The study is to investigate the pharmacokinetics of S-1 capsule (tegafur, gimeracil and potassium oxonate capsule) in patients with advanced gastric cancer after single and multiple oral administration. Twelve patients with advanced gastric cancer were recruited to the study. The dose of S-1 for each patient was determined according to his/her body surface area (BSA). The dose for single administration was 60 mg every subject. The dose for multiple administration for one subject was as follows: 100 mg x d(-1) or 120 mg x d(-1), 28-days consecutive oral administration. The pharmacokinetic parameters of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil after single oral administration were as follows: (2,207 +/- 545), (220.0 +/- 68.2), (374.9 +/- 103.0), (110.5 +/- 100.8) and (831.1 +/- 199.9) ng x mL(-1) for Cmax; (11.8 +/- 3.8), (4.4 +/- 3.3), (7.8 +/- 5.1), (3.1 +/- 0.9) and (8.8 +/- 4.1) h for t1/2, respectively. After six days oral administration, the average steady state plasma concentrations (Cav) of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil were (2,425 +/- 1,172), (73.88 +/- 18.88), (162.6 +/- 70.8), (36.89 +/- 29.35) and (435.3 +/- 141.0) ng x mL(-1), respectively, and the degree of fluctuation (DF) were (1.0 +/- 0.2), (2.5 +/- 0.4), (3.1 +/- 0.8), (2.4 +/- 0.8) and (1.5 +/- 0.3), respectively. The cumulative urine excretion percentage of tegafur, 5-fluorouracil, gimeracil and potassium oxonate in urine within 48 h were (4.2 +/- 2.8) %, (4.7 +/- 1.6) %, (18.5 +/- 6.0) % and (1.7 +/- 1.2) %, repectively, after single oral administration of S-1. The results exhibited that tegafur had some drug accumulation observed, and gimeracil, potassium oxonate, 5-fluorouracil and uracil had no drug accumulation observed.

ObjectiveTo investigate the relationship between the level of plasma D-dimer(D-D) and hepatic functional reserve status in patients with hepatitis B (HB).Methods77 cases with HB were divided into two groups, hepatic function compensated group and hepatic function decompensated group.Plasma D-D, hepatic functional indexes and PT of all patients were detected.ResultsThe level of D-D in the hepatic function decompensated group was higher than that in the hepatic function compensated group(299.0 ± 498.5) μg/L vs (27.9 ± 34.0) μg/L(t =3.1, P ＜ 0.01).D-D negatively correlated with ALB and PA(r =-0.6,-0.6, all P ＜ 0.01), and positively correlated with TBIL and PT(r = 0.4,0.6, all P ＜ 0.01).ConclusionThe level of plasma D-D related with hepatic functional reserve status,and detecting the level of D-D could be helpful to estimate hepatic functional reserve and prognosis of patients with HB.

Objective To study the effect of methylmercury on the behavioral teratogenesis in filial r ats.Method Pregnant rats were injected intra-abdominally with 0 ,0.75,1.50,3.00 mg/kg methylmercury every other day,then early physiological fun ctions and behavioral functions of their filial rats were observed. Results The results indicated that when impregnated female ra ts were heavily exposed to methylmercury, early physiological development and be havioral development of their filial rats were retarded.Conclusion The methylmercury likely has the effect on behavioral teratogenesis of rats. J Appl Clin Pediatr,2005,20(2):153-155

BACKGROUND:Mesenchymal stem cel transplantation has a certain controversy in the treatment of liver cirrhosis, and its effects on the receptor liver structure and function need further studies.
OBJECTIVE:To study the changes in liver ultrastructure, stereology parameters and liver function indexes of rat models with liver cirrhosis treated by bone marrow mesenchymal stem cel transplantation.
METHODS:Rat models of liver cirrhosis were made using carbon tetrachloride and treated by bone marrow mesenchymal stem cel transplantation. Liver ultrastructure of al the rats were observed by transmission electron microscope, the stereology parameters of the hepatic sinusoid were analyzed by a stereology analysis software, and the serum liver function indexes were detected by a biochemical analyzer.
RESULTS AND CONCLUSION: (1) The hepatic cels in the rat models exhibited acute hypoxia, lots of mitochondria were destroyed, and obvious karyopycnosis and capilarization of the hepatic sinusoid were found. The liver ultrastructure of rats undergoing cel transplantation was improved remarkably, the hepatic cel nucleus was nearly normal, mitochondrial sweling relieved notably and nuclear pore clogging lessened. (2) The number of hepatic sinusoids in the model group was reduced dramaticaly, but the total area and mean diameter of the hepatic sinusoid were enlarged significantly as compared with the cel transplantation and normal groups (P < 0.05). (3) Compared with the model group, the albumin level was significantly increased, but the levels of alanine aminotransferase and direct bilirubin were significantly decreased in the cel transplantation (P < 0.05). In addition, there was no significant difference in the level of aspartate aminotransferase between the model and cel transplantation groups (P > 0.05). These findings indicate that bone marrow mesenchymal stem cel transplantation can improve liver function and structure of rats with liver cirrhosis and lessen pathological changes of hepatic sinusoid, so it is an effective treatment for liver cirrhosis.

Aim Bupivacaine is a kind of long-acting amide local anesthetics.This paper aims to explore the effects of bupivacaine on the short-circuit currents in human alveolar epithelial monolayers and study the possible mechanisms.Methods Short-circuit currents were recorded by ussing-chamber setup.Amiloride-sensitive currents were defined as the difference be-tween the total current and the amiloride-resistant cur-rent.ERK1 /2 phosphorylation protein levels were ana-lyzed by Western blot at 0,1 5,30 and 60 min after administration of 1 00 μmol·L -1 bupivacaine.Results Bupivacaine could inhibit the short-circuit currents in H441 monolayers dose-dependently,which could be inhibited by amiloride.Western blot analysis showed that bupivacaine increased the level of ERK1 /2 phos-phorylation.Conclusion These data demonstrate that bupivacaine can reduce the alveolar ion transport by in-hibiting the amiloride-sensitive currents,possibly by the enhancement of ERK1 /2 phosphorylation. The effects of alveolar fluid clearance following application of bupivacaine should be considered clinically when the patient is complicated with lung injury.

Objective: To establish a method to determine 4 active ingredients in Jindan tablets by HPLC.
Methods: Agilent Eclipse X DB C₁₈ (4.6 mm×250 mm, 5 μm) column was adoped using acetonitrile (phase A) -0.1% phophoric acid solution (phase B) as the mobile phase with gradient program at the flow rate of 1.0 mL·min^-1, the detection wavelength was 270 nm, Column temperature was set at 30 ℃.
Results: The linear ranges of gentiopicrin, polydatin, quercetin and emodin were 7.875-78.75 μg·mL^-1（r=0.999 9）, 6.75-67.50 μg·mL^-1（r=0.999 7）, 7.726-77.26 μg·mL^-1（r=0.999 4）, 3.809-38.09 μg·mL^-1（r=0.999 8), respectively, the peak area had a good linear relationship with the mass concentration of 4 components, the average recovery were 99.31%, 99.21%, 99.04%, 99.59%, (n=6) respectively, and RSDs were 1.86%, 1.24%, 1.37%, 1.15%, respectively.
Conclusion: This method is reliable, repeatable and stable, and has strong specificity. This method can provide a reference for the quality control and standard improvement of Jindan tablets.

AIM:To investigate the effects of celecoxib,a selective cyclooxygenase-2 inhibitor,on antioxidative capability and apoptosis of cardiac myocytes after myocardial infarction.METHODS:24 New Zealand rabbits were divided into three groups randomly(8 in each group):sham-operated group(sham group),myocardial infarction group(MI group),celecoxib group(Cele group,10 mg kg-1?d-1,qd,with the drugs gastric gavage for six weeks).The NO concentration,total antioxidative capability(T-AOC),the activity of constitutive nitric oxide synthase(cNOS)and inducible NOS(iNOS)in cardiac tissue homogenate,adjacent to the infracted area,were detected.The pathological changes were observed by light microscope and electron microscopy.The expressions of Bcl-2 and Bax protein in myocytes were observed using immunohistochemistry,and the degree of apoptosis were examined by TUNEL.RESULTS:Cardiac tissue in MI group presented interstitial edema,fibroplastic proliferation,inflammatory cellular infiltration,and vacuolar degeneration in cardiac myocytes.The results of electron microscopy showed that myocytes presented more changes caused by ischemic injury:widened interspace of myofibril,disordered myofibrillae,focal lysis of myofilament,ectasia of sarcoplasmic reticulum.In Cele group,the pathological changes were light,the NO-_2/NO-_3 concentration,the activity of iNOS were lower(P

Aged ; Humans ; Male ; Neoplasms, Muscle Tissue ; Skull Neoplasms ; Temporal Bone ; pathology

Background and purpose:Carcinoma of the kidney is the most common malignant renal parenchymal carcinoma;its biological behavior is extremely complicated and is not sensitive to radiotherapy and chemotherapy.Studies have shown that the hypoxia-inducible factor HIF1-? and HIF2-? are related to the occurrence and development process of the clear-cell carcinoma of kidney.So,we intend to construct psilencer3.0-HIF-? siRNA recombinant plasmid in this study through RNA interference method,thereby providing an effective tool for further exploration of the role of HIF in the occurrence and development of clear-cell carcinoma of kidney.Methods:Design and chemically synthesize the DNA fragments of coding HIF-1? and HIF-2? siRNA and make them up into siRNA expression vector through gene recombination.Adopting the real-time quantitative PCR and Western blot tested the inhibitive effect of the constructed siRNA expression vector on mRNA and protein levels on the target gene expression.Results:After 786-0 cells transfecting with psilencer3.0-HIF-1?siRNA and psilencer3.0-HIF-2?,the inhibitory rate of mRNA expression of HIF-1? and HIF-2? reached 82.1% and 87.4% respectively,and OS-RC-2 cells transfecting psilencer3.0-HIF-1? siRNA and psilencer3.0-HIF-2?,the inhibition rate reached 91.2% and 81.2% respectively.The protein expression of the experimental group with 786-0 cells and OS-RC-2 cells transfecting HIF-1? interference plasmid and HIF-2? interference plasmid were lower at different levels than that from the blank control group.Conclusions:The constructed siRNA expression vector can effectively inhibit the expression of target gene HIF-1 and HIF-2 at mRNA and protein levels.

The purpose of the study was to observe the effect of rapamycin (RAPA) on the differentiation and maturation of rat bone marrow-derived dendritic cells (BMDCs) in vitro. BMDCs from Wistar rats were cultured with granulocyte-macrophage colony-stimulating factor plus interleukin-4 in the presence or absence of RAPA (20 ng/mL), and stimulated with lipopolysaccharide (LPS) for 24 h before cells and supernatants were collected. Surface phenotype of BMDCs was flow-cytometrically detected to determine the expression of maturation markers, MHC class II and CD86. Supernatants were analyzed for the production of IL-12 and IFN-gamma cytokines by using ELISA. BMDCs were co-cultured with T cells from Lewis rats and mixed lymphocyte reaction was assessed by MTT method. The morphology of BMDCs stimulated with LPS remained immature after RAPA pretreatment. RAPA significantly decreased the CD86 expression, impaired the IL-12 and IFN-gamma production of BMDCs stimulated with LPS, and inhibited the proliferation of allogeneic T cells. In conclusion, RAPA can inhibit the maturation of BMDCs stimulated with LPS in terms of the morphology, surface phenotype, cytokine production, and ability of BMDCs to stimulate the proliferation of allogeneic T cells in vitro.