OBJECTIVETo study pharmacokinetic effect of Aikeqing Granule (AG) by different medication ways on zidovudine (AZT) in highly active antiretroviral therapy ( HAART) of rats.

METHODSTotally 36 rats were administered with corresponding medications by gastrogavage, group I [HAART: AZT 31.5 mg/kg +3TC 31.5 mg/kg + Efavirenz (EFV) 63.0 mg/kg], group II (HAART+AG525 mg/kg), group III (HAART and AG 525 mg/kg after a 2-h interval). Drug concentrations of AZT were determined by high performance liquid chromatography-mass spectroscopy (HPLC-MS) before HAART, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h after HAART, respectively. Pharmacokinetic parameters [such as t1/2, Tmax, Cmax, AUCo-t, plasma clearance rate (CL)] were calculated by DAS2.0 Software.

RESULTSThe-equation of linear regression of AZT was good, with the precision, coefficient of recovery, and stability definitely confirmed. AUC in group II and III was larger than that of group I. There was no statistical difference in t1/2, Tmax, Cmax, AUC0-12 h, or AUC0-∞ among groups (P > 0.05).

CONCLUSIONAG combined HAART could enhance the Cmax of AZT.

Animals ; Antiretroviral Therapy, Highly Active ; Benzoxazines ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; Mass Spectrometry ; Rats ; Zidovudine ; pharmacokinetics ; pharmacology

There are 250 species of Zanthoxylum (Rutaceae) in the world. This genus distributed in tropical and subtropical regions. Alkaloids are the major and representative ingredients in these plants including quinolines, isoquinolines, and amide alkaloids, with such biological activities as anti-tumor, anti-inflammatory, analgesic, anti-virus, anti-platelet aggregation, anti-bacteria and anti- oxidant. These species have been used for a long time to treat toothache, urinary and venereal diseases, lumbago and rheumatism. This review summarizes the chemical constituents and pharmacological activities from the Z. sppplants, in an effort to the systematic research and application of the alkaloids of this genus.
Alkaloids ; chemistry ; pharmacology ; Animals ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Zanthoxylum ; chemistry

Anti-Infective Agents ; pharmacology ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Medicine, Chinese Traditional ; Phytotherapy ; Research Design

AIM: To investigate the differences of Alzheimer's disease(AD)-related parameters in the SAM-P/8, the SAM-R/1 and the Kunming mice.METHODS: The changes of ethology, neurobiochemistry (true choline esterase, TchE), ultrastructure and gene expression(gene chips) were determined in mice of three groups: SAM-P/8 mice (n=14), SAM-R/1 mice (n=14) and Kunming mice (n=14), which were 6 months old[weight(20?5)g].RESULTS: The SAM-P/8 mice had the inabilities of learning and memory compared with the SAM-R/1 mice and the Kunming mice (P

OBJECTIVETo observe the effects of tetrandrine (Tet) on the pulmonary capillary permeability in rats with acute lung injury induced by intravenous injection of lipopolysaccharide (LPS).

METHODSThirty-two healthy male Wistar rats were randomly divided into 4 groups: the model group, the normal group, the Tet prevention group and the Tet treatment group, 8 in each group. All rats except those in the normal group, were established into acute lung injury model by intravenous injection of LPS. Intravenous injection of Tet (20 mg/ kg) were given to the Tet prevention group 30 min before and to the Tet treatment group 30 min after modeling respectively, and equal volume of normal saline was given to the other two groups instead. Arterial blood samples were collected to determine PaO2 and PaCO2 at the time points of immediately after modeling (0 h), 0.5 h, 2 h, 4 h, 6 h. The animals were sacrificed by the end of the experiment, the wet/dry weight ratio of lung (W/ D), neutrophil percentage in bronchoalveolar lavage fluid (BALF), concentration of TNF-a in peripheral blood and BALF by ELISA, and content of malonaldehyde (MDA) in lobus inferior pulmonis homogenate by thio barbituric acid colorimetric method were determined. Pathological change of the upper lobe of lung was examined and lung injury was scored as well.

RESULTSAs compared with that in the model group, the level of PaO2 was higher in Tet prevention group at 0.5 h, 2 h, 4 h, 6 h and in the Tet treatment group at 2 h, 4 h, 6 h (P< 0.05); and the content of TNF-alpha, MDA and neutrophil percentage in BALF, as well as W/D and lung injury score were lower in the Tet prevention group and the Tet treatment group (P <0.05). Pathological changes of lung in the two Tet groups were all better than those in the model group.

CONCLUSIONEarly intervention with tetrandrine shows a protectiv effect on rats against acute lung injury induced by intravenous injection of LPS.

Acute Lung Injury ; chemically induced ; pathology ; physiopathology ; Animals ; Benzylisoquinolines ; pharmacology ; Capillary Permeability ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Lipopolysaccharides ; Lung ; blood supply ; Male ; Random Allocation ; Rats ; Rats, Wistar

To study the effect of Wansheng Huafeng Dan (WSHFD) and mercuric chloride on renal mercury (Hg) extraction transporters (Oat1, Oct2), renal mercury excretion transporters (Mrp4, Mate2K), renal mercury accumulation and kidney injury molecule-1 (Kim-1). The ancient prescription of WSHFD containing 10-fold Hg caused much lower renal mercury accumulation and renal toxicity than HgCl2 in rats, with less effect on renal transporters than HgCl2. The above indicators had no significant difference in WSHFDO, WSHFD2 and WSHFD3 groups, indicating no effect of WSHFD with reduced or no cinnabar.
Animals ; Ardisia ; chemistry ; Biological Transport ; drug effects ; Cell Adhesion Molecules ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Gene Expression ; drug effects ; Kidney ; drug effects ; metabolism ; Male ; Mercuric Chloride ; metabolism ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective To investigate technical skills on outflow reconstruction in right lobe graft adult-adult living donor liver transplantation for avoiding of venous congestion. Methods The clinical data of 21 donors and recipients who underwent right lobe living donor liver transplantation were analyzed retrospectively. Donor's standard liver volume was between 1150. 1 and 1629. 8 cm3,graft weight was between 585 and 920 g, the ratio of graft volume to recipient's estimated standard liver volume (GV/ESLV) was between 43 % and 67 %, graft-recipient weight ratio (GRWR) was between 0. 82 % and 1.59 %, the ratio of remnant liver volume to donor's standard liver volume(RLV/SLV) was between 32 % and 55 %, all graft macrosteatosis was less than 10 %. For graftwith middle hepatic vein (MHV), a triangle large orifice was made by joining MHV to right hepatic vein (RHV), then anastomosed to recipient' s enlarged orifice of RHV. For graft without MHV, if tributary of MHV＞5 mm, autologous or allogenic blood vessel was used as interposition graft to connect to IVC, and if no large MHV tributary, graft RHV was anastomosed to IVC directly. Graft's right portal vein was anastomosed to main trunk of recipient's portal vein, graft's right hepatic artery to recipient's hepatic artery, and graft's right hepatic duct to recipient's right hepatic duct. Results Among the 21 right lobe grafts, 4 right lobe grafts had MHV, 17 right lobe grafts had no MHV.Autologous greater saphenous veins were adopted in 2 cases, cryopreserved iliac arteries were adopted in 5 cases, and RHV was anastomosed directly to IVC in 10 cases. Outflow was all patent in 7 cases having reconstruction of MHV tributaries one month after operation. One-year survival rate was 75 %, 85. 7 % and 70 % respectively in MHV group, MHV tributaries reconstructed group and RHV directly anastomosed to IVC group with the difference being not significance among these three groups (P＞0. 05). Biliary complications occurred in 7 cases during the follow-up period. One case developed small-for-size syndrome, which was cured by splenic artery embolization. No severe complication occurred in donors. All donors returned to normal life during a follow-up period of 6 to 31 months. Conclusion If outflow tract was reconstructed properly, right lobe graft without MHV has equivalent clinical outcomes to right lobe graft with MHV. Using of autologous or allogenic blood vessel as interposition vessel graft for right lobe graft without MHV is an effective modality to prevent hepatic congestion and secure functional graft volume to meet recipients metabolic demand.

OBJECTIVETo observe the impairing effects of triptolide on liver mitochondria in isolated rat-liver mitochondria and human normal liver HL7702 cell line.

METHODSRat-liver mitochondria were isolated from adult female Sprague-Dawley (SD) rats. Liver mitochondria were incubated with 0, 1.25, 2.5, 5 and 10 μmol/L triptolide for detecting mitochondrial swelling and with 0, 2.5, 5 and 10 μmol/L triptolide for mitochondrial permeability transition pore (MPTP) activity. Mitochondrial swelling was estimated by measuring the apparent absorbance change during 600 s in the mitochondrial suspensions at 520 nm with a mitochondrial swelling examining kit. The effect of triptolide on MPTP was determined with a fluorescence detection kit by detecting the fluorescence intensity at an excitation wavelength of 488 nm emitted at 527 nm. Human normal liver HL7702 cells were treated without or with 0.02, 0.1 and 0.5 μmol/L triptolide for 24 h for analyzing mitochondrial transmembrane potential (Δψm) and reactive oxygen species (ROS). Δψm was measured using the fluorescent probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1). ROS was measured using fluorescent probe 2',7'-dichlorofluorescin diacetate (DCFH-DA). The cells were harvested and dyed with JC-1 and DCFH-DA, and analyzed by flow cytometry, respectively.

RESULTSIncubation of isolated mitochondria with triptolide results in swollen mitochondria in a concentration-dependent manner. Moreover, triptolide significantly activated mitochondrial permeability transition at 5 and 10 μmol/L (P<0.05 and P<0.01). When HL7702 cells were exposed to a various concentration triptolide for 24 h, mitochondrial membrane depolarization and increase of ROS were caused by triptolide in a concentration-dependent manner. Triptolide significantly induced the mitochondrial membrane depolarization at 0.1 and 0.5 μmol/L (P<0.05 and P<0.01) and the increase of ROS at 0.1 and 0.5 μmol/L (P<0.05 and P<0.01).

CONCLUSIONTriptolide could induce mitochondrial impairment, which may be one of the mechanisms by which hepatotoxicity occurs.

Animals ; Cell Line ; Diterpenes ; chemistry ; pharmacology ; Epoxy Compounds ; chemistry ; pharmacology ; Female ; Humans ; Membrane Potential, Mitochondrial ; drug effects ; Mitochondria, Liver ; drug effects ; metabolism ; Mitochondrial Membrane Transport Proteins ; metabolism ; Mitochondrial Swelling ; drug effects ; Phenanthrenes ; chemistry ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism

Objective To review the techniques used in biliary reconstruction for adult-adult living donor liver transplantation using a right lobe graft. Methods The clinical data of 21 pairs of donor and recipient who underwent right lobe living donor liver transplantation from April 2007 to May 2009 at Beijing Youan Hospital were analyzed retrospectively. Biliary anastomoses consisted of 10 single right hepatic duct to common hepatic duct anastomoses, 5 donor double branched ducts to recipient double branched ducts anastomoses, 5 single anastomoses between a donor double branched duct which had been converted to a single duct by ductoplasty to a single recipient bile duct, and 1 hepaticojejunostomy. A T-tube was inserted through the anterior wall of the common hepatic duct and splinted across the anastomosis in 2 recipients and a Y-tube was used in 1 recipient. Results 4 recipients died during the first post-transplant month. Another recipient received a retransplantation for acute liver necrosis. The remaining recipients were alive. The 1-year survival rate of the recipients was 77.65 %.5 patients developed biliary leakage and 2 patients developed biliary stricture. The 7 biliary complications were treated and cured by further surgical procedures. There was no significant difference in the biliary complications among the three different types of biliary anastomotic groups (x2 = 0. 659,P=0. 719). Conclusion The different types of biliary anastomoses can be used in living donor liver transplantation depending on the situations found in the donors and recipients. Continuous suturing on the posterior wall of the bile duct, interrupted suturing on the anterior wall and microsurgical techniques in biliary reconstruction are effective modalities to minimize biliary complications.

To determine whether Smac/DIABLO (second mitochondrial activator of caspases/direct inhibitor of apoptosis protein-binding protein of low isoelectric point [PI]) and XIAP (X-chromosome-linked inhibitor of apoptosis protein) serve to regulate neuronal apoptosis following seizures, we investigated seizure-induced changes in caspase-9, Smac/DIABLO and XIAP protein expression and the in vivo effect of caspase-9 inhibition. Animals received unilateral intra-amygdaloid injection of kainic acid (0.5 microg) to induce seizures for 1 h. The seizures were then terminated by diazepam (30 mg/kg). Animals were killed 0, 2, 4, 8, 24 or 72 h following diazepam administration. The apoptotic and surviving neurons in hippocampus were observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and cresyl violet staining, the expression of Smac/DIABLO, XIAP and caspase-9 was detected with immunofluorescence and western blot. The results showed that the levels of XIAP and the 46-kDa proenzyme form of caspase-9 were unaffected by the seizures. The expression of Smac increased at 2 h and the 37-kD cleaved fragment of caspase-9 was detected at 4 h, TUNEL-positive neurons appeared at 8 h and reached maximal at 24 h following seizure cessation within the ipsilateral (the same side as the intra-amygdaloid injection of kainic acid) CA3 subfield of the hippocampus. Intracerebroventricular infusion of caspase-9 inhibitor z-LEHD-fluoromethyl ketone (z-LEHD-fmk) significantly decreased TUNEL-positive neurons and increased the number of surviving cells. Caspase-9 immunoreactivity increased and Smac/DIABLO, XIAP immunoreactivity became extensive within the ipsilateral CA3 neurons. TUNEL-positive neurons and the alterations of the expression of Smac/DIABLO and XIAP within the ipsilateral CA3 were not detected within the contralateral hippocampus. These results suggest that seizures lead the translocation of Smac/DIABLO into the cytosol, the activation of caspase-9 and the change of subcellular locoalization of XIAP. These changes may play a role in the brain damage induced by seizures. Caspase-9 is possibly a potential therapeutic target in the treatment of brain injury associated with seizures.
Amygdala ; physiology ; Animals ; Caspase 9 ; Caspases ; biosynthesis ; genetics ; Complement Membrane Attack Complex ; Complement System Proteins ; Glycoproteins ; biosynthesis ; genetics ; Hippocampus ; metabolism ; Kainic Acid ; Limbic System ; Male ; Microinjections ; Protein Biosynthesis ; Proteins ; genetics ; Rats ; Rats, Sprague-Dawley ; Seizures ; chemically induced ; metabolism ; X-Linked Inhibitor of Apoptosis Protein