Objective: To study the mechanisms of absorption and transport of 3-acetyl-11-keto-β-boswellic acid (AKBA) from Boswellia carterif in Caco-2 cell, MDCK-MDR1, and MDCK-Wild cell models. Methods: The Caco-2, MDCK-MDR1, and MDCK-Wild cell monolayer models were used to study the bi-directional transport of AKBA in apical (AP)→basal (BL) or BL→AP; The concentration of AKBA was measured by LC-MS/MS and apparent permeability coefficient (Papp) was calculated. Results: Papp (AP→BL) and Papp (BL→AP) values of AKBA (50 μmol/L) in Caco-2 cell model were 7.9 × 10-7 and 1.5 × 10-7 cm/s, respectively; Papp (AP→BL) and Papp (BL→AP) values of AKBA (50 μmol/L) in MDCK-MDR1 cell model were 2.6 × 10-7 and 0.8 × 10-7 cm/s, respectively; Papp (AP→BL) and Papp (BL→AP) of AKBA (50 μmol/L) in MDCK-Wild cell model was 2.4 × 10-7 and 0.6 × 10-7 cm/s, respectively; The rates of efflux (RE) for AKBA in Caco-2 and MDCK-MDR1 cell monolayers were both smaller than 2. Conclusion: AKBA is not the substrate of P-gp and its absorption rate is low. AKBA is absorbed through the intestinal epithelial cells by active transport absorption and passive diffusion possibly.

Objective: In this study, primary cultured human hepatocytes were used to study the induction of P450 enzyme by the sesquiterpene lactone derivative ACT001, which provided reference for the clinical use of ACT001. Methods Three batches of frozen primary human hepatocytes were inoculated and cultured, and CYP1A2, CYP2B6 and CYP3A4 were induced by ACT001. Real-time fluorescence quantitative PCR was used to determine the mRNA expression level of P450 enzyme, and the activity of P450 enzyme was determined by LC-MS/MS method. Results The expression level of P450 enzyme mRNA and the activity of P450 enzyme showed that the P450 enzyme induction model was successfully established. Compared with the control group, the CYP1A2 mRNA expression level and enzyme activity of ACT001 1 μmol/L and 6 μmol/L group showed no significant changes. The mRNA expression level of CYP1A2 in ACT001 30 μmol/L group was significantly decreased, and the enzyme activity was decreased, but not as significantly as that of mRNA. With the increase of ACT001 concentration, the expression level of CYP2B6 mRNA was gradually increased. Compared with the control group, the expression level of CYP2B6 mRNA in the ACT001 group at 30 μmol/L was significantly increased, which was seven times higher than that in the control group, and the increase of enzyme activity was four times higher than that in the control group, which was 40% higher than that in the phenobarbital sodium induction multiple. Compared with the control group, the CYP3A4 mRNA expression level of cells in the ACT001 1 μmol/L group was significantly increased, which was four times higher than that of the control group, but did not reach 40% of the positive inducer rifampicin, and the CYP3A4 mRNA expression level was decreased gradually with the increase of ACT001 concentration. At the same time, there was no significant increase in CYP3A4 enzyme activity after ACT001 administration at different concentrations, which was less than two times of that in the control group. Conclusion The data indicated that ACT001 had no induction potential for CYP1A2 and CYP3A4, and had potential for CYP2B6 induction. In combination with CYP2B6 substrates, it should be avoided in clinical combination therapy to reduce adverse reactions caused by P450-mediated drug drug interaction.

OBJECTIVETo establish determination method of formic acid, lactic acid, acetic acid and succinic acid in dental plaque with high performance liquid chromatography (HPLC).

METHODSAfter the samples were centrifuged, 2 microL supernatant was transferred to a 1 mL centrifuge tube and diluted in water, then was determined with HPLC. The mixture of phosphate buffer and methanol (97:3) as mobile phase throughout the experiment. The determination of organic acid was performed on Phenomenex C18 column and at their maximum absorption wave.

RESULTSThe linear ranges of formic acid, lactic acid, acetic acid and succinic acid were 0.110-500, 0.049-500, 0.047-500, 0.084-500 microg/mL. The detection limits were 0.110, 0.049, 0.047, 0.084 microg/mL. The relative standard derivation were 9.5%, 7.9%, 4.3%, 4.2%. The average recoveries of samples were 82%-112%, 82%-102.5%, 90%-115%, 80%-110%.

CONCLUSIONThe method was simple, quick and adapt for analysis of organic acid in dental plaque.

Chromatography, High Pressure Liquid ; Dental Plaque ; Formates

OBJECTIVETo analyze the complication rate and survival rate of the patients whose graft-recipient weight ratio (GRWR) less than 0.8% following living donor liver transplantation (LDLT).

METHODSThere were 92 consecutive LDLT patients from January 2001 to December 2007 in West China Hospital, Sichuan University. There were 85 males and 7 females aged from 18 to 65 years old (averaged, 42 years old) and among which 89 patients were involved in the study. There were 15 patients whose GRWR less than 0.8% (group 1), while other 74 recipients were in group 2. Comparing the two groups' complication rates and survival rates and finding out the potential influencing factor of small-size-graft recipients' survival rate.

RESULTSThe survival rates of group 1 and group 2 were 73.3% (11/15) and 71.6% (53/74), respectively. The grade II-V complication rates of group 1 and group 2 were 46.7% (7/15) and 48.6% (36/74), respectively. There were no difference in survival rates (chi(2) = 0.058, P = 0.811) and complication rates (chi(2) = 0.000, P = 1.000) between the two groups. Ascites volume of group 1 and group 2 were (1532 +/- 322) ml and (1466 +/- 110) ml, respectively (t = 0.234, P = 0.815). The condition of the graft's middle hepatic vein had significant influence on small-size-liver recipients' survival rates (chi(2) = 6.821, P = 0.009).

CONCLUSIONSGRWR < 0.8% is not the limitation of the living donor liver transplantation but the outflow tract of the graft must be unobstructed.

Adolescent ; Adult ; Aged ; Female ; Follow-Up Studies ; Graft Survival ; Humans ; Liver Transplantation ; Living Donors ; Male ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; Survival Analysis ; Young Adult

OBJECTIVETo analyze risk factors of marginal donors in living donor liver transplantation.

METHODS98 living donor liver transplantation (LDLT) patients over the 7-year period from 2001 to 2007 in our transplantation center were retrospected. Potential risk factors, including donor age, gender-mismatch, steatotic donors and graft-recipient weight ratio (GRWR), and their relationship with 6-month patient survival rate were analyzed.

RESULTSThe 4 patients received livers with more than 30% steatosis died within 6 months, and 6-month survival rate was 91.7% in patients received livers with less than 30% steatosis. The 6-month survival rate was 86.9% and 87.8% in patients with grafts of GRWR more than 0.8% and in patients with graft of GRWR less than 0.8%, respectvely (x2=0.022, P more than 0.05), however, middle hepatic vein reconstruction significantly affected the survival rate of small-size-liver recipients (x2=10.612, P less than 0.01). Donor age and gender-mismatch were not associated with the survival rate of recipients (P more than 0.05).

CONCLUSIONSSteatosis is an important risk factor in living donor liver transplantation. Lower GRWR is not a limitation but we must reconsider its importance in liver transplantation. The donor age and gender-mismatch are not associated with the survival rate of recipients.

Humans ; Liver Transplantation ; Living Donors ; Organ Size ; Risk Factors

The src homology 2 (SH2)-domain containing inositol-5-phosphatase (SHIP) is another recently identified lipid phosphatase after phosphatase and tensin homology deleted on chromosome ten gene (PTEN). It plays an important role in negatively regulating the proliferation of hematopoietic cells. The relationship between SHIP and the inhibition of tumor proliferation is rarely reported. The purpose of this study is to evaluate the apoptosis induced by SHIP gene in K562 cell line and to explore the involved signaling pathway. The K562 cells were transfected with human SHIP gene by using the lentiviral vector containing SHIP, and the transfection was verified by fluorescent quantitative PCR (FQ-PCR) and Western blot. Then the effects of SHIP protein expression on cell growth and apoptosis were measured. The levels of p-Akt, bcl-2 family, caspase and the activity of NFkappaB were assayed by Western blot and ELISA, respectively. The results are as follows: (1) Human leukemia cell line K562 was SHIP-negative; (2) Transfection with SHIP gene led to the re-expression of SHIP mRNA and protein in K562, as shown by FQ-PCR and Western blot; (3) The expression of SHIP protein inhibited cell growth and significantly increased apoptosis in K562 cells; (4) Compared to that in control group, the expression level of p-Akt-308 and p-Akt-473 in SHIP-expressing cell group decreased significantly (P<0.01); SHIP activated caspase-9, caspase-3, up-regulated protein levels of bad, p27, down-regulated expression of bcl-xL, while it had no effect on the expression of bcl-2 and bax. Furthermore, the inhibition of NF-kappaB was achieved along with the inactivation of Akt. These data suggest that SHIP gene has potential abilities to inhibit K562 leukemic cell proliferation and induce its apoptosis via inactivating PI3K/Akt pathway. The loss of SHIP might be the explanation of aberrant high-level p-Akt in human leukemia. It may be at least one of the mechanisms by which the loss of SHIP expression contributes to leukemia progression.
Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Cell Proliferation ; Down-Regulation ; Genetic Vectors ; Humans ; Inositol Polyphosphate 5-Phosphatases ; K562 Cells ; NF-kappa B ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphoric Monoester Hydrolases ; genetics ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; Transfection

OBJECTIVESince 2011 EB-APS conference, we hypotheses that phase switching of inspiration-expiration is dominantly initiated by oscillatory information PaO2, PaCO2 and [H+] via fast peripheral chemical receptors. However, the evidence of the waveform of ABG is lack.

METHODSSix surgery patients with normal heart function and negative Allen test, had been placed the arterial catheterization directly connected to 3 x 1 000 mm pre-heparin plastic pipe for continuous collecting arterial blood. We counted the number of heart beat for the blood collecting time, and separated the blood pipe into the heart beat numbers' short pieces using haemostatic forceps, then put pipe into iced water at once fir analyzing PaO2, PaCO2, pH and SaO2 as soon as possible. We selected two breaths cycles of waveform from each patient for data calculations of magnitudes and time interval.

RESULTSThe heart beat numbers for filling blood into pipe were 16 ± 2, and all covered more than 2 breathing cycles. Each breathing cycle is cover 5 ± 0.6 heart beat. There were significant changes of PaO2, PaCO2, [H+] a and SaO2 (i.e. the highest high values compare to the next lowest values, P < 0.05). The time interval of changing PaO2, PaCO2, [H+]a and SaO2 magnitudes were 11.28 ± 1.13 mmHg, 1.77 ± 0.89 mmHg, 1.14 ± 0.35 nmol/L and 0.52% ± 0.44% respectively.

CONCLUSIONThis simple continuous beat-by-beat arterial blood sampling and ABG analyzing method is new and practicable. We obtain a clear evidence of periodic parameters ABG waveform, which following breathing cycle.

Arteries ; physiology ; Blood Gas Analysis ; Heart Rate ; Humans ; Monitoring, Physiologic ; methods ; Respiration

Diving medicine is one of the branches of military medicine, and plays an important role in naval development. This review introduces the progress of researches on undersea and hyperbaric physiology and medicine in the past few years in China. The article describes our research achievement in conventional diving and its medical support, researches on saturation diving and its medical support, submarine escape and its medical support, effects of hyperbaric environments and fast buoyancy ascent on immunological and cardiological functions. Diving disorders (including decompression sickness and oxygen toxicity) are also introduced.
China ; Decompression Sickness ; Diving ; physiology ; Humans ; Military Medicine ; Submarine Medicine

This study is to establish an artificial neural network (ANN) for predicting blood tacrolimus concentration in liver transplantation recipients. Tacrolimus concentration samples (176 samples) from 37 Chinese liver transplantation recipients were collected. ANN established after network parameters were optimized by using momentum method combined with genetic algorithm. Furthermore, the performance of ANN was compared with that of multiple linear regression (MLR). When using accumulated dose of 4 days before therapeutic drug monitoring (TDM) of tacrolimus concentration as input factor, mean prediction error and mean absolute prediction error of ANN were 0.02 +/- 2.40 ng x mL(-1) and 1.93 +/- 1.37 ng x mL(-1), respectively. The absolute prediction error of 84.6% of testing data sets was less than 3.0 ng x mL(-1). Accuracy and precision of ANN are superior to those of MLR. The correlation, accuracy and precision of ANN are good enough to predict blood tacrolimus concentration.
Adult ; Aged ; Drug Monitoring ; methods ; Female ; Humans ; Immunosuppressive Agents ; blood ; Linear Models ; Liver Transplantation ; Male ; Middle Aged ; Neural Networks (Computer) ; Tacrolimus ; blood

Objective:To observe the effect of moxibustion on the protein and mRNA expressions of corticotropin-releasing factor (CRF)and corticotropin-releasing factor receptor 1 (CRFR1) in hypothalamus of trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis rats,and to explore the central mechanisms of moxibustion in improving visceral pain and the pain-related emotions in experimental colitis rats.Methods:Thirty-six Sprague-Dawley (SD) rats were randomly divided into a normal group (NG),a model group (MG),a herb-partitioned moxibustion group (HPMG) and a sham herb-partitioned moxibustion group (SHPMG).Except the NG,rats in the remaining three groups all received TNBS enema to establish experimental colitis models.The HPMG received herb-partitioned moxibustion (HPM) at bilateral Tianshu (ST 25) and Qihai (CV 6) for intervention;for the SHPMG,the herbal cakes and moxa cones were only placed on the acupoints but not ignited;rats in the MG and NG were only fixed in the same way as those in the HPMG but did not receive any treatment.At the end of the intervention,the abdominal withdrawal reflex (AWR) score,the open field test (OFT) score and the elevated plus maze (EPM) score were observed to measure the changes in visceral pain and pain-related emotions of the rats.The enzyme-linked immunosorbent assay (ELISA) was used to examine the expressions of CRF and CRFR1 proteins in hypothalamus;the fluorescence-based quantitative polymerase chain reaction (PCR) was used to detect the expressions of CRF and CRFR1 mRNAs in hypothalamus.Results:Compared with the NG,the AWR score increased significantly and the OFT and EPM scores dropped significantly in the MG (all P＜0.05),and the expressions of hypothalamic CRF and CRFR1 proteins and mRNAs increased significantly (all P＜0.01).Compared with the MG and SHPMG,the AWR score dropped significantly and the OFT and EPM scores increased significantly in the HPMG (all P＜0.01),and the expressions of hypothalamic CRF and CRFR1 proteins and mRNAs decreased significantly (all P＜0.05).There were no significant differences between the MG and the SHPMG (all P＞0.05).Conclusion:HPM can down-regulate the abnormally increased expressions of CRF and CRFR1 proteins and mRNAs in hypothalamus of the TNBS-induced experimental colitis rats,which is plausibly one of its action mechanisms in mitigating visceral pain and the pain-related emotions in the experimental colitis rats.