The S1P1 regulator IMMH002 and its therapeutic effect and mechanism on autoimmune hepatitis / 药学学报

This study assessed and explored the pharmacological effects and mechanisms of action of IMMH002 {2-amino-2-(2-(4ʹ-(2-ethyloxazol-4-yl)-[1,1ʹ-biphenyl]-4-yl)ethyl)propane-1,3-dio}, a selective sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, in a concanavalin A (ConA)-induced autoimmune hepatitis (AIH) mouse model. The experimental protocol strictly adhered to the guidelines of the Ethics Committee for Animal Research of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00004046). Male ICR mice were pre-treated with the drug for four days, followed by induction of AIH through tail vein injection of ConA protein. Liver function, hepatic tissue pathology, peripheral blood parameters, as well as immunoglobulin G (IgG), inflammatory cytokines, T cell distribution, and inflammatory pathways were evaluated in mice. Results demonstrated that IMMH002 significantly reduced liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated hepatic tissue inflammation and necrotic damage, decreased serum IgG levels, and lowered the expression of inflammatory mediators including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Additionally, it facilitated T lymphocyte homing, downregulated the phosphorylation of nuclear factor kappa-B (NF-κB), IκB kinase β (IKKβ) and nuclear factor inhibitor protein-α (IκBα) proteins in hepatic tissue and cellular inflammation models. Collectively, IMMH002 effectively ameliorated ConA-induced autoimmune hepatitis in mice, exhibiting extensive anti-inflammatory and anti-necrotic effects, thereby laying a theoretical foundation for AIH clinical treatment.

Research progress on reproductive toxicity and reproductive system tumors induced by environmental endocrine disrupting chemicals / 环境与职业医学

Environmental endocrine disrupting chemicals are a kind of exogenous chemicals that generally exist in the environment, and can disturb the endocrine homeostasis and adversely affect reproductive, immune, neurological, and other functions after entering the body, among which the damage to the reproductive system is the most significant one. Studies have confirmed that the long-term exposure to environmental endocrine disrupting chemicals have irreversible and harmful effects on primordial germ cell growth, reproductive organ development, and reproductive endocrine regulation, and also have obvious correlations with the occurrence and development of various reproductive system tumors. This paper reviewed various reproductive toxicities induced by common environmental endocrine disrupting chemicals in the developmental and reproductive stages, and associated mechanisms involved in the occurrence and development of reproductive system tumors.

Improving the positional adaptability: structure-based design of biphenyl-substituted diaryltriazines as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines (NP-DATAs), synthesis of a series of novel biphenyl-substituted diaryltriazines (BP-DATAs) with a flexible side chain attached at the C-6 position is presented. These compounds exhibited excellent potency against wild-type (WT) HIV-1 with EC values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant strains. Compounds and had the best activity against WT, single and double HIV-1 mutants and reverse transcriptase (RT) enzyme comparable to two reference drugs (EFV and ETR) and our lead compound NP-DATA (). Molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the HIV-1 reverse transcriptase non-nucleoside binding pocket (NNIBP) attributing to the improved activity. The preliminary structure-activity relationship and PK profiles were also discussed.

Determination of related genotoxic impurities in olmesartan medoxomil by HPLC-MS / 中国药科大学学报

@#The aim of this study was to establish a high performance liquid chromatography-mass spectrometry method for the determination of 5-(4′-(bromomethyl)-［1, 1′-biphenyl］-2-yl)- 1H-tetrazole(BBT1)and 5-(4′-(dibromomethyl)-［1, 1′-biphenyl］-2-yl)-1H-tetrazole(BBT2), which are two genotoxic impurities in olmesartan medoxomil. Chromatographic separation was based on an Agilent Zorbax Eclipse Plus C18(250 mm × 4. 6 mm, 5 μm)column using water(containing 0. 1% formic acid)- acetonitrile as mobile phase in gradient elution mode. Mass spectrometry was operated in positive ion mode. Selective ion monitors were set at m/z 315 for BBT1 and at m/z 395 for BBT2. Good linear correlations were observed in the range of 0. 009 4- 0. 561 0 μg/mL(r=0. 998)with the quantification limit at 9. 35 ng/mL and the detection limit at 3. 12 ng/mL for BBT1, and in the range of 0. 018 2- 0. 547 5 μg/mL(r=0. 999)with the quantification limit at 18. 25 ng/mL and the detection limit at 6. 08 ng/mL for BBT2. Furthermore, the average recoveries of the three spiked concentration level were 96. 5%(n=9, RSD=4. 8%)and 98. 0%(n=9, RSD=5. 1%)for BBT1 and BBT2, respectively. The proposed method is simple, specific and accurate, and quite suitable for the determination of BBT1 and BBT2 in olmesartan medoxomil.

Regional analysis of potential polychlorinated biphenyl degrading bacterial strains from China

ABSTRACT Polychlorinated biphenyls (PCBs), the chlorinated derivatives of biphenyl, are one of the most prevalent, highly toxic and persistent groups of contaminants in the environment. The objective of this study was to investigate the biodegradation of PCBs in northeastern (Heilongjiang Province), northern (Shanxi Province) and eastern China (Shanghai municipality). From these areas, nine soil samples were screened for PCB-degrading bacteria using a functional complementarity method. The genomic 16S rDNA locus was amplified and the products were sequenced to identify the bacterial genera. Seven Pseudomonas strains were selected to compare the capacity of bacteria from different regions to degrade biphenyl by HPLC. Compared to the biphenyl content in controls of 100%, the biphenyl content went down to 3.7% for strain P9-324, 36.3% for P2-11, and 20.0% for the other five strains. These results indicate that a longer processing time led to more degradation of biphenyl. PCB-degrading bacterial strains are distributed differently in different regions of China.

Study on four polymorphs of bifendate based on X-ray crystallography

Bifendate, a synthetic anti-hepatitis drug, exhibits polycrystalline mode phenomena with 2 polymorphs reported (forms A and B). Single crystals of the known crystalline form B and 3 new crystallosolvates involving bifendate solvated with tetrahydrofuran (C), dioxane (D), and pyridine (E) in a stoichiometric ratio of 1:1 were obtained and characterized by X-ray crystallography, thermal analysis, and Fourier transform infrared (FT-IR) spectroscopy. The differences in molecular conformation, intermolecular interaction and crystal packing arrangement for the four polymorphs were determined and the basis for the polymorphisms was investigated. The rotation of single bonds resulted in different orientations for the biphenyl, methyl ester and methoxyl groups. All guest solvent molecules interacted with the host molecule via an interesting intercalative mode along the [1 0 0] direction in the channel formed by the host molecules through weak aromatic stacking interactions or non-classical hydrogen bonds, of which the volume and planarity played an important role in the intercalation of the host with the guest. The incorporation of solvent-augmented rotation of the C-C bond of the biphenyl group had a striking effect on the host molecular conformation and contributed to the formation of bifendate polymorphs. Moreover, the simulated powder X-ray diffraction (PXRD) patterns for each form were calculated on the basis of the single-crystal data and proved to be unique. The single-crystal structures of the four crystalline forms are reported in this paper.

Effect of Dimethyl Dicarboxylate Biphenyl (DDB) on the Proliferation, Apoptosis and PPARγExpression of Hepatic Stellate Cells / 中国药师

Objective: To investigate the effect of dimethyl dicarboxylate biphenyl ( DDB) on the proliferation, apoptosis and PPARγ expression of hepatic stellate cells. Methods: HSC-T6 cells were cultured in 96-well plates and 6-well plates, and after the 24-hour drug treatment, the influence of DDB on the proliferation and apoptosis of HSC-T6 were detected respectively by CCK-8 kit and flow cytometry. Quantitative real-time-PCR ( Q-PCR) and Western blotting were adopted to determine the effect of DDB on the PPARγmRNA level and the protein expression in HSC-T6 cells. Results:DDB obviously inhibited the proliferation of HSC-T6 (P<0. 05) and significantly promoted the apoptosis of HSC-T6 (P<0. 05) at the experimental concentration (8-64 μmol·L-1) when compared with the control group (0 μmol·L-1). The expression of PPARγ in drug-treated HSC-T6 was notably improved. Conclusion: DDB can inhibit the proliferation and promote the apoptosis of HSC-T6 cells by up-regulating the expression of PPARγ.

Chemical constituents of the leaves of magnolia grandiflora linn and their antitumor activities / 中国药学杂志

OBJECTIVE: To study the chemical constituents of the leaves of Magnolia grandiflora Linn and their antitumor activities. METHODS: The constituents were isolated and purified by various chromatographic methods, including column chromatographies on silica gel, Sephadex LH-20, as well as recrystallization. Their structures were identified by analysis of physical and spectral data and confirmed by comparison of their spectral data with the reported values in the literature or those of authentic samples. The antiproliferative activities of the purified compounds were evaluated by MTT assay. RESULTS: Twelve compounds were isolated and identified as parthenolide(1), ergosterol peroxide(2), N-formyl-annonain(Z)(3Z), N-formyl-annonain(E)(3E), vitamin E quinone(4), β-sitosterol(5), 11,13-dehydrocompressanolide(6), scoparone(7), liriodenine(8), aurantiamide acetate(9), michelenollide(10), and 2,6,2',6'-tetramethoxy-4,4'-bis(2,3-epoxy-1-hydroxypropyl)biphenyl(11). CONCLUSION: Compounds 2, 3Z, 3E, and 4 are isolated from this plant for the first time. Compounds 9 and 11 are isolated from the plants in Magnoli Linn for the first time.

Therapeutic effect of dimethyl dimethoxy biphenyl dicarboxylate on collagen-induced arthritis in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis (CIA).</p><p><b>METHODS</b>Wistar rat model of CIA was set up using bovine collagen type II. Fifty rats were divided into five groups randomly: normal, CIA model, DDB treatment, methotrexate (MTX) treatment, and combined DDB+MTX treatment. Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints. Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining. Plasma levels of vascular endothelial growth factor (VEGF), platelet derived growth factor, interleukin-8 (IL-8), IL-4, tumor necrosis factor α (TNF-α), and cyclooxygenase-2 (COX-2) were quantified by enzyme-linked immunosorbent assay. Nitric oxide levels were detected by Griess reagent.</p><p><b>RESULTS</b>Compared with the CIA model group, a remarkable reduction in various angiogenic (VEGF and IL-8) and inflammatory mediators (TNF-α, IL-4 and COX-2) after treatment with DDB either alone or combined with MTX P<0.05 or P<0.01). Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect. The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal.</p><p><b>CONCLUSION</b>Our data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis (RA) compared with a choice drug (MTX) and it may be offered as a second-line drug in the treatment of RA.</p>

Metabonomics analysis of effects induced by PCBs and high fat diet combined expo-sure in SD rats / 军事医学

Objective To explore the effect on metabolism of glucose and lipids, potential toxicity mechanism and possible biomarker candidates by analyzing urine metabonome changes of rats after oral administration of polychlorinated biphenyl congeners( PCBs) and high fat diet alone or in combination.Methods Male SD rats were divided randomly into control group,high fat diet group, PCBs group and combination group of PCBs and high fat diet.Urine samples were collected after 6-week treatment, 1 H NMR spectra were performed and analyzed by principal component analysis ( PCA) . Results The PCA scores plot of urine 1 H NMR data showed that the combined group could be easily distinguished from the other three groups, suggesting great difference in metabolism.The loading plot of the PCA revealed significant increase in the levels of lactate, glucose, creatine, 2-hydroxy-isovaleric acid and reduction in the levels of citrate, succinate, taurine, hippurate and trimethylamine oxide ( TMAO) in the combined exposure group after six-week exposure.Conclusion The altered levels of metabolites induced by combined exposure of PCBs and high fat diet may be related to the injury to mitochondrial function, reduction of energy metabolism in tricarboxylic acid cycle (TAC).These effects possibly lead to perturbations in the metabolism of glucose, lipid and amino acids.The altered metabolites may be considered biomarker candidates of toxicity induced by exposure to PCBs and high fat diet.

The PERFECT Study (PEnnel Real liFe Efficacy Clinical Trial), a Double-Blind, Randomized, Multicenter Trial Examining the Efficacy of Biphenyl Dimethyl Dicarboxylate Combined with Garlic Oil in Patients with Transaminase Elevated Chronic Liver Disease / 대한내과학회지

BACKGROUND/AIMS: Biphenyl dimethyl dicarboxylate (DDB) combined with garlic oil (pennel) has been used to treat chronic liver disease. A randomized, double-blind, active- and placebo-controlled clinical trial was conducted to investigate the efficacy, safety and quality of life in chronic liver disease patients. METHODS: A total of 237 patients with chronic liver disease were randomized into three groups; 100 patients were administered pennel, 102 patients Legalon as an active-control and 35 patients placebo for 12 weeks. The primary endpoint was the rate of alanine aminotransferase (ALT) normalization. We assessed differences in ALT levels and malondialdehyde (MDA) as an oxidative biomarker between 0 and 12 weeks, the improvement in quality of life using a chronic liver disease questionnaire (CLDQ) and the incidence of adverse events. RESULTS: Among 237 patients, there were 157 patients with non-alcoholic fatty liver disease, 36 patients with alcoholic liver disease, and 28 patients with chronic hepatitis B and C. The incidence of ALT normalization at 12 weeks was 89% for the pennel group, 18.6% for the active-control group, and 22.9% for the placebo-control group (p < 0.001). The difference in serum ALT level between 0 and 12 weeks was significantly higher in the pennel group (p < 0.001) and the level of MDA was decreased in the pennel group, statistically (p < 0.001). There was no difference in incidence of adverse events among groups. The pennel group showed significant improvement based on the CLDQ (p < 0.001). CONCLUSIONS: Pennel can effectively improve the rate of ALT normalization and the quality of life with a safety profile in chronic liver disease.

The PERFECT Study (PEnnel Real liFe Efficacy Clinical Trial), a Double-Blind, Randomized, Multicenter Trial Examining the Efficacy of Biphenyl Dimethyl Dicarboxylate Combined with Garlic Oil in Patients with Transaminase Elevated Chronic Liver Disease / 대한내과학회지

BACKGROUND/AIMS: Biphenyl dimethyl dicarboxylate (DDB) combined with garlic oil (pennel) has been used to treat chronic liver disease. A randomized, double-blind, active- and placebo-controlled clinical trial was conducted to investigate the efficacy, safety and quality of life in chronic liver disease patients. METHODS: A total of 237 patients with chronic liver disease were randomized into three groups; 100 patients were administered pennel, 102 patients Legalon as an active-control and 35 patients placebo for 12 weeks. The primary endpoint was the rate of alanine aminotransferase (ALT) normalization. We assessed differences in ALT levels and malondialdehyde (MDA) as an oxidative biomarker between 0 and 12 weeks, the improvement in quality of life using a chronic liver disease questionnaire (CLDQ) and the incidence of adverse events. RESULTS: Among 237 patients, there were 157 patients with non-alcoholic fatty liver disease, 36 patients with alcoholic liver disease, and 28 patients with chronic hepatitis B and C. The incidence of ALT normalization at 12 weeks was 89% for the pennel group, 18.6% for the active-control group, and 22.9% for the placebo-control group (p < 0.001). The difference in serum ALT level between 0 and 12 weeks was significantly higher in the pennel group (p < 0.001) and the level of MDA was decreased in the pennel group, statistically (p < 0.001). There was no difference in incidence of adverse events among groups. The pennel group showed significant improvement based on the CLDQ (p < 0.001). CONCLUSIONS: Pennel can effectively improve the rate of ALT normalization and the quality of life with a safety profile in chronic liver disease.

Effects of Rosuvastatin and Losartan on expression of caveolin-1 in cultured human monocyte-macrophage cells induced by oxidized low density lipoprotein / 中国医师杂志

Objective To investigate the effects,mechanisms,and the optimum doses of Rosuvastatin and Losartan on expression of caveolin-1 in cultured human monocyte-macrophage cells which were induced by oxidized low density lipoprotein(ox-LDL).Methods Human-monocyte cells were separated and changed into the human monocyte-macrophage cells.The model of amerosclerosis was set up.These cells were incubated in different doses of Rosuvastatin(0.1,1.0,5.0 μmol/L) and Losartan (10,50,100 μmol/L),and then cultured in combination of two drags (5.0 μmol/L + 100 μmol/L).Expression of caveolin-1 mRNA was determined with real-time fluorescent quantitative polymerase chain reaction (RT-PCR).Results In ox-LDL group,caveolin-1 mRNA was decreased sharply relative to control group [(0.2533 ±0.00973) vs (0.9410 ±0.03677)] in a concentration-dependent manner (P ＜0.01).Compared to ox-LDL group,expressions of Caveolin-1 mRNA were increased gradually in different doses of Rosuvastatin alone and Losartan alone group [(0.5198 ± 0.04840),(0.6183 ± 0.06740),(0.7257 ± 0.03052) vs (0.2533 ± 0.00973) ; (0.3350 ± 0.04177),(0.4428 ± 0.03804),(0.6049 ± 0.02627) vs (0.2533 ± 0.00973)] in a concentration-dependent manner (P ＜ 0.01) ; the summit expressions of caveolin-1 mRNA were emerged in using Rosuvastatin and Losartan together (F =59.119,P ＜ 0.01).Conclusions Rosuvastatin and Losartan may be responsible for the expression of caveolin-1 in human monocyte-macrophage cells that were induced by ox-LDL.The expressions were up-regulated with dose dependent manner of these drugs,and got the crest stage when using optimum doses of Rosuvastatin and Losartan together.

Comparison on the Efficacy and Safety of Biphenyl Dimethyl Dicarboxylate and Ursodeoxycholic Acid in Patients with Abnormal Alanine Aminotransferase: Multicenter, Double-blinded, Randomized, Active-controlled Clinical Trial / 대한소화기학회지

BACKGROUND/AIMS: Chronic hepatocellular damage is closely associated with hepatic fibrosis and fatal complication in most liver diseases. The aim of this study is to compare the efficacy and safety of biphenyl dimethyl dicarboxylate (DDB) and ursodeoxycholic acid (UDCA) in patients with abnormal ALT. METHODS: One-hundred thirty-five patients with elevated ALT were randomized to receive either 750 mg/day of DDB or 300 mg/day of UDCA for 24 weeks in 4 referral hospitals. Ninety-three (69%) patients had non-alcoholic steatohepatitits, 27 (20%) had alcoholic hepatitis, and 15 (11%) had chronic hepatitis. The primary end point was the rate of ALT normalization at week 24. The secondary endpoints were changes in AST, liver stiffness, and the incidence of adverse events. RESULTS: A total of 101 patients completed 24 weeks of therapy. ALT normalization at week 24 was observed in 44 (80.0%) patients in DDB group and 16 (34.8%) in UDCA group (p<0.001). Higher mean reduction of ALT levels from baseline to 24 weeks was seen in DDB group compared with UDCA group (-70.0% vs. -35.9%, p<0.001). Normalization of AST level (p=0.53) and change in the liver stiffness (p=0.703) were not significantly different between the two groups. Severe adverse drug reaction occurred in 1 patient in DDB group but the subject continued therapy during the study period. CONCLUSIONS: DDB was not inferior to UDCA for normalizing ALT level. Furthermore it was safe and well tolerated by patients with abnormal ALT.

Interaction of plant secondary metabolites and organic carbon substrates affected on biodegradation of polychlorinated biphenyl.

Using plant secondary metabolites (PSM) as an inducer to stimulate biodegradation of polychlorinated biphenyl (PCB) is considered a promising strategy to remove PCB from the environment. In this study, the effects of PSM including naringin, salicylic acid or biphenyl on PCB biodegradation using soil isolates were tested in mineral salt medium using either soil organic carbon (MSMS) or glucose (MSMG). In addition, the effects of surfactant hydroxypropyl-b-cyclodextrin (HP-b-CD) were examined. The results indicated that PCB removal was higher in medium with glucose as carbon substrate than in medium with SOC, and further enhanced with biphenyl amendment. However, interactions between salicylic acid and glucose limited PCB removal in treatments using both chemicals as carbon substrate while PCB removal was sustained in treatment using salicylic acid and SOC. Removal of tetra-chlorinated PCB was improved by adding HP-b-CD, suggesting increased bioavailability due to surfactant. These results suggest that interaction of organic carbon substrates could influence PCB degradation in contaminated environments.

Synthesis and antimicrobial activity of some newer biphenyl imidazo [2,1-b] [1,3,4] thiadiazole derivatives.

In the present study, we have reported the synthesis of some novel heterocyclic derivatives comprising imidazole and 1,3,4-thiadiazole containing moiety. Imidazothiadiazoles are of interest because of their diverse biological activities and clinical applications. Reactions of biphenyl carboxylic acid with thiosemicarbazide in the presence of phosphorous oxychloride resulted in biphenyl containing 2-amino-1,3,4-thiadiazole which is then further subjected to condensation with α-bromoarylketone under reflux in dry ethanol. The structures of the newly synthesised compounds were characterized by various spectral techniques and screened for antibacterial activity against strains of Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis, and antifungal activity against Candida albicans, Saccharomyces cerevisiae and Aspergillus niger. The compounds exhibited moderate to good activity when compared with standards.

Persistent Organic Pollutants and Obesity-Related Metabolic Dysfunction: Focusing on Type 2 Diabetes / 한국역학회지

Even though obesity is a well-established risk factor of type 2 diabetes, there is emerging evidence that persistent organic pollutants (POPs), a variety of lipophilic chemicals accumulated in adipose tissue, may be critically involved in the pathogenesis of type 2 diabetes. Among various POPs, serum concentrations of organochlorine pesticides and polychlorinated biphenyls (PCBs) were the most strongly and consistently linked to type 2 diabetes in both cross-sectional and prospective studies. In particular, obesity did not seem to be related to type 2 diabetes among persons with very low serum concentrations of POPs, suggesting a more fundamental role of chlorinated POPs in the pathogenesis of type 2 diabetes. These POPs were also associated with obesity, insulin resistance, and adverse lipid profiles like high triglyceride and low high-density lipoprotein (HDL) cholesterol among persons without diabetes, all metabolic dysfunctions commonly observed before developing type 2 diabetes. Recent animal studies supported the findings from epidemiological studies. If all these findings on POPs are true, it suggests that any effort to reduce the external and internal exposure to POPs would be necessary to decrease the social burden of type 2 diabetes.

Efficacy of two treatment combination on hypertension in very elderly patients / 中国医师杂志

Objective To compare the clinical effect of valsartan/amlodipine combination or irbesartan/hydrochlorothiazide(HCTZ)combination in very elderly hypertensives.Methods After a 4-week placebo period,94 hypertensives,aged 75-89 years were random given valsartan 160 mg/amlodipine 5 mg or irbesartan 300 mg/HCTZ 12.5 mg for 24 weeks according to a rospective study.After 4 weeks,amlodipine or HCTZ was doubled in non-responders.Patients were checked every 4 weeks.At each visit,sitting,lying and standing blood pressure(BP),systolic BP(SBP)and diastolic BP(DBP)were measured. At the end of placebo period and treatment period,electrolytes and uric acid were evaluated.Results Blood pressure was significantly decreased in both treatment groups,however,there was no statistical significance between two groups.BP changes from lying to standing position were significantly greater in the irbosartan/HCTZ group(-17.2/-9.1 mmHg)than that in the valsartan/amlodipine group(-10.1/-1.9 mmHg,t=2.14,P＜0.05 for SBP and t=3.11,P＜0.01 for DBP vs.irbesartan/HCTZ).Potassium significantly decreased and uric acid significantly increased(-0.4 mmol/L,t = 2.33,P＜ 0.05 and+29.7μ mol/L,t =2.54,P＜0.05 vs.baseline,respectively)only in the irbesartan/HCTZ group.Conclusions Both combinations had similarly effective in reducing clinical BP in very elderly hypertensives.However,valsartan/amlodipine offered some advantage and less pronounced BP orthostatic changes and absence of metabolic adverse effects.

Effect of irbesartan on clyclooxygenase-2 expression in experimental type 2 diabetic rat / 中国医师杂志

Objective To investigate the effect of angiotensin Ⅱ (AngⅡ) type 1 receptor block irbesartan on the expression of renal cyclooxygenase-2 ( COX-2 ) in rats with type 2 diabetes mellitus.Methods 18 rats were divided into control group, diabetes mellitus group and treating group.Immunohistochemistry was used to measure the expression of COX-2, matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1).The urinary TXB2,6-Ket-PGF1 αconcentration was determined by radioimmunoassay at the 6th week .Results There was an increasing expression of COX-2,TIMP-1 and decreasing M MP-9 ( COX-2:0.39 ± 0.02 vs 0.24 ± 0.04, TIMP :0.41 ± 0.03 vs 0.24 ± 0.02,MMP-9:0.24 ± 0.02 vs 0.32 ± 0.02, P ＜ 0.05 ) expression in the diabetes mellitus group ( P ＜ 0.05 ).Irbesartan could increase MMP-9 (0.29 ± 0.03 ) and depress TIMP-1 (0.34 ± 0.02) expression through inhibiting the expression of COX-2(0.31 ± 0.03) in renal tissue.Conclusions COX-2 was involved in the pathogenesis of the injury of type 2 diabetic nephropathy.Irbesartan might exert its renoprotective effects through inhibiting COX-2 activity, modulating the expression of MMP-9 and TIMP-1.

Investigation on Levels of Polychlorinated Dibenzo-p-dioxins,Polychlorinated Dibenzo-p-furan and Polychlorinated Biphenyl in Milk in a City / 环境与健康杂志

Objective To know the levels of polychlorinated dibenzo-p-dioxins(PCDDs),polychlorinated dibenzo-p-furan (PCDFs)and polychlorinated biphenyl(PCBs)in milk and milk powder.Methods From Feb.2007 to Jun.2007,the milk and milk powder samples were collected and PCDDs,PCDFs and PCBs were extracted from the samples by Soxhlet extraction,cleaned up by FMS and quantified by HRGC-HRMS,using isotope dilution methodology.Results PCDDrFs and PCBs were detected in all samples.The mean levels of PCDD/Fs and dl-PCBs TEQ in the milk powder were 0.43 pg/g lipid(median:0.34 pg/g lipid),and in the packed milk were 3.83pg/g)lipid(median:2.04 pg/g lipid).The mean levels of PCDD/Fs and dl-PCBs TEQ in all samples were 2.13 pg/g lipid(median:0.815 pg/g lipid).The levels of PCDD/Fs and dioxin-like PCBs in the detected samples were far below the limitation of EU except of two milk samples,and the levels of PCDD/Fs and dioxin-like PCBs were higher in the packed milk than those in the milk powder.Conclusion Some of the milk and milk powder in the investigated city has been polluted by polychlorinated dibenzo-p-dioxins(PCDDs),polychlorinated dibenzo-p-furan(PCDFs)and polychlorinated biphenyl(PCBs).