Anti-HIV type 1 Tat Monoclonal antibody

The transcription of HIV1 provirus is regulated by both cellular and viral factors. Various evidence suggests that Tat protein secreted by HIV1-infected cells may have additional action in the pathogenesis of AIDS because of its ability to also be taken up by non-infected cells. Curcumin [diferuloylmethane or 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is the yellow pigment in turmeric Curcuma longa (Linn). it exhibits a variety of pharmacological effects including antiinflammatory and antiretroviral activities. Here, we demonstrated that curcumin used at 10 to 100 nM inhibited Tat transactivation of HIV1-LTR lacZ by 70 to 80% in HeLa cells. In order to develop more efficient curcumin derivatives, we synthesized and tested in the same experimental system the inhibitory activity of reduced curcumin (C-1), which lacks the spatial structure of curcumin; allyl-curcumin (C-2), which possesses a condensed allyl derivative on curcumin that plays the role of metal chelator; and tocopheryl-curcumin (C-3), which enhances the antioxidant activity of the molecule. Results obtained with C-1, C-2 and C-3 curcumin derivatives showed a significant inhibition (70 to 85%) of Tat transactivation. Despite the fact that tocopheryl-curcumin (C-3) failed to scavenge O-2(.-), this curcumin derivative exhibited the most activity; 70% inhibition was obtained at 1 nM, while only 35% inhibition was obtained with the curcumin.

Background: The management of abdominal fat accumulation and metabolic disorders in HIV1-infected patients, by an aerobic training program, is considered. Methods: Seventeen lipodystrophic and 2 dyslipidemic (without body modification) adults were studied before and after 4 months of training. The training load was individualized on a ventilatory threshold basis, determined during a maximal exercise test on cycle ergometer. Total (TAT), Visceral (VAT) and Subcutaneous Adipose Tissue (SAT) were assessed by CT-scan. Total (TC) and High Density Lipoprotein (HDL-C) Cholesterol, Triglycerides (TG), lactate (La), insulin and glucose were measured after a 12-hour-overnight fast. LDL, TC/HDL, TG/HDL, HOMA-insulin resistance index and coronary heart disease (CHD) relative risk (RRCHD) were calculated. Results: Besides a significant improvement of aerobic fitness, trained patients exhibited a reduction in TAT (-12.8%, p < 0.001), specially at the visceral level (- 12%, p < 0.01) and in TC, TG and La (- 23%, - 43% and - 19% respectively, p < 0.01). HDL-C was increased (+ 6%, p < 0.01). All these effects were above changes that could be expected by a possible regression to the mean artefact. Both TC/HDL and TG/HDL were reduced (p < 0.01) and the estimated RRCHD decreased by &SIM;13% (p < 0.01). No significant training effect was observed on the 9 available HOMAs. Significant correlations were found between changes in blood lipid values and baseline measures (r range - 0.55 to - 0.79, p < 0.05), indicating a larger improvement when baseline lipid parameters were higher. Conclusion: Aerobic training reduced visceral fat, lipid disorders, basal blood lactate and CHD markers in HIV patients. Training effects were particularly important for patients with marked dyslipidemia.