Enhanced activity of plasmin and plasminogen activation in the presence of oleic acid.
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Amino Acid Sequence↗
Biomedical subjects
M Mayer
Publications and source records attributed to M Mayer.
Stimulation of plasmin activity by oleic acid.
The amidolytic activity of plasmin with the chromogenic substrate H-D-valyl-L-leucyl-L-lysine p-nitroanilide (S-2251) is stimulated by oleic acid in a dose-dependent and saturable fashion. The activity of plasmin on S-2251 in the presence of oleic acid followed a sigmoidal kinetic pattern, with an almost 4-fold stimulation of activity at 60 microM-oleic acid. Half-maximal stimulation occurred at an oleic acid level of 19.5 microM. The amino acid analogue 6-aminohexanoic acid (AHA), which is known to bind to lysine-binding sites in plasmin, suppressed the stimulatory effect of oleic acid in a concentration-dependent manner; at 0.3 mM-AHA, about 70% of the oleic acid-dependent enhancement of plasmin activity was abolished. The l/v versus 1/[S] plot for plasmin changed in the presence of oleic acid from a linear to a non-linear curve, suggesting positive co-operativity. 14C-labelled oleic acid bound to plasmin, and the bound ligand was displaced by an excess of unlabelled oleic acid. Oleic acid also produced a marked (40-fold) stimulation of the plasminogen-dependent cleavage of S-2251 by urokinase. A half-maximal effect on plasminogen activation was obtained at 40 microM-oleic acid. The present findings suggest that the ability of oleic acid to stimulate plasmin activity and to enhance the conversion of plasminogen to plasmin depends on the interaction of oleic acid with specific lysine-binding sites in plasmin.
Aminocaproic Acid↗
Direct inhibition of proteases and cervical plasminogen activator by antibiotics.
OBJECTIVES: Preterm premature rupture of the fetal membranes and premature delivery are sometimes linked to genital tract infection and activation of proteolytic enzymes that degrade the extracellular matrix. The possible beneficial effect of antibiotics in prevention of preterm premature rupture of fetal membranes and retardation of the onset of labor in some patients with clinical or subclinical infection was explained via their antibacterial efficacy. The aim of this study was to determine the effect of antibiotics on proteolytic enzymes as a possible explanation for the ability of antibiotics to retard preterm labor. STUDY DESIGN: The direct effect of four antibiotics on the proteolytic activities of purified collagenase, elastase, plasmin, trypsin, and chymotrypsin and on streptokinase and human cervical plasminogen activator was measured. RESULTS: The macrolide antibiotic erythromycin and the beta-lactam antibiotics penicillin G, cloxacillin, and ampicillin exerted, in most of the tested combinations with the different proteases, inhibitory effects on the proteolytic activities. CONCLUSION: The present finding that antibiotics directly inhibit proteases may offer an explanation for the beneficial response to antibiotic therapy in some cases of idiopathic preterm labor even in absence of pathogenic bacterial infection.
Ampicillin↗
Does etomidate cause haemolysis?
Etomidate is currently presented as a solution with propylene glycol as solvent. This organic solvent has an extremely high osmolality and is probably responsible for some of the side effects of this drug. In order to detect haemolysis, an indication for cell damage, we have measured serum haptoglobin concentrations in 12 healthy male volunteers after administration of etomidate 0.3 mg kg-1. Six subjects received etomidate in propylene glycol (EtoPG) with an osmolality of 4965 mosmol kg-1 and six received etomidate in lipid emulsion (EtoLip, 400 mosmol kg-1). Haptoglobin concentrations in the EtoPG group decreased by 44% and 43% from baseline values at 2 and 4 h after administration, respectively, and were significantly smaller than after administration of EtoLip. After 24 h, haptoglobin concentrations had not reached baseline values.
Adult↗
Onset and recovery of rocuronium (Org 9426) and vecuronium under enflurane anaesthesia.
We have studied the onset, duration of action and recovery index of twice the ED90 of rocuronium (Org 9426) (0.6 mg kg-1) and of vecuronium (0.08 mg kg-1) in patients during enflurane anaesthesia. Rocuronium had a significantly shorter mean onset time of 1.8 (SD 0.4) min, compared with vecuronium 3.4 (0.8) min. Clinical duration (time for the first twitch in the train-of-four to recover to 25% of control) was similar for both drugs (29 (10) min vs 31 (12) min). Spontaneous recovery times (TOF ratio 70%) did not differ significantly between rocuronium (47 (10) min) and vecuronium (44 (11) min).
Adolescent↗
Brain MRI and electrophysiologic abnormalities in preclinical and clinical adrenomyeloneuropathy.
We describe the neurophysiologic abnormalities in 17 patients with clinical adrenomyeloneuropathy (AMN), an adult phenotype of X-linked adrenoleukodystrophy (ALD). These abnormalities also allowed the early recognition of the AMN phenotype in three asymptomatic boys with biochemically proven ALD. In 14/16 adult AMN patients, there were cerebral white matter abnormalities on MRI which were severe and comparable with cerebral ALD in four of the patients.
Addison Disease↗
Osmolalities of propylene glycol-containing drug formulations for parenteral use. Should propylene glycol be used as a solvent?
Propylene glycol (PG) is a widely used vehicle for water-insoluble drugs. Injection of drugs formulated with this solvent often results in pain, thrombosis, or thrombophlebitis that can be reduced by premedication with local anesthetics or opioids. Because osmolality and pH that are unphysiologic may cause these adverse effects, we assessed the contribution of PG to the osmolality of parenteral drug formulations. Osmolality of PG measured in distilled water showed that PG content and osmolality were directly related: 2% wt/vol PG, 264 mOsm/L; 100% PG, 15, 200 mOsm/L. The osmolalities of commercially available preparations of drugs dissolved in PG ranged from 365 mOsm/L (2% PG content) to 12,800 mOsm/L (83.46% PG), with most above 1000 mOsm/L. Replacement of PG by a solvent with lower osmolality in Germany has effectively reduced the incidence of side effects for one drug. Until PG can be replaced in drugs, we recommend diluting drugs in a large volume of saline solution; this may help to minimize the undesirable effects of this solvent.
Anesthesiology↗
Antigliadin antibody, D-xylose, and cellobiose/mannitol permeability tests as indicators of mucosal damage in children with coeliac disease.
A dual sugar (cellobiose/mannitol) permeability test using an iso-osmolar solution was performed, to compare its ability to predict small-bowel mucosal damage in children affected by coeliac disease with the determination of serum levels of D-xylose and antigliadin antibody. Eighty-three children (67 on gluten-containing diet and 16 on gluten-free diet) were investigated. The D-xylose and the serum antigliadin antibody test predicted accurately 70% and 78% of the small-bowel biopsy results, respectively, whereas the cellobiose-mannitol permeability test predicted 93%. These data confirm the superiority of the permeability test over the D-xylose test, although the former cannot be advocated as a substitute for jejunal biopsy. Our results suggest a complementary use of the permeability test and the antigliadin antibody measurement as screening tests for coeliac disease before applying more invasive procedures.
Adult↗
Secondary metabolites by chemical screening. 20. Decarestrictines, a new family of inhibitors of cholesterol biosynthesis from Penicillium: III. Decarestrictines E to M.
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Acetates↗
Secondary metabolites by chemical screening. 8. Decarestrictines, a new family of inhibitors of cholesterol biosynthesis from Penicillium. I. Strain description, fermentation, isolation and properties.
A family of new 10-membered lactones was detected by chemical screening. Taxonomic studies and fermentation conditions of the producing organisms, which belong to the species Penicillium simplicissimum and Penicillium corylophilum, are presented. The isolation as well as physico-chemical data of the new compounds named decarestrictines A to D are reported. In vitro testing using the HEP-G2 cell assay showed the decarestrictines to be inhibitors of cholesterol biosynthesis, which could be confirmed in vivo. In addition to the decarestrictines from P. corylophilum epoxyagroclavine-I (1) was isolated.
Animals↗
Oxidation markedly reduces bilirubin interference in the Jaffé creatinine assay.
Bilirubin causes underestimation of serum creatinine in the Jaffé alkaline picrate assay. We report an approach for preventing bilirubin interference by pretreating serum samples with peroxidase and H2O2. The dissociation of bilirubin from albumin and its subsequent oxidation markedly reduces the bilirubin interference and enables accurate determination of creatinine concentrations by the Jaffé reaction even in hyperbilirubinemic sera. Within-run CVs were 2.6%, 4.0%, and 3.8% at mean creatinine concentrations of 88, 165, and 349 mumol/L, respectively (n = 20). Day-to-day CVs were 4.0%, 6.3%, and 5.8% for mean creatinine concentrations of 87, 168, and 364 mumol/L, respectively (n = 12). Average recovery of creatinine added to serum in the presence of 600 mumol/L bilirubin was 97% (n = 15). This method requires only small serum volumes (70 microL) and is easily applicable to automated analyzers that can be programmed to add three reagents consecutively.
Bilirubin↗
Luminol-dependent chemiluminescence and the clinical course of multiple sclerosis.
The luminol-dependent chemiluminescence activity before and after the ACTH (Synacthen) treatment was investigated in multiple sclerosis patients and the dependence of the changes of chemiluminescence upon the disease course was evaluated. The tests were performed with granulocytes and monocytes in the presence or in the absence of autologous thrombocytes and, further, the activity of whole blood was tested. All the test were performed both without additional stimuli (spontaneous activity) and with opsonized zymosan. Of the parameters tested, only the spontaneous chemiluminescence activity of whole blood displayed an evidence of dependence on clinical course of the disease. In clinically improved patients a decrease of the whole blood chemiluminescence was found. Similar trend was observed in chemiluminescence of whole blood stimulated by zymosan and in spontaneous granulocyte activity in the presence of autologous thrombocytes. The results show that the whole blood chemiluminescence is decreased in improved patients and suggest that this decrease might be related to the leukocyte-thrombocyte interaction.
Adrenocorticotropic Hormone↗
[The action of S-(+)-ketamine on serum catecholamine and cortisol. A comparison with ketamine racemate].
The S(+)-isomer of ketamine has about twice the anaesthetic potency of the commercially available racemic mixture of ketamine. It is assumed that the known side-effects of ketamine are significantly reduced when administering half the usual dose with the same pharmacodynamic effect [17, 25]. The aim of the present study was to determine the haemodynamic effects, the catecholamine and cortisol plasma levels after administration of equally potent doses of S-(+)-Ketamine and racemic mixture of ketamine. In addition, the effect of premedication with i.v. midazolam was assessed. METHOD. After approval by the ethics committee and written informed consent, 30 healthy male volunteers were randomly allocated to three groups (n = 10). Group 1 received 2 mg/kg ketamine racemate, group 2 1 mg/kg S-(+)-Ketamine, and group 3 1 mg/kg S-(+)-Ketamine 5 min after i.v.-premedication with 0.1 mg/kg midazolam. Non-invasive blood pressure (BP) and heart rate (HR) were continuously recorded. Blood samples were drawn 7 min before, and 2, 4, 8, 16, 32, 64 and 128 min after drug administration. Plasma epinephrine and norepinephrine (NE) levels were determined by HPLC and cortisol plasma levels by RIA. Data were analysed with the Kruskal-Wallis test (P < or = 0.05) for differences between groups. RESULTS. HR and BP showed a significant rise after injection of racemate and isomer, without any significant differences between groups. This was also seen for norepinephrine and cortical plasma levels. Epinephrine levels, however, differed between groups, showing a significant rise after racemate compared to isomer. Premedication with midazolam, in contrast, blunted major haemodynamic and hormonal changes. DISCUSSION. The haemodynamic changes did not differ between the racemate and isomer group despite a reduced isomer dose. HR and BP rise were similar, although epinephrine levels were significantly lower after isomer than racemate. Hence we assume that the increase in the haemodynamic parameters were mainly caused by NE. Midazolam apparently prevented the centrally mediated sympathetic stimulation caused by ketamine and its isomers. Therefore, i.v. premedication with midazolam should be applied when racemate or isomer is used, especially in high-risk cardiac patients.
Adult↗
[Ketamine racemate or S-(+)-ketamine and midazolam. The effect on vigilance, efficacy and subjective findings].
Ketamine is a racemic mixture containing equal amounts of optical isomers that have almost identical pharmacokinetic properties but different pharmacodynamic effects. The S-(+)-isomer of ketamine has about twice the anaesthetic and analgesic potency of the racemic ketamine preparation and is judged to induce less psychic emergence reactions and to be followed by a more rapid recovery of vigilance. The present study was designed to assess whether the S-(+)-isomer of ketamine is superior to the racemic mixture in cardiovascular characteristics, emergence reactions and cognitive functions, and whether side effects may be reduced or prevented by administration of midazolam prior to injection of S-(+)-ketamine. METHODS. Following ethics committee approval and informed consent, 30 volunteers were randomly allocated in this double-blind study to three groups of 10 each. Group 1 received 2 mg/kg bw racemic ketamine, group 2, 1 mg/kg bw S-(+)-ketamine and group 3, 1 mg/kg bw S-(+)-ketamine after premedication with 0.1 mg/kg midazolam i.v. Cardiovascular changes, state of vigilance, cognitive performance, subjective mood and acceptance of anaesthesia were assessed by means of haemodynamic routine monitoring, electroencephalography (EEG), psychometric tests and interview. RESULTS. The increases in mean arterial pressure and heart rate following the injection of racemic ketamine and S-(+)-ketamine were identical and the differences from baseline values significant after both. Premedication with midazolam ensured stable haemodynamics after injection of S-(+)-ketamine. EEG analysis displayed the characteristic changes well known from ketamine anaesthesia for both racemic and S-(+)-ketamine. The vigilosomnoscript showed an identical profile of vigilance up to 30 min after injection of both drugs. The vigilance status after 125 min was less impaired by S-(+)-ketamine than by racemic ketamine. Psychological assessment showed a prompter recovery of visual attentiveness and sensorimotor performance in the S-(+)-ketamine group. Subjective mood was judged by the volunteers to be significantly better after S-(+)-ketamine, and volunteers found S-(+)-ketamine to be more acceptable than racemic ketamine. The frequency of dreams was the same after both drugs. No unpleasant dreams were reported after S-(+)-ketamine, but one of the volunteers who received racemic ketamine had uncomfortable dreams. Midazolam prevented any unpleasant emergence sequelae. On the other hand, the cognitive performance could not be restored to the baseline values until at least 240 min after injection of S-(+)-ketamine, because of the sedative effects of midazolam. DISCUSSION. These results suggest that S-(+)-ketamine offers the advantages of faster recovery of cognitive performance, greater acceptance by the volunteers and identical depth of anaesthesia after injection of half the dose compared with racemic ketamine. The clinical use of S-(+)-ketamine therefore seems to be justified. Premedication with benzodiazepines, e.g. midazolam, is essential. The dose to be administered, however, should be carefully selected in order not to abolish the positive effect of S-(+)-ketamine on vigilance by the sedative effects of the benzodiazepine.
Adult↗
Molecular neurobiology. NMDA receptors cloned at last.
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Animals↗
Stimulation of plasmin activity by aspirin.
This study demonstrates an enhancing effect of aspirin on the amidolytic activity of plasmin. The stimulation of plasmin by aspirin was concentration-dependent and was attained at aspirin concentrations above 2 x 10(-4) M. Aspirin produced a small, reproducible and statistically significant stimulation of the chromogenic activity of plasmin upon H-D-Valyl-L-Leucyl-L-Lysine-p-nitroanilide (S-2251) or pyro-Glu-Gly-Arg-p-nitroanilide (S-2444). Kinetic analysis demonstrated a slight decrease in the affinity of plasmin for substrate S-2251 in the presence of aspirin, reflected by a change of the Km from 3.2 x 10(-4) M to 3.8 x 10(-4) M, and an increase of the Vm. The reciprocal Lineweaver-Burk curve indicated an uncompetitive type of stimulation. The stimulatory effect of aspirin was abolished by the lysine analogue 6-aminohexanoic acid (AHA) but not by the alpha-amino acid glutamic acid. The effect of AHA suggests a specific involvement of lysine binding sites (LBS) on plasmin in the interaction of the enzyme with aspirin. Transient acidification of plasmin abolished its response to aspirin, to AHA and to their combination. The addition of aspirin to diluted human control or pregnancy plasma in vitro stimulated the plasma-mediated cleavage of the chromogenic substrate S-2251. In contrast to its effect on plasmin, aspirin failed to change the activity of tissue-type or urokinase-type plasminogen activators. It is conceivable that in addition to the antithrombotic effect of aspirin ascribed to its interaction with the platelets, aspirin also directly stimulates plasmin activity.
Amino Acid Sequence↗
[Unnecessary laboratory tests in diagnosis and treatment].
The beneficial contact between the practitioner and the clinical laboratory is jeopardized by poor use and overuse of laboratory services. Physicians who order tests excessively put an unjustified burden on the laboratory. This overuse does not contribute to the quality of medical care, does not shorten hospital stay, nor reduce mortality. In clinical departments of another large university hospital there were differences of up to 82% in the number of tests performed, despite similar size and function of the departments. Among the reasons for overuse of laboratory tests is lack of an incentive for patient, physician or clinical department to reduce costs. The fragmentation of laboratory services, the conflicting interests of hospitals, as well as the multitude of personal, institutional and professional interests, also contribute to the variety and excess of superfluous laboratory tests. Analysis leads to suggestions for simple methods to contain the number and cost of laboratory services. Introduction of a reimbursement structure and introduction of new test request forms without a "menu" of tests, and education of practitioners in appropriate test-ordering would promote more appropriate utilization of laboratory services. The educational initiatives would provide guidelines for the clinician as to optimal test selection, the availability of cost-efficient tests, and optimal utilization of the laboratory. Based on decision-analysis methodologies, available test profiles should be restructured to match clinical problems, treatment, and patterns of clinical thinking. Improved access to information and computer-based analysis of data should improve test selection. The suggested methods of reducing unnecessary test ordering, and strategies for more discerning use of laboratory services will undoubtedly improve the practice of medicine and improve the laboratory-physician relationship.
Clinical Laboratory Techniques↗
Nucleotide sequence and genome organization of the murine polyomavirus, Kilham strain.
The polyomavirus Kilham strain (KV) represents a second murine member of the polyomavirus family. However, in contrast to other polyomaviruses, KV exhibits a stringent host and cell specificity. To determine the relationship of these viruses, the complete DNA sequence of KV consisting of 4754 bp was determined. The predicted organization of K virus was found to be comparable to that of other members of the polyomavirus family with two strands coding in an opposite direction of an intergenic region harboring putative control elements for gene expression. These include consensus elements for the origin of DNA replication as well as predicted promoter protein binding domains. Inferred signal sequences for 3' and 5' end formation of mRNAs and splice/branch site consensus sequences resemble those found among the SV40 group of viruses. From the organization of the genome two nonstructural proteins, large T and small t antigen, are predicted, both of which share the same amino-terminal sequence. Three putative capsid proteins VP1, VP2, and VP3 are encoded by alternative open reading frames. The nucleotide sequence in the proposed origin of DNA replication and the inferred amino acid sequence of the viral proteins suggest an evolutionary relationship placing KV between the murine PyV and the SV40 group of viruses. In the region bearing putative transcriptional control elements less nucleotide similarity to that of other polyomaviruses is found and this may reflect the unique host and cell specificity of KV.
Amino Acid Sequence↗