Search Results (18)

Background: Reliable intraoperative tools for donor liver assessment are needed, particularly in the context of steatotic and extended-criteria grafts. While histology remains the reference standard, it is limited by sampling variability and logistical constraints. Preservation fluid may provide a complementary, whole-organ source of biochemical information. Methods: In this single-center prospective exploratory pilot study, liver tissue and preservation fluid were collected from 30 donation-after-brain-death grafts during the back-table procedure. Biochemical parameters, including arginase activity, β-hydroxybutyrate (βHB), acetoacetate, and total protein, were measured using standard assays. Associations with histological steatosis on wedge biopsy were assessed using nonparametric correlation analyses, and paired preservation fluid samples were compared. Results: Most grafts demonstrated absent or mild steatosis; only two exhibited moderate steatosis, and none were severely steatotic. No preservation fluid biomarker showed a statistically significant association with histological steatosis. Weak, non-significant positive correlations were observed for βHB and arginase activity (Spearman r ≈ 0.33–0.35). Protein concentration and arginase activity decreased between start and end samples, whereas ketone body levels remained relatively stable. Conclusions: Preservation fluid biomarker measurement during routine graft preparation is feasible. Although no significant associations with histological steatosis were identified, the observed weak correlations suggest possible associations requiring validation in larger studies. Larger, adequately powered studies, including a broader spectrum of steatosis and clinically relevant outcomes, are required to determine potential clinical applicability. Full article

Background/Objectives: Rapid and accurate ketone detection is clinically valuable for both diabetic and non-diabetic individuals. Breath acetone represents an attractive non-invasive and real-time alternative for monitoring ketones. This study aimed to explore the correlation between breath acetone measured by proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) and ketone bodies in blood and urine in individuals with normoglycemia, prediabetes and diabetes. Methods: A total of 4000 participants were recruited. Urinary ketone levels, blood β-hydroxybutyrate (βHB) concentrations, and breath acetone (measured by PTR-TOF-MS) were assessed. Participants were classified into urine ketone-negative and urine ketone-positive groups. They were further divided according to the semiquantitative degree of urinary ketone (−, +, ++, +++ and ++++). Spearman rank correlation analysis was performed to evaluate the relationship between breath acetone and blood βHB. Receiver operating characteristic (ROC) curve analysis was conducted to determine the preliminary thresholds of breath acetone for detecting blood βHB positivity. Multiple linear regression, including a quadratic term for blood βHB, was performed, and the inflection point of the curve was calculated. Results: Blood βHB and breath acetone were significantly higher in the urine ketone-positive group than in the urine ketone-negative group (p < 0.001). A progressive elevation in blood βHB and exhaled breath acetone concentrations was observed with increasing urinary ketone levels (p < 0.001). The Spearman rank correlation coefficient between breath acetone and blood βHB was 0.493, 0.522, 0.379, and 0.636 in the general population, normoglycemia, prediabetes, and diabetes groups, respectively (all p < 0.001). The preliminary thresholds of breath acetone concentration for detecting blood βHB positivity were 2.37 ppmv in diabetes, 1.10 ppmv in prediabetes, and 2.05 ppmv in normoglycemia, respectively. Blood βHB exhibited a significant quadratic association with breath acetone in the general population, normoglycemia, and diabetes (B = −1.698, −1.409, and −16.070, respectively; p < 0.001), with inflection points of the quadratic curves at 2.73 mmol/L, 3.28 mmol/L and 1.61 mmol/L, respectively, whereas in prediabetes, the relationship did not significantly deviate from linearity. Conclusions: In normoglycemia and diabetes, breath acetone based on PTR-TOF-MS exhibited an inverted U-shaped relationship with blood βHB, while in prediabetes, breath acetone showed a linear positive correlation with blood βHB. In populations where blood βHB is below the quadratic inflection point, breath acetone measured by PTR-TOF-MS holds promise as a non-invasive ketone-monitoring tool. Full article

Purpose: Ketone bodies could be useful biomarkers in multiple sclerosis (MS) because the pathophysiological processes underlying MS disease progression induce metabolic stress. The purpose was to assess the relationships of ketone bodies with biomarkers of metabolic, inflammatory, and oxidative stress in MS. Methods: Blood samples and neurological assessments were obtained from 153 healthy controls (HC), 187 relapsing-remitting (RRMS), and 91 progressive MS (PMS) patients. AcAc, BHB, and acetone were measured using proton nuclear magnetic resonance spectroscopy. Indices of inflammatory vulnerability (IVX), metabolic malnutrition (MMX), and metabolic vulnerability (MVX) were computed from the NMR profiles. Cholesterol, apolipoprotein, lipid peroxidation, and antioxidant profiles were obtained. Regression analysis adjusted for age, sex, body mass index, and HC, RRMS, or PMS disease status. Results: AcAc and BHB levels were greater in MS compared to HC. BHB and ketone bodies were positively associated with disability on the MS Severity Scale and ambulation time. BHB was positively associated with IVX, MMX, and MVX. AcAc was positively associated with MMX and negatively associated with IVX and MVX. Total ketone body concentration was positively associated with MMX and MVX. BHB and AcAc levels were negatively associated with the amino acids alanine, valine, and leucine. Conclusions: Ketone bodies are associated with inflammatory vulnerability, metabolic vulnerability, and ambulatory disability measures in MS. Full article

P-15 is a 15-amino-acid-long biomimetic peptide widely demonstrated to enhance osteogenesis in vivo. Despite the prevalence of polyether-ether-ketone (PEEK) in interbody device manufacturing, a growing body of evidence suggests it may produce an unfavorable immune response. The purpose of this preliminary study was to characterize the immune response and new bone growth surrounding PEEK implants with and without a P-15 peptide-based osteobiologic. A bilateral femoral defect model was conducted using New Zealand white rabbits. A total of 17 test subjects received one implant in each distal femur, either with or without bone graft material. Animals were allowed to survive to 4 or 8 weeks, at which time the femurs were collected and subjected to micro-computer tomography (microCT) or cytokine analysis. MicroCT analysis included the quantification of bone growth and density surrounding each implant. The cytokine analysis of periprosthetic tissue homogenates included the quantification of interleukins (ILs) and TNF-α expression via ELISA kits. Improvements in bone volume were observed in the P-15 cohort for the regions of interest, 500–136 and 136–0 µm from the implant surface, at 8 weeks post-op. Concentrations of IL-1β, IL-4, and IL-6 cytokines were significantly higher in the P-15 cohort compared to the PEEK cohort at the 4-week timepoint. Significant reductions in the concentrations of IL-4 and IL-6 cytokines from the 4- to 8-week cohort were observed in the P-15 cohort only. The P-15 peptide has the potential to modulate the immune response to implanted materials. We observed improvements in bone growth and a more active micro-environment in the P-15 cohort relative to the PEEK control. This may indicate an earlier transition from the inflammatory to remodeling phase of healing. Full article

This review paper provides an in-depth analysis of three critical metabolic diseases affecting dairy cattle such as subacute ruminal acidosis (SARA), ketosis, and hypocalcemia. SARA represents a disorder of ruminal fermentation that is characterized by extended periods of depressed ruminal pH below 5.5–5.6. In the long term, dairy herds experiencing SARA usually exhibit secondary signs of the disease, such as episodes of laminitis, weight loss and poor body condition despite adequate energy intake, and unexplained abscesses usually 3–6 months after an episode of SARA. Depressed milk-fat content is commonly used as a diagnostic tool for SARA. A normal milk-fat test in Holstein dairy cows is >4%, so a milk-fat test of <3% can indicate SARA. However, bulk tank testing of milk fat is inappropriate to diagnose SARA at the herd level, so when >4 cows out of 12 and <60 days in milk are suspected to have SARA it can be considered that the herd has a problem. The rapid or abrupt introduction of fresh cows to high-concentrate diets is the most common cause of SARA. Changes in ruminal bacterial populations when exposed to higher concentrate rations require at least about 3 weeks, and it is recommended that concentrate levels increase by no more than 400 g/day during this period to avoid SARA. Ketosis, a prevalent metabolic disorder in dairy cattle, is scrutinized with a focus on its etiological factors and the physiological changes leading to elevated ketone bodies. In total mix ration-fed herds, an increased risk of mastitis and reduced fertility are usually the first clinical signs of ketosis. All dairy cows in early lactation are at risk of ketosis, with most cases occurring in the first 2–4 weeks of lactation. Cows with a body condition score ≥3.75 on a 5-point scale at calving are at a greater risk of ketosis than those with lower body condition scores. The determination of serum or whole blood acetone, acetoacetate, beta-hydroxybutyrate (BHB) concentration, non-esterified fatty acids (NEFA), and liver biopsies is considered the best way to detect and monitor subclinical ketosis, while urine or milk cowside tests can also be used in on-farm monitoring programs. Concentrations >1.0 mmol/L or 1.4 mmol/L blood or serum BHB are considered diagnostic of subclinical ketosis. The standard threshold used for blood is 1.2 mmol/L, which corresponds to thresholds of 100 mcmol/L for milk and 15 mg/dL for urine. Oral administration of propylene glycol (250–400 g, every 24 h for 3–5 days) is the standard and most efficacious treatment, as well as additional therapy with bolus glucose treatment. Hypocalcemia is a disease of adult dairy cows in which acute hypocalcemia causes acute to peracute, afebrile, flaccid paralysis that occurs most commonly at or soon after parturition. Dairy cows are at considerable risk for hypocalcemia at the onset of lactation, when daily calcium excretion suddenly increases from about 10 g to 30 g per day. Cows with hypocalcemia have a more profound decrease in blood calcium concentration—typically below 5.5 mg/dL. The prevention of parturient paresis has been historically approached by feeding cows low-calcium diets during the dry period. Negative calcium balance triggers calcium mobilization before calving and better equips the cow to respond to the massive calcium needs at the onset of lactation. Calcium intake must be limited to <20 g per day for calcium restriction to be effective. The most practical and proven method for monitoring hypocalcemia is by feeding cows an acidogenic diet for ~3 weeks before calving. Throughout the review, emphasis is placed on the importance of early diagnosis and proactive management strategies to mitigate the impact of these metabolic diseases on dairy cattle health and productivity. The comprehensive nature of this paper aims to serve as a valuable resource for veterinarians, researchers, and dairy farmers seeking a deeper understanding of these prevalent metabolic disorders in dairy cattle. Full article

Ketone bodies (KBs) are energy-efficient substrates utilized by the heart depending on its metabolic demand and substrate availability. Levels of circulating KBs have been shown to be elevated in acute and chronic cardiovascular disease and are associated with severity of disease in patients with heart failure and functional outcome after myocardial infarction. To investigate whether this pattern similarly applies to patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB), we analysed prospectively collected pre- and postoperative blood samples from 192 cardiac surgery patients and compared levels and perioperative changes in total KBs with Troponin T as a marker of myocardial cell injury. We explored the association of patient characteristics and comorbidities for each of the two biomarkers separately and comparatively. Median levels of KBs decreased significantly over the perioperative period and inversely correlated with changes observed for Troponin T. Associations of patient characteristics with ketone body perioperative course showed notable differences compared to Troponin T, possibly highlighting factors acting as a “driver” for the change in the respective biomarker. We found an inverse correlation between perioperative change in ketone body levels and changes in troponin, indicating a marked decrease in ketone body concentrations in patients exhibiting greater myocardial cell injury. Further investigations aimed at better understanding the role of KBs on perioperative changes are warranted. Full article

We compared the 24 h changes in interstitial fluid glucose concentration (IGC) following a simulated soccer match between subjects consuming a high-carbohydrate (HCHO; 8 g/kg BW/day) diet and those consuming a moderate-carbohydrate (MCHO; 4 g/kg BW/day) diet. Eight active healthy males participated in two different trials. The subjects were provided with the prescribed diets from days 1 to 3. On day 3, the subjects performed 90 min (2 bouts × 45 min) of exercise simulating a soccer match. The IGC of the upper arm was continuously monitored from days 1 to 4. No significant difference in the IGC was observed between trials during exercise. The total area under the curve (t-AUC) value during exercise did not significantly differ between the HCHO (9719 ± 305 mg/dL·90 min) and MCHO (9991 ± 140 mg/dL·90 min). Serum total ketone body and beta-hydroxybutyrate concentrations were significantly higher in the MCHO than in the HCHO after a second bout of exercise. No significant differences in the IGC were observed between trials at any time point during the night after exercise (0:00–7:00). In addition, t-AUC value during the night did not significantly differ between the HCHO (32,378 ± 873 mg/dL·420 min) and MCHO (31,749 ± 633 mg/dL·420 min). In conclusion, two days of consuming different carbohydrate intake levels did not significantly affect the IGC during a 90 min simulated soccer match. Moreover, the IGC during the night following the exercise did not significantly differ between the two trials despite the different carbohydrate intake levels (8 vs. 4 g/kg BW/day). Full article

In glucose-deprived conditions, ketone bodies are produced by the liver mitochondria, through the catabolism of fatty acids, and are used peripherally, as an alternative energy source. Ketones are produced in the body under normal conditions, including during pregnancy and the neonatal period, when following a ketogenic diet (KD), fasting, or exercising. Additionally, ketone synthesis is also augmented under pathological conditions, including cases of diabetic ketoacidosis (DKA), alcoholism, and several metabolic disorders. Nonetheless, diet is the main regulator of total body ketone concentrations. The KDs are mimicking the fasting state, altering the default metabolism towards the use of ketones as the primary fuel source. Recently, KD has gained recognition as a medical nutrition therapy for a plethora of metabolic conditions, including obesity and diabetes mellitus (DM). The present review aims to discuss the role of ketones, KDs, ketonemia, and ketonuria in DM, presenting all the available new evidence in a comprehensive manner. Full article

The combination of ketogenic diet (KD) with intermittent fasting (IF) has, for years, aroused a great interest in the scientific world and among healthy lifestyle enthusiasts. Its importance is even greater when the study subjects are physically active individuals. The aim of the study was a determination of the effect of strict calculated ketogenic menu combined with IF and with caloric deficit on the selected biochemical markers and body composition in a 23-year-old man performing strength training. At the same time, we decided to conduct the first so-deeply investigated and controlled case study in this respect. The study protocol included a 13-week-long ketogenic diet with intermittent fasting (of delayed time-restricted eating 16:8 type) and caloric deficit. A detailed menu was designed and was used by the man throughout the whole study duration. A number of blood tests were performed before and after the implemented dietary intervention. Additionally, body composition was determined weekly and the concentrations of glucose and ketone bodies, as well as pulse rate and arterial pressure, were measured daily. The most important changes noted included a significant increase in testosterone and vitamin D concentrations and significant reduction in the HOMA-IR index and concentrations of hepatic enzymes, insulin, glucose, iron, urea, and free triiodothyronine (FT3). Moreover, a significant improvement of body composition occurred (the ratio of total body mass to the adipose and muscular tissue and water mass improved). Favourable changes were also noted in heart rate and arterial pressure values. In view of that, the KD with IF and caloric deficit exerted favourable effects on most biochemical parameters and on body composition and caused an almost twofold increase in serum testosterone concentration. Full article

Recently, the secondary use of by-products of the processing industry resulting from the production of poultry meat, which can be included in animal diets, has become a popular topic in the feed industry. For studying the effects of partial replacement of rapeseed cake (RC) with the by-product source of animal protein concentrate Agro-Matic (PCAM) on growth dynamics, nutrient absorption and nitrogen balance, as well as blood biochemical parameters during the growing period, a total of 48 Russian Ayrshire dairy heifers were selected for this experiment and they were divided into three experimental groups (16 in each group, including the control group). The heifers of the control group were fed the basal diet which contained rapeseed cake (30%), while the second (RC + PCAM) and third groups (PCAM + RC) were fed the basal diet after replacing a part of the rapeseed cake with 2.25% and 4.5% of protein concentrate Agro-Matic respectively. The results showed that the weight of heifers treated with PCAM at 3 months of age exceeded the control by 2.3 kg (p > 0.05) in group 2 by 4.4 kg (p < 0.05). Similar results were obtained at the age of 6 months of raising. Feeding 4.50% protein concentrate Agro-Matic has a positive effect on the digestibility of nutrients; in particular, there was a significant increase in the digestibility of crude protein in the PCAM + RC group (77.23 vs. 73.42%) compared with the control group. Moreover, a similar trend was found in the digestibility of nitrogen in the diet. At the age of 3 months, heifers showed a significant decrease in the concentration of ketone bodies in the second group (1.82 vs. 2.20 mmol/L) relative to the control group. Urea was significantly lower in the RC + PCAM group (5.05 vs. 6.62 mmol/L) relative to the PCAM + RC group, while acid capacity (alkaline reserve) was higher by 2.41% (p < 0.05) relative to the control. In the 10th month of age, a positive effect on the blood of heifers was observed, as in the second and the third experimental groups, β-globulin and phosphorus increased (p < 0.05), while in the second group aspartate aminotransferase decreased (p < 0.05). Consequently, replacing the rapeseed cake with the protein concentrate Agro-Matic revealed an improvement in the dynamics of growth, nutrient digestibility and nitrogen balance, and it has an effect on improving some biochemical parameters of the blood. Full article

Most university students do not follow recommendations for fruit and vegetable intake, with a consequent increase in the prevalence of cardiovascular disease (CVD) risk factors. The aim of this study was to compare obesity prevalence and biomarkers of metabolic status between Italian and Spanish university students, in relation with the consumption of fruits and vegetables. Food consumption, adherence to a Mediterranean diet (MD), level of physical activity (PA), blood glucose, total cholesterol, triglycerides and ketones, blood pressure, and body composition were evaluated. Among CVD risk factors, only glucose was significantly higher in Spaniards (SP), and only 3.1% of SP presented ketosis. SP had a higher percentage of energy from fat. Although adherence to MD and fruit and vegetable consumption did not differ between Italians and SP, students who consumed at least four servings of fruit and vegetables (FV group) showed better values for pressure and metabolic parameters than the no FV group. We observed an association between consumption of fruit and PA. Students who consumed more vegetables than fruit reported a better body composition profile and lower glucose concentrations. As previously suggested, in addition to PA, two servings of fruit and three servings of vegetables per day should be recommended. Full article

A variety of atherosclerosis and cardiovascular disease (ASCVD) phenotypes are tightly linked to changes in the cardiac energy metabolism that can lead to a loss of metabolic flexibility and to unfavorable clinical outcomes. We conducted an association analysis of 31 ASCVD phenotypes and 97 whole blood amino acids, acylcarnitines and derived ratios in the LIFE-Adult (n = 9646) and LIFE-Heart (n = 5860) studies, respectively. In addition to hundreds of significant associations, a total of 62 associations of six phenotypes were found in both studies. Positive associations of various amino acids and a range of acylcarnitines with decreasing cardiovascular health indicate disruptions in mitochondrial, as well as peroxisomal fatty acid oxidation. We complemented our metabolite association analyses with whole blood and peripheral blood mononuclear cell (PBMC) gene-expression analyses of fatty acid oxidation and ketone-body metabolism related genes. This revealed several differential expressions for the heart failure biomarker N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in peripheral blood mononuclear cell (PBMC) gene expression. Finally, we constructed and compared three prediction models of significant stenosis in the LIFE-Heart study using (1) traditional risk factors only, (2) the metabolite panel only and (3) a combined model. Area under the receiver operating characteristic curve (AUC) comparison of these three models shows an improved prediction accuracy for the combined metabolite and classical risk factor model (AUC = 0.78, 95%-CI: 0.76–0.80). In conclusion, we improved our understanding of metabolic implications of ASCVD phenotypes by observing associations with metabolite concentrations and gene expression of the mitochondrial and peroxisomal fatty acid oxidation. Additionally, we demonstrated the predictive potential of the metabolite profile to improve classification of patients with significant stenosis. Full article

(1) Background: Multiple sclerosis (MS) is pathogenically characterized by high oxidative stress and symptomatically by progressive muscle loss and increased body fat associated with the presence of depression. Epigallocatechin gallate (EGCG) (particularly present in green tea) and ketone bodies (in particular beta-hydroxybutyrate (BHB)), whose main source is coconut oil, have shown emotional benefits and body fat loss. The aim of this study was to assess the impact of EGCG and coconut oil on cortisol activity related to fat loss and depression in MS patients. (2) Methods: The study involved 51 MS patients who were randomly divided into an intervention group or a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, which were included in their daily diet for four months. The control group received placebo and all patients followed an isocaloric diet. A blood sample was collected before and after the four-month period, and levels of cortisol, albumin and BHB were measured in serum. In addition, immediately before and after the intervention, anthropometric variables were measured: waist-to-hip ratio (WHR), body fat mass percentage, fat weight, total weight, and muscle mass percentage. Depression was assessed with the Beck Depression Inventory II (BDI-II). (3) Results: No significant changes were obtained in cortisol levels in any of the groups, and there was a significant increase in albumin in the blood of the intervention group only that could lead to a decrease in serum free cortisol. In addition, it was observed a significant decrease in levels of depression and abdominal fat. (4) Conclusions: EGCG combined with coconut oil increase the concentration of albumin in blood and produce less depression in MS patients. Full article

This study was performed to evaluate anti-obesity potential of Commiphora myrrha resin ethanolic extract (CME) with the respect to expression of leptin, adiponectin and uncoupling protein 1 (UCP1) in rats. Control rats fed basal diet. Second group fed basal diet and administered CME (500 mg/kg bw) orally for 14 weeks. Third group fed high fat diet (HFD) for 14 weeks. Fourth group fed HFD and administered CME as second group. Fifth group fed HFD for 8 weeks then fed basal diet and administered CME as third group for another 6 weeks. Phytochemical analysis of CME identified the presence of germacrene B, 1,4-benzoquinone, benzofuran, hexadecanoic acid, 9,12-octadecnoic acid methyl ester, reynosin, 11, 14-eicosadienoic acid, isochiapin B, bisabolene epixod, elemene and 1-heptatriacotanol. High fat diet significantly increased food intake, body weight, hyperglycemia, serum levels of total cholesterol, triacylglycerol, low density lipoprotein and ketone bodies, AST and AST activities, concentration of malondialdehyde and histopathological changes in hepatic tissues. However, it significantly reduced serum levels of high density lipoprotein, leptin and adiponectin, activity of hepatic glutathione reductase (GR) and brown adipose tissue UCP1 protein expression. In contrast, CME ameliorated HFD increased body weight, hyperglycemia, dyslipidemia, ketonemia, hepatic tissues lipid peroxidation, restored hepatic tissue architecture and enhanced protein expression of leptin, adiponectin and UCP1 and activity of hepatic GR. This study indicated that CME ameliorated HFD induced hyperglycemia and dyslipidemia through normalization of HFD reduced leptin, adiponectin and UCP1 proteins production and antioxidant activity. Full article

Background: Quantifying mildly elevated ketone bodies is clinically and pathophysiologically relevant, especially in the context of disease states as well as for monitoring of various diets and exercise regimens. As an alternative assay for measuring ketone bodies in the clinical laboratory, a nuclear magnetic resonance (NMR) spectroscopy-based test was developed for quantification of β-hydroxybutyrate (β-HB), acetoacetate (AcAc) and acetone. Methods: The ketone body assay was evaluated for precision, linearity and stability and method comparisons were performed. In addition, plasma ketone bodies were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1198; 373 type 2 diabetes mellitus (T2DM) subjects). Results: β-HB and AcAc quantified using NMR and mass spectrometry and acetone quantified using NMR and gas chromatography/mass spectrometry were highly correlated (R² = 0.996, 0.994, and 0.994 for β-HB, AcAc, acetone, respectively). Coefficients of variation (%CVs) for intra- and inter-assay precision ranged from 1.3% to 9.3%, 3.1% to 7.7%, and 3.8% to 9.1%, for β-HB, AcAc and acetone, respectively. In the IRAS, ketone bodies were elevated in subjects with T2DM versus non-diabetic individuals (p = 0.011 to ≤0.001). Age- and sex-adjusted multivariable linear regression analysis revealed that total ketone bodies and β-HB were associated directly with free fatty acids (FFAs) and T2DM and inversely with triglycerides and insulin resistance as measured by the Lipoprotein Insulin Resistance Index. Conclusions: Concentrations of the three main ketone bodies can be determined by NMR with good clinical performance, are elevated in T2DM and are inversely associated with triglycerides and insulin resistance. Full article