Here, cocultures of infected HIV-1 cells with primary CD4(+) T cells or BV-6 supplier lymphoid cells were used to evaluate virus transmission and the effect of known antiretrovirals. Transfer of HIV antigen from infected to uninfected cells was resistant to the reverse transcriptase inhibitors (RTIs) zidovudine (AZT) and tenofovir, but was blocked by the attachment inhibitor IgGb12. However, quantitative measurement of viral DNA production demonstrated that all anti-HIV agents blocked virus replication with similar potency to cell-free virus infections. Cell-free and cell-associated
infections were equally sensitive to inhibition of viral replication when HIV-1 long terminal repeat (LTR)-driven green fluorescent protein (GFP) expression in target cells was measured. However, detection of GFP by flow cytometry may incorrectly estimate the efficacy of antiretrovirals in cell-associated virus transmission, due to replication-independent click here Tat-mediated LTR transactivation as a consequence of cell-to-cell events that did not occur in short-term (48-h) cell-free virus infections. In conclusion, common markers of virus replication may not accurately correlate and measure infectivity or drug efficacy in cell-to-cell virus transmission. When accurately quantified, active drugs blocked proviral DNA and virus replication in cell-to-cell transmission, recapitulating the efficacy of antiretrovirals
in cell-free virus infections and in vivo.”
“Low doses of psychostimulants, including methylphenidate (MPH), are highly effective in the treatment of attention-deficit/hyperactivity disorder (ADHD). At these doses, psychostimulants improve prefrontal cortex (PFC)-dependent function. Recent evidence indicates that low and clinically Acetophenone relevant doses of psychostimulants target norepinephrine
(NE) and dopamine (DA) signaling preferentially in the PFC. To better understand the neural mechanisms responsible for the regional selectivity of low-dose psychostimulant action, it is important to first identify the underlying neurocircuitry. The current study used reverse microdialysis to test the hypothesis that the preferential targeting of PFC catecholamines by low-dose psychostimulants involves direct action within the PFC, reflecting an intrinsic property of this region. For these studies, the effects of varying concentrations of MPH (0.25, 1.0, and 4.0 mu M) on NE and DA efflux were examined within the PFC and select subcortical fields in unanesthetized rats. Low concentrations of MPH elicited significantly larger increases in extracellular levels of NE and DA in the PFC than in subcortical regions linked to motor-activating and arousal-promoting actions of psychostimulants (nucleus accumbens and medial septal area, respectively). The differential action of MPH across regions disappeared at higher concentrations.