Alzheimer disease (AD) is a common neurodegenerative disease. Drosophila has been regard as one of the ideal models for Alzheimer because of its unique advantage on genetic manipulation. AD transgenic drosophila models not only help to elucidate the pathogenesis of Alzheimer disease, but also provide potential screening models for drugs to treat the disease. In this review, we summarize the recent research progress using AD transgenic drosophila.

Objective To observe the effects of intranasal dexmedetomidine (DM)as premedi-cation on postoperative behavioral outcomes in children.Methods Sixty ASA physical status Ⅰ or Ⅱchildren of both genders,2-5 years,weighing 10-30 kg,undergoing hernia surgery,were equally as-signed into three groups (n =20 each)using a random number table:control group (group C),mid-azolam group(group M)and dexmedetomidine group(group D).Thirty minutes before anesthesia in-duction,the children were respectively received intranasal normal saline 0.02 ml/kg (group C),in-tranasal midazolam 0.2 mg/kg (group M)and intranasal DM 2 μg/kg (group D).The sedation score of children apart from parents,the receipt score of face mask for sevoflurane anesthesia induction,the postoperative recovery time,adverse effects,and the percentage of patients requiring rescue analgesic were recorded.To observe the postoperative behavioral outcomes on 1th、7th、30th day using the PH-BQ.Results Compared with group C,the sedation score and the receipt score of face mask of groups M and D were significantly increased (P <0.05).Compared with groups C and M,the adverse effects and the percentage of patients requiring rescue analgesic of group D were decreased (P <0.05).The incidence of the postoperative behavioral outcomes of group C was higher than groups M and D on 1th,7th day (P <0.05).And on 30th day after operation,there was no significant difference among three groups.Conclusion Intranasal dexmedetomidine as premedication can significantly decrease the incidence of the postoperative behavioral outcomes in children.

The work aims to study the drug metabolizing enzymes involved in the metabolism of butylphthalide and evaluate the induction and inhibition activities of butylphthalide on CYP450 isoenzymes by using in vitro (liver microsome incubation system of rats and human) and in vivo (CYP induced model of rats) method. Butylphthalide was incubated with selective inhibitors of CYP450, and its metabolic rate was determined to identify the metabolizing isoenzymes of NBP in rat (normal and induced rats) and human liver microsomes. The in vitro inhibition effect of butylphthalide on 6 main liver microsomal CYP450 isoenzymes was evaluated by using probe drugs; the induction and inhibition activities in vivo of butylphthalide on CYP450 isoenzymes were evaluated by NBP ig dosing (160 mg x kg(-1)) and iv dosing (20 mg x kg(-1)) in rats. After adding the specific inhibitors of CYP2C11, 2E1 and 3A 1/2 for rat, CYP2C19, 2E1 and 3A4/5 for human, the metabolism of NBP in rat and human liver microsomes were reduced 38.8%, 86.2%, 78.4% and 51.0%, 92.0%, 58.9% of control, respectively. The metabolic rates of NBP in CYP2E1 and 3A 1/2 induced rat liver microsomes were increased 25.5% and 68.9%. High concentration of NBP (≥ 200 μmol x L(-1), in vitro) could inhibit the activities of CYP1A2, 2C6, 2C11 and 2D2 in rats, and high concentration of NBP ( ≥ 15 μmol x L(-1), in vitro) could inhibit the activity of CYP2C19 in human. All the results indicated that NBP should be mainly metabolized by CYP2E1, 2C11 and 3A 1/2 in rats and CYP2E1, 2C19 and 3A4/5 in human. High concentration of NBP could inhibit human CYP2C19 in vitro. No significant induction/inhibition effects of NBP were observed on rat liver CYP450 isoforms after ig 160 mg x kg(-1) NBP or iv 20 mg x kg(-1) NBP.

Adaptation, Physiological ; Animals ; Brain Stem ; Cloning, Molecular ; DNA, Complementary ; Gene Expression ; Gene Library ; Motion Sickness ; genetics ; Rats

Animals ; Disease Models, Animal ; Male ; Motion Sickness ; Rats ; Rats, Sprague-Dawley

A 29-year-old woman was admitted to the Department of Rheumatology,Peking Union Medical College Hospital due to intermittent rashes,fever and headache.Palpable purpura were symmetrically distributed on the extremities and trunk.Other manifestations included headache with nausea and vomiting.Elevated white blood cell (WBC) count,platelet (PLT) count,erythrocyte sedimentation rate (ESR) and C-reactive protein were the main laboratory findings.Antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative.Examination of the cerebrospinal fluid (CSF) revealed high intracranial pressure,while routine cytology and biochemical tests of CSF were normal.Head MRI scan and PET-CT did not detect remarkable findings.A diagnosis of systemic vasculitis was confirmed by the biopsy of skin lesion which showed inflammatory infiltration of the muscular vessel wall.Combination therapy of corticosteroids and cyclophosphamide lead to a rapid improvement in clinical symptoms and laboratory parameters.The patient was in stable remission till 6 month follow-up.

Objective To evaluate the effects of color Doppler ultrasound guided percutaneous aspiration and absolute alcohol sclerotherapy on abdominal viscera cysts.Methods38 abdominal cysts in 33 cases were treated under Color Doppler ultrasound guided percutaneous aspiration and sclerotherapy with injection of absolute alcohol.Results After absolute alcohol treatment for 38 cysts in 33 cases,the cure rate was 89%,the efficacy rate was 100%.Con- clusion Color Doppler ultrasound Guided puncture sclerosing therapy of abdominal viscera cyst is a simple,safe and effective method.

The work aims to study the drug metabolizing enzymes involved in the metabolism of butylphthalide and evaluate the induction and inhibition activities of butylphthalide on CYP450 isoenzymes by using in vitro (liver microsome incubation system of rats and human) and in vivo (CYP induced model of rats) method. Butylphthalide was incubated with selective inhibitors of CYP450, and its metabolic rate was determined to identify the metabolizing isoenzymes of NBP in rat (normal and induced rats) and human liver microsomes. The in vitro inhibition effect of butylphthalide on 6 main liver microsomal CYP450 isoenzymes was evaluated by using probe drugs; the induction and inhibition activities in vivo of butylphthalide on CYP450 isoenzymes were evaluated by NBP ig dosing (160 mg x kg(-1)) and iv dosing (20 mg x kg(-1)) in rats. After adding the specific inhibitors of CYP2C11, 2E1 and 3A 1/2 for rat, CYP2C19, 2E1 and 3A4/5 for human, the metabolism of NBP in rat and human liver microsomes were reduced 38.8%, 86.2%, 78.4% and 51.0%, 92.0%, 58.9% of control, respectively. The metabolic rates of NBP in CYP2E1 and 3A 1/2 induced rat liver microsomes were increased 25.5% and 68.9%. High concentration of NBP (≥ 200 μmol x L(-1), in vitro) could inhibit the activities of CYP1A2, 2C6, 2C11 and 2D2 in rats, and high concentration of NBP ( ≥ 15 μmol x L(-1), in vitro) could inhibit the activity of CYP2C19 in human. All the results indicated that NBP should be mainly metabolized by CYP2E1, 2C11 and 3A 1/2 in rats and CYP2E1, 2C19 and 3A4/5 in human. High concentration of NBP could inhibit human CYP2C19 in vitro. No significant induction/inhibition effects of NBP were observed on rat liver CYP450 isoforms after ig 160 mg x kg(-1) NBP or iv 20 mg x kg(-1) NBP.
Animals ; Benzofurans ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; pharmacology ; Cytochrome P-450 Enzyme System ; metabolism ; Humans ; Isoenzymes ; metabolism ; Liver ; metabolism ; Microsomes, Liver ; metabolism ; Rats

Objective To report outcomes of patients with PSA ≥ 30 μg/L with initial negative transperineal template-guided saturation biopsy (TTSB). Methods From 2003 to 2010,a total of 1824 patients underwent transperineal saturation biopsies with the prostate template at the Peking Union Medical College Hospital.44 of them had initial negative biopsy with PSA ≥ 30 μg/L were reviewed in this study.The mean age was 68 years old (range,51 to 80).The mean biopsy cores were 28.7 (range,11 to 44).The median PSA level was 40 μg/L (range,30 to 128),and the median prostate volume was 73 ml (range,30 to 190).They were divided into four groups:TURP group,chronic prostatitis group,repeat biopsy group and miscellaneous group. Results Patients were followed up for a mean of 49 months (range,12 to 91).All patients of TURP group (15 cases) were identified as prostatic hyperplasia by postoperative pathology.2 of them had a second TTSB for PSA ＞ 10 μg/L after TURP,which were negative.5 patients of chronic prostatitis group had a declining PSA level after antibiotic therapy for 3 to 4 weeks.One patient took a second biopsy,which was identified as prostatitis.All patients of repeat biopsy group (18 cases) showed no significant decrease in PSA level during follow-up and undertook biopsies 2 to 4 times,6 of which were proved to be prostate cancer.All patients of the miscellaneous group (6 cases) had a declining PSA and didn't take a second biopsy. Conclusions Close follow-up and regular PSA testing for patients who had a high PSA level with initial negative biopsy would be help to avoid both false negative of prostate cancer and unnecessary biopsy.

Rutaecarpine (Rut) is a type of indole quinazoline alkaloid exracted from Ruticarpum. Studies showed that Rut has a wide range of pharmacological effects, such as anti-hypertension, anticancer, anti-inflammation, anti-thrombus formation. Currently, many scholars are committed to developing it into a new antihypertensive and anti-inflammatory drug with all new mechanisms. But studies found that Rut is a highly fat-soluble drug with low water and oil solubility. Its high insolubility is the main obstacle in its oral absorption and application, which greatly reduced its bioavailability. Therefore, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was used as the inclusion material to prepare Rut-HP-beta-CD inclusion complex in this experiment, in order to increase its water solubility and bioavailability. In this experiment, the inclusion complex was prepared by the stirring-freeze-dry method. The preparation process was optimized by the orthogonal test, with the inclusion rate as the index, and molar ratio between host and guest molecules, inclusion temperature, time and stirring speed as the impacting factors. Moreover, the inclusion complex was verified by detecting the apparent solubility, thin layer chromatography, microscopic identification, melting point detection and dissolution study. The results showed that under the conditions of the molar ratio between Rut and HP-beta-CD of 1: 1, temperature at 60 degrees C, inclusion time of 4h and stirring speed at 600 r x min(-1), the inclusion rate of Rut-HP-beta-CD reached 91.04%. Therefore, the preparation process of Rut-HP-beta-CD inclusion under the optimum conditions is simple and feasible, with a highest inclusion rate and reproducibility, and could significantly improve Rut's solubility and bioavailability, and provide a reliable experimental basis for its clinical application.
2-Hydroxypropyl-beta-cyclodextrin ; Alkaloids ; chemistry ; Chemistry, Pharmaceutical ; methods ; Drug Carriers ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Rutaceae ; chemistry ; Solubility ; beta-Cyclodextrins ; chemistry