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No data in the literature have evaluated sex hormone dose escalation for treating abnormal sleep of ovariectomized rats--nor studies on the role of sex hormones in GABA synthesis of rats' sleep-related areas. The main aim of this study was to determine the maximum tolerated dose (MTD) of estradiol (ET), progesterone (PT), and the mixture of both (EPT) to restore normal sleep in a model of menopause in rats. The second purpose was to describe the in vitro activity of glutamate decarboxylase (GAD) in sleep-related brain areas in the presence or absence of sex hormones. A weekly dose-escalation design of ET, PT, or EPT was implemented in ovariectomized rats (six per group). Dose escalation continued until the dose at which 100% of the rats exhibited a state of 'complete somnolence.' Doses that were not toxic or did not show side effects were considered. For in vitro experiments, sleep-related brain areas were separated and incubated with radiolabeled glutamate. Estradiol (17[beta]-[E.sub.2]), progesterone (P), and pyridoxal phosphate (PLP) were added to this assay, and GAD activity was determined. Under the same conditions, a second test was carried out, but the P antagonist RU486 was added to assess the role of P in GAD activity. Ovariectomy increased periodic awakenings compared to those determined for the SHAM group. The EPT for ovariectomized rats was very effective by the fifth week in decreasing arousal and achieving a similar sleep behavior to the SHAM-control group. Rats tolerated the ET, PT, and EPT well to the maximum planned dose (0.66 mg/kg and 4.4 mg/kg, respectively). No lethal events occurred; the MTD was reached. The in vitro studies indicated that the presence of 17[beta]-[E.sub.2] plus P in the assay triggered the activity of isotype 65 GAD in all the studied brain areas. RU486 in the incubation medium blocked such activity; however, the action of isotype 67 GAD was not blocked by RU486. A dose-escalation model was determined; the MTD coincided with the maximum dose of ET and PT used. However, the EPT combination restored normal sleep in the menopause model compared to the SHAMs without toxic effects. The in vitro model demonstrated that 17[beta]-[E.sub.2] plus P presence in the assay increased the activity of [GAD.sub.65] in the studied brain tissues. Keywords: menopause, intermittent awakenings, glutamate decarboxylase activity, GABAergic brain regions, disturbed sleeping, female sex hormone., 1. Introduction Menopause marks the cessation of menstruation due to the loss of follicular function (Santoro 2005; Brown and Gervais 2020) Some women in this stage report symptoms that prevent [...]

Liver X receptors (LXRs) are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. However, exactly how LXRs modulate inflammation during infection remains unknown. To explore this, we used a mouse model of Mycobacterium tuberculosis infection. Upon intratracheal infection with M. tuberculosis, LXRs and LXR target genes were induced in [CD11c.sup.+] lung and alveolar cells. Furthermore, mice deficient in both LXR isoforms, LXR[alpha] and LXR[beta] (Lxra-/-Lxrb-/- mice), were more susceptible to infection, developing higher bacterial burdens and an increase in the size and number of granulomatous lesions. Interestingly, mice solely deficient in LXR[alpha], but not those lacking only LXR[beta], mirrored the susceptibility of the Lxra-/-Lxrb-/- animals. Lxra-/-Lxrb-/- mice failed to mount an effective early neutrophilic airway response to infection and showed dysregulation of both pro- and antiinflammatory factors in [CD11c.sup.+] lung cells. T cell responses were strongly affected in Lxra-/-Lxrb-/- mice, showing near-complete abrogation of the infection-induced Th1 function--and even more so Th17 function--in the lungs. Treatment of WT mice with the LXR agonists TO901317 and GW3965 resulted in a 10-fold decrease of the pulmonary bacterial burden and a comparable increase of Th1/Th17 function in the lungs. The dependence of LXR signaling on the neutrophil IL-17 axis represents what we believe to be a novel function for these nuclear receptors in resistance to M. tuberculosis infection and may provide a new target for therapeutics., Introduction An estimated one-third of the world population is latently infected with Mycobacterium tuberculosis (1), creating a vast reservoir from which most active cases of tuberculosis arise. The success of [...]

The reader of a comprehension is required to continuously change the content of memory in order to maintain the important information and to remove the unimportant information. The hypothesis that poor comprehenders' deficiencies are associated with a specific difficulty in the working memory updating process, particularly in controlling for information that is no longer relevant, is tested.