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Biomedical subjects

O Wassermann

Publications and source records attributed to O Wassermann.

At least 19 recordsLinked to original sources

[Regional distribution of stomach and colon cancer mortality in the Dithmarschen and Nordfriesland districts--cartographic presentation].

In two counties (Dithmarschen and Nordfriesland) of the Federal State of Schleswig-Holstein (in the northern part of Germany) the cancer mortality rates, especially those of stomach and colon cancer, were evaluated for the time period 1980-1991. For this purpose the corresponding death certificates collected in these counties were analysed. The counties were subdivided into 16 and 17 smaller areas, respectively. The age-adjusted mortality rates were calculated and the obtained data scaled into eight sections, which were graphically mapped over the smaller areas of the two counties. The frequency of these cancer mortality rates reflects a wide range of distribution pattern in the smaller areas of the two counties, which greatly differ from the cancer mortality values calculated for the two counties as a whole. In comparison with the frequency of stomach cancer mortality for men published in the German Cancer Atlas in 1984 it could be demonstrated that this cancer mortality further decreased in these counties. However, in some smaller areas of these counties, especially in rural areas, the mortality rates of stomach cancer in men were still rather high. The opposite seems to be reflected regarding the frequency of colon cancer mortality. Here higher frequencies of mortality were seen in the small cities of these counties. We suggest that a more subtile cancer mortality mapping can be performed easily without any risk of hurting the requirements of personal data securities, because cancer mortality data are already continuously evaluated by a trained staff at the offices of statistical affairs. These data may be transferred and used for cancer mortality mapping as described in the present paper. In order to guarantee that there will be no violation of personal data secrecy the cancer mortality mapping must be restricted to cancer sites with high frequencies of mortality. All published data should be supervised by an official with special knowledge of the requirements of personal data protection. This study underlines the necessity for higher resolution (smaller areas) in cancer registries as essential prerequisite for systematical exploration of the origins of cancer mortality and as a basis for preventive measures.

Colonic Neoplasms

[Public health risk caused by emissions from refuse incinerators].

An irresponsible "approval on request" in favour of waste incineration written by a consulting committee of the German Federal Board of Physicians has meanwhile been widely distributed both nationally and internationally. The aim of this politically motivated paper is to dramatically increase the present number of 49 waste incinerators in Germany. It is our duty to warn of this intention. Health problems are known to exist both in workers at waste incinerators and in humans living in their vicinity. Furthermore, in the long run negative impact also to ecosystems should be expected from the emissions. Health problems in patients living downwind of waste incinerators repeatedly have been reported on by physicians. "Lack of statistical significance", often used as counter-argument, is only due to absence of funding of comprehensive epidemiological studies in Germany. Analyses of soil samples reveal the pollution from waste incineration. Considering the pre-load of the region, additional emissions caused by waste incineration and other sources have to be assessed. The application of preventive limit values is imperative. The presently used "limit values", being about 100 times too high, bear an unacceptable risk. Therefore, reliable regional registers of emissions have to be established immediately. Limit values continuously have to be adjusted to the progress of scientific knowledge. In this respect it is imperative to consider that the actual composition of emissions is unknown; isolated risk assessment of single compounds underestimates the total risk; the negative impact, e.g. of dioxins, on both the immune and hormone systems occurs at concentrations 100 times lower than those causing carcinogenic effects; the assumption of "threshold values" is obsolete; a considerable lack of knowledge exists about accumulation in food webs and in ecosystems; the demand of preservation of natural, geogenic situations is indispensable in assessments of soil and water pollution. Essential prerequisites for risk assessments of emissions from waste incineration are 1. actual, continual and comprehensive qualitative and quantitative analytical knowledge of the composition of emissions; 2. region-specific meteorologic dispersion models of the emissions; 3. evaluation of the complex mixtures in emissions for their kinetics in and toxicity for ecosystems and humans. Neither of these demands is so far fulfilled. Facing these problems, the present propagation of waste incineration must be stopped. As an alternative, efforts to optimize waste-avoiding and recycling concepts considerably have to be reinforced, and low-risk procedures, like compost and other decomposing methods, hydrogenation or freeze-griding of plastics, have to be widely promoted.

Air Pollution

A new procedure for the isolation of anti-HIV compounds (polysaccharides and polyphenols) from the marine alga Fucus vesiculosus.

Anti-HIV-active polysaccharides and polyphenols were isolated from the brown seaweed Fucus vesiculosus by hot H2O extraction of both the intact and the homogenized algae. This was followed by XAD2 chromatography and by sequential precipitation of the non-adsorbed compounds with glacial HOAc and thereafter with EtOH. The precipitate was solubilized, dialyzed against distilled H2O, and chromatographed on SP-Sephadex C25 and on QAE-Sephadex A25. This was followed by gel filtration on Sephadex G50 and Sephadex G100 and finally by hplc on a Shodex Ionpak S-804 column. For comparison, the commercial product fucoidan, a sulfated algal polysaccharide, was also further purified by the chromatographic techniques mentioned above. The isolated freeze-dried fractions obtained by these procedures were tested for inhibition of both HIV-induced syncytium formation and HIV reverse transcriptase enzyme activity. Some of these fractions inhibited both of these activities at concentrations that were not cytotoxic.

Antiviral Agents

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