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Biomedical subjects

O Wassermann

Publications and source records attributed to O Wassermann.

At least 19 recordsLinked to original sources

Organochlorine pesticides, octachlorostyrene, and mercury in the blood of Elb River residents, Germany.

Blood samples of 135 residents living near the estuary of the Elb River (Schleswig-Holstein, Germany) were analyzed for organochlorines (e.g., beta-hexachlorocyclohexane (HCH) (less than 0.5-22.9 ng/ml), benzene hexachloride (HCB) (0.8-55.2 ng/ml), DDE (less than 0.5-29.2 ng/ml) and for mercury (Hg, n = 44) (1.1-79.2 ng/ml). It was the first time that octachlorostyrene (OCS) (n.d.-9.2 ng/ml) could be detected in Germans. The pollutants were determined by means of capillary gas chromatography and atomic absorption spectroscopy, respectively. Covariance analysis and log-linear models revealed correlation between increasing age and blood concentrations of HCB, beta-HCH, DDE and OCS, between relative body weight and HCB or DDE, between locality and all pollutants analyzed, and, finally, between fish consumption and OCS and Hg. Regarding the influence of locality on the body burden of pollutants it may be assumed that additional routes of uptake, e.g., via drinking water or air, might be important.

Age Factors

The epidemiology of toxic stews.

'Toxic stews' is a term which refers to the innumerable manmade chemicals to which we are exposed today. Neither their composition nor their toxicity in humans and the environment is sufficiently understood. Little interest has been aroused thus far by synergisms between these substances. The sources of toxic stews are many and diverse: chemical products and associated impurities; industrial and household waste water; emissions from combustion, incineration and other industrial processes; exhaust fumes from traffic and power plants; etc. These negative aspects of modern life contribute to the development of chronic diseases such as cancer, allergies, and diseases of the respiratory tract and central nervous system. There are severe obstacles to, and deficiencies, in official monitoring of pollutants, including problems of data access, chemical analysis, and toxicological and epidemiological research. It is urgent that the role of the physician as guardian of human health be expanded to include a stronger emphasis on environmental protection as an important component of preventive medicine.

Animals

Short-term effects of chlorophenols on the function and viability of primary cultured rat hepatocytes.

Primary cultured rat hepatocytes were used as an experimental model to detect adverse effects of five chlorophenols (CP) in vitro (penta-CP, 2,3,4,5-tetra-CP, 2,4,5,-tri-CP, 2,4-di-CP, and 4-mono-CP). Monolayer cultures were exposed to the test compounds for 1 h, and concentration-response curves were established with respect to the effects on phase I and phase II metabolism of 7-ethoxycoumarin (7-EC) and on cellular ATP content. All CP tested inhibited the O-dealkylation of 7-EC, with half-maximum effective concentrations (EC50) ranging from about 36 microM for the three highest chlorinated phenols to 215 microM for 4-mono-CP, which proved to be least effective. The subsequent conjugation of the primary metabolite 7-hydroxycoumarin was even more sensitive towards CP exposure than the O-deethylation process. The concentrations which reduced the percentage of conjugated metabolite to 50% of the respective control cultures ranged from 7 microM for penta-CP to 48 microM for 4-mono-CP. Treatment of cultured hepatocytes with CP additionally resulted in a depletion of cellular ATP at EC50 concentrations ranging from 6 microM for penta-CP to 1330 microM for 4-mono-CP. Cellular viability, as measured by the leakage of lactate dehydrogenase from the cells, was not affected by any of the CP within the 1-h exposure period.

7-Alkoxycoumarin O-Dealkylase

Bovine spermatozoa as an in vitro model for studies on the cytotoxicity of chemicals: effects of chlorophenols.

The suitability of ejaculated bovine spermatozoa as an in vitro model for the assessment of the cytotoxic potential of chemicals was evaluated using several endpoints: swimming activity, adenine nucleotide content, membrane integrity and oxygen consumption. A series of chlorophenols inhibited sperm motion (motility and velocity) in a concentration-dependent manner. This could be determined quantitatively and reproducibly by means of videomicrography and automatic computer image analysis. The sperm immobilizing potency increased with increasing chlorination and was positively correlated with lipophilicity. Concentrations which reduced the percentage of moving sperm to 50% of controls ranged from 43 microM for pentachlorophenol (PCP) to 1440 microM for 4-monochlorophenol (4-MCP). Determinations of adenine nucleotides and percentages of viable cells revealed qualitative differences between the action of PCP and the lower chlorinated phenols. While the latter decreased the total adenine nucleotide contents and the percentage of unstained cells in parallel to motion inhibition, no such changes occurred after exposure to immobilizing concentrations of PCP. Penta-, tetra- and trichlorinated phenols stimulated cellular respiration, indicating their uncoupling activity, at concentrations lower than those necessary for motion inhibition. The results indicate that bovine spermatozoa may become a useful in vitro model for the toxicological evaluation of chemicals providing quantitative as well as qualitative data.

Adenine Nucleotides

Cultured myotubes from skeletal muscle of adult rats. Characterization and action of Anemonia sulcata toxin II.

Mononucleated myogenic cells (satellite cells) were isolated from skeletal muscle of adult rats and grown in culture. These cells replicated and, beginning with the 6th day in culture, they fused and differentiated into multinucleated myotubes, which accumulated creatine kinase and developed cross striation and spontaneous contractions. The differentiation of the excitable membrane and the action of sea anemone toxin ATX II were investigated with microelectrode techniques. Mature myotubes reached a stable membrane potential of -47.3 mV (+/- 6.5 mV) with the 11th day in culture. Action potentials could be generated in all myotubes. During maturation they became faster (increasing rate of rise) and shorter in duration. In spontaneously contracting myotubes spontaneous action potentials were recorded, which were often associated with subthreshold oscillations of membrane potential. ATX II reduced the membrane potential and prolonged the action potential duration with the lowest effective concentrations being 1 nmol/l and 0.5 nmol/l, respectively. Furthermore, ATX II induced electrical activity in quiescent myotubes. After fusion the development of the membrane electrical properties of satellite cell derived muscle cells followed essentially the same pattern as in primary cultures of embryonic myotubes. Electrophysiologically and with respect to their sensitivity to ATX II the mature myotubes resemble denervated muscle fibres.

Action Potentials

Organochlorines and mercury in blood of a fish-eating population at the River Elbe in Schleswig-Holstein, FRG.

The blood of people living near the River Elbe who eat contaminated fish from the river was checked for organochlorines (n = 136): Hexachlorobenzene, HCB, the Hexachlorocyclohexanes beta-HCH, gamma-HCH, Octachlorostyrene, OCS, p,p-DDE and Mercury, Hg (n = 43). The concentrations (ng/ml blood) of OCS (less than 0.5-9.2) and Hg (1.1-79.2) can be attributed to fish consumption, those of the organochlorines--exept gamma-HCH--are related to age.

Age Factors

A method for the isolation of the caribbean palytoxin (C-PTX) from the coelenterate (zooanthid) Palythoa caribaeorum.

Chromatographically pure toxin was isolated from the zooanthid Palythoa caribaeorum. Toxin isolation was achieved by extraction with 50% ethanol from the homogenized specimens, gel filtration on Sephadex G-50 and ion exchange chromatography on QAE- and SP-Sephadex. Final purification was obtained by gel filtration on Biogel P-6. The LD50 tested on the shore crab Carcinus maenas was 62.5 ng/kg.

Acrylamides

Quantitative structure-pharmacokinetic relationships derived on antibacterial sulfonamides in rats and its comparison to quantitative structure-activity relationships.

Quantitative structure-pharmacokinetic relationships have been derived for a series of substituted 2-sulfapyridines. Pharmacokinetic parameters, such as elimination rate constant (ke), clearance (Cl), and protein-binding constant (Kassoc), have been determined in rats. The observed variation is statistically significant, explained by changes in the lipophilic (deltaRm), electronic (pKa), and steric effects (I, ES) of the substituents. The obtained correlations are discussed with respect to the previously derived correlations for the antibacterial activity of these compounds. A scale up of the results opens up the possibility of a rational synthesis of highly active sulfonamides with special pharmacokinetic properties because lipophilicity influences strongly the pharmacokinetic properties, whereas no influence on the degree of antibacterial effect is observed. Steric substituent influence is opposite on specific binding to bacterial enzymes and unspecific binding to serum proteins.

Animals

[Chloroquine keratopathy as an example of drug-induced phospholipidosis (contribution to the pathogenesis of cornea verticillata) (author's transl)].

Chronic treatment with certain drugs induces morphological alterations in the eye which are histologically and electron microscopically identical with those found in hereditary lipidoses (cornea verticillata, e.g. in M. Fabry). Hereditary storage diseases are the consequence of enzyme defects, the mechanism underlying the side effect of certain drugs, however, is quite different. "Amphiphilic" drugs from completely different pharmacological groups, like chloroquine, amiodarone, chlorpromazine form complexes with cellular phospholipids which cannot be metabolised by lysosomal phospholipases. Thus in all tissues with high phospholipid content or turnover typical intracellular deposites with lamellary or crystalloid structure may occur (myelin figures). Such deposites were observed in different parts of the eye and are known e.g. from the cornea as "cornea verticillata".

Adrenal Glands

Drug-induced phospholipidosis. II. Alterations in the phospholipid pattern of organs from mice, rats and guinea-pigs after chronic treatment with chlorphentermine.

In three species chronic treatment with the anorectic drug chlorphentermine causes a profound alteration of the phospholipid/lipid metabolism in the organism, resulting in an increase of the fractions of phospholipids and lipids, e.g. in lungs, livers and adrenals. The results are interpreted as drug-induced generalized phospholipidosis, which is caused by amphiphilic drugs, like chlorphentermine and others. Its extent depends on several factors, like content, pattern and turnover rate of phospholipids in different organs, and on the species.

Adrenal Glands