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Structure of the toxin isolated from carp (Cyprinus carpio) bile.

Attempts were made to elucidate the structure of the toxin isolated from the bile of carp Cyprinus carpio, which is possibly responsible for carp poisoning. By fast atom bombardment (FAB) mass spectrometry, along with 1H- and 13C-NMR, a molecular formula of C27H48O8S containing a sulfate ester group was deduced. Those and other analytical data allowed us to conclude the structure of carp toxin to be 5 alpha-cholestane-3 alpha, 7 alpha, 12 alpha, 26, 27-pentol 26-sulfate, which agreed essentially with that of 5 alpha-cyprinol, an alcohol specific to carp bile, in which the sulfate ester at the C-26 position is lacking.

Animals↗

Lead levels in whole blood of an adult population group from Rome.

Pb-blood levels of 801 adult non-occupationally exposed subjects from Rome are reported. The investigation was carried out according to EEC Directive No. 77/312 with acceptable quality control of analytical data. A mean Pb-blood level of 173 micrograms/l (198 micrograms/l for males and 150 micrograms/l for females) was found; good correlations were found between Pb-blood levels and age, sex and smoking habits but no correlation was found in relation to drinking habits, residence and other variables which were examined. In the present survey all the three EEC reference levels were observed.

Adolescent↗

Radioactivity in environmental samples taken in the Sellafield, Ravenglass and Morecambe Bay areas of west Cumbria.

Seaborne sediments deposited in the estuaries of the Esk, Duddon, Leven and Kent have been analysed for fission products and actinides discharged in waste from the Sellafield processing works in west Cumbria, and the values compared with the generally expected values due to fallout from atmospheric nuclear weapons tests. Analyses of tissues from sheep grazing the marshes of these estuaries show that the internal radiation dose of the general public through eating mutton or liver from these animals would be at most a few percent of recommended limits. Analytical data are presented on the actinide content of beef cattle, and on potato crops grown under field conditions; these data show that, as with the sheep data, the radiation dose to the consumer would be small.

Animals↗

Environmental specimen banking and poisons control--a new challenge.

Today clinical toxicology and poisons control are widely lacking objective criteria, e.g., analytical data, figures of kinetics and metabolism in acute and chronic poisoning. Co-operation between clinical toxicology and an environmental specimen bank for human tissue will help to overcome many difficulties and complement one another. The possible power of such a co-operation is demonstrated by the example of the institutions in Münster, Germany. The successful strategies used for setting-up an environmental specimen bank for human tissue may also be applied in clinical toxicology and experimental toxicology. The frame of a university medical clinic seems to be the ideal basis of an effective co-operation of an Environmental Specimen Bank for Human Tissue, a Poisons Control Centre and clinical toxicology. In general a co-operation of an environmental specimen bank for human tissue and a poisons control centre will be cost-saving and beneficial to both and an environmental specimen bank for human tissue will gain the status of a unique tool for risk assessment of xenobiotics.

Animals↗

The geobiochemistry of cobalt.

In the crust of the Earth cobalt is present in a greater abundance than lead, molybdenum or cadmium. The concentration and distribution of cobalt is discussed in relation to major terrestrial, aquatic and atmospheric systems. The processes which control or influence the transfer of this element in major ecosystems are evaluated in terms of bioavailability to plants, animals and man. The concept of geochemical provinces is considered in relation to the regional availability of cobalt and then its transfer along foodchains to man. Areas and environments which contain high or low concentrations of cobalt are considered in relation to the health of plants, animals and man; the special case of exposure to cobalt from the manufacturing industry is discussed. The association between cobalt and hard metal disease is noted. The use of various radionuclides of cobalt is considered as a means of tracing cobalt through complex ecosystems. The state of the art for measuring the concentration of cobalt is discussed with special reference to the quality of analytical data and the availability of suitable reference materials.

Air↗

Fibrinolytic study in a homozygous protein C deficient patient.

The fibrinolytic system was evaluated in a patient with homozygous protein C deficiency as well as in several members of his family with a partial deficiency of this protein. Before anticoagulant therapy the patient showed skin lesions which quickly disappeared after administration of fresh plasma. After anticoagulant treatment, the propositus suffered two clinical episodes of "ecchymotic" lesions, which were controlled with fresh plasma. The patient has remained free of new lesions and other clinical episodes up to the present date. The fibrinolytic activity of both the propositus and his family was normal. The patient's father showed adequate release of tissue plasminogen activator after controlled physical exercise. According to clinical and analytical data from our patient and his family, it is suggested that, in spite of the preservation of the fibrinolytic system in this case, a localized deficiency in fibrinolysis could exist in view of the clinical behaviour of the skin lesions described.

Anticoagulants↗

Structure-activity relationship of antithrombotic polysaccharide derivatives.

Heparin has been the drug of choice in clinical pre-surgical and post-surgical prophylaxis of thrombotic events. However, because of its side-effects, such as bleeding and other disadvantages (i.e. chemical inhomogeneity and variability of its physiological activities), alternatives to heparin are an important field of research. A necessary procedure in the development of new drugs is the evaluation of structure-activity relationships. Genuine neutral polysaccharides were chemically modified and examined for their anticoagulant activities. The linear beta-1,3-glucan curdlan, an easily available bacterial polysaccharide, served as the basic polymer. It could be established that the anticoagulant activity was dependent on the degree of sulfation and the molecular weight. For heparin, the sulfation pattern, i.e. the actual location of the sulfate groups along the heparin chain, was of importance in addition to the degree of sulfation. Therefore, we investigated whether there was also a relationship between the substitution pattern of the curdlan sulfates and their anticoagulant activity. For determination of the substitution pattern of the sulfated polysaccharides, a method was developed that is based on synthesis of the partially alkylated alditol acetates of the polymer and examination of these derivatives using combined gas chromatography-mass spectrometry. In addition to the analytical data, the structure-activity relationship of anticoagulative curdlan sulfates is presented.

Animals↗

Lipids of nervous tissue: composition and metabolism.

As indicated in the Introduction, the many significant developments in the recent past in our knowledge of the lipids of the nervous system have been collated in this article. That there is a sustained interest in this field is evident from the rather long bibliography which is itself selective. Obviously, it is not possible to summarize a review in which the chemistry, distribution and metabolism of a great variety of lipids have been discussed. However, from the progress of research, some general conclusions may be drawn. The period of discovery of new lipids in the nervous system appears to be over. All the major lipid components have been discovered and a great deal is now known about their structure and metabolism. Analytical data on the lipid composition of the CNS are available for a number of species and such data on the major areas of the brain are also at hand but information on the various subregions is meagre. Such investigations may yet provide clues to the role of lipids in brain function. Compared to CNS, information on PNS is less adequate. Further research on PNS would be worthwhile as it is amenable for experimental manipulation and complex mechanisms such as myelination can be investigated in this tissue. There are reports correlating lipid constituents with the increased complexity in the organization of the nervous system during evolution. This line of investigation may prove useful. The basic aim of research on the lipids of the nervous tissue is to unravel their functional significance. Most of the hydrophobic moieties of the nervous tissue lipids are comprised of very long chain, highly unsaturated and in some cases hydroxylated residues, and recent studies have shown that each lipid class contains characteristic molecular species. Their contribution to the properties of neural membranes such as excitability remains to be elucidated. Similarly, a large proportion of the phospholipid molecules in the myelin membrane are ethanolamine plasmalogens and their importance in this membrane is not known. It is firmly established that phosphatidylinositol and possibly polyphosphoinositides are involved with events at the synapse during impulse propagation, but their precise role in molecular terms is not clear. Gangliosides, with their structural complexity and amphipathic nature, have been implicated in a number of biological events which include cellular recognition and acting as adjuncts at receptor sites. More recently, growth promoting and neuritogenic functions have been ascribed to gangliosides. These interesting properties of gangliosides wIll undoubtedly attract greater attention in the future.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Genotoxic, carcinogenic, and teratogenic hazards in the marine environment, with special reference to the Mediterranean Sea.

Genotoxic, carcinogenic, and teratogenic hazards arising out of pollution in the marine environment are discussed in this article, with special reference to the situation in the Mediterranean area. A number of chemical compounds or complex mixtures relevant to marine pollution, either natural or of anthropogenic origin, are tentatively listed, along with protective factors which may play a counteracting role in the same environment. Harmful substances tend to undergo interactions and transformations in seawater, sediments, and marine biota, due to physical, chemical, microbial, or light-mediated mechanisms. Bioaccumulation phenomena in marine organisms may result from food-chain biomagnification processes or from concentration of pollutants by filter feeders. A variety of sources can account for marine pollution by genotoxic, carcinogenic, and teratogenic compounds, but there is a relative paucity of analytical data concerning the Mediterranean. Metabolic transformations of xenobiotics occur in all marine organisms, the biochemical mechanisms in fish being comparable to those which have been extensively investigated in mammals. Induction of metabolic pathways, and especially of the mixed-function oxygenase system, represents the earliest warning signal of exposure to pollutants. Occurrence of neoplastic diseases is documented by experimental and field studies in marine vertebrates as well as in invertebrates. The association with local pollution phenomena has been recognized in several studies, but other etiopathogenetic factors may be also involved, and in some cases tumors have been reported to be unrelated to chemical pollution. Genotoxic agents have been detected by means of suitable techniques in seawater, sediments, and marine organisms. Several studies have investigated the presence of carcinogen-DNA adducts, DNA damage and repair processes, and cytogenetic alterations, such as chromosomal aberrations, sister-chromatid exchanges, and micronuclei, in tissues of marine organisms. However, monitoring of these end-points under field conditions encounters some limitations and problems. Even more fragmentary is the information on teratogenic effects in marine organisms, although interesting test systems have been set up. On the whole, a quite extensive database on all these toxicological issues is already available in the literature, but further studies are warranted for an adequate assessment of genotoxic, carcinogenic, and teratogenic hazards, and possibly counteracting factors in the marine environment, and specifically in the Mediterranean Sea.

Animals↗

The treatment validity of DSM-III melancholic subtyping.

Because melancholic subtyping is associated with pretreatment symptom severity, the type of data-analytic technique used in examining treatment validity may affect one's conclusions. We examined the relationship between the presence or absence of melancholia and the response to electroconvulsive therapy (ECT) in 87 depressed inpatients. Depending on the definition of improvement used, melancholic subtyping was either not associated with ECT response, or non-melancholics had a better outcome than melancholics. We suggest that standard methods of outcome evaluation be required in therapy outcome studies.

Adult↗

Oscillations in coupled enzymic reactions at high concentration of enzyme.

The transient-state kinetic consequences of the coupling of a single-enzyme reaction to other metabolic reactions have been examined in generalized terms. Analytical data are presented which specify under what conditions such coupling may lead to an oscillatory transient rate behaviour of a reaction system involving an enzyme operating by a Michaelian mechanism. The results indicate that the presence of enzyme in concentrations comparable to those of substrate and product may represent a hitherto unforeseen possible source of weakly damped, or even sustained, oscillations in metabolic networks. This observation has some important implications with regard to the occurrence of oscillations in biochemical reaction systems and to transient-state kinetic modelling of metabolic systems.

Enzyme Activation↗

Antinociceptive and other opioid effects of a new series of dermorphin analogues after subcutaneous administration in the rat.

A series of hepta-, hexa-, penta- and tetrapeptide analogues of dermorphin have been evaluated in the rat for antinociceptive activity after subcutaneous (SC) administration at the screening dose of 4 mg/kg. Effective doses (ED50) were calculated for the most active compounds. Presence of spontaneous movements, defecation, micturition and corneal reflex were also recorded. Syntheses and analytical data of new derivatives are briefly reported.

Amino Acid Sequence↗

Concentration levels of 2,4-D and 2,4,5-T in forensic material.

Concentration levels, of 2,4-D and 2,4,5-t in blood and viscera in a case of fatal intoxication with "Tributon" are given. Since the toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-t), widely used as herbicides in domestic and agricultural situations is very low, little information exists on human toxicology and particularly on analytical data in forensic material in cases of fatal poisoning. The reason of this paper is to provide further information on the concentration levels of these compounds in viscera in cases of fatal, accidentally or suicidal, poisoning.

2,4,5-Trichlorophenoxyacetic Acid↗

Ethnographic methodologic assessment of pain perceptions by verbal description.

This study was designed to use known anthropologic methods to gather and analyze qualitative data about verbal descriptors of pain among 25 Chinese, and 60 Western subjects (25 Anglo-Americans and 35 Scandinavians). The sample consisted of 54 patients and 31 dentists. Key pain descriptors from each cultural context were selected for construction of pain assessment instruments which allowed multidimensional statistical techniques to translate these data into cross-cultural quantitative indices. Results revealed dimensions of pain which were universal in all cultures examined. These included time, intensity, location, quality, cause and curability. More culture-specific dimensions included the Chinese concept suantong, a multidimensional concept of bone, muscle, joint, tooth and gingival pain. 'Real' and 'imagined' pains were contrasts described by Western subjects, especially dentists; 'imagined pain' being the conversion of fear or anxiety into perceived pain. These data indicate that the data gathering and data analytic methods were reliable and sensitive to cultural variables and that ethnicity played a stronger role in determining perceptions of pain description than professional socialization for this population sample of Chinese and Western subjects.

Adult↗

Synthesis of a fluorogenic mucopolysaccharide by chondrocytes in cell culture with 4-methylumbelliferyl beta-D-xyloside.

Culture of chondrocytes in the presence of 4-methylumbelliferyl beta-D-xyloside resulted in a synthesis of protein-free, fluorogenic chondroitin sulfate which was heterogeneous on DEAE-cellulose chromatography. Degradation of the major chromatographic fraction with chondroitinase-ABC yielded, in addition to a large quantity of delta4-glucuronic acid-containing disaccharides, two fluorogenic oligosaccharides of different size. Quantitative analysis showed that delta4-glucuronic acid, galactose, xylose, and 4-methylumbelliferone were present in the small oligosaccharide fragment in a molar ratio of 1:2:1:1. Since these analytical data are analogous to those reported for glycopeptides derivedfrom proteochondroitin sulfates, it may be suggested that 4-methyl-umbelliferyl beta-D-xyloside replaces the need for xylosyl protein core in the normal synthesis of proteochondroitin sulfate with a resultant production of the unusual polysaccharide bearing the added xyloside at the reducing end.

Animals↗

Structures of the asparagine-linked sugar chains of laminin.

This investigation describes the isolation and characterization of oligosaccharides of the basement membrane glycoprotein, laminin. Pronase-released glycopeptides of isolated laminin, from a mouse Engelbreth-Holm-Swarm tumor, were fractionated using a combination of gel permeation chromatography and Con A-Sepharose affinity chromatography. The glycopeptides were analyzed for sugar linkage patterns by methylation analysis. Glycopeptides and hydrazine-released oligosaccharides were further analyzed using endo-beta-galactosidase, endo-beta-N-acetylglucosaminidase H and specific exoglycosidases in conjunction with calibrated gel permeation chromatography. Based on these experiments, murine tumor laminin was shown to contain asparagine-linked oligosaccharides with the following structures: bi-, tri- and tetraantennary complex-type oligosaccharides; polylactosaminyl side chains containing Gal(beta 1----4)GlcNAc(beta 1----3) repeating units attached to the trimannose core portion of the bi-, tri- and tetraantennary complex-type oligosaccharides; unusual complex-type oligosaccharides terminated at the nonreducing end with sialic acid, alpha-galactose, beta-galactose and beta-N-acetylglucosamine; alpha-galactosyl residues linked to N-acetyllactosamine sequences; high-mannose-type oligosaccharides. These results, in conjunction with analytical data, indicate that most of the carbohydrate of this laminin is N-linked to asparagine and that there are about 43 such N-linked oligosaccharides per laminin molecule.

Animals↗

The density and free water of cholinergic synaptic vesicles as a function of osmotic pressure.

Synaptic vesicles from the cholinergic electromotor nerve terminals of Torpedo marmorata are among the most uniform subcellular organelles known and are osmotically sensitive. Changes in density accompanying osmotic perturbation have enabled changes in water content to be calculated; when referred to a standard state of known volume and water content, fractional and absolute water contents could be calculated for the perturbed states and compared with the fractional free water content as measured by the glycerol space. Under hyperosmotic conditions, discrepancies were found between these two estimates, the glycerol space falling more rapidly than the water space predicted from the density change. This is attributed to a failure of glycerol to displace water imbibed by the membrane as it collapses round an aqueous core of decreasing volume. 'Reserve' vesicles obeyed a relationship between density, osmotic load and osmolality derived for a perfect osmometer, and independent estimates of fractional free water content under standard conditions and osmotic load were made. The former of these agreed well with the glycerol space under standard conditions and the latter agreed with previous estimates of the osmotic load using morphological and analytical data and an assumed activity coefficient of 0.65. Finally, it was possible to model the interconversion of reserve and recycling vesicles more accurately than in previous work.

Acetylcholine↗

Sulfation in vitro of mucus glycoprotein by submandibular salivary gland: effects of prostaglandin and acetylsalicylic acid.

Enzymatic sulfation of mucus glycoprotein by rat submandibular salivary gland and the effect of prostaglandin and acetylsalicylic acid on this process were investigated in vitro. The sulfotransferase enzyme which catalyzes the transfer of sulfate ester group from 3'-phosphoadenosine-5'-phosphosulfate to submandibular gland mucus glycoprotein has been located in the detergent extracts of Golgi-rich membrane fraction of the gland. Optimum enzyme activity was obtained at pH 6.8 with 0.5% Triton X-100, 25 mM NaF and 4 mM MgCl2, using the desulfated glycoprotein. The enzyme was also capable of sulfation of the intact mucus glycoprotein, but the acceptor capacity of such glycoprotein was 68% lower. The apparent Km of the submandibular gland sulfotransferase for salivary mucus glycoprotein was 11.1 microM. The 35S-labeled glycoprotein product of the enzyme reaction gave in CsCl density gradient a 35S-labeled peak which coincided with that of the glycoprotein. This glycoprotein upon reductive beta-elimination yielded several acidic 35S-labeled oligosaccharide alditols which accounted for 75% of the 35S-labeled glycoprotein label. Based on the analytical data, the two most abundant oligosaccharides were identified as sulfated tri- and pentasaccharides. The submandibular gland sulfotransferase activity was stimulated by 16,16-dimethyl prostaglandin E2 and inhibited by acetylsalicylic acid. The rate of enhancement of the glycoprotein sulfation was proportional to the concentration of prostaglandin up to 2.10(-5) M, at which point a 31% increase in sulfation was attained. The inhibition of the glycoprotein sulfation by acetylsalicylic acid was proportional to the drug concentration up to 2.5.10(-4) M at which concentration a 48% reduction in the sulfotransferase activity occurred. The apparent Ki value for sulfation of salivary mucus glycoprotein in presence of acetylsalicylic acid was 58.9 microM. The results suggest that prostaglandins may play a role in salivary mucin sulfation and that this process is sensitive to such nonsteroidal anti-inflammatory agents as acetylsalicylic acid.

16,16-Dimethylprostaglandin E2↗