Search PubMed⌕ Search

Biomedical subjects

Liming Zhang

Publications and source records attributed to Liming Zhang.

At least 37 records · Page 2Linked to original sources

Orthogonal signal correction used for noise elimination of open path Fourier transform infrared spectra.

Open path Fourier transform infrared (OP-FTIR) spectroscopy is qualified in detecting mixtures by multivariate calibration methods such as partial least squares (PLS); however, its applications are still restricted by background noise, which is unavoidable for OP-FTIR spectra and cannot be resolved solely by multivariate calibration methods. Hence OP-FTIR spectra are often pretreated before the data are subjected to the multivariate calibration model. A new preprocessing technique, orthogonal signal correction (OSC), was presented in this paper. The principle of OSC is to remove the part in X orthogonal to Y, and it is implemented based on PLS and nonlinear iterative partial least squares (NIPALS) algorithm. The approach was applied to three different data sets of PLS model. It performed much better than classical PLS when handling data with noise but comparably when processing on the simulated data. Moreover, OSC could reduce the complexity of model, which would facilitate the interpretation of the models. The results reveal that the proposed method gives much better prediction than the classical PLS and is very promising for the wide use of OP-FTIR. The preprocessing technique, auto-scaling, and second-order derivatives (SOD) were also considered.

Air Pollutants↗

Image shadow removal using pulse coupled neural network.

This paper introduces an approach for image shadow removal by using pulse coupled neural network (PCNN), based on the phenomena of synchronous pulse bursts in the animal visual cortexes. Two shadow-removing criteria are proposed. These two criteria decide how to choose the optimal parameter (the linking strength beta). The computer simulation results of shadow removal based on PCNN show that if these two criteria are satisfied, shadows are removed completely and the shadow-removed images are almost as the same as the original nonshadowed images. The shadow removal results are independent of changes of intensities of shadows in some range and variations of the places of shadows. When the first criterion is satisfied, even if the second criterion is not satisfied, as to natural grey images that have abundant grey levels, shadows also can be removed and PCNN shadow-removed images retain the shapes of the objects in original images. These two criteria also can be used for color images by dividing a color image into three channels (R, G, B). For shadows varying drastically, such as the noisy points in images, these two criteria are still right, but difficult to satisfy. Therefore, this approach can efficiently remove shadows that do not include the random noise.

Algorithms↗

In vitro ADME phenotyping in drug discovery: current challenges and future solutions.

Drug-metabolizing enzymes and drug transporters are key regulators of drug disposition and pharmacodynamics, which are closely linked to drug efficacy and safety. In this article, current challenges and future solutions to predicting their influence on pharmacokinetics and inter-organ distribution in humans, from data generated during the drug discovery decision-making process, are presented. In vitro phenotyping strategies for drug metabolizing enzymes (eg, CYP3A4, UGT1A1) and transporters (eg, OATP1B1) are offered, including perspectives on a selection of in vitro systems, novel in vitro phenotyping reagents and remaining technology gaps, challenges in extrapolating in vitro data to the in vivo situation, in silico models for the prediction of whether compounds are enzyme or transporter substrates, and the impact of pharmacogenomics.

Animals↗

Radical deoxygenation of hydroxyl groups via phosphites.

A highly efficient, two-step sequence method for the deoxygenation of hydroxyl groups has been developed. The method involves the preparation of the 2-(2-iodophenyl)ethyl methyl phosphite derivative of an alcohol using methyl dichlorophosphite and 2-(2-iodophenyl)ethanol. Treatment of the phosphite intermediate with (n-Bu)3SnH/AIBN in refluxing benzene cleanly produces the deoxygenation product of the original alcohol.

Journal Article↗

Gold-catalyzed cycloisomerization of siloxy enynes to cyclohexadienes.

We have described the first Au-catalyzed cycloisomerization of 1-siloxy-5-en-1-ynes. The reaction is efficiently catalyzed by AuCl (1 mol %) to afford siloxy cyclohexadienes, which can be readily converted to the corresponding 1,2- and 1,3-cyclohexenones. The catalytic process displays a broad substrate scope and exceedingly mild reaction conditions (30 min, 20 degrees C). The presence of a siloxy alkyne moiety is crucial for enabling the skeletal reorganization process, which is postulated to proceed via a novel reaction mechanism involving a cascade of 1,2-alkyl migrations.

Journal Article↗

Atrial ionic remodeling induced by atrial tachycardia in the presence of congestive heart failure.

BACKGROUND: Atrial fibrillation (AF) and congestive heart failure (CHF) produce discrete forms of atrial ionic remodeling. The in vivo effects of atrial tachycardia (AT) remodeling are altered by CHF. This study evaluated underlying mechanisms at the level of ionic remodeling. METHODS AND RESULTS: We studied 4 groups of dogs: (1) unpaced controls (CTLs); (2) CHF caused by 2-week ventricular tachypacing (VTP, 240 bpm); (3) AT (400 bpm x 7 days); and (4) CHF+AT (2-week VTP with AT for the last 7 days). CHF and CHF+AT groups equally increased left atrial pressure. AF duration was increased in all paced groups. Effective refractory period (ERP) was decreased by 42% in AT versus CTL but by only 24% in AT+CHF versus CHF. CHF reduced L-type Ca2+ (I(Ca)), transient-outward (I(to)), and the slow delayed-rectifier (I(Ks)) currents while increasing the Na+-Ca2+ exchanger (I(NCX)) and not affecting the inward-rectifier (I(K1)) current. AT reduced I(to) and I(Ca) while increasing I(K1) and leaving I(Ks) unaltered. The addition of AT to CHF failed to alter I(to), I(Ks), or I(NCX) beyond the effect of CHF alone, decreased I(Ca) slightly compared with CHF alone, but had smaller effects on I(Ca) and I(K1) compared with AT alone. Thus, CHF+AT, as would occur in a CHF patient who develops AF, produced an ionic remodeling pattern different from that of CHF or AT alone and from what would have been predicted from additive effects of CHF and AT. CONCLUSIONS: The presence of CHF alters AT-induced ionic remodeling. Thus, the ionic remodeling caused by cardiac arrhythmias in the presence of cardiac pathology is not necessarily predictable from the effects of either alone, with important potential implications for understanding the pathophysiology of arrhythmias in the diseased heart.

Animals↗

Brønsted acid-promoted cyclizations of siloxyalkynes with arenes and alkenes.

We have described the first Brønsted acid-mediated cyclizations of siloxyalkynes with simple arenes and alkenes to afford substituted tetralone and cyclohexenone derivatives. The most notable aspect of the carbocyclizations involving siloxyalkynes is the ability to employ a range of substrates that are not restricted to those containing electron-rich arenes and alkenes. The key mechanistic feature of the reaction is the generation of a highly reactive ketenium ion upon protonation of siloxyalkyne. We believe that the low nucleophilicty of the counteranion is crucial for enabling the formation and effective interception of this highly reactive intermediate.

Journal Article↗

Ranolazine: ion-channel-blocking actions and in vivo electrophysiological effects.

Ranolazine is a novel anti-ischemic drug that prolongs the QT interval. To evaluate the potential mechanisms and consequences, we studied: (i) Ranolazine's effects on HERG and IsK currents in Xenopus oocytes with two-electrode voltage clamp; (ii) effects of ranolazine, compared to d-sotalol, on effective refractory period (ERP), QT interval and ventricular rhythm in a dog model of acquired long QT syndrome; and (iii) effects on selected native currents in canine atrial myocytes with whole-cell patch-clamp technique. Ranolazine inhibited HERG and IsK currents with different potencies. HERG was inhibited with an IC(50) of 106 micromol l(-1), whereas the IC(50) for IsK was 1.7 mmol l(-1). d-Sotalol caused reverse use-dependent ERP and QT interval prolongation, whereas ranolazine produced modest, nonsignificant increases that plateaued at submaximal doses. Neither drug affected QRS duration. d-Sotalol had clear proarrhythmic effects, with all d-sotalol-treated dogs developing torsades de pointes (TdP) ventricular tachyarrhythmias, of which they ultimately died. In contrast, ranolazine did not generate TdP. Effects on I(Kr) and I(Ks) were similar to those on HERG and IsK. Ranolazine blocked I(Ca) with an IC(50) of approximately 300 micromol l(-1). I(Na) was unaffected. We conclude that ranolazine inhibits I(Kr) by blocking HERG currents, inhibits I(Ca) at slightly larger concentrations, and has modest and self-limited effects on the QT interval. Unlike d-sotalol, ranolazine does not cause TdP in a dog model. The greater safety of ranolazine may be due to its ability to inhibit I(Ca) at concentrations only slightly larger than those that inhibit I(Kr), thus producing offsetting effects on repolarization.

Acetanilides↗

Characterization of a hyperpolarization-activated time-dependent potassium current in canine cardiomyocytes from pulmonary vein myocardial sleeves and left atrium.

Cardiomyocytes from the pulmonary vein sleeves (PVs) are known to play an important role in atrial fibrillation. PVs have been shown to exhibit time-dependent hyperpolarization-induced inward currents of uncertain nature. We observed a time-dependent K(+) current upon hyperpolarization of PV and left atrial (LA) cardiomyocytes (I(KH)) and characterized its biophysical and pharmacological properties. The activation time constant was weakly voltage dependent, ranging from 386 +/- 14 to 427 +/- 37 ms between -120 and -90 mV, and the half-activation voltage averaged -93 +/- 4 mV. I(KH) was larger in PV than LA cells (e.g. at -120 mV: -2.8 +/- 0.3 versus-1.9 +/- 0.2 pA pF(-1), respectively, P < 0.01). The reversal potential was approximately -84 mV with 5.4 mm[K(+)](o) and changed by 55.7 +/- 2.4 mV per decade [K(+)](o) change. I(KH) was exquisitely Ba(2+) sensitive, with a 50% inhibitory concentration (IC(50)) of 2.0 +/- 0.3 microm (versus 76.0 +/- 17.9 microm for instantaneous inward-rectifier current, P < 0.01), and showed similar Cs(+) sensitivity to instantaneous current. I(KH) was potently blocked by tertiapin-Q, a selective Kir3-subunit channel blocker (IC(50) 10.0 +/- 2.1 nm), was unaffected by atropine and was significantly increased by isoproterenol (isoprenaline), carbachol and the non-hydrolysable guanosine triphosphate analogue GTPgammaS. I(KH) activation by carbachol required GTP in the pipette and was prevented by pertussis toxin pretreatment. Tertiapin-Q delayed repolarization in atropine-exposed multicellular atrial preparations studied with standard microelectrodes (action potential duration pre- versus post-tertiapin-Q: 190.4 +/- 4.3 versus 234.2 +/- 9.9 ms, PV; 202.6 +/- 2.6 versus 242.7 +/- 6.2 ms, LA; 2 Hz, P < 0.05 each). Seven-day atrial tachypacing significantly increased I(KH) (e.g. at -120 mV in PV: from -2.8 +/- 0.3 to -4.5 +/- 0.5 pA pF(-1), P < 0.01). We conclude that I(KH) is a time-dependent, hyperpolarization-activated K(+) current that likely involves Kir3 subunits and appears to play a significant role in atrial physiology.

Action Potentials↗

Total synthesis of (+)-acanthodoral by the use of a Pd-catalyzed metal-ene reaction and a nonreductive 5-exo-acyl radical cyclization.

[reaction: see text] The first total synthesis of the antibiotic acanthodoral (1) has been achieved from 3-methyl-2-cyclohexen-1-one in 19 steps in 2.1% overall yield. The synthesis features the use of a Pd-ene reaction in the presence of CO to form the endocyclic alkene 8, a nonreductive acyl radical cyclization reaction, and a ring contraction reaction by the Wolff rearrangement. (+)-Acanthodoral has also been synthesized starting from (+)-S-2,2-dimethyl-6-methylenecyclohexanecarboxylic acid.

Animals↗

Dissociation between ionic remodeling and ability to sustain atrial fibrillation during recovery from experimental congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) downregulates atrial transient outward (I(to)), slow delayed rectifier (I(Ks)), and L-type Ca(2+) (I(Ca,L)) currents and upregulates Na(+)-Ca(2+) exchange current (I(NCX)) (ionic remodeling) and causes atrial fibrosis (structural remodeling). The relative importance of ionic versus structural remodeling in CHF-related atrial fibrillation (AF) is controversial. METHODS AND RESULTS: We measured hemodynamic and echocardiographic parameters, mean duration of burst pacing-induced AF (DAF), and atrial-myocyte ionic currents in dogs with CHF induced by 2-week ventricular tachypacing (240 bpm), CHF dogs allowed to recover without pacing for 4 weeks (REC), and unpaced controls. Left ventricular ejection fraction averaged 58.6+/-1.2% (control), 36.2+/-2.3% (CHF, P<0.01), and 57.9+/-1.6% (REC), indicating full hemodynamic recovery. Similarly, left atrial pressures were 2.2+/-0.3 (control), 13.1+/-1.5 (CHF), and 2.4+/-0.4 (REC) mm Hg. CHF reduced I(to) density by approximately 65% (P<0.01), decreased I(Ca,L) density by approximately 50% (P<0.01), and diminished I(Ks) density by approximately 40% (P<0.01) while increasing I(NCX) density by approximately 110% (P<0.05). In REC, all ionic current densities returned to control values. DAF increased in CHF (1132+/-207 versus 14.3+/-8.8 seconds, control) and remained increased with REC (1014+/-252 seconds). Atrial fibrous tissue content also increased in CHF (2.1+/-0.2% for control versus 10.2+/-0.7% for CHF, P<0.01), with no recovery observed in REC (9.4+/-0.8%, P<0.01 versus control, P=NS versus CHF). CONCLUSIONS: With reversal of CHF, there is complete recovery of ionic remodeling, but the prolonged-AF substrate and structural remodeling remain. This suggests that structural, not ionic, remodeling is the primary contributor to AF maintenance in experimental CHF.

Animals↗

Administration of aerosolized terbutaline and budesonide reduces chlorine gas-induced acute lung injury.

BACKGROUND: The pathophysiology and treatment of chlorine gas-induced acute lung injury is poorly characterized and based on anecdotal data. This study aimed to assess the effects of aerosolized beta-2 adrenergic agonist and corticosteroid therapy on chlorine gas-induced lung injury. METHODS: Anesthetized, ventilated pigs were exposed to chlorine gas (400 parts per million for 20 minutes), then assigned randomly 30 minutes later to receive aerosolized terbutaline, budesonide, terbutaline followed by budesonide or placebo (6 pigs in each group). Hemodynamics, gas exchange, and lung mechanics were evaluated for another 5 hours. RESULTS: All the animals demonstrated an immediate increase in airway and pulmonary artery pressure as well as sharp drops in arterial oxygen tension (PaO2) and lung compliance (CL). Recovery of PaO2 and CL was greatest in the terbutaline plus budesonide group, but therapy with terbutaline and budesonide alone also was associated with significant improvement in PaO2 and CL, as compared with placebo. CONCLUSIONS: Treatment of acute chlorine gas lung injury with aerosolized terbutaline followed by aerosolized budesonide improved lung function. Combined treatment was more effective than treatment with either drug alone.

Adrenergic beta-Agonists↗

Pulse-coupled neural networks for contour and motion matchings.

Two neural networks based on temporal coding are proposed in this paper to perform contour and motion matchings. Both of the proposed networks are three-dimensional (3-D) pulse-coupled neural networks (PCNNs). They are composed of simplified Eckhorn neurons and mimic the structure of the primary visual cortex. The PCNN for contour matching can segment from the background the object with a particular contour, which has been stored as prior knowledge and controls the network activity in the form of spike series; The PCNN for motion matching not only detects the motion in the visual field, but also extracts the object moving in an arbitrarily specified direction. The basic idea of these two models is to encode information into the timing of spikes and later to decode this information through coincidence detectors and synapse delays to realize the knowledge-controlled object matchings. The simulation results demonstrate that the temporal coding and the decoding mechanisms are powerful enough to perform the contour and motion matchings.

Action Potentials↗

[Therapeutic effects of rhEPO, rhG-CSF on sulfur mustard induced toxicity in dogs].

OBJECTIVE: To evaluate the therapeutic effects of recombinant human erythropoietin (rhEPO) and recombinant human granulocyte colony stimulating factor (rhG-CSF) on sulfur mustard (SM) induced toxicity in dogs. METHODS: Ten dogs were used as the animal model. Control group had four dogs while treatment group had six. Half an hour after subcutaneously injected with 12 mg/kg (body weight) of SM, the dogs of the treatment group were treated by rhEPO, rhG-CSF and other medicines. General examinations of blood were measured before injecting SM and were continually watched for a week after poisoning. RESULTS: Three dogs in control group died in three days after poisoning, dogs in treatment group all survived. WBC of the control group decreased significantly 3 days after poisoning. RBC of the control group had a slight increase at first, then came down. While WBC and RBC of treatment group remained constant. LYM of both groups descended notably right after poisoning, especially in control group. Two days after poisoning, RC in treatment group began to rise and remained at high level for about a week. No obvious changes of RC in control group were found. CONCLUSION: The use of rhEPO and rhG-CSF after SM exposure can stimulate the growth of the erythrocyte, reticulocyte and leucocyte in dogs. Therefore, rhEPO and rhG-CSF may be significant assistant drugs in future experiment of SM.

Animals↗

Corticothalamic inhibition in the thalamic reticular nucleus.

Mutual inhibition between the GABAergic cells of the thalamic reticular nucleus (RTN) is important in regulating oscillations in the thalamocortical network, promoting those in the spindle range of frequencies over those at lower frequencies. Excitatory inputs to the RTN from the cerebral cortex are numerically large and particularly powerful in inducing spindles. However, the extent to which corticothalamic influences can engage the inhibitory network of the RTN has not been fully explored. Focal electrical stimulation of layer VI in the barrel cortex of the mouse thalamocortical slice in vitro resulted in prominent di- or polysynaptic inhibitory postsynaptic currents (IPSCs) in RTN cells under the experimental conditions used. The majority of cortically induced responses consisted of mixed PSCs in which the inhibitory component predominated or of large IPSCs alone, implying inhibition of neighboring cells by other, cortically excited RTN cells. Within the mixed PSCs, fixed and variable latency components could commonly be identified. IPSCs could be blocked by application of ionotropic glutamate receptor antagonists or of GABA(A) receptor antagonists, also indicating their dependence on corticothalamic excitation triggering disynaptic or polysynaptic inhibition. Spontaneous GABA(A) receptor-dependent IPSCs were routinely observed in the RTN and, taken together with the results of cortical stimulation, indicate the existence of a substantial network of intrareticular inhibitory connections that can be effectively recruited by the corticothalamic system. These results suggest activation of cortical excitatory inputs triggers the propagation of inhibitory currents within the RTN and support the view that activation of the RTN from the somatosensory cortex, although focused by the topography of the corticothalamic projection, is capable of disynaptically engaging the whole inhibitory network of the RTN, by local and probably by reentrant GABA(A) receptor-based synapses, thus spreading the corticothalamic influence throughout the RTN.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

The formation of beta-beta structures in lignin biosynthesis--are there two different pathways?

Based on results from 2D NMR studies, both pinoresinol and secoisolariciresinol structures were found to be present in native lignin from spruce wood as well as in spruce kraft lignin and residual kraft pulp lignin. These two structures constitute the major types of beta-beta inter-unit linkages present in spruce lignin, but their formation in the lignin polymer may follow different pathways leading to their different bonding patterns with the rest of the lignin polymer. The mechanisms involved are discussed.

Butylene Glycols↗

Cellular electrophysiology of canine pulmonary vein cardiomyocytes: action potential and ionic current properties.

Pulmonary vein (PV) cardiomyocytes play an important role in atrial fibrillation; however, little is known about their specific cellular electrophysiological properties. We applied standard microelectrode recording and whole-cell patch-clamp to evaluate action potentials and ionic currents in canine PVs and left atrium (LA) free wall. Resting membrane potential (RMP) averaged -66 +/- 1 mV in PVs and -74 +/- 1 mV in LA (P < 0.0001) and action potential amplitude averaged 76 +/- 2 mV in PVs vs. 95 +/- 2 mV in LA (P < 0.0001). PVs had smaller maximum phase 0 upstroke velocity (Vmax: 98 +/- 9 vs. 259 +/- 16 V s(-1), P < 0.0001) and action potential duration (APD): e.g. at 2 Hz, APD to 90% repolarization in PVs was 84 % of LA (P < 0.05). Na+ current density under voltage-clamp conditions was similar in PV and LA, suggesting that smaller Vmax in PVs was due to reduced RMP. Inward rectifier current density in the PV cardiomyocytes was approximately 58% that in the LA, potentially accounting for the less negative RMP in PVs. Slow and rapid delayed rectifier currents were greater in the PV (by approximately 60 and approximately 50 %, respectively), whereas transient outward K+ current and L-type Ca2+ current were significantly smaller (by approximately 25 and approximately 30%, respectively). Na(+)-Ca(2+)-exchange (NCX) current and T-type Ca2+ current were not significantly different. In conclusion, PV cardiomyocytes have a discrete distribution of transmembrane ion currents associated with specific action potential properties, with potential implications for understanding PV electrical activity in cardiac arrhythmias.

Action Potentials↗