Hypercholesterolaemia due to familial defective apolipoprotein B-100 in two Australian families.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
R Bais
Publications and source records attributed to R Bais.
New method for the determination of pancreatic amylase evaluated.
We have carried out a multicenter evaluation of a new reagent carrier for Reflotron, specific for pancreatic amylase where the salivary isoenzyme is inhibited by two specific monoclonal antibodies. This new procedure combines easy handling with low imprecision (median CV less than 3%) in control material, serum, heparinized blood, and plasma) and close correlation (r = 0.991 to 0.999) with established manual and automated methods. The same close correlation was found with values obtained from either venous or capillary finger-stick blood. Salivary amylase up to 54 kU/L (37 degrees C) was inhibited to about 97%. Endogenous interference by hemoglobin, bilirubin, triglycerides, cholesterol, or hematocrit was found to be negligible within a wide range of interferent concentrations. Out of a panel of 28 commonly used drugs it was shown that only two (ascorbic acid and paracetamol), and then only at toxic concentrations, caused a deviation in amylase activity of greater than 10%. From the results of this study we conclude that this new method is suitable for highly precise and accurate measurements of pancreatic amylase in emergency and routine laboratories.
Amylases↗
The inhibition of metabolic oxalate production by sulfhydryl compounds.
A number of sulfhydryl compounds were shown to inhibit CO2 and oxalate formation from glyoxylate by rat liver homogenates and hepatocytes. The most significant inhibition occurred with cysteine and this inhibition was concentration-dependent. In rats made hyperoxaluric by administering ethylene glycol in their drinking water, daily intraperitoneal injections of cysteine caused a rapid and marked decrease in urinary oxalate excretion which was maintained over the duration of the treatment (28 days). Over this time period, the level of urinary oxalate excretion in these ethylene glycol-treated rats was reduced to that of the controls. It is postulated that the decrease is due to the formation of a cysteine-glyoxylate adduct, 2-carboxy-4-thiazolidine carboxylate, which prevents glyoxylate being further oxidized to oxalate. Cysteine or similar sulphydryl compounds may therefore have potential as therapeutic agents in the prevention of renal stones.
Aluminum↗
Investigations into the effect of glyoxylate decarboxylation and transamination on oxalate formation in the rat.
The decarboxylation and transamination reactions of glyoxylate, which divert this precursor from oxalate formation, have been investigated. Decarboxylation of glyoxylate is synergistic with 2-oxoglutarate and catalysed by 2-oxoglutarate:glyoxylate carboligase which co-chromatographs with the 2-oxoglutarate dehydrogenase complex. The activity is located in the mitochondrial fraction and is probably due to the E1 subunit of the complex. A greater amount of decarboxylation occurs from 2-oxoglutarate than from glyoxylate but the presence of 2-oxoglutarate does not affect oxalate formation from glyoxylate. There is no oxalate formation from 2-oxoglutarate. Studies with rat liver homogenates showed that a number of amino acids can participate in glyoxylate transamination. However, using isolated rat hepatocytes, these reactions did not have a significant effect on oxalate formation from glyoxylate with the exception of cysteine which caused an 80% reduction in oxalate formation. Investigation of this inhibition indicated that it was most likely due to the formation of a cysteine-glyoxylate adduct which makes glyoxylate unavailable for oxidation to oxalate. This cysteine inhibition of oxalate formation was also demonstrated in normal rats and rats made hyperoxaluric by injecting them with either glyoxylate or glycolate. The results indicate that sulphydryl compounds, which can have a therapeutic role as oxalate-lowering agents, may be able to be developed.
Aldehyde-Ketone Transferases↗
Macromolecular lactate dehydrogenase: an innocent bystander.
Lactate dehydrogenase (LD) activity is often increased in malignancy, and may occasionally be a useful tumor marker. In the case reported here, a persistently increased LD activity led to an extensive search for a neoplasm. Results of routine investigations were normal, but LD electrophoresis followed by gel filtration and immunofixation confirmed the presence of a circulating macromolecular LD, comprising IgAK bound to LD. Altogether it may provoke unnecessary investigations, the LD-IgA complex currently has no diagnostic significance.
Adult↗
The relation of clinical catastrophes, endogenous oxalate production, and urolithiasis.
A dose-related toxicity syndrome of renal, cerebral, and liver dysfunction; metabolic acidosis; and deposition of calcium oxalate crystals in tissues is reported in association with various apparently unrelated treatments for a wide range of diseases. The parenteral nutrient xylitol, the hyperosmolar agent glycerol, the polysorbate emulsifiers (e.g., in vitamin E preparations), the anesthetic methoxyflurane, and possibly the experimental hypoglycemic agent dichloroacetate all produce a toxicity syndrome very similar to that of ethylene glycol poisoning. In long-term, high-dose oral toxicity studies with rodents, these or similar agents also produce calcium oxalate bladder stones and bladder tumors. Studies with both unlabeled and labeled agents in humans and animals and in vitro experiments with purified enzymes, tissue homogenates, and isolated hepatocytes have provided both strong circumstantial and direct evidence for the existence of minor pathways of carbohydrate metabolism and of oxidative dealkylation and dehalogenation reactions in drug biotransformations that link these agents to endogenous oxalate production. Because urinary oxalate is now considered to be a critical factor in stone formation and because it is increasingly accepted that 80-90% of urinary oxalate is produced endogenously, it is now possible to formulate pathways that link oxalate production with dietary macronutrients. Therapeutic modifications of diet, in vivo hormonal milieu, and intracellular metabolic controls in relation to endogenous oxalate production may provide new forms of treatment for urolithiasis.
Animals↗
Metabolic response to insulin and glucose infusions in starved tumor-bearing rats.
Tumor-induced alterations in insulin sensitivity and glucose metabolism were investigated by examining the effect of glucose and insulin infusions in 72-h-starved tumor-bearing (TB) rats. Following glucose infusion, the rate of glucose disappearance from the blood was similar in TB and non-tumor-bearing (NTB) rats, even though insulin concentrations were lower in TB rats. Blood lactate was increased in TB rats prior to treatment and increased immediately following glucose infusion. Insulin alone decreased blood glucose in NTB but not TB rats. When insulin was infused together with glucose, the rate of glucose disappearance increased similarly in both TB and NTB rats. The immediate increase in blood lactate seen in TB rats following glucose infusion was not apparent in the TB rats receiving insulin and glucose. TB rats infused with glucose and insulin showed a greater rise in blood alanine concentrations, compared with all other infusion regimens. While ketone body concentrations decreased in both TB and NTB rats in response to the different infusion regimens, plasma free fatty acids in TB rats were not decreased by insulin and glucose treatments. TB rats therefore not only have decreased insulin release, but adipose tissue is also less sensitive to insulin action. In vivo studies using 2-deoxy[U-14C]glucose showed that glucose uptake by the muscle and adipose tissue, but not the tumor, was significantly increased by the infusion of insulin, thereby demonstrating one of the mechanisms by which insulin may act to conserve host tissue.
Adenocarcinoma↗
Inhibition of endogenous oxalate production: biochemical considerations of the roles of glycollate oxidase and lactate dehydrogenase.
1. Both the peroxisomal, flavin-linked glycollate oxidase [(S)-2-hydroxy-acid oxidase; EC 1.1.3.15] and the cytosolic, nicotinamide-adenine dinucleotide (NAD)-linked lactate dehydrogenase (L-lactate dehydrogenase; EC 1.1.1.27) are thought to contribute to the formation of oxalate from its immediate precursors, glycollate and glyoxylate, but the relative contributions of each enzyme to endogenous oxalate production is not known. 2. In rat liver homogenates, [14C]oxalate production from labelled glycollate is halved and that from labelled glyoxylate is increased fourfold by the addition of either NAD or NADH. 3. In isolated rat hepatocytes, the 3-hydroxy-1H-pyrrole-2,5-dione derivatives of glycollate, which are specific inhibitors of glycollate oxidase, have a greater effect on glycollate metabolism than on glyoxylate metabolism. 4. These findings are consistent with an important role for lactate dehydrogenase in oxalate formation from glyoxylate. 5. With human and rat liver homogenates and with purified human liver glycollate oxidase and rabbit muscle lactate dehydrogenase, DL-phenyl-lactate (2 mmol/l) completely inhibits glycollate oxidase but has not effect on lactate dehydrogenase. On the other hand, the reduced form of a chemically synthesized, NAD-pyruvate adduct (1 mmol/l) almost completely inhibited lactate dehydrogenase but had no effect on glycollate oxidase. 6. Either alone or in combination, DL-phenyl-lactate and reduced NAD-pyruvate adduct reduce oxalate production from glycollate and glyoxylate in isolated rat hepatocytes, but do not abolish it completely. 7. These findings support a role for another enzyme, probably glycollate dehydrogenase (EC 1.1.99.14), in oxalate production in integrated cell metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol Oxidoreductases↗
Whole-blood quality-control material for Reflotron assays of cholesterol.
Explore the source record for details and available documents.
Blood Chemical Analysis↗
Alpha-amylase determination with the Reflotron reagent carrier system: use of whole blood, plasma, and serum, and effect of isoenzymes.
In the Reflotron Amylase dry-reagent carrier system (Boehringer Mannheim GmbH) a new substrate is used for determining total amylase (EC 3.2.1.1) activity:indolyl-alpha-D-maltoheptaoside. The procedure shows low imprecision (median CV less than 3.2%), and results for sera, plasma, and capillary and venous blood (y) correlate well with those of a conventional alpha-amylase method involving p-nitrophenyl (PNP)-maltoheptaoside substrate (x) (for 209 blood samples: y = 0.981x + 9.7; r = 0.994). Correlation was also excellent with a method involving maltotetraose as substrate (r = 0.987). Attachment of an indoxyl residue rather than a PNP group to the maltoheptaoside did not affect the substrate response to pancreatic or salivary isoenzyme activity. Therefore, the relative proportion of these isoenzymes did not affect the correlation between the Reflotron Amylase reagent carrier and the alpha-amylase PNP-maltoheptaoside method. With a reaction time of less than 3 min, this system is especially suitable for amylase determination in situations where a prompt result is required.
Humans↗
The effect of tumour-bearing on 2-deoxy[U-14C]glucose uptake in normal and neoplastic tissues in the rat.
The extent to which normal and neoplastic tissues of the rate take up glucose was assessed by the 2-deoxy[U-14C]glucose tracer technique. Measurements of glucose uptake were made over 40 min in anaesthetized rats under conditions where the blood glucose concentration was constant. In fed tumour-bearing rats, the relative rates of glucose uptake per g wet wt. of tissue were tumour (100), small intestine (72), brain (61), heart (61), spleen (50), lung (42), adipose tissue (11) and muscle (8). Normal tissues of the fed tumour-bearing rats had decreased rates of glucose uptake as compared with the same tissues in fed non-tumour-bearing control rats. Blood glucose concentrations were similar in both groups, but insulin concentrations were decreased in tumour-bearing rats. Starvation decreased the rates of glucose uptake by normal tissues in both control and tumour-bearing rats, but the difference between the fed and starved states was greater in the control rats. Starvation did not decrease glucose uptake by the tumour. On an organ basis, the tumour (12-14% of body wt.) took up 4 times more glucose than did muscle (40% of body wt.).
Adenocarcinoma↗
Inactivation of chicken liver pyruvate carboxylase by 1,10-phenanthroline.
Inactivation of chicken liver pyruvate carboxylase by the chelating agent 1,10-phenanthroline follows pseudo-first-order kinetics. The hyperbolic dependence of the apparent first-order rate constant on 1,10-phenanthroline concentration is consistent with a two-step inactivation mechanism, in which 1,10-phenanthroline binds firstly to the enzyme, and secondly to the enzyme-bound Mn(II) ion. Binding of 1,10-phenanthroline to pyruvate carboxylase results in complete loss of ATP/Pi exchange activity, but only a 61% decrease in pyruvate/oxaloacetate exchange activity. The rate of inactivation is greater at low enzyme concentrations, implying that binding of 1,10-phenanthroline to monomers and dimers is preferred relative to that of tetramers. Furthermore, in the presence of acetyl-CoA, which stabilizes the tetrameric structure, no dependence of inactivation on enzyme concentration is observed. As monitored by gel-permeation liquid chromatography, formation of the enzyme-Mn(II)-phenanthroline complex results in loss of the tetrameric structure of the enzyme. From atomic-absorption measurements, inactivation by 1,10-phenanthroline also causes some loss of Mn(II) from the enzyme. It is concluded that the Mn(II) atom does not participate directly in the reaction mechanism, but may play a structural role essential to the integrity of the enzyme's tetrameric structure.
Acetyl Coenzyme A↗
Creatine kinase reference intervals determined from a multi-centre data pool.
Reference intervals for creatine kinase assayed at 37 degrees C using N-acetyl cysteine-activated methods have been determined on data obtained from 10 laboratories throughout Australia. The pooled distributions for males and females are skewed towards higher values and cannot be transformed to Gaussian distributions. The reference interval for females was calculated to be 34 to 180 U/l and for males it was 46 to 300 U/l. However, if creatine kinase is to be used in the diagnosis of myocardial infarction, the upper limit of the reference interval for males is considered to be too high. It is concluded that for males, the upper limit may need to be determined on specific populations such as hospital inpatients.
Australia↗
The effects of recombinant tumour necrosis factor (cachectin) on metabolism in isolated rat adipocyte, hepatocyte and muscle preparations.
Tumour necrosis factor (TNF) did not stimulate lipolysis in isolated rat adipocytes, though preincubation with TNF increased adrenaline-stimulated fatty acid release. Glycogenolysis, gluconeogenesis and ketogenesis in isolated rat hepatocytes were not influenced by TNF in short-term (30-60 min) incubations. TNF stimulated 14CO2 production from [U-14C]glucose in rat hemidiaphragm preparations, but lactate production and alanine release were not significantly altered. It is concluded that TNF does not regulate short-term metabolism in adipocytes, hepatocytes and muscle preparations in the manner of a catabolic hormone.
Adipose Tissue↗
Oxalosis and the E-Ferol toxicity syndrome.
Explore the source record for details and available documents.
Humans↗
Ketone-body metabolism in tumour-bearing rats.
During starvation for 72 h, tumour-bearing rats showed accelerated ketonaemia and marked ketonuria. Total blood [ketone bodies] were 8.53 mM and 3.34 mM in tumour-bearing and control (non-tumour-bearing) rats respectively (P less than 0.001). The [3-hydroxybutyrate]/[acetoacetate] ratio was 1.3 in the tumour-bearing rats, compared with 3.2 in the controls at 72 h (P less than 0.001). Blood [glucose] and hepatic [glycogen] were lower at the start of starvation in tumour-bearing rats, whereas plasma [non-esterified fatty acids] were not increased above those in the control rats during starvation. After functional hepatectomy, blood [acetoacetate], but not [3-hydroxybutyrate], decreased rapidly in tumour-bearing rats, whereas both ketone bodies decreased, and at a slower rate, in the control rats. Blood [glucose] decreased more rapidly in the hepatectomized control rats. Hepatocytes prepared from 72 h-starved tumour-bearing and control rats showed similar rates of ketogenesis from palmitate, and the distribution of [1-14C] palmitate between oxidation (ketone bodies and CO2) and esterification was also unaffected by tumour-bearing, as was the rate of gluconeogenesis from lactate. The carcinoma itself showed rapid rates of glycolysis and a poor ability to metabolize ketone bodies in vitro. The results are consistent with the peripheral, normal, tissues in tumour-bearing rats having increased ketone-body and decreased glucose metabolic turnover rates.
Animals↗
The effect of dietary refined sugars and sugar alcohols on renal calcium oxalate deposition in ethylene glycol-treated rats.
The effect of administering refined carbohydrates in the diet on calcium oxalate deposition in the kidneys of rats given 1% (v/v) ethylene glycol in their drinking-water was investigated. The rats were given 0, 2.5, 10, 30 or 60% sucrose in the feed (w/w) and/or drinking-water (w/v) or 20% (w/w) starch, glucose, sucrose, fructose, galactose, xylitol or sorbitol in the feed for 3 wk. All of the animals remained healthy over the test period as far as could be assessed by the measurement of 19 plasma biochemical parameters. The inclusion of 30 or 60% (w/w) sucrose in the diet resulted in a more than tenfold increase in the deposition of calcium oxalate in the kidneys. However, this deposition could not be predicted from data on urinary pH and urinary excretion of calcium, oxalate and urate, which have been reported to be risk factors for stone formation. There was no evidence of increased rates of oxalate production from ethylene glycol. The administration of fructose, xylitol or sorbitol was associated with the greatest renal deposition of calcium oxalate, and glucose was associated with by far the least.
Animals↗