Biomedical subjects

Z W Li

Publications and source records attributed to Z W Li.

At least 19 recordsLinked to original sources

PubMed2006

A novel method for analysis of single ion channel signal based on wavelet transform.

A single ion channel signal was analysed by the power distribution fraction constructed by a discrete wavelet transform. Average opening time and energy distribution of the signal can be obtained directly by this method. The method can also be used when the signal is corrupted by noise. By contrast, the conventional frequency domain analysis method--power spectral density--is less effective. Power distribution fraction will therefore give more useful information in analysis of experimental ion channel signals, principally by giving values of the mean channel opening time. The method may be applied to distinguish different ion channels more efficiently and to find their reactions to drugs.

Algorithms↗

PubMed2003

Synthesis and characterization of trans-[Os(en)2py(H)]2+ and related studies.

trans-[Os(en)(2)pyH](Otf)(2), 2, is recovered from an acidic solution of trans-[Os(en)(2)py(H(2))](OTf)(2), 1, which has been subjected to one electron oxidation. The structures of both 1 and 2 have been determined by single crystal X-ray analysis. In cyclic voltammetry, 2 shows a one electron oxidation wave at 0.95 V and a one electron reduction wave at -1.2 V, neither accompanied by a signal for the reverse process. Reduction of 2 by Zn/Hg in methanol solution leads to quantitative formation of [Os(en)(2)(py)H(2))](2+), predominantly in the trans-form. In aqueous solution, species 2 reacts rapidly with N-methylacridium ion, [MAH](+), by hydride transfer. One electron chemical oxidation of 2 to the corresponding Os(IV) is slower than that of 1 to 2 owing to the increase in coordination number when Os(IV) is produced. Treatment of 1, or the cis-form, 1', in DMSO by sodium t-butoxide produces mainly the corresponding isomers of the monohydrides of Os(II), that derived from 1' is deep red in color while the trans-monohydride is colorless. Both react with [MAH](+) to form [MAH](2), and both disappear rapidly in acetone or acetonitrile, presumably by reducing the solvents. Reaction of trans-[Os(NH(3))(4)(H(2))H(2)O](BPh(4))(2), 4, in acetone-d(6) as solvent with either CH(3)CHO or styrene leads to hydrogenation of the substrate. Reactions which compete with trans-[Os(en)(2)(eta(2)-H(2))(CF(3)SO)(3)]CF(3)SO(3) release of substrate from the trans-complex before isomerization to the cis-form, required for hydrogenation to occur, result in the trans-derivative of the added solute. When H(2)C=CH-CH(2)-SCH(3) is the substrate, binding takes place at sulfur. Complete conversion to the cis-substrate isomer is observed, without hydrogenation occurring even though contact between dihydrogen and the double bond is possible.

Journal Article↗

PubMed2001

Neurokinin B potentiates ATP-activated currents in rat DRG neurons.

This study aimed to explore whether NKB could modulate the responses mediated by ATP receptor (P2X purinoceptor). Whole-cell patch clamp and repatch experiments were performed on cultured rat DRG neurons. The majority of neurons examined were sensitive both to ATP and to NKB (77.1%, 54/70). NKB preapplied could potentiate ATP-activated currents (I(ATP)) markedly; this effect was concentration-dependent and could be blocked by SR 142801, an NK3 receptor antagonist. Preapplication of 0.001, 0.01, 0.1 and 1.0 microM NKB increased ATP-activated currents by 55.1+/-18.8, 75.2+/-17.4, 84.1+/-18.8 and 81.0+/-21.7%, respectively. The concentration-response curves for ATP with and without preapplication of NKB show that: (1) preapplication of NKB shifted the curve upwards; (2) the maximal amplitude of I(ATP) with NKB preapplication increased by 78.5%, while the threshold value remained unchanged; (3) the EC(50) values of the two curves were very close (44 vs. 42 microM). Intracellular dialysis of H-7 by using repatch clamp technique could block the potentiation of I(ATP) by NKB. It suggests that this potentiating effect was caused by phosphorylation of ATP receptor, which resulted from the activation of G protein coupled NK3 receptor and consequential intracellular signal transduction cascade.

Adenosine Triphosphate↗

PubMed2001

Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta.

We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IkappaB kinase beta (IKKbeta) attenuated insulin signaling in cultured cells, whereas IKKbeta inhibition reversed insulin resistance. Thus, IKKbeta, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikkbeta+/-) protected against the development of insulin resistance during high-fat feeding and in obese Lep(ob/ob) mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKbeta pathway as a target for insulin sensitization.

Animals↗

PubMed2001

IKKbeta is essential for protecting T cells from TNFalpha-induced apoptosis.

Transcription factor NF-kappaB, whose activation depends on the IKKbeta catalytic subunit of the IkappaB kinase, was assigned with both anti- and proapoptotic functions in T lymphocytes. To critically evaluate these functions, we transferred Ikkbeta-/- or wild-type (wt) fetal liver (FL) stem cells into lethally irradiated mice. Ikkbeta-/- radiation chimeras show thymic rudiments, aberrant lymphoid organs, and absence of T cells. T lymphopoiesis is rescued when Ikkbeta-/- stem cells are cotransferred with wt bone marrow, suggesting that IKKbeta may mediate its lymphopoietic function via extrinsic factors. However, almost normal development of Ikkbeta-/- T cells is observed upon removal of type 1 TNFalpha receptor, indicating that TNFalpha signaling accounts for the absence of Ikkbeta-/- T cells. Indeed, Ikkbeta-/- radiation chimeras exibit elevated circulating TNFalpha, and Ikkbeta-/- thymocytes display increased TNFalpha sensitivity.

Adoptive Transfer↗

PubMed2001

Prevention of fat-induced insulin resistance by salicylate.

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may involve fat-induced activation of a serine kinase cascade involving IKK-beta. To test this hypothesis, we first examined insulin action and signaling in awake rats during hyperinsulinemic-euglycemic clamps after a lipid infusion with or without pretreatment with salicylate, a known inhibitor of IKK-beta. Whole-body glucose uptake and metabolism were estimated using [3-(3)H]glucose infusion, and glucose uptake in individual tissues was estimated using [1-(14)C]2-deoxyglucose injection during the clamp. Here we show that lipid infusion decreased insulin-stimulated glucose uptake and activation of IRS-1-associated PI 3-kinase in skeletal muscle but that salicylate pretreatment prevented these lipid-induced effects. To examine the mechanism of salicylate action, we studied the effects of lipid infusion on insulin action and signaling during the clamp in awake mice lacking IKK-beta. Unlike the response in wild-type mice, IKK-beta knockout mice did not exhibit altered skeletal muscle insulin signaling and action following lipid infusion. In summary, high-dose salicylate and inactivation of IKK-beta prevent fat-induced insulin resistance in skeletal muscle by blocking fat-induced defects in insulin signaling and action and represent a potentially novel class of therapeutic agents for type 2 diabetes.

Animals↗

PubMed2001

Distribution of trace elements in normal and tumor-bearing mice using the multitracer technique.

A multitracer solution obtained from the nuclear reaction of selenium with 25-MeV/nucleon 40Ar ions was orally administered to normal and tumor-bearing Balb/c male mice. After 96 h, the mice were sacrificed and the elemental distribution was determined in various tissues, organs, and blood. The uptake of Na, Rb, Ga, Sc, V, Cr, Mn, Co, Fe, Zn, Y, Zr, Tc, Ru, Ag, and In in normal and, except for zinc, in tumor-bearing mice was simultaneously detected. Most elements were distributed in about the same manner in the skin and liver of animals in both groups. The distribution of Rb, Ga, V, Cr, Tc, and In showed little or no significant differences between the two study groups. The distribution of Na, Mn, Fe, Ag, Sc, and Co showed significant differences between normal and tumor-bearing mice. In the blood, spleen, and kidney of the normal mice, there was good absorption of Na, Mn, Fe, Ag, Co, and Zn. In the heart, these elements were well absorbed, except for Na and Mn.

Animals↗

PubMed2001

[Substance P depresses GABA-activated currents in cultured hippocampal pyramidal neurons of rats].

The purpose of the present study was to explore whether substance P (SP) modulates the response mediated by GABAA receptors. Experiments were carried out on cultured hippocampal pyramidal neurons of rats. GABA-activated inward currents were recorded using the whole-cell-patch-clamp technique. The majority of the neurons examined (66/92, 72%) were sensitive to both GABA and SP. When the neurons were treated with SP prior to application of GABA, the GABA-activated current (IGABA) was inhibited markedly, which was concentration-dependent and could be blocked by spantide, an NK1 receptor antagonist. With 10(-8), 10(-7), 10(-6) and 10(-5) mol/L SP, IGABA was inhibited by 18%, 24.8%, 25.9% and 28% respectively. Intracellular application of H7, a potent inhibitor of PKC, abolished inhibition of IGABA by SP, suggesting that the inhibition of IGABA by SP may be a result of intracellular phosphorylation of the GABAA receptor.

Animals↗

PubMed2001

Modulation by divalent cations of GABA rho 1 receptor from human retina expressed in Xenopus oocytes.

OBJECTIVE: To investigate functional homooligomeric GABA rho 1 receptors expressed in Xenopus oocytes and the modulation of divalent cations. METHODS: GABA rho 1 cDNA from human retina was transcribed in vitro to obtain sense rho 1 mRNA, which was microinjected into Xenopus oocytes. Two-electrodes voltage clamp technique was performed to record GABA-induced currents. RESULTS: Expressed receptors were found to have similar properties to GABAc receptors characterized in the retina. Cl-currents induced by GABA were blocked by picrotoxin instead of bicuculline. GABA-induced currents reversed at -19 +/- 2.5 mV, and EC50 was 3.3 mumol/L. Zn++ modulated GABA-induced currents with an IC50 = 9.6 mumol/L. Ni++, Cu++ and Cd++ inhibited GABA rho 1 obviously, too. Their rank order of potency was Zn++ > Ni++ > Cu++ > Cd++. CONCLUSION: Zinc (10 mumol/L) inhibited GABA-induced currents in a competitive manner, and its action was sensitive to extracellular pH. Site-directed mutagenesis revealed that substitution of a single histidine residue (H44 and H48) failed to affect zinc sensitivity.

Animals↗

PubMed2001

[Current responses mediated by endogenous GABA(B) and GABA(C) receptors in Xenopus oocytes].

The properties of GABA-activated current in Xenopus oocytes and its underlying mechanism were studied using the two-electrode voltage-clamp technique. External application of GABA (10(-10) - 10(-3)mol/L) induced a concentration-dependent outward current in a proportion of oocytes (35.5%, 55/155). Selective GABA(A) receptor antagonist bicuculline (10(-5) mol/L) did not block the GABA-activated current (n=6). However, 2-hydroxysaclofen (10(-4) mol/L), a GABA(B) receptor antagonist, reversed the GABA-activated outward current to an inward current (n=9), which was abolished completely by application of I4AA (10(-5) mol/L), a GABA(C) receptor selective antagonist (n=6). In 20% (12/60) of oocytes, application of baclofen (10(-10) - 10(-4) mol/L), a GABA(B) receptor agonist, also induced a concentration-dependent outward current 2-Hydroxysaclofen at the concentrations of 3 x 10(-6), 3 x 10(-5) and 3 x 10(-4) mol/L blocked the baclofen(10(-5) mol/L)-activated outward current by (6.3+/-3.2) %, (44.1+/-2.2) %, and (86.0+/-1.6) %, respectively (n=6). The reversal potential for baclofen-activated current was around 96.8+/-7.2 mV (n=6), and the baclofen-activated current could be blocked by TEA (n=5) and Ba(2+) (n=5). These results suggest that there exist endogenous GABA receptors, GABA(B) receptors mediating a slow and sustained outward current and GABA(C) receptors mediating an inward current in follicular Xenopus oocytes.

Animals↗

PubMed2001

[Study on gas chromatographic method for the evaluation of residual solvents by using wide bore open tubular columns].

A GC method using wide bore open tubular columns was developed to evaluate residual organic solvents. Sixteen organic solvents commonly used for pharmaceutical synthesis were analysed. The effects of different polarity columns and extraction solvents on the assay of residual solvents were studied in this work. It showed that most solvents can be well separated from each other on non-polar or less polar wide-bore columns. Extraction solvents differed in their extraction recovery and peak shape. Satisfactory results can be obtained when the proposed method was employed and a suitable extraction solvent was selected. The procedures summarized in this paper can be used as a guidance for the evaluation of residual organic solvents in bulk pharmaceuticals.

Chromatography, Gas↗

PubMed2001

[Study on schistosomiasis control strategy in Ertan reservoir].

OBJECTIVE: To explore means and strategies of preventing the spread of schistosomasis transmission due to the building of Ertan Dam. METHODS: To eliminate the infection sources and Oncomelania snails. To install concrete irrigation and piping system of water supply. To encourage the immigrants to build methane-generating tanks and improve sanitary facilities and conditions for families who live near the water-retaining line. RESULTS: 2,360 people and 152 cattle were treated for schistosome infection. Mollusciciding and environmental modification were made for eliminating snails at an area of 3,634,580 m2 and 67,105.5 m2 respectively. The length of concrete irrigation and piping system installed was 51.13 and 104.895 km respectively. Methane-generating tanks, water-heating instruments using solar energy and other sanitary facilities were established in 1,781 households. After three-year intervention, no infected snails were found and no infected human being, cattle and wild rats were detected. CONCLUSION: Schistosomiasis control was financially supported since the very beginning of the Ertan Dam project, which provided a condition for sustainable development. Continued surveillance of snails and infection sources should be carried out, which will provide scientific basis for schistosomiasis control in the Three Gorges region as well as other new projects of hydropower and water conservancy in endemic area.

Animals↗

PubMed2001

[Inhibition of ATP-activated current by met-Enk in isolated DRG neurons of the rat].

The present study aimed to explore modulation of ATP-activated currents (I(ATP)) by met-Enk in rat DRG neurons. I(ATP) was recorded using the whole-cell patch clamp technique. The majority of the neurons examined responded to ATP (90.0 percent;, 45/50) with inward currents. In the 45 ATP sensitive neurons three kinds of responses to application of met-Enk were distinguished: (l) inward currents (29/45), (2) outward currents (9/45), and (3) no effect (7/45). Pretreatment with met-Enk (10(-9)~10(-5) mol/L) suppressed I(ATP) (10(-4) mol/L) in 29 neurons responding to met-Enk with inward currents. The inhibition by met-Enk of I(ATP) could be blocked by naloxone (10(-7) mol/L) in a concentration-dependent manner. Met-Enk of 10(-9), 10(-8), 10(-7), 10(-6) and 10(-5) mol/L suppressed I(ATP) by l3.2+/-5.4 percent; (n=5); 39.2+/-8.6 percent; (n=8), 54.l+/-8.6 percent; (n=8),43.3+/-7.9 percent; (n=7) and 43.l+/-7.9 percent; (n=7) (mean+/-MSE), respectively. A comparison of concentration - response relations of ATP with and without preapplication of met-Enk indicated that after pretreatment with met-Enk (10(-7) mol/L) the curve shifted downward markedly with a decrease of 25 percent; of the maximum value of I(ATP) and unchanged K(d) value. The suppression of I(ATP) by met-Enk was reversed as evidenced by intracellular dialysis of H-9 by using the repatch technique. Taken together, it is suggested that the inhibition by met-Enk of I(ATP) is caused by activation of opiate receptor, which eventually results in phosphorylation of ATP receptor, mediated by modulation of G protein coupling and intracellular signal transduction.

Adenosine Triphosphate↗

PubMed2000

[Modulation of GABA-activated currents by oxytocin in rat dorsal root ganglion neurons].

Experiments were performed on freshly isolated dorsal root ganglion (DRG) neurons of rat. GABA(A)-activated currents were recorded using the whole-cell patch clamp technique. The majority of the neurons (48/52, 90.5%) were sensitive to GABA (10( 6)~10( 3) mol/L). Application of oxytocin (OT) induced outward membrane responses in 51.3% (20/39) of the neurons, no apparent responses in 43.6% (17/39) and inward responses in 5.1% (2/39). 10( 12), 10( 11), 10( 10) and 10( 9) mol/L OT increased 10( 4) mol/L GABA-activated currents to 24.1+/-7.6% (n=6), 33.4+/-6.9% (n=9), 40.2+/-6.5% (n=13) and 67.2+/-14.8% (n=5), respectively. After preapplication of OT, the Kd value for GABA(A)-activated currents decreased, while the response obtained at the maximum concentration increased. The results suggest that the enhancement of GABA-activated currents by OT may suppress primary sensory transmission by potentiating pre-synaptic inhibition of GABA.

Animals↗

PubMed2000

[Stable life prediction for a complex injection of Chinese materia medica by initial average rate stability test].

OBJECTIVE: To predict the stable life for a complex injection of Chinese materia medica. METHOD: The prediction was carried out by initial average rate stability tests, and the contents of puerarin and danshensu (major active components of the injection) were assayed by HPLC. RESULT: The degradation of puerarin followed the first order action, while danshensu was hard to determine; the t0.9,25 degrees C was 3.49 years and 1.69 years respectively. CONCLUSION: The stable life of the injection has been determined as 1.5 years.

Drug Combinations↗

PubMed1999

The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis.

The IkappaB kinase (IKK) complex is composed of three subunits, IKKalpha, IKKbeta, and IKKgamma (NEMO). While IKKalpha and IKKbeta are highly similar catalytic subunits, both capable of IkappaB phosphorylation in vitro, IKKgamma is a regulatory subunit. Previous biochemical and genetic analyses have indicated that despite their similar structures and in vitro kinase activities, IKKalpha and IKKbeta have distinct functions. Surprisingly, disruption of the Ikkalpha locus did not abolish activation of IKK by proinflammatory stimuli and resulted in only a small decrease in nuclear factor (NF)-kappaB activation. Now we describe the pathophysiological consequence of disruption of the Ikkbeta locus. IKKbeta-deficient mice die at mid-gestation from uncontrolled liver apoptosis, a phenotype that is remarkably similar to that of mice deficient in both the RelA (p65) and NF-kappaB1 (p50/p105) subunits of NF-kappaB. Accordingly, IKKbeta-deficient cells are defective in activation of IKK and NF-kappaB in response to either tumor necrosis factor alpha or interleukin 1. Thus IKKbeta, but not IKKalpha, plays the major role in IKK activation and induction of NF-kappaB activity. In the absence of IKKbeta, IKKalpha is unresponsive to IKK activators.

Animals↗

PubMed1999

Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the beta-amyloid-precursor protein.

We previously have reported corpus callosum defects in transgenic mice expressing the beta-amyloid precursor protein (betaAPP) with a deletion of exon 2 and at only 5% of normal levels. This finding indicates a possible involvement of betaAPP in the regulation or guidance of axon growth during neural development. To determine to what degree the betaAPP mutation interacts with genetic background alleles that predispose for forebrain commissure defects in some mouse lines, we have assessed the size of the forebrain commissures in a sample of 298 mice. Lines with mixed genetic background were compared with congenic lines obtained by backcrossing to the parental strains C57BL/6 and 129/SvEv. Mice bearing a null mutation of the betaAPP gene also were included in the analysis. We show that, independently of genetic background, both lack and underexpression of betaAPP are associated with reduced brain weight and reduced size of forebrain commissures, especially of the ventral hippocampal commissure. In addition, both mutations drastically increase the frequency and severity of callosal agenesis and hippocampal commissure defects in mouse lines with 129/SvEv or 129/Ola background.

Amyloid beta-Protein Precursor↗

PubMed1999

Distinct ATP-activated currents in different types of neurons dissociated from rat dorsal root ganglion.

Rat dorsal root ganglion neurons can be classified into at least three distinct groups based on cell size, afferent fiber diameter, electrophysiological properties, sensitivity to vanilloid agonists such as capsaicin, and function. In the present study, ATP-activated current in these neurons was characterized using whole-cell patch-clamp recording. Small diameter (<30 microm) cells had high capsaicin sensitivity, high affinity for ATP, and rapidly desensitizing ATP-activated current. Medium diameter (30-50 microm) cells had no capsaicin sensitivity, lower affinity for ATP and slowly desensitizing ATP-activated current. Large diameter (>50 microm) cells were insensitive to both capsaicin and ATP. These findings suggest that distinct types of ATP receptor-ion channels are expressed in different types of dorsal root ganglion neurons, and may contribute to the functional differences among these types of neurons.

Adenosine Triphosphate↗