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Biomedical subjects

J Meier

Publications and source records attributed to J Meier.

At least 109 records · Page 6Linked to original sources
PubMed1986

Approximate LD50 determinations of snake venoms using eight to ten experimental animals.

A method is described for the assessment of lethal toxicity of venoms using a modified LD50 assay. With this test it is possible to obtain an LD50 using only 8-10 experimental animals, instead of 30 or more. It is suggested for ethical, scientific and economic reasons that this method be tested in laboratories involved in screening of venoms for lethality and, if found satisfactory, it should replace the classical LD50 assay.

Animals↗
PubMed1986

Protein C activators in snake venoms.

Venoms of 32 snake species were tested for protein C (PC) activating potency. As measured with the chromogenic PC substrate D-Pro-L-Pro-L-Arg-pNA, eleven venoms were able to generate amidolytic activity from purified bovine PC. In five venom solutions (Bothrops moojeni, B. pradoi, Cerastes cerastes, Vipera lebetina and V. russellii) the PC activating potency was destroyed during 10 min heating at 70 degrees C at pH 3, whereas in six venom solutions (Agkistrodon contortrix contortrix, A. c. mokasen, A. c. pictigaster, Agkistrodon piscivorus, A. p. leucostoma and A. bilineatus) the PC activator was stable under these conditions. PC activator from A. c. contortrix (Protac) was purified to homogeneity and characterized as a single chain polypeptide with a molecular weight of approx. 39-42,000 Dalton. Protac does not exert proteinase activity and is not inhibited by proteinase inhibitors; PC activation with Protac seems to be a stoichiometric reaction. The use of Protac in quantitative PC determination bears significant advantages over the use of thrombin as an activator. In rabbits, i.v. injection of Protac caused a prolonged APTT and did not provoke acute toxic reactions.

Animals↗
PubMed1985

Chromogenic proteinase substrates as possible tools in the characterization of Crotalidae and Viperidae snake venoms.

Proteinase activities have been determined photometrically in 25 different Crotalidae and Viperidae snake venoms by using five different chromogenic proteinase substrates. The activity profiles obtained by listing the identity numbers of substrates hydrolyzed by the venoms in a decreasing potency order remained quite stable within a given snake population. Submission of a venom to various physical and chemical treatments did not alter its activity profile. It is therefore concluded that this simple method of determining proteinase activities could be of help in snake venom characterization, as well as in studying the influence of metallic ions and inhibitors of snake venom proteinases.

Animals↗
PubMed1984

[Malignant neuroleptics syndrome].

The neuroleptic malignant syndrome is clinically characterised by the presence of severe muscular rigidity, altered consciousness, hyperthermia and by signs of autonomic dysfunction. A severe form of the syndrome lasting several weeks was observed in a 20-year-old, mentally retarded female patient while under fluphenazine treatment. Cerebrospinal fluid was examined for monoamine metabolites by high-performance liquid chromatography both during the acute and the convalescent phases of the disease. Since the disease carries a considerable mortality, early diagnosis and rapid withdrawal of all neuroleptic medication is of primary importance.

Adult↗
PubMed1984

Comparative carcinogenic and mutagenic activity of coal tar and petroleum asphalt paints used in potable water supply systems.

Coal tar and petroleum asphalt paints are among the products used as coatings for water pipes and storage tanks to retard corrosion. Formulations of these coatings were tested in the Ames mutagenesis and the mouse skin carcinogenesis bioassays. To test the mutagenicity of the paints, six doses ranging from 0.005 to 10 microliters per plate were assayed. In the mouse skin bioassay, doses of the coal tar paints ranging from 0.2 to 200 microliters were administered topically to 30 SENCAR mice per group. These initiating doses were followed by applications of 1.0 micrograms of 12-o-tetradecanoyl-phorbol-13-acetate (TPA) in 0.2 ml acetone topically, three times weekly for 20 weeks. Petroleum asphalt paints were tested in groups of 40 animals at 200 and 600 microliters doses. All coal tar paints showed mutagenic activity after metabolic activation with S-9, with the highest response being in strains TA 98 and TA 100. None of the petroleum asphalt paints gave mutagenic responses. Both types of coatings resulted in positive responses in the initiation/promotion study. The coal tar paints gave rise to 1000-1800 times the tumor response observed with petroleum asphalt products. One coal tar product was positive when tested as a complete carcinogen in the mouse at 2 microliters per application once weekly for 30 weeks, whereas the asphalt paint was negative at 100 times the dose. The biological responses to the products were greater than expected from their polycyclic aromatic hydrocarbon (PAH) content. These findings suggest that the hazard posed by these coatings may not be fully explained by their PAH contents.

Animals↗
PubMed1984

Influence of various prostaglandin synthesis inhibitors on DMH-induced rat colon cancer.

To evaluate the influence of inhibitors of prostaglandin synthesis on the incidence of DMH-induced colon cancer, 90 male Sprague-Dawley rats were randomly assigned to: indomethacin 20 mg per liter drinking water, meclofenamate 50 mg per liter drinking water, or normal drinking water (control group). Dimethylhydrazine was given by weekly subcutaneous injections (20 mg/kg body weight) during the first 20 weeks. Thirty-two weeks after the start of treatment and carcinogen exposure, the animals were killed and examined for the number, size, location, and spread of intestinal tumors. Colon cancer incidence was significantly lower in animals receiving indomethacin (56 per cent) compared with the control group (88 per cent) and with the meclofenamate group (90 per cent) (P less than 0.005). The corresponding figures for tumors in the small intestine were 31, 46, and 35 per cent, respectively. The tumors in indomethacin-treated animals did not differ in number, size, location, or spread from tumors of the other groups, suggesting that indomethacin might influence the carcinogenic process itself, rather than the natural course of the established disease. We conclude that indomethacin significantly reduces the incidence of large-bowel cancer in this animal model and that this observation may have some potential for future chemopreventive studies in human high-risk groups (e.g. ulcerative colitis, familial polyposis).

1,2-Dimethylhydrazine↗
PubMed1984

Penicillin fermentation in a 200-liter tower fermentor using cells confined to microbeads.

The scale-up of the penicillin fermentation through cell confinement in a 200-L tower fermentor is described. P. chrysogenum spores were adsorbed into Celite microbeads having diameters greater than 180 microns. Fed-batch fermentations were performed using both free and confined cells. Cell growth and penicillin concentrations were measured during the fermentation. In addition, the oxygen transfer rate, the aeration rate, and the level of dissolved oxygen were also measured. Significant improvement in the mass transfer coefficient was found when the cells were anchored onto the microbeads. This improved oxygen transfer rate was accompanied by higher production of penicillin at a lower aeration rate. Besides the improved oxygen transfer rate into the mycelial broth, a reduction of the energy input for the oxygen transfer was observed. The confinement of the cells to this microcarrier furthermore allowed the intermittent harvesting of fermentation broth without reducing the cell mass in the fermentor.

Fermentation↗
PubMed1984

[Modification of the toxicity of Bothrops atrox poison by interventions in the coagulation and kallikrein system of prey].

LD50-determinations with venom mixtures from different age groups of Bothrops atrox were carried out on differently pretreated mice. No differences were seen in the LD50 when comparing untreated mice with mice previously defibrinogenated with batroxobin. Inhibition of the coagulation-, kallikrein-kinin- and fibrinolytic system by pretreatment with batroxobin and aprotinin led to a significantly decreased toxicity of the venom mixtures of all age groups. The age-related difference in toxicity had practically disappeared. Furthermore, the number of mice of the latter group dying within one hour after the venom injection was strongly reduced as compared to untreated and only batroxobin-treated animals. Tests performed on rats showed that the rapidly occurring lethality following the venom injection as a consequence of circulatory disturbances (strong fall of arterial blood pressure, bradycardia, dyspnea), may be prevented almost completely by preincubation of the venom with aprotinin.

Age Factors↗
PubMed1982

Deoxynucleotide-interconverting enzymes and the quantification of deoxynucleoside triphosphates in mammalian cells.

We have demonstrated that methanol extracts of human cells are heterogeneous with regard to content of dNDP (deoxynucleoside diphosphate) and dNMP (deoxynucleoside monophosphate) kinases. The presence of these enzymes can affect the reliability of techniques used to measure intracellular pools of deoxynucleotides. An optimized extraction procedure and enzymic assay for dNTP species in haematopoietic cells are described which provide sensitivity to measure 0.1-40pmol of dATP, dTTP and dGTP, and 1.0-40pmol of dCTP. The extraction and assay give linear results with (2.5-15)x10(6) nucleated cells and (0.1-1.5)x10(9) red blood cells. Under these conditions, extracts equivalent to ~0.5x10(6) nucleated haematopoietic cells catalyse the phosphorylation of 0-8% of dNDP and dNMP standards to dNTP and incorporate them into deoxynucleotide polymer under circumstances where 100% of an equimolar dNTP standard would be incorporated. By contrast, extracts of 0.4x10(6) HeLa cells totally converted dADP, dTDP and dGDP into dNTP with subsequent polymerization. Conversion of dCDP was somewhat less efficient. The results demonstrate conclusively that the activities of deoxynucleotide interconverting enzymes differ in different types of human cells. They can interfere with assay of nucleotides, but may not do so in many types of cell extracts. In particular, dNTP concentrations can be measured in human haematopoietic cells after extraction with 60% (v/v) methanol and are not artificially elevated by deoxynucleotide interconversions. It is apparent that extraction and assay procedures for measurement of dNTP species should be analysed for each cell type in order to minimize contaminating enzyme activities and ensure accuracy of dNTP quantification.

Cell Line↗
PubMed1982

[Percutaneous cholecysto- and cholangiography (author's transl)].

Combined sonographic and radiographic investigations of the biliary duct system using direct percutaneous transhepatic fine needle puncture under constant visualisation and contrast medium demonstration were done in 37 patients. The results show numerous advantages of the method: 1. It is very safe as all tissue and organ areas are under constant surveillance. 2. There is almost no risk of infection. 3. The investigation can be performed on predamaged liver parenchyma. 4. Cytologic material can be obtained; there are no extravasates. The information value of this combined investigation method is greater in a similar group of indications than with radiographic or sonographic methods alone. It appears possible that the risks of ERCP and PTC may be reduced. Further investigations will have to establish the clinical value and risks of this new method.

Biliary Tract Neoplasms↗
PubMed1982

Metabolism of pindolol in patients with renal failure.

Increased metabolism of pindolol in renal impairment has previously been suggested by pharmacokinetic calculations. The present study was a pharmacokinetic and metabolic investigation in 7 patients with severe renal impairment (endogeneous creatinine clearance below 5 ml/min). All the patients received pindolol 5 mg t.d.s. 5 days. On the sixth day, after an overnight fast, 14C-pindolol 5 mg was given orally as a solution to drink. Blood samples were taken for up to 72 h and urine was collected at intervals up to 96 h for measurement of unchanged pindolol by a fluorimetric method and total radioactivity by liquid scintillation counting. Metabolites in blood and urine were analysed after separation by HPLC. It was found that the plasma levels following a single dose of 14C-pindolol were similar to those observed in healthy volunteers, but the elimination half-life was slightly increased u tp 11.5 h. The observed steady state plasma concentrations of pindolol were twice as high but they are still in the therapeutic range of 10 to 100 ng/ml. Therefore, the dose of pindolol could have been reduced by a factor 2, but the reduction was not essential. No active metabolite of pindolol was found in plasma or urine, but elimination of the metabolites was decreased. The elimination half-life following multiple doses was prolonged compared to normal and it was quite comparable to that found fort pharmacodynamic half-life in renal patients. The discrepancy between the present findings and the previous results for metabolism and pharmacodynamic half-life was probably due to the sensitivity of the fluorimetric assay of pindolol.

Aged↗
PubMed1982

Elimination of pindolol in liver disease.

The elimination of pindolol was studied in 32 patients suffering from various liver diseases, mainly acute hepatitis and hepatic cirrhosis. The total body clearance of antipyrine was measured simultaneously as a parameter of liver microsomal enzyme activity. The doses given were antipyrine 1000 mg orally and pindolol 3 mg i.v. Plasma samples were taken and urine was collected for up to 72 h for the measurement of drug concentrations. In addition, conventional biochemical laboratory tests were done. The total body clearance of antipyrine was compared with the pharmacokinetic parameters calculated for pindolol, and the results of the biochemical tests. No correlation was found between antipyrine clearance and the routine biochemical parameters in liver disease or with the total body clearance of pindolol. A significant correlation was seen with the nonrenal clearance of pindolol taken as representing its major metabolic degradation. Higher correlation coefficients were observed when two subgroups of patients with acute hepatitis and hepatic cirrhosis were separated. In some patients suffering from hepatic cirrhosis a higher urinary excretion of unchanged pindolol was observed as liver function become decompensated, a finding due to an unknown mechanism but based on intact renal function. In patients with acute hepatitis a much higher nonrenal clearance was found than in many other patients, which might be based on increased liver blood flow.

Adolescent↗
PubMed1982

Pharmacokinetic comparison of pindolol with other beta-adrenoceptor-blocking agents.

Many beta-adrenoceptor-blocking agents are well studied today. They differ from one another not only in their pharmacologic profiles (cardioselectivity, intrinsic sympathomimetic activity, membrane-stabilizing activity) but also in their metabolic and pharmacokinetic profiles. The profiles of the following 10 beta blockers have been compared: acebutolol, atenolol, labetalol, metoprolol, nadolol, oxprenolol, pindolol, propranolol, sotalol, and timolol. Differences in the aromatic ring structure lead to differences in lipophilic characteristics. They in turn influence the pharmacokinetic parameters such as hepatic extraction ratio, protein binding, volume of distribution, and the ratio of renal versus hepatic clearance. Incomplete oral bioavailabilities are reported both for the lipophilic drugs (e.g., labetalol, oxprenolol, and propranolol) due to extensive first-pass metabolism and for the more hydrophilic drugs (e.g., atenolol, acebutalol, and nadolol) due to medium or low absorption. Low bioavailabilities (as in the case of propranolol) are the source of large biologic variations, nonlinearities, or increased plasma levels with food, with age, in nonsmokers, or in disease states (e.g., hypothermia and renal, hepatic, celiac, Crohn's, or inflammatory disease). The pharmacokinetic comparison in this series of beta blockers reveals that pindolol with its medium lipophilicity has some important advantages. A low daily dosage is possible because of the high bioavailability, the low first-pass effect, the moderate metabolism, and the potency of this drug. Due to the low first-pass effect and the low daily dosage there are no saturation effects, and a good dose linearity is observed. This, combined with moderate metabolism and low protein binding, results in small variability and a good predictability in plasma levels and drug effects. Due to the balanced renal and hepatic clearance, no relevant drug accumulation has to be expected in patients with liver or kidney impairment.

Adrenergic beta-Antagonists↗
PubMed1982

Thrombin-like snake venom proteinases.

Proteinases affecting one or several physiological thrombin substrates are current components of Crotalidae and Viperidae venoms. Enzymes causing in vitro coagulation of fibrinogen without affecting other thrombin-susceptible blood constituents as well as enzymes affecting platelets, F. V. VIII and XIII with only minor action on fibrinogen have been isolated. Fibrinogen affecting proteinases may catalyze the release of either fibrinopeptide (Fp) A (e.g. ancrod, batroxobin) or Fp B (Agk, contortrix proteinase) or of both Fp A and B (B. gabonica proteinase). Some of these enzymes are inhibited by AT III-heparin complex (e.g. Agk. contortrix proteinase) some are not inhibited by either AT III-heparin or hirudin (e. g. batroxobin). The application of Fp A releasing venom proteinases into animals causes transformation of fibrinogen into fibrin I monomer which is rapidly degraded by fibrinolysis and thereby leads to a state of afibrinogenaemia. The administered enzyme is gradually bound to serum proteinase-inhibitors and inactivated. A species dependent interaction between venom enzyme, fibrinogen and serum proteinase inhibitors creates specific differences in dose response relationship. Thus, batroxobin isolated from B. moojeni (HOGE) proved to be a superior defibrinogenating agent in man, as compared to the closely related enzyme isolated from B. atrox (L.). LD50 of B. atrox venom in previously batroxobin defibrinogenated mice is not significantly different as compared to normal animals, indicating an only minor role of batroxobin in Bothrops venom poisoning.

Aging↗
PubMed1982

[Ultrasound-controlled fine needle puncture of gastrointestinal tumors with continuous view].

On account of its principle, ultrasound tomography cannot be recommended as a screening method for intestinal tumors; nevertheless, it may sometimes demonstrate larger tumors not producing typical signs. These neoplasms show a characteristic pattern ("cockade phenomenon"). In the region of the antrum they appear occasionally as a rigid thickening of the gastric wall. The nature of such an expansive lesion may be evaluated quickly and safely by a fine-needle puncture performed under sonographic control. No complications have been observed so far.

Biopsy, Needle↗