OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats, specifically, to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent drug and its major metabolites. METHODS liquid chromatography/ion trap mass spectrometry (LC/MSn) and ultra-liquid chromatography coupled with mass spectrometry (UPLC/MS) were combined in the current study for qualitative and quantitative determinations of herbacetin and its metabolites in bile, urine and feces after both oral and intravenous administration of herbacetin to rats. Enzyme kinetic studies on the intestinal and hepatic metabolism of herbacetin were further conducted to elucidate metabolic profiles of herbacetin in rat tissues and organs. Additionally, plasma concentration profiles of herbacetin and its metabolites in rats were obtained to characterize the overall pharmacokinetic behavior of herbacetin. RESULTS It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations. Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin- glucuronides in systemic circulation. The clearance, half- life and bioavailability of herbacetin in rats were determined as (16.4±1.92)mL·kg-1·min-1, (11.9±2.7)min, and 1.32%, respectively. On basis of these findings, a comprehensive metabolic pathway of herbacetin in rats was composed. In addition, a physiology based pharmacokinetic (PBPK) model was successfully developed with the aid of the GastroPlus to simulate the pharmacokinetic process of herbacetin in rats. Application of the PBPK modeling can provide a useful starting point to understand and extrapolate pharmacokinetic parameters among different species, populations, and disease states. CONCLUSION After oral administration, herbacetin was subjected to colonic degradation and extensive first pass metabolism, with glucuronidation as its dominating in vivo metabolic pathway.

OBJECTIVE To investigate the effect of hypoxia on the pharmacokinetic process of salidrosidein rats and to explore its underlying mechanisms. METHODS The Caco-2 cell monolayerwas exposed to 1% oxygen (O2) concentration for 24 h to build the hypoxiccell model. The transportation mode of salidroside was investigated with the aid of this hypoxia model by detecting the apparent permeability coefficient(Papp). Healthy Sprague Dawley (SD) rats were exposed to 9% O2 for 72 h for the construction of hypoxic rat model. Liver sample was subsequently collected from the hypoxic rats with an aim to identify enzymes responsible for salidroside metabolism. The expression levels of sali?droside-transporting and salidroside-metabolizing enzymes, including Sodium-dependent glucose cotrans?porters (SGLT1), β-glucosidase (GBA3)and sulfotransferase (SULT2A1), were thereafter detected by RT-PCR and Western blot. The metabolic activity of GBA3 and SULT2A1 was monitored by rat liver microsome incubation.In addition, the renal function of rats under hypoxia was assessed by detecting concentrations of blood urea nitrogen and creatinine. RESULTS The AUC and t1/2 values of salidroside in hypoxic rats were more than doubled, while the in vivo clearance was significantly reduced. Mechanistic study demonstrated that the PappA- B/PappB- A eualsto 10.3, indicating the potential active transport of salidrosile. The expression of SGLT1 and GBA3 was significantly decreased, which indicated a reduced metabolism of salidroside under hypoxia. Moreover, rat under hypoxia was found to suffer from renal dysfunction, with an abnormal value of blood urea nitrogen. CONCLUSION Due to the reduced metabolism and the abnormal renal function under hypoxia, the systemic exposure of salidroside in rats was signifi?cantly enhanced.

OBJECTIVETo study zedoary turmeric oil (ZTO) and the pharmacokinetics of its homemade compound antiviral preparation in New Zealand rabbits.

METHODRP-HPLC was used to determinate the content of germacrone in rabbit plasma after oral administration.

RESULTAfter oral administration of ZTO and its homemade compound antiviral preparation, the plasma concentration-time curve of germacrone is in conformity to two-compartment open model. The pharmacokinetic parameters of ZTO: t1/2alpha, t1/2beta, Vd, CL, AUC and Ka were (1.52 +/- 0.59), (1.97 +/- 0.27) h, (47.59 +/- 2.29) L x kg(-1), (176.77 +/- 7.65) L x h(-1) x kg(-1), (5.70 +/- 0.70) mg x h x L(-1) and (0.97 +/- 0.11) h(-1), respectively, while those of compound preparation were (0.41 +/- 0.03), (1.47 +/- 0.35) h, (75.21 +/- 5.21) L x kg(-1), (287.79 +/- 6.39) L x h(-1) x kg(-1), (3.91 +/- 0.53) mg x h x L(-1) and (5.14 +/- 1.26) h(-1), respectively. There was no significant difference between the above two groups of pharmacokinetic parameters, expect that Ka of compound preparation was significantly higher than that of ZTO (P < 0.05).

CONCLUSIONHypericum perforatum in compound preparation doesn't impact the distribution and elimination of active ingredients of ZTO in New Zealand rabbits, but it improves the absorption speed, and shortens the time of drug absorption, which contributes to rapid efficacy of ZTO in rabbits.

Animals ; Antiviral Agents ; pharmacokinetics ; Curcuma ; chemistry ; Drug Compounding ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; Hypericum ; chemistry ; Male ; Plant Oils ; pharmacokinetics ; Rabbits ; Sesquiterpenes, Germacrane ; pharmacokinetics

OBJECTIVETo provide experimental data for the quality control of processed Paeonia lactiflora, a Chinese herbal medicine.

METHODTraditional processing of P. lactiflora was simulated, content of paeoniflorin and water extracts among different preparations were assayed by HPLC; The quantitative correlations among different processing conditions were analyzed, the effects of processing parameters on the contents of paeoniflorin and water extracts were assayed a nanalysed.

RESULT AND CONCLUSIONThe controlled processing parameters were correlated with covariables which showed that processing procedures was controllable, and the heating temperature was a factor impacting the content of paeoniflorin.

Benzoates ; analysis ; Bridged-Ring Compounds ; analysis ; Glucosides ; analysis ; Hot Temperature ; Monoterpenes ; Paeonia ; chemistry ; Plants, Medicinal ; chemistry ; Quality Control ; Technology, Pharmaceutical ; methods ; Temperature

To investigate transcription factor PAX5 expression characteristics in childhood acute leukemic cells, expression levels of PAX5 and CD19 mRNA in 6 hematological tumor cell lines and bone marrow cells of 6 normal children, 58 de novo patients and 4 relapse acute leukemic children, including 39 cases of B-ALL, 10 cases of T-ALL and 13 cases of AML, were detected by a real-time RT-PCR. The results showed that PAX5 and CD19 mRNA expression levels were 2.35% and 2.52% in Namalwa (B-cell lines) respectively, but almost not detectable in other T- and myeloid cell lines. Among clinical samples, expression of PAX5 mRNA in B-ALL was significantly higher than that in T-ALL and AML (P = 0.029 and P = 0.013 respectively). PAX5 expression was significantly lower in T-ALL and AML than that in normal controls. The difference of PAX5 mRNA expression levels between T-ALL and AML was not significant. Individual difference of PAX5 mRNA expression levels in children with B-ALL was great. Moreover, PAX5 mRNA expressions in de novo and relapse patients with B-ALL were significantly higher than those in remission (P = 0.011 and P = 0.006 respectively). As binding sites for B-cell specific activator protein have been identified in the promoter regions of CD19, the study found that in B-ALL, there was clear correlation between the expression levels of PAX5 and CD19, which was also studied by real-time RT-PCR. It is concluded that PAX5 transcripts are readily detectable and quantifiable in clinical materials with B-ALL by real-time RT-PCR. The strong PAX5 mRNA expression in some B-ALL can be considered to be particularly interesting for further analysis.
Adolescent ; Antigens, CD19 ; biosynthesis ; genetics ; Cell Line, Tumor ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; PAX5 Transcription Factor ; biosynthesis ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; RNA, Messenger ; biosynthesis ; genetics ; Transcription Factors ; biosynthesis ; genetics

BACKGROUNDDuring the process of bone cement joint replacement, some patients show a series of complications, such as a sudden drop in blood pressure or dyspnea. The cause of the complication is considered to be due to emboli caused by the femur prosthesis insertion. The purpose of the present study was to detect the pulmonary embolism in rabbits after bone cement perfusion by radioimmunoimaging, and to explore its protective measures.

METHODSForty rabbits, 2.5 - 3.0 kg weight, were randomly assigned to four groups, with ten rabbits in each group. Group I (no intervention): Bone cement perfusion was done after medullary cavity reaming and pressurizing. Group II (epinephrine hydrochloride intervention): The medullary cavity was rinsed with a 1:10 000 normal saline-diluted epinephrine hydrochloride solution followed by bone cement perfusion after medullary cavity reaming and pressurizing. Group III (fibrin sealant intervention): The medullary cavity was precoated with fibrin sealant followed by bone cement perfusion after medullary cavity reaming and pressurizing. Group IV (blank control group): The medullary cavity was not perfused with bone cement after reaming. In each group, the rabbits underwent femoral head resection and medullary cavity reaming. Before bone cement perfusion, 2 ml of developing tracer was injected through the ear vein. Radionuclide imaging was performed at 60, 120, and 180 minutes after bone cement perfusion, and the pulmonary radioactivity in vivo was measured. The rabbits were immediately sacrificed, and the pulmonary tissue was removed and its radioactivity was measured in vitro. Pulmonary tissue was then fixed and the pulmonary embolism and the associated pathological changes were observed.

RESULTSThe pulmonary radioactivity in vivo was measured at 60, 120, and 180 minutes after bone cement perfusion. The radioactivities of the four groups were 11.67 ± 2.16, 14.59 ± 2.92 and 18.43 ± 4.83 in group I; 8.37 ± 3.05, 10.35 ± 2.24 and 11.48 ± 2.96 in group II; 3.91 ± 1.19, 5.53 ± 2.95 and 7.25 ± 1.26 in group III; 1.04 ± 0.35, 1.14 ± 0.87 and 1.43 ± 0.97 in group IV. The radioactivities of groups I, II, III at 60, 120 and 180 minutes were significantly higher than group IV (P < 0.05). The pulmonary embolism could be detected. Pretreatment with epinephrine hydrochloride and fibrin sealant significantly decreased the pulmonary radioactivity in group II and group III, but it was still higher than in the group IV.

CONCLUSIONSRadioimmunoimaging is an alternative method for the dynamic observation of rabbit pulmonary embolism after bone cement perfusion. Radioimmunoimaging is the optional way to evaluate the effect of pretreatment with epinephrine hydrochloride or fibrin sealant on pulmonary embolism after bone cement perfusion.

Animals ; Bone Cements ; Pulmonary Embolism ; diagnosis ; Rabbits ; Radioimmunodetection ; methods

OBJECTIVETo study the clinical and genetic characteristics of a Chinese family with benign familial convulsions (BFNC).

METHODSThe clinical data of this family was analyzed. The blood samples were collected from 13 members of this family. By four microsatellite markers which are located in the gene loci of both K+ channel KCNQ2 and KCNQ3, the linkage analysis was performed in the family. With DNA direct sequencing and restriction endonuclease cutting analysis, the mutation analysis of KCNQ3 gene was made for the proband, other 12 family members and 76 unrelated normal individuals.

RESULTSThere were 7 patients with BFNC observed in the three generation of family. The BFNC seizures of all patients disappeared during one month and no recurrence of seizures was found. The linkage analysis suggested the disease gene linked to KCNQ3 gene locus in the family. The mutation 988(C to T) of KCNQ3 gene was found in the proband by DNA-direct sequencing. Cosegregation of this mutation with BFNC was confirmed by restriction endonuclease cutting analysis.

CONCLUSIONChinese patients with BFNC can be caused by KCNQ3 gene mutation.

Base Sequence ; Child ; China ; DNA Mutational Analysis ; Epilepsy, Benign Neonatal ; genetics ; pathology ; Family Health ; Female ; Genetic Linkage ; genetics ; Genotype ; Humans ; KCNQ3 Potassium Channel ; genetics ; Male ; Mutation ; Pedigree ; Sequence Analysis, DNA

We explore the association of the mycoplasma infection with genital system tumor.Some index word including prostate cancer,cervical cancer,ovarian cancer and mycoplasma were used in some electronic databases (including PubMed,Web of Science,Chinese biomedical database,wanfang database,CNKI) to search literatures.The R software was used for the meta-analysis.The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the literature.Publication bias was evaluated by funnel figure,and the fail-safe number (Nfs) was calculated to estimate the reliability of the meta-analysis.Result showed that 20 articles were included,the numbers of cases and controls were 2 345 and 2 728 respectively.The pooled OR of Ureaplasma urealyticum(Uu),Mycoplasma hominis(Mh),other mycoplasma,mixture of mycoplasma and the whole mycoplasma was 2.19(95％CI:1.27-3.79),1.74(95％CI:1.28-2.35),1.97(95％CI:1.03-3.77),3.54 (95％CI:1.33-9.41),1.29(95％CI:1.53-2.60),respectively.The fail-safe number of Uu,Mh,other mycoplasma and mixture of mycoplasma was 254,42,31,157 respectively.There are some possibility about the association between the mycoplasma infection and the genital system cancer;maybe the infection would increase the tumorigenesis risk.It is necessary to research further about these associations in different mycoplasmas respectively.

Objective:To test the reliability and validity of Work-ability Support Scale (WSS) in stroke patients. Methods:WSS was translated into Chinese with the standard translation-retroversion. From December, 2018 to March, 2019, 193 middle-aged and young stroke patients from two community health service centers in Zhengzhou were conveniently selected, and investigated with Chinese WSS by two nurses. The data were analyzed with item analysis, content validity, exploratory factor analysis, internal consistency reliability and inter-rater reliability. Results:The content validity was 0.94 in WSS A and 0.90 in WSS B. Three factors were extracted from 16 items in WSS A, with cumulative variance contribution of 67.747%; while three factors were extracted from 12 items in WSS B, with cumulative variance contribution of 56.056%. Cronbach's α was 0.933 and 0.778 in WSS A and WSS B, respectively. The kappa coefficient was above 0.6 between two raters in every item, except items B8 and B10. Conclusion:Chinese WSS is satisfactory in validity and reliability for using in young and middle-aged stroke patients during their return to work.