Establishment of orthotopic implantation model of human U87-MG brain glioma cell line in nude mice / 中国药理学通报

Aim To establish human U87-MG glioma model in nude mice brain and to observe the characteristics of the tumor growth. Methods Human U87-MG glioma cells were cultured in vitro. 5 μL of cell suspension containing 3.0 ×1010·L-1, 4.0×1010·L-1and 5.0×1010·L-1respectively was inocula-ted into the right caudate nucleus of 18 male nude mice brain un-der the guidance of stereotaxic apparatus, separately, whereas another 6 nude mice as the control group, were inoculated into the same volume of Hanks solution. The moving and survival state of rats with gliomas were observed. The examinations of the tumors formation, volumes, metastasis and histopathology were performed and the obtained brain samples were stained with HE and immunohistochemistry. Results All the tested rats of dif-ferent inoculation doses developed brain tumors without extracra-nial metastasis. The mean survival time of three groups was (46.50 ± 3.27) d,(38.50 ± 3.28) d and (30.67 ± 3.51) d,respectively. The tumors showed the similar morphological fea-tures and immunophenotype to human glioma. There was positive expression of GFAP and S-100 in the tumors. Conclusions The orthotopic implantation model of human U87-MG glioma, by in-oculating quantitative U87-MG cells stereotaxically into the brains of the nude mice, is successfully established with 100 yield of intracranial tumor and no extracranial growth extension. It resembles the histopathological and morphological features of human glioma,which can be used as a reliable animal model for the study of the tumorigenesis, pathogenesis, biological charac-teristics and therapy of glioma.

Management of sternal osteomyelitis and mediastinal infection following median sternotomy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Median sternotomy is considered the most usually performed procedure in cardiac operations. This study aimed to assess clinical effectiveness of bilateral pectoralis major muscle flaps (BPMMF) for management of sternal osteomyelitis and mediastinal infection following median sternotomy.</p><p><b>METHODS</b>Clinical data were collected and retrospectively analyzed from twelve patients who underwent the BPMMF transposition for management of sternal osteomyelitis and mediastinal infection following median sternotomy from January 2006 to June 2009. Procedure consisted of rigorous debridement of necrotic tissues, dead space obliteration using the BPMMF, and placement of drainage tubes connected to a negative pressures generator for adequate drainage.</p><p><b>RESULTS</b>No patients died of drainage, and all 12 patients had viable BPMMF when discharged from hospital. At 1 week post discharge, 2 patients presented with sternal infection but recovered following local debridement and medication. No patients showed infection recurrence during the follow-up period over 10 months.</p><p><b>CONCLUSIONS</b>Sternal osteomyelitis and mediastinal infection following median sternotomy may be effectively managed through rigorous debridement of infected soft tissues, resection of the damaged sternal segment, transposition of the BPMMF to fill the damaged sternum resulting from debridement, and adequate postoperative drainage.</p>

Biliary excretion of genistein and its metabolite at different doses in rats / 药学学报

<p><b>AIM</b>To study the biliary excretion of genistein and its metabolite at different doses in rats.</p><p><b>METHODS</b>Suspended in 0.5% CMC-Na solution, genistein was orally administered to rats at the dose of 6.25, 12.5 and 50 mg x kg(-1), separately. At various time intervals, the bile was collected. The bile was treated with beta-glucuronidase. The genistein in bile was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. Twenty microL solution was drawn and detected by high-performance liquid chromatography.</p><p><b>RESULTS</b>The accumulative biliary excretion of genistein was (42.56 +/- 6.54) , (75.17 +/- 18.87) and (126.60 +/- 34.78) microg at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. The total drug (genistein plus glucuronidated genistein) excreted from bile was (108.46 +/- 35.23), (423.46 +/- 158.31) and ( 853.74 +/- 320. 84) microg, and the ratio of glucuronidated genistein was 60.76% , 82.25% and 85.17% at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively.</p><p><b>CONCLUSION</b>The genistein was excreted mainly in the form of glucuronidated genistein in rat bile. The genistein and glucuronidated genistein were excreted in a nonlinear dose-dependent manner.</p>

Dose-dependent pharmacokinetic study of genistein in Beagle dogs / 药学学报

<p><b>AIM</b>To study the pharmacokinetics of genistein at different doses in Beagle dogs.</p><p><b>METHODS</b>Suspended in 0.5% CMC-Na solution, genistein was orally administered to Beagle dogs at doses of 2.67, 5.34 and 10.68 mg.kg(-1). At various time intervals, 1.5 mL of blood was drawn from the femoral vein of dogs in their front legs. The plasma was treated with beta-glucuronidase. The genistein in plasma was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (v/v = 8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. 20 microL solution was drawn and detected by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.</p><p><b>RESULTS</b>The plasma drug concentration-time data were fitted to the two-compartment model. When the dose was 2.67 mg.kg(-1), the MRT and AUC of parent compound were 52.9 min and 6.7 mg.min. L(-1), respectively. When the dose rose to 5.34 mg.kg(-1), the MRT and AUC of parent compound became 224.8 min and 26.1 mg.min.L(-1), respectively. However, when the dose increased to 10.68 mg .kg(-1), the MRT and AUC of parent compound increased to 267.7 min and 33.2 mg.min L(-1), respectively. The AUC of glucuronidated genistein was 33.9, 70.1 and 140.5 mg.min.L(-1) at the dose of 2.67, 5.34 and 10.68 mg.kg(-1), respectively.</p><p><b>CONCLUSION</b>Due to significant first pass metabolism, the drug was mainly existed in the form of glucuronidated genistein in the plasma. With the increase of dose, the absorption of genistein became saturated and the half life prolonged.</p>

Metabolic kinetics of MN9202 in Beagle dog liver microsomes / 药学学报

<p><b>AIM</b>To study the metabolic kinetics of MN9202 in Beagle dog liver microsome.</p><p><b>METHODS</b>Beagle dog liver microsomes were prepared by using ultracentrifuge method. After incubating 0.4 micromol x L(-1) MN9202 with 1 g x L(-1) microsomes for 30 min at 37 degrees C, the reaction was terminated by adding 0.5 mL alkalization. The RP-HPLC was used to determine the drug in the incubation mixture. The Michaelis-Menten parameters Km, and Vmax in Beagle dog liver microsomes were initially estimated by analyzing Lineweave-Brurk plot. Various selective CYP inhibitors were used to investigate their inhibitory effect on the metabolism of MN9202.</p><p><b>RESULTS</b>The Km, Vmax and CLint of MN9202 were (22.6 +/- 8.0) micromol x L(-1), (0.54 +/- 0.17) micromol x g(-1) x min(-1) and (0.0242 +/- 0.0009) L x g(-1) x min(-1), respectively. The metabolism of MN9202 was significantly inhibited by ketoconazole (Ket) and troleandomycin (Tro) in Beagle dog liver microsomes. Tranylcypromine (Tra) could inhibit the metabolism of drug as well. While other inhibitors showed little inhibitory effect on the metabolism of MN9202.</p><p><b>CONCLUSION</b>It was shown that CYP3A and CYP2C19 were involved in MN9202 metabolism. The inhibitors of human CYP3A and CYP2C19 may have potential interaction with MN9202, and this can reduce the metabolism rate and increase the toxicity of MN9202.</p>

Pharmacokinetics of m-nifedipine in Beagle dogs / 药学学报

<p><b>AIM</b>To study the pharmacokinetics of m-nifedipine (m-Nif) in Beagle dogs.</p><p><b>METHODS</b>The Beagle dogs were divided into two groups. m-Nif was intravenously administered to the Beagle dogs in group 1 at the dose of 0. 288 mg x kg(-1), and it was orally administered to the Beagle dogs in group 2, 3 and 4 at the dose of 1.152, 3.456 and 10.370 mg x kg(-1), respectively. m-Nif in plasma was detected by reversed phase high performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.</p><p><b>RESULTS</b>When m-Nif was intravenously administered, the plasma concentration-time curve was fit to a two-compartment model and T1/2beta was 117 min. When m-Nif was orally administered, the plasma concentration-time curve was fit to a one-compartment model. T1/2 (Ke) and Cmax were 147 min and 20 microg x L(-1); at the low dose of 1.152 mg x kg(-1). T1/2 (Ke) was 122 min and Cmax was 36 microg x L(-1) at the middle dose of 3.456 mg x kg(-1). T1/2 (Ke) was 144 min and Cmax was 69 microg x L(-1) at the high dose of 10.37 mg x kg(-1), respectively.</p><p><b>CONCLUSION</b>It was showed that the speed of elimination of m-Nif was high in Beagle dogs. The absolute bioavailability of m-Nif given orally was very low.</p>