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Liming Zhang

Publications and source records attributed to Liming Zhang.

50 records · Page 3Linked to original sources
PubMed2002

Stereocontrolled synthesis of kelsoene by the homo-favorskii rearrangement.

[reaction: see text] (+/-)-Kelsoene (4) has been synthesized from 2,5-dihydroanisole in 16 steps in 12.5% overall yield. The key step involves a base-catalyzed reaction of gamma-keto tosylate (5), which effects a homo-Favorskii rearrangement to 16 as well as the corresponding intramolecular S(N)2 product 15 from the enolate of 5. Ketone 15 can efficiently be isomerized to cyclobutanone 17 having the kelsoene carbon skeleton upon acid treatment.

Journal Article↗
PubMed2002

Properties of potassium currents in Purkinje cells of failing human hearts.

Cardiac Purkinje fibers play an important role in cardiac arrhythmias, but no information is available about ionic currents in human cardiac Purkinje cells (PCs). PCs and midmyocardial ventricular myocytes (VMs) were isolated from explanted human hearts. K(+) currents were evaluated at 37 degrees C with whole cell patch clamp. PCs had clear inward rectifier K(+) current (I(K1)), with a density not significantly different from VMs between -110 and -20 mV. A Cs(+)-sensitive, time-dependent hyperpolarization-activated current was measurable negative to -60 mV. Transient outward current (I(to)) density was smaller, but end pulse sustained current (I(sus)) was larger, in PCs vs. VMs. I(to) recovery was substantially slower in PCs, leading to strong frequency dependence. Unlike VM I(to), which was unaffected by 10 mM tetraethylammonium, Purkinje I(to) was strongly inhibited by tetraethylammonium, and Purkinje I(to) was 10-fold more sensitive to 4-aminopyridine than VM. PC I(sus) was also reduced strongly by 10 mM tetraethylammonium. In conclusion, human PCs demonstrate a prominent I(K1), a time-dependent hyperpolarization-activated current, and an I(to) with pharmacological sensitivity and recovery kinetics different from those in the atrium or ventricle and compatible with a different molecular basis.

Adult↗
PubMed2002

Atypical dose-route-dependent food effects of eplerenone in the dog: presence of food effects following intravenous dosing and lack of food effects of following oral dosing.

This study was conducted to investigate why a food effect was observed following an intravenous dose of eplerenone (EP) in the dog, but not following oral dosing. Three female dogs were implanted with a chronic portal vein access port and received radiolabeled EP doses orally (15 mg/kg in solution) and intravenously (7.5 mg/kg via cephalic and portal veins) under fasted and fed conditions. Mean AUC values for EP after infusion through the cephalic vein were 23.0 +/- 2.7 and 18.2 +/- 1.1 h.microg/mL under fasted and fed conditions, respectively. Corresponding values after infusion through the portal vein were 20.7 +/- 3.2 and 12.9 +/- 1.3 h.microg/mL, respectively. After oral administration, EP was absorbed 82.0 +/- 6.9 and 98.0 +/- 8.3% under fasted and fed conditions; corresponding mean AUC values were 32.0 +/- 2.0 and 30.8 +/- 3.6 h.microg/mL, respectively. The AUC value for SC-70303 acid (the open lactone form of EP) was lower under fed conditions after cephalic vein infusion, but was greater under fed conditions after portal vein infusion or oral solution administration. The hepatic first-pass effect of EP was 12.6 +/- 6.3% under fasted conditions and 27.1 +/- 6.0% under fed conditions. Pharmacokinetic analysis of EP concentrations after portal vein infusion and oral administration showed that under fed conditions the rate constants for bile excretion and for liver metabolism and urinary excretion were increased while the rate constant for elimination and/or metabolism in the gastrointestinal tract was reduced. In conclusion, the apparent lack of food effect after oral administration was observed because enhanced clearance was compensated by increased absorption.

Administration, Oral↗
PubMed2002

Interconversion pharmacokinetics of eplerenone, a selective aldosterone blocker, and its lactone-ring open form.

The interconversion pharmacokinetics of eplerenone and its lactone-ring open form, SC-70303, were examined in dogs using a stable isotope method. [13CD3]EP and SC-70303 were coadministered orally (10 mg/kg) and intravenously (5 mg/kg) as aqueous solutions under fasted conditions. After I.V. administration of [13CD3]EP, the mean AUC of [13CD3]EP was 16.0 h. microg/mL, while the C(max), T(max), and AUC for [13CD3]SC-70303 acid were 0.744 microg/mL, 0.5 h, and 3.49 h. microg/mL, respectively. After I.V. administration of SC-70303, the AUC for SC-70303 acid was 6.36 h. microg/mL, while the C(max), T(max), and AUC for EP were 2.26 microg/mL, 0.5 h, and 9.48 h. microg/mL, respectively. After oral administration of [13CD3]EP, the C(max), T(max), and AUC for [13CD3]EP were 6.01 microg/mL, 0.5 h, and 27.7 h. microg/mL, respectively, and the corresponding values for [13CD3]SC-70303 acid were 0.972 microg/mL, 0.75 h, and 5.52 h. microg/mL, respectively. After oral administration of SC-70303, the C(max), T(max), and AUC for EP were 1.38 microg/mL, 0.83 h, and 9.29 h. microg/mL, respectively, and the corresponding values for SC-70303 acid were 0.330 microg/mL, 0.67 h, and 2.19 h. microg/mL, respectively. The systemic availability was 90% for [13CD3]EP and 17.5% for SC-70303 acid. EP and SC-70303 acid were rapidly interconvertible in the dog. The percentage of dose converted to [13CD3]SC-70303 acid following I.V. administration of [13CD3]EP was 55.0%, while the percentage of dose converted to EP following I.V. administration of SC-70303 was 60.2%.

Aldosterone↗
PubMed2002

Polymerization of monolignols by redox shuttle-mediated enzymatic oxidation: a new model in lignin biosynthesis I.

Lignin is one of the most abundant biopolymers, and it has a complex racemic structure. It may be formed by a radical polymerization initiated by redox enzymes, but much remains unknown about the process, such as how molecules as large as enzymes can generate the compact structure of the lignified plant cell wall. We have synthesized lignin oligomers according to a new concept, in which peroxidase is never in direct contact with the lignin monomers coniferaldehyde and coniferyl alcohol. Instead, manganese oxalate worked as a diffusible redox shuttle, first being oxidized from Mn(II) to Mn(III) by a peroxidase and then being reduced to Mn(II) by a simultaneous oxidation of the lignin monomers to radicals that formed covalent linkages of the lignin type. Furthermore, a high molecular mass polymer was generated by oxidation of coniferyl alcohol by Mn(III) acetate in a dioxane and water mixture. This polymer was very similar to natural spruce wood lignin, according to its NMR spectrum. The possible involvement of a redox shuttle/peroxidase system in lignin biosynthesis is discussed.

Acrolein↗
PubMed2002

Involvement of CYP3A in the metabolism of eplerenone in humans and dogs: differential metabolism by CYP3A4 and CYP3A5.

In vitro studies were conducted to identify the major metabolites of eplerenone (EP) and the cytochrome p450 (p450) isozymes involved in its primary oxidative metabolism in humans and dogs. The major in vitro metabolites were identified as 6 beta-hydroxy EP and 21-hydroxy EP in both humans and dogs. EP was metabolized by cDNA-expressed human CYP3A4 and dog CYP3A12 but only minimally by human CYP3A5. In human microsomes, inhibition of total metabolism by the CYP3A-selective inhibitors ketoconazole, troleandomycin, and 6',7'-dihydroxybergamottin, each at 10 micro M concentration, was 83 to 95%, whereas inhibition with inhibitors selective for other p450 isozymes was minimal. In dog liver microsomes, the percentages of inhibition were 53 to 76% with the CYP3A-selective inhibitors. A monoclonal anti-CYP3A4 antibody inhibited EP metabolism by 84%, whereas other monoclonal antibodies had minimal effects. The formation of 6 beta-hydroxy and 21-hydroxy metabolites in human liver microsomes was best correlated with CYP3A-selective dextromethorphan N-demethylation and testosterone 6 beta-hydroxylation activities. EP moderately inhibited only CYP3A (testosterone 6 beta-hydroxylase) activity in human liver microsomes by 23, 34 and 45% at concentrations of 30, 100, and 300 micro M, respectively. With human microsomes, the V(max) and K(m) for 6 beta-hydroxylation and 21-hydroxylation were 0.973 nmol/min/mg and 217 micro M, and 0.143 nmol/min/mg and 211 micro M, respectively. The human hepatic clearance calculated from total in vitro EP metabolism was 2.30 ml/min/kg, which agrees with in vivo data. In conclusion, 6 beta- and 21-hydroxylation of EP is primarily catalyzed by CYP3A4 in humans and CYP3A12 in dogs. Also, it is unlikely that EP would substantially inhibit the metabolism of other drugs that are metabolized by CYP3A4 or other p450 isoforms.

Animals↗
PubMed2002

Differential distribution of Kir2.1 and Kir2.3 subunits in canine atrium and ventricle.

Ventricular inward rectifier K(+) current (I(K1)) is substantially larger than atrial, producing functionally important action potential differences. To evaluate possible molecular mechanisms, we recorded I(K1) with patch-clamp techniques and studied Kir2.1 and Kir2.3 subunit expression. I(K1) density was >10-fold larger in the canine ventricle than atrium. Kir2.1 protein expression (Western blot) was 78% greater (P < 0.01) in the ventricle, but Kir2.3 band density was 228% greater (P < 0.01) in the atrium. Immunocytochemistry showed transverse tubular localization of Kir2.1 in 89% (17 of 19) of ventricular and 26% (5 of 19, P < 0.0001) of atrial cells. Both exhibited a weakly positive Kir2.1 signal at intercalated disks. Kir2.3 was strongly expressed at the intercalated disks in all cells and in the transverse tubular regions in 78% (14 of 18) of atrial and 22% (4 of 18, P < 0.001) of ventricular cells. Tissue immunohistochemical results qualitatively resembled isolated cell data. We conclude that the expression density and subcellular localization of Kir2.1 and Kir2.3 subunits differ in the canine atrium versus ventricle. Overall protein density differences are insufficient to explain I(K1) discrepancies, which may be related to differences in subcellular distribution.

Animals↗
PubMed2002

Muscarinic and nicotinic presynaptic modulation of EPSCs in the nucleus accumbens during postnatal development.

We have studied the modulatory effects of cholinergic agonists on excitatory postsynaptic currents (EPSCs) in nucleus accumbens (nAcb) neurons during postnatal development. Recordings were obtained in slices from postnatal day 1 (P1) to P27 rats using the whole cell patch-clamp technique. EPSCs were evoked by local electrical stimulation, and all experiments were conducted in the presence of bicuculline methchloride in the bathing medium and with QX-314 in the recording pipette. Under these conditions, postsynaptic currents consisted of glutamatergic EPSCs typically consisting of two components mediated by AMPA/kainate (KA) and N-methyl-D-aspartate (NMDA) receptors. The addition of acetylcholine (ACh) or carbachol (CCh) to the superfusing medium resulted in a decrease of 30-60% of both AMPA/KA- and NMDA-mediated EPSCs. In contrast, ACh produced an increase ( approximately 35%) in both AMPA/KA and NMDA receptor-mediated EPSCs when administered in the presence of the muscarinic antagonist atropine. These excitatory effects were mimicked by the nicotinic receptor agonist 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) and blocked by the nicotinic receptor antagonist mecamylamine, showing the presence of a cholinergic modulation mediated by nicotinic receptors in the nAcb. The antagonistic effects of atropine were mimicked by pirenzepine, suggesting that the muscarinic depression of the EPSCs was mediated by M(1)/M(4) receptors. In addition, the inhibitory effects of ACh on NMDA but not on AMPA/KA receptor-mediated EPSC significantly increased during the first two postnatal weeks. We found that, under our experimental conditions, cholinergic agonists produced no changes on membrane holding currents, on the decay time of the AMPA/KA EPSC, or on responses evoked by exogenous application of glutamate in the presence of tetrodotoxin, but they produced significant changes in paired pulse ratio, suggesting that their action was mediated by presynaptic mechanisms. In contrast, CCh produced consistent changes in the membrane and firing properties of medium spiny (MS) neurons when QX-314 was omitted from the recording pipette solution, suggesting that this substance actually blocked postsynaptic cholinergic modulation. Together, these results suggest that ACh can decrease or increase glutamatergic neurotransmission in the nAcb by, respectively, acting on muscarinic and nicotinic receptors located on excitatory terminals. The cholinergic modulation of AMPA/KA and NMDA receptor-mediated neurotransmission in the nAcb during postnatal development could play an important role in activity-dependent developmental processes in refining the excitatory drive on MS neurons by gating specific inputs.

Acetylcholine↗
PubMed2002

[Design of axial flaps with color Doppler flow imaging technique].

OBJECTIVE: To study the effect of the color doppler flow imaging (CDFI) technique in the design of the axial pattern flap. METHODS: From March 1996 to June 1999, ten patients were included in this study. Among them, there were seven males and three females. Their defects ranged from 6 cm x 8 cm to 15 cm x 20 cm. Before operation, an axial flap was designed by the traditional method. Then CDFI technique of high frequency (5.0-7.5 MHz) was used to examine the major arterial supply of the flap and modify the design accordingly. At last, the modified flap was transferred to cover the defect. RESULTS: All the patients except one underwent the operation successfully. The cosmetic and functional results of the flap were excellent. CONCLUSION: CDFI is a simple, direct and accurate method for detecting the vascular supply of an axial pattern flap. This technique should be popularized to avoid blindness of flap design.

Adolescent↗
PubMed2001

Inhaled budesonide in experimental chlorine gas lung injury: influence of time interval between injury and treatment.

OBJECTIVE: To examine the time window between injury and treatment during which nebulized corticosteroid lessens lung injury induced by chlorine gas inhalation. DESIGN: An experimental laboratory study. SETTING: Academic research laboratory. SUBJECTS: Twenty-four juvenile female pigs. INTERVENTIONS: Twenty-four mechanically ventilated pigs were exposed to chlorine gas (400 PPM in air) for 20 min, then divided into four groups (six in each group). Nebulized budesonide (BUD) was given immediately (BUD 0 min), 30 min (BUD 30 min) or 60 min (BUD 60 min) after chlorine gas exposure. Six pigs receiving nebulized saline served as controls. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, gas exchange and lung mechanics were evaluated for 5 h after chlorine gas exposure. All animals had an immediate increase in airway and pulmonary artery pressure and a sharp drop of arterial oxygenation. The mean arterial oxygen tension of BUD 0 min and BUD 30 min animals was significantly higher than in the control and the BUD 60 min groups ( p<0.001). The recovery of lung compliance in the BUD 0 min and the BUD 30 min groups was significantly more rapid than in the control and the BUD 60 min groups ( p<0.001). The pulmonary wet to dry weight ratio was greater in the control group than in the BUD-treated groups ( p<0.05). CONCLUSION: Treatment with inhaled budesonide immediately or 30 min after chlorine gas lung injury had similar positive effects on symptoms and signs of pulmonary injury, whereas treatment delayed for 60 min was less effective.

Administration, Inhalation↗
PubMedDate not supplied

Towards a new concept of lignin condensation in kraft pulping. Initial results.

In kraft pulping, a comparatively large amount of lignin remains in the fibres after the cook. Based on various analytical techniques for lignin, such as thioacidolysis, GPC and NMR, it is suggested that lignin condensation reactions take place during the cook. The reaction seems, however, not to involve ionic intermediates as has been suggested previously but rather a one-electron mechanism with elemental sulphur as the initiator. Support for such a reaction has been found through kraft cooks in the presence of an added phenol, 2,6-xylenol, as well as through NMR analysis of kraft lignin. It was found that the added phenol is incorporated in the pulp lignin with linkages indicative of radical coupling. Furthermore, kraft lignin was found to contain substantial amounts of chemically linked fatty acids. By complementary analyses of sulphur and polysulphide in an industrial black liquor, the presence of these compounds throughout a kraft cook was demonstrated.

Chromatography, Gel↗
PubMedDate not supplied

Shaping up simple cell's receptive field of animal vision by ICA and its application in navigation system.

Scientists and experts have explored the mechanism of visual systems for decades for smart image processing and pattern recognition in order to satisfy sophisticated engineering applications. In this paper we apply independent component analyses' (ICA) unsupervised learning to natural images, topography images and other special environment images for demonstrating the simple-cell's process in animal vision. Our results confirm an early biological experiment (Nature 228 (1970) 419) about the growth of simple cells in cat's V1 area. Furthermore, by applying ICA methodology and the simplex algorithm, the unsupervised neural synapse's learning can obtain the receptive fields in visual cortex and can simulate the growth of the visual cortex of young animal in the special environment. These findings imply that an input image can be efficiently represented by ICA bases. An application of image matching in the navigation by ICA is shown that the animal visual system method is indeed better than those classical methods at least more than 5%.

Animals↗
PubMedDate not supplied

Synthesis of novel porous magnetic silica microspheres as adsorbents for isolation of genomic DNA.

An improved procedure is described for preparation of novel mesoporous microspheres consisting of magnetic nanoparticles homogeneously dispersed in a silica matrix. The method is based on a three-step process, involving (i) formation of hematite/silica composite microspheres by urea-formaldehyde polymerization, (ii) calcination of the composite particles to remove the organic constituents, and (iii) in situ transformation of the iron oxide in the composites by hydrogen reductive reaction. The as-synthesized magnetite/silica composite microspheres were nearly monodisperse, mesoporous, and magnetizable, with as typical values an average diameter of 3.5 microm, a surface area of 250 m(2)/g, a pore size of 6.03 nm, and a saturation magnetization of 9.82 emu/g. These magnetic particles were tested as adsorbents for isolation of genomic DNA from Saccharomyces cerevisiae cells and maize kernels. The results are quite encouraging as the magnetic particle based protocols lead to the extraction of genomic DNA with satisfactory integrity, yield, and purity. Being hydrophilic in nature, the porous magnetic silica microspheres are considered a good alternative to polystyrene-based magnetic particles for use in biomedical applications where nonspecific adsorption of biomolecules is to be minimized.

Adsorption↗