studies was analyzed using the CONSORT checklist. A study was conducted on 29 quality interventional studies; 28 of which were RCT type, and on various factors such as anticoagulants (heparin, enoxaparin, Dalteparin and Nadroparin), aspirin, paravastatin, nitric oxide, yoga, micronutrients Such as l-Arginine, Folic Acid, Vitamin E and C, Phytonutrient, Lycopene and Vitamin D alone or in combination with Calcium. The results of this study showed that low molecular weight heparin, enoxaparin, PETN, yoga, L arginine, folic acid, vitamin D prevented preeclampsia alone or combined with calcium.

Urine metabolome alterations in malnutrition and the impact of glycerol or rumen-protected choline chloride supplementation in advanced pregnant ewes.

The objective of this study was to explore the metabolic profiles of pregnancy malnutrition induced by feed restriction (FR) and the counteracting effects of glycerol and rumen-protected choline chloride supplementation. Two feeding trials were conducted. In the first experiment, twenty pregnant Hu sheep carrying multiple fetuses with a gestation period of 108 d were randomly divided into two groups. The ewes in the control (CON) group were offered 100 % of their nutritional requirements as recommended by the National Research Council (NRC), while the FR group was offered 30 % of feed intake of CON for 15 d. In the second experiment, eighteen pregnant Hu sheep were offered a feed intake comprising 30 % of the NRC-recommended nutritional requirements twice daily. The sheep were randomly divided into three groups: the FR group in the second experiment (FR2), with no supplementation, the glycerol (GLY) group, which received 40 ml of glycerol per d, and the rumen-protected choline chloride (RPC) group, which received 10 g of rumen-protected choline chloride per d for 9 d. In the first experiment, the urine metabolome of sixteen ewes showed significant difference between the CON group and FR group. Compared with the CON group, FR decreased the level of d-glucose, lactic acid, levoglucosan, α-ketoglutarate, phosphohydroxypyruvic acid, glucose 6-phosphate and the methyl donors, while increasing the level of pyruvate, fumaric acid and carnitines in urine. Both the GLY and RPC treatments counteracted some of these changes and modulated the urine metabolome in advanced pregnant ewes suffering from malnutrition.