Objective To study the effects of localized thermochemotherapy on angiogenesis and the expression of VEGF protein of C6 gliomas in rats,and explore the mechanisms of angiogenesis inhibition by localized thermochemotherapy. Methods Following the establishment of animal models, 40 rats harboring the C6 gliomas were randomly allocated to 4 groups,the rats in the fore 3 groups were treated by localized thermochemotherapy, hyperthermia and chemotherapy, respectively, the remaining group served as control. The expression of VEGF and FⅧ RA protein were detected by S P immunohistochemistry. The vascular structure in rat's glioma was observed by immunohistochemistry and electron microscopy technique. Results As compared with the control group, the expression of VEGF protein was decreased in the hyperthermia and chemotherapy groups,as well as in the thermochemotherapy group.The expression of VEGF was positively correlated with the microvessel density in the tumor ( r =0.9798, P

Objective To study the effects of localized thermochemotherapy on cellular proliferation and the expression of PCNA and IGF-I protein of C6 gliomas in rat, and explore the possibility of developing new therapeutic method of gliomas. Methods C6 glioma cells were injectcd subcutaneously to rats. The rats were randomly assigned to 4 groups,and treatment were initiated on day 22 after tumor inoculation. Prior to treatment, the subcutaneous gliomas were examined to verify tumor size, which were ranged 1.5 to 2.0 cm. Then localized thermochemotherapy, hyperthermia and chemotherapy were given, respectively. The size and weight of subcutaneous tumors were measured. PCNA and IGF-I protein expression were detected by the technique of S-P immunohistochemistry. Glioma cells proliferation was detected by HE staining method and electron-microscopic observation. Results Compared with the control group, the tumor size of rats in the hyperthermia and chemotherapy as well as thermochemotherapy groups was decreased,the tumor weight was also decreased significantly (2.95g vs 1.95g vs 1.86g vs 1.09g, P

AIMTo prepare recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) -loaded stealth nanoparticles with different PEG chain lengths and sizes, and investigate the stability of nanoparticle suspensions.

METHODSThe poly( MePEG cyanoacrylate-co-hexadecyl cyanoacrylate) (MePEG-PHDCA) and poly(hexadecyl cyanoacrylate) (PHDCA) were synthesized and characterized with Fourier transform infrared spectrum (FTIR), 1HNMR, 13CNMR and gel permeation chromatography (GPC). Uniform design was used to optimize the entrapment efficiency. The nanoparticle suspensions were stored at 2 - 8 degrees C for 4 weeks, and the particle size evolution was studied.

RESULTSFTIR, 1HNMR and 13CNMR were consistent with the structures of MePEG-PHDCA and PHDCA whose polydispersity indexes were all less than 1.1, indicating narrow distributions. The entrapment efficiency of all nanoparticles was satisfactory. The three different mean diameters of MePEG-PHDCA and PHDCA nanoparticles were about 80 nm, 170 nm and 240 nm, separately. The nanoparticle suspensions maintained their sizes at 2 - 8 degrees C for 4 weeks

CONCLUSIONMePEG-PHDCA with three different molecular weight MePEG and PHDCA were synthesized successfully. There are negligible aggregations and bulk or surface erosion as for both stealth MePEG-PHDCA and conventional PHDCA nanoparticles in distilled water.

Cyanoacrylates ; chemistry ; Drug Carriers ; Drug Delivery Systems ; Drug Stability ; Humans ; Nanotechnology ; Polyethylene Glycols ; chemistry ; Recombinant Proteins ; administration & dosage ; Tumor Necrosis Factor-alpha ; administration & dosage

AIM To study the improvement of quercetin on Pseudomonas aeruginosa-induced lung infection in rats.METHODS Forty SPF SD rats were randomly divided into five groups,eight rats in each group:normal group,P.aeruginosa infection group,quercetin group,levofloxacin group,levofloxacin combined with quercetin group (combined group),the rats were anesthetized and then injected with P.aeruginosa in bronchus.The pathological changes of lung tissue in rats were observed,the contents of IL-4 and IFN-γcytokines,changes of transcription factors T-bet and Gata-3 in lung tissue were detected,and then semi-quantitative RT-PCR was used for the detection of IL-4,IFN-γ,T-bet and Gata-3 mRNA expressions.RESULTS The content of IL-4,levels of IL-4 and Gata-3 mRNA in lung tissue in the quercetin group,the levofloxacin group and the combined group were lower than those in the P.aeruginosa infection group,but the opposite was true in the levels of IFN-γ and T-bet mRNA.CONCLUSION Quercetin and levofloxacin can induce the differentiation from type Th2 to type Th1 for rat organism,but there is no synergistic effect between them.

BACKGROUNDTumor necrosis factor alpha (TNF-α) is important in promoting relative adrenal insufficiency (RAI) due to systemic inflammatory response syndrome (SIRS). We identified the TNF-α receptor involved in the inhibition of adrenal corticotrophin (ACTH)-stimulated hydrocortisone release by studying the expression of TNF-α receptors in adrenal cortex Y1 cells and the effect of downregulating TNF receptors on ACTH-stimulated hydrocortisone release.

METHODSWe used real-time PCR and immunocytochemistry to evaluate the expression of TNF receptors on Y1 cells. TNF-receptor 1 (TNF-R1) DNA fragments corresponding to the short hairpin RNA (shRNA)-sequences were synthesized and cloned into pcDNA(TM) 6.2-GW/EmGFP expression vector. Knockdown efficiency of TNF-R1 expression was evaluated in miRNA transfected and mock-miRNA transfected Y1 cells by quantitative real-time PCR (Q-PCR). Hydro-cortisone expression levels were determined in TNF-R1-knockdown and control Y1 cells treated with TNF-α and ACTH.

RESULTSMouse adrenal cortex Y1 cells were positive for type I TNF-R1, but not type II TNF-receptor (TNF-R2). Blocking TNF-R1 expression resulted in loss of TNF-α-mediated inhibition of ACTH-stimulated hydrocortisone expression, suggesting a role for the TNF-R1 related signaling pathway in ACTH-stimulated hydrocortisone synthesis.

CONCLUSIONThe inhibitory effect of TNF-α on ACTH-stimulated hydrocortisone synthesis was mediated via TNF-R1 in adrenal cortex.

Adrenal Cortex ; cytology ; drug effects ; metabolism ; Animals ; Cell Line ; Hydrocortisone ; metabolism ; Immunohistochemistry ; Mice ; Real-Time Polymerase Chain Reaction ; Receptors, Tumor Necrosis Factor, Type I ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; pharmacology

Objective To evaluate the clinical efficacy and safety of domestic produced losartan potassium in aged patients with essential hypertension and hyperuricemia.Methods Eighty patients diagnosed with hypertension with hyperuricemia were randomly divided into treat-ment group ( n=40 ) and control group ( n=40 ).Patients in treatment group were given losartan potassium 50 mg· d -1 , and patients in control group given candesartan 4 mg · d-1.The treatment lasted for 8 weeks.Clinical efficiency , serum uric acid levels and blood pressure of the two groups were measured after treatment.Results After treatment , the total effective rate was equal 95.0%in treatment group and control group and the markedly effective rate were 55.0% and 57.5% respectively (P>0.05).After treatment, the reduction of systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) were ( 19.65 ±12.23 )/( 11.80 ±8.21 ) mmHg vs ( 24.78 ±15.38 )/( 13.93 ±10.60 ) mmHg in treatment group and control group ( P<0.05 ) , there was no significant difference between the two groups ( P>0.05 ).After treatment , the level of uric acid decreased apparently in treatment group was (435.04 ±53.57 )μmol L-1 , and (483.68 ±63.50 ) μmol· L-1 in control group and treatment group was significantly lower than control group and before treatment ( P<0.05 ).There was no adverse reaction in treatment group , 1 case in control group ( 2.5%) .There was no significant change in heart rate in two groups before and after treatment.Conclusion Domes-tic produced losartan potassium was proved to be a stable and effective antihypertensive medication with little adverse drug reactions.

OBJECTIVETo study the kinetics of MG7 expression in the process of gastric cancer development.

METHODSThe expression level of antigen MG7 on gastric mucosa in 406 cases was determined by immunohistochemical techniques. The classification of intestinal metaplasia of gastric mucosa was determined by histochemistry techniques on gastric mucosa in 82 cases.

RESULTSThe positive rates of MG7 expression in normal gastric mucosa, intestinal metaplasia and dysplasia of gastric mucosa and gastric cancer all increased gradually (P < 0.01). The positive rates of MG7 expression in superficial gastritis, atrophic gastritis and gastric cancer increased in sequence (P < 0.01). The positive rate of antigen MG7 expression in III intestinal metaplasia of gastric mucosa was significantly different with I and II intestinal metaplasia (P < 0.05).

CONCLUSIONSMG7 was quite specific in gastric cancer thus could be used as a good index in the screening of gastric cancer. Patients with III intestinal metaplasia of gastric mucosa, atrophic gastritis and dysplasia of gastric mucosa should be closely followed in order to improve the early detection on gastric cancer. It seemed that MG7 was clinically valuable in the dynamic follow-up of gastric precursors.

Adult ; Aged ; Antigens, Neoplasm ; analysis ; Female ; Gastric Mucosa ; chemistry ; Humans ; Immunohistochemistry ; Male ; Metaplasia ; Middle Aged ; Precancerous Conditions ; diagnosis ; immunology ; pathology ; Stomach Neoplasms ; diagnosis ; immunology ; pathology

AIMTo investigate the influence of cytochrom P450 CYP2C9 polymorphism on the pharmacokinetics of tolbutamide.

METHODSAn oligonucleotide microarray was designed and fabricated to genotype the CYP2C9 accurately and quickly. 137 healthy volunteers were genotyped with the array to investigate the frequency of CYP2C9 functional SNPs. Moreover, 1 homozygous mutant, 9 heterozygous and 10 wild-genotypes subjects in the assay were selected randomly and sequenced directly. After orally taking tolbutamide, blood samples and urine samples were collected, and their pharmacokinetics was studied with HPLC.

RESULTSCYP2C9 *1/*3 were found in 9 of 137 volunteers, CYP2C9 *3/*3 in only one, others were all CYP2C9 *1/*1 wild types. CYP2C9 *2, CYP2C9 *4 and CYP2C9 *5 alleles were not detected. Direct sequencing of the purified PCR products of the heterozygotes, mutant homozygotes and ten wild type individuals gave a corresponding result to that genotyped by microarray. Pharmacokinetic outcome showed that the individuals with CYP2C9 *1/*3 or CYP2C9 *3/*3 had slower metabolic elimination of tolbutamide than those with CYP2C9 *1/*1.

CONCLUSIONCYP2C9 genetic polymorphism has a significant influence on the pharmacokinetics of tolbutamide. Pharmacogenomic study will be helpful in guiding rational and individualized medication. Key words: tolbutamide; cytochrom P450 CYP2C9; allele; single nucleotide polymorphism; genotyping

Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2C9 ; Genotype ; Heterozygote ; Homozygote ; Humans ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Random Allocation ; Tolbutamide ; pharmacokinetics

OBJECTIVETo observe the expression of adrenomedullin (AM) in the patients with laryngeal carcinoma.

METHODSTwo-step immunohistochemistry method was used to examine the expression of AM in the patients with laryngeal carcinoma. Radioimmunoassay was applied to determine the concentration of AM in the laryngeal carcinoma tissues, adjacent laryngeal mucosa of carcinoma tissues and in the plasma of patients and controls.

RESULTSPositive stainings for AM were found in all 21 specimen examined,distributed mainly in the cytoplasm of the laryngeal carcinoma cells. Positive stainings were more stronger in the circumference than in the center of tumor tissue for the highly and moderately differentiated tumors. While the stainings were distributed homogeneously for poorly and moderately differentiated tumors. The concentration of AM in the laryngeal carcinoma tissues (n = 44) and the adjacent mucosa (n = 44) were (49.67 +/- 28.33) pg/ml and (14.71 +/- 7.17) pg/ml (x +/- s) respectively and laryngeal tumor showed much higher concentration of AM than the adjacent mucosa (u = 135.00, P < 0.01). The concentration of AM in patients with laryngeal carcinoma of T2, T3 and T4 stage were (31.52 +/- 15.22), (56.63 +/- 18.51) and (96.12 +/- 18.22) pg/ml (x + s) respectively,and there were statistically significant difference among them. In the N stage, patients with higher stages were found to express significantly higher AM concentration, but there was not statistically significant difference between NO stage and N1 stage. In the M stage,patients with M1 stage were found to express significantly higher AM concentration (u = 31.00, P < 0.01). But there was not statistically significant difference between AM plasma concentration of laryngeal carcinoma patients and that of healthy controls.

CONCLUSIONSThe results suggested that high expression of AM in tissues of laryngeal carcinoma was related with the TNM stage of laryngeal carcinoma, AM may play an important role in the development of the laryngeal neoplasma.

Adrenomedullin ; metabolism ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Female ; Humans ; Laryngeal Mucosa ; metabolism ; pathology ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging

AIMPoly (methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate) (PEG-PHDCA) and PHDCA niosomes were prepared and the influence of the PEG chain length on the niosomes physicochemical characteristics, complement consumption and phagocytic uptake were studied.

METHODSThe physicochemical parameters of PEG-PHDCA niosomes were characterized in terms of particle size, zeta aqueous layer thickness. The relationship between physicochemical characteristics and in vitro complement consumption and phagocytic uptake was further illustrated.

RESULTSExperimental results showed that PEG10,000-PHDCA had most loose structure and least PEG surface density among three groups. Configuration simulation through fixed aqueous layer thickness confirmed that PEG folding and less flexibility of the PEG chains of PEG10,000-PHDCA niosomes were accountable for its poor stealth effects. Compared with PEG2,000-PHDCA, PEG5,000-PHDCA showed a thicker fixed aqueous layer (FALT) of 4.20 nm, less negative zeta potential of -10.03 mV, and enhanced PEG surface density of 0.49 PEG x nm(-2), leading to the best effects of reduction of complement consumption and phagocytic uptake.

CONCLUSIONExcessive chain length of PEG was not necessary for stealth effects of PEG-PHDCA niosomes. PEG5,000-PHDCA niosomes had best effects on evading complement consumption and subsequent phagocytic uptake.

Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; Camptothecin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Complement System Proteins ; metabolism ; Cyanoacrylates ; chemical synthesis ; chemistry ; Drug Carriers ; Macrophages ; physiology ; Male ; Mice ; Particle Size ; Phagocytosis ; Polyethylene Glycols ; chemical synthesis ; chemistry ; Surface Properties