Photothermoplastic films for holographic recording

The electrophotographic and sensitometric characteristics of poly-N-vinyl carbazole photothermoplastic films, sensitized by an amorphous-Se sublayer are examined. It is shown that the photosensitivity of the material can be improved and its spectral range can be expanded by sensitization of amorphous Se with additions of Te, As, and Sb; this can be accomplished without a significant reduction in diffraction efficiency and resolving power

Treatment of Mycobacterium tuberculosis with antisense oligonucleotides to glutamine synthetase mRNA inhibits glutamine synthetase activity, formation of the poly-L-glutamate/glutamine cell wall structure, and bacterial replication.

New antibiotics to combat the emerging pandemic of drug-resistant strains of Mycobacterium tuberculosis are urgently needed. We have investigated the effects on M. tuberculosis of phosphorothioate-modified antisense oligodeoxyribonucleotides (PS-ODNs) against the mRNA of glutamine synthetase, an enzyme whose export is associated with pathogenicity and with the formation of a poly-L-glutamate/glutamine cell wall structure. Treatment of virulent M. tuberculosis with 10 microM antisense PS-ODNs reduced glutamine synthetase activity and expression by 25-50% depending on whether one, two, or three different PS-ODNs were used and the PS-ODNs' specific target sites on the mRNA. Treatment with PS-ODNs of a recombinant strain of Mycobacterium smegmatis expressing M. tuberculosis glutamine synthetase selectively inhibited the recombinant enzyme but not the endogenous enzyme for which the mRNA transcript was mismatched by 2-4 nt. Treatment of M. tuberculosis with the antisense PS-ODNs also reduced the amount of poly-L-glutamate/glutamine in the cell wall by 24%. Finally, treatment with antisense PS-ODNs reduced M. tuberculosis growth by 0. 7 logs (1 PS-ODN) to 1.25 logs (3 PS-ODNs) but had no effect on the growth of M. smegmatis, which does not export glutamine synthetase nor possess the poly-L-glutamate/glutamine (P-L-glx) cell wall structure. The experiments indicate that the antisense PS-ODNs enter the cytoplasm of M. tuberculosis and bind to their cognate targets. Although more potent ODN technology is needed, this study demonstrates the feasibility of using antisense ODNs in the antibiotic armamentarium against M. tuberculosis

Cytotoxic triterpenoid saponins from the roots of Cephalaria gigantea

Three new oleanane-type saponins, giganteosides L (1)(I), M (2) and N (3) along with eight known ones were isolated from the roots of Cephalaria gigantea. Their structures were established as 3-O-[-D-galactopyranosyl-(12)--D-glucuronopyranosyl]-28-O-[-D-glucopyranosyl-(16)--D-glucopyranosyl]-oleanolic acid, 3-O-[-D-galactopyranosyl-(12)--D-glucuronopyranosyl]-28-O-[-D-glucopyranosyl-(16)--D-glucopyranosyl]-hederagenin, 3-O-[-L-rhamnopyranosyl-(12)--D-glucuronopyranosyl]-28-O-[-D-glucopyranosyl-(16)--D-glucopyranosyl]-hederagenin, resp., by means of spectroscopic methods (1D and 2D NMR, HR-ESI-MS). Cytotoxic activity of monodesmosides was investigated in vitro using three cancer cell lines, namely, human non pigmented melanoma MEL-5 and human leukemia HL-60. Giganteosides D (4) and E (5) showed antiproliferative effect on human cell lines with IC50 values in the range 3.15-7.5 M

Hairpin extensions enhance the efficacy of mycolyl transferase-specific antisense oligonucleotides targeting Mycobacterium tuberculosis

We have investigated the efficacy of modifying gene-specific antisense phosphorothioate oligodeoxyribonucleotides (PS-ODNs) by the addition of 5′ and 3′ hairpin extensions. As a model system, we have targeted the Mycobacterium tuberculosis 30/32-kDa mycolyl transferase protein complex genes encoding three highly related enzymes (antigens 85 A, B, and C). Whereas the addition of a hairpin extension at only one end of the PS-ODNs did not improve their inhibitory capacity, the addition of hairpin extensions at both ends enhanced their capacity to inhibit M. tuberculosis multiplication in comparison with unmodified PS-ODNs. A combination of three 5′-, 3′-hairpin-modified PS-ODNs (HPS-ODNs) targeting each of the three mycolyl transferase transcripts inhibited bacterial growth in broth culture by ≈1.75 log units (P < 0.0001) and in human THP-1 macrophages by ≈0.4 log units (P < 0.0001), which to our knowledge has not previously been demonstrated for any PS-ODN; reduced target gene transcription by ≥90%; caused ≈90% reduction in mycolyl transferase expression; and increased bacterial sensitivity to isoniazid by 8-fold. The growth-inhibitory effect of the HPS-ODNs was gene-specific. Mismatched HPS-ODNs had no growth-inhibitory capacity. This study demonstrates that 5′- and 3′-HPS-ODNs are highly efficacious against M. tuberculosis and supports the further development of antisense technology as a therapeutic modality against tuberculosis