Inhibitory effect of oxymatrine on serum hepatitis B virus DNA in HBV transgenic mice

To study the inhibitory effect of oxymatrine on serumhepatitis B virus (HBV) DNA in HBV transgenic mice.

Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai:an epidemiological survey

AIM: To determine the prevalence of nonalcoholic fatty liver in a specific population in Shanghai by an epidemiological survey, and to analyze risk factors of fatty liver.METHODS: Total 4009 administrative officers who denied regular alcohol drinking participated in the survey, and underwent physical examination and laboratory tests. The important parameters were body mass index (BMI), waist hip circumferences ratio (WHR) and levels of serum lipids.Diagnosis of fatty liver was based on established real-time ultrasonographic criteria, the presence of an ultrasonographic pattern consistent with 'bright liver', with evident ultrasonographic contrast between hepatic and renal parenchyma, vessel blurring, and narrowing of the lumen of the hepatic veins. Analysis of data was performed through SPSS for Windows statistical package.RESULTS: The overall prevalence of fatty liver was 12.9 %,15.8 % in males and 7.5 % in females, and the prevalence of fatty liver in males younger than 50 years old, was significantly higher (13.3 %) than that of in females (2.7 %).But the difference between the sexes became less significant in people older than 50 years (19.1% vs 18.1%). The prevalence of fatty liver was increased with age; this was markedly presented in females younger than 50 years.Multiple variant regression analysis demonstrated that the prevalence of fatty liver was positively correlated to several risk factors, including male, aging (＞50yr), hyperlipidemia,impaired glucose tolerance/diabetes mellitus, hypertension and overweight/obesity.CONCLUSION: There is a high prevalence of nonalcoholic fatty liver among certain population in Shanghai, to which overweight and hyperlipidemia are closely relevant.

Effects of histone acetylation and DNA methylation on p21^(WAF1)regulation

Cell cycle progression is regulated by interactions betweencyclins and cyclin-dependent kinases (CDKs). p21wAF1 is oneof the CIP/KIP family which inhibits CDKs activity. Increasedexpression of p21WAF1 may play an important role in thegrowth arrest induced in transformed calls. Although thestability of the p21wAF1 mRNA could be altered by differentsignals, cell differentiation and numerous influencingfactors. However, recent studies suggest that two knownmechanisms of epigenesis, i. e. gene inactivation bymethylation in promoter region and changes to an inactivechromatin by histone deacetylation, seem to be the bestcandidate mechanisms for inactivation of p21WAF1. To date,almost no coding region p21wAF1 mutations have been foundin tumor cells, despite extensive screening of hundreds ofvarious tumors. Hypermethylation of the p21WAF1 promoterregion may represent an alternative mechanism by which thep21WAF1/ClPl gene can be inactivated. The reduction of cellularDNMT protein levels also induces a corresponding rapidincrease in the cell cycle regulator p21wAF1 proteindemonstrating a regulatory link between DNMT and p21WAF1which is independent of methylation of DNA. Both histonehyperacetylation and hypoacetylation appear to be importantin the carcinoma process, and induction of the p21WAF1 geneby histone hyperacetylation may be a mechanism by whichdietary fiber prevents carcinogenesis. Here, we review theinfluence of histone acetylation and DNA methylation onp21WAF1 transcription, and affection of pathways or factorsassociated such as p53, E2A, Sp1 as well as several histonedeacetylation inhibitors.

Effects of bile reflux on gastric mucosal lesions in patients with dyspepsia or chronic gastritis

AIM: To investigate the influences of bile reflux on profiles of gastric mucosal lesions in patients with dyspepsia or chronic gastritis.METHODS: A total of 49 patients diagnosed with dyspepsia and chronic gastritis underwent 24-h ambulatory andsimultaneous monitoring of intragastric bilirubin absorbance and pH values, and then they were divided into bile refluxpositive group and bile reflux negative group. Severity of pathological changes in gastric mucosa including activeinflammation, chronic inflammation, intestinal metaplasia, atrophy and dysplasia as well as Helicobacter pylori (H pylori) infection at the corpus, incisura and antrum were determined respectively according to update Sydney system criteria. The profiles of gastric mucosal lesions in the two groups were compared, and correlations between time-percentage of gastric bilirubin absorbance ＞0.14 and severity of gastric mucosal lesions as well as time-percentage of gastric pH ＞4 were analyzed respectively. RESULTS: Thirty-eight patients (21 men and 17 women, mean age 44.2 years, range 25-61 years) were found existing with bile reflux (gastric bilirubin absorbance ＞0.14) and 11 patients (7 men and 4 women, mean age 46.2 years,range 29-54 years) were bile reflux negative. In dyspepsia patients with bile reflux, the mucosal lesions such as active inflammation, chronic inflammation, intestinal metaplasia, atrophy or H pylori infection in the whole stomach, especially in the corpus and incisura, were significantly more severe than those in dyspepsia patients without bile reflux. Moreover, the bile reflux time was well correlated with the severity of pathological changes of gastric mucosa as well as H pylori colonization in the near-end stomach, especially in the corpus region. No relevance was found between the time of bile reflux and pH ＞4 in gastric cavity. CONCLUSION: Bile reflux contributes a lot to mucosal lesions in the whole stomach, may facilitate H pylori colonization in the corpus region, and has no influence on acid-exposing status of gastric mucosa in patients with dyspepsia or chronic gastritis.

Capsule endoscopy in diagnosis of small bowel Crohn's disease

AIM: To evaluate the effectiveness of wireless capsule endoscopy in patients with suspected Crohn's disease (CD) of the small bowel undetected by conventional modalities,and to determine the diagnostic yield of M2A Given Capsule.METHODS: From May 2002 to April 2003, we prospectively examined 20 patients with suspected CD by capsule endoscopy. The patients had the following features:abdominal pain, weight loss, positive fecal occult blood test, iron deficiency anaemia, diarrhoea and fever. All the patients had normal results in small bowel series (SBS) and in upper and lower gastrointestinal endoscopy beforethey were examined. Mean duration of symptoms before diagnosis was 6.5 years.RESULTS: Of the 20 patients, 13 (65%) were diagnosed as CD of the small bowel according to the findings of M2A Given Capsule. The findings detected by the capsule were mucosal erosions (2 patients), aphthas (5 patients),nodularity (1 patient), large ulcers (2 patients), and ulcerated stenosis (3 patients). The distribution of the lesions was mainly in the distal part of the small bowel,and the mild degree of lesions was 54%.CONCLUSION: Wireless capsule endoscopy is effective in diagnosing patients with suspected CD undetected by conventional diagnostic methods. It can be used to detect early lesions in the small bowel of patients with CD.

Capsule oxymatrine in treatment of hepatic fibrosis due to chronic viral hepatitis:A randomized,double blind,placebo-controlled,multicenter clinical study

AIM: To evaluate the efficacy and safety of oxymatrine capsule in treatment of hepatic fibrosis in patients with chronic viral hepatitis. METHODS: It was a randomized, double blind, placebocontrolled, multicenter clinical study. One hundred and fortyfour patients were divided into oxymatrine capsule group (group A) and placebo group (group B). The course was 52wk. Patients were visited once every 12wk and the last visit was at 12wk after cessation of the treatment. All patients had liver biopsy before treatment, part of them had a second biopsy at the end of therapy. Clinical symptoms, liver function test, serum markers of hepatic fibrosis were tested. Ultrasound evaluation was performed before, during and at the end of therapy. RESULTS: One hundred and forty-four patients enrolled in the study. Of them 132 patients completed the study according to the protocol, 49 patients had liver biopsy twice (25 patients in group A and 24 in group 13). At the end of therapy, significant improvements in hepatic fibrosis and inflammatory activity based on Semi-quantitative scoring system (SSS) were achieved in group A. The total effective rate of the treatment was 48.00%, much higher than that of 4.17% in group B (P<0.05). Significant improvement in serum markers of hepatic fibrosis such as hyaluronic acid (HA) and type Ⅲ procollagenic peptide (PⅢ P) in group A was seen (P<0.05). The total effective rate of serum markers at the end of therapy in group A was 68.19%, much higher than that of 34.85% in group B (P<0.05). The total effective rate of noninvasive markers at the end of therapy in group A was 66.67%, much higher than that of 30.30% in group B (P<0.05). The rate of adverse events was similar in two groups. CONCLUSION: Oxymatrine capsule is effective and safe in treatment of hepatic fibrosis due to chronic viral hepatitis.

An Association of Elevated Serum Prolactin with Phthalate Exposure in Adult Men

Objective To investigate the associations of hormone circulation with phthalate exposure in adult men. Methods Semen and serum samples were collected from 118 men who were suspected of infertility. Phthalate diesters including dibutyl phthalate （DBP） and diethylhexyl phthalate （DEHP） in both semen and serum samples were measured, along with serum levels of follicle stimulating hormone （FSH）, luteinizing hormone （LH）, testosterone （T）, estradiol （E 2 ） and prolactin （PRL）. Results Serum PRL was positively associated with serum DBP and DEHP and semen DEHP in all models of Spearman correlation, linear regression and binary logistic regression. In linear regression models adjusted for potential confounders and excluding subjects with undetectable phthalates, a 10‐fold increase in semen DEHP was associated with a 23% increase in serum PRL, as well as a 26% increase in serum DBP and a 20% increase in serum DEHP. In logistic regression models all subjects demonstrated a dose‐response relationship between above reference value PRL and semen DEHP （odds ratio per tertile adjusted for potential confounders = 1.0, 1.70, 3.50; P for trend = 0.01）, and serum DBP （1.0, 1.10, 2.62; P for trend = 0.04）, and serum DEHP （1.0, 1.46, 4.69; P for trend 0.01）. A positive correlation between serum estradiol and semen DEHP （linear regression）, and an inverse correlation between semen DBP and serum testosterone and T：E 2 ratio （Spearman correlation） were also established. Conclusions Serum PRL is suggested to be positively associated with both DBP and DEHP exposure in adult men.

Low dose gossypol for male contraception

Aim: To ascertain whether the side effects of gossypol, hypokalemia and irreversibility, could be avoided on dose re-duction. Methods: Seventy-seven male volunteers were divided into 3 groups: control (22 cases), 10 mg gossypol(29 cases) and 12.5 mg (26 cases). Serum levels of testosterone, FSH and LH were measured by RIA and potassiumby flame photometry. Spema counts and motility were examined before and regularly after treatment for the evaluationof contraceptive efficacy. Results: The average sperm density and motility started to decrease significantly by theend of month 2 of medication and gradually reached the infertility levels ( < 4 million /mL) in both treated groups. Af-ter that the 10 mg group was asked to take the same dose every other day for up to a total observation period of 16-18months for the maintenance of infertility. Subjects in the 12.5 mg group did not take gossypol any more so as to ob-serve the length of the loading dose required, but in a few, a maintenance dose of 12.5 mg every other day was insti-tuted for a few more months. In both treated groups, none of the spouses was pregnant during the maintenance dose pe-riod. Serum levels of potassium, FSH, LH and testosterone were not significantly changed and not a single volunteercomplained of myoasthenia. After cessation of drug administratioin, the semen data returned to pretreatment levels.Conclusion: A regimen with 10 or 12.5 mg of gossypol as the daily loading dose and 35 or 43.75 mg as the week-ly maintenance dose could induce infertility in male volunteers without developing hypokalemia or irreversibility.(Asian J Androl 2000 Dec; 2: 283-287)

Histone acetylation regulates p21^(WAF1) expression in human colon cancer cell lines

AIM: To investigate the effect of histone acetylation on regulation of p21^WAF1 gene expression in human colon cancer cell lines.METHODS: Two cell lines, Colo-320 and SW1116 were treated with either trichostatin or sodium butyrate.Expressions of p21^WAF1 mRNA and protein were detected by real-time RT-PCR and Western blotting, respectively.Acetylation of two regions of p21^WAF1 gene-associated histones and total cellular histones were examined by chromatin immunoprecipitation assay and Western blotting.RESULTS: Trichostatin or sodium butyrate re-activated p21^WAF1 transcription resulted in up-regulated p21^WAF1 protein level in colon cancer cell lines. Those effects were accompanied by an accumulation of acetylated histones in total cellular chromatin and p21^WAF1 gene-associated region of chromatin.CONCLUSION: Histone acetylation regulates p21^WAF1 expression in human colon cancer cell lines, Colo-320 and SW1116.

Oxymatrine therapy for chronic hepatitis B:A randomized doubleblind and placebo-controlled multi-center trial

AIM: To evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B.METHODS: A randomised double-blind and placebocontrolled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 weeks, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo.After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed.RESULTS: Among the 216 patients, six were dropped off,and 11 inconsistent with the standard were excluded.Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47 % became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33 % became normal in ALT level,43.33 % and 39.29 % became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00 % became normal in ALT level, 7.46 % and 6.45 % became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84 % in the capsule treated patients, and 33.33 % and 50.00 % in the injection treated patients, and 2.99 % and 41.79 % in the placebo treated patients, respectively.There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule,injection and placebo were 7.77 %, 6.67 % and 8.82 %,respectively. There was no statistically significant difference among them.CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.

Relationship between clinical and pathologic findings in patients with chronic liver diseases

AIM: To explore the relationship between clinical findings of patients with chronic liver diseases and the pathologic grading and staging of liver tissues.METHODS: The inflammatory activity and fibrosis of consecutive liver biopsies from 200 patients were determined according to the diagnosis criteria of chronic hepatitis in China established in 1995. A comparative analysis was carried out for 200 patients with chronic liver diseases by comparing their clinical manifestations, serum biochemical markers with the grading and staging of liver tissues.RESULTS: It was revealed that age, index of clinical symptoms and physical signs were obviously relevant to the pathologic grading and staging of liver tissues (P＜0.05). Blood platelet, red blood cells, aspartate aminotransferase (AST),N-terminal procollagen Ⅲ (PⅢ NP) were apparently correlated with the degree of inflammation. PGA (prothrombin time,GGT, apoprotein A1) index, PGAA (PGA+△2-macroglobublin)index, albumin and albumin/globulin were relevant to both inflammation and fibrosis. Hyaluronic acid (HA) was an accurate variable for the severity of hepatic inflammation and fibrosis. The combination of serum markers for fibrosis could increase the diagnostic accuracy. It was notable that viral replication markers were not relevant to the degree of inflammation and fibrosis.CONCLUSION: There is a good correlation between clinical findings and the pathologic grading and staging of liver tissues, which may give aid to the noninvasive diagnosis of liver fibrosis.

Grading and staging of hepatic fibrosis,and its relationship with noninvasive diagnostic parameters

AIM: To explore the grade and stage of pathology and the relationship between grading and staging of hepatic fibrosis and noninvasive diagnostic parameters.METHODS: Inflammatory activity and fibrosis of consecutive liver biopsies from 200 patients with chronic liver disease were determined according to the Diagnostic Criteria of Chronic Hepatitis in China, 1995. A comparative analysis was made in these patients comparing serum markers,Doppler ultrasonography, CT and/or MR imaging with the findings of liver biopsy.RESULTS: With increase of inflammatory activity, the degree of fibrosis also rose. There was a close correlation between liver fibrosis and inflammatory activity. AST, GGT, albumin,albumin/globulin, ALP, AFP, hyaluronic acid, N-terminal procollagen Ⅲ(P Ⅲ NP), collagen type Ⅳ(Col Ⅳ), tissue inhibitors of metalloproteinases-1(TIMP-1), alpha-2-macroglobulin, natural killer cells(NK), some parameters of Doppler ultrasonography, CT and/or MR imaging were all related to the degree of inflammatory activity. GGT, albumin,albumin/globulin, ALP, AFP, hyaluronic acid, Col Ⅳ, TIMP1, alpha-2- macroglobulin, transforming growth factor-beta 1(TGFβ1), NK, some parameters of Doppler ultrasonography,CT and/or MR imaging were all related to the staging of fibrosis. By regression analysis, the parameters used in combination to differentiate the presence or absence of fibrosis were age, GGT, the parameter of blood flow of portal vein per minute, the maximum oblique diameter of right liver by B ultrasound, the wavy hepatic surface contour by CT and/or MR. The sensitivity, specificity and accuracy of the above parameters were 80.36 %, 86.67 %, and 81.10 %,respectively.CONCLUSION: There is close correlation between liver fibrosis and inflammatory activity. The grading and staging of liver fibrosis are related to serum markers, Doppler ultrasonography, CT and/or MR imaging. The combinationof the above mentioned noninvasive parameters are quite sensitive and specific in the diagnosis of hepatic fibrosis.

Preoperative evaluation of pancreaticobiliary tumor using MR multi-imaging techniques

AIM: To evaluate the clinical value of MR multi-imaging techniques in diagnosing and preoperative assessment of pancreaticobiliary tumor.METHODS: MR multi-imaging techniques, including MR cross-sectional imaging, MR cholangiopancreatography (MRCP) and 3D dynamic contrast-enhanced MR angiography (3D DCE MRA), were performed to make prospective diagnosis and preoperative evaluation in 28 patients with suspected pancreaticobiliary tumors. There were 17 cases of pancreatic adenocarcinoma, 8 cases of biliary system carcinoma and 3 cases of non-neoplastic lesions.RESULTS: Using MR multi-imaging techniques, the accuracy in diagnosing the patients with pancreaticobiliary tumors was 89.3% (25/28). The accuracy in detecting the range of tumor invasion was 80.3% (57/71). The sensitivity, specificity, accuracy, positive and negative predictive value of MR multi-imaging techniques in preoperative assessment of the resectability of pancreaticobiliary tumor were 83.3%, 89.5%, 88.0%, 71.4%, and 94.4%, respectively. There was well diagnostic consistency between MRmulti-imaging techniques and CT (κ = 0.64, P＜0.01). The fusion image could be made from MRCP and 3D DCE MRA images.CONCLUSION: MR multi-imaging techniques can integrate the advantages of various MR images. The non-invasive 'all-in-one' MR imaging protocol is the efficient method in diagnosing, staging and preoperative assessment of pancreaticobiliary tumor.

Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients:a multicenter,open-label,phase Ⅲ study

BACKGROUND:Contrast agents help to improve visibility in magnetic resonance(MR)imaging.However,owing to the large interstitial spaces of the liver,there is a reduction in the natural contrast gradient between lesions and healthy tissue.This study was undertaken to evaluate the efficacy and safety of the liverspecific MR imaging contrast agent gadoxetate disodium(GdEOB-DTPA)in Chinese patients.METHODS:This was a single-arm,open-label,multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR imaging.MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA(0.025 mmol/kg body weight).Images were evaluated by clinical study investigators and three independent,blinded radiologists.The primary efficacy endpoint was sensitivity in lesion detection.RESULTS:Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46%compared with pre-contrast imaging for the average of the three blinded readers(94.78%vs 85.32%for Gd-EOB-DTPA vs pre-contrast,respectively).Improvements in detection were more pronounced in lesions less than 1cm.Gd-EOB-DTPA improved diagnostic accuracy in lesion classification.CONCLUSIONS:This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions,particularly in those smaller than 1 cm.Gd-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification,and furthermore,Gd-EOB-DTPA is safe in Chinese patients with liver lesions.

Role of PGI_2 in the formation and maintenance of hyperdynamic circulatory state of portal hypertensive rats

AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH)group by injection of CCl4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitroL-arginine (L-NNA)group (n = 21) group, indomethacin (INDO)group (n = 22) and high-dose heparin group (n = 24). The for one week, then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-)levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α,a stable hydrolytic product of PGI2, was determined by radioimmunoassay.RESULTS: The concentrations of plasma 6-keto-PGF1α(pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats(1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11,75.21±6.89) were significantly higher than those in SO rats(725.53±105.54, 58.79±8.47) (P＜0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P＜0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGF1α and serum NO2-/NO3-in IHPH and PHPH rats (P＜0.05) .Meanwhile, CI, FPP and PVI lowered but MAP,TPR and SVR increased(P＜0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI2, NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters.After administration of high-dose heparin, plasma 6-ketoPGF1α concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle(P＜0.05). On the contrary, levels of serum NO2-/NO3- in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P＜0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P＜0.05), while TPR and SVR increased significantly (P＜0.05).CONCLUSION: It is NO rather than PGI2 that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.

BIOAVAILABILITY AND PHARMACOKINETICS OF ANASTROZOLE IN HEALTHY MALE VOLUNTEERS

Objective To evaluate bioavailability and pharmacokinetics of domestic and imported anastrozole tablets.Methods Twenty Chinese healthy male volunteers were enrolled in a randomized crossover study with a single oral dose of 2mg of the two formulations respectively. The anastrozole in plasma was measured by gas chromatography with electron-capture detection. The linear range was 1. 325-106ng /ml plasma. The extraction recovery rates for plasma concentration of 5.3, 21.2 and 53. 0ng/ml were 76.8%,87.0% and 78.7%, respectively. Inter-day and intra-day precisions of the method were < 9%. Area underconcentration-time curve ( AUC0-1), maximum plasma concentration (Cmax) and reach peak time (Tmax) were evaluated by variance analysis and two one-side t-test . Results A two-compartment model was adopted in anastrozole plasma concentration-time data analysis. The main pharmacokinetic parameters of domestic and imported anastrozloe tablets such as Cmax, Tmax, AUC0 - 1 and T1/2β were (36.5± 6.9) ng /ml and (35.6±9.4)ng/ml, (1.56 ±0.41)h and(1.53 ±0.49)h, (1403.6± 321.2)ng·h/ml and (1371.6±329.4)ng.h/ml, ( 42.57 ±10.15) h and ( 43.41 ±8.59 ) h, respectively, and there were no significant differences be-tween the two formulations. Conelusion Domestic and imported anastrozole tablets were of bioequivalence.The relative bioavailability of the domestic tablet was ( 102.7± 5.6 )%.

EFFECTS OF PML AND PML/RMRα ANTISENCE OLIGO-NUCLEOTIDE ON PROMYELOCYTIC LEUKEMIA CELL NB4

Objective: To investigate the effects of anti-PML (promyelocytic leukemia) or anti-PML/RAR( (promyelocytic leukemia/retionic acid receptor() antisense oligonucleotides on cell growth, expression of PML-RAR( mRNA and PML-RAR(/PML protein location of NB4 cell lines. Methods: RT-PCR was used for detecting PML-RAR( mRNA expression, trypan blue exclusion for cell count, methylcellose assay for leukemic colony forming unit detection, immuno- fluorescence for PML-RAR(/PML protein location. Results: Both anti-PML start codon region antisence (STAS) and anti-PML-RAR( fusion region antisence (FUAS) could inhibit cell growth and the formation of acute myelocytic colony forming unit of cells(AML-CFU). Cells become partial differentiated at days 5, being more obvious in FUAS-treated cells than in STAS ones. Down regulation of PML-RAR( mRNA expression occurred at 24 hours in STAS and FUAS-treated cells and maintained for up to 72 hours. Immuno-fluorescence analysis with anti-PML monoclonal antibody showed a remarkable decrease even complete disappearance of microgranules. The residual granules became enlarged as discrete dots (<10 per cell), similar to normal POD structure in some STAS-treated cells at 24 hours. At 72 hours, nearly all the granules disappeared. Similar changes were observed in FUAS-treated cells. Conclusion: Both PML and PML-RAR( antisence oligonucleotides can specially block the expression of PML-RAR( at mRNA and protein levels. PML protein is implicated in the regulations of cell differentiation.

Experiment and research on development and characterizations of anodic alumina membrane for use in hemodialysis

Objective: The correlation between various formative conditions and the pore characterizations of the anodic alumina membrane is investigated to seek the optimal conditions for the formation of anodic alumina membrane. Methods: High purity aluminum foils are used as the starting materials. The anodization is conducted in three types of electrolytes, 3% sulfuric acid, 5% sulfuric acid and 2.7% oxalic acid, respectively, with different voltages at 0℃ for 48h. The characterizations of the pore size, the effective porosity and the pore porosity are observed and determined by scanning electron microscopy. The hydraulic conductances of the membranes are measured to confirm that the pores are open and evaluate the permselectivity of the membranes. Results: The experimental result shows that the ordered pore arrays are obtained for oxidation under our experimental conditions. With the increasing of the voltage, the pore size and pore porosity increased significantly ( P < 0.05) , while the effective porosity decreased significantly ( P < 0.05 ) with the same electrolyte. The pore size formed in 3% sulfuric acid or 5% sulfuric acid is much smaller than in 2.7% oxalic acid as an electrolyte. The hydraulic conductance of anodic alumina membrane that formed under our experimental condition is higher than those of the membranes are available currently used in clinical. Conclusion: The results suggest that the optimal conditions for the formation of anodic alumina membrane that used in hemodialysis are in 3% or 5% sulfuric acid with 12.5V to 17.5V at 0℃ for 48h.

Experimental Study of the Prophylactic and Therapeutic Effects of Venin on Metastasis and Recurrence of Liver Cancer

OBJECTIVE To study the inhibitory effect of venin on adhesion and invasive ability of SMMC-7721 cells and to examine the prophylactic and therapeutic effect of venin on liver cancer metastasis and recurrence after hepatectomy.METHODS The blocking effect of venin on the intercellular adhesive molecule (ICAM-1) of 7721 cells was analyzed by immunofluorescence flow cytometry. The influence of venin on the invasive ability of 7721 cells was observed by cell-migration experimentation and detachment of 7721 cells attached to fibronectin (FN), and the influence of venin on adhesion of 7721 cells to FN by the MTT method, 7721 cells to 7721 cells, 7721 cells to lymphocytes, and 7721 cells to endothelial cells by a cellular adhesion test. The preventive and therapeutic effect of venin onmetastasis and recurrence of a liver cancer model was observed in nudemice after hepatectomy. RESULTS The expression of ICAM-1 in the venin-treated group was significantly lower than that in the untreated group. Venin could not inhibit the invasive ability of 7721 cells, and could not exfoliate the 7721 cells adhered to FN. It could inhibit the adhesion between 7721 cells and 7721 cells, and between 7721 and endothelial cells, but could not inhibit the adhesion between 7721 and lymphocytes. The nude mice treated with venin had less intrahepatic or extrahepatic metastases and recurrences after hepatectomy. CONCLUSION Venin can inhibit the adhesive ability of SMMC-7721 cells and can also prevent and treat the metastasis and recurrence of liver cancer in nude mice after hepatectomy.