To evaluate the effects of p-octyl polyethylene glycol phenyl ether (Triton X-100), polyoxyl 35 caster oil (EL35) and polyoxyl 40 hydrogenated caster oil (RH40) on the activity of Cytochrome P450 3A (CYP3 As) in vivo. Rats were administered with saline, ketoconazole (75 mg x kg(-1) x d(-1)), Triton X-100 (30 mg x kg(-1) x d(-1)), EL35 (150 mg x kg(-1) x d(-1)) and RH40 (150 mg x kg(-1) x d(-1)) intragastrically for 5 consecutive days, and then given midazolam 10 mg x kg(-1) 20 min after the last treatment of ketoconazole or three surfactants with the same dose through duodenal administration. Pharmacokinetics parameters for midazolam and its metabolite 1'-hydroxymidazolam were estimated from the plasma concentration-time data by a noncompartmental approach. The results showed that multiple dose administration of Triton X-100, EL35 and RH40 decreased the ratios of 1'-hydroxymidazolam and midazolam AUC0-infinity from 1.14 to 0.90, 1.03 and 0.64, respectively. In contrast, multiple dose administration of ketoconazole caused the ratios of 1'-hydroxymidazolam and midazolam a significant decrease to 0.50. This study indicated that Triton X-100 and EL35 would have no inhibition on CYP3A, while RH40 had significant inhibition on CYP3A. Therefore, RH40 might be used to prepare drug formulations in pharmaceutical industry and would increase the bioavailability of some drugs transformed by CYP3As and further lead to significant clinical pharmacologic effects.
Animals ; Area Under Curve ; Biological Availability ; Biotransformation ; Cytochrome P-450 CYP3A ; metabolism ; Ketoconazole ; pharmacology ; Male ; Midazolam ; analogs & derivatives ; pharmacokinetics ; Octoxynol ; pharmacology ; Polyethylene Glycols ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Surface-Active Agents ; pharmacology

Bias ; Confounding Factors (Epidemiology) ; Epidemiologic Methods ; Humans

OBJECTIVETo elucidate the effect of the low dosage endotoxin damage on the expression of the organic cation transporter 1 (OCT1) mRNA in hepatocytes and make an approach to the probable effect of dexamethasone on the expression of the OCT1 mRNA after endotoxin damage.

METHODS(1) The endotoxin damage model was established in rats; (2) The change of the expression of OCT1 mRNA in hepatocytes after endotoxin damage was observed by in situ hybridization method; (3) The change of the ultra structure of hepatocytes after endotoxin damage was observed with the electron microscope; (4) Dexamethasone was injected intraperitoneally before endotoxin damage in order to determine the influence of dexamethasone on the expression of OCT1 mRNA after endotoxin treatment.

RESULTSThe expression of OCT1 mRNA decreased until 16 hours (0.5745+/-0.012, P<0.01) after endotoxin treatment and then increased after this time point, which was still lower than the normal control; The expression of OCT1 mRNA in rat hepatocytes increased at each time point after endotoxin damage with dexamethasone treatment. It was highest at 16 hours (0.6327+/-0.007, P<0.01) after endotoxin damage, but it was still lower than that of the normal control.

CONCLUSIONEndotoxin could repress the expression of OCT1 mRNA even before the low dosage endotoxin inducing serious damage to the structure of hepatocytes; Dexamethasone could not induce the expression of OCT1 mRNA in normal hepatocytes, but could lighten the repression of endotoxin on the expression of OCT1 mRNA. And then the expression of OCT1 mRNA could increase at some extent after endotoxin damage with dexamethasone treatment.

Animals ; Dexamethasone ; pharmacology ; Endotoxins ; toxicity ; Male ; Organic Cation Transporter 1 ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar

This study purposed to investigate the effects of different oxygen concentrations and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and their possible mechanisms through simulating oxygen environment to which the peripheral blood HSC are subjected in peripheral blood HSCT. The proliferation ability, cell cycle, directed differentiation ability, ROS level and hematopoietic reconstitution ability of Lin(-)c-kit(+)Sca-1(+) BMHSC were detected by using in vitro amplification test, directional differentiation test, cell cycle analysis, ROS assay and transplantation of Lin(-)c-kit(+)Sca-1(+) HSC from sublethally irradiated mice respectively. The results showed that oxygen concentrations lower than normal oxygen concentration, especially in hypoxic oxygen environment, could reduce ROS generation and amplify more primitive CD34(+)AC133(+) HSC and active CD34(+) HSC, and maintain more stem cells in the G(0)/G(1) phase, which is more helpful to the growth of CFU-S and viability of mice. At the same time, BMHSC exposed to normal oxygen level or inconstant and greatly changed oxygen concentrations could produce a high level of ROS, and the above-mentioned features and functional indicators are relatively low. It is concluded that ROS levels of HSC in BMHSCT are closely related with the oxygen concentration surrounding the cells and its stability. Low oxygen concentration and antioxidant intervention are helpful to transplantation of BMHSC.
Animals ; Bone Marrow Cells ; cytology ; metabolism ; Cell Differentiation ; Cells, Cultured ; Female ; Hematopoietic Stem Cells ; cytology ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Oxygen ; administration & dosage ; pharmacology ; Reactive Oxygen Species ; metabolism

OBJECTIVETo explore the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and microsatellite instability (MSI) in patients with gastric cancer.

METHODSMTHFR gene C677T and A1298C polymorphism were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and MSI was examined with PCR.

RESULTSMTHFR gene C677T and A1298C polymorphisms were analyzed on 122 gastric cancers and 110 normal controls The genotype frequencies of MTHFR 677CC, 677CT and 677TT were 47.5%, 39.3% and 13.1% on patients with gastric cancer, and 48.5%, 42.6%, 8.9% in the controls respectively. There was no significant difference of genotype frequency between the two groups (P > 0.05). The individuals with 677CT genotype, 677TT genotype and 677CT + TT genotype exhibited significantly reduced risk (OR = 0.38,95% CI: 0.15-0.98; OR = 0.26,95% CI: 0.03-2.18 and OR = 0.36,95% CI: 0.07-0.98) of developing gastric cardia cancer compared with those harboring the wild-type(677CC). The individuals with 677TT genotype having a 3.03-fold (95% CI: 1.07-8.65) increased risk of developing gastric corpus cancer. The genotype frequency of MTHFR 1298AA, 1298AC and 1298CC were 59.8%, 36.1% and 4.1% in gastric cancer patients, and 57.4%, 7.6%, 5.0% in the controls, respectively. The distribution of MTHFR A1298C genotype was not significantly different between gastric cancer and controls (P > 0.05). The individuals with 1298CC genotype had a reduced risk of developing gastric antrum cancer (OR = 0.41- fold, 95% CI: 0.03-2.18, 0.05-3.72) when comparing with those having 1298AA genotype. Patients with MSI+ gastric cancer had an increased frequency of the MTHFR 677TT genotype when comparing with those suffering from MSI- gastric cancer (P = 0.009) and with controlled subjects (P = 0.008). There was no significant association found between MTHFR A1298C polymorphism and MSI (P>0.05).

CONCLUSIONPolymorphism of MTHFR C677T was associated with increased risk on gastric corpus cancer and reduced risk on gastric cardia cancer. The polymorphism of MTHFR A1298C was associated with reduced risk for gastric antrum cancer while MSI pathway was possibly involved in the development of gastric cancer with MTHFR 677TT genotype.

Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Microsatellite Instability ; Middle Aged ; Polymorphism, Genetic ; Stomach Neoplasms ; genetics

OBJECTIVETo study the effect of Hath1 gene transfer on the proliferation of colonic cancer cells in vitro.

METHODSThe recombinant plasmid pcDNA3.1(+)-Hath1 was transfected into HT29 colonic cancer cells, and 3 positive cell clones were randomly selected to test the levels of Hath1 mRNA, Muc2 mRNA, Hath1, Muc2, cyclin D1 and p27 by quantitative real-time RT-PCR and Western blotting. The proliferation of the transfected HT29 cells was observed by means of colony formation assay and xenograft growth in nude mice.

RESULTSHath1 significantly down-regulated of cyclin D1 and up-regulate of p27 expressions and inhibited the proliferation of HT29 cells.

CONCLUSIONHath1 gene may be an anti-oncogene in colon carcinogenesis.

Animals ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Colonic Neoplasms ; pathology ; Cyclin D1 ; genetics ; metabolism ; Gene Transfer Techniques ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mucin-2 ; genetics ; metabolism ; Proliferating Cell Nuclear Antigen ; genetics ; metabolism ; RNA, Messenger ; genetics

Objective To evaluate the associations between polymorphisms of LEPR Gln223Arg,LEPR Pro 1019Pro and the risk on obesity.Methods A computerized search on literature was carried out in Wanfang,CNKI,VIP databases and CBM,PubMed,EMBASE databases to collect articles published between 1979 and 2010 concerning the associations between polymorphisms of LEPR Gln223Arg and/or LEPR Pro 1019Pro and risk of obesity in the Chinese population.Odds ratios (ORs) were used to assess the strength of the association,and 95％ confidence intervals (CIs) to present the precision of the estimates.Meta-analysis was performed using the STATA statistical software.Results Fifteen literature were collected for Meta-analysis by the uniform inclusion and exclusion criteria.There were 1096 obese patients and 949 controls for polymorphisms of LEPR Gln223Arg in 9 papers,together with 961 obese patients and 818 controls for polymorphisms of LEPR Prol019Pro in 8 papers.Overall,there were significant associations between decreased risk of obesity and LEPR Gln223Arg polymorphisms (-668 A→G) (G versus A,OR=0.66,95％CI:0.49-0.89; AG and GG versus AA,OR=0.50,95％CI:0.32-0.77; respectively).There were significant associations between increased risk of obesity and LEPR Prol019Pro polymorphisms (-3057 G→A) (A versus G,OR=1.61,95％CI:1.15-2.26; AG and AA versus GG,OR=1.50,95％CI:1.08-2.08; respectively).Conclusion Variant alleles at both LEPR-668 and LEPR-3057 were associated with obesity in the Chinese Han-dominated population.

Objective To compare the clinical diagnosis effect of high and common iodine concentration of contrast agent to patients with liver cirrhosis hepatocarcinoma in 64-MDCT.Methods Ninety patients who diagnosed with cirrhosis and hepatoma by biopsy in our hospital from January 2015 to December 2016 were randomly divided into observation group(n =45) and control group(n =45).The observation group and the control group separately accepted 350 mgI/mL and 300 mgI/mL Lohexol enhancement.The CT values of different enhanced parts,detection rate of lesions and the incidence of adverse reactions were chosen as clinical diagnosis indexes.Results The CT value of liver parenchyma,aorta and portal vein in observation group were particularly or very particularly higher than those of control group (P ＜ 0.05).145 and 110 lesions were respectively detected in observation group and control group.It showed higher diagnostic sensitivity of observation group in three phases (P ＜ 0.05) and good safety in 64-MDCT.Conclusion High concentration iodine contrast agent can remarkably improve the detection CT value and detection rate of liver cancer patients with liver cirrhosis in 64-MDCT,with less adverse reactions.

OBJECTIVETo study the cost of the hypertensive outpatients.

METHODSThe study randomly selected 460 insured patients with hypertension and investigated their cost on each case in the out-patient department through 2002, based on the electronic system of medical insurance.

RESULTSAs a whole, the distribution of hypertensive outpatient expenditure takes on the positively skewed, with the median of 1 567.9 Yuan RMB. With the increase of age, the average expenses in each age group increased accordingly. In the study, the average number of outpatient attendances per patient was 19.5, the average expenses per visit was 115.4 Yuan RMB. In age groups 40 - 49 and 50 - 59, expenses of outpatient in male and female groups are obviously different in 2002 (Wilcoxon W(40 - 49) = 36, P(40 - 49) = 0.037; Wilcoxon W(50 - 59) = 374, P(50 - 59) = 0.023), as well as the number of out-patients (Wilcoxon W(40 - 49) = 52.5, P(40 - 49) = 0.007; Wilcoxon W(50 - 59) = 379, P(50 - 59) = 0.028). When considering the factors of gender and age at one time, the outpatient expenditures in the male group were significantly different between the different age groups (chi(2) = 22.3, P < 0.001), as well as the number of outpatients (chi(2) = 25.4, P < 0.001). In addition, the expenditure of drugs, which took a large proportion of the total expenditure of hypertensive outpatients (about 83.6 percent), was divided into three parts according to the degree of correlation with hypertension: direct expenses related to the with disease, the indirect expenses and the irrespective. The proportions of each part were 19.9 percent, 32.3 percent and 47.8 percent respectively.

CONCLUSIONWhen economic evaluation of community prevention is carried out, the cost and cost-benefit analysis based on the analysis of outpatient expenditure and the proportion of expenses on hypertension should be taken into account. Additionally, to provide appropriate mode of medicare, to impact the behaviors and expenditure of patients, and to provide low-cost but good effective drug are also essential and important factors.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; Ambulatory Care ; China ; Female ; Health Care Costs ; statistics & numerical data ; Hospitals, Community ; economics ; statistics & numerical data ; Humans ; Hypertension ; economics ; therapy ; Male ; Middle Aged ; Outpatients ; statistics & numerical data ; Sex Factors ; Time Factors

Objective To compare the cost-effectiveness of two anti-hypertensive therapy regimens,Compound anti-hypertensive tablets and other common anti-hypertensive agents,in the treatment program of Primary Hypertension.Methods We conducted a cost-effectiveness analysis based on a community trial.Two communities'primary hypertensive patients were enrolled to receive different therapy drugs:Compound anti-hypertensive tablets(Group A)or other common anti-hypertensive agents(Group B).Blood pressure,medicine used,and adverse drug reactions were observed and recorded for one year,and then costeffectiveness ratio of the two groups and incremental ratio were calculated.We considered a 30%drug price fluctuating load to make the sensitivity analysis.Results 2505 cases were enrolled with 1529 cases in group A and 976 cases in group B.The cost-effectiveness ratios were 418.1 and 1057.7 for Group A and B respectively while the incremental cost-effectiveness of Group B vs.Group A was 19 202.2.The results were insensitive to variation in the costs of drugs over clinically reasonable ranges.Conclusion Compound anti-hypertensive tablets appeared to be relatively cost-effective when compared to common drugs for the treatment of primary hypertension.