Infantile postnatal exposure to lead (Pb) enhances tau expression in the cerebral cortex of aged mice: Relevance to AD

The sporadic nature in over 90% of Alzheimer\u27s disease (AD) cases, the differential susceptibility and course of illness, and latent onset of the disease suggest involvement of an environmental component in the etiology of late onset AD (LOAD). Recent reports from our lab have demonstrated that molecular alterations favor abundant tau phosphorylation and immunoreactivity in the frontal cortex of aged primates with infantile lead (Pb) exposure (Bihaqi and Zawia, 2013). Here we report that developmental Pb exposure results in elevation of protein and mRNA levels of tau in aged mice. Western blot analysis revealed aberrant site-specific tau hyperphosphorylation accompanied by elevated cyclin dependent kinase 5 (CDK5) levels in aged mice with prior Pb exposure. Mice with developmental Pb exposure also displayed altered protein ratio of p35/p25 with more Serine/Threonine phosphatase activity at old age. These changes favored increase in tau phosphorylation, thus providing evidence that neurodegenerative diseases may be in part due to environmental influences that occur during development

Influence of modafinil on early ejaculation - Results from a double-blind randomized clinical trial

BACKGROUND For men, early ejaculation is a serious health concern. Here, we tested the influence of modafinil (Profinil®) on early ejaculation. To this end, we performed a double-blind randomized clinical trial among men with early ejaculation. METHODS A total of 46 men with early ejaculation (mean age: 37.35 years) and in stable marital relationships with regular weekly penile-vaginal intercourse were randomly assigned either to the modafinil (100 mg) or to the placebo condition. Compounds were taken about 4-6h before intended penile-vaginal intercourse. At baseline and four weeks later at the end of the study, participants completed a series of self-rating questionnaires covering early ejaculation. Female partners also rated their male partners' early ejaculation profile. RESULTS Dimensions of early ejaculation improved over time, but only so in the modafinil condition, while no improvements were observed in the placebo condition. CONCLUSIONS Among male adults in stable marital relationships with regular weekly penile-vaginal intercourse modafinil improved dimensions of early ejaculation, always compared to placebo. Given the strong effect of modafinil on cognitive-executive processes, it is conceivable, that modafinil acted both via physiological and cognitive-executive pathways

Influence of modafinil on early ejaculation - Results from a double-blind randomized clinical trial

BACKGROUND For men, early ejaculation is a serious health concern. Here, we tested the influence of modafinil (Profinil®) on early ejaculation. To this end, we performed a double-blind randomized clinical trial among men with early ejaculation. METHODS A total of 46 men with early ejaculation (mean age: 37.35 years) and in stable marital relationships with regular weekly penile-vaginal intercourse were randomly assigned either to the modafinil (100 mg) or to the placebo condition. Compounds were taken about 4-6h before intended penile-vaginal intercourse. At baseline and four weeks later at the end of the study, participants completed a series of self-rating questionnaires covering early ejaculation. Female partners also rated their male partners' early ejaculation profile. RESULTS Dimensions of early ejaculation improved over time, but only so in the modafinil condition, while no improvements were observed in the placebo condition. CONCLUSIONS Among male adults in stable marital relationships with regular weekly penile-vaginal intercourse modafinil improved dimensions of early ejaculation, always compared to placebo. Given the strong effect of modafinil on cognitive-executive processes, it is conceivable, that modafinil acted both via physiological and cognitive-executive pathways

Infantile exposure to lead and late-age cognitive decline: Relevance to AD

Background: Early-life lead (Pb) exposure induces overexpression of the amyloid beta precursor protein and its amyloid beta product in older rats and primates. We exposed rodents to Pb during different life span periods and examined cognitive function in old age and its impact on biomarkers associated with Alzheimer\u27s disease (AD). Methods: Morris, Y, and the elevated plus mazes were used. Western blot, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay were used to study the levels of AD biomarkers. Results: Cognitive impairment was observed in mice exposed as infants but not as adults. Overexpression of AD-related genes (amyloid beta precursor protein and β-site amyloid precursor protein cleaving enzyme 1) and their products, as well as their transcriptional regulator—specificity protein 1 (Sp1)—occurred only in older mice with developmental exposure to Pb. Conclusions: A window of vulnerability to Pb neurotoxicity exists in the developing brain that can influence AD pathogenesis and cognitive decline in old age