Mutagenicity of derivatives of the flame retardant tris(2,3-dibromopropyl) phosphate: halogenated propanols.

The sensitivity of larval populations of Drosophila melanogaster to the lethal action of methyl methanesulfonate (MMS) was determined. Wild-type strains were compared with strains carrying X-linked mutations that increase mutagen sensitivity. The determination of dose—response relationships for MMS-induced lethality allowed for a quantitative comparison of the MMS sensitivity of the mutants. The sensitivity difference, measured by the LD-50 values, between the most resistant and the most sensitive stock used in this study was 40-fold. Stocks containing mutations in the meiotic genes mei-41 and mei-9 were by far the most sensitive ones. These mutants are known to be repair-deficient.The meiotic mutants were tested in various stocks with different genetic backgrounds. It turned out that the larval MMS sensitivity strongly depended on the genotype of the parental females used to obtain the larval populations for MMS treatment. These maternal effects were not simulated by an age-dependent variation in MMS sensitivity because no differences in developmental time between the strains with different genetic constitution were found. Furthermore, a maternal effect on the relative frequency of spontaneous lethality of genetically identical mutant progeny derived from different types of female was demonstrated.These maternal effects, both on spontaneous lethality and on larval MMS sensitivity, are of interest because they extend beyond the embryonic stages of development.     

Ethanol Causes Protein Precipitation—New Safety Issues for Catheter Locking Techniques

Objective

The ethanol lock technique has shown great potential to eradicate organisms in biofilms and to treat or prevent central venous catheter related infections. Following instillation of ethanol lock solution, however, the inherent density gradient between blood and ethanol causes gravity induced seepage of ethanol out of the catheter and blood influx into the catheter. Plasma proteins so are exposed to highly concentrated ethanol, which is a classic agent for protein precipitation. We aimed to investigate the precipitating effect of ethanol locks on plasma proteins as a possible cause for reported catheter occlusions.

Methods

Plasma samples were exposed in-vitro to ethanol (concentrations ranging from 7 to 70 v/v%) and heparin lock solutions. In catheter studies designed to mimic different in-vivo situations, the catheter tip was placed in a plasma reservoir and the material contained within the catheter was analyzed after ethanol lock instillation. The samples underwent standardized investigation for protein precipitation.

Results

Protein precipitation was observed in plasma samples containing ethanol solutions above a concentration of 28%, as well as in material retrieved from vertically positioned femoral catheters and jugular (subclavian) catheters simulating recumbent or head down tilt body positions. Precipitates could not be re-dissolved by dilution with plasma, urokinase or alteplase. Plasma samples containing heparin lock solutions showed no signs of precipitation.

Conclusions

Our in-vitro results demonstrate that ethanol locks may be associated with plasma protein precipitation in central venous catheters. This phenomenon could be related to occlusion of vascular access devices locked with ethanol, as has been reported. Concerns should be raised regarding possible complications upon injection or spontaneous gravity induced leakage of such irreversibly precipitated protein particles into the systemic circulation. We suggest limiting the maximum advisable concentration of ethanol to 28 v/v% in catheter lock solutions.     

Die Esche (Fraxinus excelsior) auf den Bergen des Wienerwaldes

Ohne Zusammenfassung     

Varroa-tolerant Italian honey bees introduced from Brazil were not more efficient in defending themselves against the mite Varroa destructor than Carniolan bees in Germany

In Europe and North America honey bees cannot be kept without chemical treatments against Varroa destructor. Nevertheless, in Brazil an isolated population of Italian honey bees has been kept on an island since 1984 without treatment against this mite. The infestation rates in these colonies have decreased over the years. We looked for possible varroa-tolerance factors in six Italian honey bee colonies prepared with queens from this Brazilian island population, compared to six Carniolan colonies, both tested at the same site in Germany. One such factor was the percentage of damaged mites in the colony debris, which has been reported as an indicator of colony tolerance to varroa. A mean of 35.8% of the varroa mites collected from the bottoms of the Italian bee colonies were found damaged, among which 19.1% were still alive. A significantly greater proportion of damaged mites were found in the Carniolan bees (42.3%) and 22.5% were collected alive. The most frequent kind of damage found was damaged legs alone, affecting 47.4% of the mites collected from debris in Italian bees, which was similar to the amount found in Carniolan colonies (46%). The mean infestation rate by the varroa mite in the worker brood cells in the Italian bee colonies was 3.9% in June and 3.5% in July, and in drone brood cells it was 19.3% in June. In the Carniolan honey bee colonies the mean infestation rates in worker brood cells were 3.0 and 6.7%, respectively in the months of June and July and 19.7% in drone brood cells in June. In conclusion, the 'Varroa-tolerant' Italian honey bees introduced from Brazil produced lower percentages of damaged mites (Varroa destructor) in hive debris and had similar brood infestation rates when compared to 'susceptible' Carniolan bees in Germany. In spite of the apparent adaptation of this population of Italian bees in Brazil, we found no indication of superiority of these bees when we examined the proportions of damaged mites and the varroa-infestation rates, compared to Carniloan bees kept in the same apiary in Germany.     

Transmission disequilibrium and sequence variants at the leptin receptor gene in extremely obese German children and adolescents

Genetic determinants of the degree of obesity and body fat distribution have been demonstrated by family studies. The heritability has been estimated to be in the range 0.2–0.7. Mutation leading to obesity in humans has been described for only two genes, one of them the leptin gene. The leptin gene codes for a cytokine secreted by fat cells that binds to the leptin receptor (Lep-R), which exerts some of its biological functions by expression in the brain. Hence, the Lep-R gene appears to be a promising candidate for the determination of obesity in humans. We isolated genomic DNA clones from the Lep-R gene region and identified a new polymorphic microsatellite marker (OBR-CA) within 80 kb of the translation start of Lep-R. We genotyped this and a second, intragenic microsatellite marker (D1S2852) in 130 nuclear families consisting of extremely obese children and adolescents and both parents. Using the most frequent parental allele of both markers, our analysis revealed a significant transmission disequilibrium for the 266-bp allele of D1S2852 (corrected P-value=0.042). No significant result was obtained with the most frequent allele of OBR-CA (corrected P-value=1.0). However, two rare alleles showed transmission disequilibrium and were subsequently used for constructing a haplotype with the 266-bp allele. This haplotype had a transmission rate of 80% (nominal P-value=0.02). In order to identify the underlying mutation, we sequenced all coding exons of Lep-R and the partially overlapping gene encoding the obese receptor gene-related protein (ob-rgrp) in individuals carrying this haplotype. We found one new mutation (Ser675Thr) in the Lep-R gene in one proband and several other mutations known to be not associated with obesity in other study groups. As this new mutation cannot explain our positive linkage result, the transmission disequilibrium of the 266-bp allele and the high transmission rate of the identified haplotype point towards a mutation in close proximity to marker D1S2852. Received: 9 March 1998 / Accepted: 17 July 1998     

Structural basis of the genotoxicity of nitrosatable phenols and derivatives present in smoked food products

The CASE methodology for studying structure-activity relationships has been applied to investigating the basis of the genotoxicity of phenols and derivatives following exposure to nitrous acid. The structural features identified include availability of positions para or ortho to the hydroxyl groups, that one meta position must remain unoccupied and one ortho or para position must be unsubstituted as well. The analyses revealed that genotoxicity is dependent upon the ease of formation of the active phenyldiazonium intermediate and is influenced only secondarily by the nature of the genotoxicant or its ease of entry into the cell. With this data base, CASE predicts the genotoxicity, following nitrosation, of a number of agents, including serotonin, acetaminophen, and of some naturally-occurring pesticides present in edible plants.