Objective To study the inhibitory effects of total flavonoids of scutellaria baicalensis georgi(TFSB) on S180,Hep-A-22 and Bcap-37 tumor cell proliferation in vitro and on S180,Hep-A-22 in mice bearing tumor in vivo.Methods In vitro,S180,Hep-A-22 and Bcap-37 cells were divided into control group and TFSB groups(12.5,25.0,50.0,100.0 mg?L-1).The inhibitory effects of TFSB on proliferation of S180 and Hep-A-22 were measured by XTT colorimetric assay,and Bcap-37 cells were measured by MTT colorimetric assay.In vivo,the mice bearing tumor were divided into control group,CTX group(30 mg?kg-1),high,middle,low doses TFSB groups(200,100,50 mg?kg-1).After the mice bearing S180 and Hep-A-22 tumor cells were treated with TFSB for 15 d,the tumor weights were measured,the inhibitory rates of S180 and Hep-A-22 were calculated and survival of Hep-A22 was measured after administration of TFSB for 10 d.Results TFSB inhibited the proliferation of S180,Hep-A-22 and Bcap-37 cells,IC50 values were 16.04,17.74 and 9.05 mg?L-1,respectively.The tumor weight of mice bearing S180 and Hep-A-22 cells in TFSB groups(200,100,50mg?kg-1) were lowered than that in control(P

AIMTo investigate the effects of Angelica sinensis polysaccharide fraction AP-3 on IL-2 and IFN-gamma induction and its further immunomodulatory feature.

METHODSThe percentage of CD4+ lymphocyte was detected by flow cytometric method, the production of IL-2 and IFN-gamma in cell culture supernatant were determined by ELISA, mRNA expressions of IL-2 and IFN-gamma cytokines were detected by RT-PCR.

RESULTSAt the range of 0. 6 - 2 micromol x L(-1), AP-3 significantly enhanced the percentage of CD4+ lymphocytes in total splenocytes. At the range of 2 - 6 micromol x L(-1), the treatment of AP-3 augmented both productions of IL-2 in cell culture supernatant and cell IL-2 mRNA transcription level in a time and dose dependent manner. While in the case of IFN-gamma, AP-3 stimulated at early time after exposure but down-regulated thereafter.

CONCLUSIONAngelica sinensis polysaccharide could regulate the immune response through upregulating IL-2, IFN-gamma expression and activating Th1 cell.

Angelica sinensis ; chemistry ; Animals ; CD4-Positive T-Lymphocytes ; cytology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Female ; Interferon-gamma ; biosynthesis ; genetics ; Interleukin-2 ; biosynthesis ; genetics ; Lymphocyte Activation ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Spleen ; cytology ; metabolism

AIMTo study the pharmacokinetics of m-nifedipine (m-Nif) in Beagle dogs.

METHODSThe 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.

RESULTSWhen 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.

CONCLUSIONIt 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.

Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Calcium Channel Blockers ; administration & dosage ; pharmacokinetics ; Dogs ; Injections, Intravenous ; Isomerism ; Nifedipine ; administration & dosage ; pharmacokinetics

AIMTo study the metabolic kinetics of MN9202 in Beagle dog liver microsome.

METHODSBeagle 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.

RESULTSThe 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.

CONCLUSIONIt 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.

Animals ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; Calcium Channel Blockers ; metabolism ; pharmacokinetics ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP3A Inhibitors ; Dihydropyridines ; metabolism ; pharmacokinetics ; Dogs ; Ketoconazole ; pharmacology ; Microsomes, Liver ; metabolism ; Mixed Function Oxygenases ; antagonists & inhibitors ; Nitrobenzenes ; metabolism ; pharmacokinetics ; Tranylcypromine ; pharmacology ; Troleandomycin ; pharmacology

Objective The purpose of this study was to approach the relation of SNP43,SNP44 locus, main haplotypes and haplotype combinations with type 2 diabetes mellitus(T2DM).Methods According to the theory and principles of systematic review,data from case-control studies regarding the association between calpain-10(CAPN10) gene and T2DM were derived through electronic search of PubMed and Chinese journals databases.To gain a more precise estimation of the relationship,a stratified Meta-analysis with four subgroups was pertbrmed according to the races.Publication bias Was also assessed.Results The association with T2DM in different races was evaluated.In Mongoloid race,SNP43-G allele,G/G genotype and 111/221 haplotype combination showed notable association with T2DM with Ors (95%CI) as 1.368(1.155-1.620),1.437(1.186-1.741) and 2.762 (1.287-5.927) respectively.In Caucasoid race,SNP44-C allele,111/111 hapotype combination showed strong relationship with T2DM with Ors(95%CI) as 1.144(1.023-1.278),1.291(1.050-1.586) respectively.In Hybrid race,only one positive finding Was obtained which Was SNP44-C allele with OR(95%CI)as 1.653(1.025-2.665).Conclusion SNP43-G allele,G/G genotype,111/221 were risk factors to Mongoloid race.And SNP-C allele,111/111 haplotype combination were risk factors to Caucasoid race,and SNP44-C allele to Hybrid race.

OBJECTIVETo investigate perioperative patterns of melatonin and cortisol secretion rhyme in patients undergoing coronary artery bypass grafting surgery.

METHODSEleven male patients scheduled for elective coronary artery bypass grafting surgery (CABG) under hypothermic cardiopulmonary bypass (CPB) were enrolled in the study. Anesthesia was induced and maintained with propofol (3 mg.kg-1.h-1) and supplemented with fentanyl (15 micrograms/kg). Blood samples were taken during surgery at specific time-points and every 3 h in the immediate postoperative period and postoperative day 2 and day 3. Plasma melatonin and cortisol levels were measured by radioimmunoassay and enzyme-linked immunosorbent assay respectively.

RESULTSDuring surgery, plasma melatonin levels were below the minimum sensitivity level but low levels, without circadian variation, were measured during the immediate postoperative period. During postoperative day 2 and day 3, circadian secretion patterns of melatonin were present in 10 patients and showed an inverse correlation with light intensity exposed (r = -0.480, P = 0.01). Plasma cortisol levels in the immediate postoperative period were significantly higher than those before induction of anesthesia (P < 0.01). During postoperative day 2 and day 3, only 3 patients regained circadian secretion of cortisol.

CONCLUSIONSIt is concluded that melatonin and cortisol secretion are disrupted during cardiac surgery and in the immediate postoperative period.

Cardiopulmonary Bypass ; Circadian Rhythm ; Coronary Artery Bypass ; Coronary Disease ; physiopathology ; surgery ; Humans ; Hydrocortisone ; secretion ; Intraoperative Period ; Male ; Melatonin ; secretion ; Middle Aged ; Monitoring, Intraoperative ; Postoperative Period

OBJECTIVETo construct a recombinant adenovirus expression vector containing the anti-oncogene PTEN and to investigate the effects of the PTEN gene on the proliferation of prostate cancer PC-3 cells and the expressions of cyclin D1 and p21 in the PC-3 cells.

METHODSThe PTEN gene was amplified from the rat hippocampus by RT-PCR and cloned into the shuttle plasmid pEN-TR2A. The plasmids were constructed and amplified in 293A cells. Prostate cancer PC-3 cells were cultured in vitro and infected with the adenoviral vector carrying the PTEN gene (Ad-PTEN). The up-regulation of the PTEN protein was measured by indirect immuno-fluorescence assay; the expressions of PTEN, cyclin D1 and p21 in the cells infected with Ad-PTEN and Ad-LacZ were determined by

RESULTSThe Western blot; and the effect of PTEN on the cell proliferation was detected by MTT assay and plate colony formation. recombinant adenoviral vector Ad-PTEN was successfully constructed. Western blot showed a significantly increased expression of the PTEN protein in the PC-3 cells infected with Ad-PTIEN (0.215 +/-0.065) as compared with that in the control ([0.052 +/-0.009], t = 4. 30, P <0.05) and the Ad-LacZ group ( [0. 056 +/- 0.008 ] , t =4.21, P <0.05). The expression of cyclin D1 was significantly lower in the Ad-PTEN-infected PC-3 cells (0. 256 +/- 0. 072) than in the control ( [0. 502 +/- 0. 087 ], t = 3.77, P < 0.05) and the Ad-LacZ group ([0.498 +/-0.081] , t =3.87, P <0.05), while the expression of p21 remarkably higher in the Ad-PTEN-infected PC-3 cells (0.589 +/-0. 076) than in the control ([0. 146 +/-0.026] , t = 9.55, P<0. 01) and the Ad-LacZ group ([0. 163 +/-0. 024] , t = 9.26, P <0.01). Ad-PTEN significantly inhibited the growth of the PC-3 cells (21.98%) at 48 h (t = 6.80, P <0.01). The colony formation rate of the PC-3 cells was (37.4 +/-4. 18)% in the Ad-PTEN group, significantly lower than (54.9 +/-4.81)% in the control (t =4.76, P<0.01) and (56.5 +/- 5.42)% in the Ad-LacZ group (t=4.83, P<0.01).

CONCLUSIONThe expression of PTEN induced by Ad-PTEN can significantly inhibit the proliferation of PC-3 cells, down-regulate the expression of cyclin D1, and up-regulate the expression of p21.

Adenoviridae ; genetics ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Humans ; Male ; PTEN Phosphohydrolase ; genetics ; Prostatic Neoplasms ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley

To study the phenolic constituents from the dry stem of Juncus effusus L. , the constituents were isolated by normal-phase and reverse-phase silica gel column chromatography from the EtOAc extract. Their structures were elucidated by spectral analysis. Six phenolic constituents were purified and identified as 7-carboxy-2-hydroxy-1-methyl-5-vinyl-9,10-dihydrophenanthrene (1) , 2,3-isopylidene-1-O-ferulic acid glyceride ( 2 ) , ( 2S )-2, 3-isopylidene-1-0-p-coumaroyl glyceride (3 ) , dehydroeffusal ( 4 ) , p-hydroxybenzaldehyde (5) and luteolin-5,3'-dimethyl ether (6). Compounds 1 and 2 are new compounds. Compounds 5 and 6 were isolated from Juncaceae plant for the first time. 13C NMR data of compound 6 were reported for the first time.
Anthracenes ; chemistry ; isolation & purification ; Benzaldehydes ; chemistry ; isolation & purification ; Coumaric Acids ; chemistry ; isolation & purification ; Flavones ; chemistry ; isolation & purification ; Magnoliopsida ; chemistry ; Molecular Conformation ; Molecular Structure ; Phenols ; chemistry ; isolation & purification ; Plants, Medicinal ; chemistry