The association of polymorphisms of calcium channel?1 subunit ( Cav1.1 ) gene ( - 1551T/C at exon 11 ) with thyrotoxic periodic paralysis (TPP) was investigated by PCR-RFLP.The distributions and frequencies of - 1551TC + CC genotype and C allele in TPP group were significantly higher than those in hyperthyroidism (HT) and normal control (CON) groups.There was no statistic difference between HT and CON groups.Cavl.1 gene - 1551TC + CC genotype and allele may contribute to the development of TPP in male HAN population from North China.

The rat single-pass intestinal perfusion model was applied to study the effect of CYP3A and P-glycoprotein on the absorption of buagafuran in lumen of rats. Buagafuran concentrations in intestinal perfusate and blood in vena mesenterica collected at different time points after perfusion were determined by GC-MS. Permeability coefficient of buagafuran was calculated by the equation [P(lumen) = -(Q/2pirl)Ln(C(out)/C(in)) and P(blood) = (deltaM(B)/deltat)/(2pirl)]. The effects of troleandomycin (TAO, CYP3A inhibitor), cyclosporin A (CYP3A/p-glycoprotein inhibitor) on the absorption of buagafuran in lumen were observed. After rat single-pass intestinal perfusion, the cumulative amount of buagafuran in mesenteric vein of rat was 73.4, 82.9, and 98.3 pmol x cm(-2) and were increased 3.9, 4.6, and 5.6 fold by addition of inhibitor of P-gp (LSN335984), CYP3A (TAO) or P-gp and CYP3A (CsA), respectively. Moreover, the metabolized fraction of buagafuran was decreased by 12%, 11% and 21% with inhibitors. The results suggested that the poor bioavailability of buagafuran was mostly due to the interplay of P-gp and CYP3A on the absorption, transport and metabolism of buagafuran in intestine of rats.

A simple, rapid and sensitive method was developed for the quantification of tenofovir in plasma of Beagle dogs using HPLC-MS/MS analysis. The analytes tenofovir and internal standard (IS) adefovir were separated on a Zorbax SB-C18 column (3.5 microm, 100 mm x 2.1 mm, Agilent, USA) with mobile phase of methanol/water containing 0.3% formic acid using a gradient elution mode at a flow rate of 0.2 mL x min(-1). The plasma sample preparation was a simple deproteinization by the addition of 20% trichloroacetic acid followed by centrifugation. The detection was performed in positive selected reaction monitoring (SRM) mode with an electrospray ionization (ESI) source. The reactions monitored were m/z 288.1-176.2 for tenofovir and m/z 274.1-162.2 for adefovir (IS). Linear detection responses were obtained for tenofovir ranging from 10 to 5 000 ng x mL(-1). The intra- and inter-day precisions (RSD%) was no more than 6.3% with high recovery and good stability for the quantification, indicating the present method was specific, fast, accurate and reliable. The method was successfully applied to the pharmacokinetic study of two tenofovir agents. Tenofovir dipivoxil fumarate (BP0018, test agent) and tenofovir disoproxil fumarate (reference agent) were orally administrated to 8 Beagle dogs according to the 2 x 2 crossover design. Comparing with the reference agent, the longer MRT and t1/2 were obtained in the group of BP0018, while no significant difference was observed in AUC(0-t), AUC(0-infinity), C(max) and t(max) between them, suggesting that tenofovir dipivoxil fumarate was bioequivalent to the tenofovir disoproxil fumarate in Beagle dogs.

It is valuable to establish a chemical-pharmacokinetic (PK)-pharmacodynamics (PD) fingerprint of traditional Chinese medicine (TCM) for comprehensively understanding the TCM integrated conception and revealing the material foundation. The chemical, metabolic in vitro, and PK/PD in vivo fingerprints of Schisandra chinensis (SC) alcoholic extract were established and comparatively analyzed using HPLC-UV-MS method, rat liver microsomes in vitro and CCl4 intoxicated rats in vivo. Four known effective lignans, schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin, were detected as the standard references in SC alcoholic extract with high concentration. SC alcoholic extract and four lignans when incubated with rat liver microsomes produced several metabolites in NAPDH-dependent manner. Chemical fingerprint of some components with bioactivities were also identified in PK and PD fingerprints in normal and ALI rats that explained the material foundation of SC alcoholic extract for multiple pharmacological effects. Schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin could be considered as the "PK marker" of SC alcoholic extract or its relevant preparations, while two metabolites of the four lignans, 7, 8-dihydroxy-schizandrin and another one (M(W) 432), could be recognized as drug-metabolism (DM) Marker. This work provides experimental data for the further studies of metabolism or material foundation of SC components.

Effects of constituents from Schisandra chinensis (Wuweizi) on six liver microsomal CYP450 isozymes (CYP1A2, CYP2C6, CYP2C11, CYP2D2, CYP2E1 and CYP3A1/2) were studied in rats in vivo and in vitro. The in vitro incubation was conducted using liver microsomes of rats after multiple dosing of alcoholic/water extract from Schisandra chinensis. A HPLC-MS method was applied to determine the metabolites formation of six CYP450s probe substrates (phenacetin-CYP1A2, dextromethorphan-CYP2D2, diclofenac sodium-CYP2C6, mephenytoin-CYP2C11, chlorzoxazone-CYP2E1 and midazolam-CYP3A1/2) in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. Alcoholic extract of Schisandra chinensis (28-120 microg x mL(-1)) showed significant inhibitory effect on six CYP450 isozymes to a certain extent in vitro. Multiple dosing of Schisandra chinensis alcoholic extract (1.5 g x kg(-1), qd x 7d) had significant induction on CYP2E1 and CYP3A1/2, inhibition on CYP2D2 and CYP2C11, and no effect on CYP2C6 and CYP1A2. Water extract of Schisandra chinensis (100-500 microg x mL(-1)) also exhibited inhibition on the activity of CYP450 isozymes in vitro, whereas multiple administrations (1.5 g x kg(-1), qd x 7d) had significant induction of CYP2E1 and inhibition on CYP2D2, no effect on CYP2C6, CYP3A1/2, CYP1A2 or CYP2C11. The results suggested that the constituents from Schisandra chinensis exhibited the inhibition and induction on six rat liver microsomal CYP450 isozymes to a certain extent in vivo and in vitro. The possibility of interaction between Schisandra chinensis and coadministrative drugs will be considered base on the levels and subtype of CYP450 involved in the drug metabolism.

AIM: To study the quality standard of Compound Shencha Granuls (Radix et Rhizoma Glycyrrhizae, Radix Rehmanniae, etc.). METHODS: Radix et Rhizoma Glycyrrhizae and Rhizoma et Radix Polygoni Cuspidati in Compound Shencha Granule were distinguished by TLC. Ursolic acid was determinated by TLCS. RESULTS: The methods of TLC to distinguish Radix et Rhizoma Glycyrrhizae and Rhizoma Polygoni Cuspidati were feasible without negative inference. Ursolic acid content in three groups of samples was 1.24 - 1.58 mg?g -1 . CONCLUSION: The method is accurate and reproducible. It can be used for the quality control of Compound Shencha Granule.

Objective To investigate the clinical features, brain imaging significance and the possible pathogenesis of posterior reversible encephalopathy syndrome (PRES) in childhood acute lymphoblastic leukemia (ALL) followed by chemotherapy induction.Methods The diagnosis and treatment of ALL were performed according to the guidelines of the Pediatric Association of Chinese Medical Association.There were 11 cases of pediatric ALL who developed PRES after chemotherapy induction.The clinical presentations, initial and follow-up radiologic features, and the neurologic outcomes of these 11 cases were investigated for one-year follow-up.All patients were reexamined 1,3,6, and 12 months after first imaging.Results Headache (10/1 1 cases), epileptic seizure (7/11 cases), high blood pressure (4/11 cases) ,visual impairment (6/11 cases) ,disturbance of consciousness (5/11 cases) and walking instability (2/11 cases) were the most common symptoms of these ALL patients with PRES.Magnetic resonance imaging (MRI) scanning revealed that lesions were mainly distributed in occipital lobe (9/11 cases), parietal lobe (8/11 cases), frontal lobe (5/11 cases) ,temporal lobe (3/11 cases), the deep white matter of bilateral periventricular and centrum semiovale (2/11 cases) and hemisphaerium cerebelli (1/11 cases).The radiological findings indicated that lesions had multifocal,symmetrical and posteriorly distributed characteristics in the cerebral hemispheres.After the diagnosis of PRES,patients stopped chemotherapy courses promptly and received symptomatic treatment, and then the clinical and imaging symptoms of most cases gradually disappeared.After 1-year follow-up,9 patients had good prognosis and no sequelae, 1 patient had symptomatic epilepsy (brain magnetic resonance imaging scan showed lesions in the left temporal lobe) ,and 1 patient had slight visual impairment.After the craniocerebral symptoms disappeared clinically ALL chemotherapy continued in all patients and no recurrent PRES was observed.Conclusions Although the clinical and imaging features of PRES may be diverse ,PRES should be recognized as a possible important complication of ALL when neurological symptoms appear.However, PRES is reversible when the patients are diagnosed and treated at an early stage.Thus,the occurrence of PRES should be considered and investigated to optimize the early induction schemes for ALL treatment.

PEI Xue-yi has 60 years,experience in treating pediatric diseases with traditional Chinese medicine,especially obtains good effect in children's nephrapiathy.Based on the regulation and characteristics of children's zang-fu,yin-yang,blood-qi and children's nephrapiathy,he makes different therapeutic plans in different phases.In clinical treatment,he emphasizes the lung,the spleen and the kidney and combines syndrome differentiation with disease diagnosis.Eliminaing pathogens,excessive damp-heat is used in acute phase and strengthening healthy qi,securing the spleen and kidney is used in recovery phase.Children's nephrapiathy is treated by three phases as the edema,protein urine and rescovery stage.He adopts the methods of dispersing lung qi and invigorating spleen for diuresis,clearing heat-damp,nourishing spleen and kidney,nourishing yin for protecting lower jiao.

Objective To investigate the intensity of HBsAg and HBcAg expression in liver tissue of patients with chronic hepatitis B virus (HBV) infection and its clinical significance.Methods A total of 994 HBV infected patients underwent liver biopsy and histopathological examination.The expression of HBsAg and HBcAg in liver tissue was detected by histoimmunochemistry.Patients were divided into HBeAg (+)/HBVDNA(+), HBeAg(-)/HBV DNA(+) and HBeAg(-)/HBV DNA(-) groups according to HBeAg and HBV DNA levels;patients were divided into ＜2 × normal (ULN) group, 2-＜5 × ULN groupand ≥5 × ULN group according to the alanine aminotransferase (ALT) levels.The histologic activity (A), fibrosis (F), the expression of HBsAg and HBcAg in liver tissue and their correlations with clinical features were analyzed.Logistic regression analysis was used to study the factors affecting the expression of HBsAg and HBcAg in liver tissue.Results Among 994 HBV infected patients, 941 cases (94.67％) were intrahepatic HBsAg positive and 553 cases (55.63％) were intrahepatic HBcAg positive;403 cases (40.85％) were ≥A2 in histologic activity and 371 cases (36.09％) were ≥F2 in fibrosis.The degree of A and F was the highest in HBeAg (-) / HBV DNA (+) group, followed by HBeAg (-) / HBV DNA (-) group, and was the lowest in HBeAg (+) / HBV DNA (+) group.The intensity of intrahepatic HBsAg expression was significantly different among three groups (x2 =6.299, r =-0.760, P ＜ 0.05), however, the difference was not showed in pairwise comparisons.The difference of intrahepatic HBcAg intensity among three groups was statistically significant (x2 =282.995, r =-0.645, P ＜ 0.01), the intensity was the highest in HBeAg (+) / HBV DNA (+) group and the lowest in HBeAg (-) / HBV DNA (-) group.The constituent ratio of HBeAg positive and HBV DNA level were higher and the average age was lower in intrahepatic HBsAg positive group than those in HBsAg negative group.The constituent ratio of positive HBeAg, the levels of ALT, AST, PLT and HBV DNA were higher and the average age, the average FIB-4 level were lower in intrahepatic HBcAg positive group than those in HBcAg negative group.The HBV DNA level was an independent risk factor for intrahepatic HBsAg intensity, and the HBeAg positive and HBV DNA level were independent risk factors for intrahepatic HBcAg intensity.There were no significant differences in A and F among different groups of intrahepatic HBsAg intensity (x2 =1.943 and 2.630, both P ＞ 0.05).There was significant difference in F among different groups of intrahepatic HBcAg intensity (x2 =12.352, P ＜ 0.01), but not in A.The degree of F was the highest in intrahepatic HBcAg negative group.There was significant difference in intrahepatic HBcAg intensity among different groups of ALT level (x2 =16.349, P ＜ 0.01), but not in intrahepatic HBsAg intensity.The intrahepatic HBcAg intensity in ALT ＜ 2 × ULN group was lower than that in other two groups.Conclusions Most of patients with chronic HBV infection are intrahepatic HBsAg positive and more than half of them are intrahepatic HBcAg positive.The intrahepatic HBsAg intensity is not associated with A and F, but correlates with HBV DNA level.The intrahepatic HBcAg intensity is not associated with A, but it is negatively correlated with F and positively correlated with positive HBeAg expression, HBV DNA level and ALT level.