Day-to-day variation in urinary excretion of the histamine metabolite methylimidazoleacetic acid.
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Adult↗
Biomedical subjects
B Kågedal
Publications and source records attributed to B Kågedal.
Are electrocardiographic Q-wave criteria reliable for diagnosis of perioperative myocardial infarction after coronary surgery?
OBJECTIVE: A major assumption in cardiovascular medicine is that Q-waves on the electrocardiogram indicate major myocardial tissue damage. The appearance of a new Q-wave has therefore been considered the most reliable criterion for diagnosis of perioperative myocardial infarction (PMI) in cardiac surgery. In a study, originally intended to evaluate troponin-T as a marker of PMI, analysis of our data aroused the need to address the reliability of Q-wave criteria for diagnosis of PMI. METHODS: In 302 consecutive patients undergoing coronary surgery, Q-wave and other electrocardiogram (ECG) criteria were compared with biochemical markers of myocardial injury and the postoperative course. All ECGs were analysed by a cardiologist blinded to the biochemical analyses and the clinical course. RESULTS: The incidence of positive Q-wave criteria was 8.1%. Combined biochemical (CK-MB > or = 70 microg/l) and Q-wave criteria were found in 1.0%. Patients with new Q-waves did not have CK-MB or troponin-T levels significantly different from those without Q-waves. More than 25% of the Q-waves were associated with plasma troponin-T below the reference level (< 0.2 microg/l) on the fourth postoperative day. Q-wave criteria alone did not influence the postoperative course. In contrast, biochemical markers correlated with clinical outcome. CONCLUSIONS: The majority of Q-waves appearing after coronary surgery were not associated with major myocardial tissue damage, and according to troponin-T one-fourth of the Q-waves were not associated with myocardial necrosis. Furthermore, the appearance of Q-waves had little influence on short term clinical outcome. Therefore, the use of Q-wave criteria as the gold standard for diagnosis of PMI may have to be questioned.
Aged↗
Urinary excretion of 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid in children.
5-S-Cysteinyldopa (5SCD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) are formed during biosynthesis of melanins. They are used as indicators of pigment formation and markers of melanoma progression in adults and could possibly be used as markers of activity, growth and even malignant transformation in large pigmented naevi in children. We investigated the urinary excretion of these pigment precursor metabolites from 136 children, 5 to 15 years of age. The mean 5SCD excretion was 38.1 mumol/mol creatinine. A significant age-related decrease from a mean of 60.4 mumol/mol creatinine at 5 years of age to 28.0 mumol/mol creatinine at age 15 was found. In a reference group (29 adults, 20-33 years of age) the mean excretion was 48.9 mumol/mol creatinine. The mean excretion of 6H5MI2C was 42.8 mumol/mol creatinine at 5 years of age and 26.1 mumol/mol creatinine at the age of 15. The mean value for the young adults was 33.4 mumol/mol creatinine. No correlation between the mean excretion of 5SCD and 6H5MI2C was demonstrated. We suggest an upper reference level of 90 mumol/mol creatinine for the excretion of 5SCD in the age group 5-11 years and of 60 mumol/mol creatinine in the age group 13-15 years. Corresponding figures for the indole 6H5MI2C are 70 and 60 mumol/mol creatinine. The establishment of reference values in children will make it possible to use 5SCD and 6H5MI2C measurements as diagnostic tools, indicating growth or malignant transformation in giant melanocytic naevi during childhood.
Adolescent↗
Why "urea nitrogen" when urea is measured?
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Blood Urea Nitrogen↗
Vitamin A metabolism and mRNA expression of retinoid-binding protein and receptor genes in human epidermal melanocytes and melanoma cells.
Retinoids inhibit proliferation of melanocytes and melanoma cells and affect disorders of hypo- and hyperpigmentation. Such effects might involve retinoid-binding proteins, retinoid metabolites and nuclear retinoid receptors for transcriptional activation. We detected messenger RNA transcripts for the cellular retinol- and retinoic acid-binding proteins (CRBP, CRABP I and II) in cultured epidermal melanocytes. In the melanoma cell lines the major transcript was CRABP II. Nuclear retinoic acid (RA) receptor transcripts and the 9-cis-retinoic acid receptor transcript were detected in all cells. The endogenous concentrations of retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) in melanocytes were five times those in melanoma cells. When cells were incubated with [3H]ROH the main metabolites in the melanocytes were [3H]ddROH (4%) and [3H]RA (0.4%). Formation of [3H]RA was only detected in one melanoma cell line. Both melanocytes and melanoma cells produced an unidentified metabolite when incubated with [3H]ROH and [3H]RA. Dissimilarities in the metabolism and endogenous concentration of retinoids between benign and malignant melanocytes might play a key role in differentiation and growth regulation.
Cells, Cultured↗
Effects on interstitial glutathione, cysteine and 5-S-cysteinyldopa of buthionine sulphoximine in human melanoma transplants.
Using microdialysis of human melanoma transplants in athymic mice we have shown that interstitial glutathione levels decreased during treatment with buthionine sulphoximine (BSO) and recovered after cessation of treatment. The cysteine concentrations also decreased, while 5-S-cysteinyldopa tended to increase during BSO treatment. Restoration of the glutathione levels was not seen after either N-acetylcysteine (NAC) or L-2-oxothiazolidine-4-carboxylate (OTC) injections, given on the third day of BSO treatment. These results were to be expected since NAC and OTC were given during the BSO treatment, and BSO is a specific and potent inhibitor of glutathione synthesis. Cysteine levels, however, increased after the NAC injection but remained unaltered after the OTC injection, while 5-S-cysteinyldopa remained unaltered after both the NAC and the OTC injections.
Acetylcysteine↗
S100B protein, 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid as biochemical markers for survival prognosis in patients with malignant melanoma.
Elevated levels of the phaeomelanin metabolite 5-S-cysteinyldopa and the eumelanin metabolite 6-hydroxy-5-methoxyindole-2-carboxylic acid in urine and serum have been shown in previous studies to correlate with disseminated malignant melanoma. Immunohistochemical detection of S100B protein is an acknowledged method for the diagnosis of malignant melanoma, and it has been suggested that rising serum levels of S100B protein are associated with the survival rate of patients with malignant melanoma. In the present study serum levels of S100B protein and urinary concentrations of 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid were measured in 91 patients with histopathologically verified malignant melanoma. At the time of sampling 13 patients were in clinical stage I, 13 in stage II and 65 in stage III. The urinary levels of the melanin metabolites were determined by automated high performance liquid chromatography, and the serum levels of S100B protein by an immunoradiometric assay with two monoclonal antibodies. The overall survival rate was most strongly associated with the serum levels of S100B protein (P < 0.001), but there was also a significant correlation to urinary levels of 5-S-cysteinyldopa (P < 0.001). A corresponding association with urinary levels of 6-hydroxy-5-methoxyindole-2-carboxylic acid was found in only a very few patients with extremely high urinary concentrations. A statistically significant increase in relative hazard was found for S100B protein levels exceeding 0.6 microgram/l (P < 0.001), and predictably for patients in clinical stage III (P < 0.001). An analysis of S100B protein levels in patients in clinical stage III showed a significant correlation to survival (P = 0.005). Our study suggests that of the three biochemical tumour markers, S100B and to a lesser extent 5-S-cysteinyldopa have the greatest potential to be used as predictors of survival prognosis in patients with malignant melanoma.
Adult↗
Correlation of DNA ploidy and S-phase fraction with chemotherapeutic response and survival in a randomized study of disseminated malignant melanoma.
DNA ploidy and S-phase fraction were measured by flow cytometry in the tumour tissue of 87 patients with disseminated malignant melanoma, who had been classified either as responders or with progressive disease in a study of the effects of 2 chemotherapeutic regimens. The patients had been randomized to receive treatment with dacarbazine (DTIC) and vindesine (Eldesine) with or without addition of cisplatin (Platinol). Tumour tissue was obtained from both the primary tumours and the last histologically verified metastases, but in some cases only the primary tumours or the last metastases could be evaluated. There was a significantly higher mean S-phase value in melanoma metastases from patients with complete or partial responses compared with patients with progressive disease. Neither the S-phase fraction of the primary tumour, nor the DNA ploidy of the primary tumour or of the last histologically verified metastases taken before inclusion into the study were associated with therapeutic response. In the multivariate analysis, both the anatomical location of the metastases and the S-phase fraction measured on the last metastases remained significant prognostic factors of response. In the univariate survival analysis, there was an association between high S-phase fractions of the metastases and longer survival. In the multivariate survival analysis, the S-phase fraction, the number of involved metastatic sites and the treatment response were independent predictive factors. We conclude that, in disseminated melanoma treated with chemotherapy, a high S-phase fraction measured in the last histologically verified metastases is associated with a higher response rate and a longer survival. Our results clearly support the role of S-phase measurement as a potential tool for selecting patients for treatment.
Adolescent↗
Cyanide detoxification in rats exposed to acetonitrile and fed a low protein diet.
Different neurological syndromes have been associated with exposure to cyanide. Dietary cyanide exposure from cassava roots combined with a low intake of the sulfur amino acids necessary for cyanide detoxification has been implicated in the causation of konzo, an upper motoneuron disease identified in Africa. We have investigated the effect of a low protein diet on the capacity for cyanide detoxification. Rats were fed normal chow containing 18% protein or a low protein diet with 5% protein. To expose rats to cyanide the drinking water was supplemented with 40 or 80 mM acetonitrile (CH3CN) for up to 4 weeks. Weight gain was monitored and 24-hr urines were collected for analyses of total sulfur, inorganic sulfate, thiocyanate, and 2-aminothiolazine-4-carboxylic acid (ATC). Blood was collected for analyses of cyanide and cyanate. Rats on a normal diet grew throughout the experiment, while those on a low protein diet initially lost weight and then stabilized at a constant weight. Rats exposed to acetonitrile all progressively lost weight, those on a low protein diet at the highest rate. Signs of neurological damage were not observed. Rats not exposed to acetonitrile excreted < 0.2% of sulfur as thiocyanate and those on a low protein diet reduced their total sulfur excretion to one-third that of rats of the normal diet. Rats on the normal diet did not change total sulfur excretion during exposure to acetonitrile, although thiocyanate now contributed more than two-thirds of excreted sulfur. Rats on a low protein diet exposed to acetonitrile increased both total sulfur and thiocyanate excretion to the levels of rats on a normal diet. Rats exposed to acetonitrile had manyfold increases of circulating concentrations of cyanide and cyanate and of urinary excretion of ATC. There was a positive correlation between blood cyanide concentrations and the plasma concentration of cyanate. It is concluded that the rat has a high capacity for detoxification of cyanide. During adaptation to a low protein intake, sulfur is conserved but cyanide detoxification is still possible at the cost of extensive protein catabolism. It is thus possible that subclinical cyanide exposure could interfere with normal growth and development. The observation of a relationship between circulating cyanide on the one hand and circulating cyanate and urinary excretion of ATC on the other highlights the possibility that cyanide metabolites may mediate neurotoxic effects of cyanide.
Acetonitriles↗
Correlations of Ki-67 and PCNA to DNA ploidy, S-phase fraction and survival in uveal melanoma.
In 79 patients with uveal melanoma, the tumours were investigated by DNA flow cytometry and immunohistochemical staining of PCNA and Ki-67. S-phase as a continuous variable was significantly correlated with Ki-67 (P = 0.033), but not with PCNA. DNA ploidy was not correlated with either of the two antigens. Ki-67 was significantly correlated with histopathological type (P < 0.001) and tumour size (P < 0.001). Large tumours and epithelioid cell type were associated with a high frequency of Ki-67 positive cells. A high level of Ki-67 positivity (> or = 6.5%) was also associated with a shorter survival (P = 0.0037), and when adjusted for DNA ploidy, histopathological type and tumour size, Ki-67 in the multivariate analysis remained an important prognostic factor (P = 0.017).
Antigens, Neoplasm↗
Altered glutathione levels in ischemic and postischemic skeletal muscle: difference between severe and moderate ischemic insult.
The purpose of the present study was to investigate how the duration of ischemia and reperfusion affect the glutathione (GSH) levels in skeletal muscle and to assess the presence of oxidative stress by quantitating oxidized glutathione (GSSG) and the ratio of GSSG/GSH. The amounts of GSH and GSSG were quantitated in the tibialis anterior muscle of the rat hind limb after 2 and 4 hours of tourniquet ischemia and after 1 and 5 hours of reperfusion, and the levels were compared to those in nonischemic control tibialis anterior muscles. In muscles subjected to 2 hours of ischemia, the levels of GSH, GSSG, and the ratio GSSG/GSH did not differ significantly from those of nonischemic controls. After 4 hours of ischemia without reperfusion, the GSH levels were slightly increased, compared to controls (p < 0.05). After 1 hour of reperfusion following 4 hours of ischemia, the levels of GSH decreased by 50% compared to control (p < 0.01), and still after 5 hours of reperfusion the levels of GSH were 50% lower than control levels. The GSSG/ GSH ratio did not change during 1 and 5 hours of reperfusion compared to control. A major finding in this study was that, during reperfusion after severe ischemia of 4 hours, there was a marked depletion of glutathione, which was not seen after a moderate ischemic insult of 2 hours.
Animals↗
In situ microdialysis for monitoring of extracellular glutathione levels in normal, ischemic and post-ischemic skeletal muscle.
Microdialysis probes were inserted into the tibialis anterior muscle and into the femoral vein of anaesthetised Sprague-Dawley rats for monitoring of reduced (GSH) and oxidized (GSSG) extracellular glutathione. The dialysates were analysed using HPLC. The levels of GSH and GSSG were high immediately after implantation in the skeletal muscle and declined to steady state levels after 90 minutes into the same range as that found in the venous dialysate. Total ischemia was induced two hours after implantation of the dialysis probe after steady state levels had been reached. The extracellular levels of GSH increased during total ischemia and had doubled at the end of the ischemic period compared to preischemic values. During the following initial 30 minutes of reperfusion the levels increased further to four-fold the preischemic levels. The levels of GSSG also increased (100%) during the initial 30 minutes of reperfusion. The extracellular GSH levels remained elevated for 1 hour of reperfusion, but the GSSG levels returned to preischemic levels. The results indicate that intermittent hypoxia or anoxia in muscle tissue through hypoperfusion or ischemia decreases intracellular GSH stores by leakage, reducing the intracellular antioxidative capacity and increasing the risk for oxidative reperfusion injury upon final normalization of tissue blood supply.
Animals↗
Plasma cyanate concentrations in chronic renal failure.
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Cyanates↗
Analysis of the cyanide metabolite 2-aminothiazoline-4-carboxylic acid in urine by high-performance liquid chromatography.
The cyanide metabolite 2-aminothiazoline-4-carboxylic acid (ATC) was converted to N-carbamylcysteine and analyzed by high-performance liquid chromatography (HPLC) and fluorometric detection. ATC was first separated from interfering substances by passing through the cation exchanger AG 50W-X8. Interfering disulfides were converted to thiols by reduction of the eluate with thiopropyl-Sepharose 6B. The thiols were then absorbed to the organomercurial absorbent p-acetoxymercurianiline-Sepharose 4B while ATC was obtained in the effluent. ATC was then converted to N-carbamylcysteine by ring opening at high temperature in an alkaline environment. Derivatization of N-carbamylcysteine was with N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide. The imprecision (CV) of the method was 3.6% and the analytical recovery was quantitative. The detection limit was 0.3 microM. ATC in urine was stable for at least 3 months when stored at -196 to +20 degrees C. The ATC concentration in urine was below the limit of detection in health nonsmokers. The utility of the method was demonstrated by the finding of up to 10.5 microM ATC concentrations in urine samples from human subjects in Mozambique living on a high dietary intake of cyanide from the cassava root. In a metabolic study rats were exposed to acetonitrile in the drinking water. After 4 weeks very high ATC levels were found in the urine, representative values from two rats being 195 and 525 microM, respectively.
Animals↗
High-performance liquid-chromatographic analysis of dopachrome and dihydroxyphenylalanine.
A high-performance liquid-chromatographic system for the determination of dopachrome and dihydroxy-phenylalanine (dopa) is described. The retention of dopa and dopachrome on C18 reversed-phase columns was investigated as a function of pH in the mobile phase, and as expected the capacity factors were found to be pH dependent. The chromatographic behavior is explained by the change in net charge and polarity of dopachrome and dopa when pH varies. Satisfactory separation of dopachrome and dopa was obtained. An advantage of the method is that the measurements of dopachrome stability and disappearance are uninfluenced by concomitant formation of melanochromes which, however, is the case when the disappearance is followed by measurement of the decrease in absorbance at 475 nm. The utility of the method is illustrated by following the disappearance of dopachrome as a measure of dopachrome tautomerase activity.
Animals↗
DNA ploidy and S-phase fraction as prognostic factors in patients with uveal melanomas.
In 96 patients with uveal malignant melanomas the tumours were investigated by DNA flow cytometry. Thirty-eight per cent of the melanomas were aneuploid. By univariate analysis significant correlations with survival were found for histological type, tumour size, DNA ploidy, evidence of 'blind eye' and S-phase fraction. By multivariate analysis, significant prognostic variables were found to be histological type (P = 0.0008), tumour size (P < 0.0001) and DNA ploidy (P = 0.0038). Evidence of 'blind eye' was not significantly correlated with survival after adjustments for the other variables mentioned above. The S-phase fraction could be estimated in all 60 diploid tumours and in 12 of 36 aneuploid melanomas. By univariate analysis this variable was found to be a significant prognostic factor, but did not remain so after adjustment for ploidy, histological type and tumor size. We further conclude that patients with small DNA diploid uveal melanomas of spindle cell type have a rather favourable prognosis.
Adult↗
An improved method for determination of thiocyanate in plasma and urine.
An improved spectrophotometric method is described for the determination of thiocyanate in plasma and urine. Thiocyanate is adsorbed on a weak anion-exchange resin with strong affinity for chaotropic ions, and eluted with perchlorate. Thiocyanate is then chlorinated by hypochlorite and quantified according to the König (J Prakt Chem 1904; 69:105-37) reaction by use of isonicotinic acid and 1,3-dimethyl-barbituric acid. The method affords a simple, rapid and sensitive assay for thiocyanate and has a detection limit of 0.93 mumol/l. At thiocyanate concentrations of 107.1 and 167.4 mumol/l in plasma and urine the within-day CVs were 0.69% and 1.1% respectively, and the total imprecision measured for a period of 65 days was 0.98%. Analytical recoveries were quantitative both with urine and plasma samples.
Barbiturates↗
Urinary excretion of melanocyte metabolites during treatment with chloroquine phosphate.
The antimalarial drug chloroquine is also used in the prevention of photodermatoses and in patients with inflammatory connective diseases. The drug binds strongly to melanin. Melanocytic activity can be studied by analysis of the urinary markers of eumelanin (6-hydroxy-5-methoxyindole-2-carboxylic acid, 6H5MI-2-C) and phaeomelanin (5-S-cysteinyl-dopa, 5-S-CD). To determine whether chloroquine interacts with this activity, we measured the urinary excretion of the two metabolites in 16 patients with either systemic or discoid lupus erythematosus, polymorphic light eruption or rheumatoid arthritis, during a period with and without treatment with chloroquine phosphate. Two control groups consisting of 7 untreated patients and 10 healthy subjects were also included in the study. During medication, there was a significant increase in 5-S-CD excretion, while the excretion of 6H5MI-2-C was not significantly affected. No significant changes in the excretion of any of the two urinary markers were found in the untreated patients, while a non-significant increase in 5-S-CD excretion was seen in the healthy controls at the follow-up.
Adult↗