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Biomedical subjects

X G Liu

Publications and source records attributed to X G Liu.

At least 19 recordsLinked to original sources
PubMed2004

Effect of cyclo-oxygenase inhibitors on Helicobacter pylori susceptibility to metronidazole and clarithromycin.

BACKGROUND: We previously reported that aspirin inhibited Helicobacter pylori growth and suppressed the mutagenic effect of metronidazole. AIM: To determine the effects of a cyclo-oxygenase (COX)-2-specific inhibitor, SC-236, and a non-selective COX inhibitor, indometacin, on the growth, urease activity and antimicrobial susceptibility of H. pylori. METHODS: Three H. pylori reference strains, and 18 clinical isolates were treated with SC-236 or indometacin for 24 and 48 h. Growth, urease activity and susceptibility to clarithromycin and metronidazole of the bacteria were assessed by viable colony counting, spectrophotometry and E-test respectively. RESULTS: SC-236 and indometacin inhibited H. pylori growth in a dose-dependent manner with the lowest inhibitory concentrations of 0.03 and 0.1 mm, and the lethal concentrations of 0.09 and 0.3 mm, respectively. The numbers of CFU/mL in Brucella broth containing 0.09 mm SC-236 were 2 log lower at 24 h, and even 3 log lower at 48 h than that at 0 h (P = 0.035, compared with the vehicle control). Treatment of 0.3 mm indometacin reduced the number of CFU/mL by 1 log at 24 h compared with that at 0 h (P = 0.037 compared with the vehicle control). Helicobacter pylori urease activity began to decrease with 0.06 mm SC-236 at 24 h (P = 0.016), and 0.3 mm indometacin at 48 h (P = 0.025). MICs of metronidazole and clarithromycin against H. pylori were decreased significantly in the presence of 0.03 mm SC-236 or 0.1 mm indometacin (all P < 0.001). CONCLUSION: Both SC-236 and indometacin suppressed the growth and urease activity of H. pylori in a dose-dependent manner, and increased its susceptibility to the antibiotics.

Anti-Bacterial Agents↗
PubMed2001

Time-dependent plasticity of synaptic transmission produced by long-term potentiation of C-fiber evoked field potentials in rat spinal dorsal horn.

Our previous work has shown that repetitive stimulation of Adelta-fibers depresses long-term potentiation (LTP) of C-fiber evoked field potentials in spinal dorsal horn. Here, we tested the effects of the Adelta stimulation on the spinal LTP at different time points following LTP induction. Fifteen minutes after LTP induction Adelta stimulation depressed LTP by 44.1+/-4.2% (mean+/-SEM, n=7) for 69.3+/-18.5 min and 1 h after LTP the same Adelta stimulation depressed spinal LTP by only 16.9+/-3.1% for 21.9+/-2.0 min (n=7). Three hours after LTP, however, the Adelta stimulation produced a further potentiation (31.9+/-6.3%, n=7) lasting for all the recording periods (1-3 h). These data indicate that the effects of repetitive stimulation of Adelta-fibers on established spinal LTP of C-fiber evoked field potentials is time-dependent.

Animals↗
PubMed2001

TrkA signal transduction pathways in neuroblastoma.

BACKGROUND: Favorable neuroblastomas frequently express high levels of the TrkA receptor, and these tumors have a propensity to either differentiate or regress, but the mechanisms responsible for these two fates are unclear. PROCEDURE: To study TrkA signal transduction in neuroblastoma (nb), we stably expressed wild-type TrkA and five TrkA mutants in the human nb cell line SH-SY5Y. Resulting single cell clones were characterized by TrkA mRNA and protein expression and by autophosphorylation of the receptor. RESULTS: Introduction of TrkA restored nerve growth factor (NGF) responsiveness of SH-SY5Y cells, demonstrated by morphological differentiation and induction of immediate-early genes. TrkA overexpression leads to growth inhibition in the absence of NGF, whereas NGF treatment results in increased proliferation. CONCLUSIONS: Analysis of downstream signaling elements in mutated TrkA receptors indicates that NGF-induced differentiation is dependent on TrkA kinase activity, but several redundant pathways seem to be used farther downstream. This suggests differences from TrkA pathways identified in PC12 cells.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Three-day lansoprazole quadruple therapy for Helicobacter pylori-positive duodenal ulcers: a randomized controlled study.

AIM: To compare the efficacy and tolerability of a 3-day quadruple therapy with a standard 7-day triple therapy in eradicating Helicobacter pylori infection and healing duodenal ulcers. METHODS: Patients with H. pylori-positive duodenal ulcers were randomized to receive either lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 400 mg twice daily for 7 days (LCM-7) or lansoprazole 30 mg, clarithromycin 500 mg, metronidazole 400 mg, and bismuth subcitrate 240 mg twice daily for 3 days (LCMB-3). No pre- or post-treatment acid suppression was used. Follow-up endoscopy was performed at week 6. RESULTS: A total of 118 patients were recruited. Sixty patients in the LCM-7 group and 53 patients in the LCMB-3 group returned for endoscopy. Intention-to-treat eradication rates were 87% and 86% (P=0.94) and per protocol eradication rates were 87% and 94% (P=0.29) in the LCM-7 and LCMB-3 groups, respectively. Per protocol and intention-to-treat ulcer healing rates were 98% and 98% in LCM-7 and 100% and 91% in LCMB-3, respectively. There were no significant differences in efficacy in relation to the initial metronidazole and clarithromycin susceptibility. Significant reduction in the duration of side-effects was found in the LCMB-3 group. CONCLUSION: The 3-day quadruple therapy is highly effective, better tolerated and can be considered as a first-line therapy in duodenal ulcer management.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Effects of repeated rifabutin administration on the pharmacokinetics of intravenous and oral ciprofloxacin in mice.

The combination of rifabutin and ciprofloxacin is potentially useful for the treatment of disseminated Mycobacterium avium-intracellulare (MAC) diseases in HIV-infected patients. Rifabutin is a metabolic enzyme inducer structurally similar to its predecessor, rifampin. Using a mouse model, the effects of repeated exposure of rifabutin on the pharmacokinetics of ciprofloxacin after intravenous (i.v.) and oral (p.o.) dosing were investigated in the present study. Results showed that repeated exposure of rifabutin, relative to control, caused a 16% increase in the plasma clearance (CL) of ciprofloxacin after i.v. dosing (4.19 vs. 4.87 L/h/kg). Estimates of elimination half-life (T1/2) were not affected by rifabutin (control: 0.81 vs. rifabutin pretreated: 1.18 h). The data obtained after oral dosing showed that repeated rifabutin dosing caused a significant reduction in the maximal plasma concentration (Cmax: 1.34 vs. 0.91 microg/mL) and a longer time to Cmax (Tmax: 0.17 vs. 0.33 h). These changes might be in part attributable to the increase in oral clearance (CL/F) by 18%. With or without rifabutin pretreatment, the T1/2 estimates of ciprofloxacin for p.o. dosing were similar (2.37-2.58 h) and were approximately twice as long as those obtained after i.v. dosing. Since the changes in systemic exposure as a result of rifabutin pretreatment were similar after i.v. and p.o. dosing, the oral bioavailability (F) of ciprofloxacin remained unaffected by rifabutin at approximately 38%. The effects of rifabutin on the pharmacokinetics of ciprofloxacin appear to be moderate in the mouse model which might be attributable to the absorption and distribution behavior of the quinolone antibiotic. The therapeutic implications of this interaction, if any, remain to be defined.

Absorption↗
PubMed2000

Expression of neurotrophin receptor TrkA inhibits angiogenesis in neuroblastoma.

BACKGROUND: Mechanisms regulating the expression of angiogenic factors in tumor cells are largely unknown. High expression of the neurotrophin receptor TrkA in neuroblastomas (NB) is associated with favorable prognosis, whereas TrkB is expressed on aggressive, MYCN-amplified NB. PROCEDURE: To investigate the biological effects of TrkA and TrkB expression on angiogenesis in NB, we examined the expression of angiogenic factors in the human NB cell line SY5Y and its TrkA and TrkB transfectants. RESULTS: In comparison to parental SY5Y cells, mRNA and protein levels of angiogenic factors were significantly reduced in SY5Y-TrkA cells, whereas SY5Y-TrkB cells did not demonstrate a significant change. Conditioned medium (CM) of parental SY5Y and SY5Y-TrkB cells induced endothelial cell proliferation, but this effect was completely absent in SY5Y-TrkA cells. TrkA expression also resulted in severely impaired tumorigenicity in a mouse xenograft model, and was associated with reduced angiogenic factor expression and less vascularization of tumors, as determined by immunohistochemistry and an in vivo Matrigel assay.

Cell Division↗
PubMed2000

Different effects of TrkA expression in neuroblastoma cell lines with or without MYCN amplification.

BACKGROUND: Expression of the neurotrophin receptor TrkA is associated with a favorable prognosis in neuroblastoma (NB) and promotes growth inhibition and neuronal differentiation. Aggressive, MYCN-amplified NB tumors express little or no TrkA mRNA, suggesting that MYCN overexpression may inhibit TrkA expression. PROCEDURE: To study the interactions of TrkA expression and MYCN amplification in NB, we stably expressed the TrkA receptor in the MYCN single copy cell lines SH-SY5Y and NB69 as well as in the MYCN amplified cell lines CHP134 and IMR5. RESULTS: All four transfected cell lines demonstrated high TrkA expression and similar activation of the TrkA receptor and of mitogen-activated protein kinases as well as induction of immediate-early genes in response to nerve growth factor (NGF). Introduction of TrkA restored NGF responsiveness of SH-SY5Y and NB69 cells, as demonstrated by morphologic differentiation, growth inhibition, and enhanced survival in serum-free medium. However, no morphologic, growth, or survival responses to NGF were detected in MYCN-amplified CHP134 and IMR5 TrkA transfectants. CONCLUSIONS: Thus, transfection of TrkA into MYCN amplified NB cell lines only partly restored the TrkA/NGF signaling pathway, suggesting additional inhibitory effects of MYCN overexpression on TrkA signaling.

Cell Division↗
PubMed2000

[Complete nucleotide sequences and genome structure of two Chinese tobacco mosaic virus isolates deduced from full-length infectious cDNA clones].

The complete nucleotides of two Chinese tobacco mosaic virus (TMV) isolates, TMV-Cv (vulgare strain) and TMV-N14 (an attenuated virus originated from a tomato strain), were determined from their respective full-length infectious cDNA clones and compared with published TMV sequences. The genome structure of TMV-Cv contained 6395 nucleotides, in which four functional open reading frames (ORF), coding for replicase (126 kD/183 kD), movement protein (MP, 30 kD) and coat protein (CP, 17.6 kD) respectively, could be recognized. TMV-N14 contained 6384 nucleotides in its genome. In contrast to TMV-Cv, five functional ORFs encoding the replicase 98.5 kD/126 kD/183 kD, MP(27 kD) and CP(17.6 kD), respectively, were detected in the TMV-N14 genome. TMV-Cv is 99% homologous to a Korean TMV isolate belonging to the vulgare strain at the nucleotide level. TMV-N14 is 99% homologous to a highly virulent Japanese isolate TMV-L (tomato strain) at the nucleotide level. In TMV-N14, one opal nulation (UGA) occurred in the replicase gene and one ochre nutation (UAA) in the MP gene. The former mutation created a potential, additional ORF within the replicase gene, the latter reduced the size of the MP to 27 kD. In addition, there were also 13 amino acid substitutions in the replicase gene of TMV-N14 when compared to that of TMV-L. Collectively, these changes may have significant implications in the attenuation of the virulence of TMV-N14.

Amino Acid Sequence↗
PubMed2000

Cryodamage to plasma membrane integrity in head and tail regions of human sperm.

AIM: To investigate the effect of cryopreservation on the plasma membrane integrity in the head and tail regions of individual sperm, and the relationship between intact cryopreserved sperm and its motility and zona-free hamster oocyte penetration rate. METHODS: The eosin Y exclusion and the hypoosmotic swelling tests were combined to form a single test (HOS-EY test) to identify the spermatozoa with four types of membrane integrity. RESULTS: After cryopreservation, there was a marked decline in the percentage of spermatozoa with Type IV membrane integrity (head membrane intact/tail membrane intact), and a significant increase in those with Type I (head membrane damaged/tail membrane damaged) and Type III (head membrane damaged/tail membrane intact) membrane integrity (n = 50, P < 0.01). The value of Type II integrity had a wide range of variability, whereas Type II (head membrane intact/tail membrane damaged) was uncommon after thawing. A high correlation was observed between the percentage of Type IV integrity and sperm motility ( n = 50, r = 0.74, P < 0.01). However, the values of Type IV integrity were usually lower than those of post-thaw motility in most cryopreserved samples. The value of Type IV integrity did not correlate with the sperm penetration rate (n = 25, r = 0.22, P > 0.05). CONCLUSION: (1) The HOS-EY test has the advantage of showing four patterns of membrane integrity in individual spermatozoon; (2) Cryopreservation causes a significant membrane rupture in the head and tail regions of spermatozoa; Type III is the main transitional state of membrane cryodamage; (3) Cryodamage to head and tail membrane may occur independently; the presence of an intact tail membrane does not necessarily indicate the intactness of head membrane. (4) Intact membranes are closely related to post-thaw motility, but do not reflect the fertilizing potential.

Adult↗
PubMed1999

Zinc sulphate solution enema decreases inflammation in experimental colitis in rats.

BACKGROUND: It has been reported that zinc sulphate contributes an anti-inflammatory action in many animal models; however, the impact of zinc in colitis remains unclear. The aim of the present study was to examine the role of zinc sulphate in experimental colitis. METHODS: Colitis was induced by 2,4,6-trinitrobenzenesulphonic acid (TNB) in rats. Beginning at the first day of TNB colitis, the rats were treated with a zinc sulphate enema once daily for 6 days. The rats were examined 8 days later. RESULTS: The TNB induced severe colitis as evidenced by increased mucosal lesion area, mucosal myeloperoxidase (MPO) activity and prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels. Six days after the application of the zinc sulphate enema, the mucosal lesion area, MPO activity, PGE2 and LTB4 levels all decreased significantly. Mucosal superoxide dismutase activity remained unchanged after zinc treatments. CONCLUSIONS: Our data suggest that zinc sulphate enemas have an anti-inflammatory action on experimental colitis.

Animals↗
PubMed1998

Activation of spinal N-methyl-D-aspartate or neurokinin receptors induces long-term potentiation of spinal C-fibre-evoked potentials.

The use-dependent increase in synaptic strength between primary afferent C-fibres and second-order neurons in superficial spinal dorsal horn may be an important cellular mechanism underlying central hyperalgesia. This long-term potentiation can be blocked by antagonists of the N-methyl-D-aspartate subtype of glutamate receptor, the neurokinin 1 or the neurokinin 2 receptor. We have tested here whether activation of these receptors by superfusion of the spinal cord with corresponding agonists in the absence of presynaptic activity is sufficient to induce long-term potentiation. In urethane anaesthetized rats C-fibre-evoked field potentials were elicited in superficial laminae of lumbar spinal cord by electrical stimulation of the sciatic nerve. In rats with intact spinal cord, controlled superfusion of the spinal cord at recording segments for 60 min with N-methyl-D-aspartate, substance P or neurokinin A never induced long-term potentiation. Spinal superfusion with a mixture of N-methyl-D-aspartate, substance P and neurokinin A also failed to induce long-term potentiation in four rats tested. In spinalized rats, however, long-term potentiation was induced by either N-methyl-D-aspartate (at 10 microM, to 173 +/- 16% of control) substance P (at 10 microM, to 176 +/- 13% of control) or by neurokinin A (at 1 microM, to 198 +/- .20% of control). The induction of long-term potentiation by N-methyl-D-aspartate, substance P or neurokinin A was blocked by intravenous application of the receptor antagonists dizocilpine maleate (0.5 mg/kg), RP67580 (2 mg/kg) or SR48968 (0.2 mg/kg), respectively. Thus, activation of N-methyl-D-aspartate or neurokinin receptors may induce long-lasting plastic changes in synaptic transmission in afferent C-fibres and this effect may be prevented by tonic descending inhibition.

Animals↗
PubMed1998

Long-term depression of C-fibre-evoked spinal field potentials by stimulation of primary afferent A delta-fibres in the adult rat.

Long-term potentiation (LTP) of spinal C-fibre-evoked field potentials can be induced by brief electrical stimulation of afferent C-fibres, by natural noxious stimulation of skin or by acute nerve injury. Here, we report that in urethane anaesthetized, adult rats prolonged high frequency burst stimulation of the sciatic nerve at Adelta-fibre strength produced long-term depression (LTD) of C-fibre-evoked field potentials, and also depressed the increased amplitudes of C-fibre-evoked field potentials recorded after LTP had been established (depotentiation). Electrical stimulation of Abeta-fibres failed to induce LTD or depotentiation. In spinalized rats, prolonged Adelta-fibre conditioning stimulation induced LTP rather than LTD of C-fibre-evoked field potentials. Thus, tonic descending inhibition may determine the direction of plastic changes in C-fibre-mediated synaptic transmission. Spinal application of the N-methyl-D-aspartic acid receptor antagonist D-APV blocked induction of LTD in intact rats and LTP in spinalized rats. The presently described LTD and the depotentiation of established LTP of C-fibre-evoked field potentials in spinal dorsal horn may underlie some forms of prolonged analgesia induced by peripheral nerve stimulation procedures.

2-Amino-5-phosphonovalerate↗
PubMed1998

Assessment of presystemic factors on the oral bioavailability of rifampicin following multiple dosing.

This study was carried out to elucidate the possible mechanism(s) responsible for reduced oral rifampicin bioavailability after multiple dosing. In addition to autoinduction, the relative contribution of the two possible controlling factors, e.g., intestinal metabolism and microbial degradation, was investigated using a rat model. Pharmacokinetic studies were carried out to assess the absolute rifampicin bioavailability by both oral and intravenous drug administration before and after 8 daily doses of 25 mg/kg. To estimate the possible involvement of microbial degradation, rifampicin kinetics were also assessed in rats on day 8 after receiving multiple oral dosing and concurrent administration of nonabsorbable triple antibiotics for gut sterilization 3 days prior to the study day. Pharmacokinetic parameters were generated by noncompartmental analysis. The results revealed a significant decrease in rifampicin levels for rats after multiple exposure, compared to single dosing; the mean clearance determined by intravenous dosing increased by 43% from 3.7 ml/min/kg and the half-life decreased by 24% from 238 min. However, the extent of decrease in rifampicin exposure following multiple dosing was substantially greater for rats dosed orally than intravenously; estimated absolute oral bioavailability decreased by 15% from 0.89 on day 1 to 0.76 on day 8. No apparent alterations in any of the pharmacokinetic parameters were observed after gut sterilization, suggesting minimal contribution of microbial degradation to the reduction in oral rifampicin absorption after multiple dosing. In addition to hepatic enzyme autoinduction, these results strongly suggest the involvement of enhanced intestinal metabolism as a contributing factor to the decrease in oral rifampicin bioavailability following prolonged exposure.

Absorption↗
PubMed1997

Expression and function of Trk-C in favourable human neuroblastomas.

Human neuroblastomas express the neurotrophin receptors trk-A and trk-B. Favourable outcome is associated with expression of trk-A, while unfavourable, MYCN amplified tumours express trk-B. In this study we examined the expression of trk-C in primary neuroblastoma tumour-derived cell lines. We found by Northern blot analysis that trk-C mRNA is expressed in 14 of 55 (25%) primary tumours. Trk-C was expressed in significantly more lower stage tumours (stage 1, 2, 4S) than higher stage tumours (stage 3, 4, P < 0.04). The expression of trk-C was correlated positively with survival and negatively correlated with MYCN amplification. We also studied the function of trk-C in transfected cell lines and found that NT-3 promotes both cell survival and differentiation. Our results suggest that trk-C is involved in the biology of favourable neuroblastomas.

Blotting, Northern↗
PubMed1997

Expression of TrkA, TrkB and TrkC in human neuroblastomas.

There is considerable interest in the role of the TRK family of neurotrophin receptors in regulating the survival, growth and differentiation of normal and neoplastic nerve cells. Indeed, there is increasing evidence that TRK genes play an important role in the biology and clinical behavior of neuroblastomas, tumors of the peripheral nervous system. Evidence from several independent studies suggests that high expression of TrkA is an indicator of favorable outcome, and there is an inverse correlation between TrkA expression and N-myc amplification. In addition, some primary neuroblastomas differentiate in vitro in the presence of NGF but die in its absence. We have evidence that coexpression of full-length TrkB and BDNF is associated with N-myc amplification and may represent an autocrine survival pathway. Conversely, truncated TrkB is expressed predominantly in differentiated tumors. Finally, Trk-C is expressed in favorable neuroblastomas, essentially all of which also express TrkA. In summary, the study of neurotrophin receptor expression and function in neuroblastomas may provide important insights into the role that these pathways play in the pathogenesis and clinical behavior of this tumor. Ultimately, these pathways may provide attractive targets for the development of therapy aimed at inducing differentiation or programmed cell death in these tumors.

Brain-Derived Neurotrophic Factor↗
PubMed1996

Expression of TrkC in favorable human neuroblastomas.

Human neuroblastomas have been found to express the neurotrophin receptors TrkA and TrkB. Expression of TrkA correlates with favorable outcome, while expression of full-length TrkB is associated with unfavorable, more aggressive, N-myc amplified tumors. In this study we have determined the expression of TrkC in neuroblastoma primary tumors and cell lines. Using probes for the extracellular domain and the tyrosine kinase domain of human TrkC, we found by Northern analysis that TrkC mRNA is expressed in 14 of 55 (25%) tumors from a representative panel of neuroblastomas. A 14 kb transcript was detected by both probes, indicating that it would encode the full-length TrkC protein. A significant association was found between TrkC mRNA expression detected by Northern analysis and lower stage tumors [stage 1, 2, 4S, 11 of 30 (37%); vs stage 3, 4, 3 of 25 (12%), chi2 = 4.4, P < 0.04]. Only one of eight primary tumors with N-myc amplification had detectable TrkC mRNA expression and none of the eight neuroblastoma cell lines expressed TrkC by Northern analysis. Our results suggest that TrkC is involved in the biology of favorable neuroblastomas.

Base Sequence↗
PubMed1996

The massive expression of c-fos protein in spinal dorsal horn neurons is not followed by long-term changes in spinal nociception.

It has been suggested that the expression of c-fos and other immediate early genes in spinal dorsal horn neurons would trigger changes in the phenotype of nociceptive neurons which may lead to long-term changes in spinal nociception. To test this hypothesis, we have used a minimally invasive intrathecal stimulation and injection technique which can be applied to adult Sprague-Dawley rats under brief ether anesthesia to induce massive c-fos expression in spinal neurons without affecting peripheral nociceptors. Electrical intrathecal stimulation (0.5 ms pulses, 15 V, 3 Hz for 15 min) or intrathecal injection of N-methyl-D-aspartate (25 nmol) produced massive c-Fos immunoreactivity in neurons throughout the sacral spinal cord and the dorsal horn of the lumber spinal cord. Immunoreactivity declined to control values at mid-thoracic levels. To assess effects of these intrathecal stimuli on nociception, hot-plate and tail-flick latencies and mechanical thresholds of hindlimb withdrawal reflexes were measured once every day for 14 days before and up to 14 days after conditioning stimulation. Spontaneous locomotion of each animal was video-taped daily for 5 min and analysed off-line. On the day of the intrathecal stimulation the tests were performed 1 h before and also 6 h after conditioning stimulation. Thermal and mechanical nociceptive thresholds were temporarily enhanced 6 h after intrathecal stimulation but they were not different from controls one to 14 days later. Thus, the massive expression of c-fos in spinal neurons is not, as previously suggested, a sufficient condition for the induction of long-term changes in spinal nociception.

Animals↗