AIMTo quantify progesterone (P) and one of its metabolites 20alpha-hydroxy-4-pregnen-3-one (20alpha-OHP) in rat plasma and uterus after im administration of progesterone.

METHODSPlasma and uterus samples were prepared by liquid-liquid extraction and separated through Shimadzu VP-ODS column (150 mm x 4.6 mm ID, 5 microm). The mobile phase consisted of acetonitrile and water (60: 40, adjusted to pH 4.0 with phosphoric acid). The detector was set at 240 nm. Norgestrel was used as the internal standard.

RESULTSCmax of P in plasma was (508 +/- 62) microg x L(-1), Tmax was (3.2 +/- 0.4) h, T1/2 (ke) was (10 +/- 4) h and mean AUC0-48h was (5886 +/- 1573) microg x L(-1) x h. The maximum concentration of P in uterus was (1.7 +/- 1.1) microg x g(-1) and the peak time was (5.2 +/- 1.11) h. 20alpha-OHP showed a similar Tmax with P.

CONCLUSIONThe method is accurate and convenient. It can be used to determine P and its main metabolite 20alpha-OHP simultaneously for studying their preclinical pharmacokinetics.

20-alpha-Dihydroprogesterone ; blood ; pharmacokinetics ; Animals ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Female ; Injections, Intramuscular ; Progesterone ; blood ; metabolism ; pharmacokinetics ; Rats ; Rats, Wistar ; Uterus ; metabolism

AIMTo determine Danshensu in urine and study its pharmacokinetics in human.

METHODSA solid phase extraction-HPLC method was used for determination of Danshensu in urine of human. HPLC separation is performed on a Shim-pack CLC-ODS column (150 mm x 6.0 mm ID, 5 microns) with a mobile phase composed of acetonitrile -0.01 mol.L-1 KH2PO4 (adjusted to pH 2.8 with phosphoric acid). The flow rate was 1.0 mL.min-1 and the UV detector was set at 280 nm. The linear range of Danshensu was 0.2-50 mg.L-1 (r = 0.9999), and its limit of detection was 1.5 ng. The mean recovery was 99.4% (RSD = 2.9%).

RESULTSThe pharmacokinetics of Danshensu after p.o. administration of two kinds of pharmaceutical preparations containing Danshen (with 20 mg of Danshensu) were investigated in 6 healthy human volunteers by determining the Danshensu in urine samples. The elimination half lives (T1/2) of Danshensu after p.o. administration of compound granule preparation A and decoction of Danshen were (0.92 +/- 0.16) h and (0.94 +/- 0.21) h, respectively. Their excretions of Danshensu in urine were (6.2 +/- 2.8)% and (14 +/- 4)% of the dose in 8 hours, respectively.

CONCLUSIONUnder normal doses, Danshensu can be eliminated from kidney. There is no evident difference on elimination half lives of Danshensu after p.o. administration of the two doses, but the excretions of Danshensu by urine after p.o. administration of compound granule preparation A were lower than that of decoction of Danshen.

Adult ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; Humans ; Lactates ; pharmacokinetics ; urine ; Male ; Plants, Medicinal ; chemistry ; Salvia miltiorrhiza ; chemistry

AIMTo separate and quantitatively determine six alkaloids: aconitine, mesaconitine, hypaconitine, beiwutine, benzoylaconine and benzoylmesaconine in the Chinese traditional medicine Radix Aconiti Lateralis Preparata (Fuzi).

METHODSA RP-ion-pair HPLC method was established. An AichromBond-1 C18 column was used at a column-temperature of 35 degrees C. The mobile phase was CH3CN5 mmol x L(-1) NaH2PO4(50:50) containing 7 mmol x L(-1) SDS at a flow-rate of 1.0 mL x min(-1). The detector was set at UV 235 nm.

RESULTSThese six alkaloids can be completely separated and determined quantitatively.

CONCLUSIONThis method is accurate and suitable for the determination of six alkaloids in Fuzi.

Aconitine ; analogs & derivatives ; analysis ; isolation & purification ; Aconitum ; chemistry ; Alkaloids ; analysis ; isolation & purification ; Chromatography, High Pressure Liquid ; methods ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry

In order to affirm the cardioactive components in Fuzi, we identified a group of aminoalcohol- diterpenoid alkaloids in Fuzi using ultra high-performance liquid chromatography coupled with electrospray ionization mass spectrometer (UPLC-ESI-MS) method. Among a total of forty-one isolated ingredients, thirteen major aminoalcohol-diterpenoid alkaloids were identified by comparing their retention times and MS spectra with those of the reference substances. Moreover, Fuzi samples from different places of origin and with different processing methods were examined and their components displayed a pattern of high similarity, though the relative abundance varies probably due to their different processing methods. Furthermore, the cardiac effect of each identified alkaloid was individually evaluated using the isolated bullfrog heart perfusion experiment. Among the thirteen aminoalcohol diterpenoid alkaloids tested, six of them significantly enhanced the amplitude rates. Taken together, we affirm that the cardioactive components in Fuzi are aminoalcohol-diterpenoid alkaloids, shedding light on future studies of the mechanisms and development of these cardioactive compounds.
Aconitum ; chemistry ; Alkaloids ; chemistry ; Amino Alcohols ; chemistry ; Animals ; Cardiotonic Agents ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Heart ; drug effects ; In Vitro Techniques ; Plant Extracts ; chemistry ; Rana catesbeiana ; Spectrometry, Mass, Electrospray Ionization

To identify the structure of three related substances in potassium sodium dehydroandrographolide succinate (PSDS), an HPLC preparation method was used to separate the impurities. These main impurities were identified using LC-ESI/TOFMS, LC-ESI/MSn, NMR, UV and IR. One of the main impurities was a hydrolyzed and oxidized product of PSDS, which has not been reported previouely. The other two impurities were hydrolyzed products of PSDS after losing different succinic acids. The results indicate that PSDS can be easily hydrolyzed and oxidized. It should be stored at cool and dry places.
Andrographis ; chemistry ; Antiviral Agents ; chemistry ; isolation & purification ; Chromatography, High Pressure Liquid ; Diterpenes ; chemistry ; isolation & purification ; Drug Contamination ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Molecular Structure ; Plants, Medicinal ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Objective To detect the neuronal network activity of specific brain areas in heroin addicts under craving state induced by heroin related cues with independent component analysis (ICA) of functional MRI (fMRI) data. Methods Fifteen heroin addicts,admitted to our hospital from February 2010 to December 2010, and 15 healthy controls were recruited in the case-control study; they were performed whole brain scan with 3.0Tesla MR scanner when being presented with heroin related cues.ICA was performed on these data and their neuronal network activities were compared. Results As compared with those in the controls,the bilateral prefrontal cortex,the left anterior cingulated cortex,the bilateral posterior cingulated cortex, the left inferior temporal gyrus and the left parietal lobe enjoyed obviously decreased activity, while bilateral nucleus accumbens, the right hippocampus, part of the temporal lobe and the occipital lobe enjoyed significantly increased activity (P＜0.05). Conclusion ICA is an advanced approach to identify fMRI data induced by related cues; the specific neuroanatomy mediated to cue-elicited heroin craving mostly locates in the learn-memory system and reward system,which involves the frontal cortex,the parietal lobe,the anterior eingulate,the posterior cingulate,the hippocampus and the nucleus accumbens.

Objective To explore the changes of functional connectivity of anterior cingulate cortex (ACC) in online game addicts during the resting state,and to analyze the function of ACC in the pathogenesis of online game addiction from a perspective of resting-state functional connectivity.Methods Seventeen online game addicts treated in our hospital from March 2011 to October 2011 were recruited as addiction group and 17 healthy controls at the same period were recruited as HC group.The baseline characteristics of all 34 subjects were investigated and compared between the addiction group and the HC group.All fMRI data were preprocessed after a resting-state fMRI scan,and then,the left and right anterior cingulate cortexes were selected as regions of interest (ROIs) to calculate the linear correlation between the ACC and the entire brain to compare the differences between the online game addicts and normal controls.Results Obvious differences between the addiction group and HC group were noted in hours and days of online game using and degree of thirst to play online games (P＜0.05);within the functional connectivity of ACC during the resting state,in contrast to the controls,the online game addicts showed increased connectivity with posterior cingulate,medium cingulate,midbrain,nucleus accumbens and supplementary motor area,but reduced connectivity with prefrontal cortex,temporal lobe and occipital lobe (P＜0.05).Conclusion Altered functional connectivity of the ACC reflects the dysfunction in ACC of online game addicts,which may be linked to the forming and maintaining of the online game addiction.

OBJECTIVETo evaluate the effectiveness of thymectomy for myasthenia gravis (MG) and the relative risk factors for postoperative myasthenic crisis.

METHODSThe clinic data of 78 cases with MG who underwent thymectomy from June 1985 to June 2005 were analyzed retrospectively. The relative risk factors of postoperative myasthenic crisis were analyzed and the differences between new and old region of perioperative management were compared.

RESULTSThe symptom of MG was complete remission in 21 cases, significantly improved in 38 cases, improved in 11 cases and unchanged in 8 cases, respectively. The symptom duration before operation, preoperative serum level of anti-acetylcholine receptor antibody, Osserman stage and pathological type of thymoma were independent relative risk factors for postoperative myasthenic crisis. The new region of perioperative management was significant better than the old one.

CONCLUSIONSurgical treatment shows significant clinical benefits for patients with MG.

Adolescent ; Adult ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle Weakness ; etiology ; prevention & control ; Myasthenia Gravis ; surgery ; Postoperative Complications ; prevention & control ; Retrospective Studies ; Thymectomy ; adverse effects ; methods ; Treatment Outcome

Objective To explore the current sources of stress for medical graduates, their personality characteris-tics and social support. Methods 208 postgraduates of Peking Union Medical College were surveyed by question-naire with the Graduate Student Stressor Scale, Symptom Checking List ( SCL-90) , NEO Five-Factor Inventory and Perceived Social Support Scale ( PSSS) . Results According to the five common stressors such as academic, economic, employment, physical and mental health, and tutor relationship, single-factor analysis of variance ( ANOVA) showed that there were significant differences in the composition of pressure sources between different sexes and grades. Univariate correlation analysis showed that all five dimensions of stressors had a significant posi-tive correlation with anxiety and depression symptom. There was a positive correlation between stressor and neurotic personality, and significant negative correlation with extroversion and rigorous personality. Furthermore, the stressors were significant negative correlation with perceived social support. Conclusions Medical graduate students are under various pressures at present. It is necessary to pay more attention to the education and training in the fu-ture and adopt diversified measures to rationalize them.

Objective To study the impairnlent of cognitive function and the change of P300 event-related potential(ERP)parameters in the patients with tumor in frontal lobe so as to investigate the role of the front lobe in cognitive function and the P300 production. Methods P300 examination and neuropsychological tests for cognition,including Stroop Test,Symbol Digit Modalities Test,and Verbal Fluency Test,et al,were performed in 31 patients with tumor in front lobe(left 15 and right 16)and 30 healthy controls. Results Compared with healthy controls, in the patients with front lobe tumor,cognitive function was degraded(P＜0.05),the latency of N3,P3 of P300 was significantly longer,and the amplitude of P3 was significantly lower(P＜0.05).Funhermore,the patients with tumor in right front lobe had signmcantly lower scores in cognitive tests compared with healthy controls (P＜0.05), but the ones with tumor in left front lobe were demonstrated obviously impaired only in Verbal Fluency Test(P＜0.05).Compared with healthy controls, the patients with tumor in eimer right or left flront lobe, the latency of N3,P3 of P300 was significantly longer,the amplitude of P3 was significantly lower(P＜0.05),while in the comparison of two sides, there was no statistically significantly difference in P300 (P＞0.05).Conclusions The cognitive function is obviously impaired in the patients with tumor in frontal lobe,and the impainnent is more serious in the ones with right frontal lobe tumor. Frontal lobe may be related to the generation and transmission of P300,and it is not significantly different in between left and right frontal lobes.