Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats

Summary The long-term consequences of neonatal exposure to triethyl lead, the putative neurotoxic metabolite of the anti-knock gasoline additive tetraethyl lead, were examined with respect to central nervous system (CNS) development. We presently report a series of studies in which exposure of neonatal rats to organic lead produces profound CNS damage in adulthood as indicated by dose-dependent, persistent behavioral hyperreactivity as well as dose-dependent, preferential, and permanent damage to the hippocampus. General morphological parameters of brain development were not altered. Pharmacological probes of neurotransmitter system integrity suggested a functional and dose-dependent relationship between this behavioral hyperreactivity and hippocampal damage via cholinergic, but not dopaminergic, pathways. Furthermore, these alterations were not accompanied by long-term alterations in motor activity and were not attributable to the presence of lead in adult neural tissue. Finally, these behavioral, anatomical, and pharmacological indices of developmental exposure to organic lead were dissociable from any effects of early undernutrition. These data collectively indicate that organolead compounds may pose a potent neurotoxic threat to the developing CNS.     

Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats

The long-term consequences of neonatal exposure to triethyl lead, the putative neurotoxic metabolite of the anti-knock gasoline additive tetraethyl lead, were examined with respect to central nervous system (CNS) development. We presently report a series of studies in which exposure of neonatal rats to organic lead produces profound CNS damage in adulthood as indicated by dose-dependent, persistent behavioral hyperreactivity as well as dose-dependent, preferential, and permanent damage to the hippocampus. General morphological parameters of brain development were not altered. Pharmacological probes of neurotransmitter system integrity suggested a functional and dose-dependent relationship between this behavioral hyperreactivity and hippocampal damage via cholinergic, but not dopaminergic, pathways. Furthermore, these alterations were not accompanied by long-term alterations in motor activity and were not attributable to the presence of lead in adult neural tissue. Finally, these behavioral, anatomical, and pharmacological indices of developmental exposure to organic lead were dissociable from any effects of early undernutrition. These data collectively indicate that organolead compounds may pose a potent neurotoxic threat to the developing CNS.     

铅在土壤及其组分中吸附行为研究

本文研究铅在土壤及其组分中的吸附,并用Freundlich等温吸附方程对实验结果进行拟合。结果显示土壤中各项组分对铅吸附能力的大小为：土壤胡敏酸〉土壤〉土壤矿物质;铅在土壤中的吸附满足线性吸附,铅在土壤胡敏酸和土壤矿物质中的吸附不属于线性吸附;pH值是影响土壤吸附铅的主要因素,随着溶液pH值的升高,土壤对铅的吸附能力增加,当pH值达到一定程度时,土壤对铅的吸附能力增加缓慢。     

Embryonic death in mouse due to lead exposure.

Female mice which displayed a vaginal plug after mating were given a diet containing 0, 0.125, 0.250, 0.500% of lead as lead acetate and were dissected 16 to 18 days later. Lead treatment was found to reduce significantly the incidence of pregnancies and to increase the postimplantation loss in the pregnant females.     

Effect of lead microparticles introduced into the respiratory system of the sensitivity of mice to Pasteurella multocida infection via aerosol]

Lead microparticles, resulting from the pyrolysis of organic lead used as an anti-knock agent in gasoline, were introduced into the lungs of Mice, during a short single exposure. When 6 microgram of lead were retained in the lungs (mean value per Mouse), the phagocytic ability of the pulmonary alveolar macrophages harvested 6 and 18 hrs. later, was significantly reduced. It was observed, in the same conditions, that the resistance of Mice to experimental infection by aerosolized Pasteurella multocida, was significantly reduced. When 3 microgram of lead were retained in the lungs, there was no significant difference between control and intoxicated Mice.     

Plasma hormone levels in normal and lead-treated pregnant mice

Summary Dietary lead (0.5%) was given to mice which, after mating, exhibited a vaginal plug. Estradiol, progesterone and prostaglandins E and F 2 were determined in, the plasma by radioimmuno assay at different times thereafter. The increase in estradiol and decrease in prostaglandins prior implantation are not greatly altered by lead treatment, whereas the subsequent increase in progesterone and later in estradiol is abolished. It is concluded that the lower number of pregnancies seen in lead-treated mothers is due to a maternal hormonal imbalance caused by lead.Supported by contract 038-74-7 ENV B of the E.C. Environmental Research Program. Publication No. 1394 of the Euratom Biology Division.     

Protective effect of tannic acid in mice receiving dietary lead

Summary Mice fed a diet containing both tannic acid and lead acetate showed increased weight gain and greater fecundity when compared with those on a diet containing lead acetate alone. The most significant improvement was provided by adding 2% tannic acid (wt/wt) to ground food containing 3% lead acetate. The affinity of tannic acid for heavy metals is suggested as a reason for this protective effect.     

Protein NMR in biomedical research

Nuclear magnetic resonance (NMR) spectroscopy is a versatile biophysical technique with wide applicability in drug discovery research, particularly for the detection and characterization of molecular interactions. This review highlights in a comprehensive manner the aspects of biomolecular NMR which are most beneficial for pharmaceutical research and presents them as contributions to the different stages of a drug discovery program: target selection, assay development, lead generation and lead optimization. Emphasis is put on the concept of the particular NMR application, rather than on technical details, and on recent examples. Finally, an appendix of frequently asked questions is given.Received 7 October 2003; received after revision 11 November 2003; accepted 27 November 2003This revised version was published online in September 2004. In the previous version, the authors were listet in reverse order.     

Lead metabolism in lactation

Summary A 2-fold increase in lead absorption was observed in lactating animals which received 2 mg Pb/1 in drinking water. About one-half of the absorbed lead was transferred to the litters.Acknowledgments. This work was partially supported by a research grant from the US Environmental Protection Agency and the US Public Health Service.     

Oncogenes and angiogenesis: a way to personalize anti-angiogenic therapy?

The acquisition of oncogenic mutations and promotion of angiogenesis are key hallmarks of cancer. These features are often thought of as separate events in tumor progression and the two fields of research have frequently been considered as independent. However, as we highlight in this review, activated oncogenes and deregulated angiogenesis are tightly associated, as mutations in cancer cells can lead to perturbation of the pro- and anti-angiogenic balance thereby causing aberrant angiogenesis. We propose that normalization of the vascular network by targeting oncogenes in the tumor cells might lead to more efficient and sustained therapeutic effects compared to therapies targeting tumor vessels. We discuss how pharmacological inhibition of oncogenes in tumor cells restores a functional vasculature by bystander anti-angiogenic effect. As genetic alterations are tumor-specific, targeted therapy, which potentially blocks the angiogenic program activated by individual oncogenes may lead to personalized anti-angiogenic therapy.     

Lead distribution in the nervous system of 8-month-old rats intoxicated since birth by lead

Lead levels in the nervous system of rats intoxicated for 8 months by lead acetate (0.2% in drinking water) varied according to the region: the lowest levels were observed in sciatic nerve and the highest in hippocampus and cerebral neocortex, while intermediate levels were observed in pons medulla, cerebellum, midbrain, hypothalamus and striatum.     

Increased ALA dehydratase activity and spleen weight in lead-intoxicated rats. A consequence of increased blood cell destruction

Lead was given in the diet (1%) to rats from birth and at different times the animals were studies for delta amino levulinic acid dehydratase (ALAD) activity, spleen weight, 59Fe incorporation in erythrocytes and 51Cr-labeled erythrocytes survival. The increased ALAD and spleen weight found after lead treatment is explained as a consequence of a shortened survival, which results in a younger age of circulating erythrocytes with higher ALAD activity.     

Determination of cerebrospinal fluid and serum lead levels in patients with amyotrophic lateral sclerosis and other neurological diseases

In a total of 62 samples of cerebrospinal fluid (CSF) and an equal number of serum samples obtained from 16 patients suffering from amyotrophic lateral sclerosis, 22 patients suffering from miscellaneous neurological diseases, and 24 controls, lead was measured by atomic absorption spectrophotometry. No statistical difference in lead concentration was found between the above three groups.     

Europe's Infrastructure Transition: Economy,War, Nature

In his many uses of the pendulum as a model for other motions, Galileo also described several of the properties of pendular motion. All but a small number of his apparently observational reports ring true because of his use of such qualifiers as ‘almost’. His report of observations of two lead balls on equal long strings is shown by reconstruction to have been a real experiment. His report of similar observations with balls of cork and lead is shown to be an imaginary experiment. His claim that the period of a pendulum is independent of amplitude is shown to be based more on mathematical deduction than on experimental observation.     

Lead potentiation of endotoxin lethality in rats: lack of effect of kininase inhibition.

Although lead and SQ20881 are potent in vitro inhibitors of kininase II activity, SQ20881 does not alter the sensitivity of rats to endotoxin. These results indicate that marked changes in plasma kininase activity do not contribute to endotoxin morbidity and that kininase inhibition is not the mechanism whereby lead ions sensitize rats to endotoxin.     

Lead metabolism in lactation.

A 2-fold increase in lead absorption was observed in lactating animals which received 2 mg Pb/l in drinking water. About one-half of the absorbed lead was transferred to the litters.     

Über die Konstitution der Visnagane und Khellactone ausAmmi visnaga L.

Summary The visnagans fromAmmi visnaga L. and the stereoisomeric khellactones and methyl-khellactones derived from them were transformed into seselin and umbelli-ferone-8-aldehyde. These transformations and other degradations lead to revised formulas for these natural compounds.     

Molecular mechanisms in male determination and germ cell differentiation

Sex determination and gametogenesis are key processes in human reproduction, and any defect can lead to infertility. We describe here the molecular mechanisms of male sex determination and testis formation; defects in sex determination lead to a female phenotype despite the presence of a Y chromosome, more rarely to a male phenotype with XX chromosomes, or to intersex phenotypes. Interestingly, these phenotypes are often associated with other developmental malformations. In testis, spermatozoa are produced from renewable stem cells in a complex differentiation process called spermatogenesis. Gene expression during spermatogenesis differs to a surprising degree from gene expression in somatic cells, and we discuss here mechanistic differences and their effect on the differentiation process and male fertility.Received 23 January 2004; received after revision 30 March 2004; accepted 6 April 2004     

Quality control of homologous recombination

Exogenous and endogenous genotoxic agents, such as ionizing radiation and numerous chemical agents, cause DNA double-strand breaks (DSBs), which are highly toxic and lead to genomic instability or tumorigenesis if not repaired accurately and efficiently. Cells have over evolutionary time developed certain repair mechanisms in response to DSBs to maintain genomic integrity. Major DSB repair mechanisms include non-homologous end joining and homologous recombination (HR). Using sister homologues as templates, HR is a high-fidelity repair pathway that can rejoin DSBs without introducing mutations. However, HR execution without appropriate guarding may lead to more severe gross genome rearrangements. Here we review current knowledge regarding the factors and mechanisms required for accomplishment of accurate HR.     

Single‐index and portfolio models for forecasting value‐at‐risk thresholds

The variance of a portfolio can be forecast using a single index model or the covariance matrix of the portfolio. Using univariate and multivariate conditional volatility models, this paper evaluates the performance of the single index and portfolio models in forecasting value‐at‐risk (VaR) thresholds of a portfolio. Likelihood ratio tests of unconditional coverage, independence and conditional coverage of the VaR forecasts suggest that the single‐index model leads to excessive and often serially dependent violations, while the portfolio model leads to too few violations. The single‐index model also leads to lower daily Basel Accord capital charges. The univariate models which display correct conditional coverage lead to higher capital charges than models which lead to too many violations. Overall, the Basel Accord penalties appear to be too lenient and favour models which have too many violations. Copyright © 2008 John Wiley & Sons, Ltd.