Total Ketone Body Concentrations Research Articles

Continuous Monitoring of Interstitial Fluid Glucose Responses to Endurance Exercise with Different Levels of Carbohydrate Intake.

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).

Longitudinal Changes in Circulating Ketone Body Levels in Patients With Acute Heart Failure: A Post Hoc Analysis of the EMPA-Response-AHF Trial

BackgroundKetone bodies are endogenous fuels produced by the liver under conditions of metabolic or neurohormonal stress. Circulating ketone bodies are increased in patients with chronic heart failure (HF), yet little is known about the effect of acute HF on ketosis. We tested the hypothesis that ketogenesis is increased in patients with acute decompensated HF. Methods and resultsThis was a post hoc analysis of 79 patients with acute HF included in the EMPA-RESPONSE-AHF trial, which compared sodium-dependent glucose-cotransporter protein 2 inhibitor treatment with empagliflozin for 30 days with placebo in patients with acute HF [NCT03200860]. Plasma concentrations of ketone bodies acetone, β-hydroxybutyrate, and acetoacetate were measured at baseline and 5 different timepoints. Changes in ketone bodies over time were monitored using repeated measures analysis of variance. In the total cohort, median total ketone body concentration was 251 µmol/L (interquartile range, 178–377 µmol/L) at baseline, which gradually decreased to 202 µmol/L (interquartile range, 156–240 µmol/L) at day 30 (P = .041). Acetone decreased from 60 µmol/L (interquartile range, 34–94 µmol/L) at baseline to 30 µmol/L (interquartile range, 21–42 µmol/L) ( P < .001), whereas β-hydroxybutyrate and acetoacetate remained stable over time. Higher acetone concentrations were correlated with higher N-terminal pro brain natriuretic peptide levels (r = 0.234; P = .039). Circulating ketone bodies did not differ between patients treated with empagliflozin or placebo throughout the study period. A higher acetone concentration at baseline was univariately associated with a greater risk of the composite end point, including in-hospital worsening HF, HF rehospitalizations, and all-cause mortality after 30 days. However, after adjustment for age and sex, acetone did not remain an independent predictor for the combined end point. ConclusionsCirculating ketone body concentrations, and acetone in particular, were significantly higher during an episode of acute decompensated HF compared with after stabilization. Treatment with empagliflozin did not affect ketone body concentrations in patients with acute HF.

Exogenous glucose oxidation during endurance exercise under low energy availability.

The present study was conducted to determine the effect of endurance exercise under low energy availability (EA) on exogenous glucose oxidation during endurance exercise. Ten active males (21.4 ± 0.6 years, 170.4 ± 1.4 cm, 62.4 ± 1.5 kg, 21.5 ± 0.4 kg/m2) completed two trials, consisting of two consecutive days (days 1 and 2) of endurance training under low EA (19.9 ± 0.2 kcal/kg fat free mass [FFM]/day, LEA trial) or normal EA (46.4 ± 0.1 kcal/kg FFM/day, NEA trial). The order of these two trials was randomized with at least a 1-week interval between trials. As an endurance training, participants performed 60 min of treadmill running at 70% of maximal oxygen uptake () during two consecutive days (on days 1 and 2). On day 1, the endurance training was performed with consumed individually manipulated meals. During the endurance exercise on day 2, exogenous glucose oxidation was evaluated using 13C-labeled glucose, and respiratory gas samples were collected. In addition, blood glucose and lactate concentrations were measured immediately after exercise on day 2. Body composition, blood parameters, and resting respiratory gas variables were evaluated under overnight fasting on days 1 and 2. Body weight was significantly reduced in the LEA trial on day2 (day1: 61.8 ± 1.4 kg, day 2: 61.3 ± 1.4 kg, P < 0.001). There were no significant differences between trials in 13C excretion (P = 0.33) and area under the curve during the 60 min of exercise (LEA trial: 40.4 ± 3.1 mmol•60min, NEA trial: 40.4 ± 3.1 mmol•60min, P = 0.99). However, the respiratory exchange ratio (RER, LEA trial: 0.88 ± 0.01, NEA trial: 0.90 ± 0.01) and carbohydrate oxidation (LEA trial: 120.1 ± 8.8 g, NEA trial: 136.8 ± 8.6 g) during endurance exercise showed significantly lower values in the LEA trial than in the NEA trial (P = 0.01 for RER and carbohydrate oxidation). Serum insulin and total ketone body concentrations were significantly changed after a day of endurance training under low EA (P = 0.04 for insulin, P < 0.01 for total ketone). In conclusion, low EA during endurance exercise reduced systemic carbohydrate oxidation; however, exogenous glucose oxidation (evaluated by 13C excretion) remained unchanged during exercise under low EA.

Effects Of Exercise Training On Circulating Branched-chain Amino Acid And Ketone Levels In Diabetics

PURPOSE: Elevated levels of circulating branched-chain amino acid (BCAA) and ketone bodies are recognized as biomarkers for cardiovascular disease (CVD) and other pathological conditions in type-2 diabetes mellitus (T2DM). Aerobic exercise interventions have previously shown decreases in levels of these markers, suggesting improved metabolic status and reduced risk of CVD. However, the efficacy of resistance training and concurrent programs in reducing BCAA and ketone body levels has not been well researched. METHODS: The current study was performed as a secondary analysis of the HART-D trial, a 9-month randomized, controlled exercise-training trial of 262 participants with T2DM. Participants were randomized to one of four groups; non-exercise control, aerobic training (AT), resistance training (RT), or a combined aerobic-resistance training (ATRT). The effects of the 9-month intervention on BCAAs (leucine, valine, and isoleucine) and ketone bodies (β-hydroxy-butyrate, BHB; acetoacetate, AcAc; and acetone) were examined across groups using generalized linear models adjusting for age, race, sex, and baseline BMI. We performed per-protocol analyses limited to all control participants (n=33) and only the exercise group participants who met the criteria of at least 70% adherence to their exercise prescription for 6 months (AT, n=62; RT, n=55; ATRR, n=64). RESULTS: AcAc (-17.6 ± 6.4, p=0.006), acetone (-10.6 ± 3.6, p=0.003), and total ketone body (-51.4 ± 20.0, p=0.01) concentrations (shown as mean ± SE in μmol/L) decreased in the RT group compared to the control group. Acetone also decreased in ATRT compared to the control group (-10.2 ± 3.5 μmol/L, p=0.004). CONCLUSIONS: Our results suggest that RT and ATRT programs could improve ketone body metabolism in those with T2DM.

Effect Of Wearing Compression Tights On Muscle Oxygenation And Exogenous Glucose Utilization During Prolonged Cycling

PURPOSE: To determine effect of wearing compression tights on muscle oxygenation and exogenous glucose utilization during prolonged cycling in endurance athletes. METHODS: Ten triathletes (19.9 ± 1.2 years, 172.2 ± 4.4 cm, 62.0 ± 3.8 kg,BMI; 20.9 ± 0.7 kg·m-2; VO2max; 59.3 ± 4.4 ml·kg -1·min -1) completed 3 trials under respective conditions: 1) wearing a compression tight with approximately 15 mmHg [MED trial], 2) wearing a compression tight with approximately 30 mmHg [HIGH trial], and 3) wearing a tight with below 5 mmHg [CON trial]. The exercise consisted of 90 min of cycling at 65% of VO2max. Changes in exogenous glucose utilization (13C excretion in expired gas after consuming 13C labeled glucose), muscle oxygenation (oxy-hemoglobin, deoxy-hemoglobin, total hemoglobin and tissue saturation index), blood parameters (blood glucose and lactate, and serum glycerol, insulin and total ketone body concentrations), blood gas parameters (pH, pO2, pCO2, HCO3-, Na+ and K+), respiratory variables (VO2, VCO2, VE, RER), heart rate and rating of perceived exertion were evaluated throughout the exercise. Time to exhaustion test (at 85% of VO2max) was performed after completing 90 min of cycling to evaluate endurance performance. RESULTS: Exercise rapidly increased 13C excretion, but highest value of 13C excretion was significantly shown earlier in the MED trial (47.1 ± 9.9 min) compared with in the other trials (HIGH trial: 67.3 ± 23.7 min, CON trial: 54.0 ± 9.5 min, P = 0.033). Although MED trial showed significant lower oxy-hemoglobin throughout the exercise (P = 0.003), the changes in deoxy-hemoglobin, total hemoglobin and tissue oxygenation index did not differ among the trials. No significant difference was observed for changes in other variables among the trials. CONCLUSION: Wearing a compression tights exerting approximately 15 mmHg on thigh facilitated exogenous glucose utilization during 90 min of cycling.

Lauric Acid Stimulates Ketone Body Production in the KT-5 Astrocyte Cell Line.

Coconut oil has recently attracted considerable attention as a potential Alzheimer's disease therapy because it contains large amounts of medium-chain fatty acids (MCFAs) and its consumption is thought to stimulate hepatic ketogenesis, supplying an alternative energy source for brains with impaired glucose metabolism. In this study, we first reevaluated the responses of plasma ketone bodies to oral administration of coconut oil to rats. We found that the coconut oil-induced increase in plasma ketone body concentration was negligible and did not significantly differ from that observed after high-oleic sunflower oil administration. In contrast, the administration of coconut oil substantially increased the plasma free fatty acid concentration and lauric acid content, which is the major MCFA in coconut oil. Next, to elucidate whether lauric acid can activate ketogenesis in astrocytes with the capacity to generate ketone bodies from fatty acids, we treated the KT-5 astrocyte cell line with 50 and 100 μM lauric acid for 4 h. The lauric acid treatments increased the total ketone body concentration in the cell culture supernatant to a greater extent than oleic acid, suggesting that lauric acid can directly and potently activate ketogenesis in KT-5 astrocytes. These results suggest that coconut oil intake may improve brain health by directly activating ketogenesis in astrocytes and thereby by providing fuel to neighboring neurons.

Impaired mitochondrial β-oxidation in patients with chronic hepatitis C: relation with viral load and insulin resistance

BackgroundHepatic steatosis is often seen in patients with chronic hepatitis C (CH-C). It is still unclear whether these patients have an impaired mitochondrial β-oxidation. In this study we assessed mitochondrial β-oxidation in CH-C patients by investigating ketogenesis during fasting.MethodsThis study consisted of thirty patients with CH-C. Serum levels of insulin and hepatitis C virus (HCV) core protein were measured by chemiluminescence enzyme immunoassay. The subjects were then fasted, and venous blood samples were drawn 12 h and 15 h after the start of fasting. The levels of blood ketone bodies were measured by an enzymatic cycling method. The rate of change in total ketone body concentration was compared with that in eight healthy volunteers.ResultsThe rate of change in total ketone body concentration between 12 h and 15 h after the start of fasting was significantly lower in CH-C patients than in healthy volunteers (129.9% (8.5-577.3%) vs. 321.6% (139.6-405.4%); P <0.01). The rate of change in total ketone body concentration in patients with a serum level of HCV core protein of 10000 fmol/L or higher was significantly lower than in patients with a level of less than 10000 fmol/L (54.8% (8.5-304.3%) vs. 153.6% (17.1-577.3%); P <0.05). The rate of change in total ketone body concentration in patients with a homeostasis model assessment of insulin resistance (HOMA-IR) of 2.5 or higher was significantly lower than in patients with a HOMA-IR of less than 2.5 (56.7% (8.5-186.7%) vs. 156.4% (33.3-577.3%); P <0.01).ConclusionsThese results suggest that mitochondrial β-oxidation is impaired, possibly due to HCV infection in patients with CH-C.

Age-related effects of fasting on ketone body production during lipolysis in rats

The age-related effects of fasting on lipolysis, the production of ketone bodies, and plasma insulin levels were studied in male 3-, 8-, and 32-week-old Sprague-Dawley rats. The rats were divided into fasting and control groups. The 3-, 8- and 32-week-old rats tolerated fasting for 2, 5, and 12days, respectively. Fasting markedly reduced the weights of perirenal and periepididymal white adipose tissues in rats in the three age groups. The mean rates of reduction in both these adipose tissue weights during fasting periods were higher in the order of 3>8>32-week-old rats. Fasting transiently increased plasma free fatty acid (FFA), total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups. However, plasma FFA, total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the 3-week-old rats reached maximal peak within 2days after the onset of fasting, although these concentrations in the 8- and 32-week-old rats took more than 2days to reach the maximal peak. By contrast, the augmentation of plasma FFA, total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups had declined at the end of each experimental period. Thus, the capacity for fat mobilization was associated with tolerance to fasting. Plasma insulin concentrations in the rats in the three age groups were dramatically reduced during fasting periods, although basal levels of insulin were higher in the order of 32>8>3week-old rats. These results suggest that differences in fat metabolism patterns among rats in the three age groups during prolonged fasting were partly reflected the metabolic turnover rates, plasma insulin levels, and amounts of fat storage.

Regional variations in the concentrations of ketone bodies in cirrhosis and hepatic encephalopathy: a study in patients with TIPSS

Little is known about the metabolism of acetoacetate and β-hydroxybutyrate in patients with cirrhosis and encephalopathy. We investigated the fate of ketone bodies in these conditions. We studied 18 cirrhotic patients with encephalopathy and 17 cirrhotics without. At the time of insertion of a transjugular intrahepatic portosystemic stent shunt (TIPSS) or at the time of portographical assessment of the shunt's patency, we collected blood from the internal jugular, the right atrium, the inferior vena cava, the hepatic, the portal, the splenic veins and the radial artery. We used nuclear magnetic resonance spectroscopy to measure the concentrations of acetoacetate and β-hydroxybutyrate. There was no difference in the total ketone body concentrations between the two groups. The mitochondrial redox potential was significantly higher in the encephalopathics (142/54=2.63 vs 52/83=0.62) (P<0.01). β-hydroxybutyrate was significantly lower in the portal vein of encephalopathics (52 ± 4 vs 28 ± 3) (P<0.02) and in the splenic vein (48 ± 6 vs 32 ± 5) (P<0.04). Acetoacetate was significantly higher in encephalopathics in the internal jugular vein (134 ± 12 vs 92 ± 16) (P<0.03), the right atrium (112 ± 18 vs 68 ± 11) (P<0.03), the hepatic vein (162 ± 25 vs 115 ± 19) (P<0.05), the portal vein (133 ± 20 vs 81 ± 14) (P<0.02) and the splenic vein (167 ± 24 vs 122 ± 21) (P<0.04). All measurements are expressed in μmols/L. There are significant variations in the regional concentrations of the ketone bodies in encephalopathy.

CD36 deficiency predisposing young children to fasting hypoglycemia

Fatty acid (FA) β-oxidation defects cause hypoglycemia. Our aim was to determine if CD36—a membrane transporter for long-chain FAs—deficiency predisposes children to hypoglycemia. After overnight fasting, we measured parameters for carbohydrate and FA metabolisms at 12-, 14-, and 16-hour fasting points in 51 preschool children with histories of episodic hypoglycemia and 49 age-matched healthy controls. Simultaneously, the expressions of CD36 on platelets and monocytes were examined to determine the phenotypes. Six of the 51 hypoglycemic children and none of the 49 control children were diagnosed as having type I CD36 deficiency. Four and 3 children were diagnosed as having type II CD36 deficiency, respectively. Hypoglycemia was often recurrent in the type I CD36 group. At any fasting point, the type I CD36 group showed significantly lower blood glucose and insulin concentrations than the other groups: glucose, P < .001 vs control group and P < .01 or P < .001 vs type II/wild-type CD36 hypoglycemic groups; insulin, P < .001 vs control group and P < .01 vs type II/wild-type CD36 hypoglycemic groups. Free FA concentration in the type I group was always 1.5- to 2.0-fold higher than that in the other groups, whereas the total ketone body concentration was consistently about two thirds of that in the other groups. Among the type II, wild-type, and control groups, there were no significant differences in the parameters except that the wild-type group showed significantly lower FFA concentration ( P < .05). These results suggested that type I CD36 deficiency but not type II CD36 deficiency predisposes preschool children to hypoglycemia.

Changes in Insulin, Glucose and Ketone Bodies, But Not Leptin or Body Fat Content Precede Restoration of Luteinising Hormone Secretion in Ewes

The reproductive system, including pulsatile luteinising hormone (LH) secretion, is inhibited by deficits in energy availability and restored by energy surfeits. Plasma LH, insulin, leptin, ghrelin, glucose, ketone body, and nonesterified fatty acid concentrations were measured in ovariectomised, food-restricted ewes before and after return to ad libitum feeding to determine the factors that change in time to account for the restoration of pulsatile LH secretion. At 07.00 h, blood was sampled every 10 min for 5 h from ovariectomised, hypogonadotrophic, chronically food-restricted and ad libitum-fed ewes (Fed). At 12.00 h, four of the food-restricted sheep were given ad libitum access to food (Re-Fed), while three ewes continued to be food restricted (Restricted). Sampling continued for 5 h and resumed again on the mornings of days 2, 4, and 9. A pulse of LH was seen within 1 h of re-feeding in all Re-Fed ewes, and interpulse interval (IPI) was significantly shorter in Re-Fed compared to Restricted ewes and longer than in Fed ewes during the period after re-feeding. Re-Fed LH IPI was not restored to that of Fed ewes until sometime between days 4 and 9. The first pulse occurred within minutes, whereas restoration of IPI occurred after 4-8 days. Prior to the initial LH pulses seen in Re-Fed ewes, plasma ketone bodies first fell and then rose to levels significantly above those in Restricted ewes. Significant changes in circulating insulin, ghrelin, glucose, and total ketone body concentrations, daily food intake and lean body mass preceded restoration of Re-Fed LH IPI some time between days 4 and 9, but there were no significant changes in adiposity or circulating leptin concentrations, consistent with the hypothesis that LH pulses are reinitiated by changes in the availability of oxidisable metabolic fuels and possibly insulin, but not leptin concentrations.

Hepatic Mitochondrial Redox Potential in Patients with Liver Metastatic Cancers and Circulatory Insufficiency

Arterial ketone body ratio (AKBR), which reflects hepatic intramitochodrial redox potential, was measured in 20 patients with Carcinoma hepatis metastaticum and good circulatory condition (group A), and 16 patients with Carcinoma hepatis metastaticum and chronic cardiogenic circulatory insufficiency (group B). Total ketone body concentration (TKB) and arterial oxygen tension (PaO2) was simultaneously determined. We have stated that AKBR values in both groups of patients were decreased below the normal level. AKBR values in group B were significantly lower than in group A. At the same time TKB values in both groups were statistically equal and significantly increased above the normal level. The levels of arterial oxygen tension (PaO2) in group A were physiologically high, whereas in group B were significantly decreased. Furthermore arterial oxygen tension of patients in group B correlated with AKBR values significantly. In group A we found statistically significant negative correlation between TKB and AKBR values. Our study indicate that the main mechanism which may explain the decrease of intrahepatic mitochondrial redox potential in patients with liver metastatic cancers and good circulatory condition, is the enhanced beta-oxidation of fatty acids, when the efficiency of NAD+ to NADH reduction in beta-oxidation pathway and tricarboxylic acid cycle is higher than re-oxidation of NADH to NAD+ in the oxidative phosphorylation. In patients with coexisting chronic cardiogenic circulatory insufficiency deprivation of blood oxygen supply initiate the irreversible dysfunction of oxidative phosphorylation.

Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis

Purpose: Diabetic ketoacidosis (DKA) and alcoholic ketoacidosis (AKA) are two medical emergencies characterized by elevated total ketone body concentration. We aimed to determine differences in pathogenesis of ketoacidosis and its metabolic consequences by comparing both at presentation and during treatment, the different metabolic products and hormones involved in the ketoacidotic state. Materials and Methods: We studied 12 patients with DKA and 8 patients with AKA. On admission and every 4 hours for 24 hours during treatment, samples were drawn for determination of serum ketone bodies, lactate and pyruvate, insulin, and counterregulatory hormones (glucagon, cortisol, growth hormone, and catecholamines). Results: At presentation, with a similar β-hydroxybutyrate concentration, patients with DKA had a higher plasma glucose (32 mmol/L vs. 6.6 mmol/L), lower β-hydroxybutyrate/acetoacetate ratio (3:1 vs. 7:1), and a lower lactate/pyruvate ratio (11:1 vs. 19:1) than patients with AKA (all, P < .01). The mean time to resolve ketoacidosis in patients with AKA (6 ± 1 hour) was significantly shorter than in patients with DKA (16 ± 2 hours). At presentation, the mean insulin concentration in patients with DKA and AKA were similarly decreased (7.8 ± 2 and 10.3 ± 3 μU/mL, P = not significant [NS]).The mean glucagon level before therapy was 203 ± 15 pg/mL and 188 ± pg/mL for patients with DKA and AKA, respectively (P = NS). Levels of cortisol, growth hormone, and epinephrine at presentation and during the first 8 hours of treatment were higher in patients with DKA; however, the difference in these values did not reach statistical significance. During therapy, levels of counterregulatory hormones declined at similar rates and returned to normal values after resolution of ketoacidosis. Conclusions: Our results indicate that, in addition to a history of diabetes or alcoholism, patients with DKA and AKA differ in their metabolic parameters more than in their hormonal profile. The metabolic profile of DKA is characterized by a higher plasma glucose concentration, and lower β-hydroxybutyrate to acetoacetate and lactate to pyruvate ratios compared with patients with AKA. The initial hormonal profile in both ketoacidotic states is characterized by similarly decreased insulin levels and elevated levels of counterregulatory hormones. Copyright © 2000 by W.B. Saunders Company

The influence of hypoxia and hyperoxia on the kinetics of propofol emulsion.

To study the effect of hypoxia and hyperoxia on the pharmacokinetics of propofol emulsion, hepatic blood flow and arterial ketone body ratio in the rabbit. Twenty four male rabbits were anesthetized with isoflurane (1.5-2%) in oxygen. After the surgical procedure, isoflurane administration was discontinued and intravenous propofol infusion (30 mg x kg(-1) x hr(-1)) was started. The infusion rate of propofol was maintained throughout the study. After an initial 90 min period of propofol infusion, rabbits were randomly allocated to one of three groups: hypoxia (F(I)O2 = 0.1), normoxia (F(I)O2 = 0.21), and hyperoxia (F(I)O2 = 1.0). Propofol infusion was continued under the allocated F(I)O2 for 60 min. Propofol concentrations in arterial blood, total body clearance of propofol, hepatic blood flow and arterial ketone body ratio were measured. The mean arterial propofol concentration at the end of infusion was higher in the hypoxia group (15.2 +/- 2.8 microg x mL(-1), mean +/- SD) than in the normoxia (7.4 +/- 1.7) and hyperoxia (8.0 +/- 1.9) groups (P < 0.05). Total body clearance of propofol, hepatic blood flow and arterial ketone body ratio were all reduced in the hypoxia group (P < 0.05). Total ketone body concentration in arterial blood increased in the hyperoxia group (P < 0.01). Hypoxia produced an accumulation of propofol in blood and reduced propofol clearance. These changes could result from decreased hepatic blood flow and low cellular energy charge in the liver. Hyperoxia, on the other hand, increased total ketone body in arterial blood.

Contribution of the Renal Medulla to Enhanced Ketogenesis with Ringer's Acetate Administration during Hepatic Inflow Occlusion RID="" ID="" This International Society of Surgery (ISS)/Soci&amp;eacute;t&amp;eacute; Internationale de Chirurgie (SIC) article was presented at the 37th World Congress of Surgery International Surgical Week (ISW97), Acapulco, Mexico, August 24&amp;ndash;30, 1997.

We have reported that the administration of Ringer's acetate solution (AR) maintains plasma ketone body concentrations even during hepatic ischemia due to enhanced ketogenesis in the kidney. In this study we tried to clarify which part of the kidney, cortex or medulla, contributes to the enhanced ketogenesis. During 20 minutes of hepatic inflow occlusion, AR or Ringer's lactate solution (LR) was administered. Ketone body concentrations in arterial and renal venous blood and renal cortical and medullary tissue were measured enzymatically. Results are expressed as means +/- SEM. At 20 minutes of hepatic inflow occlusion, arterial ketone body concentrations decreased to 38% of preischemic values with the LR infusion but increased under AR administration and were four times higher than that with LR. The renal arteriovenous difference in ketone body concentration was 16 +/- 14 micromol/ml before hepatic inflow occlusion and -52 +/- 14 with AR administration, indicating that renal ketogenesis occurred during hepatic ischemia. Total ketone body concentrations in the renal cortex and medulla were 56 +/- 6 and 61 +/- 5 micromol/g, respectively with LR, but increased to 186 +/- 29 and 248 +/- 25 micromol/g, respectively during AR administration. The concentration in the medulla was higher (p = 0. 12) than that in the cortex but did not reach statistical difference. Renal ketogenesis increases during hepatic inflow occlusion with AR administration. It is likely that the enhancement of ketogenesis takes place predominantly in the medulla of the kidney.

Acute effects of distal pancreatectomy on portal and peripheral blood insulin concentrations in patients undergoing total gastrectomy.

The influence of distal pancreatectomy on portal and peripheral blood immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) concentrations was evaluated in patients undergoing total gastrectomy. There were 22 patients studied, 12 of whom did not undergo distal pancreatectomy (group 1), and 10 who did (group 2). In group 2, the increase in portal blood IRI concentrations after a glucose infusion of 25 g over 30 min was suppressed, and reelevation of the portal blood IRG concentration after the glucose-induced depression was inhibited compared to group 1. In contrast, the peripheral blood IRI concentration did not reflect these changes in the portal blood IRI concentration. The rise in the arterial ketone body ratio (AKBR) and the fall in the total ketone body concentration after glucose infusion were also attenuated after distal pancreatectomy in group 2. These findings suggest that distal pancreatectomy has an immediate suppressive effect on the pancreatic secretion of insulin and glucagon, and might disturb metabolism in the liver.

Clinical and Pathological Studies in Cattle with Hepatic Disease

West, H.J., 1997. Clinical and pathological studies in cattle with hepatic disease. Veterinary Research Communications, 21 (3), 169-185In cattle with hepatic lipidosis, hepatic abscessation, leptospirosis, biliary calculi or fasciolosis, the progression of the disease was studied by serial measurements of serum total bile acid concentrations, plasma glutamate dehydrogenase, γ-glutamyltranserase, 5′-nucleotidase and leucine aminopeptidase activities Terminalia avicennioides and by liver biopsy. Regardless of the cause of the hepatic disease, weight loss, anorexia, dullness and depression were consistent features. Signs of hepatic encephalopathy, such as blindness, head pressing, excitability, ataxia and weakness were less common and, together with pyrexia and jaundice, were grave prognostic signs. Plasma ammonia concentrations were significantly elevated compared to clinically normal cattle, but such changes were not always accompanied by a decline in plasma urea concentrations. In normal, healthy cattle, the plasma ammonia:urea concentration ratio is 9:1 and the plasma ammonia:glucose concentration is 11:1. In hepatic disease, a plasma ammonia:glucose ratio >40:1 or plasma ammonia:urea ratio >30:1, particularly with a rising total ketone body concentration and a declining glucose concentration, carried a guarded prognosis. The study suggested that other factors, such as hypokalaemia, alkalosis, short-chain volatile fatty acids, and false and true neuro-transmitters, may be important in the pathogenesis of hepatic coma in cattle.

Enzymatic method for determining ketone body ratio in arterial blood

We have developed a new, sensitive, and rapid method for measuring the ketone body concentration in arterial blood and determining the arterial blood ketone body ratio. The procedure involves the sequential use of the enzymes 3-hydroxybutyrate dehydrogenase (3-HBDH; EC 1.1.1.30) and NADH oxidase, followed by a color-generating reaction with the hydrogen peroxide produced by the oxidase reaction. The amount of oxidized chromogen produced is proportional to the 3-hydroxybutyrate (3-HBA) concentration. The acetoacetate (AcAc) concentration is obtained after complete conversion of the AcAc to 3-HBA, in the presence of 3-HBDH. The total 3-HBA concentration is measured and then subtracted from the total ketone body concentration to give the AcAc concentration. This procedure may be applied to plasma samples and the absorbance change measured with an automated chemistry analyzer. Ketone body concentration may be determined over the range 0 to 400 mumol/L. The analysis takes approximately 12 min and requires only 30 microL of plasma.

The Effect of a Bolus Injection of TNF-α and IL-1β on Hepatic Energy Metabolism in Rats

The effects of intravenous bolus injection of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) on hepatic mitochondrial energy metabolism were investigated in rats. The rats were injected with 15 μg/kg body wt of human recombinant TNF-α and IL-1β. The hepatic energy charge decreased to 0.794 ± 0.005 and 0.789 ± 0.006 in comparison with the sham control value of 0.838 ± 0.007 and 0.835 ± 0.011 at 12 and 24 hr after the treatment. The mitochondrial redox state (NAD +/NADH) increased from 17.4 ± 1.9, 16.6 ± 1.4, and 19.2 ± 2.1 to 33.5 ± 3.5, 27.8 ± 2.8, and 30.9 ± 2.6 concomitant with an increase in arterial blood ketone body ratio (acetoacetate/β-hydroxybutyrate) from 0.49 ± 0.04, 0.34 ± 0.04, and 0.44 ± 0.09 to 1.00 ± 0.16, 0.69 ± 0.13, and 0.86 ± 0.15 at 3, 12, and 24 hr after the treatment. Total ketone body concentration in liver tissue and arterial blood was significantly lower at 24 hr after the treatment. State 3 respiration rate of isolated mitochondria increased by 29.2, 30.3, and 19.2% concomitant with an increase in oxidative phosphorylation rate by 26, 33.7, and 24.3% at 3, 12, and 24 hr after the treatment. These results showed that the administration of TNF-α and IL-1β in rats induced a hypermetabolic state in hepatic mitochondrial energy metabolism, which is a pattern similar to sepsis and presumably a compensatory reaction to the increased energy consumption.

Effects of the short-chain triglyceride triacetin on intestinal mucosa and metabolic substrates in rats.

Diets containing either triacetin (the water-soluble triglyceride of acetate) or long-chain triglycerides (LCTs) were fed to rats to determine the effects on intestinal mucosa cells and plasma substrates. Male Sprague-Dawley rats were fed one of three diets, a control diet containing 5% of energy as LCTs or one of two experimental diets that contained 30% of energy as lipid. The lipid component of the two experimental diets was either 100% LCTs or 95% triacetin/5% LCTs. Plasma lactate, glucose, and total ketone body concentrations were not significantly different among dietary treatment groups. Compared with animals fed LCTs and control diet, plasma pyruvate and free fatty acid concentrations were decreased in animals fed triacetin. In contrast, plasma triglyceride concentrations were elevated in animals fed triacetin compared with other groups. Intestinal biochemical measures included total DNA, RNA, protein, and the protein:DNA ratio. Histologic indices measured were villus height in the jejunum and crypt depth in the colon. No significant difference in mucosal protein concentration was observed in the jejunum and colon. Jejunal RNA was significantly decreased in animals fed triacetin compared with other diets. Triacetin feeding significantly increased the DNA content in the jejunum and colon (thereby lowering the protein:DNA ratio), indicating smaller, more numerous cells. Jejunal villus height and colonic crypt depth were not significantly different among dietary treatment groups. Provision of a balanced diet containing 28.5% of the total calories as triacetin had no adverse effects on metabolic substrates and resulted in smaller and more numerous mucosal cells in the jejunum and colon.(ABSTRACT TRUNCATED AT 250 WORDS)