Inhibition of human immunodeficiency virus type 1 replication by combination of transcription inhibitor K-12 and other antiretroviral agents in acutely and chronically infected cells. (1/274)

8-Difluoromethoxy-1-ethyl-6-fluoro-1,4-dihydro-7-[4-(2-methoxyp hen yl)-1- piperazinyl]-4-oxoquinoline-3-carboxylic acid (K-12) has recently been identified as a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) transcription. In this study, we examined several combinations of K-12 and other antiretroviral agents for their inhibitory effects on HIV-1 replication in acutely and chronically infected cell cultures. Combinations of K-12 and a reverse transcriptase (RT) inhibitor, either zidovudine, lamivudine, or nevirapine, synergistically inhibited HIV-1 replication in acutely infected MT-4 cells. The combination of K-12 and the protease inhibitor nelfinavir (NFV) also synergistically inhibited HIV-1, whereas the synergism of this combination was weaker than that of the combinations with the RT inhibitors. K-12 did not enhance the cytotoxicities of RT and protease inhibitors. Synergism of the combinations was also observed in acutely infected peripheral blood mononuclear cells. The combination of K-12 and cepharanthine, a nuclear factor kappa B inhibitor, synergistically inhibited HIV-1 production in tumor necrosis factor alpha-stimulated U1 cells, a promonocytic cell line chronically infected with the virus. In contrast, additive inhibition was observed for the combination of K-12 and NFV. These results indicate that the combinations of K-12 and clinically available antiretroviral agents may have potential as chemotherapeutic modalities for the treatment of HIV-1 infection.  (+info)

Effects of dauricine, quinidine, and sotalol on action potential duration of papillary muscles in vitro. (2/274)

AIM: To compare the characteristics of dauricine, sotalol, and quinidine on action potential duration (APD). METHODS: Using intracellular microelectrode method to record APD in guinea pig papillary muscles. RESULTS: Dauricine 20 mumol.L-1 prolonged action potential at 90% repolarization, the percent of APD prolongation were 22 +/- 8, 11 +/- 6, 9 +/- 5, 7 +/- 5, 6 +/- 3, 4.3 +/- 2.8, 4.5 +/- 2.8 at the cycle lengths of 200-2000 ms, dauricine became more effective in lengthening APD at short cycle lengths. The effect of dauricine on prolonging APD exhibited normal use-dependence, whereas quinidine 1 mumol.L-1 and sotalol 10 mumol.L-1 were less effective in lengthening APD at short cycle lengths. The effect of quinidine and sotalol on APD exhibited reverse use-dependence. CONCLUSSION: The effect of dauricine on APD depends on activation frequency.  (+info)

Effect of tetrandrine on proto-oncogene c-fos expression in rat cerebrum. (3/274)

AIM: To detect the effect of tetrandrine (Tet) on c-fos gene expression in cerebrum induced by lindane, a neurotoxicant which activates Ca2+ channels. METHODS: Northern and dot blotting, dual wavelength thin layer chromatography scanner, were used in this study. RESULTS: Lindane 30 mg.kg-1 given by intragastric gavage (i.g.) increased the expression of c-fos gene to 146 mm2 in rat cerebrum 1 h after treatment. Tet 1, 2, and 4 mg.kg-1 given by i.g. 30 min prior to lindane reduced c-fos gene expression in a concentration-dependent manner. Expressed genes reached only 86, 40, and 39 mm2, respectively. CONCLUSION: Tet inhibited c-fos gene expression in rat cerebrum induced by Ca2+ agonist-lindane.  (+info)

Stimulation of pregnant rat uterine contraction by the polychlorinated biphenyl (PCB) mixture aroclor 1242 may be mediated by arachidonic acid release through activation of phospholipase A2 enzymes. (4/274)

The polychlorinated biphenyl (PCB) mixture Aroclor 1242 (A1242) increases frequency of contractions of pregnant rat uteri, suggesting a possible mechanism for decreased gestational age and increased spontaneous abortion in women and animals exposed to PCBs. In the present study, we hypothesized that A1242-induced stimulation of uterine contraction is mediated by arachidonic acid released by phospholipase A2 (PLA2) enzymes. Isometric uterine contraction was measured in longitudinal uterine strips isolated from gestation day 10 rat. Pretreatment of uterine strips with the PLA2 inhibitor (E)-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (HELSS) or manoalide, or an inhibitor of the G protein of PLA2, isotetrandrine, completely prevented the increase of contractile frequency induced by 50 microM A1242. However, the phospholipase C inhibitors 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC) and neomycin were unable to block stimulation of uterine contraction by A1242. In accordance, A1242 (100 microM) did not release inositol phosphates from myo-[3H]inositol-labeled myometrial cells, whereas myometrial cells prelabeled with [3H]arachidonic acid released arachidonic acid in a concentration- and time-dependent manner after exposure to A1242 (10-100 microM). A1242 significantly stimulated arachidonic acid release in the absence of extracellular calcium, although the release was attenuated. Analysis of the eicosanoids released by A1242 indicated that only 0.83% of released [3H]arachidonic acid was metabolized to eicosanoids and 99.07% remained as free arachidonate. Uterine contraction increased in strips exposed to exogenous arachidonic acid (1-100 microM). This study suggests that A1242 stimulates contraction in pregnant rat uterus by a mechanism involving PLA2-mediated arachidonic acid release, and that arachidonic acid, rather than eicosanoids, may mediate A1242 uterotonic action in the uterus.  (+info)

Tetrandrine inhibited chronic "inflammatory" pulmonary hypertension in rats. (5/274)

AIM: To study the effects of tetrandrine (Tet), on pulmonary hypertension. METHODS: An "inflammatory" chronic pulmonary hypertension induced by monocrotaline (Mon) in rats was used. RESULTS: Tet 50, 100, and 150 mg.kg-1.d-1 i.g. 3 wk inhibited Mon-induced increase of pulmonary artery pressure (PAP) by 23.8%, 34.9% (P < 0.05), and 42.0%, (P < 0.05); the right heart index by 2.0%, 25.0%, and 30.0% (P < 0.05) respectively compared with those from Mon group, without significant influence on the systemic artery pressure (SAP). Using histological exam by Verhoeff elastic stain and computer scanning analysis, it was found that Tet (100 mg.kg-1.d-1) for 3 wk, inhibited the increase of medial thickness and cross sectional area by 57.8% (P < 0.01) and 54.6% (P < 0.01), respectively vs Mon group. CONCLUSION: Tet ameliorated the development of pulmonary vascular and lung tissue injury induced by Mon in rats.  (+info)

Dauricine inhibited L-type calcium current in single cardiomyocyte of guinea pig. (6/274)

AIM: To study the effect of dauricine (Dau) on L-type calcium current in guinea pig ventricular myocytes. METHODS: Using whole-cell recording method to record L-type calcium current (ICa) in single ventricular cell of guinea pig. RESULTS: Dau 1, 10, and 100 mumol.L-1 markedly reduced ICa by 15.2% +/- 2.2%, 41% +/- 5%, and 82% +/- 8%, respectively. After washing out, ICa partially recovered. Dau inhibited ICa at 3 Hz and 1 Hz to a similar extent, its effect on ICa appeared to be not frequency-dependent. CONCLUSION: Dau had a calcium channel blocking effect.  (+info)

Effects of anti-rheumatic herbal medicines on cellular adhesion molecules. (7/274)

OBJECTIVE: To test the hypothesis whether herbal medicines ameliorate inflammatory diseases via the modulation of cellular adhesion molecules (CAMs). METHODS: Human neutrophils, synovial fibroblasts, and endothelial cells were incubated with different concentrations of Tripterygium Wilfordii Hook-f (TWH-f) or Tetrandrine in the presence or absence of interleukin 1 (IL1). The amount of soluble E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) secreted by cells were determined by ELISA. The cell surface expression of these three CAMs was detected by flow cytometry. RESULTS: TWH-f at high concentration (50 ng/ml) has a significant (p<0.05) inhibitory effect on both the secretion and the expression of the cellular adhesion molecules. However, Tetrandrine did not demonstrate the same effects. CONCLUSIONS: The cellular adhesion molecules of the endothelium and leucocytes may constitute excellent targets for the development of new anti-inflammation medicines. These results indicate that TWH could be a potential therapeutic agent in the treatment of inflammatory diseases.  (+info)

Effects of N-methyl berbamine on delayed outward potassium current in isolated rat hepatocytes. (8/274)

AIM: To study the effects of N-methyl berbamine (NMB) on the delayed outward potassium currents (Ik) in isolated rat hepatocytes. METHODS: With patch-clamp techniques and whole-cell recording method, holding potential -50 mV, command potential +30 to +140 mV, duration 900 ms. RESULTS: NMB reduced Ik in a concentration-dependent manner. When the concentrations of NMB were 20, 50, 400 nmol.L-1 and 50 mumol.L-1, the amplitude values of Ik were decreased to 3.6 +/- 0.4 (P > 0.05), 2.1 +/- 1.6 (P > 0.05), 3.7 +/- 1.6 (P < 0.05), 2.3 +/- 1.3 nA (P < 0.01) from 4.4 +/- 1.0 (n = 4), 2.5 +/- 1.8 (n = 4), 5.8 +/- 2.1 (n = 5), 4.6 +/- 1.3 (n = 6) nA of control, respectively. The inhibitory rates were 10%, 15%, 37%, and 51%, respectively. CONCLUSION: NMB was a K+ channel inhibitor.  (+info)

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