Blood Concentrations Research Articles

Evaluation of Blood Lactate among Different Player Roles: A Pilot Study on Competitive Young Male Soccer Players.

Soccer match requires anaerobic and aerobic energetic metabolism. The aim of this pilot study was to investigate the changes in blood lactate concentration in young male soccer players in different playing roles at different time points after the soccer match. Following an initial screening of 134 young soccer athletes, 8 male athletes (average age of 15.5 ± 5 SD) were chosen for their characteristics similar to those of competitive athletes. Players were categorized as goalkeeper, central defender, central midfielder, and forward. Blood lactate concentrations were determined using a portable device at different times (10 min, 5 and 16 h) after the soccer match by a maximum effort test on a treadmill. The data were analyzed by one-way analysis of variance ANOVA, followed by Bonferroni's post-hoc test. The following results (mean ± SD) were obtained: VO2max (%) 60.33 ± 3.10; blood lactate (mM) end match (10 min) 2.17 ± 0.78, post-match-early (after 5 h) 2.2 ± 0.42, postmatch-late (16 h) 3.2 ± 0.84. ANOVA analysis indicated that the blood LA concentrations at end-match (10 min) and post-match-early (5 h) were statistically significative lower than those determined at post-match-late (16 h) (p < 0.05). These results suggest that aerobic mechanisms can also use LA as an energy source, contributing to the reduction of its blood concentration. This effect can be due to reduced maximal work during a soccer match and to the LA removal during exercise at reduced intensity. These data can provide indications for planning suitable training strategies for young male soccer players.

Exploration of microRNAs from blood extracellular vesicles as biomarkers of exposure to polycyclic aromatic hydrocarbons

Exposure to polycyclic aromatic hydrocarbons (PAHs), ubiquitously environmental contaminant, leads to the development of major toxic effects on human health, such as carcinogenic and immunosuppressive alterations reported for the most studied PAH, i.e., benzo(a)pyrene (B(a)P). In order to assess the risk associated with this exposure, it is necessary to have predictive biomarkers. Thus, extracellular vesicles (EVs) and their microRNA (miRNA) contents, have recently been proposed as potentially interesting biomarkers in Toxicology. Our study here explores the use of vesicles secreted and found in blood fluids, and their miRNAs, as biomarkers of exposure to B(a)P alone and within a realistic occupational mixture. We isolated EVs from primary human cultured blood mononuclear cells (PBMCs) and rat plasma after PAH exposure and reported an increased EV production by B(a)P, used either alone or in the mixture, in vitro and in vivo. We then investigated the association of this EV release with the blood concentration of the 7,8,9,10-hydroxy (tetrol)-B(a)P reactive metabolite, in rats. By performing RNA-sequencing (RNA-seq) of miRNAs in PBMC-derived EVs, we analyzed miRNA profiles and demonstrated the regulation of the expression of miR-342-3p upon B(a)P exposure. We then validated B(a)P-induced changes of miR-342-3p expression in vivo in rat plasma-derived EVs. Overall, our study highlights the feasibility of using EVs and their miRNA contents, as biomarkers of PAH exposure and discusses their potential in environmental Toxicology.

A VAMS‐based LC–MS/MS method for precise cenobamate quantification in epilepsy (patients)

AbstractObjectiveCenobamate (CNB), a recently approved antiseizure medication by the European Medicines Agency (EMA), serves as an adjunctive therapy for focal‐onset seizures in adult patients unresponsive to at least two other treatments. Administered in polytherapy, CNB can potentially interact with co‐administered drugs in epilepsy patients, necessitating dose adjustments and the need for effective therapeutic drug monitoring (TDM).MethodsIn this study, we introduce a novel LC–MS/MS method for precise CNB quantification using Volumetric Absorptive Microsampling (VAMS), following validation according to ICH guidelines M10. VAMS samples are efficiently extracted with 200 μL of methanol, with chromatographic separation achieved using an Acquity UPLC HSS PFP column. The method's efficacy was confirmed through its application to real samples from adult CNB‐treated patients.ResultsOur results demonstrate that the method exhibits linearity within the range of 0.05–30 mg/L, with intra‐ and inter‐run precision ranging from 1% to 8% and accuracy from 1% to 10% based on 30 μL of sample. Furthermore, CNB stability in VAMS is confirmed for up to 15 days at 25°C and −20°C. Importantly, no significant difference was observed between CNB concentrations in VAMS samples and those in plasma obtained from venous blood.SignificanceThis VAMS‐based LC–MS/MS method presents a robust alternative for TDM in CNB‐treated patients. Future investigations should explore CNB concentrations in capillary blood and assess their correlation with plasma levels to further enhance its clinical utility.Plain Language SummaryCenobamate is an antiepileptic drug and used for treatment of focal‐onset seizures in adult patients (≥18 age). TDM can prevent drug interactions and minimize drug toxicity. The aim of this work is to evaluate volumetric absorptive microsampling (VAMS) from capillary blood as an alternative strategy for TDM in patients treated with the newly antiepileptic drug. Our method is suitable for TDM, and this study suggests that VAMS allows monitoring of cenobamate concentration and can offer valuable support for personalized therapy in refractory epilepsy.

N-acetylaspartate promotes glycolytic-to-oxidative fiber-type switch and resistance to atrophic stimuli in myotubes

N-acetylaspartate (NAA) is a neuronal metabolite that can be extruded in extracellular fluids and whose blood concentration increases in several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Aspartoacylase (ASPA) is the enzyme responsible for NAA breakdown. It is abundantly expressed in skeletal muscle and most other human tissues, but the role of NAA catabolism in the periphery is largely neglected. Here we demonstrate that NAA treatment of differentiated C2C12 muscle cells increases lipid turnover, mitochondrial biogenesis and oxidative metabolism at the expense of glycolysis. These effects were ascribed to NAA catabolism, as CRISPR/Cas9 ASPA KO cells are insensitive to NAA administration. Moreover, the metabolic switch induced by NAA was associated with an augmented resistance to atrophic stimuli. Consistently with in vitro results, SOD1-G93A ALS mice show an increase in ASPA levels in those muscles undergoing the glycolytic to oxidative switch during the disease course. The impact of NAA on the metabolism and resistance capability of myotubes supports a role for this metabolite in the phenotypical adaptations of skeletal muscle in neuromuscular disorders.

Higher Plasma Copper Exposure was Adversely Associated with Skeletal Muscle Indicators in Chinese Children Aged 6-9 Years: A Cross-Sectional Study.

It is unclear whether blood concentrations of copper (Cu), magnesium (Mg), and calcium (Ca) influence skeletal muscle mass and strength in children. We aimed to explore the associations between plasma Cu, Mg, and Ca and skeletal muscle indicators in Chinese children. A total of 452 children aged 6 to 9 years old were recruited for this cross-sectional study. Whole body lean soft tissue mass (WLSTM), trunk lean soft tissue mass (TLSTM), and appendicular skeletal muscle mass (ASMM) were measured using dual-energy X-ray absorptiometry. Parameters of these indicators divided by Height2 (Ht2) and Weight (Wt) at the corresponding sites were calculated. Handgrip strength was also measured. Parameters of skeletal muscle indicators and handgrip strength that were below the sex-specific 20th percentile were considered low levels. Plasma concentrations of Cu, Mg, and Ca were measured using ICP-MS. After adjusting for several potential covariates, among the total subjects, for every one standard deviation increase in Cu concentrations, there was a 0.939% decrease in WLSTM/Wt, a 0.415% decrease in TLSTM/Wt, and a 0.47% decrease in ASMM/Wt. For every one standard deviation increase in Cu concentrations, there was a higher odd (OR: 1.36, 95%CI 1.06, 1.75) of low WLSTM/Wt, TLSTM/Wt (OR: 1.33, 95%CI 1.03, 1.71), ASMM/Ht2 (OR: 1.32, 95%CI 1.02, 1.69), as well as ASMM/Wt (OR: 1.56, 95%CI 1.23, 1.99). No significant associations were found between Mg, Ca, and most skeletal muscle indicators. Higher plasma Cu concentrations were adversely associated with skeletal muscle indicators at multiple sites in Chinese children.

Degradation and preservation of nitrites in whole blood

Understanding the factors that influence nitrite degradation in whole blood and developing methods for its stable preservation are crucial for ensuring accurate and reliable forensic identification in cases of nitrite poisoning. This study systematically monitored nitrite degradation and changes in hemoglobin proportions across different initial nitrite concentrations and blood samples. It was revealed that high nitrite concentrations rapidly reduced deoxyhemoglobin levels within the first 15 minutes and subsequently reacted with oxyhemoglobin at a slower rate. Therefore, the proportions of these two hemoglobin forms are key factors in determining nitrite degradation rates. Regarding preservation, the study examined the effects of low temperatures (4°C and −20°C) and various preservatives (potassium ferricyanide, N-ethylmaleimide) on nitrite stability. The results indicate that adding 6.6 g/L potassium ferricyanide can rapidly eliminate all deoxyhemoglobin and reduce oxyhemoglobin proportions to below 60 %, enabling stable preservation of high nitrite concentrations in whole blood for over 30 days at −20°C. The efficacy of potassium ferricyanide was further validated in forensic-acquired postmortem heart blood samples.

Association of Therapeutic Monitoring of Tacrolimus with Laboratory Markers of Kidney Function in Receptors of Kidney Allograft

Introduction: Kidney transplantation is the most commonly performed type of transplant in Brazil. Tacrolimus is one of the primary drugs used in post-transplant immunosuppressive therapy, and one of its main adverse effects is nephrotoxicity. Laboratory tests to assess renal function are of great importance in monitoring post-kidney transplant patients, helping to diagnose events indicative of graft dysfunction. Objective: !e present study aimed to evaluate the association between laboratory changes in renal function and blood levels of tacrolimus in post-kidney transplant patients. Methods: Observational, analytical and cross-sectional study. !e results of blood levels of tacrolimus and measurements of urea, creatinine and estimated Glomerular Filtration Rate (eGFR) were analyzed, as well as the sociodemographic data of kidney transplant recipients followed at a university hospital who underwent laboratory tests between months from January 2021 to July 2022 in a period close to 1 year after the transplant. !e variables analyzed in the research were collected from the patient's medical records and subsequently analyzed; the statistical analyses considered p &lt; 0.05. !e project was approved by the Ethics Committee of the Walter Cantídio University Hospital under opinion number 5,436,434 and CAAE number 57396622.1.0000.5045. Results: !e sample was mainly composed of males, mixed race, with an average age of 51.5 years (SD ± 12.5) and from cities in the interior of Ceará. Regarding the percentage of patients with laboratory changes, 50.62% (n = 45) showed changes in tacrolimus blood levels. 56.79% (n = 46) had changes in serum creatinine levels, 49.38% (n = 40) had changes in serum urea levels, and 59.26% (n = 48) had altered eGFR. !e correlation analyses suggested a low signi#cance between variations of the variables studied. Conclusion: !e results indicate no relationship between variations in tacrolimus blood concentrations and the appearance of changes in the results of classic renal biomarkers at the end of the #rst year post-transplant. However, it is necessary to carry out new studies to understand better the impact of changes in blood levels of tacrolimus on the renal function of renal allograft recipients.

PSLBII-1 Enhancing cattle health and performance through targeted supplement optimization and evaluation

Abstract Our objective is to evaluate and optimize Bovi-MV formulation through its effect on serum mineral/vitamin (M/V) concentrations in cattle and develop a systems approach to oral M/V supplementation through the lifecycle of beef cattle to determine the best management strategy to help reduce M/V deficiencies in young and mature animals. Cow/calf pairs (n = 300 over 2 yr) and follow the calves to harvest late in yr 2. The research is timed to coincide with typical management handling processes (e.g., vaccination of cows before calving and calf processing after birth, before pasture, at weaning time, on induction to the feedlot, and at reimplanting). The calf herd will be divided at birth into treatment (calves whose dams received BoviMV supplement) and control (~150 calves per group). Vitaferst-Care will be provided to the treatment group at processing (vaccination, antiparasitic application) before going to grass (~ 3 mo of age). Bovi-MV will only be given to the treatment group. All calves will be administered a tracer vaccine to assess their immune response. Blood samples will be collected from all calves for antibody titer testing at weaning (~ 6 mo of age). The treatment calves will also receive a booster dose of Bovi-MV at that time. Approximately 90 d after weaning (~ 9 mo of age) antibody titer will be determined immune response was. Calf morbidity, mortality, and performance (average daily gain) will be monitored in the feedlot. An accredited lab will conduct M/V blood analysis; antibody titer testing will be done at a Lakeland College lab. Based on MV and titer to the Bovi-MV supplement and tracer vaccine, the formulation of the Bovi-MV will be evaluated, and recommendations will be made. Based on results from two previous studies evaluating M/V blood concentrations in cattle (Neonatal supplement and Itchy Cow) in Western Canada, vitamin and mineral concentrations tended to be below optimum values, especially in herds provided supplementation free choice. All cows were deficient in vitamin A at calving, averaging 66.27 ± 2.51 ppb, with 50% having nondetectable concentrations. With vitamin E, 8 animals had nondetectable concentrations, only 8 had sufficient concentrations, and those with detectable concentrations averaged 3.16 ppm ± 2.17. Cows had sufficient iron ug/mL averaging 2.14 ± 1.02 and selenium ug/mL 0.09 ± 0.02. As Cheryl Waldner et al. (2023) reported, 24 to 43% copper deficiency is prevalent in cattle in the southern halves of the three prairie provinces. Armed with this information, this study is the first step in developing a systems approach to year-round management of the cow herd’s vitamin and mineral supplementation.

225 Kidney function and nitrogen excretion in Brown Swiss and Holstein dairy cows

Abstract The agricultural sector contributes to nitrogen (N) emissions since farm animals excrete considerable N amounts via feces and urine. To reduce N emissions by dairy cattle, methods predicting accurately individual N emissions are of great interest. Recent data showed that Brown Swiss (BS) cows have greater urea concentrations in milk and blood than Holstein (HO) cows. However, it is still unknown if greater BUN concentrations in a particular breed are congruently reflected by concomitantly increased contents of nitrogenous compounds in other media (e.g., urine and saliva). Thus, the present study simultaneously assessed biomarkers for kidney function like urea, and creatinine and symmetric dimethylarginine (SDMA) concentrations in several body fluids (i.e., blood, urine, milk, and saliva) as well as nitrogen excretion in feces in BS and HO cows under identical feeding conditions. Blood, saliva, urine, and feces were sampled in 31 multiparous BS and 46 HO cows kept under identical feeding and management conditions. Samples were collected at different lactational stages after the monthly DHIA control test-day. Concentrations of urea and creatinine were measured in serum, urine, and saliva. Symmetric dimethylarginine was determined in serum, which is an established indicator for glomerular filtration rate (GFR). Feces were analyzed for dry matter content and nitrogen concentrations. Data on milk urea and protein concentrations, and daily milk yield were obtained from the monthly DHIA test-day records. The effects of breed, time, and parity number on blood, saliva, urine, feces, and milk parameters were evaluated with the GLM procedure with breed, time, and parity number as fixed effects. Differences between BS and HO were assessed by the Tukey-corrected t-test at P &amp;lt; 0.05. Dry matter intake and body weight were similar in BS and HO cows (P &amp;gt; 0.05). No differences between BS and HO were observed for milk yield, fecal DM and nitrogen content. BS cows showed greater urea concentration (25.8 ± 0.7 vs 21.8 ± 0.7 mg/dL), and protein content in milk (3.70 ± 0.08 vs 3.45 ± 0.07%) than HO cows (P &amp;lt; 0.01). Concentrations of urea, creatinine, and SDMA in serum, were greater in BS than in HO cows (P &amp;lt; 0.01) with 5.46 ± 0.19 vs 4.72 ± 0.13 mmol/L for urea, 105.96 ± 2.23 vs 93.07 ± 1.50 mmol/l creatinine, and 16.78 ± 0.69 vs 13.39 ± 0.44 µg/dL SDMA, respectively. Urea and creatinine concentrations in urine and saliva did not differ among breeds. Despite greater urea and creatinine concentrations in blood, and milk urea content in BS compared with HO, excretion of these parameters did not differ between breeds in urine. Our results suggest a reduced renal glomerular filtration rate in BS compared with HO. The underlying mechanisms require further investigations.

Gene-based drug therapy for children and youth treated with psychoactive medications.

Psychoactive medications are increasingly used to treat children and youth with mental health conditions, but individual variations in response highlight the need for precision medicine. Pharmacogenetic (PGx) testing is a key component of precision medicine. The number of commercial pharmacogenetic testing companies promoting PGx, with the promise of achieving individualized and effective treatment of mental health conditions, has grown exponentially in recent years. Scientific evidence supporting the use of PGx to manage mental health conditions is limited, especially for paediatric populations. This practice point outlines steps guiding the use and interpretation of PGx testing for psychoactive medications in clinical settings, along with key supportive resources. Practice guidelines have been developed for variants in pharmacogenes encoding cytochrome P450 drug-metabolizing enzymes (e.g., CYP2C19, CYP2D6, CYP2C9) as one determinant of drug concentrations in blood, which can support both drug choice and dosing strategy for certain anti-psychotics, anti-depressants, and anti-epileptics. Adverse drug reactions to some anti-epileptic drugs (e.g., carbamazepine and phenytoin) have been associated with certain human leukocyte antigen types and variants in DNA polymerase gamma (POLG; valproic acid). Evidence remains limited for genetic variants of drug target proteins, making it challenging to identify patients with altered treatment responses at a therapeutic blood concentration.

483 DMI, gastrointestinal tract fermentation and permeability, and white blood cell responses in beef heifers provided post-ruminal yeast cell wall extract following feed restriction

Abstract The objectives of this study were to 1) evaluate gastrointestinal fermentation characteristics and permeability, and white blood cell concentrations as beef heifers recovered from a feed restriction (FR) challenge, and 2) determine whether post-ruminal provision of a yeast cell wall extract (YCW) modulated responses. Ruminally cannulated beef heifers (n = 8) were used in a 2 × 2 crossover design. Treatments (TRT) included an abomasal infusion of a placebo (PLC; maltodextrin) or YCW derived from Saccharomyces cerevisiae (2 g/dose) infused at 0600 and 1800 h. Heifers were subject to 5-d of FR (offering 30% of ad libitum DMI) followed by five 5-d recovery phases (REC1, REC2, REC3, REC4, and REC5). Daily DMI, and rumen, fecal, and blood samples were collected on d 5 of FR, REC1, REC3, and REC5 with an additional collection on d 2 of REC1. Total gastrointestinal and post-ruminal permeability were measured using a ruminal dose of Cr-EDTA and an abomasal dose of Co-EDTA, respectively, during FR, REC1, REC3, and REC5 with concurrent urine collection. Data were analyzed to determine the effects of YCW provision, day, and the 2-way interaction. There were no TRT or TRT×day effects for any variables except DMI (interaction, P = 0.04), where DMI did not differ during the FR challenge; however, heifers provided YCW had a greater increase by REC1 compared with PLC heifers without any means differing. DMI progressively increased from FR, to REC1, REC2, and REC5. Ruminal acetate concentration increased (P &amp;lt; 0.01) from FR (45.4 mmol/L) to REC1 d5 (60.1 mmol/L) and increased further to REC3 (67.3 mmol/L) with no change thereafter (68.3 mmol/L in REC5). Ruminal propionate concentration increased (P &amp;lt; 0.01) from FR (14.5 mmol/L) to REC1 d2 (27.7 mmol/L) and was not different thereafter. Similarly, butyrate concentration increased (P &amp;lt; 0.01) from FR (7.9 mmol/L) to REC1 (d 5; 15.0 mmol/L) and was not different thereafter. Fecal acetate, propionate, and butyrate concentrations were not affected by day (P ≥ 0.12). Total gastrointestinal and post-ruminal permeability were greatest during FR (P &amp;lt; 0.01; 2.6% and 2.2% of the infused marker was excreted in urine, respectively) and decreased to 1.6% and 1.1%, respectively, in REC3 followed by an increase in REC5 for total (2.0% of infused) but not post-ruminal (1.0% of infused) permeability. The concentration of neutrophils (P &amp;lt; 0.01) was greatest on REC1 d2 (4.84 ×106 μmol/mL) and eosinophil concentration (P &amp;lt; 0.01) was greatest during FR (0.53 ×106 μmol/mL), least on d 2 of REC1 and increased on d 5 of REC1 but was not different thereafter. WBC (P &amp;lt; 0.01) gradually decreased (P = 0.02) from FR and REC1 d2 to REC3 and REC5. Post-ruminal provision of YCW may accelerate increases in DMI early in the recovery from FR, yet treatment did not modulate ruminal or fecal SCFA, blood concentrations, or gastrointestinal permeability.

311 Effect of feeding butyric acid on growth performance and metabolic indicators of dairy calves before weaning: A meta-analysis

Abstract This meta-analysis aimed to evaluate the effect of feeding butyric acid (BA) on growth performance and metabolic indicators in dairy calves. A literature search was conducted to identify in vivo research studies carried out on BA supplementation in dairy calves. Inclusion criteria were in vivo studies, dairy calves, weaning, BA, and inclusion doses of BA. Twenty-three papers with 80 data and 1,132 calves were selected. Data extracted included the number of calves in control and treatment groups and measures of variance of responses (standard error or standard deviation). The response variables were production performance including body weight (BW), average daily gain (ADG) feed efficiency (FE), and metabolic indicators including blood glucose and beta-hydroxybutyrate (BHB) concentrations. A random effect of model was used to examine the raw mean difference and standardized mean difference between BA supplementation and the control group. The analysis was conducted using the metafor package of Rstudio. Butyric acid moderately improved the growth performance and metabolic indicators responses of calves with substantial heterogeneity (59 &amp;lt; I2 &amp;lt; 73%, P &amp;lt; 0.01). Final BW and ADG were increased by 2.7 kg and 48.1 g/day, or &amp;gt; 0.6 and &amp;gt; 0.4 standard deviation units (P &amp;lt; 0.05), respectively. However, FE was increased by BA supplementation but not significantly different. For metabolic indicators, glucose concentration was greater with BA supplementation with &amp;gt; 0.4 standard deviation unit, (P &amp;lt; 0.05). However, BA supplementation did not affect the blood concentration of BHB (P &amp;gt; 0.05). In conclusion, the meta-analysis results demonstrated that BA constitutes an important energy source for dairy calves. Butyric acid is effective in promoting growth performance and intestinal health and, yet, increasing production profits.

The Rise of Bromazolam in Postmortem Cases from Travis County, Texas and Surrounding Areas: 2021-2023.

As novel psychoactive substances (NPS) have continued to emerge over the last decade, NPS benzodiazepines have likewise increased in prevalence. They pose an evolving threat to public health and safety with regard to postmortem cases, particularly when used in combination with opioids. Bromazolam was first detected in Travis County, Texas (TX) in April 2021. Given the recent onset of the fentanyl epidemic in this region, the international rise of bromazolam, and increased reports of "benzo-dope", a retrospective study was conducted to characterize bromazolam-positive deaths in Travis County and surrounding counties from 2021-2023. Bromazolam was identified in 112 deaths from 2021-2023, accounting for 1.57% of cases submitted for toxicology testing (n=7,129). During that interval, a 7.5-fold increase was observed in postmortem bromazolam-related drug toxicities from 2021 (n=7) to 2023 (n=53). Fatalities primarily occurred in males in their early-30's. Postmortem concentrations ranged from 21-220 ng/mL, with mean (median) concentrations of 69.4 ± 48.4 (53.5) ng/mL. Polydrug use was present in 99% of bromazolam-positive deaths with co-occurrence with other drugs and drug classes widely varying over time. Bromazolam was attributed as the sole cause of death in one case with a postmortem blood concentration of 23 ng/mL. Polydrug use in bromazolam-related drug toxicities commonly involved fentanyl (82%), methamphetamine (41%), and cocaine (28%). Similarly, cases where bromazolam was an incidental finding and non-contributory to the cause of death often involved methamphetamine (38%), alprazolam (33%), and cocaine (33%). In light of the significant increase in fentanyl-related deaths in Travis County, the increasing prevalence of bromazolam accompanying fentanyl was particularly alarming due to the heightened risk of toxicity when used in combination. Identifying and evaluating bromazolam-related deaths clarifies the impact of bromazolam on this population, promotes awareness, and aids in identifying meaningful harm reduction strategies to decrease bromazolam-related morbidity and mortality.

123 Effects of a Saccharomyces cerevisiae based direct-fed microbial on performance, health, and rumen bacterial community of newly weaned beef steers during a 56-d receiving period

Abstract We examined the effects of a blend of Saccharomyces cerevisiae, multiple live probiotic bacteria and their fermentation products on performance, health, and the ruminal bacterial community of newly weaned beef steers during a 56-d receiving period. Newly weaned Angus crossbred steers [n = 40; 221 ± 25.6 kg body weight (BW); 180 ± 17 d of age] were stratified by BW into four pens (10 steers per pen) such that each pen had a similar average BW at the beginning of the experiment. The pens were randomly assigned to receive a corn silage basal diet (CON; n = 20) or the basal diet supplemented with 9 g·steer⁻¹·d⁻¹of PRO feed additive (PRO; n = 20). The PRO additive is a blend of Saccharomyces cerevisiae and the fermentation products of Enterococcus faecium, Bacillus licheniformis, Bacillus subtilis, Lactobacillus animalis, Propionibacterium freudenreichii. The DMI and water consumed were monitored using the GrowSafe intake nodes and custom flow meters, respectively. Body weights were recorded weekly to calculate average daily gain (ADG). Before morning feeding, 10 mL of blood was taken from each steer on d 0 to 7, and thereafter weekly for analyses of immune cells, plasma glucose and NEFAs. On d 56, rumen fluid samples (200 mL each) were collected from all the steers for microbiome analysis. Over the 56-d receiving period, the supplemental PRO had no effects on DMI, water intake, or ADG. However, compared with CON, beef steers fed supplemental PRO tended to have greater ADG (P = 0.08) and BW (P = 0.07) during the first 14 d of the study. There was a treatment × day interaction (P ≤ 0.05) for WBC, neutrophils and monocytes over the 56 d such that beef steers fed supplemental PRO had decreased blood concentrations on certain days during the first 7 d after weaning, indicating reduced inflammation or stress response. The results of the rumen microbiome analysis revealed that the relative abundance of complex fiber degrading or obligate proton-reducing bacterial genera such as Bacteroides, Ruminococcus gauvreauii group, Desulfovibrio, Syntrophococcus, and Acetitomaculum were greater (P ≤ 0.05) in beef steers fed supplemental PRO compared with CON. This study demonstrated that dietary supplementation of PRO improved the growth performance, reduced stress or inflammatory response during the initial days after weaning and altered the ruminal bacterial community towards increased relative abundance of bacterial genera associated with improved rumen function.

321 Application of the Fick Principle for the study of visceral nutrient absorption and metabolism

Abstract In 1870, Adolf Fick introduced the concept for the calculation of cardiac output by measuring gas exchange in the lungs at a meeting of the Würzburg Physiology and Medical Society. It was not until around 1930 after the development of cardiac catheterization that it was fully verified. Fick’s equation also serves as the basis for all indicator dilution methods for measuring blood flow and has been applied to several tissues throughout the body. By measuring the blood concentration of nutrients supplying and draining a tissue bed, coupled with the flow of blood, the net nutrient exchange can be calculated. Researchers first began investigating the movement of nutrients into the portal system of ruminants in the 1950s and the first method for measuring nutrient exchange in small ruminants was published in the 1960s. This approach requires the implantation of vascular catheters into an artery and the hepatic portal vein which drains the stomach, intestines, and spleen. An additional catheter is implanted upstream in a mesenteric vein for infusion of a blood flow marker, and the addition of a catheter in a hepatic vein allows the measure of blood flow and nutrient transfer in the liver. These methods were adapted for calves and dairy cows in the 1970s. The 1980s brought further refinement of the methodologies such as improved catheter materials allowing animals to be maintained for extended periods and, several researchers published data from cattle, sheep, and goats. These methods have been coupled with measures of ruminal and intestinal disappearance as well as isotopic tracers to examine nutrient exchange and metabolism by tissues. The goal of this presentation is to review the development of this approach for studying nutrient absorption in vivo, and to highlight specific advancements in its application.

Strong associations between fasting lipids and glucose concentrations and ALT levels strengthened with increasing ALT quantiles

BackgroundA persistent redox state and excessive reactive species involved in carbohydrate and lipid metabolism lead to oxidative damage in the liver, however, how fasting plasma concentrations of lipids and glucose are associated with fasting blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) remains to be evaluated in large-scale population.MethodsA cross-sectional study with 182,971 residents aged 18 to 92 years; multidimensional stratified analyses including quantile linear regression analysis and sex stratification were adopted to improve the quality of the evidence.ResultsThe associations between the concentrations of non-HDL-C and triglyceride and ALT levels were positive, stronger in males in each quantile of ALT levels and the coefficients expanded with increasing ALT levels at slopes of 3.610 and 5.678 in males and 2.977 and 5.165 in females, respectively. The associations between the HDL-C concentrations and ALT levels were negative, also stronger in males in each quantile and the coefficients expanded with increasing ALT levels at slopes of -7.839 in females and − 5.797 in males. The associations between glucose concentrations and ALT levels were positive, but stronger in females in each quantile and the coefficients expanded with increasing ALT levels at slopes of 1.736 in males and 2.177 in females, respectively. Similar pattern consist of relatively weaker coefficients and slops were observed between concentrations of non-HDL-C, triglyceride and glucose and AST levels. The associations between albumin concentration and concentrations of blood lipids and glucose were relatively steady across all quantiles.ConclusionsThe dose dependent effect between blood concentrations of lipids and glucose and liver function changes suggests that excessive carbohydrate and lipid metabolism may cause subclinical liver damage. Long term sustained primary and secondary inflammatory factors produced in the liver might be transmitted to adjacent organs, such as the heart, kidneys, and lungs, to cause and/or exacerbate pathological changes in these visceral organs.

Neurotoxic Effects of Mixtures of Perfluoroalkyl Substances (PFAS) at Environmental and Human Blood Concentrations.

Per- and polyfluoroalkyl substances (PFAS) may cause various deleterious health effects. Epidemiological studies have demonstrated associations between PFAS exposure and adverse neurodevelopmental outcomes. The cytotoxicity, neurotoxicity, and mitochondrial toxicity of up to 12 PFAS including perfluoroalkyl carboxylates, perfluoroalkyl sulfonates, 6:2 fluorotelomer sulfonic acid (6:2 FTSA), and hexafluoropropylene oxide-dimer acid (HPFO-DA) were tested at concentrations typically observed in the environment (e.g., wastewater, biosolids) and in human blood using high-throughput in vitro assays. The cytotoxicity of all individual PFAS was classified as baseline toxicity, for which prediction models based on partition constants of PFAS between biomembrane lipids and water exist. No inhibition of the mitochondrial membrane potential and activation of oxidative stress response were observed below the cytotoxic concentrations of any PFAS tested. All mixture components and the designed mixtures inhibited the neurite outgrowth in differentiated neuronal cells derived from the SH-SY5Y cell line at concentrations around or below cytotoxicity. All designed mixtures acted according to concentration addition at low effect and concentration levels for cytotoxicity and neurotoxicity. The mixture effects were predictable from the experimental single compounds' concentration-response curves. These findings have important implications for the mixture risk assessment of PFAS.

Effects of maternal dietary supplementation with antioxidants on clinical status of mares and their foal

BackgroundThe peripartum period constitutes a delicate physiological moment in mares showing a transient state of oxidative stress. Diet supplementation with antioxidants during pregnancy in women appears to have a beneficial effect on mother and neonate health. The aim of this work was to evaluate the effects of diet supplementation with a commercial product containing a mix of antioxidants (Oxyliver®, Candioli) on the length of gestation, weight, and haemato-biochemical parameters in Italian Salernitano mares and their newborn foals. Eight late-term pregnant mares were randomly divided into two groups: Antiox group receiving 30 g/day of antioxidants, and Car group receiving the same amount of carrot powder, from 290 to 320 days of gestation. The following parameters were evaluated in mares: weight, colostrum composition, haemato-biochemical parameters, progesterone, and cortisol blood concentrations, along with blood oxidant/antioxidant status. Assessments were conducted at specific time points: immediately before the start of diet supplementation (T0), 15 days after (T1), at the end of diet supplementation (T2), within 8 h after parturition (T3), and 10 days post-partum (T4). Foal parameters such as weight, haemato-biochemical values, cortisol concentration, and blood oxidative stress variables were assessed within 8 h of birth (TF0) and at 10 days of age (TF1).ResultsPregnancy was shorter in the Antiox group (P < 0.05) compared with the Car group; the foals’ weight increase of group Antiox (40%) was higher (P < 0.05) compared to those of the Car group (28.6%). The colostrum of the Antiox group exhibited higher levels of Brix, total solids, protein, nonfat solids, casein, urea, density, free fatty acids, and glucose, while lower levels of fat and lactose were observed compared to the Car group (P < 0.05). Mares’ serum albumin at T1 and T3, creatinine, glucose, total proteins, total bilirubin, AST, and ALT at T3 were lower in Antiox than in the Car group. No significant differences were found in foals.ConclusionsWhile the limited sample size and the potential variability of evaluated parameters, the observed outcomes suggest that Oxyliver® supplementation in mares might safely decrease gestation length and enhance liver function, thus potentially improving colostrum quality and offspring development.

Cadmium Associated Preeclampsia: A Systematic Literature Review of Pregnancy and Birth Outcomes.

Preeclampsia (PE), caused by multiple factors, is one of the most serious complications of pregnancy. Cadmium (Cd) is a heavy metal environmental pollutant, reproductive toxicant, and endocrine disruptor, which can increase the risk of PE. Cd toxicity due to occupational, diet, and environmental factors has worsened the risk. Studies showed elevated Cd concentration in maternal blood and placenta of PE women. However, the implicit association between Cd associated PE is still not highlighted. We systematically reviewed Cd-associated PE and its effect on pregnancy and birth outcomes. Based on "Preferred reporting items for systematic reviews and meta-analyses (PRISMA)" guidelines, eighty-six studies were identified by PubMed, Web of Science (WOS), and Scopus databases. Publications were included until October 2023 and articles screened based on our inclusion criteria. Our study identified that the exposure of controlled and uncontrolled Cd induces PE, which negatively affects pregnancy and birth outcomes. Given the serious nature of this finding, Cd is a potential adverse agent that impacts pregnancy and future neonatal health. Further comprehensive studies covering the whole trimesters of pregnancy and neonatal developments are warranted. Data on the molecular mechanisms behind Cd-induced PE is also essential for potential preventive, diagnostic, or therapeutic targets.

Relationship between TIGIT expression on T cells and the prognosis of patients with hepatocellular carcinoma

BackgroundTranscatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC.MethodsClinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed.ResultsPatients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment.ConclusionsPatients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.