Biomedical subjects

Bing Zhu

Publications and source records attributed to Bing Zhu.

At least 55 records · Page 3Linked to original sources

PubMed2004

[Connotation of channel and its relation with nerve].

Originated for the recognition on the anatomy and physiology of "vessel", the theory of channel treats the running pathway of the vessel as jing mai (channel vessel), with its transverse branches as mai (vessel), thus the idea of jing luo and jing mai was gradually formed and the connotation of "channel (jing luo)" is with the etymological connotation of function of the nerve. The challenge to channel theory comes from the introduction of western medicine, or in other words, people interpret the communication among the body surface and the upper and lower parts of the surface, the special connection between the body surface and the internal organs, the adjusting and reaction function. During the introduction of western anatomy-physiology in the late Ming dynasty or the eastward introduction of western medical science at the late Qing dynasty, the terms of traditional Chinese medicine (TCM) connected with channel functions, including "minute tendon (xi jin)", "connection (xi)" had been rendered as the Chinese translation of "nerve". Thus, the language transforming basis between channel and nerve function was laid down at the first stage of confluence between TCM and western medicine.

China↗

PubMed2003

Relationship between CYP3A activity and breast cancer susceptibility in Chinese Han women.

BACKGROUND: Breast cancer is the most frequent type of tumor in women. The main cause of breast cancer remains unknown. Extensive studies have shown that endogenous steroid hormones, especially estrogens, are important in the development and the progression of breast cancer, and the carcinogenesis of estrogens is related to their major oxidative metabolites, 16alpha-hydroxyestrogens and 4-hydroxyestrogens. CYP3A plays a major role in the 4- and 16alpha-hydroxylation of estrogens. Furthermore, CYP3A is present in human mammary epithelial cells and expressed higher and more frequently in malignant breast cells than in the adjacent normal breast tissue. Hence, it will be significant to perform more work to determine the association between CYP3A activity and breast cancer susceptibility. AIMS: To evaluate the relationship of CYP3A activity to breast cancer susceptibility in Chinese Han women using the plasma 1-hydroxymidazolam (1-OHMDZ) to midazolam (MDZ) ratio as the marker of CYP3A activity. METHODS: One hundred and twenty-nine Chinese Han female breast tumor patients and 121 healthy unrelated female volunteers were enrolled in the current study. After an overnight fast, each subject was administered a single oral dose (7.5 mg) of midazolam. Blood samples (5 ml) were drawn at 1 h after the drug administration. The concentration of parent MDZ and its major metabolite 1-OH-MDZ was measured in all the plasma samples using high-performance liquid chromatography. RESULTS: Complete chromatographic data on plasma ratios of 1-OHMDZ to MDZ for 103 cases of breast cancer and 114 controls were available. The plasma concentration ratios of 1-OHMDZ to MDZ were 0.4520+/-0.2318 and 0.3298+/-0.1610 for the malignant cases and the controls, respectively. A higher CYP3A activity was found in the breast cancer cases than in the controls ( P<0.001), and the CYP3A activity of patients with lymph-node metastasis was higher than that of patients without lymph-node metastasis ( P=0.028). CYP3A activity in estrogen receptor or progesterone receptor positive cases was the same as in estrogen receptor or progesterone receptor negative cases ( P=0.124, 0.175). CONCLUSIONS: Our results indicate that high CYP3A activity may contribute to breast cancer disease genesis and may promote breast cancer to lymph-node metastasis.

Aryl Hydrocarbon Hydroxylases↗

PubMed2003

Application of LC-NMR for the study of the volatile metabolite of MK-0869, a substance P receptor antagonist.

LC-NMR was applied to identify the polar volatile metabolite of MK-0869. MK-0869, a morpholine-based compound containing a triazolone ring, is a very potent NK(1) receptor antagonist. Currently, it is in development as an anti-emesis agent in chemotherapy treatments. The primary metabolites of MK-0869, M1 and M2, are non-polar and lack the triazolone ring. Incubation of [14C]M1 with liver microsomes from male rats produced a very polar and volatile metabolite, M3. Analysis was not possible by LC-MS or by conventional NMR because of poor ionization, small molecular weight and volatility, leaving chemical derivatization and LC-NMR as alternative methods. Reduction of M3 with NaBH(4) resulted in a derivative that had the same retention time as p-fluorophenylethylene glycol on HPLC. A small aliquot of the solution containing M3 was passed through the LC of the LC-NMR system, which was connected on-line with a radioactivity detector. The simultaneous UV and radioactivity chromatograms thus identified the chromatographic UV peak that was associated with the metabolite. Analysis was carried out by stop-flow on another portion of this fraction. From the chemical derivatization and the analysis by LC-NMR, M3 is shown to be p-fluoro-alpha-hydroxyacetophenone. Further studies using LC-NMR showed that M3 could be generated from both M1 and M2 in NADPH-dependant reactions catalyzed by microsomes containing recombinant human CYP2C19, CYP1A2 or CYP3A4.

Animals↗

PubMed2003

Dendritic and synaptic pathology in experimental autoimmune encephalomyelitis.

Evidence has shown that excitotoxicity may contribute to the loss of central nervous system axons and oligodendrocytes in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Because dendrites and synapses are vulnerable to excitotoxicity, we examined these structures in acute and chronic models of EAE. Immunostaining for microtubule-associated protein-2 showed that extensive dendritic beading occurred in the white matter of the lumbosacral spinal cord (LSSC) during acute EAE episodes and EAE relapses. Retrograde labeling confirmed that most motoneuron dendrites were beaded in the white matter of the LSSC in acute EAE. In contrast, only mild swelling was observed in the gray matter of the LSSC. Dendritic beading showed marked recovery during EAE remission and after EAE recovery. In addition, synaptophysin, synapsin I, and PSD-95 immunoreactivities were significantly reduced in both the gray and white matter of the LSSC during acute EAE episodes and EAE relapses, but showed partial recovery during EAE remission and after EAE recovery. Pathologically, both dendritic beading and the reduction in synaptic protein immunoreactivity were well correlated with inflammatory cell infiltration in the LSSC at different EAE stages. We propose that dendritic and synaptic damage in the spinal cord may contribute to the neurological deficits in EAE.

Acute Disease↗

PubMed2003

Genotype-phenotype correlation for histamine N-methyltransferase in a Chinese Han population.

BACKGROUND: Two potential single-nucleotide polymorphisms (SNP) (C314T and A595G) exist in the gene for human histamine N-methyltransferase (HNMT). METHODS: A radiochemical microassay was used to measure the erythrocyte HNMT activities, whereas the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed to perform the genetic analysis in 247 unrelated Chinese Han subjects. RESULTS: All subjects had detectable HNMT activity. The activity of HNMT was gender related (males>females, p<0.0001), with a 5.5-fold individual variation. The distribution of HNMT activity was compatible with a normal distribution. There were 28 heterozygotes for the variant T314 allele among the 247 subjects, whereas no A595G transition was observed. All heterozygotes for the T314 allele displayed an intermediate or low HNMT activity, with an average HNMT activity being 34.0% lower than those with wild-type genotype (623.1+/-136.0 vs. 944.8+/-249.3 U/ml red blood cells [RBC], p<0.0001). CONCLUSION: The C314T polymorphism was functionally important and contributes in part to phenotypic variance of HNMT activity in Chinese Han population. Additional unknown genetic or epigenetic factors should also play important roles in the regulation of HNMT activity.

Adolescent↗

PubMed2003

Bilirubin as a potent antioxidant suppresses experimental autoimmune encephalomyelitis: implications for the role of oxidative stress in the development of multiple sclerosis.

Increasing evidence shows that oxidative stress plays an important role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). In recent years, bilirubin has been demonstrated to be a potent antioxidant in vitro. In this study, we administered bilirubin to rats with acute and chronic EAE. Bilirubin prevented both acute and chronic EAE effectively. More significantly, bilirubin suppressed ongoing clinical EAE and halted EAE progression when given after disease onset. Subsequent histological examination showed that if administered to rats before the onset of EAE, bilirubin interfered with the invasion of inflammatory cells into the central nervous system (CNS) because it protected the blood-brain barrier (BBB) from free radical-induced permeability changes. However, in some cases, inflammation still occurred even when no clinical illness was observed. In rats with treatment initiated after the onset of EAE, despite the clinical improvements, treatment with bilirubin did not reduce the degree of CNS inflammation, or change cytokine expression in CNS lesions, indicating a lack of immunosuppressive effect of this treatment. By contrast, bilirubin treatment significantly alleviated oxidative damage in the spinal cord, and the clinical signs of EAE correlated well with the degree of oxidative injury in the lesions. Our results suggest that free radicals play an important role in the final effector stages of EAE, and that antioxidant therapies may have potential for the treatment of MS.

Animals↗

PubMed2003

The distribution and gender difference of CYP3A activity in Chinese subjects.

AIMS: To investigate the distribution of CYP3A activity in the Chinese population, and to test for gender-related differences in CYP3A activity. METHODS: Using midazolam as a probe drug, CYP3A activity in 202 Chinese healthy subjects (104 men) was measured by plasma 1'-hydroxymidazolam:midazolam (1'-OH-MDZ:MDZ) ratio at 1 h after oral administration of 7.5 mg midazolam. The different phases of the menstrual cycle including preovulatory, ovulatory and luteal phases of 66 women phenotyped with midazolam were recorded. The concentrations of 1'-OH-MDZ and MDZ in plasma were measured by HPLC RESULTS: A 13-fold variation of CYP3A activity (log1'-OH-MDZ:MDZ: range -0.949-0.203) was shown. The CYP3A activity was normally distributed as indicated by the frequency distribution histogram, the probit plot and the Kolmogorov-Smirnov test (P > 0.05). The CYP3A activity of women was higher than that of men (median: -0.36 vs -0.43, P < 0.05; 95% CI for difference: -0.127, -0.012). There was a significant difference in CYP3A activity between the three phases of the menstrual cycle. The activity was highest in the preovulatory phase and decreased sequentially in the ovulatory and luteal phases (P < 0.05). CONCLUSIONS: A normal distribution of CYP3A activity was observed in the Chinese population. The CYP3A activity is higher in female subjects than in males. CYP3A activity differed across the phases of the menstrual cycle.

Administration, Oral↗

PubMed2003

Inhibitory effect of troleandomycin on the metabolism of omeprazole is CYP2C19 genotype-dependent.

1. Eighteen healthy CYP2C19 genotyped male subjects were administered a 20-mg oral dose of omeprazole (OP) alone or received troleandomycin (TAO) 500 mg daily for 2 days before the dose of OP was administered. Blood samples were obtained and OP 5-hydroxyomeprazole (5-OH-OP) and OP sulfone in plasma were determined by reversed-phase HPLC. 2. The mean C(max), AUC and CL for OP in poor metabolizers (PMs) were greater with TAO than without TAO. The C(max) and AUC of 5-OH-OP in PMs were significantly (p < 0.05) less with TAO than without TAO. The differences in 5-OH-OP between heterozygous extensive metabolizers (EMs) with TAO versus without TAO were similar to those observed in PMs, except for the AUC. However, in homozygous EMs, there were no statistical differences for the effect of TAO. 3. The effect of TAO on the metabolism of OP and its two principal metabolites differs in different genotype groups of CYP2C19. CYP3A4 not only plays a dominant role in the formation of OP sulfone, but also it contributes to the 5-hydroxylation of OP. Both CYP2C19 and CYP3A contribute to the further elimination of 5-OH-OP and OP sulfone.

Adult↗

PubMed2003

The pain-relieving effects induced by electroacupuncture with different intensities at homotopic and heterotopic acupoints in humans.

The purpose of the present study was to investigate the relationship between the distribution of the analgesic area when different intensities of stimulation were applied to homotopic and heterotopic acupoints. The experiments were performed on volunteers; the left sural nerve was stimulated by a volley of eight rectangular pulses delivered at a frequency of 400 Hz. Electromyographic reflex responses (EMGs) were recorded from the ipsi-lateral biceps femoris muscle. Electroacupuncture stimuli were given on the skin overlying the Zusanli point (St 36), and the strengths chosen were times of the threshold eliciting a nociceptive reflex (T(RIII)) response (0.6, 0.8, 1.0, T(RIII) and T(supra-RIII), respectively). The effects of homotopic and heterotopic stimuli applied to St 36 on the pain sensation and the R(III), reflex elicited by stimulation of the left sural nerve were observed to explore the pain-relief and R(III) reflex-inhibition produced by stimulation of the St 36 point with different intensities. Both the nociceptive reflex and painful sensation evoked by stimulating the sural nerve were similarly inhibited by electroacupuncture at less than T(RIII) applied to the ipsi-lateral acupoint. In other words, acupuncture with an innocuous intensity can produce homotopic pain-alleviating effects and reflex suppression. With contra-lateral electroacupuncture at the St 36 acupoint, innocuous intensities cannot produce heterotopic pain-relieving effects; these inhibitions were only observed at electroacupuncture intensities similar to the T(RIII) threshold. These results suggest that local acupuncture-induced analgesia is effective with activation of large afferent fibers, whereas heterotopic acupuncture-induced analgesia is only effective with intensities strong enough to excite small afferent fibers. Local analgesic effects of acupoint stimulation involve segmental inhibition, whereas systemic analgesic effects of acupoint stimulation are involved in contra-lateral effects. The latter may recruit the diffuse noxious inhibitory controls (DNIC) system. The specific function of an acupoint is determined by the anatomical relationship between the disease focus and the segmental location of the acupoint.

Acupuncture Points↗

PubMed2003

Regulatory functions of CD8+CD28- T cells in an autoimmune disease model.

CD8+ T cell depletion renders CD28-deficient mice susceptible to experimental autoimmune encephalomyelitis (EAE). In addition, CD8-/-CD28-/- double-knockout mice are susceptible to EAE. These findings suggest a role for CD8+ T cells in the resistance of CD28-deficient mice to disease. Adoptive transfer of CD8+CD28- T cells into CD8-/- mice results in significant suppression of disease, while CD8+CD28+ T cells demonstrate no similar effect on the clinical course of EAE in the same recipients. In vitro, CD8+CD28- but not CD8+CD28+ T cells suppress IFN-gamma production of myelin oligodendrocyte glycoprotein-specific CD4+ T cells. This suppression requires cell-to-cell contact and is dependent on the presence of APCs. APCs cocultured with CD8+CD28- T cells become less efficient in inducing a T cell-dependent immune response. Such interaction prevents upregulation of costimulatory molecules by APCs, hence decreasing the delivery of these signals to CD4+ T cells. These are the first data establishing that regulatory CD8+CD28- T cells occur in normal mice and play a critical role in disease resistance in CD28-/- animals.

Amino Acid Sequence↗

PubMed2003

[Genotype of human calicivirus from infants with diarrhea in Guangzhou city in 2001].

OBJECTIVE: To understand the characteristics of human calicivirus (HuCV) infection in infants with diarrhea in Guangzhou city and to study genotype of the virus. METHODS: The authors collected fecal specimens from 22 children with acute nonbacterial gastroenteritis from November to December, 2001. HuCV was detected from the specimens by RT-PCR. The PCR products were cloned into the PMD18-T cloning vector and sequenced. RESULTS: HCV was detected from the specimens of 2 cases (9%, 2/22). The nucleotide sequence analysis revealed that the virus strains belonged to genotype 2 of Norwalk-like viruses. CONCLUSION: HuCV is one of the pathogens causing diarrhea in infants and young children in Guangzhou area. HuCV infection occurred sporadically in autumn and winter.

Base Sequence↗

PubMed2003

[The effects of traditional Chinese medicines on the adherence of Streptococcus mutans to salivary acquired pellicle in vitro].

OBJECTIVES: To investigate the effects of traditional Chinese medicines on the preliminary adherence of Streptococcus mutans to salivary acquired pellicles. METHODS: The hydroxyapatites beads were coated by saliva to form S-HA, an in vitro model of experimental pellicle. Streptococcus mutans was chosen as the experiment strain, and radiolabeled with 3H-thymidine. Two parts of adherence inhibit study were carried on with medicines pretreated S-HA and medicines pretreated bacteria. The numbers of 3H-thymidine labeled bacteria attached to S-HA were counted by scintillation counting to indicate the amount of adherence. RESULTS: It was found that most of the traditional Chinese medicines tested could inhibit the adherence to S-HA to different extent, especially the Galla Chinensis, which has significant inhibitory action. CONCLUSION: Galla Chinensis may be a prospective medicine to inhibit the cariogenic bacteria's preliminary adherence to salivary acquired pellicles.

Bacterial Adhesion↗

PubMed2002

Derivatization of ethinylestradiol with dansyl chloride to enhance electrospray ionization: application in trace analysis of ethinylestradiol in rhesus monkey plasma.

The extensive metabolism and administration of low doses of ethinylestradiol (EE) in preclinical animal species necessitates a sensitive analytical method to quantify the drug at low picogram-per-milliliter concentrations in biological matrixes. A highly sensitive and accurate method based on the derivatization of EE with dansyl chloride coupled with liquid chromatography/tandem mass spectrometry is described. The dansyl derivatization of EE introduced a basic secondary nitrogen into the molecule that was readily ionized in commonly used acidic HPLC mobile phases. The derivative showed an intense protonated molecular ion at m/z 530 under positive turbo ion spray ionization. The collision-induced dissociation of this ion formed a distinctive product at m/z 171, corresponding to the protonated 5-(dimethylamino)naphthalene moiety. The selected reaction monitoring, based on the m/z 530 --> 171 transition, was highly specific for EE, since no background signal was observed from blank plasma obtained from rhesus monkeys. The limit of detection, at a signal-to-noise ratio of 5, was 0.2 fg/mL EE spiked into blank plasma. This allowed for a lower limit of quantitation of 5 pg/mL using a 50-microL plasma sample and 10-microL injection of dansylated derivative into the CTC-PAL Leap autosampler coupled to a Sciex API 4000 mass spectrometer. Using fast-gradient liquid chromatography, the analyte peak eluted at 1.6 min. The validation results showed high accuracy (% bias < 4) and precision (% CV < 7.5) at broad linear dynamic ranges (0.005-20 ng/mL), using deuterated EE as internal standard. Therefore, the facile dansyl derivatization coupled with tandem mass spectral analysis allowed the development of a highly sensitive and specific method for quantitation of trace levels of EE in the plasma of rhesus monkeys dosed orally and intravenously with EE.

Animals↗

PubMed2002

Intrathecal Fas ligand infusion strengthens immunoprivilege of central nervous system and suppresses experimental autoimmune encephalomyelitis.

Fas ligand (FasL) is an essential molecule strongly expressed in some immunoprivileged sites, but is expressed at very low levels in normal CNS. In this study, acute experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats with guinea pig myelin basic protein. Intrathecal infusion of recombinant FasL before EAE onset dose dependently suppressed acute EAE and alleviated pathological inflammation in lumbosacral spinal cord. This treatment greatly increased apoptosis in CNS inflammatory cells, but did not inhibit systemic immune response to myelin basic protein. Systemic administration of a similar dose of rFasL was ineffective. In vitro, encephalitogenic T cells were highly sensitive to rFasL-induced cell death, and activated macrophages were also susceptible. In addition, in vitro rFasL treatment potentiated the immunosuppressive property of rat cerebrospinal fluid. We conclude that intrathecal infusion of rFasL eliminated the initial wave of infiltrating T cells and macrophages, and therefore blocked the later recruitment of inflammatory cells into CNS. Although Fas receptor expression was observed on spinal cord neurons, astrocytes, and oligodendrocytes, no damage to these cells or to the myelin structure was detected after rFasL infusion.

Animals↗

PubMed2002

Regulation of cyclic AMP in rat pulmonary microvascular endothelial cells by rolipram-sensitive cyclic AMP phosphodiesterase (PDE4).

We report here studies on the regulation of the metabolism of adenosine 3',5'-monophosphate (cAMP) in established and primary cultures of rat pulmonary microvascular endothelial cells (RPMVEC). Inhibition by rolipram, a selective inhibitor of cAMP phosphodiesterase (PDE) of the PDE4 gene family, was required to achieve maximal cAMP accumulation induced by direct or receptor-mediated adenylate cyclase activation when measured by [3H]-adenine prelabeling. Rolipram increased cAMP accumulation more effectively than did forskolin, isoproterenol, or adenosine derivatives alone, although extensive synergy was seen with combined agents. High-affinity PDE4 inhibitors, but not low-affinity or non-selective inhibitors, were effective inducers of cAMP accumulation in intact cells. The maximum effects (i.e. intrinsic activities) of these agents in the intact cell did not correlate with their in vitro PDE4 inhibitory affinities. RPMVEC were shown to express almost exclusively the PDE4 gene family isoforms A6 and B3. Guanosine 3',5'-monophosphate hydrolysis, observed in other types of endothelial cells was not found in early or late passage RPMVEC. Reverse transcription-polymerase chain reaction identification of mRNAse supported these conclusions with the exception that PDE2 and PDE4D mRNA isoform transcripts were present. These studies also support the conclusion that the mechanism of rolipram reversal of rat lung ischemia-reperfusion-induced permeability involves PDE4 inhibition in the microvascular endothelial cells of the lung.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2002

Phenotype distribution and gender-related differences of CYP2E1 activity in a Chinese population.

1. The aim was to investigate the phenotype distribution characteristic and gender-related differences of CYP2E1 activity in a healthy Chinese population. 2. Two hundred and three healthy Chinese subjects (105 men, 98 women) were enrolled in this study. 3. CYP2E1 activity was determined by plasma 6-hydroxychlorzoxazone-to-chlorzoxazone concentration ratio (CHZ-MR) 4h after chlorzoxazone dosing. The concentrations of 6-hydroxychlorzoxazone and chlorzoxazone in plasma were detected by reversed-phase HPLC. 4. The results showed an almost 9-fold variation of CYP2E1 activity at a range of from 0.23 to 1.99. The coefficient of variation CY % was demonstrated with skewness and kurtosis of the ratios in the studied population were 44%, 0.96 and 1.10, respectively. 5. CYP2E1 activity was normally distributed in logarithmic form of 6-OH-CHZ/CHZ as evaluated by Kolmogorov-Smirnov test of normality (p = 0.20). Probit plots of the CYP2E1 activity index of men shifted to the right as compared with that of women. The mean CHZ-MR in men was significantly higher than that in women (0.76 +/- 0.30 versus 0.60 +/- 0.28, p < 0.001), and this difference still existed when normalized by weight (0.73 +/- 0.28 versus 0.66 +/- 0.32, p = 0.016). Body weight correlated positively with CYP2E1 activity in the total group(r < 0.212, p < 0.01).

Adolescent↗

PubMed2002

O-Dealkylation of fluoxetine in relation to CYP2C19 gene dose and involvement of CYP3A4 in human liver microsomes.

This work evaluated the kinetic behavior of fluoxetine O-dealkylation in human liver microsomes from different CYP2C19 genotypes and identified the isoenzymes of cytochrome P450 involved in this metabolic pathway. The kinetics of the rho-trifluoromethylphenol (TFMP) formation from fluoxetine was determined in human liver microsomes from three homozygous (wt/wt) and three heterozygous (wt/m1) extensive metabolizers (EMs) and three poor metabolizers (PMs) with m1 mutation (m1/m1) with respect to CYP2C19. The formation rate of TFMP was determined by gas chromatograph with electron-capture detection. The kinetics of TFMP formation was best described by the two-enzyme and single-enzyme Michaelis-Menten equation for liver microsomes from CYP2C19 EMs and PMs, respectively. The mean intrinsic clearance (V(max)/K(m)) for the high- and low-affinity component was 25.2 microl/min/nmol and 3.8 microl/min/nmol of cytochrome P450 in the homozygous EMs microsomes and 12.8 microl/min/nmol and 2.9 microl/min/nmol of cytochrome P450 in the heterozygous EMs microsomes, respectively. Omeprazole (a CYP2C19 substrate) at a high concentration and triacetyloleandomycin (a selective inhibitor of CYP3A4) substantially inhibited O-dealkylation of fluoxetine. Furthermore, fluoxetine O-dealkylation was correlated significantly with S-mephenytoin 4'-hydroxylation at a low substrate concentration and midazolam 1'-hydroxylation at a high substrate concentration in liver microsomes of 11 Chinese individuals, respectively. Moreover, there were obvious differences in the O-dealkylation of fluoxetine in liver microsomes from different CYP2C19 genotypes and in microsomal fractions of different human-expressed lymphoblast P450s. The results demonstrated that polymorphic CYP2C19 and CYP3A4 enzymes were the major cytochrome P450 isoforms responsible for fluoxetine O-dealkylation, whereas CYP2C19 catalyzed the high-affinity O-dealkylation of fluoxetine, and its contribution to this metabolic reaction was gene dose-dependent.

Algorithms↗

PubMed2002

Genotype of CYP3AP1 associated with CYP3A activity in Chinese Han population.

AIM: To investigate the distribution of genotype of CYP3AP1 in Chinese Han population and the correlation with CYP3A activity. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed in CYP3AP1 genotype analysis; using midazolam as probe drug, CYP3A activity of 191 Chinese healthy subjects was measured by plasma 1'-hydroxymidazolam/midazolam (1'-OH-MDZ/MDZ) ratio at 1 h after oral administration of 7.5 mg midazolam. RESULTS: There was significant difference of CYP3A activity in different genotypes of CYP3AP1 in vivo (P <0.05). The activity of CYP3A in homozygous A(-44) (CYP3AP1*3/CYP3AP1*3) is lower than heterozygous A(-44)G (CYP3AP1*1/CYP3AP1*3), and the CYP3A activity in homozygous G(-44) (CYP3AP1*1/CYP3AP1*1) is t he highest. CONCLUSION: There was association between the genotype of CYP3AP1 and increased activity of CYP3A in vivo.

Adolescent↗