The paper is to report the study of pharmacokinetics of transdermal administered nicotine in the brain of freely moving rat by using microdialysis with stable labeled isotope as internal standard. The pharmacokinetic behavior of nicotine in Sprague Dawley rat brain was investigated after intranasal administration (3.75 mg). Brain fluid samples were collected by intracerebral microdialysis with DL-nicotine as internal standard. Concentrations of nicotine and DL-nicotine in the sample were measured by HPLC-MS/MS. Main pharmacokinetic parameters were calculated and analyzed by Das 2.0 pharmacokinetic software. The recovery of nicotine and the delivery of DL-nicotine were the same. The fate of absorption and distribution was two compartment model and the values of t1/2alpha was 170.31 min, t1/2beta was 263.30 min and the AUC(0-infinity) was 2.75 x 10(5) microg x L(-1) min separately. DL-nicotine can be used to calibrate the recovery of nicotine, and the new method of stable isotope microdialysis can be used to study the pharmacokinetics of freely moving rat. It will make sense for the treatment of addiction of tobacco and provide a new thought for the research of pharmacokinetics-pharmacodynamic combination.

Objective:To investigate the levels of periphreal blood free carnitine and amino acids in healthy pregnant women in the third trimester and their association with maternal, fetal, and neonatal cardiac function and structure.Methods:This prospective descriptive study included healthy singleton pregnancies who underwent routine obstetric examination and delivered in two district maternal and child health hospitals (one in the urban and one in the suburb an area) in Beijing from June 2017 to February 2018. All recruiters had serology Down's syndrome screening test at (18±1) gestational weeks. Besides measurement of amino acids and free carnitine levels in whole blood and urine samples by liquid chromatography-tandem mass spectrometry, all cases underwent maternal and fetal echocardiography at (35±1) weeks of gestation. And neonatal echocardiography was performed after delivery to assess the heart function and structure. Antenatal factors were also collected, including maternal education background, age at first marriage and conception, gravidity, and folic acid supplement in early pregnancy. Statistical analysis was performed using t-test, ANOVA, Chi-square test, Pearson correlation coefficient, and Kappa test. Results:A total of 493 mother-neonate dyads were enrolled in this study. Blood free carnitine levels in the healthy pregnant women in the third trimester ranged from 5.09 to 59.17 μmol/L (reference value: 10.00-50.00 μmol/L) with an average value of (13.03±3.87) μmol/L. None was found with structural abnormalities by cardiac ultrasound, showing an average left ventricular end diastolic diameter (LVEDD) and end systolic diameter (LVESD) of (45.70±3.08) mm and (29.17±3.12) mm, respectively, and left ventricular ejection fraction (LVEF) of all cases were over 55%. No cardiac malformation was detected by the third-trimester fetal echocardiography. The average birth weight of the 493 newborns was (3 340±313) g. Those whose birth weight <2 500 g and >4 000 g were accounted for 1.0% (5 cases) and 3.0% (15 cases) with the average maternal blood free carnitine level of (13.25±2.17) μmol/L (10.46-19.21 μmol/L) and (12.64±2.50) μmol/L (8.78-17.73 μmol/L) ( t=0.42, P>0.05). The average LVEDD and LVESD of the 493 newborns were (17.21±1.27) mm and (11.03±1.30) mm, respectively. For the 64 newborns (13.0%) whose LVEF<60%, the maternal blood free carnitine level was (12.93±2.78) μmol/L (7.34-22.13 μmol/L), showing no statistical difference ( t=-0.29, P>0.05) with those 59 neonates (12.0%) whose LVEF over 75% and maternal carnitine level of (13.09±3.24) μmol/L (8.66-27.49 μmol/L). All cases were divided into four groups based on the quartiles of maternal blood free carnitine level and no significant difference in maternal or neonatal LVEDD or LVEF was observed among these groups (all P>0.05). Conclusions:Blood free carnitine concentration in healthy pregnant women in the third trimester is at the lower limit of normal range, and no significant effect on maternal cardiac function and fetal cardiac structure is seen. However, the effect of low maternal carnitine level in the third trimester on children's myocardial function and whether carnitine should be supplemented in the third trimester are worthy of further investigation with larger sample size.

Objective To study the preemptive analgesia effects and side reactions of flurbiprofen axetil in gynecological laparoscopy.Methods Sixty patients(ASAⅠ～Ⅱ)were randomly assigned into two groups with 30 cases each.GroupⅠreceived intravenous injection of flurbiprofen axetil 1mg/kg in 15 minutes before surgery.GroupⅡreceived intravenous injection of saline 1mg/kg at the same time.Postoperative analgesia efficacy was assessed by visual analogue scales(VAS)at 1,2,4,8.12,24h and side reactions were recorded after surgery.The overall satisfac- tion with analgesic therapy was evaluated after analgesia.Results VAS in groupⅠat 1,4,12,24h was lower than that in groupⅡ(P

Objective To compare the therapeutic effect of angiotensin Ⅱ antagonist (Valsartan)and angiotension-converting enzyme inhibitor (Captopril) for the improvement of left ventricular systolic function(LVSF) after acute myocardial infarction (AMI) at anterior wall. Methods A total of 75 patients with initial AMI at anterior wall were enlisted in the study. Patients were divided randomly into three groups: control group (n = 15), Captopril treated (n =30), and Valsartan treated (n =30). At 1 week and 28 weeks post AMI, the LVSF and left ventricular regional ejection fraction (LrEF) were measured by equilibrium radionuclide angiography (ERNA). The t-test was used to compare the dada. Results ( 1 ) At 28 weeks, left ventricular ejection fraction (LVEF) and left ventricular peak ejection rate (LPER) in Valsartan treated group were significantly increased as compared with those of control: ( 59.4 ± 8.6 ) % vs (44.9 ± 8.4)%, t = 3.87, P ＜ 0.01 for LVEF; (3.89 ± 1.01 ) end-diastolic volume (EDV)/s vs (2.84 ±1.05) EDV/s, t= 4.16, P ＜ 0.01 for LPER). The left ventricular time to peak ejection rate (LTPER) in Valsartan treated group was significantly decreased ( ( 116 ± 16 )ms vs ( 137 ±20) ms, t =2.16, P ＜ 0.05 ) as compared with control. (2)Compared with 1-week, 28-week Valsartan treated group had a significant increase inLrEF2, LrEF4, LrEF5, LrEF6: (71.6±18.8)% vs (57.0±11.4)%, t=2.11, P＜0.05;(78.1 ±16.8)% vs (68.9±21.0)%, t =2.06, P＜0.05; (70.5±16.9)% vs (59.9 ±23.4)%, t=1.99, P ＜ 0.05; and (58.1 ± 9.0) % vs (46.0 ± 18.9) %, t = 2.43, P ＜ 0.05, respectively. Conclusions Valsartan and Captopril are effective for the improvement of LVEF after AMI at anterior wall. The effects of the two drugs are similar.

The aim of this study was to observe and compare the endogenous circadian rhythm and photoresponse of Clock gene transcription in the suprachiasmatic nucleus (SCN) and pineal gland (PG) of rats. With free access to food and water in special darkrooms, Sprague-Dawley rats were housed under the light regime of constant darkness (DD) for 8 weeks (n=36) or 12 hour-light: 12 hour-dark cycle (LD) for 4 weeks (n=36), respectively. Then, their SCN and PG were dissected out every 4 h in a circadian day, 6 rats at each time (n=6). All animal treatments and sampling during the dark phases were conducted under red dim light (<0.1 lux). The total RNA was extracted from each sample and the semi-quantitative RT-PCR was used to determine the temporal mRNA changes of Clock gene in the SCN and PG at different circadian times (CT) or zeitgeber times (ZT). The grayness ratio of Clock/H3.3 bands was served as the relative estimation of Clock gene expression. The experimental data were analyzed by the Cosine method and the Clock Lab software to fit original results measured at 6 time points and to simulate a circadian rhythmic curve which was then examined for statistical difference by the amplitude F test. The main results are as follows: (1) The mRNA levels of Clock gene in the SCN under DD regime displayed the circadian oscillation (P<0.05). The endogenous rhythmic profiles of Clock gene transcription in the PG were similar to those in the SCN (P>0.05) throughout the day with the peak at the subjective night (CT15 in the SCN or CT18 in the PG) and the trough during the subjective day (CT3 in the SCN or CT6 in the PG). (2) Clock gene transcription in the SCN under LD cycle also showed the circadian oscillation (P<0.05), and the rhythmic profile was anti-phasic to that under DD condition (P<0.05). The amplitude and the mRNA level at the peak of Clock gene transcription in the SCN under LD were significantly increased compared with that under DD (P<0.05), while the value of corresponding rhythmic parameters in the PG under LD were remarkably decreased (P<0.05). (3) Under LD cycle, the circadian profiles of Clock gene transcription induced by light in the PG were quite different from those in the SCN (P<0.05). Their Clock transcription rhythms were anti-phasic, i.e., showing peaks at the light phase ZT10 in the SCN or at the dark time ZT17 in the PG and troughs during the dark time ZT22 in the SCN or during the light phase ZT5 in the PG. The findings of the present study indicate a synchronous endogenous nature of the Clock gene circadian transcriptions in the SCN and PG, and different roles of light regime in modulating the circadian transcriptions of Clock gene in these two central nuclei.
Animals ; CLOCK Proteins ; genetics ; Circadian Rhythm ; physiology ; Male ; Photoreceptor Cells, Vertebrate ; physiology ; Pineal Gland ; physiology ; Rats ; Rats, Sprague-Dawley ; Suprachiasmatic Nucleus ; physiology ; Transcription, Genetic

OBJECTIVEUsing the stable isotopes as the internal standard of microdialysis technology to establish a new method to study the whole and local brain dynamics of nicotine percutaneous preparations.

METHODUsing th healthy rats as experimental animals, administrating nicotine in abdominal transdermal way, then sample in the blood and brain simultaneously by microdialysis which use deuterium nicotine (DL-nicotine) as internal standard. Detecting the samples by LC-MS/MS method.

RESULTThe configuration process in blood and brain both conforms to 2 compartments model, t1/2 is 29.38 min, t1/2beta is 208.51 min, AUC(0-infinity) is 152 127.10 microg x min x L(-1) in the blood t1/2 is 86.64 min, t1/2beta is 386.00 min, AUC(0-infinity) is 152 820.90 microg x min x L(-1) in the brain.

CONCLUSIONDl-nicotine can be used as internal standard of nicotine to correcte the recovery; Stable isotopes internal standard microdialysis technology can be used for studing the whole and the local pharmacokinetic of nicotine and also provide new ideas and methods to studing the process of new drug delivery system.

Animals ; Brain ; metabolism ; Brain Chemistry ; Deuterium ; chemistry ; Isotope Labeling ; methods ; Male ; Microdialysis ; methods ; Nicotine ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate effect of root canal curvature and location of the fragment on the removal of broken file from root canal.

METHODSSixty extracted mandibular premolars were divided equally into six groups according to location of fragment (2 mm or 8 mm below root canal orifice) and root canal curvature (20 degrees, 30 degrees or 40 degrees). Broken files were removed using ultrasonic tips combined with dental operating microscope. Number of successfully removed case and operating time were recorded. Pre- and post-operative digital radiographs were input into image analyzing software to calculate diameter variance of root canal at the level of tip of broken file.

RESULTSAll the 6 groups of broken files were successfully removed with out perforation. Among same fragment location groups, diameter variance was increased in greater curvature groups and the difference was significant (P < 0.05), while operation time was not significantly different (P > 0.05). Among same root canal curvature groups, the deeper the fragment, the longer operation time, difference being significant (P < 0.05), while difference of diameter variance was not significant (P > 0.05).

CONCLUSIONThe more curvature of root canal, the more dentine removal amount at the level of broken file tip. Location of fragment has no effect on dentine removal amount. Safe straight-line access and adequate thickness of dentine are essential to removal of broken file from root canal.

Bicuspid ; Dental Pulp Cavity ; Dentin ; Humans ; Root Canal Preparation ; Root Canal Therapy

OBJECTIVETo explore the feasibility of microdialysis techniqiue to be used in pharmacokinetic study of Chinese medicine, taking Shuanghuanglian as a model drug.

METHODThe samples were obtained by retrodialysis, determined by HPLC gradient elution to calculate the in vitro recovery rate (RR) of specific components. To study the difference of RR of a certain component in different dialysis mediums, and the effect of flow rates and concentration on RR.

RESULTAlong with the increase of number of substances in the dialysis medium, the RR of specific components reduced. But the RR was independent of the concentration of the component in the dialysis medium. The RR reduced with the increasing flow rate in the same dialysis medium.

CONCLUSIONThe microdialysis technique can be used in pharmacokinetics study of Chinese medicine.

Calibration ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; isolation & purification ; pharmacokinetics ; Feasibility Studies ; Microdialysis ; methods

Objective To improve the level of early detection and treatment of pyonephrosis. Methods This study included 41 cases(17 men and 24 women;mean age,49 years)of pyonephrosis.A variety of examinations,including urinary analysis,blood analysis,kidney nuclear medicine scan,ultrasonog- raphy,intravenous urography(IVU),and CT were used for the early diagnosis of pyonephrosis.Pereutaneous nephrostomy(PCN)drainage was done for the interim management of pyonephrosis,then phase 2 operation was performed in 28 cases.The double-J tube was placed in ureter by ureteroscope for drainage,and then phase 2 operation was done in 2 cases.Emergency operation was done in 10 cases.The remaining 1 case un- derwent ESWL after anti-infective therapy.Results Definite diagnosis of pyonephrosis before operation was made by invasive examinations in 31 cases(75.6%),and by percutaneous drainage in 4 cases;the other 6 cases were detected during operation.Only 6 cases(14.6%)underwent nephrectomy;the other 35 cases (85.4%)underwent kidney-sparing operation.Follow-up of 3 months to 9 years was available in 37 cases. No nephrectomy was needed in 33 cases with spared kidney.Serum creatinine was normal in the 4 cases un- dergoing nephrectomy.Conclusions The key to the treatment of pyonephrosis by kidney-sparing surgery is early diagnosis,timely drainage and relief of obstruction.Ultrasonography plays an important role in the early diagnosis of pyonephrosis,and CT has a high sensibility in the diagnosis.Pereutaneons nephrolithotomy (PCNL)secondary to drainage through pereutaneous nephrostomy was beneficial to the patients with kidney stones or upper ureter stones.

Objective To discuss and analyze the diagnosis,management and surgical techniques for cranioplasty of skull vault defects and skull base reconstruction in order to raise the therapeutic effect. Methods The clinical data of 169 cases of skull vault and skull base defects treated with cranioplasty of skull vault defect and skull base reconstruction were retrospectively analyzed.Results Overlay tech- nique or inlay technique with imported titanium alloy mesh was used in 160 cases,and homologous bone was used in 9 cases.The surgical time ranged from 3 months to 8 years after injury.Eight cases presented with complications such as hematoma,subcutaneous effusion,infection and epilepsy postoperatively,but no operative death occurred.Conclusion For patients with skull vault defect with the diameter≥3 cm the best operative time is 3 months after injury,and for patients with intracranial and extracranial communica- ting tumors,skull base reconstruction can be performed when tumors are removed.Much attention should be paid to perioperative management and surgical skills.