Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse.

We have compared the efficacy of daily injection of recombinant leptin protein (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene (Ad-leptin) for treatment of obesity in the obese (ob/ob) mouse model. We demonstrate an improved correction profile for obesity and associated surrogate markers using the adenovirus delivery method. Rate of weight loss and percentage satiety were significantly greater in the mice treated with Adleptin. These findings were associated with lower peak serum leptin levels with Ad-leptin (22.9 +/- 2.6 ng/ml for the human gene, and 48.9 +/- 11.5 ng/ml for the murine gene) compared to rh-leptin (385.2 +/- 36.0 ng/ml). (Values are given as mean +/- standard error of the mean.) Importantly rh-leptin and ex vivo-expressed Ad-leptin were equivalently active in a functional cell-based assay. The primary difference in the two therapeutic approaches is the continuous chronic secretion of leptin mediated by gene delivery, versus the intermittent bolus delivery and rapid clearance of the daily injection of rh-leptin protein. Thus, in vivo findings suggest that leptin effects are better achieved at lower steady-state levels, a pharmacological feature attained here by gene therapy. These findings may have implications for the potential use of leptin in the treatment of obesity.

Diagnosis of Helicobacter pylori infection in a colony of rhesus monkeys (Macaca mulatta).

Twenty-three young adult rhesus monkeys from China were evaluated for the presence of Helicobacter pylori. Gastric body and antral biopsy samples were tested for H. pylori by PCR analysis, culture, rapid urease testing, and histologic evaluation. Serologic testing to detect H. pylori immunoglobulin G (IgG) antibodies was performed by using a commercially available human-based enzyme-linked immunosorbent assay (ELISA) test and an ELISA test which utilized homologous H. pylori antigens and an anti-rhesus IgG conjugate. PCR analysis with H. pylori-specific 26-kDa protein primers detected H. pylori in 21 of the 23 rhesus monkeys (91%). Culture testing identified the organism in 12 of the 23 animals (52%). Rapid urease tests were positive for all animals. H. pylori was diagnosed by histological examination in 11 of 23 monkeys (48%). Of the 21 monkeys positive for H. pylori by PCR, only 3 (14%) had positive results by the commercial ELISA test, yielding a sensitivity of 14%, a specificity of 100%, and an accuracy of 22%. However, 19 of the 21 PCR-positive animals (90%) had positive results by the ELISA test with homologous rhesus H. pylori antigen and anti-monkey conjugate, with predicted index values greater than or equal to 0.7 considered positive and values between 0.5 and 0.7 considered equivocal. This test had a sensitivity of 90%, a specificity of 100%, and an accuracy of 91%. Therefore, the ELISA test with rhesus monkey origin components was more accurate for detecting infected animals than the human-based ELISA.