On the rate of release of CK isoforms into serum of patients with myocardial infarction treated with thrombolysis.
Explore the source record for details and available documents.
Creatine Kinase↗
Biomedical subjects
F Pagani
Publications and source records attributed to F Pagani.
Effects of therapeutic coronary reperfusion on aspartate aminotransferase isoenzymes in sera of patients with acute myocardial infarction.
We examined the kinetics of the catalytic activities of aspartate aminotransferase (AST, EC 2.6.1.1) isoenzymes in serum of 28 patients with myocardial infarction who were to receive either intracoronary urokinase--reperfusion angiographically proved--or conventional therapy (control group). Cytosolic (soluble) AST (s-AST) activity in serum increased rapidly immediately after recanalization, reaching a maximum 12 h after the onset of infarction. In the control group, this peak was reached 28 h after the onset (P less than 0.001). Peak s-AST activity was similar in the two groups. Peak activity and peak time for mitochondrial AST (m-AST) were the same for the two groups of patients; intervention that affects myocardial perfusion caused only a slight additional increase in m-AST activity in the early post-infarct period. There may be advantages to measuring m-AST, which is briefly influenced by reperfusion, instead of the usual cytosolic enzymes for assessment of myocardial damage in patients with myocardial infarction treated with thrombolytic therapy.
Adult↗
Reference intervals for two bone-derived enzyme activities in serum: bone isoenzyme of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TR-ACP).
Explore the source record for details and available documents.
Acid Phosphatase↗
Pyruvate measured in whole blood with the Cobas Bio analyzer.
Explore the source record for details and available documents.
Autoanalysis↗
Characterization of genetic markers in the 3' end of the apo B gene and their use in family and population studies.
The 3' end of the apo B gene is highly polymorphic. Two point mutations in the coding sequence of the gene create EcoRI (E+, E-) and XbaI (X+, X-) RFLPs. The two loci are in random association and the frequency of the four haplotypes, E+X+, E+X-, E-X+ and E-X- in the normolipidaemic population are 0.68, 0.30, 0.02 and 0.00, respectively. Although the polymorphic nucleotide underlying the EcoRI RFLP creates an amino acid substitution in the apo B protein (Glu----Lys) in a region close to a putative LDL-receptor recognition site(s), we find no statistically significant difference in the frequency of the apo BGlu and apo BLys alleles in hyperlipidaemic patients (familial hypercholesterolaemia, type IIA with no tendon xanthomas, IIB and probably IV) and the normolipidaemic population. In contrast, we confirm previous findings, that the X+ allele is in linkage disequilibrium with a genetic locus that predisposes to the development of higher fasting plasma triglyceride levels than the X- allele. We have characterized a highly polymorphic region immediately 3' to the apo B gene. At least 5 alleles of this locus exist in the population and our family studies show it should be an extremely informative locus to use in studies where polymorphic or mutant apo B alleles are suspected to underly certain forms of familial hyperlipidaemia. DNA sequence analysis of this highly polymorphic locus shows that the variation is entirely attributable to the number of times the simple repeating sequence 5'-TTTATAATTAAAATATTTATAATTAAATAT-3' is present.
Adult↗
An alternative approach to the prevention of succinyldicholine-induced apnoea.
Succinyldithiocholine was utilized as a substrate analogue of succinyldicholine to study normal and atypical serum pseudocholinesterase (EC 3.1.1.8). In the method, the enzyme acts on succinyldithiocholine to release thiocholine, which reacts with 5,5'-dithio-bis-(2-nitrobenzoic acid) to produce a coloured compound with maximal absorbance at 410 nm. The procedure appears to be precise (between-day analysis gives a coefficient of variation between 1.1 and 3.7%) and amenable to automation, permitting routine use in any laboratory. The reference interval for 300 healthy adults with "usual" cholinesterase genotype was estimated to be 34-77 U/l, with a significant difference between males and females (40-78 U/l for men and 33-76 U/l for women, p less than 0.01). The median activity in 105 individuals with "heterozygous" cholinesterase genotype was 22 U/l (range 5-35 U/l), and for 14 "atypical" homozygotes 1.5 U/l (range 1-4 U/l). The assay with succinyldithiocholine may offer a direct procedure for preoperative screening of individuals with an abnormal response to the muscle relaxant succinyldicholine, thus avoiding the determination of genotype by measurement of inhibitor numbers.
Apnea↗
Comparison of catalytic activity and mass concentration of serum creatine kinase MB isoenzyme in the detection of coronary reperfusion in acute myocardial infarction after therapeutic thrombolysis.
Serum creatinine kinase MB isoenzyme time-activity curves are useful for the assessment of coronary reperfusion after acute myocardial infarction. The purpose of this study was to compare serum creatine kinase MB catalytic activity with mass concentration for the determination of coronary reflow after therapeutic thrombolysis. Creatine kinase MB mass was determined immunoenzymometrically. Creatinine kinase MB catalytic activity concentration was determined by electrophoresis. Serum was collected every 4 hours for 96 hours in two groups of myocardial infarction patients: A (n = 10), urokinase induced reperfusion; B (n = 10), conventional therapy without urokinase. Peaks of mass and activity occurred at similar times in groups A and B. Both were significantly earlier in the urokinase treated patients. The maximal rate of increase of creatine kinase MB (based on either mass or catalytic activity) was threefold greater in the urokinase group. There are no important differences between the behaviour of creatine kinase measured as catalytic concentration or as mass concentration. Mass concentration is therefore equally useful as an indicator of coronary reperfusion.
Adult↗
Evidence for different classes of calcitonin binding sites in rat CNS: an autoradiographic study with carbo-calcitonin.
The distribution of binding sites in the rat CNS for a synthetic analogue of eel calcitonin, [Asu1-7]eel calcitonin (carboCT) was investigated. This distribution was compared to that for the natural peptide to see whether a modified molecule would also reveal different classes of binding sites for CT. The regional distribution of 125I-carboCT binding in coronal sections of rat CNS was examined by an in vitro autoradiographic technique. Non-specific binding was assessed after addition of excess cold carboCT or eel CT and the results showed that carboCT binding is specific and that it is displaced equally by cold carboCT and by eel CT. There was dense labelling in the nucleus accumbens, in the tractus striohypothalamicus, in the anterior and posterior part of the hypothalamus except for the nucleus ventromedialis, in the amygdala, in the pars medialis of the reticular formation, in the nucleus ruber, in the periventricular gray and in the raphe magnus. Grains were less dense in the hypothalamus lateralis, in the substantia nigra and in the nucleus interpeduncularis. In contrast to eel CT, carboCT did not bind in the spinal cord, nor did carboCT prevent eel CT binding in this area, whereas it was able to prevent it in the brain. These results are consistent with the existence of different classes of binding sites for CT in rat brain and in spinal cord, and indicate that the substitution of the S-S bond with a C-C bond in the eel CT molecule makes the peptide more selective for one class of binding sites.
Animals↗
Kinetic analysis of the interaction of mifentidine with gastric H2-receptors in the conscious dog.
The H2-receptor antagonists mifentidine and cimetidine were compared for their ability to antagonize the activation of H2-receptors in the conscious dog. Dose-response curves to dimaprit in stimulating gastric secretion were displaced to the right in a dose-related fashion by both drugs. Schild and Eadie-Hofstee analysis of these data indicated that mifentidine and cimetidine inhibited in vivo activation of H2-receptors in a manner compatible with competitive surmountable antagonism. Mifentidine displayed a 24fold greater potency than cimetidine as H2 antagonist in the conscious dog.
Animals↗
Isoforms of creatine kinase isoenzymes in serum in acute myocardial infarction after intracoronary thrombolysis.
Kinetics of the catalytic activities of creatine kinase (CK;EC 2.7.3.2) for three CK-3 and two CK-2 isoforms in serum were studied in 20 patients with myocardial infarction randomly assigned to receive either intracoronary urokinase (group A) or conventional therapy (group B). The temporal characteristics of isoform changes described were (a) time at which the isoform activities are significantly greater than initial values, (b) maximal rate (Ka) at which isoforms are released into blood, (c) time lag from onset of pain until maximum activity value, (d) peak value of each serum isoform, and (e) rate (Kd) at which each isoform is cleared from serum. Thrombolytic treatment induced earlier peak times in group A: for CK-3(3), 7.4 vs 20.0 h; for CK-3(2), 11.6 vs 24.8; for CK-3(1), 18.6 vs 34.3; for CK-2(2), 9.1 vs 17.8; and for CK-2(1), 11.8 vs 26.8 (numbers given are medians; for all isoforms, P less than 0.05). Ka values were at least twofold greater and the first increase was significantly earlier in the urokinase group. Consequently, the ratio for CK-3(3) to CK-3(1) activities peaked significantly earlier in group A. Isoform peak activities and Kd were not significantly different between the two groups.
Adult↗
Activity of serum aspartate aminotransferase isoenzymes in patients with acute myocardial infarction.
Activities of aspartate aminotransferase (AST) isoenzymes were determined in serial serum samples from 40 cases of acute myocardial infarction, and compared with activities of creatine kinase, CK-MB isoenzyme, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase for temporal changes. Cytosolic (soluble) AST (s-AST) and mitochondrial AST (m-AST) respectively increased 6.6 and 9.0 h after onset of chest pain. The median time at which serum m-AST activity peaked (15.8 U/L, range 6.4-53.5 U/L) was 47.8 h after the onset of infarction, 19.8 h later than the peak s-AST activity (171 U/L, range 53-517 U/L) and m-AST also disappeared from the serum more slowly than s-AST (p less than 0.001). Serum m-AST values were above normal for at least six days after the infarct. The ratio of m-AST to total AST in serum increased after myocardial infarction, being greatest (20%, range 11-32%) on the third day after onset. For individuals, peak activities of s-AST correlated well with total CK (r = 0.91) and CK-MB (r = 0.86) peak activities, indicating that s-AST also reflects the infarct size. However, m-AST correlated poorly with the enzymes commonly used in infarct diagnosis; it apparently provides different biological information.
Adult↗
Tremor at rest episodes in unilaterally 6-OHDA-induced substantia nigra lesioned rats: EEG-EMG and behavior.
Twenty male adult Wistar rats were unilaterally lesioned in the substantia nigra (SN) with 6-hydroxydopamine (6-OHDA), and prepared with chronic cortical (ECoG) and neck muscle (EMG) electrodes. Longitudinal study over a period of up to 18 months demonstrated the emergence, in about two-thirds of the rats, of spontaneous repetitive episodes of head and neck tremor during awake at rest, of up to 20 seconds duration each, that were associated with spike and wave-like ECoG activities. These episodes of tremor at rest disappeared during sleep and REM sleep episodes, and also following the i.p. administration of L-DOPA. It is assumed that these tremor at rest episodes are analogous to those reported to occur in primates after experimentally induced dysfunction of the nigro-striatal, extrapyramidal system.
Animals↗
Relationship of analgesia induced by centrally injected calcitonin to the CNS serotonergic system.
The role of the serotonergic system in the antinociceptive effect of centrally administered salmon calcitonin (sCT) was studied in rats. The animals were given sCT either intracerebroventricularly (i.c.v.) or intrathecally (i.t.). I.c.v. administration of sCT (2,5 micrograms/rat) to animals depleted in CNS serotonin (5-HT) either by treatment with 25 mg/kg desmethylimipramine (DMI) i.p. plus 100 micrograms/rat 5,7 dihydroxytryptamine (5,7 DHT) i.c.v., ten days before or by 150 mg/kg p-chlorophenylalanine (pCPA) i.p., 72 and 24 h before, still significantly increased the hot-plate latencies comparable to those of non-depleted animals. The same result was obtained when the 5-HT receptors were blocked with metergoline. The i.t. administration of sCT (2 micrograms/rat) to animals with spinal cord 5-HT depleted by treatment with DMI plus 5,7 DHT, i.t., delayed but did not abolish the antinociceptive activity of i.t. injected sCT, which was of the same intensity as in non depleted animals. When 5,7 DHT was administered alone, either i.c.v. or i.t., without protection of the catecholaminergic neurons so that noradrenaline (NA) was greatly reduced, the antinociceptive effect of sCT was completely abolished even when NA had been depleted only in the spinal cord. We conclude that it is the catecholaminergic system, not the serotonergic, that plays a fundamental role in the anti-nociceptive effect of centrally administered sCT.
5,7-Dihydroxytryptamine↗
Evaluation of a new method for cholinesterase determination.
We report the evaluation of a new commercially available assay system for determination of the catalytic activity of serum cholinesterase (EC 3.1.1.8) and application of the method to a centrifugal fast analyzer. Serum cholinesterase activity is determined at 30 degrees C using para-hydroxybenzoylcholine as substrate. This reaction is coupled to a second reaction using para-hydroxybenzoate hydroxylase (EC 1.14.13.2) as coupling enzyme. Enzyme activity is measured kinetically by monitoring the decrease in absorbance at 340 nm of NADPH in the second reaction. The procedure is precise and the results obtained from normal and pathological sera show good correlation with those obtained by the alternative procedures employing propionylthiocholine, butyrylthiocholine and benzoylcholine as substrates. The reference range for 700 healthy subjects was estimated to be 140-345 U/L (95% central range, determined non-parametrically), with significant difference between males and females (155-353 U/L for men and 134-323 U/L for women, p less than 0.001).
Acetylcholinesterase↗
Evaluation of a commercial immunoenzymometric assay kit for creatine kinase MB isoenzyme determination using monoclonal antibodies.
A simultaneous two-site immunoenzymometric assay for creatine kinase MB determination (Hybritech Tandem-E CK-MB) using monoclonal antibodies was evaluated and compared with cellulose acetate electrophoresis using fluorometric scanning densitometry. The assay has satisfactory precision (between-day analysis gives a coefficient of variation between 2.1 and 9.4%) and is not susceptible to interference by concentrations of creatine kinase MM up to 5000 micrograms/l (3400 U/l) and creatine kinase BB up to 1000 micrograms/l (1085 U/l). The upper limit of MB isoenzyme concentration in 250 apparently healthy people was 5.5 micrograms/l. Comparison between the immunoenzymometric assay (y) and electrophoresis (x) yielded the following linear regression equation: y = 0.37x + 1.9, with a correlation coefficient of 0.828. The characteristics of the temporal kinetics of MB isoenzyme, calculated by two methods, in 49 patients with acute myocardial infarction, were nearly identical in terms of the rate of creatine kinase MB release and the time at which the peak value is obtained, but not in terms of the rate of elimination of the isoenzyme. The fractional disappearance rate of MB isoenzyme from the circulation was significantly higher if calculated with Tandem-E results rather than with electrophoresis results (-0.035 vs -0.028, p less than 0.001). Whereas in the first day after infarction immunoenzymometric assay and electrophoresis had the same clinical sensitivity for identifying patients with acute myocardial infarction, in specimens collected more than 24 hours after the onset of the chest pain, the clinical sensitivity of the immunoenzymometric method was lower. Our results show that it is still premature to draw definitive clinical conclusions from the immunoassay results.
Adult↗
Cholinergic control of gastric acid secretion.
In the perfused stomach preparation of the anaesthetized rat the cholinergic agonists acetylcholine (ACh) and bethanechol stimulated gastric acid secretion. Both agonists produced similar maximal acid output (70 mumols/15 min) when infused intravenously. However, bethanechol was more potent, eliciting half maximal stimulation at 1.98 mumols/kg/h, while the corresponding dose of ACh was 10.95 mumols/kg/h. Secretory responses to either agonist were antagonized in a dose related fashion by blockade of muscarinic receptors with atropine. In contrast, inhibition of nicotinic receptors with hexamethonium produced a striking potentiation of ACh stimulated secretion whilst the bethanechol elicited secretion remained unaffected. In the presence of full nicotinic receptor blockade the ACh response curve was shifted to the left sixfold, half maximal stimulation being produced at 1.79 mumols/kg/h. Cimetidine partially inhibited the secretory responses elicited by either ACh or bethanechol while blockade of adrenoceptors (alpha and beta) did not affect acid output induced by cholinergic agonists. Secretion elicited by ACh is interpreted as being the composite effect of pro-secretory action and an inhibitory mechanism due to the activation of nicotinic receptors. Hexamethonium, through nicotinic receptor blockade, inhibits the restricting mechanism and thus reveals the full stimulatory action of ACh.
Acetylcholine↗
Pharmacological profile of mifentidine: a novel H2-receptor antagonist.
Mifentidine, a representative compound of a novel class of H2-antagonists, has been investigated for its ability to interact with H2-receptors and to inhibit gastric acid secretion. Affinity estimates (KB) of mifentidine obtained from in vitro studies on cardiac and gastric mucosal histamine (H2) receptors were in the 20-50 nM range. Mifentidine appeared to be endowed with strong anti-secretory properties against histamine-stimulated secretion in the anaesthetized rat and in the conscious dog. Distinct features of mifentidine were considerable bioavailability and duration of anti-secretory effect.
Animals↗
Cimetidine-induced prolactin release: possible involvement of the GABA-ergic system.
The mechanism of cimetidine-induced prolactin (PRL) release was studied. Intracarotid (i.a.) administration of 1 mg/kg of impromidine, the most specific H2 histamine agonist known, did not counteract the cimetidine-induced hypersecretion of PRL. Pre-treatment with benzodiazepines (diazepam or lorazepam, 3 mg/kg/i.a.) completely suppressed it. Administration of gamma-aminobutyric acid (GABA 5 mg/kg/i.a.) was also able to prevent it, but to a lesser extent than benzodiazepines. Simultaneous administration of doses of diazepam (1.5 mg/kg/i.a.) and GABA (3 mg/kg/i.a.) ineffective per se markedly blunted the increase of PRL by cimetidine. We conclude that cimetidine does not induce hypersecretion of PRL by its action on histamine H2 receptors, but through other pharmacological activities of the drug, such as perhaps interaction with the GABA-ergic system in the pituitary.
Animals↗