Synthesis of 1-substituted phenazines as novel antichlamydial agents.

A novel series of 1-substituted phenazines 4a-4l were designed and synthesized via Palladium-catalyzed reactions from 1-phenazine trifluoromethanesulfonate. These phenazines showed antichlamydial activity with IC50 values from 1 to 10 µM. Among them, compounds 4c and 4i exhibited the best antichlamydial activity with IC50 values from 2.06 to 2.74 µM without apparent cytotoxicity to host cells.

Dihydromyricetin Attenuates Myocardial Hypertrophy Induced by Transverse Aortic Constriction via Oxidative Stress Inhibition and SIRT3 Pathway Enhancement.

Dihydromyricetin (DMY), one of the flavonoids in vine tea, exerts several pharmacological actions. However, it is not clear whether DMY has a protective effect on pressure overload-induced myocardial hypertrophy. In the present study, male C57BL/6 mice aging 8⁻10 weeks were subjected to transverse aortic constriction (TAC) surgery after 2 weeks of DMY (250 mg/kg/day) intragastric administration. DMY was given for another 2 weeks after surgery. Blood pressure, myocardial structure, cardiomyocyte cross-sectional area, cardiac function, and cardiac index were observed. The level of oxidative stress in the myocardium was assessed with dihydroethidium staining. Our results showed that DMY had no significant effect on the blood pressure. DMY decreased inter ventricular septum and left ventricular posterior wall thickness, relative wall thickness, cardiomyocyte cross-sectional areas, as well as cardiac index after TAC. DMY pretreatment also significantly reduced arterial natriuretic peptide (ANP), brain natriuretic peptide (BNP) mRNA and protein expressions, decreased reactive oxygen species production and malondialdehyde (MDA) level, while increased total antioxidant capacity (T-AOC), activity of superoxide dismutase (SOD), expression of sirtuin 3 (SIRT3), forkhead-box-protein 3a (FOXO3a) and SOD2, and SIRT3 activity in the myocardium of mice after TAC. Taken together, DMY ameliorated TAC induced myocardial hypertrophy in mice related to oxidative stress inhibition and SIRT3 pathway enhancement.

GM1 ganglioside reverses the cognitive deficits induced by MK801 in mice.

Cognitive deficits are core symptoms of schizophrenia, but effective treatments are still lacking. Previous studies have reported that the brain-derived neurotrophic factor (BDNF) signaling is closely involved in learning and memory. Monosialotetrahexosylganglioside (GM1) is a ganglioside with wide-ranging pharmacologic effects that enhances the BDNF signaling cascade. This study aimed to assess the effects of GM1 on schizophrenia-related cognitive impairments. A brief disruption of N-methyl-D-aspartate receptors with MK801 was used to generate the animal model for cognitive deficits in schizophrenia. It was found that MK801-treated mice showed significant deficits in memory ability compared with control mice in different behavior tests, and this was accompanied by decreased hippocampal BDNF signaling pathway. Consecutive administration of GM1 fully restored the MK801-induced cognitive deficits and the impaired BDNF signaling in the hippocampus. Furthermore, a BDNF system inhibitor abolished the effects of GM1 in the MK801 model. Taken together, our results show that GM1 could reverse the MK801-induced cognitive deficits, suggesting a potential usefulness of GM1 in treating the schizophrenia-related cognitive impairments.

[Analysis of surface composition of three-way catalysts of in-use vehicles].

The kinds and contents of surface elements in three-way catalysts of six light-duty in-use taxi cabs, which were mainly operated in Beijing and whose driving mileages were in the range of 34 x 10(4)-59 x 10(4) km, were determined by X-ray fluorescence spectrometry (XRF), and the effect of driving mileage on element content was investigated. Results showed that nearly 30 kinds of elements were present on the catalyst surface. The main elements of different samples were similar. The common elements of the pollutant on the front and rear catalysts were P, Ca, Zn and Mn etc., most of which are from engine oil and gasoline. S was only observed on the rear catalysts, indicating that S tends to deposit on the rear catalysts. After 34 x 10(4) km run, the P content increased very slowly and 40 x 10(4) km run S content reached a saturated value. While the contents of Ca, Zn and Mn still exhibit an increase tendency after 56 x 10(4) km. That means after 40 x 10(4) km driving mileage, the effects of P and S on the catalyst activity are minor, and the continuous deposit of Ca, Zn and Mn will lead to further decrease of the activity.

[Qualitative evaluation of thyroid nodules with gray-scale contrast-enhanced ultrasound].

OBJECTIVE: To assess the feasibility of gray-scale contrast-enhanced ultrasound for characterizing thyroid nodules. METHODS: Forty thyroid nodules from 35 patients were studied both by conventional techniques and gray-scale contrast-enhanced ultrasound. Of the nodules examined, 15 were benign and 25 malignant. The enhancement of echogenicity was evaluated. The diagnosis was confirmed by surgical biopsy and histopathological examination. RESULTS: The study using gray-scale contrast-enhanced ultrasound showed absent contrast-enhancement in 9 of 25 malignant nodules and 1 of 11 benign solitary nodules; intense enhancement in 6 of 25 malignant nodules, with perfusion defect in the center; diffuse faint enhancement in 10 of 25 malignant nodules and 10 of 11 benign solitary nodules. Benign cystic nodules all showed absent enhancement in the cystic components and 2 of 4 intense enhancement in the solitary components. CONCLUSIONS: Gray-scale contrast-enhanced ultrasonography imaging may be a useful tool for evaluating the perfusion of thyroid nodules. Solitary nodules showing absent enhancement or intense enhancement with absent enhancement in the nodular center may suggest malignant.

Effect of atorvastatin on non-ischemic heart failure and matrix metalloproteinase-2 and 9 in rats.

AIM: To examine the role of atorvastatin on volume-overload-induced heart failure and to test the hypothesis that atorvastatin inhibits MMP-2 and 9 expression in heart failure with non-ischemic etiology. METHODS: Arteriovenous (AV) fistula-treated rats were administered with atorvastatin (3 mg/kg/d) or vehicle for 17 weeks. Ventricular hypertrophy and heart failure were assessed by echocardiography, B-type natriuretic peptide BNP mRNA level and morphological measurement. MMP-2, 9 expression were measured by Western blot and zymography. RESULTS: Atorvastatin decreased left ventricular end diastolic diameter from 6.86+/-0.51 mm to 6.28+/-0.37 mm (P<0.05), increased fractioning shortening from 41.4%+/-4.5% to 52.7%+/-4.2% (P<0.01), decreased ratio of BNP/GAPDH mRNA level from 0.43+/-0.03 to 0.27+/-0.03 (P<0.05). Similar data were observed for morphological measurement. Protein expression and enzyme activity of MMP-2 and 9 in the left ventricle tissue were significantly increased 18 weeks after surgery and atorvastatin also prevented those changes. CONCLUSION: Left ventricular remodeling induced by AV fistula was profoundly changed by atorvastatin treatment. Hypertrophy was attenuated and global function was improved. These positive effects of atorvastatin on heart failure were associated with decreased MMP-2 and 9 protein expression and enzyme activity.

[Application of real-time tissue elastography in diagnosis of breast cancer].

OBJECTIVE: To investigate the clinical value of real-time tissue elastography (RTE) in the diagnosis of breast cancer. METHODS: One hundred and twenty patients with breast lumps (135 lesions) were examined with B-mode imaging, color Doppler flowing imaging (CDFI) and RTE. The elastogram was graded using 5-score evaluating method. The postoperative pathological diagnosis was used as gold standard, and the sensitivity, specificity and accuracy of RTE and two-dimensional ultrasonography combined with RTE in diagnosis of breast cancer were calculated. RESULT: When the score >4 was set for cut-off criteria of malignancy, the sensitivity, specificity and accuracy of RTE was 85.45%, 83.75% and 84.4%, respectively. While two-dimensional ultrasonography combined with RTE was used, the sensitivity, specificity and accuracy increased up to 100%, 95% and 97%, respectively. CONCLUSION: RTE combined with two-dimensional ultrasonography can improve the validity in the diagnosis of malignant breast lesions.

[Influence of fluvastatin on left ventricular remodeling after myocardial infarction in rats].

OBJECTIVE: To investigate the effect of long-term administration of fluvastatin on improvement of ventricular remodeling of rats after myocardial infarction and its mechanism. METHODS: Sprague-Dawley rats were subjected to ligation in anterior descending branch of coronary artery and treated with fluvastatin (20 mg.kg(-1) d(-1)) or distilled water for 8 weeks. Doppler echocardiography, hemodynamic study and cardiac histomorphometry were used to estimate the ventricular remodeling and cardiac function. Laser scanning confocal microscope was used to definite the distribution of superoxide anion (O(2)(*-)) and nitrogen monoxide. RT-PCR and immunohistochemistry were used to detect the expression of NOS2 and p22phox in mRNA and protein level. The level of lipid peroxidation, glutathione peroxidase, nitrogen monoxide and total cholesterol were detected too. RESULTS: Administration of fluvastatin ameliorated left ventricular remodeling without affecting the infarct size [(40 +/- 6 vs 42 +/-5)%, P>0.05]. The level of left ventricular end-diastolic pressure [(18.24 +/-6.58 vs 10.74 +/-4.71) mmHg, P<0.05], right ventricular ameliorated relative weight [(0.92 +/-0.19 vs 0.71 +/-0.13) g/kg, P<0.05], the thickness of left ventricular posterior wall [(3.04 +/-0.28 vs 2.60 +/-0.36) mm, P<0.05] decreased after fluvastatin treatment. The left ventricular ejection fraction was not influenced, the relative lung weight and the left atrium diameter reduced [(5.79 +/-2.92 vs 3.69 +/-0.68) g/kg, (0.55 +/-0.12 vs 0.45 +/-0.04) mm, P<0.05]; the expressions of LPO in the plasma and myocardium [(8.64 +/-0.59 vs 7.71 +/-0.66) U/dl, P<0.05; (3.12 +/-0.38 vs 1.93 +/-0.40) ng/microg.pro, P<0.01] were reduced, and the overexpressed NO was inhibited [(436.87 +/-47.22 vs 313.78 +/-34.35) mg/dl, P<0.01], but the expression of GPx increased [(66.13 +/-8.31 vs 79.78 +/-2.38) mg/dl, P<0.01]. The expression of O(2)(*-) and the activity of NADPH oxidase subunit p22phox increased; NOS2 and its products NO were over-expressed too. CONCLUSION: Ventricular remodeling and hemodynamics are improved profoundly in MI rats treated with fluvastatin. The effect of antioxidative stress of fluvastatin might be involved in the mechanism.

Carvedilol Protects Early Diabetic Rat Hearts through Reducing Oxidative Stress.

The risk for cardiovascular disease is significantly high in diabetes mellitus. Experimental evidence suggests that oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Carvedilol, a non-selective beta-adrenoceptor and selective alpha1-adrenoceptor blocker, also has antioxidant and free radical scavenger properties. In the present study the effect of carvedilol on the antioxidative status of cardiac tissue was investigated in streptozotocin (STZ)-induced early diabetic rats. The subjects were randomly divided into age-matched rats, STZ-induced untreated diabetic rats, small and large dosage (1mg/kg/d or 10mg/kg/d) carvedilol-administrated diabetic rats. After 5 weeks, hemodynamic parameters, echocardiography characteristics and the levels of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) in the cardiac tissues of all groups were meassured. Diabetic rats had lower ejection fraction, fractional shortening, and higher systolic pressure, diastolic pressure and developed pressure. These parameters were improved by administration of carvedilol. Diabetic rats showed elevated MDA level and CAT activity, but lower activities of SOD and GSH-Px. Carvedilol treatment increased activities of SOD and GSH-Px in diabetic rats. These results indicate that carvedilol improves cardiac function via its antioxidant property in diabetic rats.