Sensitivity and specificity of urinary N-acetyldopamine as a marker for neuroblastomas: comparison with traditional urinary catecholamine metabolites.
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Biomarkers, Tumor↗
Biomedical subjects
F A Muskiet
Publications and source records attributed to F A Muskiet.
Optimized determination of malondialdehyde in plasma lipid extracts using 1,3-diethyl-2-thiobarbituric acid: influence of detection method and relations with lipids and fatty acids in plasma from healthy adults.
We investigated the influence of different concentrations of Fe3+, phosphoric acid, butylated hydroxytoluene and glutathione on the production of the malondialdehyde-1,3-diethyl-2-thiobarbituric acid adduct in plasma lipid extracts. Following organic solvent extraction the stable product was analyzed by spectrophotometry (537 nm), fluorometry (547 nm) and high-performance liquid chromatography with fluorometric detection. Using optimized reaction conditions there was good agreement between the three methods, with slightly higher values for the spectrophotometric method. Plasma total lipid malondialdehyde reference values for 24 healthy adults amounted to 1.30 +/- 0.23 mumol/l (spectrophotometric method) and 1.11 +/- 0.31 mumol/l (fluorometric method). Plasma lipid malondialdehyde concentrations correlated significantly with plasma triglycerides (r = 0.527), total cholesterol (r = 0.612) and total fatty acids (r = 0.810) and with the total number of double bonds present in plasma fatty acids with three or more double bonds (r = 0.923).
Adult↗
[Carcinoid tumors; current viewpoints of biochemical and endocrine aspects, diagnosis and treatment].
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Blood Platelets↗
Myocardial carbohydrate, ketone, and fatty acid uptake in conscious lambs with aortopulmonary shunts.
A left to right shunt increases myocardial work and is often accompanied by increased catecholamine levels. Because both increased myocardial work and increased catecholamine levels may induce increased fatty acid utilization, which could increase resting myocardial oxygen consumption and therefore unfavorably affect coronary reserve, we studied myocardial uptake of glucose, pyruvate, lactate, beta-OH-butyrate, acetoacetate, FFA, and triglycerides in 12 7-wk-old lambs with aortopulmonary left to right shunts (58 +/- 2% of left ventricular output, mean +/- SEM) and in 10 control lambs 2 wk after surgery. Despite the shunt, systemic blood flow in the shunt lambs was maintained at the same level as in the control lambs. This was accomplished by an increased heart rate and stroke volume. Furthermore, the shunt was accompanied by an increased myocardial oxygen consumption in the shunt lambs (834 +/- 70 versus 528 +/- 43 mumol O2.min-1 x 100 g-1; p less than 0.05). There were no significant differences in arterial substrate concentrations between the two groups. The same was true for arteriovenous differences across the myocardium, with the exception of lactate, which was substantially higher in shunt than in control lambs (72 +/- 25 versus 18 +/- 23 mumol/L; p less than 0.05). As a consequence, myocardial lactate uptake in the shunt lambs was increased 15-fold (18 +/- 6 versus 1 +/- 2 mumol.min-1 x 100 g-1; p less than 0.02), whereas uptake of the other substrates merely paralleled the increased myocardial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Hydroxybutyric Acid↗
Improved diagnosis of carcinoid tumors by measurement of platelet serotonin.
Carcinoid patients are diagnosed biochemically on the basis of increased urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA); urinary and platelet serotonin concentrations are considered to provide complementary information. Using established HPLC methods with fluorometric detection, we evaluated the clinical usefulness of measurements of urinary 5-HIAA and urinary, plasma, and platelet serotonin in 30 consecutive patients with histologically proven carcinoid tumors of fore-, mid-, and hindgut origin before treatment. Ten patients showed no signs of serotonin overproduction; 14 had increased concentrations of urinary 5-HIAA and platelet serotonin; and platelet serotonin, but not urinary 5-HIAA, was increased in 6. None had increased urinary 5-HIAA excretion without an increase in platelet serotonin content. In cases with high rates of tumor serotonin secretion, platelet serotonin reached a maximum and did not correlate with serotonin secretion rate, whereas urinary 5-HIAA was correlated. Increased platelet serotonin was correlated with increased plasma serotonin and with occurrence of carcinoid syndrome. Increased urinary serotonin, allegedly caused by increases in circulating 5-hydroxytryptophan, almost invariably coincided with increased platelet serotonin, but not necessarily with above-normal urinary 5-HIAA excretion. From these results and long-term monitoring of three patients during treatment, we conclude that platelet serotonin is more sensitive than urinary 5-HIAA for detecting carcinoids that secrete only small amounts of serotonin.
Adolescent↗
Influence of a serotonin- and dopamine-rich diet on platelet serotonin content and urinary excretion of biogenic amines and their metabolites.
Using high-performance liquid chromatography and gas chromatography, we reevaluated the 24-h influence of a serotonin- and dopamine-rich diet on platelet serotonin and serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and major catecholamine metabolites in the urine of 15 healthy adults. Although there were significant responses in urinary free serotonin and catecholamine metabolites, their concentrations did not exceed the upper limits of the reference ranges for any of the participants. For urinary 5-HIAA, pronounced effects were observed within 2-4 h. After 6-8 h, results for 11 participants exceeded the upper limit of the reference range. The median recovery of dietary serotonin as urinary 5-HIAA was 20% and subject to a large range (1-50%). There was no significant change in platelet serotonin. We conclude that, using specific analytical methods, no dietary restrictions need be imposed to diagnose catecholamine (metabolite)-producing tumors. For diagnosis of carcinoids on the basis of urinary 5-HIAA it is appropriate to completely abstain from serotonin-containing foods for greater than or equal to 12 h before testing. Platelet serotonin is a more sensitive marker for carcinoids that produce only small amounts of serotonin, and is unaffected by dietary serotonin.
Adult↗
Screening cord blood for hemoglobinopathies and thalassemia by HPLC.
We evaluated the use of an HPLC method for screening hemoglobins in cord blood. We studied the genotype frequencies of the structural hemoglobin variants HbS and HbC and the synthesis variants alpha- and beta(+)-thalassemia in babies born on Curaçao. During three months, 67.2% of all (748) newborns were screened: 122 (24.3%) had an abnormal hemoglobin pattern, of which 53 (43.4%) had a hemoglobinopathy (HbS or HbC), 64 (52.2%) had alpha-thalassemia (HbBarts greater than 0.5%, corresponding to heterozygous or homozygous alpha-thalassemia-2), and 5 (4.1%) had a hemoglobinopathy plus alpha-thalassemia. None of the newborns with heterozygous HbS and HbC had concomitant beta(+)-thalassemia. The population genotype frequency of heterozygous alpha-thalassemia-2 was calculated to be 30.7%. The data are in excellent agreement with those previously established for the adult population and those available from the black population in the United States and Jamaica. Based on the HPLC results, we estimate that 67.1% of newborns with heterozygous alpha-thalassemia-2 remain undetected. A coincidental finding was a relation between demonstrable alpha-thalassemia and short gestation. Because of its superior separating power and high sensitivity for quantifying relatively low percentages of hemoglobins in the presence of HbF0, the HPLC method was preeminently suitable for screening cord-blood samples.
Chromatography, High Pressure Liquid↗
Growth inhibition of two solid tumors in mice, caused by polyamine depletion, is not attended by alterations in cell-cycle phase distribution.
We studied the effect of polyamine depletion on growth and cell cycle characteristics of subcutaneously grown Lewis lung carcinoma (LLC) and fibrosarcoma (FIO 26) in mice. Polyamine depletion was achieved by inhibition of ornithine decarboxylase using 2-(difluoromethyl)ornithine, limitation of exogenous polyamines by administration of a polyamine-poor diet and decontamination of the gastrointestinal tract, and inhibition of endogenous polyamine reutilization by N,N'-bis-(2,3-butadienyl)putrescine (MDL 72527). Determination of S-phase cells was performed in tumor-cell suspensions by flow cytometry and in tumor tissue sections by microscopy, following in vivo labelling with 5-bromo-2'-deoxyuridine (BUdR). DNA synthesis rate was estimated from the incorporation of in vivo-injected [3H]-thymidine (3H-TdR). Both solid tumors almost completely stopped growing after access to polyamines was blocked. Growth inhibition was, however, not attended by changes in cell-cycle-phase distribution. Paradoxically, we measured increased in vivo 3H-TdR incorporation rates and unaltered BUdR-linked staining intensity in treated tumors. Injection of putrescine into treated LLC-bearing mice resulted in an increase in intracellular putrescine and spermidine concentrations, a slight increase in the number of S-phase cells and a marked drop in DNA synthesis rate within the following 9 hr.
Animals↗
Separation of cholesterol esters by silver ion chromatography using high-performance liquid chromatography or solid-phase extraction columns packed with a bonded sulphonic acid phase.
Two methods for the separation of cholesterol esters, based on the number of double bonds in their fatty acid moieties, are presented. Silver ion chromatography, usually performed on thin-layer chromatographic plates, was made suitable for high-performance liquid chromatography (HPLC) and solid-phase extraction. Separation on a bonded sulphonic acid phase loaded with silver ions was achieved with cholesterol esters containing up to six double bonds in their fatty acid moieties. No cross-contamination between fractions with different numbers of double bonds was detected with the HPLC method, was demonstrated by subsequent gas chromatographic analysis of the fatty acid moieties, following transmethylation. For adequate separations with the solid-phase extraction columns it proved important to avoid overloading. The methods may be of use for the off-line analyses of the sterol compositions of the isolated fractions, which each contain sterol esters with an equal number of double bonds in their fatty acid moieties.
Animals↗
Gas chromatographic determination of N-acetylisoputreanine-gamma-lactam, a unique catabolite of N1-acetylspermidine.
A capillary gas chromatographic method with nitrogen-phosphorus detection for the determination of N-acetylisoputreanine-gamma-lactam (acisoga) in urine is described. The method was validated by comparing the results with those given by an isotope dilution mass fragmentographic method. Making use of specific inhibitors for copper-dependent amine oxidase and polyamine oxidase in rats, it was demonstrated that acisoga is formed by oxidative deamination of N1-acetylspermidine by the former enzyme. Moreover, acisoga is not a substrate for pig liver polyamine oxidase. Increased concentrations of acisoga, relative to N1-acetylspermidine, in urines of patients with non-Hodgkin's lymphoma indicated that this conversion diminishes the sensitivity of N1-acetylspermidine as a marker for (tumour) cell death.
Animals↗
Aggressive chemotherapy for acute leukaemia frequently causes intestinal protein leakage.
Cytostatic drugs are known to produce disturbances in intestinal absorption of carbohydrates. To further explore the gastrointestinal (GI) toxicity of cytostatic therapy, 37 patients with acute leukemia were investigated during and/or after remission induction courses by the use of the differential sugar absorption test (DSAT) and the intestinal clearance of alpha-1-antitrypsin (ClAAT). The ratio of the lactulose to the mannitol excretion in the urine was found abnormal in 44% of the tests. The ClAAT was increased in 74% of tests. The tests results differed considerably from patient to patient and depended on the chemotherapy course; correlation between the tests was low, probably indicating the unrelated pathophysiological processes were measured. After haematological regeneration, abnormal test results normalised. It is concluded that aggressive chemotherapy not only causes a reduction in the absorption of sugars, but commonly also protein leakage. These GI side-effects are reversible, and the application of both tests in combination provides a practical and reproducible method for investigation of GI toxicity in patients treated with cytostatic drugs.
Adolescent↗
Reduction of the intake of food and water is responsible for reduction of litter growth when dams are treated with a progesterone antagonist.
Treatment of lactating rats with the anti-progestin Mifepristone or Onapristone adversely affects growth of their litters. The present studies aimed to elucidate the underlying mechanism. The treatment did not interfere with the behavioural interactions between mothers and pups, which are required for normal litter growth. Treatment with the antagonists had a stimulatory action on ovarian oestrogen production. However, ovarian hormones did not play a role in litter growth impairment, as this also occurred with lactating ovariectomized rats. Treatment with anti-progestins did not affect the concentrations of the macronutrients in milk (protein, lactose and lipid), nor did it change the fatty acid composition of lipid. Reduced litter growth was not related to a possible direct effect of exposure of the suckling young to the drugs via the milk. Direct injections into them unequivocally affected adrenal gland and testicular development, but did not affect their body-weight development. Milk secretion, as measured by the milk weight accumulating during 6 or 24 h following sudden removal of litters in advanced lactation, was not impaired by the treatments. However, the ingestion of food and water by dams treated with Mifepristone was significantly below that of control animals. It is concluded that litter growth impairment during treatment of lactating rats with anti-progestin results from the reduction of the intake of food and water by the mother.
Animals↗
Fat absorption in neonates: comparison of long-chain-fatty-acid and triglyceride compositions of formula, feces, and blood.
We studied malabsorption of fat in neonates who were fed either a lard-modified formula (n = 22, gestational age, 33.6 +/- 3.9 wk) or an unmodified formula (n = 14, gestational age, 34.1 +/- 3.7 wk). In both groups fecal lipid consisted almost completely (greater than 90%) of free fatty acids, whose composition was highly correlated with the corresponding formula's fatty acid composition [r = 0.96 (lard modified) and r = 0.99 (standard)]. Both groups had similar relative amounts and compositions of fecal cholesterol esters and triglycerides. Plasma and, to a lesser extent, erythrocyte membrane long-chain-fatty-acid compositions correlated with those of the corresponding formulas. We suggest that the extensive intestinal hydrolysis and limited absorption of dietary lipids is, at least partly, due to lipolysis in the colon. Appearance of triglycerides in the colon may be due to a rapid small-intestinal passage in relation to small-intestinal lipolysis.
Chromatography, Gas↗
Vitamin E, lipid fractions, and fatty acid composition of colostrum, transitional milk, and mature milk: an international comparative study.
Triglycerides, cholesterol, fatty acid composition, and tocopherols were determined in colostrum, transitional milk, and mature milk in St Lucia. With progress of lactation, triglycerides and percentage medium-chain fatty acids increased whereas tocopherols, cholesterol, and percentage long-chain polyunsaturated fatty acids decreased. These changes reflect augmented de novo synthesis of fatty acids (8:0, 10:0, 12:0, and 14:0) in the mammary gland and a tendency of increasing fat-globule size as milk matures. Transitional and mature milks, but particularly colostrum, contained higher concentrations of components considered to be derived from the fat-globule membrane (cholesterol, tocopherols, percentage long-chain polyunsaturated fatty acids) compared with those reported for Western countries. Percentage medium-chain fatty acids in mature milk was two to three times higher than in developed countries. Differences from data from studies in Western countries are discussed in relation to analytical methods and possible consequences for lipid digestion, lipid absorption, growth, and brain development.
Black People↗
Supplementation of patients with homozygous sickle cell disease with zinc, alpha-tocopherol, vitamin C, soybean oil, and fish oil.
Thirteen patients (aged 0.7-17.9 y) with homozygous sickle cell disease were supplemented with alpha-tocopherol, vitamin C, zinc, and soybean oil (suppl 1; for 8 mo) and alpha-tocopherol, vitamin C, and fish oil (suppl 2; for 7 mo). Urinary zinc (suppl 1), plasma vitamin C, plasma cholesterol ester and erythrocyte (RBC) omega 3 fatty acids (suppl 2), and plasma and RBC alpha-tocopherol (suppl 1 and 2) increased. Suppl 1 decreased irreversibly sickled cells by 37.5%, decreased RBC protoporphyrin and urinary porphyrins, and increased the RBC total fatty acid-cholesterol ratio. Suppl 2 decreased plasma triglycerides, further increased the RBC alpha-tocopherol, moderately increased the RBC double-bond index, but decreased the RBC total fatty acid-cholesterol ratio. Zinc, copper, and porphyrins showed prolonged changes. The supplements did not change hemoglobin concentrations, RBC age (reticulocytes, polyamines), or number of aplastic and vasoocclusive crises. Zinc reduces irreversibly sickled cells. Augmentation of RBC antioxidant status by alpha-tocopherol and vitamin C and incorporation of omega 3 fatty acids into RBCs do not affect hemolytic component. Effects on vasoocclusive component are unclear.
Adolescent↗
Potential of descriptive linear discriminant analysis for studying clinical chemical and haematological data from persons with heterozygous sickle cell disease.
To study the potential of multivariate classification methods in order to obtain more insight into abnormal laboratory data from patients with sickle cell disease, we investigated standard haematological and clinical chemical variables of 18 controls and 37 apparently healthy persons with heterozygous sickle cell disease (Hb AS), all women, using both univariate and multivariate classification methods. In the univariate method, those with Hb AS showed decreased serum log aspartate aminotransferase (log AST) activity, mean corpuscular volume and mean corpuscular haemoglobin (MCH) and increased sodium concentration. The multivariate method identified sodium, potassium, urea, uric acid, log AST, alanine aminotransferase and MCH as the variables that produced maximal separation between persons with Hb As and controls. It increased the 'non-error rate' for classification of persons with Hb AS by 16.4% compared with classification based on the variable, MCH, that produced maximal separation by the univariate method. The frequency distribution of percentage Hb S in the Hb AS group proved bimodal with maximal separation at 37.0% Hb S. The subgroup with 37.0% or less (n = 16) was considered to have concomitant heterozygous alpha-thalassaemia-2. In the univariate method the subgroup characterized by greater than 37.0% Hb S (n = 21) had increased serum sodium and uric acid concentrations, perhaps related to sickle cell nephropathy, whereas the subgroup with less than or equal to 37% Hb S did not. The multivariate method added information to the univariate method by additionally identifying abnormalities in serum potassium and urea concentrations in the former subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The effect of dietary energy percentage of fat and its P/S ratio on incorporation of n-3 PUFA and leukotriene production during fish oil supplementation in healthy volunteers.
The effect of low (25 per cent of energy) and high (35 per cent of energy) fat diets with either low (less than 0.4) or high (greater than 1.0) polyunsaturated/saturated fatty acid (P/S) ratios on fatty acid compositions of plasma cholesterol esters and neutrophil phospholipids, and leukotriene production was studied in four groups of healthy volunteers supplemented with 6 g fish oil daily for four weeks. Except for three subjects, eicosapentaenoic acid (20:5n-3) content markedly increased from baseline in the plasma cholesterol ester fraction and to a lesser extent in the neutrophil phospholipid fraction. The increase in the plasma cholesterol ester fraction was inversely, though weakly related to the dietary intake of linoleic acid (18:2n-6). At supplementation endpoints, the 20:5n-3/20:4n-6 ratio in both plasma cholesterol esters and neutrophil phospholipids was highest in the groups consuming diets with low P/S ratio. In vitro leukotriene B5 production by neutrophils, did not differ between groups and there was no consistent suppression of LTB4 production in this four-week study. It is suggested that factors other than the actual dietary 18:2n-6 intake additionally influence the accumulation of 20:5n-3 in tissue during dietary fish oil supplementation.
Adult↗
Urinary polyamine and metabolite excretion by children with Zellweger's syndrome.
In order to investigate whether, due to a lack of peroxisomes, polyamine degradation is altered in patients with the cerebro-hepato-renal syndrome of Zellweger, we determined total, free and acetylated polyamines and some of their catabolites in urines of six patients and age-matched healthy children. The normal polyamine excretion patterns of the patients, compared to the control group, suggest that either the intracellular localisation of the polyamine degrading enzyme, polyamine oxidase, is not exclusively limited to peroxisomes or that the enzyme is located in the peroxisomal matrix.
Amino Acids, Diamino↗