Megastigmane and iridoid glucosides from Clerodendrum inerme

From the aerial parts of Clerodendrum inerme, two megastigmane glucosides (sammangaosides A and B) and a iridoid glucoside (sammangaoside C) were isolated together with 15 known compounds. The structural elucidations were based on analyses of physical and spectroscopic data.     

Iridoid glucosides from Barleria lupulina

From the aerial part of Barleria lupulina, 8-O-acetyl-6-O-trans-p-coumaroylshanzhiside, saletpangponosides A-C and 8-O-acetylmussaenoside were isolated together with 13 known compounds. The structural elucidations were based on analyses of physical and spectroscopic data.     

Cardiac glycosides from Cryptostegia grandiflora

From the leaves of Cryptostegia grandiflora, four new cardiac glycosides oleandrigenin 3-O-beta-glucopyranosyl-(1-->4)-beta-cymaropyranosyl-(1-->4)-beta-digitoxopyranoside, cryptostigmin I, oleandrigenin 3-O-beta-glucopyranosyl-(1-->4)-alpha-rhamnopyranoside, cryptostigmin II, 16-propionylgitoxigenin 3-O-beta-glucopyranosyl-(1-->4)-alpha-rhamnopyranoside, cryptostigmin III and oleandrigenin 3-O-beta-glucopyranosyl-(1-->6)-beta-glucopyranosyl-(1-->4)-beta-cymaropyranosyl-(1-->4)-beta-digitoxopyranoside, cryptostigmin IV have been isolated together with two known cardenolides subalpinosid and 16-O-acetyl-digitalinum verum. The structures of the isolated compounds were verified by means of MS and NMR spectral analyses.     

Specific binding and biological effects of tumor promoting phorbol esters on sponges

Sponges grown in the presence of 12-O-tetradecanoyl phorbol-13-acetate (TPA) show deep alterations of their structure and development. Their aquiferous system (flagellated cells and canals) is largely altered and the tissues show an unusually high cell density. This focalized effect of TPA on the aquiferous system seems specific and is reversible at low concentrations (100 ng/ml). A toxic, non-specific effect is also noted, particularly at high concentrations (5000 ng/ml). Using 3H-phorbol-12, 13-dibutyrate (3H-PDBu), we demonstrate a class of specific binding sites for phorbol esters in the homogenates of sponges. These binding sites have high affinity (Kd = 26.0 nM) for PDBu and at saturation about 20 pmoles of 3H-PDBu is bound per mg protein of sponge homogenates. The binding of 3H-PDBu was inhibited by other phorbol esters and their congeners, and there was a good correlation between their potency in binding inhibition and their tumor promoting activity. It is concluded that sponges have a class of specific saturable and high affinity receptors for phorbol esters and that there is a very high conservation of these receptors during evolution. Such specific binding may be responsible for subsequent biological effect of TPA on sponges.     

Differential effects of interferon-gamma on production of trypanosome-derived lymphocyte-triggering factor by Trypanosoma brucei gambiense and Trypanosoma brucei brucei

Trypanosome-derived lymphocyte-triggering factor (TLTF) produced by Trypanosoma brucei brucei stimulates production of interferon-gamma (IFN-gamma) by CD8+ T cells, and it is reported that, in turn, IFN-gamma stimulates proliferation of T. b. brucei. We studied the role of TLTF in trypanosome proliferation using the Wellcome strain (WS) of Trypanosoma brucei gambiense and the ILtat 1.4 strain (IL) of T. b. brucei. Increase in the number of WS in infected rats is more rapid than IL and corresponds with comparatively higher levels of IFN-gamma. Production of IFN-gamma, as measured by protein and messenger RNA (mRNA) levels, was maintained by splenocytes from WS-infected rats, whereas levels decreased in IL-infected rats, accompanied by prolongation of infection. Expression of TLTF mRNA by in vitro-cultured WS was promoted in a dose-dependent fashion by addition of recombinant rat IFN-gamma at all concentrations tested. The addition of lower concentrations of IFN-gamma to cultured IL increased expression of TLTF mRNA, whereas, in contrast to WS, addition of 100 and 1,000 U/ml IFN-gamma decreased expression of TLTF by IL. These results show that unlike WS, elevated IFN-gamma concentrations lead to decreased TLTF production by IL. It is believed that decreased TLTF production in IL-infected rats leads to lowered IFN-gamma production, thereby slowing IL proliferation.     

Age-dependent decreases of sulfur and magnesium in human round ligaments of the uterus and relationships among elements

To elucidate the compositional change of ligaments with aging, the authors investigated both age-related changes of elements and relationships among elements in the round ligaments of the uterus (round ligaments) by inductively coupled plasma-atomic emission spectrometry. The bilateral round ligaments were resected from 20 cadavers and also from the uteri removed surgically from 11 patients bearing uterine myoma or cancer. Thirty-one subjects ranged in age from 34 to 92 yr. It was found that both S and Mg decreased gradually in the round ligaments with aging, but Ca, P, Zn, Fe, and Al did not change significantly with aging. Regarding the relationships among elements, very significant direct correlations were found among the contents of Ca, P, S, and Mg in the round ligaments, whereas significant inverse correlations were found between the contents of Zn and elements, such as Ca, P, S, and Mg. It should be noted that there was an extremely significant direct correlation between Ca and P contents in the round ligaments.     

Induction of apoptosis by ionizing radiation and CI-1033 in HuCCT-1 cells

CI-1033 is a quinazoline-based HER family tyrosine kinase inhibitor that is currently being evaluated as a potential anticancer agent. The present study examines the molecular mechanism by which CI-1033 induces apoptosis either as a single agent or in combination with radiation. Although CI-1033 alone did not induce apoptosis, the simultaneous exposure of cells to CI-1033 and radiation induced significant levels of apoptosis. The sequential treatment of cells with CI-1033 followed by radiation induced an even greater effect with 62.6% of cells undergoing apoptosis but this enhanced effect was not seen if cells were treated first with radiation and then CI-1033. The combination treatment induces apoptosis of HuCCT-1 via upregulation of FasL and Bid cleavage. These data suggest that modulation of the Fas-FasL pathway and activation of Bid could be useful for increasing the anti-tumor effect of CI-1033 in this type of cancer.