SEARCH · PubMed Health

Results for “Acetoacetates”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources

PubMed2002

Stereospecific substitution of enantiomerically pure 1-(2-pyridinyl)ethyl methanesulfonate with beta-dicarbony compounds.

The alkylation of the sodium salt of the malonic acid diester with (R)-1-(2-pyridinyl)ethyl methanesulfonate (2) gave the dimethyl (R)-[1-(2-pyridinyl)ethyl]malonate (3a), stereospecifically. The alkylation reaction of methyl acetoacetate gave the methyl (2'S,2R/2S)-3-oxo-2-[1-(2-pyridinyl)ethyl]butanoate (3d) along with the methyl (S)-3-[1-(2-pyridinyl)ethoxy]-2-butenoate (4d). The acid hydrolysis and decarboxylation of 3d under acidic conditions gave (R)-4-(2-pyridinyl)pentan-2-one (6), and the alkylation of methyl (R)-[1-(2-pyridinyl)ethyl]acetoacetate with benzyl bromide gave a mixture of C-benzylated and O-benzylated products 7 and 8.

Acetylene↗

PubMed2000

Activation of glycolysis by zinc is diminished in hepatocytes from metallothionein-null mice.

The influence of hepatic metallothionein (MT) and zinc (Zn) on glycolysis was investigated in primary cultures of mouse hepatocytes prepared from MT-normal (+/+) and MT-null (-/-) mice. In MT +/+ mice, a close relationship was observed between the Zn concentration in the incubation medium (10-150 microM), increased MT levels in the cells, and increased glycolysis (accumulation of lactate + pyruvate) over 24 h, with significant effects seen at physiological levels of Zn (10-25 microM). Hepatocytes from MT -/- mice had significantly lower basal rates of glycolysis and demonstrated increased glycolysis only at Zn concentrations of 50 microM or greater. The lactate:pyruvate ratio was higher in the MT +/+ hepatocytes. The oxidation of endogenous fatty acid (accumulation of the ketone bodies, 3-hydroxybutyrate and acetoacetate) was initially greater in the MT +/+ hepatocytes, although only MT -/- hepatocytes showed increased ketone body production in response to Zn. The 3-hydroxybutyrate:acetoacetate ratio was higher in the MT +/+ hepatocytes and increased with increasing Zn concentrations. Intracellular Zn accumulation was 60% greater in the MT +/+ hepatocytes, with approximately 80% of the extra Zn associated with MT. The results implicate MT-associated Zn rather than increased intracellular Zn per se in the regulation of hepatic carbohydrate metabolism.

Animals↗

PubMed1990

Enhanced ketone body uptake by perfused skeletal muscle in trained rats.

Training effect on exercise-induced hyperketonemia was investigated in normal post-absorptive rats subjected to running exercise on a treadmill. Furthermore, rat hindlimb-muscle perfusion was performed to elucidate the mechanism of the training effect. A medium intensity prolonged exercise (running at 15 m/min for 90 min) caused a greater increase in plasma 3-hydroxybutyrate than in acetoacetate both during and after the exercise. Training with medium-intensity exercise (15 m/min) for 90 min 3 times per week for 14 wks or 28 wks caused 1) a reduction of the increase in plasma ketone body (mainly 3-hydroxybutyrate), free fatty acids and glucagon induced by the exercise, and 2) an increase in ketone body (mainly acetoacetate) uptake by perfused skeletal muscle. The present study demonstrates that the reduction of exercise-induced hyperketonemia by prolonged training is caused by increased ketone body utilization in skeletal muscle, and suggested that inhibition of hepatic ketogenesis might also participate in this reduction.

Animals↗

PubMedDate not supplied

Profile of organic acid concentrations in the digestive gland and hemolymph of Biomphalaria glabrata under estivation.

Using high performance liquid chromatography (HPLC) analysis it was possible to determine simultaneously the concentration of organic acids (pyruvate, lactate, succinate, fumarate, malate, acetate, propionate, acetoacetate, and ss-hydroxybutyrate) in the digestive gland and the extracellular concentration of these same acids in the hemolymph of estivating Biomphalaria glabrata, the intermediate host of Schistosoma mansoni. After a 7 day period of estivation, there was a significant increase in the tissue levels of lactate, succinate, malate and acetate compared to non-estivating snails. After 14 days of estivation, the levels of lactate and acetate were also significantly elevated. The hemolymph concentrations of pyruvate and acetate increased significantly after 7 days and acetate concentrations continued to be significantly increased up to 14 days of estivation. The other organic acids studied, such as ketone body acetoacetate and ss-hydroxybutyrate or the volatile acid propionate, did not accumulate. Their tissue concentrations, however, increased on the 7th day of estivation and reached normal levels within two weeks of estivation for some of them. One should take into consideration how the reduction in metabolism can be handled under aerobic conditions, and what role anaerobic pathways may play in both energy formation and redox balance processes.

Acids↗

PubMed1976

Effect of diabetes mellitus and insulin on the turnover and metabolic response to ketones in man.

To determine the effect of diabetes mellitus on ketone removal rates, Na DL-beta-hydroxybutyrate was administered as a continuous three-hour infusion (3 mg./kg./min.) to healthy volunteers and insulin-dependent diabetics in the postabsorptive state. An additional group of healthy controls received intravenous glucose (50 gm.) or glucose and insulin during the ketone infusion to determine the effect of hyperinsulinemia on ketone removal. Following ketone infusion, total blood ketone levels in the diabetics were twofold greater than in controls (p less than 0.001). The metabolic clearance rate of ketones (MCRk) in the diabetics was reduced by 42% from that of controls (p less than 0.001). In contrast, the calculated production rate of ketones (PRk) in diabetics was not consistently different from that observed in controls. In diabetics with normal PRk, MCRk remained significantly below control values (p less than 0.001). The ketone infusion resulted in a fall in plasma glucose and alanine levels in the normals as well as diabetics. However, the decline in plasma glucose induced by the ketone infusion was five- to sixfold greater in the diabetics than in controls (p less than 0.005) and correlated linearly with the decline in plasma alanine (p less than 0.02). Administration of intravenous glucose during an ongoing ketone infusion in normal subjects resulted in 37 +/- 5% reduction in beta-hydroxybutyrate, but no change in acetoacetate concentration. The decline in beta-hydroxybutyrate was two- to threefold greater than would be expected if glucose had acted solely to inhibit endogenous ketone production. Similar results were observed when hyperinsulinemia without hyperglycemia was produced by simultaneous administration of insulin and glucose. It is concluded that (1) ketone disposal is reduced in diabetes even when ketone production is normal, suggesting the rate of ketone utilization may be a more sensitive index of insulin deficiency than is ketone production; (2) hyperinsulinemia stimulates beta-hydroxybutyrate utilization without influencing acetoacetate concentration; and (3) increased blood ketone levels induced by infusion of Na DL-beta-hydroxybutyrate reduce plasma glucose and alanine concentrations in diabetes. These findings thus support a role for insulin in influencing ketone disposal in normal as well as diabetic man and a role for ketones in influencing substrate availability for gluconeogenesis in diabetes.

Adult↗

PubMed1980

Ketonuria in pregnancy--with special reference to calorie-restricted food intake in obese diabetics.

Early morning ketonuria, as judged by Ketostix testing, occurred in 19% of urine samples from insulin-independent diabetic pregnant women eating 1000 calorie diets, in 14% from diabetics on higher calorie diets, and in 7% of urines from nondiabetic pregnant women. Ketostix test was never found to be positive in blood, even when it was 2+ in urine samples, and acetoacetate levels were always below 1 mmol/L. Enzymatic estimations of acetoacetate (AA) and beta-hydroxybutyrate (BB) in urine and plasma samples revealed (1) no significant differences in range or mean between the groups receiving different restricted diets or full diets, the highest value observed for plasma AA being 0.34 mmol/L; (2) that Ketostix became positive at a concentration of AA above 1 mmol/L and that such a value in urine corresponded to plasma levels of between 0.06 and 0.1 mmol/L, i.e., double the normal; and (3) a 50-100-fold increase in urine AA when blood levels exceeded 0.08 mmol/L. Neonates born to diabetic mothers with ketonuria had no fetal distress or asphyxia neonatorum. The lowest Apgar score at 5 min was 8; 80% of neonates had a score of 10. Hence, positive Ketostix tests in urine samples do not indicate toxic levels in the blood, and a 1000 calorie diet for obese pregnant diabetics appears to be safe as regards neonatal outcome.

Adult↗

PubMed2002

Succinate is a preferential metabolic stimulus-coupling signal for glucose-induced proinsulin biosynthesis translation.

The secondary signals emanating from increased glucose metabolism, which lead to specific increases in proinsulin biosynthesis translation, remain elusive. It is known that signals for glucose-stimulated insulin secretion and proinsulin biosynthesis diverge downstream of glycolysis. Consequently, the mitochondrial products ATP, Krebs cycle intermediates, glutamate, and acetoacetate were investigated as candidate stimulus-coupling signals specific for glucose-induced proinsulin biosynthesis in rat islets. Decreasing ATP levels by oxidative phosphorylation inhibitors showed comparable effects on proinsulin biosynthesis and total protein synthesis. Although it is a cofactor, ATP is unlikely to be a metabolic stimulus-coupling signal specific for glucose-induced proinsulin biosynthesis. Neither glutamic acid methyl ester nor acetoacetic acid methyl ester showed a specific effect on glucose-stimulated proinsulin biosynthesis. Interestingly, among Krebs cycle intermediates, only succinic acid monomethyl ester specifically stimulated proinsulin biosynthesis. Malonic acid methyl ester, an inhibitor of succinate dehydrogenase, also specifically increased glucose-induced proinsulin biosynthesis without affecting islet ATP levels or insulin secretion. Glucose caused a 40% increase in islet intracellular succinate levels, but malonic acid methyl ester showed no further effect, probably due to efficient conversion of succinate to succinyl-CoA. In this regard, a GTP-dependent succinyl-CoA synthetase activity was found in cytosolic fractions of pancreatic islets. Thus, succinate and/or succinyl-CoA appear to be preferential metabolic stimulus-coupling factors for glucose-induced proinsulin biosynthesis translation.

Adenosine Triphosphate↗

PubMed1996

Propionate modulation of ruminal ketogenesis.

The ruminal epithelium is the primary source, through the metabolism of butyrate, of circulating ketone bodies in fed ruminants. Volatile fatty acid metabolism was investigated in short-term (2-h) incubations of isolated sheep ruminal epithelial cells. Ruminal epithelial cells were isolated from ruminal papillae via serial tryptic digestion. Cells were incubated in the presence of various combinations of butyrate (0, .5, 1, 5, 10, or 25 mM), propionate (0, .1, .5, 1, 5, 10, 25, 50, or 100 mM), acetate (0, .5, 1, 5, 25, 50, or 100 mM), and succinate (0, 5, 15, 50 mM) to evaluate the effects of these substrates on butyrate metabolism. Variables measured included beta-hydroxybutyrate (beta-HBA) and acetoacetate (AcAc) production from butyrate, [14C]butyrate oxidation to 14CO2, and lactate and pyruvate formation from propionate and succinate. Butyrate oxidation to CO2, beta-HBA and total ketones produced (nanomoles of butyrate metabolized per 10(6) cells per minute) were linear over the 2-h incubation period (y = .805X + 2.24, r2 = .78; y = 1.02X - 9.1, r2 = .72; and y = 2.238X - 11.76, r2 = .65, respectively). Acetate inhibited beta-HBA formation from butyrate (P < .05) when present at concentrations greater than 5 mM, although a dose-dependence was not consistently exhibited. However, butyrate oxidation to beta-HBA was stimulated (P < .05) by propionate while acetoacetate production declined (P < .05), resulting in no net change in ketone body production (P > .05). A concomitant increase in lactate and pyruvate production was noted with increasing concentrations of propionate. Succinate addition also increased lactate production by the ruminal epithelial cells. In contrast to propionate, succinate addition resulted in a decrease in beta-HBA formation from butyrate (P < .05). Butyrate metabolism by isolated ruminal epithelial cells is influenced by other VFA produced in the rumen, and propionate-induced stimulation of beta-HBA from butyrate does not seem to be mediated via succinate but rather is a result of a shift in the mitochondrial NADH/NAD status.

Acetates↗

PubMed2000

Effects of diet forage:concentrate ratio and metabolizable energy intake on isolated rumen epithelial cell metabolism in vitro.

Crossbred wether lambs were used to assess the effect of altered forage:concentrate ratio and metabolizable energy intake on metabolism of substrates by ruminal epithelium using an isolated cell system. Lambs (n = 28; 20.1 +/- 3 kg BW) were assigned randomly to a factorial arrangement of dietary treatments consisting of either 75% forage or 75% concentrate fed once daily at either .099 or .181 Mcal ME x(kg BW(.75))(-1) x d(-1) for 52 d. After a 52-d feeding period, isolated rumen epithelial cells (IREC) were incubated in the presence of an oxidizable substrate with a single 14C label (acetate, propionate, butyrate, glucose, glutamate, and glutamine) at concentrations ranging from .1 to 50 mM, and substrate oxidation to 14CO2 or metabolism to beta-hydroxybutyrate (beta-HBA), acetoacetate, pyruvate, and lactate was determined. For all substrates, oxidation to CO2 was concentration-dependent and saturable within the physiological range. Differences in substrate oxidation to CO2 by IREC at specific substrate concentrations did not affect Vmax (maximal rate of substrate oxidation, nmol oxidized to CO2 x 1 x 10(6) cells(-1) x 90 min(-1)) and K(ox) (concentration of substrate at which half Vmax oxidation rate is achieved, mmoles/L) estimates for the dietary treatments. Production of beta-HBA from butyrate by IREC from the lambs fed 75% forage was not affected by ME intake; however, production was elevated by high ME intake of the 75% concentrate diet (diet x intake interaction; P < .02). Acetoacetate production from butyrate by IREC from lambs fed at high ME intake was greater (P = .001) than from those fed at low ME intake. Lactate and pyruvate production from glucose, glutamate, and propionate were generally unaffected by dietary treatment; however, rate of glutamine metabolism to lactate and pyruvate by IREC was increased with increased ME intake. The observed changes in metabolite production rates across groups did not affect the predicted Vmax and K(ox) parameter estimates. The estimated K(ox) values corroborate that VFA are the primary oxidizable fuels used by ruminal epithelial cells while illustrating that other substrates such as glucose, glutamate, and glutamine would not be expected to be oxidized extensively in vivo due to the high K(ox) relative to substrate concentrations in vivo. In conclusion, the capacity of isolated ruminal epithelial cells to oxidize substrates was largely unaffected by ME intake or dietary forage:concentrate ratio of the diet.

Animal Feed↗

PubMed2000

Sheep rumen metabolic development in response to age and dietary treatments.

This study examined the time course of rumen metabolic development in the absence of solid feed consumption and the effect of delayed solid feed consumption on sheep rumen development. Twenty-seven lambs consumed milk replacer until slaughter at nine ages from 1 to 84 d (milk group). Three additional lambs consumed milk replacer from 1 to 48 d. From 49 d until slaughter at 84 d, these lambs were weaned onto solid feed (fed group). At slaughter, rumen contents were removed for VFA analysis and rumen epithelium was preserved for morphological examination. Rumen epithelial cells were isolated and incubated in media containing 2.5 mM U-[14C]-glucose or 10 mM 1-[14C]-butyrate. Rumen VFA concentrations did not change with age in lambs given milk replacer. At 84 d of age, intraruminal VFA concentrations were elevated in lambs consuming solid feed compared to 84-d-old lambs given milk replacer (P < .05). The number of ruminal papillae per square centimeter decreased (P < .05) while papillae length and width did not change significantly with age in rumen epithelium from lambs given milk replacer. At 84 d of age, rumen epithelium from lambs in the fed group had fewer and larger papillae/per square centimeter than rumen epithelium from lambs given milk replacer (P < .05). Rates of glucose and butyrate oxidation and acetoacetate and lactate production by rumen cells isolated from lambs given milk replacer did not change with age. Beta-hydroxybutyrate (BHBA) production was undetectable before 42 d of age in lambs given milk replacer and increased to levels found in conventionally raised adults by 84 d. At 84 d there were no differences in rates of glucose and butyrate oxidation or acetoacetate and lactate production by rumen cells between the two treatment groups. Thus, the change in substrate oxidation from glucose to butyrate, indicative of rumen metabolic maturation, does not occur in the absence of solid feed consumption. However, the development of rumen ketogenesis, as evidenced by increased BHBA production, does occur in the absence of solid feed consumption. Delaying the initiation of solid feed consumption results in rumen morphological development but does not stimulate rumen metabolic development. Increased intraruminal VFA concentrations, earlier exposure to VFA, or a longer period of exposure to VFA may be required to induce the genes responsible for rumen metabolic development.

Aging↗

PubMed2002

Volatile fatty acid metabolism by epithelial cells isolated from different areas of the ewe rumen.

Cells were harvested from four rumen locations in four 2- to 3-yr-old ewes fed fescue hay to determine whether cell origin has an effect on cellular VFA metabolism. Tissue (approximately 150 cm2) was excised from the anterior cranial pillar, ventral sac floor, caudal pillar surface, and dorsal sac ceiling. Cells were isolated using serial tryptic digestion. One milliliter of isolate was incubated for 2 h in 6 mL of medium containing 25 mM propionate and 10 mM butyrate. Incubations were terminated at 0, 30, 60, 90, and 120 min and analyzed for beta-hydroxybutyrate, acetoacetate, lactate, and pyruvate. Cell yield was 22, 22, 24, and 14 (+/- 6) x 106 cells/mL, and viability was 92, 92, 94, and 87% for anterior cranial pillar, ventral sac floor, caudal pillar surface, and dorsal sac ceiling, respectively. All metabolite concentrations and ratios of redox pairs increased throughout the incubations, indicating continuous cellular activity. Final 2-h concentrations (nmol/10(6) cells) were 123, 113, 163, and 158 (+/- 35) for beta-hydroxybutyrate; 38, 42, 24, and 45 (+/- 10) for acetoacetate; 25.3, 20.6, 10.1, and 20.4 (+/- 5.6) for lactate; and 2.54, 0.98, 1.06, and 1.31 (+/- 0.61) for pyruvate in the anterior cranial pillar, ventral sac floor, caudal pillar surface and dorsal sac ceiling incubations, respectively. Origin of rumen tissue had no significant effect on metabolite production, indicating that cellular location is not a critical factor that affects rate of rumen epithelial cell VFA metabolism under these specific in vitro conditions.

Animal Feed↗

PubMed2001

Refinements in primary rumen epithelial cell incubation techniques.

The objectives of this study were to 1) determine if the number of rumen epithelial cells in primary cell incubation affects the rate of metabolite production, and 2) determine the optimum mode of data expression to standardize reporting criteria. Sections of rumen epithelial tissue were excised from five Holstein heifers and subjected to serial tryptic digestion to isolate cells. Isolated cells had a mean viability of 86% (+/- 1.29) and were incubated at concentrations of 0.5, 1, 5, 10, 20, and 40 million cells per flask. Oxidation of [1-14C]butyrate to 14CO2 and production of acetoacetate (ACAC), beta-hydroxybutyrate (BHBA), lactate, and pyruvate were measured for cell dilution comparisons. Cell number, cell dry matter, cell crude protein, epithelial wet tissue weight, body weight, and metabolic body weight were measured to generate 12 different forms of data expression. Coefficients of variation were calculated for each type of expression. Expressing data per cell number resulted in the lowest variation. Oxidation of [1-14C]butyrate to 14CO2 and pyruvate production per million cells did not significantly differ between treatments for 90-min incubation. Acetoacetate and lactate concentrations were greatest at 0.5 and 1 million cells/flask, respectively, with no differences between 5 to 40 million cells/flask. Production of BHBA for 1 million cells/flask was greater than 0.5 and 40 million cells/flask, but did not change between cell concentrations 5 to 20 million. The BHBA:ACAC concentration ratios for 0.5 and 1 million cell dilutions were both 1.1 to 1 indicating low mitochondrial redox potentials. Concomitantly, lactate:pyruvate ratios for 0.5 and 1 million cells were greater than other cell dilutions, indicating a high cytosolic redox potential. The suggested range of rumen epithelial cells to include in incubations is 5 to 20 million cells/flask. This will minimize experimental error associated with using low cell numbers and the potential for reduced metabolite production caused by incubating large cell quantities. When rumen tissue taken from animals of the same species, size, and stage of development; data adjusted by cell number is preferred. However, it is recommended that cell protein, cell DM, and animal metabolic weight be included to facilitate future comparison between species and laboratories.

Animals↗

PubMed1991

Regulation of in vitro palmitate oxidation in liver from dairy cows during early lactation.

Regulatory effects of carnitine, glucose, some glucogenic compounds (propionate, pyruvate, alanine, lactate, glycerol, and fructose), ketone bodies (acetate, acetoacetate, and beta-hydroxybutyrate), and insulin on oxidation of palmitate were studied in slices of liver obtained from high producing dairy cows during early lactation. A total of 77 biopsies of liver from 21 multiparous Holstein cows (36 +/- 16 d postpartum) was used. L-Carnitine increased oxidation of palmitate to CO2 by more than twofold and oxidation to acid-soluble products by about fourfold. Propionate decreased oxidation of palmitate in liver slices incubated without added carnitine, but the decrease was lessened by carnitine. Pyruvate, lactate, and alanine increased palmitate oxidation, especially in the presence of carnitine. Glycerol, glucose, and insulin tended to decrease palmitate oxidation in the absence of carnitine. Fructose tended to decrease oxidation to CO2 but did not affect oxidation to acid-soluble products. Acetate and acetoacetate decreased oxidation of palmitate, whereas beta-hydroxybutyrate decreased palmitate oxidation in the absence of carnitine but increased palmitate oxidation in its presence. In general, carnitine decreased the inhibitory effects of compounds that decreased palmitate oxidation but increased the stimulatory effects of compounds that increased palmitate oxidation.

Alanine↗

PubMed1983

Effects of thyroid hormone on the gluconeogenic capacity of lipemic BHE rats.

Gluconeogenesis and ketogenesis from a variety of substrates by isolated hepatocytes from thyroxine-treated and control 40-hr starved BHE rats were determined. Thyroid hormone treatment stimulated glucose production from lactate and inhibited glucose production from alanine, lactate plus NH4Cl, or glutamate. beta-Hydroxybutyrate production by cells incubated with glycerol was decreased in the cells from thyroxine-treated rats. Glycerol had a greater antiketogenic effect in the thyroxine-treated rats than in the control rats. Acetoacetate production from 10:1 lactate:pyruvate, lactate plus NH4Cl, lactate plus lysine, and lactate plus ethanol was also less in the hepatocytes from the thyroxine-treated rats. Acetoacetate production from alanine was increased by thyroxine treatment. From these results it can be suggested that the metabolic abnormalities previously reported in the BHE rats can, in part, be attributable to abnormalities in endogenous thyroid hormone action and in part due to some as yet unknown regulatory process within the liver cell.

Animals↗

PubMed1975

[Energy metabolism in the liver of rats fed a diet contaminated with dithiocarbamates].

Young male rats, Wistar CF strain, weighing about 100 g, were fed during 14 days with a well-balanced diet, but containing either 275 p.p.m. nabame, either 600 p.p.m. thirame or 3 600 p.p.m. zinebe. The animals given the non-contaminated diet were the controls. On the evening before the experiment, they were all fasted and some of them, forced to walk during 18 hours in a restraint wheel. On the morning of the experiment, some of the rats which have not been working were placed in a cold room at + 4 degrees C, and some others were given an i.p. injection of 2,6 g glucose per kg body weight. The animals were then killed, those that received the glucose treatment 30 mn after the injection, the cold-exposed rats 90 mn after the beginning of their exposure. The redox and energy potentials of the liver tissue were determined after the enzymatic assay of the following liver metabolites : lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, ATP, ADP, AMP, inorganic phosphate. The thirame group rats had the smallest body weight and the lowest food intake. All the pesticides-exposed animals has a higher liver weight than predicted by their body weight. The pesticides-containing diets decreased liver lactate concentration and the lac/pyr ratio. Thirame was the more efficient and it partly impaired the glucose induced increase of the cytoplasmic redox potential, as estimated from the variation of the lac/pyr ratio. The pesticide-containing diets also lowered the liver concentrations of beta-hydroxybutyrate, acetoacetate, and their ratio. Last the pesticides, which but slightly modified the liver contents in adenine nucleotides and inorganic phosphate in the fasting state, increased the ATP fall following cold exposure and decreased the net ATP synthesis produced by glucose administration. The thirame diet was the more efficient in our experimental conditions, the zinebe diet the least one. It was concluded in our discussion that dietary dithiocarbamates either induced a hyperthyroidic status in the animal, or acted themselves as thyroxin-like compounds, because the liver metabolism was more directed towards heat production than towards that of chemical energy available for syntheses.

Adenine Nucleotides↗

PubMed2002

Evaluation of a new handheld biosensor for point-of-care testing of whole blood beta-hydroxybutyrate concentration.

OBJECTIVES: To evaluate performance characteristics of the newly available handheld combined glucose and ketone meter for beta-hydroxybutyrate measurement. DESIGN: Laboratory method evaluation. MAIN OUTCOME MEASURES: Accuracy of beta-hydroxybutyrate measurement and effect of acetoacetate interference at clinically important beta-hydroxybutyrate levels. RESULTS: Deming regression analysis of beta-hydroxybutyrate measurements assessed by the ketone sensor and a laboratory enzymatic method revealed a coefficient of determination of 0.989 (P<0.001). Passing-Bablok regression analysis showed a linear relationship between the two methods, ie Y= -0.32+1.13X. The 95% confidence interval of the slope and y-intercept were: slope=1.13 (95% confidence interval, 1.04 to 1.22); intercept= -0.32 (95% confidence interval, -0.59 to -0.06). The Bland-Altman plot showed a small proportional bias between the two methods. The mean bias +/-2 standard deviations was between -0.53 and 0.67 mmol/L. Beta-hydroxybutyrate measurements made by the sensor were linear up to 6 mmol/L. Replicate analysis of two samples spiked with 3.6 mmol/L and 0.8 mmol/L of beta-hydroxybutyrate resulted in coefficients of variation of 3.3% and 13%, respectively. The presence of acetoacetate caused a negative interference in beta-hydroxybutyrate measurement. Beta-hydroxybutyrate recovery was 97.0% and 90.7% when the ketone body ratios were 6:1 and 3:1, respectively. CONCLUSION: The analytical performance of the sensor, when operated according to manufacturer's instructions, could meet the needs of point-of-care beta-hydroxybutyrate measurement. Additional clinical studies are needed to assess the benefits of introducing such an assay in a clinical setting.

3-Hydroxybutyric Acid↗

PubMed1991

Novel solid-phase assay of ketone bodies in urine.

This simple dip-and-read color-matching assay measures ketone bodies in urine. The result is matched with any of the seven colors provided in a color chart. The intensity and hue of the color formed depends on the concentration of acetoacetic acid and follows a gradation starting from light purple (0.2 mol/L acetoacetate) to dark purple and finally to dark violet (9 mol/L). The color developed is independent of pH in the range pH 4-9.5, and is stable for at least 1 h. 3-Hydroxybutyric acid produced no color at the concentrations tested (less than or equal to 100 mmol/L), and acetone was detectable only when greater than or equal to 15 mmol/L. The test was compared with the Ames Ketostix assay in subjects who were on restricted-calorie weight-loss programs. The two methods showed good agreement, except that 20% (21/103) of samples that were negative by Ketostix were read as positive by the new method, which may be more sensitive (detection limit = 0.2 mmol/L). Measurement of urine ketones was unreliable (in comparison with measurement of blood or breath acetone) for monitoring the rate of fat loss during a negative calorie balance.

Humans↗

PubMedDate not supplied

Embryotoxic effects of diabetes on pre-implantation embryos.

We describe the effects of metabolic diabetic factors and sera from diabetic animals and humans on the development of early pre-implantation mouse embryos. Our studies demonstrated that 20 to 24% of control mouse blastocysts failed to develop successfully when grown for 72 h in RPMI medium supplemented with 10% fetal bovine serum. D-glucose in concentrations greater than 3 mg/ml, insulin at concentrations of 0.5 and 1.0 IU/ml, glucagon in concentrations of greater than or equal to 10 micrograms/ml, beta-hydroxybutyrate in concentrations greater than 5 mg/ml, and acetoacetate at concentrations of greater than or equal to 10 micrograms/ml were all embryotoxic, the number of underdeveloped blastocysts rising to over 50%. The combination of these factors in relatively low concentrations was highly embryotoxic, especially when accompanied by hyperglycemia. The addition, to a control medium, of serum from nondiabetic rats (in concentrations of 20%) or of nondiabetic human serum (in concentrations of 50%) did not significantly change the rate of blastocystic development. Serum from streptozotocin-diabetic rats, in the same concentrations, increased the number of undeveloped embryos to 53%. With human diabetic sera the highest embryotoxic effect was found in type I diabetes with and without ketoacidosis. In type II diabetes, embryotoxic effects, although lower, were observed among all types studied [untreated, treated with insulin or with DAONIL (Hoechst, Germany)]. A high correlation was found between the number of undeveloped embryos and the blood concentrations of metabolic diabetic factors: glucose (in type I diabetes), beta-hydroxybutyrate (in type II diabetes untreated or treated with Daonil), acetoacetate (in insulin-treated type II diabetes), and HbA1c (in both insulin-treated and in Daonil-treated type II diabetes). The possible role of diabetic metabolic factors in causing increased risk of spontaneous abortions and infertility among diabetic women is discussed.

Animals↗