Effects of day-length variations on emotional responses towards unfamiliarity in Swiss mice.

Pineal melatonin secretion occurs at night in all vertebrates and the duration of its secretion is negatively correlated with day length. As an anxiolytic activity of melatonin has been shown in rats and mice, this study examined possible changes of emotional reactivity in response to day length variations in Swiss mice. Three groups of mice were observed in a free-exploratory test: a group submitted to a short-day exposure (6:18 h light-dark cycle) for 2 weeks, a group submitted to a long-day exposure (18:6 h light-dark cycle) for 2 weeks and a control group which was maintained in housing 12:12 h light-dark cycle.

Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men.

The ob gene product leptin (OB) is a feedback signal from the adipocyte to the hypothalamus and is involved in regulation of food intake and energy expenditure in rodents. A major determinant of serum OB levels is fat mass. Several studies suggest that men have lower OB levels than women even after adjustment for percent body fat.

Effects of various modes of androgen substitution therapy on erythropoiesis.

In order to investigate differential effects of androgens on erythropoiesis, 55 men with clincally and biochemical confirmed hypogonadism were randomly assigned to 4 groups receiving different forms of androgen substitution: Mesterolone (MES) 100 mg/d, testosterone undecanoate (TU) 160 mg/d, testosterone enanthate (TE) 250 mg i.m./21 days or 1200 mg crystalline testosterone (TPEL) subcutaneously implanted at study begin.

Preferential formation of deletions following in vivo exposure of postmeiotic Drosophila germ cells to the DNA etheno-adduct-forming carcinogen vinyl carbamate.

DNA sequence changes induced in the vermilion gene of Drosophila following in vivo treatment of postmeiotic male germ cells with vinyl carbamate (VCA), an etheno-adduct-forming carcinogen, are primarily deletions. With VCA, 65% (13/20) of the vermilion mutants isolated from crosses of NER+ (nucleotide excision repair) males with NER+ females and 40% (6/15) obtained from matings with NER- females were intra- or multi-locus deletions. Due to the insufficiently low mutagenic activity in NER+ genotypes of vinyl bromide (VB), another epsilon-adduct-forming carcinogen, vermilion mutants could only be isolated from crosses of VB-treated males with NER- females.

The response of germ cells to ethylene oxide, propylene oxide, propylene imine and methyl methanesulfonate is a matter of cell stage-related DNA repair.

We describe the consequences of a defect for nucleotide excision repair (NER) in oocytes for alkylation-induced mutagenesis in different germ-cell stages of Drosophila males. Mutant frequencies induced in NER+ condition (cross NER+female female x NER+male) were compared with those fixed in a NER- background (cross NER-female female x NER+male), using the X-linked recessive lethal assay (SLRL) for the measurement of forward mutations in 700 loci. In successive male germ-cell stages exposed to a low dose of 2.

Word meanings can be accessed but not reported during the attentional blink.

After the detection of a target item in a rapid stream of visual stimuli, there is a period of 400-600 ms during which subsequent targets are missed. This impairment has been labelled the 'attentional blink'. It has been suggested that, unlike an eye blink, the additional blink does not reflect a suppression of perceptual processing, but instead reflects a loss of information at a postperceptual stage, such as visual short-term memory.

Synthesis, Characterization, and Electrochemistry of sigma-Bonded Cobalt Corroles in High Oxidation States.

The synthesis, electrochemistry, spectroscopy, and structural characterization of two high-valent phenyl sigma-bonded cobalt corroles containing a central cobalt ion in formal +IV and +V oxidation states is presented. The characterized compounds are represented as phenyl sigma-bonded cobalt corroles, (OEC)Co(C(6)H(5)) and [(OEC)Co(C(6)H(5))]ClO(4), where OEC is the trianion of 2,3,7,8,12,13,17,18-octaethylcorrole. The electronic distribution in both molecules is discussed in terms of their NMR and EPR spectroscopic data, magnetic susceptibility, and electrochemistry.

Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men.

Objective: There are advantages and disadvantages with all of the presently available types of testosterone replacement for hypogonadal men. We performed this investigation to establish detailed data about the pharmacokinetics, pharmacodynamics, feasibility and side-effects of subcutaneously implanted testosterone (T) pellets.

Design And Measurement: In a single-dose, open-label, non-randomized study, 6 T-pellets, each containing 200 mg of fused crystalline T, were implanted in the subdermal fat tissue of the lower abdominal wall of 14 hypogonadal men.

Somatic recombination, gene amplification and cancer.

The principle objective of this research programme, to analyse chemical induction of somatic recombination and related endpoints, i.e., mobilization of transposing elements and gene amplification, has been approached by means of several assay systems.

DNA damage and repair in mutagenesis and carcinogenesis: implications of structure-activity relationships for cross-species extrapolation.

Previous studies on structure-activity relationships (SARs) between types of DNA modifications and tumour incidence revealed linear positive relationships between the log TD50 estimates and s-values for a series of mostly monofunctional alkylating agents. The overall objective of this STEP project was to further elucidate the mechanistic principles underlying these correlations, because detailed knowledge on mechanisms underlying the formation of genotoxic damage is an absolute necessity for establishing guidance values for exposures to genotoxic agents. The analysis included: (1) the re-calculation and further extension of TD50 values in mmol/kg body weight for chemicals carcinogenic in rodents.

Mutational spectra induced under distinct excision repair conditions by the 3 methylating agents N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine and N-nitrosodimethylamine in postmeiotic male germ cells of Drosophila.

This paper describes the analysis of mutations induced at the vermilion locus in postmeiotic male germ cell stages of Drosophila exposed to 3 different N-methyl-N-nitroso compounds: N-methyl-N-nitrosourea (MNU); N-methyl-N'-nitro-N-nitrosoguanidine (MNNG); and N-nitrosodimethylamine (DMN). With MNU and DMN, the impact of DNA nucleotide excision repair (NER) on the spectra of mutations was studied. Mutants were isolated from F1 (mutations fixed before the first mitotic replication after fertilization) and F2 (mutations fixed following one or more mitotic replications; mosaics in F1) generations.

Characterization by two-endpoint comparisons of the genetic toxicity profiles of vinyl chloride and related etheno-adduct forming carcinogens in Drosophila.

The genetic toxicity profiles of vinyl chloride (VCl), vinyl bromide (VBr), ethyl carbamate (EC), vinyl carbamate (VC) and some structurally related chemicals were investigated in both somatic and germ cells of Drosophila melanogaster. In the white/white+ eye mosaic assay, a screening system measuring predominantly homologous recombination in somatic cells, only marginal genotoxic activities were observed for acetyl chloride (ACl), glycolaldehyde (GCA), 2,2'-dichlorodiethyl ether (DDE) and methyl carbamate (MC), whereas VCl, 2-chloroacetaldehyde (CAA), VBr, 2-bromoacetaldehyde (BAA) and EC were clearly recombinogenic in the assay. Those chemicals proven to be recombinogenic in somatic cells were investigated further in postmeiotic male germ cells, utilizing as descriptors of their genotoxicity I(CL/RL) and M(exr-)/M(exr+) indices.

[A review of epidemiologic studies on ultrasound during pregnancy].

This article reviews most of the more recent epidemiological studies on the effectiveness and possible risks of conventional sonography. With the help of such a review, case reports, very often cited out of context, can be better evaluated. Publications which have attempted to study the number of malformations, diagnosable by ultrasound, and to the effect of ultrasound on postnatal mortality and morbidity are scrutinized.

Electrochemical and Spectral Characterization of Iron Corroles in High and Low Oxidation States: First Structural Characterization of an Iron(IV) Tetrapyrrole π Cation Radical.

The electrochemistry and spectroscopic properties of three iron corroles were examined in benzonitrile, dichloromethane, and pyridine containing 0.1 M tetra-n-butylammonium perchlorate or tetra-n-ethylammonium hexafluorophosphate as supporting electrolyte. The investigated compounds are represented as (OEC)Fe(CH), (OEC)FeCl, and (OEC)Fe(py), where OEC is the trianion of 2,3,7,8,12,13,17,18-octaethylcorrole.

Electrochemical and Spectral Characterization of Iron Corroles in High and Low Oxidation States: First Structural Characterization of an Iron(IV) Tetrapyrrole pi Cation Radical.

The electrochemistry and spectroscopic properties of three iron corroles were examined in benzonitrile, dichloromethane, and pyridine containing 0.1 M tetra-n-butylammonium perchlorate or tetra-n-ethylammonium hexafluorophosphate as supporting electrolyte. The investigated compounds are represented as (OEC)Fe(IV)(C(6)H(5)), (OEC)Fe(IV)Cl, and (OEC)Fe(III)(py), where OEC is the trianion of 2,3,7,8,12,13,17,18-octaethylcorrole.

Synthesis, Characterization and Solution Chemistry of trans-Indazoliumtetrachlorobis(Indazole)Ruthenate(III), a New Anticancer Ruthenium Complex. IR, UV, NMR, HPLC Investigations and Antitumor Activity. Crystal Structures of trans-1-Methyl-Indazoliumtetrachlorobis-(1-Methylindazole)Ruthenate(III) and its Hydrolysis Product trans-Monoaquatrichlorobis-(1-Methylindazole)-Ruthenate(III).

Besides intensive studies into the synthesis of the complex trans-Hlnd[RuCl(4)(ind)(2)] (Ind = indazole) 1, which differs remarkably from the usual method for the complexes of the HL[RuCl(4)L(2)] - type, competitive products and hydrolysis of this species are described. Stability and pseudo-first-order rate constant under physiological conditions of complex 1 in comparison with the analogous imidazole complex trans-Hlm[RuCl(4)im(2)] (Im = imidaZole) ICR were examined by means of HPLC, UV and conductivity measurements (K(obs.)(1) = 1.

The neurosteroid pregnenolone sulfate blocks deficits induced by a competitive NMDA antagonist in active avoidance and lever-press learning tasks in mice.

The neurosteroid pregnenolone sulfate (PREG-S) has been shown to modulate positively NMDA receptor activity and to have memory enhancing properties in mice. The present study was designed to evaluate the effects of post-training administration of PREG-S, alone or in combination with D-2-amino-5-phosphonovalerate (D-AP5), a competitive NMDA receptor antagonist, in Y-maze avoidance and appetitively motivated lever-press learning tasks and in a traction reflex test in mice. Intracerebroventricular (i.

Hexamethylmelamine is a potent inducer of deletions in male germ cells of Drosophila melanogaster.

Chemotherapy-related second tumors constitute a matter of concern in cancer treatment. Therefore, it is of great interest to elucidate the mechanisms by which cytostatic drugs exert their mutagenic and/or carcinogenic activity besides the anticancer effect and the possible relationship among them. A useful and informative approach to this problem is the analysis of the mutation spectra induced by these drugs in eukaryotic organisms.

DNA damage and repair in somatic and germ cells in vivo.

Alkylation-induced germ cell mutagenesis in the mouse versus Drosophila is compared based on data from forward mutation assays (specific-locus tests in the mouse and in Drosophila and multiple-locus assays in the latter species) but not including assays for structural chromosome aberrations. To facilitate comparisons between mouse and Drosophila, forward mutation test results have been grouped into three categories. Representatives of the first category are MMS (methyl methanesulfonate) and EO (ethylene oxide), alkylating agents with a high s value which predominantly react with ring nitrogens in DNA.

1,3-Butadiene working group report.

During the Workshop in North Carolina, the in vivo metabolism, adduct formation and genotoxicity data available from rodent and human exposure to 1,3-butadiente (BD) were reviewed and they are summarized in the present report. BD is metabolized by cytochrome P-450-dependent monoxygenases to the primary metabolite 1,2-epoxybutene-3 (epoxybutene, EB). EB is subjected to further metabolism: oxidation to 1,2:3,4-diepoxybutane (DEB), hydrolysis to 3-butene-1,2-diol and conjugation to glutathione.

The cross-linking agent hexamethylphosphoramide predominantly induces intra-locus and multi-locus deletions in postmeiotic germ cells of Drosophila.

The nature of DNA sequence changes induced by the cross-linking agent hexamethylphosphoramide (HMPA) within and in the vicinity of the vermilion locus of Drosophila melanogaster that produce a vermilion mutant phenotype was analyzed after exposure of postmeiotic male germ cells. Mutagenized males were mated to either females wild-type (exr+) for nucleotide excision repair (NER) or to females having a deficiency (exr-) for NER. Rearrangements, mostly deletions, represented by far the most frequent type of mutational events induced by HMPA that are detected as vermilion mutations.

A defect in the early phase of T-cell receptor-mediated T-cell activation in patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is characterized by an impairment of specific antibody production and a decrease in all or selected Ig isotypes. Abnormalities at the level of the B cells, T cells, and antigen-presenting cells have been described. In the present study, we have focused our attention on T-cell activation in CVID.

Impaired TCR signal transduction, but normal antigen presentation, in a patient with common variable immunodeficiency.

We describe a 27-year-old white man with common variable immunodeficiency (CVID) who has two healthy histoidentical brothers and one IgA-deficient sister who shares one HLA haplotype with the patient. T cells from the patient with CVID showed an impaired response to recall antigens (tetanus toxoid, E. coli), whereas his IgA-deficient sister and his two healthy histoidentical brothers responded normally.

Mechanism-based predictions of interactions.

Exposure to more than one toxic compound is common in real life. The resulting toxic effects are often more than the simple sum of the effects of the individual compounds. It is unlikely that it will ever be possible to test all combinations.