Allergic contact dermatitis to pyridoxine ester and hinokitiol.
Explore the source record for details and available documents.
Adolescent↗
SEARCH · Search PubMed
Results for “TROPOLONES”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Kinetic and thermodynamic aspects of tubulin-ligand interactions: binding of the colchicine analog 2-methoxy-5-(2',3',4'-trimethoxyphenyl) tropone.
Explore the source record for details and available documents.
Animals↗
[On the antibacterial effect of hinokitiol against Staphylococcus aureus showing double zone phenomenon].
We studied the antibacterial effect of Hinokitiol against Staphylococcus aureus. As reference, we studied also the antibacterial effects of the oil and water from Thujopsis dolablata var. hondai Makino which contains Hinokitiol an important element of its antibacterial effect. Interestingly, Hinokitiol showed the double zone phenomenon, i.e., minimum inhibitory concentration of hinokitiol against MSSA was 15-125 micrograms/ml and against MSSA was 125 micrograms/ml. But when the concentration of Hinokitiol was diluted to 1.87-0.94 micrograms/ml, then the growth of MSSA was inhibited (Table 1 and Fig. 1). This phenomenon was observed the study on antibacterial effect using disk containing Hinokitiol (Fig/3). Similar phenomenon were observed also in the study using water from Thujopsis dolablata (Table 2 & Fig. 2). We deduce that Hinokitiol has a strong antibacterial effect against S. aureus. But this effect shows double zone effect. The antibacterial effect of Hinokitiol is more prominent against MRSA than MSSA.
Dose-Response Relationship, Drug↗
7-Hydroxytropolone: an inhibitor of aminoglycoside-2"-O-adenylyltransferase.
Aminoglycoside-2"-O-adenylyltransferase was inhibited by 7-hydroxytropolone. Inhibition was competitive with respect to the cosubstrate ATP and appeared to require the unique vicinal arrangement of oxygens found in 7-hydroxytropolone. Combinations of 7-hydroxytropolone plus the appropriate aminoglycoside substrates were active against resistant bacteria possessing the adenylyltransferase. No potentiation was observed against other aminoglycoside-resistant or -susceptible strains. The fact that the inhibition of an aminoglycoside-modifying enzyme overcomes the poor uptake of aminoglycosides in resistant strains points to the singular importance of the inactivating enzyme as a determinant of resistance.
Aminoglycosides↗
In vitro inhibitory effects of hinokitiol on proliferation of Chlamydia trachomatis.
The inhibitory effects of hinokitiol (beta-thujaplicin) on Chlamydia trachomatis D/UW-3/Cx were shown by MIC, minimum lethal concentration (MLC), and preinoculation minimal microbicidal concentration assays using HeLa 229 cells. The MIC and the MLC were both 32 microg/ml. Further evaluation of hinokitiol as a topical agent against C. trachomatis is warranted.
Anti-Infective Agents↗
Antibacterial activity of tropilidine and tropone.
The seven-membered ring compounds tropilidine and tropone were shown to be bacteriostatic and bactericidal for a wide range of bacterial species.
Anti-Bacterial Agents↗
Thujaplicins from Thuja plicata as iron transport agents for Salmonella typhimurium.
Strains of Salmonella typhimurium which are unable to synthesize their normal iron transport agent, enterobactin, and which must be supported with an exogenous chelator (siderophore) on certain media, were used to examine various types of wood for the presence of chelators. Western red cedar wood, Thuja plicata, was observed to contain large amounts of three substances that in low concentration would serve as chelators for S. typhimurium. The chelators from T. plicata were characterized and found to be alpha-, beta-, and gamma-thujaplicin. Other planar cyclic alpha-hydroxyketones were examined, and several were found to function as chelators for S. typhimurium.
Biological Assay↗
In vivo assessment of granulocyte migration to diseased bowel in Crohn's disease.
It has been suggested, on the basis of impaired granulocyte migration to skin windows, that there is a fundamental granulocyte defect in Crohn's disease. In vitro tests of granulocyte function have, however, failed to confirm this. We have studied granulocyte migration to inflamed bowel in Crohn's disease using a new approach which utilises dynamic gamma camera imaging after injection of 111In labelled autologous granulocytes. In 20 of 22 studies there was rapid migration to diseased bowel, compatible with no migration delay. Only two patients showed delays in migration of 12 and 15 minutes respectively, but neither had any clinical characteristics to distinguish them from the other 20 patients. This study shows that the majority of patients with Crohn's disease in relapse have rapid granulocyte migration to diseased bowel and provides evidence against a significant migration defect in this condition.
Cell Movement↗
Actions of U-92032, a T-type Ca2+ channel antagonist, support a functional linkage between I(T) and slow intrathalamic rhythms.
Thalamic relay neurons express high levels of T-type Ca(2+) channels, which support the generation of robust burst discharges. This intrinsically mediated form of phasic spike firing is thought to be critical in the generation of slow (3-4 Hz) synchronous oscillatory activity of absence epilepsy. Recordings made from brain slices or whole animals have shown that slow synchronous absence-like activity can be abolished when Ca(2+)-dependent burst firing in relay neurons is interrupted by the pharmacological or genetic inactivation of T-channels. Because succinimide drugs act as incomplete and nonspecific antagonists, we tested whether the novel T-channel antagonist U-92032 could provide stronger support for a role of T-channels in slow oscillatory activity. Ca(2+)-dependent rebound (LTS) bursts were recorded using whole cell current clamp in relay cells of the ventral basal complex (VB) from thalamic slices of adult rats. We used LTS kinetics to measure the availability of T-channels in VB cells after TTX. U-92032 (1 and 10 microM) reduced the maximum rate of depolarization of the isolated LTS by 51% and 90%, respectively, compared with the 35% reduction due to 2 mM methylphenylsuccinimide (MPS), the active metabolite of the antiabsence drug methsuximide. U-92032 (1 and 10 microM) also suppressed evoked, slow oscillations in thalamic slices with a time course similar for observed intracellular effects. Unlike MPS, we observed no substantial effects of short-term U-92032 applications (< or =2 h) on the generation of action potentials in VB cells. Our findings show U-92032 is a more potent, effective, and specific T-channel antagonist than previously studied succinimide antiabsence drugs and that it dramatically reduces epileptiform synchronous activity. This suggests that U-92032 or other specific T-channel antagonists may provide effective drug treatments for absence epilepsy.
Action Potentials↗
Ca2+ channel antagonist U-92032 inhibits both T-type Ca2+ channels and Na+ channels in hippocampal CA1 pyramidal neurons.
The effects of 7-[[4-[bis(4-fluorophenyl)-methyl]-1-piperazinyl]methyl] -2-[(2-hydroxyethyl)amino] 4-(1-methylethyl)-2,4,6-cycloheptatrien-1-one (U-92032), a newly described Ca2+ channel blocker, on voltage-gated ionic currents were measured. Whole cell voltage-clamp records were obtained from acutely isolated CA1 hippocampal pyramidal neurons from 7- to 14-day-old rats. Dimethyl sulfoxide, at either 0.01% or 0.1%, partially inhibited T-type Ca2+ currents (approximately 20% inhibition) but not high-voltage-activated (HVA) Ca2+ currents. Ethanol (0.2%) did not affect Ca2+ currents. U-92032 selectively inhibited T-type Ca2+ currents (median inhibiting concentration approximately 500 nM). HVA Ca2+ currents were less sensitive, with approximately 75% of the current resistant at 10 microM. Inhibition of Ca2+ currents was reversible. U-92032 inhibited Na+ currents at concentrations similar to those required for T-type currents (> 33% block at 1 microM). Block of Na+ currents took several minutes to develop and was irreversible. Voltage-gated K+ currents were insensitive to U-92032 (1 or 10 microM). These results indicate that U-92032 inhibits both T-type Ca2+ channels and Na+ channels, constraining its utility in certain studies. Among Ca2+ channels, however, U-92032 should prove a useful tool for distinguishing physiological contributions of T-type channels.
Animals↗
Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study.
BACKGROUND AND PURPOSE: Evidence now exists for a pathogenic role for neutrophils in acute cerebral ischemia. We have studied the patterns and temporal profile of cerebral neutrophil recruitment to areas of acute ischemic stroke (IS) and have attempted to correlate this with neurological status and outcome. METHODS: Patients with cortical middle cerebral artery (MCA) IS were recruited within 24 hours of clinical onset. Neutrophil recruitment was studied using indium-111 (111In) troponolate-labeled neutrophils, planar imaging, and single-photon emission computed tomography (SPECT). Volume of brain infarction was calculated from concurrent computed tomography (CT). Hematoxylin and eosin sections were obtained postmortem (n=2). Outcome was measured using Barthel, Rankin, and National Institute of Health Stroke (NIHSS) scales. RESULTS: Fifteen patients were studied. Significant 111In-neutrophil recruitment to ipsilateral hemisphere, as measured by asymmetry index (AI), was demonstrated within 24 hours of onset in 9 patients; this response was heterogenous between patients and on repeated measurement attenuated over time. Histologically, recruitment was confirmed within intravascular, intramural, and intraparenchymal compartments. Interindividual heterogeneity in neutrophil response did not correlate with infarct volume or outcome. In an exploratory analysis, neutrophil accumulation appeared to correlate significantly with infarct expansion (Spearman rho=0.66; P=0.03, n=12). CONCLUSIONS: Neutrophils recruit to areas of ischemic brain within 24 hours of symptom onset. This recruitment attenuates over time and is confirmed histologically. While neutrophil accumulation may be associated with either the magnitude or the rate of infarct growth, these results require confirmation in future studies.
Brain Ischemia↗
Inhaled platelet-activating factor causes pulmonary neutrophil sequestration in normal humans.
Inhaled platelet-activating factor (PAF) causes bronchoconstriction and transient peripheral neutropenia in humans. We studied eight normal subjects to investigate whether inhaled PAF caused pulmonary neutrophil sequestration. All subjects received autologous 99mTc-red cells as a blood pool marker, seven received 111In-neutrophils, and one received 111In-platelets. Six subjects inhaled 48 micrograms of PAF. There was immediate pulmonary sequestration of 111In-neutrophils, maximal (218% baseline) at 6 min (p less than 0.001), returning to normal by 3 h. There was no change in circulating platelet count or pulmonary 111In-platelet transit. Methacholine inhalation caused equivalent bronchoconstriction to PAF, but it had no effect on neutrophil count or pulmonary 111In-neutrophil activity. We have demonstrated pulmonary neutrophil, but not platelet, sequestration after PAF. This supports a role for PAF as an inflammatory mediator in humans. This may be a useful model for exploring pulmonary neutrophil kinetics and preinflammatory processes.
Administration, Inhalation↗
Effects of two dual-function compounds, U92798 and U92032, on transient focal ischemia in rats.
Two newly-developed compounds (U92798 and U92032), which inhibit lipid peroxidation and block calcium entry, were studied for their effects on neocortical damage after transient focal ischemia. Ischemia was induced in Sprague-Dawley rats by simultaneous occlusion of the left middle cerebral artery and both common carotid arteries for a period of 3 hours. Compounds (1 mg/kg) were administered intravenously 30 minutes before occlusion and again 2.5 hours after the cessation of blood flow. After a 72-hour period of reperfusion, the animals were killed and examined for cerebral infarction and edema. Treatment with U92798 or U92032 significantly reduced the volume of cortical infarction. Edema was also reduced in these groups; however, this effect did not achieve statistical significance. These results suggest that dual function compounds, which both inhibit lipid peroxidation and block calcium entry, are promising therapeutic agents for the amelioration of ischemic cerebral damage.
Animals↗
Beta-thujaplicin zinc chelate induces apoptosis in mouse high metastatic melanoma B16BL6 cells.
The cytotoxic effects of beta-thujaplicin and five kinds of metal chelates were examined on mouse melanoma B16BL6 cells by cell viability and lactate dehydrogenase (LDH) release assay. Beta-thujaplicin-zinc chelate and beta-thujaplicin-copper chelate had higher cytotoxic effects than beta-thujaplicin, and the 50% effective doses (ED50) of these metal chelates were 12.5 and 25 microM, respectively. In addition, the zinc chelate induced DNA ladder formation in B16BL6 cells, as shown by the DNA fragmentation assay, suggesting that cell death induced by the zinc chelate is apoptosis. The zinc chelate also had a cytotoxic effect and induced DNA fragmentation on other tumor cell lines: HeLa, Meth A, and B16F1 cells, but not on normal human diploid fibroblasts FS-4. These results suggest that beta-thujaplicin-zinc chelate induces apoptotic cell death in various tumor cell lines and is a potent antitumor agent for tumor cells including malignant melanomas.
Animals↗
Phytogrowth-Inhibitory activities of beta-dolabrin and gamma-thujaplicin, hinokitiol-related compounds and constituents of Thujopsis dolabrata Sieb. et Zucc. var hondai Makino.
Beta-dolabrin and gamma-thujaplicin isolated from Thujopsis dolabrata Sieb. et Zucc. var hondai Makino, like hinokitiol, showed strong phytogrowth-inhibitory activities, and their growth-inhibitory activities were as high as that of sodium 2,4-dichlorophenoxyacetate used as a positive control. In particular, the phytogrowth-inhibitory activity of gamma-thujaplicin was strong and it completely inhibited the germination of this seed of Brassica campestris L. subsp. rapa Hook f. et Anders at the concentration of 30 ppm. Both compounds exhibited inhibitory activities on B. campestris L. subsp. rapa Hook f. et Anders and Sesamum indicum Linne, even at the low concentration of 10 ppm. At 7 d after treatment with beta-dolabrin and gamma-thujaplicin, the amount of chlorophyll in the cotyledons of B. campestris L. subsp. rapa Hook f. et Anders treated with both compounds was greatly decreased as compared with the control. The findings indicate that the phytogrowth-inhibitory action might be a common biological activity of hinokitiol-related compounds, suggesting that at least a part of their phytogrowth-inhibitory actions seems to be related to a decrease in chlorophyll content.
Brassica↗
Antifungal activity of Hinokitiol-related compounds on wood-rotting fungi and their insecticidal activities.
Hinokitiol (beta-thujaplicin), beta-dolabrin and gamma-thujaplicin isolated from Thujopsis dolabrata SIEB. et ZUCC var hondai MAKINO showed antifungal activities against all of the wood-rotting fungi examined. The antifungal activity of three compounds on Daedalea dickinsii IFO-4979 was especially strong, their minimum inhibitory concentration (MIC) values being 0.2 microg/ml. Their antifungal activities on D. dickinsii IFO-4979 were as high as that of amphotericin B used as a positive control. Three compounds had strong insecticidal activities on Tyrophagus putrescentiae [50%-lethal concentration (LC50 : g/m2) 0.25 in hinokitiol, 0.02 in beta-dolabrin and gamma-thujaplicin. Their insecticidal activities were higher than that of N,N-diethyl-m-toluamide (DEET, LC50 : 1.46 g/m2) used as a positive control. Three compounds also showed strong insecticidal activity on Coptotermes formosanus [LC50 (g/m2) 0.07 in hinokitiol, 0.05 in beta-dolabrin and gamma-thujaplicin], although their insecticidal activities were much lower than that of commercial chloropyrifos (LC50 : 0.00016 g/m2).
Antifungal Agents↗
Biological activity of alpha-thujaplicin, the minor component of Thujopsis dolabrata SIEB. et ZUCC. var. hondai MAKINO.
Alpha-thujaplicin, a minor component of Thujopsis dolabrata SIEB. et ZUCC. var. hondai MAKINO, which was synthesized, showed the antibacterial activity, phytogrowth-inhibitory effect, inhibition of carboxypeptidase A and cytotoxic effect. Antibacterial activity of alpha-thujaplicin on Enterococcus faecalis IFO-12965 [minimum inhibitory concentration (MIC): 1.56 microg/ml] was higher than that of gentamicin (MIC: 6.25 microg/ml) used as a positive control. Inhibitory activity of alpha-thujaplicin on carboxypeptidase A [50% inhibitory concentration (IC50): 3.24 x 10(-5) M] was higher than that of 1,10-phenanthroline used as a positive control. Alpha-thujaplicin showed germination inhibition toward the seed of Echinochloa utilis Ohwi et Yabuno even at the low concentration of 10 ppm and its growth inhibitory effect was stronger than that of sodium 2,4-dichlorophenoxyacetate used as a standard. Alpha-thujaplicin at 1.25 microg/ml inhibited cell growth of human stomach cancer KATO-IIl by 86%, and Ehrlich's ascites carcinoma by 87%, respectively. This compound even at the low concentration of 0.32 microg/ml also inhibited cell growth of the former by 66%, and the latter by 75%, respectively. The acute toxicity of alpha-thujaplicin [50% lethal dose (LD50) value: 256 mg/kg] in mice was as strong as those of beta-dolabrin (LD50 value: 232 mg/kg) and gamma-thujaplicin (LD50 value: 277 mg/kg).
Animals↗
Biological activity of 4-acetyltropolone, the minor component of Thujopsis dolabrata SIeb. et Zucc. hondai Mak.
4-Acetyltropolone, a minor component of Thujopsis dolabrata SIEB. et Zucc. hondai MAKINO, showed antimicrobial activity against various microorganisms including wood-rotting fungi, a phytogrowth-inhibitory effect with chlorophyll biosynthesis inhibition, cytotoxic effect and inhibitory activity on metalloproteases. This compound had strong antifungal activity on Daedalea dickinsii IFO-4979 [minimum inhibitory concentration (MIC): 0.2 microg/ml] and Coriolus versicolor IFO-4940 (MIC: 0.39 microg/ml). Its cytotoxic effect at 20.0/microg/ml on human stomach cancer KATO-III and Ehrich's ascites carcinoma was stronger than those of podophyllotoxin, vincristine and vinblastine, the anticancer agents isolated from higher plants and used clinically. This compound also had potent antibacterial activity against Staphylococcus epidermidis IFO-12993, its MIC being 1.56 microg/ml. However, other biological activities of 4-acetyltropolone were lower than those of hinokitiol which is the main component of this plant, suggesting that the contribution of the acetyl group at C-4 to biological activity is smaller than that of the isopropyl group at that position. The acute toxicity of 4-acetyltropolone (LD50: 335.2 mg/kg) to mice was much lower than that of hinokitiol (LD50: 191 mg/kg).
Animals↗