Purified exosomes from CD8(+) T-cell culture supernatant noncytotoxically suppressed CCR5-tropic (R5) and

CXCR4-tropic (X4) replication of HIV-1 in vitro through a protein moiety. Similar antiviral activity was also found in exosomes isolated from two HIV-1-infected subjects. The antiviral Ruboxistaurin exosomes specifically inhibited HIV-1 transcription in both acute and chronic models of infection. Our results, for the first time, indicate the existence of an antiviral membrane-bound factor consistent with the hallmarks defining noncytotoxic CD8(+) T-cell suppression of HIV-1.”
“The majority of the studies on the actions of estrogens in the ventrolateral part of the hypothalamic ventromedial nucleus (VMNvI) concern the factors that modulate the receptive component of the feminine sexual behavior and the expression of molecular markers of neuronal activation. To further our understanding of the factors that regulate synaptic plasticity in the female VMNvI, we have examined the effects of estradiol

and progesterone, and of estrogen receptor (ER) subtype selective ligands on the number of dendritic and spine synapses established by individual VMNvI neurons and on sexual behavior. In contrast to earlier studies that analyzed synapse densities, our results show that exogenous estradiol increases the number of spine as well as of dendritic synapses, irrespective of the dose and regimen of administration. They also reveal that an effective dose of estradiol administered as one single PCI-32765 clinical trial pulse induces the formation of more synapses than the same dose administered as two pulses on consecutive days. Our results further show that both ER subtypes

are involved in the mediation of the synaptogenic effects of estrogens on VMNvI neurons since the administration of the selective ER alpha, propyl-pyrazole-triol (PPT), and ER beta, diarylpropionitrile (DPN), agonists induced a significant increase in the number of synapses that, however, was more exuberant for PPT. Despite its relevant role in feminine sexual behavior, progesterone had SCH772984 concentration no synaptogenic effect in the VMNvI as no changes in synapse numbers were noticed in rats treated with progesterone alone, with estradiol followed by progesterone or with the antiprogestin mifepristone (RU486). Except for the sequential administration of estradiol and progesterone, none of the regimens was associated with lordosis response to vaginocervical stimulation. Therefore, from the sex steroids that undergo cyclic variations over the estrous cycle, only estrogens, acting through both ER alpha and ER beta, play a key role in the activation of the neural circuits involving the ventromedial nucleus of the hypothalamus. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.