To study the drug-drug interaction of morinidazole and warfarin and its application, a sensitive and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of R-warfarin/S-warfarin in human plasma. In a random, two-period crossover study, 12 healthy volunteers received a single oral dose of 5 mg racemic warfarin in the absence and presence of morinidazole. Blood samples were collected according to a pre-designed time schedule. R-warfarin, S-warfarin and methyclothiazide were extracted with ethylether : methylenechloride (3 : 2), then separated on a Astec Chirobiotic V (150 mm x 4.6 mm ID, 5 microm) column using 5 mmol x L(-1) ammonium acetate (pH 4.0) - acetonitrile as mobile phase at a flow-rate of 1.5 mL x min(-1). The mobile phase was splitted and 0.5 mL x min(-1) was introduced into MS. A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM). The resolution of warfarin enantiomers is 1.56. The linear calibration curves for R-warfarin and S-warfarin both were obtained in the concentration range of 5 - 1 000 ng x mL(-1). Intra- and inter-day relative standard deviation (RSD) for R-warfarin and S-warfarin over the entire concentration range across three validation runs was both less than 10%, and relative error (RE) ranged from -4.9% to 0.7%, separately. The method herein described is effective and convenient, and suitable for the study of metabolic interaction between morinidazole and warfarin. The results showed that coadministration of warfarin with morinidazole did not affect the pharmacokinetics of either R-warfarin or S-warfarin.

Objective To observe the clinical effects of the adjustive tractor for cervical dislocation.Methods Forty-seven patients were included between September 2007 and November 2011.There were 36 males and 11 females with age ranged from 7 to 62 (mean,35 years).The mean interval from injury to admission was 8.6 h (range,0.5-72 h).There were atlanto-occipital dislocation in 2 cases,C1.2 in 2 cases,C2.3 dislocation in 5 cases,C3.4 dislocation in 2,C4.5 in 9,C5.6 in 13,C6.7 in 14.Thirty cases were complicated by fracture.No facet locking occurred in sixteen cases.Facet locking was found in ten cases and bilateral facet locking was in 21 cases.After reduction,brace or internal fixation followed.According to American Spinal Injury Association (ASIA) spinal function impairment scale standard,there were 4 cases in level A,10 cases in level B,18 in C,10 in D,and 5 in E.According to Japanese Orthopaedic Association (JOA) spinal function rating standard,the mean JOA score was 9 (range,2-14).Results All 47 cases were reduced successfully without neuronal function aggravation.Traction power ranged from 7 to 60 kg (mean,25.6 kg),the mean time of traction was 8 min (range,3-10 min).The mean follow-up was 38 (range,6-48) months.All the patients achieved normal alignment and intervertebral height.The intervertebral body fusion was observed in all of cases,the mean fusion time was 3.3 months (range,3-6 months).One patient who experienced nonunion of vertebral arch fracture didn't receive further treatment because of absence of symptoms.At last follow-up,there were 3 cases in level A,1 in level B,4 in C,8 in D,and 31 in E according to ASIA scale.The mean JOA score was 12 (range,2-17).Conclusion The adjustive tractor is simple and safe for prompt reduction.

AIMTo inspect the effects of cold-stress on filial growth and development of pregnant mice.

METHODSPregnant mice were divided into pregnant control group(PN) and pregnant cold-stress group (PC). The PC were kept in (4 +/- 2) C from 8:00 to 12:00 every day and the PN were kept in 25 degrees C. After 18 days, the blood pressure of pregnant mice were measured, and the weight of fetus, placenta and amniotic fluid were recorded. The natal mice visceral organs weight, visceral organs weight and body weight ratio were also measured. Growth curve and increment ratio curve of body weight were protracted every day from 1 st day to 44th day. Blood pressure of all filiality were measured in 8 weeks after they were born.

RESULTSThe blood pressure in PC was increased than that in PN (P < 0.05), the weight of fetus, placenta and amniotic fluid of PC decreased significantly compared with PN (P < 0.01). The filial visceral organ weight of PC reduced obviously compared with PN (P < 0.05), while the visceral organs weight and body weight ratio had no statistical meanings between the offspring of PC and PN (P > 0.05). Obvious difference of growth curve of the two filial groups was also existed until sexual maturity, but increment ratio curve of body weight of the two filial groups was basically fitted close. Filial blood pressure of PC was evidently higher than that in PN.

CONCLUSIONCold-stress stimulations seriously affect filial growth and development of pregnant mice.

Animals ; Cold Temperature ; adverse effects ; Female ; Fetal Growth Retardation ; etiology ; Hypertension, Pregnancy-Induced ; etiology ; Male ; Mice ; Pregnancy ; Prenatal Exposure Delayed Effects ; Stress, Physiological ; physiology

OBJECTIVETo assess the significance of platelet activation in unstable angina pectoris (UA) and acute myocardial infarction (AMI), and to explore the relationship of clinical effect of Xuefu Zhuyu concentrated pill (XCP) in vivo and the serum pharmacological anti-platelet activating effect of XCP in vitro.

METHODSBy flow cytometry and special labelled antibodys to detect the whole blood platelet membranous glycoprotein CD62P and CD41/45 expressions in UA patients before and after XCP treatment, as well as those in peripheral blood of AMI rats before and after co-cultured with XCP containing serum from patients at 37 degrees C for 30 min.

RESULTSCD62P and CD41/45 expressions increased significantly in UA patients to 24.36 +/- 7.91% and 29.51 +/- 12.21% respectively. After effective treatment, they decreased to 19.57 +/- 7.22% and 20.87 +/- 8.73% respectively accompanied with increase of platelet adhesion and aggregation rate. The difference of CD62P before and after treatment was significant (P < 0.05). CD62P in blood of AMI rats was 39.73 +/- 12.36%, after being co-cultured with XCP containing serum from patients treated effectively, it reduced to 30.41 +/- 10.36% (P < 0.05), but after co-cultured with the serum from patients treated ineffectively, it showed less intervention effect (P > 0.05).

CONCLUSIONPlatelet was highly activated in UA patients and AMI rats. The consistency between clinical holistic effect of XCP and serum pharmacological effect of XCP in platelet activation inhibition reflects a good correlation between serum pharmacological effect of Chinese herbal medicine and its clinical holistic effect.

Aged ; Angina, Unstable ; blood ; drug therapy ; Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; blood ; P-Selectin ; blood ; Phytotherapy ; Platelet Activation ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; therapeutic use ; Platelet Membrane Glycoprotein IIb ; blood ; Rats ; Rats, Wistar

This study seeks to explore the early signs of cognitive impairment in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). According to polysomnography, twenty patients diagnosed with OSAHS and twenty normal controls underwent event-related potential (ERP) examination including mismatch negativity (MMN) and P300. Compared with normal controls, OSAHS patients showed significantly prolonged latency of MMN and P300 at Cz. After controlling age and body mass index (BMI), MMN latency positively correlated with apnea hypopnea index (AHI), oxygen reduction index, stage N1 sleep and arousal index, while MMN latency negatively correlated with stage N3 sleep and mean blood oxygen saturation; and P300 latency positively related to AHI and oxygen reduction index; no relationships were found among MMN latency, MMN amplitude, P300 latency and P300 amplitude. These results suggest that the brain function of automatic processing and controlled processing aere impaired in OSAHS patients, and these dysfunction are correlated with nocturnal repeatedly hypoxemia and sleep structure disturbance.
Case-Control Studies ; Cognition Disorders ; complications ; physiopathology ; Event-Related Potentials, P300 ; Humans ; Hypoxia ; physiopathology ; Oximetry ; Polysomnography ; Sleep Apnea, Obstructive ; complications ; physiopathology ; Sleep Stages

BACKGROUND:Some studies have focused on bone marrow mesenchymalstem cells (BMSCs) combined with allograft bone or artificial bone substitute materials for bonedefect repair. But there is no report on BMSCs combined with Bio-oss for repair of rabbit skull defects as yet.OBJECTIVE:To observe the effect ofBMSCs combined with Bio-oss in repairing skull defects in rabbits.METHODS:BMSCs from male rabbits were isolated, cultured, and used as seed cells. In the skull of the female rabbits,three full-thickness bone defects with the same external diameter of 6 mm were made by a ring bone drill. Ninety-six female rabbits were randomly divided into four groups, and given Bio-oss/BMSCs in combination group, Bio-oss alone in Bio-oss group, BMSCs implantation in BMSCs group, and no intervention in blank group. All the implant surfaces were covered with guided tissue regeneration membrane.RESULTS AND CONCLUSION:The osteogenic effect in the combination group was better than that in the other three groups, and the Bio-oss group showed better osteogenesis in comparison with BMSCs and blank groups. But there was no significant difference between the BMSCs and blank groups. These findings indicate that the combined use of BMSCs as seed cells and Bio-oss as a scaffold material exerts overt osteogenic effects in rabbit skull defect area, which provides a new idea for the clinical treatment of bone defects.

OBJECTIVETo explore combination rules of Chinese herbal prescriptions from effective cases for treatment of unstable angina (UA).

METHODSPrescription data from 156 UA patients effectively treated at Cardiovascular Diseases Centre of Xiyuan Hospital were analyzed using complex network method.

RESULTSAccording to multi-scale analysis of backbone network and pointwise mutual information analysis, core prescriptions from the 156 UA patients were presented as follows: Rhizoma Ligustici wallichii, Radix Paeoniae rubra, Radix Codonopsis, Rhizoma Pinelliae, poria, and Angelica sinensis. Meanwhile, core couplet medicines for these patients covered Rhizoma Ligustici wallichii and Radix paeoniaerubra, Angelica sinensis and Rhizoma Ligustici wallichii, Radix Codonopsis and Rhizoma Ligustici wallichii, Rhizoma Ligustici wallichii and Rhizoma Pinelliae, Rhizoma Atractylodis Macrocephalae and poriacocos, Bulbus Alli Macrostemi and Rhizoma Pinelliae. Among different primary symptoms, there was slightly difference in core prescriptions.

CONCLUSIONThe core prescriptions for the treatment of UA include blood-activating drug, phlem-resolving drugs. As an exploration of combination rules of Chinese herbal prescriptions in treating UA based on complex network, it can be used as a reference for further researches.

Angelica sinensis ; Angina, Unstable ; drug therapy ; Drugs, Chinese Herbal ; standards ; therapeutic use ; Humans ; Pinellia ; Plant Roots ; Practice Guidelines as Topic ; Prescriptions ; standards

Aim To investigate the effects of harpagide on cerebral ischemia and the mitochondria mediated Caspase dependent apoptotic signaling pathway in mice.Methods The MCAO was employed to establish MCAO model.When the models were established, the mice were given harpagide (4, 8, 12 mg·kg-1) and edaravone (3.2 mg·kg-1) [0.1 ml·(10 g)-1] by tail vein injection after MCAO immediately.And the model and control mice were given equivalent normal saline by the same way.After MCAO for 6 h, the behavior, volume of cerebral ischemia and pathological changes in the brain were observed.Westernblot was employed to determine the contents of Cyt C in mitochondrion and pro-caspase-3 in endochylema.Results Compared with the model group, harpagide (4, 8, 12 mg·kg-1) could significantly decrease the increased nerve functional score, brain index, brain water content and volume of cerebral ischemia induced by cerebral ischemia.Harpagide (4, 8, 12 mg·kg-1) could reduce the contents of Cyt C in mitochondrion and pro-caspase-3 in endochylema.Conclusion Harpagide may have protective effect on the cerebral ischemia injury in mice, which might be related to the inhibition of the cerebral mitochondria mediated Caspase dependent apoptotic signaling pathway.

Objective To study the diagnosis and treatment of Mycobacterium avium complex lung disease with severe renal insufficiency,and to provide a basis for improving the clinical diagnosis and treatment of MAC lung disease with severe renal insufficiency.Methods Clinical data of an elderly patient with MAC lung disease confirmed by induced sputum culture and complicated with chronic kidney disease (CKD 4) was reported.The related literatures at home and abroad were reviewed.Results A male patient aged 80 years with poor nutrition was suffering from progressive weight loss,exhaustion and night sweats.His weight was only 43-44 Kg.Chest CT showed that multiple small nodules,small spot pieces of shadow and ground glass shadows in bilateral lung tissues.PET/CT indicated that spot pieces and nodules with metabolic activity in high performance.Bronchoalveolar lavage fluid (BALF) inspection was negative.MAC was identified by induced sputum culture through high permeability brine induced sputum.It was difficult to choose drugs for the treatment of MAC lung disease due to his poor kidney function [GFR of left kidney:9.0 ml /min,GFR of right kidney:18.8 ml/min].Conventional anti-mycobacterium drugs showed a low to high resistance to MAC.Moxifloxacin was discontinued for renal insufficiency.His condition was stable after choosing trimodality therapy including azithromycin 0.25 g/d tiw,rifapentine 0.3 g/d biw,ethambutol 0.375 g /d tiw and the joining immunotherapy.Conclusions PET/ CT is not useful in identifying tuberculosis and MAC lung disease.The treatment of MAC lung disease is difficult in elderly patients with severe renal insufficiency and low weight.Individual therapy combined with immunotherapy and improving the nutrition state is a good choice for the treatment of MAC lung disease in elderly patients with severe renal insufficiency.The anti-MAC drugs should be carefully selected and the adverse reactions should be closely observed in order to obtain the satisfactory clinical results.

BACKGROUND:Insufficient oral soft tissues in the implant zone may have a negative effect on the wound healing and the aesthetic restoration in the late stage. Platelet-rich fibrin can promote the wound healing of soft tissue defects. But there is stil a lack of in-depth studies on the promotion of oral soft tissue defects in animal experiments.
OBJECTIVE: To compare the repairing effects of platelet-rich fibrin and colagen membrane on soft tissue defects of the hard palate in New Zealand rabbits.
METHODS:Fifty-four New Zealand rabbits were randomly divided into three groups (n=14 per group): platelet-rich fibrin group, colagen membrane group and blank control group. A 5 mm-diameter circular ful-thickness soft tissue defect was made in the front of the hard palate, 2 mm distant to the rear maxilary incisors and mucosal edge of the bilateral hard palates. Autologous platelet-rich fibrin membrane or colagen membrane were implanted into the defect in the platelet-rich fibrin group and colagen membrane group, respectively. No treatment was given in the blank control group. General observation of the wound and wound healing analysis were performed at days 3, 7, 14, 21, 28, 56 post operation. Hematoxylin-eosin staining, CD31 immunohistochemical staining and Masson staining were used to observe inflammatory reaction, angiogenesis and colagen formation in the surgical site.
RESULTS AND CONCLUSION:The wound healing rate was fastest in the platelet-rich fibrin group, and no obvious scar formed. At 3 days post operation, there was no difference in the wound healing rates among the three groups; at 7 days, the wound healing rate in the platelet-rich fibrin group was significantly higher than that in the colagen membrane group and blank control group (P < 0.05). At 3 and 7 days after operation, the inflammatory reaction in the platelet-rich fibrin group was less than that in the colagen membrane and blank control groups (P < 0.05); at 14, 21, 28 and 56 days, there was no significant difference between the three groups. At 7, 14, 21 days after operation, the average absorbance value of CD31 in the platelet-rich fibrin group was significantly higher than that in the colagen membrane and blank control groups (P < 0.05). The average absorbance value of colagen formation in the platelet-rich fibrin group was significantly higher than that in the colagen membrane and blank control groups at 7 days after operation (P < 0.05), significantly higher than that in the blank control group at 14 days (P < 0.05), but lower than that in the colagen membrane and blank control groups at 21, 28 and 56 days after operation (P < 0.05). These findings show that platelet-rich fibrin can reduce inflammatory reactions in the process of wound healing, accelerate the angiogenesis, regulate the metabolism of colagen, reduce the formation of scar and improve the quality of wound healing, thereby promoting the repair of oral soft tissue defects.