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A Gard

Publications and source records attributed to A Gard.

8 recordsLinked to original sources

The skin allergenic properties of chemicals may depend on contaminants--evidence from studies on coumarin.

BACKGROUND/AIMS: Positive patch tests are considered representative of a contact allergy to the tested chemical. However, contaminants and derivatives rather than the suspected chemical itself could be responsible for the allergic skin reactions. Here, we tested the importance of contaminants in the sensitizing and allergenic properties of coumarin in mice and humans. Coumarin, an ingredient in cosmetics and fragrances, was chosen as the reference chemical since conflicting results have been obtained regarding its ability to induce contact allergy. In some chemical preparations, this could be explained by the presence of coumarin derivatives endowed with allergenic properties. METHODS: In mice, three different coumarin preparations were tested in the local lymph node assay. In humans, we assessed the irritant and allergenic properties of highly pure coumarin in nonallergic and fragrance-allergic patients. RESULTS: Pure coumarin did not exhibit irritant or sensitizing properties in the local lymph node assay. In contrast, two other commercially available coumarins and three contaminants that were detected in these coumarin preparations were identified as weak and moderate sensitizers, respectively. In humans, pure coumarin was extremely well tolerated since only 1 out of 512 patients exhibited a positive patch test to the chemical. CONCLUSIONS: These results indicate that coumarin cannot be considered as a common contact allergen and further emphasize that purity of chemicals is mandatory for the assessment of their allergenicity.

Adult↗

1,2,4-trichlorobenzene marine risk assessment with special emphasis on the Osparcom region North Sea.

A risk assessment on 1,2,4-trichlorobenzene was carried out specifically for the marine environment according to the methodology laid down in the EU Risk Assessment Regulation 1488/94 and the Guidance Documents of the EU Existing Substances Regulation 793/93. The study consists of the collection and evaluation of data on effects and environmental concentrations from analytical monitoring programs in large rivers and estuaries in the North Sea area. The risk is indicated by comparing the predicted environmental concentration (PEC) with the predicted no-effect concentrations (PNEC) for the marine aquatic environment. A PNECwater) value of 0.3 microg/l and a PNECsed value of 38 microg/kgdw were derived from the results of toxicological studies in organisms representing three trophic levels, i.e. aquatic plants, invertebrates and fish. Based on monitoring data two situations are distinguished: a typical case and a worst case with a PECwater of <0.047 and 0.1 microg/l, respectively, and a PECsed of 40 and 90 microg/kgdw, respectively. The calculated PEC/PNEC ratios were 0.16 and 0.3 for water and 1 and 2.4 for sediment, respectively. It was concluded that no risks are expected for aquatic organisms. Based on the combination of worst-case assumptions risks to benthic organisms could not be fully excluded, but since all open uses of 1,2,4-trichlorobenzene will be ended following the EU risk assessment outcome of 2001 any potential risk is expected to be reduced accordingly. 1,2,4-trichlorobenzene is not considered toxic according to the EU criteria and the available data on persistence of 1,2,4-trichlorobenzene indicate a half-life in water of a few days and a significant biodegradation potential. The bioaccumulation potential is low to moderate with most BCF ratios for fish ranging from 600 to 1400 and one highest of 2020. Based on an extensive evaluation of persistence, biodegradation and bioaccumulation data it is concluded that 1,2,4-trichlorobenzene is not a PBT, since it does not fulfill any of the EU criteria. Biomagnification in the food chain is not expected due to the relatively high elimination rate constants.

Animals↗

Conservation of topology, but not conformation, of the proteolipid proteins of the myelin sheath.

The proteolipid protein gene products DM-20 and PLP are adhesive intrinsic membrane proteins that make up >/=50% of the protein in myelin and serve to stabilize compact myelin sheaths at the extracellular surfaces of apposed membrane lamellae. To identify which domains of DM-20 and PLP are positioned topologically in the extracellular space to participate in adhesion, we engineered N-glycosylation consensus sites into the hydrophilic segments and determined the extent of glycosylation. In addition, we assessed the presence of two translocation stop-transfer signals and, finally, mapped the extracellular and cytoplasmic dispositions of four antibody epitopes. We find that the topologies of DM-20 and PLP are identical, with both proteins possessing four transmembrane domains and N and C termini exposed to the cytoplasm. Consistent with this notion, DM-20 and PLP contain within their N- and C-terminal halves independent stop-transfer signals for insertion into the bilayer of the rough endoplasmic reticulum during de novo synthesis. Surprisingly, the conformation (as opposed to topology) of DM-20 and PLP may differ, which has been inferred from the divergent effects that many missense mutations have on the intracellular trafficking of these two isoforms. The 35 amino acid cytoplasmic peptide in PLP, which distinguishes this protein from DM-20, imparts a sensitivity to mutations in extracellular domains. This peptide may normally function during myelinogenesis to detect conformational changes originating across the bilayer from extracellular PLP interactions in trans and trigger intracellular events such as membrane compaction in the cytoplasmic compartment.

Antibodies, Monoclonal↗

[Multiple sclerosis--the great imitator!].

Multiple sclerosis (MS) is traditionally a clinical diagnosis based on relapsing and remitting multifocal CNS symptoms. In recent years new diagnostic tools such as cerebrospinal fluid analysis, magnetic resonance imaging and evoked potential testing have been developed. This article reviews diagnostic difficulties and discusses other medical conditions that can be mistaken for MS due to similar clinical, laboratory or radiological findings.

Central Nervous System Diseases↗