“
“APOBEC3 proteins can inhibit human immunodeficiency virus type 1 (HIV-1) replication by inducing G-to-A mutations in newly synthesized viral DNA. However, HIV-1 is able to overcome the antiretroviral activity of some of those enzymes by the viral protein Vif. We investigated the impact of different processivities of HIV-1 reverse transcriptases (RT) on the frequencies of G-to-A mutations introduced by APOBEC3 proteins. Wild-type RT or the M184V, M184I,

and K65R+M184V RT variants, which are increasingly impaired in their processivities, were used in the context of a vif-deficient R406 molecular HIV-1 clone to infect H9 cells and peripheral blood mononuclear cells (PBMCs). After two rounds of infection, a part of the HIV-1 env gene was amplified, cloned, and sequenced. The M184V mutation led to G-to-A mutation frequencies that were similar to those of the wild-type RT in H9 cells and PBMCs. The frequencies of G-to-A mutations were increased after infection with the M184I virus variant. This effect was augmented when using the K65R+M184V virus variant (P < 0.001). Overall, the G-to-A mutation frequencies were lower in PBMCs than in H9 cells. VE-821 concentration Remarkably, 38% +/- 18% (mean +/- standard deviation) of the env clones derived from PBMCs did not harbor any G-to-A mutation. This was rarely observed in H9 cells (3% +/- 3%). Our data imply that the frequency of G-to-A

mutations induced by APOBEC3 proteins can be influenced by the processivities of HIV-1 RT variants. The high number of nonmutated clones derived from PBMCs leads to several hypotheses, including that additional antiretroviral mechanisms of APOBEC3 proteins other than their deamination activity might be involved in the inhibition of vif-deficient viruses.”
“OBJECTIVE:

Thromboembolism is one of the most common and serious complications associated with the endovascular embolization of intracranial aneurysms. We report our clinical experiences with intra-arterial tirofiban infusion during aneurysm embolization.

METHODS: The clinical, radiological, and laboratory Sclareol data of 24 patients harboring 25 aneurysms (25 procedures) who underwent intra-arterial tirofiban infusion for thromboembolism during the endovascular treatment of intracranial aneurysms were reviewed retrospectively. Thrombi or emboli were resolved by superselective intra-arterial tirofiban infusion via a microcatheter.

RESULTS: The study cohort comprised 14 unruptured and 11 ruptured aneurysms. Intra-arterially infused tirofiban doses ranged from 0.2 to 1.0 mg (mean +/- standard deviation, 0.64 +/- 0.25 mg). Thromboemboli were resolved, and arteries were recanalized on all occasions except one: a case of distal middle cerebral artery embolism. No hemorrhagic complications related to intra-arterial tirofiban infusion occurred.