Israel Medical Association Journal

Objectives: To examine the effect of meloxicam, a selective COX-2 inhibitor, or low dose aspirin on the development of experimental atherosclerosis in apoE knockout (KO) compared to wild-type (WT) mice. We aimed to test the hypothesis that meloxicam, a potential vasculitis inducer, would exacerbate atherosclerotic lesions while aspirin, which is known to reduce the incidence of thrombosis occlusive events, would increase protection in this model.

Methods: We randomly divided 36 male apoE KO and 36 WT mice, 8 weeks old. Mice were treated for 10 weeks with 0.1 mg/ml aspirin, or 0.05 mg/ml meloxicam, dissolved in their drinking water. Control groups received regular drinking water. At sacrifice, the hearts were removed for histochemical staining and plaque size and composition were examined.

Results: Aspirin-treated animals displayed a decreased atherosclerotic lesion area compared to the untreated control mice, while meloxicam had a null effect on the extent of atherosclerosis in Apo E KO mice.

Conclusions: These results suggest that low dose aspirin reduces early atherosclerosis, while inhibition of COX-2 by meloxicam is not associated with an increase in atherosclerotic plaque size in this mouse model.

Background: The humanized SCID mouse model is an attractive tool for testing gene therapy to combat human immunodeficiency virus infection in vivo.

Objectives: To devise a more specific gene therapy directed against HIV, replacing the formerly used interferon with either soluble CD4 molecule immunoadhesin (sCD4-IgG) and/or anti-gp41 monoclonal antibody (2F5), or negative transdominants (Tat, Rev).

Methods: Human monocytoid cell line (U937) was transfected with IFNa[1], b or g genes. 3T3 murine fibroblastic cell line was transfected with sCD4-IgG or 2F5, or both genes, and a human T4 cell line (CEM) was grafted to SCID mice. Negative transdominant genes (Tat, Rev or both) were also transduced in CEM T cell line. Animals were then challenged with HIV-1[2]. Viral load was followed.

Results: IFNa or b were potent anti-HIV, reducing viral load in vivo and inhibiting reverse transcriptase activity in human-removed cells from animals. sCD4-IgG immunoadhesin and gp41 monoclonal antibody resulted in a dramatic reduction of HIV-1 cellular and plasmatic viral load in humanized SCID mice. The simultaneous introduction of negative Tat and Rev genes resulted in a synergistic inhibition of HIV-1 replication in vivo.

Conclusions: Despite the marked reduction of HIV-1 propagation by IFN genes or by negative Tat and Rev transdominants, the gene therapy using soluble CD4 immunoadhesin or anti-gp41 was a more efficient preventive treatment against HIV infection.