Lithium-induced Clock Gene Expression in Lymphoblastoid Cells of Bipolar Affective Patients.

INTRODUCTION: Disturbances of circadian rhythms occur in all episodes of bipolar disorder (BD). Lithium, as gold-standard in the maintenance treatment of BD, is known to influence circadian processes. METHODS: In a pilot study lymphoblastoid cell lines (LCLs) were generated from 8 BD patients and 6 healthy controls. The LCLs were treated with lithiumchloride (LiCl) for 3 weeks. Cell cycles were then synchronized and expressional analysis by quantitative Real Time PCR was done. RESULTS: BD and controls differed in the period length regarding DBP (albumin D-box binding protein) expression and DBP expression was also influenced by lithium treatment. Furthermore, baseline DBP expression was significantly different between non-treated BD and healthy controls. None of the other analyzed circadian genes showed to be influenced by chronic lithium treatment or to be differentially regulated due to the diagnosis. DISCUSSION: We here show that chronic lithium treatment of LCLs leads to decreased expression of the clock gene DBP, rendering DBP a lithium-regulated gene. We could confirm the role of the circadian clock as well in lithium mode of action as in the pathomechanisms of BD although future studies with a greater number of participants and cell lines are needed.

Trichloroacetic acid as additional factor contributing to desertification in southern Africa.

There has been an accelerated expansion of deserts in the past five decades. Recent data reveal that the atmogenically formed organic compound, trichloroacetic acid (TCA) is a contributory factor in addition to anthropogenic and natural sources. The aim of this study was to use TCA as an indicator for the possible occurrence of C2-chloroacetic acids; to assess the burden on the vegetation by using pine needles as a bio-indicator system and to deliberate on the possible role of TCA in the dynamics of the vegetation in southern Africa. Field experiments conducted on pine trees and on C3 and C4 crop plants under controlled laboratory conditions, have revealed that plants could be influenced positively or negatively by TCA. To obtain an integrated assessment of the pollution emission over a time span of at least one year, two-year-old pine needles of different Pinus species were used as a bio-indicator for TCA pollution at different measuring sites. The data of our investigation clearly indicate that areas exist in South Africa where the vegetation is burdened by ecotoxicologically relevant TCA contents comparable to those in central Europe and southern Russia where TCA was shown to play a role in the destabilisation of the steppe vegetation.

High extraction efficiency for POPs in real contaminated soil samples using accelerated solvent extraction

Systematic investigations were performed to study the dependence of the extraction efficiency of persistent organic pollutants (POPs), including chlorobenzenes, HCH isomers, DDX, PCB congeners, and PAHs, on the accelerated solvent extraction (ASE) operating variables solvent and temperature. Mixed soil samples from two locations with considerable differences in soil properties and contamination in the Leipzig-Halle region (Germany) were used. The objective was to optimize ASE for the extraction of POPs from real soil samples and to improve on the results achieved with Soxhlet extraction (SOX). Solvents with differing polarities were tested. Quadruple and triple determinations were performed on the two soils, respectively, between 20 and 180 degrees C in 20 degrees C steps. All the results were compared with those obtained by SOX, as well as, in some cases during preliminary studies, by ultrasonic extraction (USE). In ASE, the optimum conditions proved to be two extraction steps at 80 and 140 degrees C (average RSD 10.7%) with three static cycles (extraction time 35 min) using toluene as solvent and at a pressure of 15 MPa. Owing to the superior analyte/matrix separation by ASE, in many cases for real soil samples analytical values better by up to 1 order of magnitude or even more were obtained compared to SOX results.

Ecotoxicological hazard and risk assessment of heavy metal contents in agricultural soils of central Germany.

Heavy metal content of agricultural topsoils has been experimentally determined at 14 areas in the German Leipzig-Halle-Bitterfeld region covering ca. 3700 km2. For most of the locations and elements, the contamination levels are comparable to those of other agricultural sites in Germany and Europe. Application of a sequential extraction technique revealed relatively low contamination levels in the mobile fractions, which indicates a correspondingly low degree of bioavailability of the heavy metals under the current milieu conditions. In contrast, acidification of the soil due to a drastic decrease in the deposition of calciferous fly ash would lead to a significantly increased ecotoxicological hazard potential, as is analyzed by a probabilistic distribution method that quantifies the overlap of normalized exposure and effect data. The discussion includes recommendations for further improvement of risk assessment schemes addressing soil contamination.

Economic upheaval in 1990-93 and the ecological situation in central Germany.

German reunification in 1990 resulted in economic and social upheavals in all of the newly-formed German states. One typical example is the Leipzig-Halle-Bitterfeld region, where many of the industrial plants were fully or partly demolished for economic and technical reasons. Additionally, changes in the political climate led to the closure of a number of major military bases. Despite generally improved environmental standards, dismantling was sometimes accompanied by substantial emissions of chlorinated insecticides and other persistent organic pollutants, as is highlighted for the first time in the present paper. Our analyses are based on a regional biomonitoring net covering 7500 km2 in the Leipzig-Halle-Bitterfeld area during the time period 1990-93. The results enable increased concentrations of airborne contaminants to be attributed to processes linked to the economic upheaval of this time.

Anthropogenic impacts on natural nitrogen isotope variations in Pinus sylvestris stands in an industrially polluted area.

Natural variations of the nitrogen isotopes 15N/14N (delta15N values) and the N concentrations of one-year-old needles from 7-12-year-old pine trees (Pinus sylvestris L.) were determined on 27 sites in the heavily polluted Leipzig-Halle region (former GDR). At three selected sites measurements were repeated over a period of 2 years. N concentrations and delta15N values in different needle age classes were compared at the three sites. The delta15N values of the N in the humus layer and the potential plant available N in the A(h) horizon of the local soil were determined. The 15N/14N isotope ratios (delta15N values) of one-year-old pine needles in the region of Leipzig-Halle were found to vary depending on their specific location by a factor of up to one order of magnitude (-9.6 per thousand to + 0.4 per thousand ). N concentrations in one-year-old pine needles varied between 0.71 and 1.38 mmol eq N g dw(-1). Pine stands with positive or slightly negative delta15N values and high N concentrations in one-year-old needles were concentrated around the cities of Leipzig and Halle and in the industrial areas. More negative delta15N values and lower N concentrations in one-year-old pine needles were found on sites at greater distances from the industrial agglomerations, mainly in the NE forested part. Site specific differences in the delta15N values of the N in the humus layer from three selected sites were similar to those found for the needles. No site specific differences, however, were found for the delta15N values of the water soluble nitrogen fraction from the mineral soil horizons of the same sites.

Activity of organophosphorus insecticides in bacterial tests for mutagenicity and DNA repair--direct alkylation versus metabolic activation and breakdown. II. O,O-dimethyl-O-(1,2-dibromo-2,2-dichloroethyl)-phosphate and two O-ether derivatives of trichlorfon.

The following organophosphates were tested for their ability to induce DNA damage in a rec-type repair test with Proteus mirabilis strains PG713 (rec- hcr-) and PG273 (wild-type) and point mutations in the his- strain TA100 of Salmonella typhimurium: O,O-dimethyl-O-(1,2-dibromo-2,2-dichloroethyl)-phosphate (NALED); trichlorfon-O-methyl ether (TCP-O-ME), O,O-dimethyl-(1-methoxy-2,2,2-trichlorethyl)-phosphonate; trichlorfon-O-methyl ether vinyl derivative (TCP-O-MEVD), O,O-dimethyl-(1-methoxy-2,2-dichlorovinyl)-phosphonate. All compounds were negative in the repair test but induced base pair substitutions in S. typhimurium. The mutagenicity of NALED is due to the direct alkylating ability of the parental molecule and to mutagenic metabolites generated by enzymatic splitting of the side chain. Glutathion-dependent enzymes in the S9-mix eliminate the mutagenic activity of NALED completely. Mutation induction by TCP-O-ME and TCP-O-MEVD is predominantly caused by the reactive O-methyl ether configuration of the side chain and is resistant to metabolic inactivation by NADPH- or glutathion-dependent enzymatic pathways in the S9-mix of mice.

Activity of organophosphorus insecticides in bacterial tests for mutagenicity and DNA repair--direct alkylation vs. metabolic activation and breakdown. I. Butonate, vinylbutonate, trichlorfon, dichlorvos, demethyl dichlorvos and demethyl vinylbutonate.

The following organophosphates were tested for their ability to induce DNA damage in a rec-type repair test with Proteus mirabilis strains PG713 (rec- hcr-) and PG273 (wild type) and point mutations in his- strain TA100 of Salmonella typhimurium--butonate: O,O-dimethyl-(1-n-butyryloxy-2,2,2-trichloroethyl)-phosphonate; vinylbutonate: O,O-dimethyl-(n-butyryloxy-2,2-dichlorovinyl)-phosphonate; trichlorfon: O,O-dimethyl-(1-hydroxy-2,2,2-trichloroethyl)-phosphonate; dichlorvos: O,O-dimethyl-O-(2,2-dichlorovinyl)-phosphate; the demethylated derivatives--demethyldichlorvos: O-methyl-O-(2,2-dichlorovinyl)-phosphoric acid; demethyl vinylbutonate: O-methyl-(1-n-butyryloxy-2,2-dichlorovinyl)phosphonic acid. Of the six compounds tested, dichlorvos and trichlorfon induced base pair substitutions and DNA damage. No mutagenicity and DNA damage were found in experiments with butonate, vinylbutonate, demethyl vinylbutonate and demethyl dichlorvos. Genotoxic activity for dichlorvos and the absence of both mutagenic and RNA damaging properties for its non-alkylating demethyl derivative favors the hypothesis that alkylation of DNA is the essential step for mutation induction by this organophosphate. Furthermore, the absence of genetic effects after treatment with vinylbutonate and demethyl dichlorvos does not support a crucial role of vinyl or allyl groups in side chains of organophosphates for genetic activity. Microsomal enzymes decreased genetic activity of dichlorvos and trichlorfon in vitro. No evidence for a role of metabolic activation in the mutagenic activity of any of these compounds was found.