Endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in vascular smooth muscle.

Endothelin is a potent endothelium-derived vasoconstrictor peptide recently characterized from porcine and human vascular endothelial cells. Here we provide evidence that endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in porcine coronary artery smooth muscle. The vasoconstrictor action of endothelin is efficiently antagonized by low doses of the dihydropyridine Ca2+-channel blocker nicardipine. Endothelin augments the Ca2+-induced contraction in a high-K+ depolarizing solution, markedly enhances high-threshold Ca2+-channel current on the whole-cell patch clamp recording, and causes a sustained increase in the intracellular Ca2+ that is largely dependent on extracellular Ca2+. These findings suggest that endothelin exerts its vasoconstrictor effect by either directly or indirectly activating the voltage-dependent Ca2+ channel.     

Dynamic process of colonization by Haemophilus influenzae in children--is H. influenzae normal flora in the throat?]

Eighty-seven oropharyngeal isolates of Haemophilus influenzae were obtained by two time cultures six months apart from a total of 288 children who attend a kindergarten. We analyzed the strains by comparing their serotypes, biotypes, beta-lactamase activity and by performing electrophoresis of outer membrane proteins on polyacrylamide gels. Only nineteen strains were not identical, the rest of the 68 strains were classified into 23 types. During 6 months at least 15 types of strains lost from this group and 21 types of new strains were obtained. There were no children who had identical pairs of H. influenzae in their oropharynx during the 6 months. The classification of strains in oropharynx suggested that person-to-person transmission of nontypable H. influenzae can occur. We concluded that oropharyngeal colonization by nontypable H. influenzae is not a normal flora in children.     

Experimental and ab initio studies on the structural,magnetic, photocatalytic,and antibacterial properties of Cu-doped ZnO nanoparticles

Copper-doped ZnO nanoparticles with a dopant concentration varying from 1–7 mol% were synthesized and their structural, magnetic, and photocatalytic properties were studied using XRD, TEM, SQUID magnetometry, EPR, UV-vis spectroscopy, and first-principles methods within the framework of density functional theory (DFT). Structural analysis indicated highly crystalline Cu-doped ZnO nanoparticles with a hexagonal wurtzite structure, irrespective of the dopant concentration. EDX and EPR studies indicated the incorporation of doped Cu²⁺ ions in the host ZnO lattice. The photocatalytic activities of the Cu-doped ZnO nanoparticles investigated through the degradation of methylene blue demonstrated an enhancement in photocatalytic activity as the degradation rate changed from 9.89 × 10⁻⁴ M min⁻¹ to 4.98 × 10⁻² M min⁻¹. By the first-principles method, our results indicated that the Cu(3d) orbital was strongly hybridized with the O(2p) state below the valence band maximum (VBM) due to covalent bonding, and the ground states of the Cu-doped ZnO is favorable for the ferromagnetic state by the asymmetry of majority and minority states due to the presence of unpaired electron.

Magnetic, photocatalytic and antibacterial performance of ZnO NPs were enhanced as doped with Cu.     

Self-splicing of the Tetrahymena group I ribozyme without conserved base-triples

BACKGROUND: Group I introns share a conserved core region consisting of two domains, P8-P3-P7 and P4-P6, joined by four base-triples. We showed previously that the T4 td intron can perform phosphoester transfer reactions at two splice sites in the absence of both P4-P6 and the conserved base-triples, whereas it is barely able to perform the intact splicing reaction due to the difficulty of conducting the sequential reactions. RESULTS: Based on previous findings, we constructed a bimolecular ribozyme lacking a large portion of P4-P6 and the base-triples from the Tetrahymena intron, on the assumption that the long-range interactions of the peripheral regions in the two RNAs can compensate for the deteriorated core. The bimolecular ribozyme performed the intact splicing reaction. CONCLUSION: The present analysis indicates that the base-triples are nonessential, but that L4 and the distal part of P4 in P4-P6 are important for conducting the splicing reaction. The reconstituted self-splicing ribozyme provides an amenable system for analysing the role(s) of elements in the core region in the self-splicing reaction mechanism.     

Induction of beta-lactamase by various beta-lactam antibiotics in Enterobacter cloacae

The induction of beta-lactamase in Enterobacter cloacae GN5797 was studied by using 23 beta-lactam antiobiotics, including newly introduced drugs, as inducers. the beta-lactam antibiotics can be classified into three groups on the basis of their inducer activity. Among the tested cephalosporins, cephamycin derivatives such as cefoxitin, cefmetazole, and YM09330 had high inducer activity even at low drug concentrations. On the other hand, cefoperazone, cefsulodin, piperacillin, and apalcillin showed low inducer activity when compared with the other cephalosporins.     

Inhibitory Activities of Gatifloxacin (AM-1155), a Newly Developed Fluoroquinolone, against Bacterial and Mammalian Type II Topoisomerases

We determined the inhibitory activities of gatifloxacin against Staphylococcus aureus topoisomerase IV, Escherichia coli DNA gyrase, and HeLa cell topoisomerase II and compared them with those of several quinolones. The inhibitory activities of quinolones against these type II topoisomerases significantly correlated with their antibacterial activities or cytotoxicities (correlation coefficient [r] = 0.926 for S. aureus, r = 0.972 for E. coli, and r = 0.648 for HeLa cells). Gatifloxacin possessed potent inhibitory activities against bacterial type II topoisomerases (50% inhibitory concentration [IC₅₀] = 13.8 μg/ml for S. aureus topoisomerase IV; IC₅₀ = 0.109 μg/ml for E. coli DNA gyrase) but the lowest activity against HeLa cell topoisomerase II (IC₅₀ = 265 μg/ml) among the quinolones tested. There was also a significant correlation between the inhibitory activities of quinolones against S. aureus topoisomerase IV and those against E. coli DNA gyrase (r = 0.969). However, the inhibitory activity against HeLa cell topoisomerase II did not correlate with that against either bacterial enzyme. The IC₅₀ of gatifloxacin for HeLa cell topoisomerase II was 19 and was more than 2,400 times higher than that for S. aureus topoisomerase IV and that for E. coli DNA gyrase. These ratios were higher than those for other quinolones, indicating that gatifloxacin possesses a higher selectivity for bacterial type II topoisomerases.     

Permeability of the flavonoids liquiritigenin and its glycosides in licorice roots and davidigenin, a hydrogenated metabolite of liquiritigenin, using human intestinal cell line Caco-2

The present investigation focused on the transepithelial flux of liquiritigenin (LG), davidigenin (DG), liquiritin (LQ), and liquiritin apioside (LA) using the human colonic cell line Caco-2 as a model of human intestinal absorption. Apparent permeability coefficients (Papp) for the apical to basolateral flux of LG and DG were (16.0 +/- 0.727) x 10(-6) cm/s and (18.2 +/- 1.67) x 10(-6) cm/s, respectively. These Papp were higher than that of the transcellular transport marker propranolol (13.5 +/- 0.34) x 10(-6) cm/s (P < 0.01). Papp for the apical to basolateral flux of LQ and LA were (0.26 +/- 0.12) x 10(-6) cm/s and (0.075 +/- 0.005) x 10(-6) cm/s, respectively. These Papp were lower than that of the paracellular transport marker mannitol (0.64 +/- 0.04) x 10(-6) cm/s (LG, P < 0.01; LA, P < 0.001). These data suggested excellent absorption of LG and DG through the human intestinal epithelial cell line. On the contrary, poor absorption of LQ and LA was expected due to the little transepithelial flux of these compounds in the human colonic cell line Caco-2.