Tetrahdroxysqualene from Rhus taitensis shows antimycobacterial activity against Mycobacterium tuberculosis

Tuberculosis has become a major health problem, in particular with the emergence of extremely drug resistant tuberculosis (XDRTB). In our search for new therapeutic leads against TB, we isolated a new triterpene (1) from the plant Rhus taitensis collected in Papua New Guinea. Tetrahydroxysqualene (1) was isolated using bioassay-guided fractionation of the methanolic extract of R. taitensis leaves and twigs. The structure of tetrahydroxysqualene (1) was elucidated on the basis of HRESIMS and 1D and 2D NMR spectra. Tetrahydroxysqualene (1) exhibited antituberculosis activity with an MIC of 10.0 microg/mL, while showing only modest cytotoxicity.     

The influence of aging on intestinal absorption of vitamin B12 and niacin in rats

The intestinal absorption of doses of vitamin B₁₂ and of niacin was examined in 6, 12, and 24 months old female Wistar rats. Rats were dosed via stomach tube with radioactive forms of the vitamins and were killed 16 hours later. Percent of the dose remaining in the stomach and gastro intestinal tract andthe collected feces was determined. Absorption of the two vitamins was not influenced by the age of the animals.     

Granular cell myoblastoma arising from the thoracic sympathetic nerve chain.

Granular cell myoblastoma has been of interest both to the clinician and the pathologist for many years. This uncommon tumor presents the usual diagnostic problem of a mass, but the actual diagnosis of granular cell myoblastoma is rarely made prior to biospy. The origin of the tumor from either myoblastic or neural tissue remains controversial. Light and electron microscopic studies of a granular cell myoblastoma uniquely located in the posterior mediastinum and associated with the sympathetic chain support the neural origin of this tumor.     

Inhibition of tubulin polymerization by vitilevuamide, a bicyclic marine peptide, at a site distinct from colchicine, the vinca alkaloids, and dolastatin 10

Vitilevuamide, a bicyclic 13 amino acid peptide, was isolated from two marine ascidians, Didemnum cuculiferum and Polysyncranton lithostrotum. Vitilevuamide was cytotoxic in several human tumor cell lines, with LC(50) values ranging from 6 to 311nM, and analysis in a 25-cell line panel revealed a weak correlation with several taxol analogs. Vitilevuamide was strongly positive in a cell-based screen for inhibitors of tubulin polymerization. Vitilevuamide at 9 microg/mL (5.6 microM) had an effect equivalent to the maximal effect of colchicine at 25 microg/mL (62.5 microM). Vitilevuamide was active in vivo against P388 lymphocytic leukemia, increasing the lifespan of leukemic mice 70% at 30 microg/kg. We hypothesized that at least part of the cytotoxic mechanism of vitilevuamide was due to its inhibition of tubulin polymerization. Vitilevuamide was found to inhibit polymerization of purified tubulin in vitro, with an IC(50) value of approximately 2 microM. Cell cycle analysis showed that vitilevuamide arrested cells in the G(2)/M phase with 78% of treated cells tetraploid after 16hr. Therefore, vitilevuamide was tested for its ability to inhibit binding of known tubulin ligands. Vitilevuamide exhibited non-competitive inhibition of vinblastine binding to tubulin. Colchicine binding to tubulin was stabilized in the presence of vitilevuamide in a fashion similar to vinblastine. Dolastatin 10 binding was unaffected by vitilevuamide at low concentrations, but inhibited at higher ones. GTP binding was also found to be weakly affected by the presence of vitilevuamide. These results suggest the possibility that vitilevuamide inhibits tubulin polymerization via an interaction at a unique site.