Reading the unique DNA methylation landscape of the brain: Non-CpG methylation,hydroxymethylation, and MeCP2

DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.     

Inhibitory effects of powerline-frequency (60-Hz) magnetic fields on pentylenetetrazol-induced seizures and mortality in rats.

The possibility that exposure to powerline frequency (60-Hz) magnetic fields might affect the form or intensity of epileptic seizures, induced by administration of pentylenetetrazol (PTZ) in rats, was examined. Male adult rats were exposed to either 60-Hz magnetic fields with intensities of up to 1.85 gauss (185 microT) or to a sham field condition, for 1 h prior to injections of PTZ (45-75 mg/kg). The subsequent seizures were monitored and recorded on videotape and any subsequent mortalities were noted. Exposure to 60-Hz magnetic fields prior to administration of PTZ was found to significantly (P less than 0.005) reduce the lethality of the drug-induced seizures. The LD50 for the sham-exposed group was 65.88 mg/kg, whereas for the 60-Hz magnetic field-exposed rats, the LD50 was 85.33 mg/kg. In some experiments exposure to the 1.0 and 1.5 gauss magnetic fields also produced significant (P less than 0.05) reductions in seizure durations. These findings suggest that acute exposure to low intensity 60-Hz magnetic fields has an inhibitory effect on the lethality and expression of PTZ-induced seizures in rats. Some possible mechanisms, which could account for these observed effects of magnetic field exposure on seizures, are discussed.     

An unusual case of cutaneous listeriosis.

Listeria monocytogenes was identified as the etiological agent in the cutaneous and febrile illness of a 64-year-old male who acquired the organism as a result of contact with the genital tract of a cow while assisting in the delivery of a stillborn calf.     

The influence of stigma on the sexual risk behavior of rural men who have sex with men.

Research investigating predictors of risky sexual behavior of rural MSM is sparse, even though the prevalence of HIV in rural areas has increased. This study explored two sets of predictors of 93 rural MSM's levels of risky sexual behavior: mental health variables and stigma emanating from men's family members, health care professionals, and people in the rural communities in which they live. Over 47% of the men were found to be at modified high to high risk. Logistic regression using a continuation logit model was used to test the relationship of the predictor variables and the four levels of risk. Findings indicate that self-esteem was predictive of the highest sexual risk behavior but not lower levels of risk. Stigma was predictive of modified high sexual risk when compared to low and no risk categories. No variables differentiated men at low risk from men at no risk.     

Bone levels of cephradine and cefuroxime after intravenous administration in patients undergoing total hip replacement

Summary A randomised, comparative study is reported of single intravenous doses of cephradine 2 g or cefuroxime 1.5 g given as prophylactic cover for total hip replacements in 40 patients. The serum and bone levels of cephalosporin achieved were higher in the cephradine treated group in proportion to the higher dose employed. Both agents provided adequate bone levels on average, cephradine 25.34 mcg/g, cefuroxime 17.39 mcg/g, although bone penetration was more variable with cefuroxime.

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Résumé Dans cette étude comparative randomisée, 40 patients ont reçu une dose intraveineuse unique de 2 g de céphradine ou de 1,5 g de céfuroxime en tant que couverture prophylactique d'arthroplastie totale de hanche. Les concentrations sériques et osseuses de céphalosporine ont été plus élevées dans le groupe traité par la céphradine, en rapport avec l'utilisation d'une dose plus importante. Des concentrations osseuses adéquates ont été obtenues en moyenne avec les deux produits (25,34 mcg/g avec la céphradine et 17,39 mcg/g avec le céfuroxime) bien que la pénétration osseuse ait été plus variable avec le céfuroxime.

     

Cardiotonic agents. 4. Synthesis and biological evaluation of N-substituted 2,4,4a,5-tetrahydro-3H-indeno[1,2-c]pyridazin-3-ones: rigid structures derived from CI-930 and analogues

Several N-substituted 3H-indeno[1,2-c]pyridazinones (1-23) and a benzo[h]cinnolinone (24), which were designed as rigid structural modifications of 5-alkyl-4,5-dihydro-6-[4-N-substituted phenyl]-3(2H)-pyridazinones (ib-d), were synthesized and evaluated for positive inotropic activity. Most of these tricyclic pyridazinones (1-11, 14-15, 22-23) demonstrated potent positive inotropic activity comparable to the corresponding phenylpyridazinones related to I.     

The Relationship Between Daily Life Stress and Gastrointestinal Symptoms in Women with Irritable Bowel Syndrome

Research on irritable bowel syndrome (IBS), a functional disorder of the gastrointestinal (GI) system, has linked GI symptoms to stress. This study examined the relationship between daily stress and GI symptoms across women and within woman in IBS patients (n = 26), IBS nonpatients (IBS-NP; n = 23), and controls (n = 26), controlling for menstrual cycle phase. Women (ages 20–45) completed daily health diaries for two cycles in which they monitored daily GI symptoms and stress levels. The Life Event Survey (LES) was used as a retrospective measure of self-reported stress. The across-women analyses showed higher mean GI symptoms and stress in the IBS and IBS-NP groups relative to controls but no group differences in LES scores. The within-woman analyses found a significant and positive relationship between daily stress and daily symptoms in both the IBS-NP and the IBS groups. Controlling for menstrual cycle had no substantial impact on the results.