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Biomedical subjects

Bing Zhu

Publications and source records attributed to Bing Zhu.

At least 37 records · Page 2Linked to original sources
PubMed2005

Cyclic GMP-specific phosphodiesterase 5 regulates growth and apoptosis in pulmonary endothelial cells.

Sustained increases in intracellular cGMP concentrations ([cGMP]i) inhibit cell growth and induce apoptosis. We now report that a cGMP-specific phosphodiesterase, PDE5, plays a dominant role in regulating [cGMP]i transitions that inhibit cell growth and control susceptibility to apoptosis in pulmonary endothelium. Atrial natriuretic peptide (ANP) activates guanylyl cyclase A/B and induces a rapid [cGMP]i rise 2-5 min after its application, in both pulmonary arterial endothelial cells (PAECs) and pulmonary microvascular endothelial cells (PMVECs). However, increased [cGMP]i in PAECs is transient and decays within 10 min due to cytosolic PDE5 hydrolytic activity. Increased [cGMP]i in PMVECs is sustained for >3 h due to the absence of PDE5. Indeed, at any ANP concentration, the sustained (30 min) [cGMP]i rise is greater in PMVECs than in PAECs, unless PAECs are also treated with the PDE5 inhibitor zaprinast. Using RT-PCR, Western blot analysis, immunoprecipitation, and DEAE chromatography, we resolved the expression and activity of PDE 5A1/A2 only in PAECs. Similarly, PDE5 expression was restricted to extra-alveolar endothelium in vivo. ANP induced growth inhibition and apoptosis in PMVECs, but similar effects were not seen in PAECs unless ANP treatment was combined with zaprinast. ANP blocked the VEGF-induced proliferation and migration in PMVECs. Collectively, these data suggest that PDE5-regulated [cGMP]i controls endothelial cell growth and apoptosis, representing a mechanism of heterogeneity between two endothelial phenotypes.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Acupuncture inhibition on neuronal activity of spinal dorsal horn induced by noxious colorectal distention in rat.

AIM: To observe how acupuncture stimulation influences the visceral nociception in rat and to clarify the interactions between acupuncture or somatic input and visceral nociceptive inputs in the spinal dorsal horn. These will provide scientific base for illustrating the mechanism of acupuncture on visceral pain. METHODS: Experiments were performed on Sprague-Dawley rats and the visceral nociceptive stimulus was generated by colorectal distention (CRD). Unit discharges from individual single neuron were recorded extracellularly with glass-microelectrode in L(1-3) spinal dorsal horn. Acupuncture stimulation was applied at contralateral heterotopic acupoint and ipsilateral homotopic acupoint, both of which were innervated by the same segments that innervate also the colorectal-gut. RESULTS: The visceral nociception could be inhibited at the spinal level by the heterotopic somatic mechanical stimulation and acupuncture. The maximal inhibition was induced by acupuncture or the somatic noxious stimulation at spinal dorsal horn level with inhibiting rate of 68.61% and 60.79%, respectively (P<0.01 and <0.001). In reversible spinalized rats (cervical-thoracic cold block) both spontaneous activity and responses to CRD increased significantly in 16/20 units examined, indicating the existence of tonic descending inhibition. The inhibition of acupuncture on the noxious CRD disappeared totally in the reversible spinalized rats (P<0.001). CONCLUSION: The inputs of noxious CRD and acupuncture may interact at the spinal level. The nociceptive visceral inputs could be inhibited by acupuncture applied to hetero-topic acupoint. The effect indicates that the spinal dorsal horn plays a significant role in mediating the inhibition of acupuncture and somatic stimulation on the neuronal response to the noxious visceral stimulation and the inhibition is modulated by upper cervical cord and/or supra-spinal center.

Action Potentials↗
PubMed2005

Suppression of cyclic GMP-specific phosphodiesterase 5 promotes apoptosis and inhibits growth in HT29 cells.

Phosphodiesterase 5 (PDE5) is a major isoform of cGMP phosphodiesterase in a variety of human tumor cell lines and plays a key role in regulating intracellular cGMP concentrations ([cGMP]i). Here, we demonstrate that suppression of PDE5 gene expression by antisense pZeoSV2/ASP5 plasmid transfection results in a sustained increase in [cGMP]i, growth inhibition, and apoptosis in human colon tumor HT29 cells. With stable transfection, antisense transcripts exhibited a specific suppression in PDE5 activity, mRNA levels, and a 93 kDa hPDE5A1 protein. In cloned antisense cells, prolongation of the cell growth doubling times correlate positively with suppressed PDE5 activity and increased [cGMP]i. The growth inhibition in PDE5 antisense clones is due to an increased apoptotic rate and delayed cell-cycle progression. These results corroborate previous findings with the PDE5 inhibitor exisulind and its derivatives showing that sustained [cGMP]i induces apoptosis and growth inhibition in tumor cells. Furthermore, an inducible mitotic inhibitor p21WAF1/CIP1 has been found to account for the delay of cell-cycle progression in PDE5 antisense clones at G2/M phase. A proteolytic cleavage of p21WAF1/CIP1 in the antisense clones is also increased at the later stage of serum stimulation. The protein kinase G (PKG) inhibitor, KT5823, can prevent the cleavage of p21(WAF1/CIP). These data substantiate a pivotal role for PDE5 as a modulator of apoptosis and cell-cycle progression for human carcinoma via a mechanism involving the activation of [cGMP]i/PKG signaling pathways.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Association of polymorphisms in the cyclin D1 and XPD genes and susceptibility to cancers of the upper aero-digestive tract.

DNA repair enzyme genetic polymorphisms have been postulated to increase the risk of certain cancers in the presence of tobacco carcinogen exposures. The XPD protein is an important component of the TFIIH transcription factor complex. XPD genetic polymorphisms resulting in amino acids substitutions may lead to alterations in TFIIH helicase activity, resulting in repair and transcription defects. Cyclin D1 is a key regulatory protein for the transition of cells from the G(1)-S cell cycle phase. The CCND1 G870A polymorphism has been reported to enhance alternate splicing of a stable mRNA variant, which may result in the bypass of the G(1)/S cell cycle checkpoint. In this study, XPD G23591A (Asp312Asn) and A35931C (Lys751Gln) polymorphisms and the CCND1 G870A splice variant frequencies were determined in 273 upper aero-digestive tract cancer cases and 269 controls. The XPD Asp312Asn variant frequency was significantly different among cases and controls and conferred an odds ratio (OR) of 1.3 (95% CI 1.0-1.8). However, individuals with the CCND1 G870A and XPD Lys751Gln variants had higher age adjusted ORs of 3.2 (95% CI 2.2-4.6) and 2.2 (95% CI 1.5-3.2), respectively. Furthermore, a significant gene-gene interaction was observed among cases with at least two variant alleles for both CCND1 and XPD genes [OR 7.09 (95% CI 4.03-12.5)]. Smokers with a combination of at least one variant allele of both CCND1 and XPD genes also had an elevated risk as compared to nonsmokers. This is the first study to suggest an associative interaction between XPD and CCND1 genetic polymorphisms, tobacco exposure, and cancer risk.

Alternative Splicing↗
PubMed2005

[Expression of SARS coronavirus nucleocapsid protein and construction of its DNA vaccine].

AIM: To express the nucleocapsid (N) protein of SARS coronavirus (SARS-CoV) in E. coli and construct its DNA vaccine. METHODS: The prokaryotic expression vector pQEN containing N gene was constructed and transformed into the E. coli. The recombinant N protein was then expressed and purified by Ni(2+)-NTA affinity resin. In addition, the N gene was cloned into the eukaryotic expression plasmid pSecTagB and the eukaryotic recombinant expression vector pSecN was obtained. The DNA vaccine pSecN was injected to immunize the BALB/c mice to produce the antiserum against N protein of SARS-CoV. Subsequently, the reactivity of the antiserum with recombinant N protein and SARS-CoV particles was assayed by ELISA. RESULTS: Recombinant N protein reacted strongly and specifically with the sera from immunized mice and SARS patients. Similarly, the sera of immunized mice could also react specifically with SARS-CoV particles. CONCLUSION: The recombinant N protein could be used as a good antigen to detect SARS. The DNA vaccine pSecN could also efficiently induce the production of IgG against N protein of SARS-CoV, which offered clues to the development of a potential DNA vaccine.

Coronavirus Nucleocapsid Proteins↗
PubMed2005

[Comparison of Galla Chinesis and sodium fluoride on growth and metabolism of bacteria in biofilm model].

OBJECTIVE: To compare the antibacterial effect between sodium fluoride and Galla Chinesis in bioflim model. To evaluate the feasibility of application of Gala Chinesis in the clinical practice of caries prevention. METHODS: Streptococcus mutans, Streptococcus sanguis, Streptococcus salivarius and Actinomyces naeslundii had been chosen as the experimental bacteria. In the experiment, biofilmn model was constructed, and two agents were added in the media. After a period of continuous culture, the number of bacteria adhering on the HA disc was examed, the planktonic pH in the flow cell was recorded continuously, and the morphology of the biofilmn formed on the HA disc was observed by SEM. RESULTS: (1) Galla Chinesis could inhibit the growth of the four oral bacteria in the biofilm just as sodium fluoride. (2) Galla Chinesis and sodium fluoride could prevent the descent of the planktonic pH in the flow cell, but Galla Chinesis was less efficient than sodium fluoride. (3) The biofilms formed after application of Galla Chinesis and fluoride, but the bacterial cells had less matrix than those applicated with sucrose. CONCLUSION: Galla Chinesis is one kind of effective cariostatic natural agents.

Actinomyces↗
PubMed2005

[Analysis on blood-pressure-decreasing effect of electric pulse stimulation of auricular acupoint Jiangyagou in the patient of hypertension].

OBJECTIVE: To investigate the blood-pressure-decreasing action of stimulating auricular acupoint Jiangyagou in the patient of hypertension. METHODS: One hundred and twenty-nine cases of stage I - III hypertension were treated by electric pulse stimulation of auricular acupoint Jiangyagou with a MEDI/calma Nerve and Muscle Stimulator, 20-30 min each time, once daily. After treatment of 3 courses (21 days), changes of blood pressure were observed. RESULTS: Of the 129 cases, 44 cases were markedly effective, 73 cases were effective and 12 cases were ineffective, the total effective rate being 90.70%. The systolic pressure was decreased by (18.64 +/- 1.48)mmHg and the diastolic pressure by (8.01 +/- 0.68)mmHg on average, with very significant differences before and after treatment in both the systolic pressure and the diastolic pressure. CONCLUSION: Electric pulse stimulation of Jiangyagou can effectively decrease both the systolic pressure and diastolic pressure in the patient of hypertension.

Acupuncture Points↗
PubMed2005

[Are there imported components for channels and collaterals?].

The medical papyri in ancient Egypt written before 1500 B. C, recorded the metu system which could not be explained by modern anatomic location and was difficultly expounded by biological functions. Most of diseases were treated by dredging the metu, regulating the metu, balancing the metu, removing noxious substances from the metu, restoring the normal functions of the metu. The ancient Egyptian held that the metu forms mutual connecting channel network to carry out flowing of energy and information, with the functions of linking up external and internal organs, which is similar to linking functions of meridians-zang- and fu- organs. In the works of Hippocrates, the father of ancient Greece medicine, 2nd century B. C, also described the linking channels "phleps" on human surface. And in other country with an ancient civilization, India, had a similar channel system. About 15th century B. C, Charaka Samitha of ancient India described human "nadis" channel system. The system carried "rasas" (life liquid) connected with the whole body from the navel. Therefore, it can be held that at the embryonic stage of medicine development, the linking tube similar to channel or vessel was described, but it is interested that met and Chinese "mai" (vessel) have similar pronunciation. And mai in China was created after met.

China↗
PubMed2005

[Acupuncture inhibiting responses of spinal dorsal dorsal horn neurons induced by noxious dilation rectum and colon].

OBJECTIVE: To study on mechanisms of acupuncture in relieving visceral pain. METHODS: In SD rats CRD was used as noxious visceral stimuli. Activities of spinal dorsal horn wide dynamic (WDR) neurons of L1-L13 were recorded by extracellular microelectrode technique. Acupuncture was given at ipsi-lateral and contra-lateral Zusanli (ST 36) of the same segmental innervation of rectum and colon. RESULTS: Visceral noxious afferent could significantly activate spinal dorsal horn convergent neurons, and mechanical stimulation of contra-lateral body surface and hand acupuncture at Zusanli (ST 36) could inhibit this noxious response. When the spinal cord was acutely blocked, the inhibiting CRD effect of needling CRD effect of needling contra-lateral Zusanli (ST 36) completely disappeared. CONCLUSION: Acupuncture and visceral noxious afferent signals converge and interact each other in spinal level, and acupuncture at acupoint can inhibit the spinal dorsal horn neuron respon se activated by visceral noxious afferent and this action needs the participation of the center above the spinal cord.

Animals↗
PubMed2005

[Study of antibacterial effect of Galla Chinensis on the bacteria biofilm in chemostat].

OBJECTIVE: To compare the antibacterial effect of Galla Chinensis with that of chlorhexidine by means of chemostat and provide experimental foundation for caries prevention with Chinese medicine instead of chemicals in future. METHOD: A multispecies consortium biofilm (BF) model was construted in the chemostat. The growth-inhibition on bacterial biofilm coated on HA was investigated by means of the colony-forming units (CFU). Acid-inhibition was inspected by continual pH-recording in the flow cells. And the profile on the biofilm treated by both experimental medicines was observed with the scanning electromicroscopy (SEM). RESULT: Both of the experimental medicines could inhibit the growth of the BF bacteria. And Galla Chinensis had no obvious influence on the ecological composing of the BF bacteria. Both of the experimental medicines could inhibit the acid producion of experimental bacteria. But the final pH of Galla Chinensis was lower than that of chlorhexidine. A typical biofilm formed on HA was observed by SEM. Both of Galla chinensis and chlorhexidine could inhibit the production of extracellular matrix and make the BF profile on the surface of the HA clearer and simpler. CONCLUSION: Galla Chinensis had definite antibacterial effect. No obvious difference is found between Galla Chinensis (4 g x L(-1)) and chlorhexidine (0.5 g x L(-1)). Therefore, it is possible for Chinese medicine to gradually replace the chemical medicine in clinic and it will give a new choice for caries prevention.

Actinomyces↗
PubMed2004

Metabolic activation of fluoropyrrolidine dipeptidyl peptidase-IV inhibitors by rat liver microsomes.

The current study evaluated the potential for two dipeptidyl peptidase-IV (DPP-IV) inhibitor analogs (1S)-1-(trans-4-([(4-trifluoromethoxyphenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride and (1S)-1-(trans-4-([(2,4-difluorophenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride (MRL-A and MRL-B), containing a fluoropyrrolidine moiety in the structure, to undergo metabolic activation. The irreversible binding of these tritium-labeled compounds to rat liver microsomal protein was time- and NADPH-dependent and was attenuated by the addition of reduced glutathione (GSH) or N-acetylcysteine (NAC) to the incubation, indicating that chemically reactive intermediates were formed and trapped by these nucleophiles. Mass spectrometric analyses and further trapping experiments with semicarbazide indicated that the fluoropyrrolidine ring had undergone sequential oxidation and defluorination events resulting in the formation of GSH or NAC conjugates of the pyrrolidine moiety. The bioactivation of MRL-A was catalyzed primarily by rat recombinant CYP3A1 and CYP3A2. Pretreatment of rats with prototypic CYP3A1 and 3A2 inducers (pregnenolone-16alpha-carbonitrile and dexamethasone) enhanced the extent of bioactivation which, in turn, led to a higher degree of in vitro irreversible binding to microsomal proteins (5- and 9-fold increase, respectively). Herein, we describe studies that demonstrate that the fluoropyrrolidine ring is prone to metabolic activation and that GSH or NAC can trap the reactive intermediates to form adducts that provide insight into the mechanisms of bioactivation.

Animals↗
PubMed2004

Activation and induction of cyclic AMP phosphodiesterase (PDE4) in rat pulmonary microvascular endothelial cells.

Regulation of the rolipram-sensitive cAMP-specific phosphodiesterase 4 (PDE4) gene family was studied in rat pulmonary microvascular endothelial cells (RPMVECs). Total PDE4 hydrolysis was increased within 10 min after addition of forskolin (10 microM), reached a maximum at 20-40 min, and then gradually declined in the cells. A similar activation of PDE4 activity was observed using a protein kinase A (PKA) activator, N(6)-monobutyryl cAMP. Both the forskolin and the N(6)-monobutyryl cAMP activated PDE4 activities were blocked by the PKA-specific inhibitor, H89. This forskolin-stimulated and PKA-mediated short-term activation of PDE4 activity was further confirmed by in vitro phosphorylation of 87kDa PDE4A6 and 83kDa PDE4B3 polypeptides using exogenous PKA Calpha. Increased immunoreactivity of phosphorylated PDE4A6 in situ was detected in Western blots by a PDE4A-phospho antibody specific to the putative PKA phosphorylation sites. Following long-term treatment of RPMVECs with rolipram and forskolin medium (RFM) for more than 60 days, PDE4 activity reached ten-fold higher values than control RPMVECS with twenty-fold increases detected in intracellular cAMP content. The RFM cells showed increased immunoreactivities of the constitutive 4A6 and 4B3 isoforms plus two novel splice variants at 101kDa (4B1) and 71kDa (4B2). Treatment with H89 did not inhibit the PDE4 elevation in RFM cells. In addition to the increased levels of PDE4 in RFM cells, immunofluorescence showed a translocation of PDE4A and 4B to a nuclear region, which was normally not observed in RPMVECs. The PDE4 activity in RFM cells decayed rapidly with an even faster decline of intracellular cAMP content when forskolin/rolipram were removed from the medium. These results suggest that both the activation (short-term) and induction (long-term) of PDE4A/4B isoforms in RPMVECs are closely modulated by the intracellular cAMP content via both post-translational and synthetic mechanisms.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2004

A C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic and heterotopic acupoints in rats selectively destructive effects on myelinated and unmyelinated afferent fibers.

The aims of this study were to explore the C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic or heterotopic acupoints, and to determine the influence selectively destroyed myelinated and unmyelinated afferent fibers on the C-fiber reflex inhibition. In the ipsilateral local acupoint, the general behavior of the C-fiber reflex can be depressed by electroacupuncture below the threshold of Adelta-fiber activation. Electroacupuncture stimulation within the intensity of Adelta-fiber activation applied to the ipsilateral limb pretreated with cobra venom did not elicit inhibition of C-fiber reflex in rats with demyelinated sciatic nerve. However, heterotopic electroacupuncture below the threshold of Adelta-fiber activation was totally ineffective. In contralateral heterotopic acupoints, the C-fiber reflex can be depressed only by electroacupuncture with stimulating intensities exceeding thresholds of Adelta and C-fiber activation. Electroacupuncture stimuli applied to capsaicin-pretreated limb in the intensities of threshold of Adelta-fiber and treble thresholds of C-fiber activation produced only a little inhibition of C-fiber reflex. Inhibitory intensity was roughly similar to that induced by the stimulation with intensity for the activation of Adelta-fiber in normal animal. In the spinalized animals transections at T6-T7 segments, regardless of intensities, the homotopic electroacupuncture stimulation only induced moderate depression of C-fiber reflex similar to that of Adelta-fiber activation; whereas, no matter what intensities of application, the inhibitory effects of C-fiber reflex disappeared totally by using heterotopic noxious electroacupuncture in these animals.

Acupuncture Points↗
PubMed2004

St John's wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole.

OBJECTIVE: St John's wort, an extract of the medicinal plant Hypericum perforatum, is widely used as an herbal antidepressant. Although the ability of St John's wort to induce cytochrome P450 (CYP) 3A4-mediated reaction has been well established, the effect on CYP2C19 is still not determined. Thus the objective of this study was to determine the impact of St John's wort on the pharmacokinetic profiles of omeprazole and its metabolites. METHODS: Twelve healthy adult men (6 CYP2C19*1/CYP2C19*1, 4 CYP2C19*2/CYP2C19*2 and 2 CYP2C19*2/CYP2C19*3) were enrolled in a 2-phase randomized crossover design. In each phase the volunteers received placebo or a 300-mg St John's wort tablet 3 times daily for 14 days. Then all subjects took a 20-mg omeprazole capsule orally. Blood samples were collected up to 12 hours after omeprazole administration. Omeprazole and its metabolites were quantified by use of HPLC with ultraviolet detection. RESULTS: Omeprazole and its metabolites all exhibit CYP2C19 genotype-dependent pharmacokinetic profiles. After a 14-day treatment with St John's wort, substantial decreases in plasma concentrations of omeprazole were observed. The peak plasma concentration (C(max)) significantly decreased by 37.5% +/- 13.3% (P =.001) in CYP2C19*2/CYP2C19*2 or *3 and by 49.6% +/- 20.7% (P =.017) in CYP2C19*1/CYP2C19*1; the area under the concentration-time curve extrapolated to infinity [AUC(0- infinity )] decreased by 37.9% +/- 21.3% (P =.014) and 43.9% +/- 23.7% (P =.011) in CYP2C19 mutant and wild genotypes, respectively. Moreover, the C(max) and AUC(0- infinity ) of omeprazole sulfone increased by 160.3% +/- 45.5% (P =.001) and by 136.6% +/- 84.6% (P =.014), 155.5% +/- 58.8% (P =.001), and 158.7% +/- 101.4% (P =.017) in mutant and wild genotypes, respectively. St John's wort increased the C(max) of 5-hydroxyomeprazole by 38.1% +/- 30.5% (P =.028) and the AUC(0- infinity ) by 37.2% +/- 26% (P =.005) in CYP2C19 wild-type subjects, whereas it did not produce any significant alterations to the corresponding pharmacokinetic parameters in subjects with variant genotypes. CONCLUSION: St John's wort induces both CYP3A4-catalyzed sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole and enormously decreases the plasma concentrations of omeprazole. Clinically relevant interactions with other drugs may occur and must be taken into account when St John's wort is being taken.

Adolescent↗
PubMed2004

Lanthanide ions promote the hydrolysis of 2,3-bisphosphoglycerate.

The 31P NMR studies showed that lanthanide ions promote the site-specific hydrolysis of 2,3-Bisphosphoglycerate (BPG) at pH 7.4 by cleaving the 2' phosphomonoester bond. The effect of fourteen trivalent lanthanide ions and Sc3+, and Y3+ were compared by the percentage of hydrolysis obtained by determining the inorganic phosphate produced. All the trivalent lanthanide ions promote the hydrolysis, but Sc3+ not. Among them, Ce3+ affects the reaction mostly. This was mainly attributed to the autooxidation of Ce3+ to Ce4+, since the promoting effect of Ce3+ is related to the increasing Ce4+ amount in the solution and depressed by adding sulphite. Ce4+ promotes the hydrolysis more efficiently than Ce3+ do. The pseudo first-order rate constant for the hydrolysis of BPG by Ce(SO4)2 (18.7 mM) at pH 1 and pH 2, 37 degrees C is 3.1 h(-1) and 0.65 h(-1) respectively. A mechanism with a hydroxo species as reactive intermediate was proposed for the trivalent lanthanide ions. The site-specificity was explainable by this mechanism.

2,3-Diphosphoglycerate↗
PubMed2004

The influence of St John's Wort on CYP2C19 activity with respect to genotype.

Induction of cytochrome p450 isozymes is the major cause for clinical drug interactions of St. John's wort. The relationships of St. John's wort to cytochrome p450 isoforms have been fully investigated, but its effect on CYP2C19 is lacking. Thus, the aim of the present study was to observe the effect of St. John's wort on CYP2C19 activity using CYP1A2 as a control. Twelve healthy adult men-6 extensive metabolizers of CYP2C19 (2C19(*)1/2C19(*)1) and 6 poor metabolizers (4 2C19(*)2/2C19(*)2 and 2 2C19(*)2/2C19(*)3)-were enrolled in a two-phase, randomized, crossover manner. All subjects took a 300-mg St. John's wort tablet or placebo three times daily for 14 days, and then the activities of CYP2C19 and CYP1A2 were measured using mephenytoin and caffeine. It was found that St. John's wort treatment significantly increased CYP2C19 activity in CYP2C19 wild-genotype subjects, with urinary 4'-hydroxymephenytoin excretion raised by 151.5% +/- 91.9% (p = 0.0156), whereas no significant alteration was observed for CYP2C19 poor metabolizers. Repeated St. John's wort administration did not affect the CYP1A2 phenotypic ratio for both CYP2C19 genotype subjects. In conclusion, St. John's wort is an inducer to the human CYP2C19, and clinicians should pay great attention when St. John's wort is added to or withdrawn from an existing drug regimen containing substrates for such enzymes.

Adult↗
PubMed2004

Effect of nano-hydroxyapatite/collagen composite and bone morphogenetic protein-2 on lumbar intertransverse fusion in rabbits.

OBJECTIVE: To investigate the effect of nano-hydroxyapatite/collagen (nHA/collagen) composite as a graft extender and enhancer when combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) on lumbar intertransverse fusion in rabbits. METHODS: Sixty-four adult female New Zealand white rabbits, aged 1 year and weighing 3.5-4.5 kg, underwent similar posterolateral intertransverse process arthrodesis and were randomly divided into 4 groups based on different grafts: autogenous cancellous bone alone (ACB group), nHA/collagen alone (HAC group), half autogenous cancellous bone and half nHA/collagen (ACB+HAC group) and nHA/collagen combined with rhBMP-2 (HAC+BMP group). The fusion masses were analyzed by manual palpation, radiography, biomechanical testing and histological examination. RESULTS: Fusion was observed in 4 cases in the 6th week and in 5 cases in the 10th week after surgery in ACB group. No case showed fusion in HAC group. In ACB+HAC group, there was fusion in 3 cases in the 6th week and in 4 cases in the 10th week after surgery. In HAC+BMP group, fusion in 1 case was found in the 4th week, in 5 cases in the 6th week and in 6 cases in the 10th week after surgery. It suggested that ACB, ACB+HAC and HAC+BMP groups showed similar fusion ratio and mechanical strength in the 6th and 10th week after surgery. According to the microstructure analysis of the samples, nHA/collagen had no negative effect when implanted together with ilium autograft. In HAC+BMP group, new bone-like tissue was observed in the 2nd week postoperatively, and nearly all of the implanted composites were replaced by mature bone matrix and new bones in 10th week postoperatively. CONCLUSIONS: The nHA/collagen, especially combined with rhBMP-2, is a promising bone substitute, for it has quick biodegradation, fine bone-bending ability, and high osteoconductivity on posterolateral spinal fusion in rabbits.

Analysis of Variance↗