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↗
Biomedical subjects
M Mayer
Publications and source records attributed to M Mayer.
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↗
Linoleic-acid-dependent slowing of erythrocyte sedimentation in multiple sclerosis.
The influence of linoleic acid upon the sedimentation of washed erythrocytes from multiple sclerosis patients and controls was investigated in the present study. Linoleic acid, especially in the concentration of 250 microM and 500 microM, caused slowing of erythrocyte sedimentation and this effect was significantly greater in multiple sclerosis than in controls. These findings with all probability reflect an unsaturated fatty acid-dependent membrane alteration in multiple sclerosis and are analogues to results obtained earlier by several authors by using cytopherometric measurements.
Blood Sedimentation↗
Intestinal permeability after single dose gluten challenge in coeliac disease.
The changes of intestinal permeability before and after a gluten load were studied. The study group comprised 27 patients with coeliac disease (mean age 12.3 years) and 19 healthy controls matched by sex and age. Intestinal permeability was studied by measuring the urinary excretion of two sugars, lactulose and L-rhamnose, before and six hours after the ingestion of five palatable biscuits made with 50 g of gluten powder. The patients with coeliac disease had been on a gluten free diet during the previous two years. After the gluten load lactulose and L-rhamnose urinary excretion changed significantly in patients, and a significant increase in the lactulose: L-rhamnose ratio was also observed. No significant changes were observed in the controls. In view of the modification of the three biopsies diagnostic protocol made by the European Society for Paediatric Gastroenterology and Nutrition, permeability tests associated with single gluten challenges may be an added contribution to the accuracy of the diagnosis in childhood.
Adolescent↗
Compliance of adolescents with coeliac disease with a gluten free diet.
A cohort of 123 patients with coeliac disease, diagnosed in the first three years of life and followed up for at least 10 years, was reevaluated during the teenage period in terms of compliance with the diet and clinical state. Mucosal structure and lymphocytes were assessed in small intestinal biopsy specimens obtained from 36 subjects, by computerised image analysis. Of these adolescents with coeliac disease, 65% were adhering to a strict gluten free diet, 11.4% were on a gluten free diet but with occasional gluten intake, and 23.6% were on a gluten containing diet. Clinical symptoms occurred more frequently in patients on a gluten containing diet, but not in patients on a semi-strict diet. Occasional intake of small amounts (0.06-2 g/day) of gluten did not produce increased concentrations of antigliadin antibodies but resulted in an appreciably increased crypt epithelial volume and expanded crypt intraepithelial lymphocyte population.
Adolescent↗
[The neuromuscular blocking effects of ORG 9426].
ORG 9426 is a new non-depolarizing steroidal muscle relaxant with a short onset time and intermediate duration of action. Its ED90 ist estimated to be between 0.25 and 0.36 mg/kg. The present study investigated the onset time, duration of action and time to spontaneous recovery after 0.3 and 0.9 mg/kg ORG 9426, respectively (i.e. about single or triple ED90). METHODS. Following the consent of the ethics committee and informed patient consent, two groups of 18 patients (ASA I or II) were formed, each scheduled for general or ORL surgery. After premedication with lormetazepam, anesthesia was induced with midazolam (0.07 mg/kg) and etomidate (0.3 mg/kg) and maintained with N2O/O2 at a 65:35 ratio, enflurane (0.8-1.5%) and supplements of fentanyl as needed. The ulnar nerve was stimulated with supramaximal 2 Hz Train-of-four (TOF) every 20 s. Neuromuscular twitch response was registered with EMG. Muscle relaxation was achieved by administration of ORG 9426 0.3 (group 1) and 0.9 mg/kg (group 2), respectively. The following parameters were measured: onset time (time interval from injection to maximal or total block), T125/75 (time for T1 to reach 25% or 75% of control), TOF70 (time for TOF ratio to reach 70% of control), heart rate and blood pressure. RESULTS. (mean +/- SD). At a dosage of 0.3 mg/kg, the onset time was 3.1 +/- 0.8 min and the maximum blockade was 87 +/- 9%. A dosage of 0.9 mg/kg led to complete paralysis (100%) in all patients within 1.2 +/- 0.3 min. The time for recovery of T1 to 25 and 75% of baseline was 18 +/- 7 and 26 +/- 8 min in group 1, in group 2 46 +/- 11 and 53 +/- 17 min, respectively. TOF70 (i.e., time to adequate spontaneous recovery of neuromuscular function) was achieved after 30 +/- 10 and 63 +/- 14 min, respectively. CONCLUSIONS. At a dosage of 0.3 mg/kg, ORG 9426 has an onset time of about 3 min and a duration of activity of nearly half an hour. Its neuromuscular effects are similar to a single ED90 dose of vecuronium. In contrast to a previous study, we observed a much shorter onset time of 70 s following the administration of 0.9 mg/kg. The clinical duration of action and spontaneous recovery of neuromuscular function, however, were significantly prolonged to more than 1 h. The hemodynamic parameters showed only slight alterations.
Adult↗
[Selective and routine use of mediastinoscopy for staging of bronchial cancer].
Because of low rate of mediastinal lymphnode metastases of lung cancer in patients who seem to be able to undergo operative treatment, in most clinics mediastinoscopy for preoperative assessment is only used selectively when lymphnodes were found by CT before. Even though most US- and Canadian clinics use mediastinoscopy staging preoperatively because of differing sensitivity in CT. Analysis of CT and mediastinoscopy will be made by a special computer-program. It is focused that in T1 and T2 lung cancer selective mediastinoscopy is in favour. In T3 and T4 cancer mediastinoscopy should still be routine in the evaluation of mediastinal nodes for preoperative assessment.
Carcinoma, Bronchogenic↗
Luminol-dependent chemiluminiscence of monocytes and granulocytes in multiple sclerosis: the effect of autologous thrombocytes.
The luminol-dependent chemiluminiscence of monocytes and granulocytes and the effect of autologous thrombocytes upon the chemiluminiscence activity were investigated in multiple sclerosis patients, patients with other neurological diseases and healthy controls. The spontaneous monocyte chemiluminiscence was found to be significantly higher in multiple sclerosis patients than in healthy controls. However, no differences were found between multiple sclerosis patients and the group of other neurological diseases. Addition of autologous thrombocytes did not substantially alter both the spontaneous and the zymozan-stimulated monocyte chemiluminiscence. No significant differences in granulocyte spontaneous and stimulated chemiluminiscence were found between the multiple sclerosis patients and both control groups. In all multiple sclerosis patients the addition of autologous thrombocytes markedly depressed the spontaneous and stimulated granulocyte chemiluminiscence and a similar effect was observed in most of the patients with other neurological diseases. In healthy controls, the effect of autologous thrombocytes was rather more heterogenous and both a thrombocyte-dependent increase and a decrease of the granulocyte chemiluminiscence were found. The results suggest that platelets are able to suppress the granulocyte oxidative burst and that this scavenger mechanism can be activated in multiple sclerosis and some other neurological diseases.
Blood Platelets↗
[Congenital hereditary motor and sensory neuropathy].
The authors report 6 cases of hereditary sensorimotor neuropathy (HSMN) presenting with the following clinical features: (1) severe outcome (3 out of 6 patients died before the age of 4 years), and (2) intellectual impairment (3 out of 6 cases). Histopathological study of nerve biopsies gave heterogeneous results: there was one case of axonal neuropathy (HSMN II of Dyck and Lambert), one case of demyelinating neuropathy with Schwann's cell proliferation (HSMN III of Dyck and Lambert), and one case of giant axonal neuropathy. The last three cases displayed an original pattern hitherto unknown in classical delayed HSMN, with complete disappearance of myelinated sheaths and Schwann's cell proliferation. This particular pattern did not seem to be due to the biopsy being performed at an early stage, since in one case a second biopsy showed the same histological features.
Female↗
[Appendicitis in the aged].
From 1984 to 1989 78 patients over the age of 60 years were operated on acute appendicitis. Compared to appendicitis in younger people these older patients showed 3 times longer an interval between the first appearance of symptoms and their contact to the doctor, or surgical treatment. As result of this longer period appeared the high perforation rate 53.8%. In this group of patients with perforation the complication rate was 4 times higher than the intraoperative and histologically confirmed acute appendicitis. From these facts results a mortality rate of 4%. In the retrospective evaluation was also seen that there was no conclusion between the laboratory parameters, the physical symptoms and the degree of the inflammation of the evidence of perforation with local or diffused peritonitis. The inclusion of appendicitis in the differential diagnosis of acute abdominal pain in older people offers the chance of an earlier surgical treatment, so reducing the risk of postoperative complication and mortality.
Abdomen, Acute↗