Puerarin attenuates angiotensin II-induced cardiac fibroblast proliferation via the promotion of catalase activity and the inhibition of hydrogen peroxide-dependent Rac-1 activation.

The aims of the present study were to evaluate the effects of puerarin on angiotensin II-induced cardiac fibroblast proliferation and to explore the molecular mechanisms of action. Considering the role of H2O2 in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, we hypothesized that modulating catalase activity would be a potential target in regulating the redox-sensitive pathways. Our results showed that the activation of Rac1 was dependent on the levels of intracellular H2O2. Puerarin blocked the phosphorylation of extracellular regulated protein kinases (ERK)1/2, abolished activator protein (AP)-1 binding activity, and eventually attenuated cardiac fibroblast proliferation through the inhibition of H2O2-dependent Rac1 activation. Further studies revealed that angiotensin II treatment resulted in decreased catalase protein expression and enzyme activity, which was disrupted by puerarin via the upregulation of catalase protein expression at the transcriptional level and the prolonged protein degradation. These findings indicated that the anti-proliferation mechanism of puerarin was mainly through blocking angiontensin II-triggered downregulation of catalase expression and H2O2-dependent Rac1 activation.

Puerarin inhibits angiotensin II-induced cardiac hypertrophy via the redox-sensitive ERK1/2, p38 and NF-κB pathways.

AIM: To investigate the effects of puerarin (Pue), an isoflavone derived from Kudzu roots, on angiotensin II (Ang II)-induced hypertrophy of cardiomyocytes in vivo and in vitro. METHODS: C57BL/6J mice were infused with Ang II and treated with Pue (100 mg·kg(-1)·d(-1), po) for 15 d. After the treatment, systolic blood pressure (SBP) and left ventricular wall thickness were assessed. The ratios of heart weight to body weight (HW/BW) and left ventricular weight to body weight (LVW/BW) were determined, and heart morphometry was assessed. Expression of fetal-type genes (ANP, BNP and ß-MHC) in left ventricles was measured using semi-quantitative RT-PCR. Mouse primary cardiomyocytes were treated with Pue (50, 100, 200 µmol/L), then exposed to Ang II (1 µmol/L). ROS level was examined with flow cytometry, the binding activity of NF-κB was determined using EMSA. Western blot was used to measure the levels of ERK1/2, p38 and NF-κB pathway proteins. [(3)H]leucine incorporation was used to measure the rate of protein synthesis. RESULTS: Oral administration of Pue significantly suppressed Ang II-induced increases in the myocyte surface area, HW/BW, LVW/BW, SBP and left ventricular wall thickness. Furthermore, Pue significantly suppressed Ang II-induced increases in ANP, BNP and ß-MHC expression in the left ventricles in vivo. Treatment of cardiomyocytes with Pue (50-500 µmol/L) did not affect the viability of cardiomyocytes in vitro. Pretreatment of cardiomyocytes with Pue dose-dependently inhibited Ang II-induced increases in ROS production, NF-κB binding activity, protein synthesis and cell breadth. Furthermore, pretreatment with Pue significantly suppressed Ang II-induced activation of ERK1/2, p38 and the NF-κB pathway proteins and the expression of ANP and ß-MHC in cardiomyocytes. The positive drug valsartan exerted similar effects on Ang II-induced cardiac hypertrophy in vivo and in vitro. CONCLUSION: Pue attenuates Ang II-induced cardiac hypertrophy by inhibiting activation of the redox-sensitive ERK1/2, p38 and the NF-κB pathways.

[A hospital-wide intervention program to optimize the utilization quality of carbapenems and glycopeptides].

OBJECTIVE: To investigate the impact of intervention program upon improvement of utilization quality of carbapenems and glycopeptides. METHODS: Multifaceted intervention program of carbapenems and glycopeptides was conducted at our hospital. It involved written justification forms, expert consultation committee meetings, audit, feedback and re-feedback. From November 1, 2007 until October 31, 2008, retrospective audit and feedback were performed on all patients dosed with carbapenems or glycopeptides. Case reports were reviewed and data of ratio of appropriate antibiotic use, length of hospital stay, total cost, mortality and rate of vancomycin-resistant Enterococci (VRE) were collected and compared between the first and second half year of antibiotic intervention program. RESULTS: A total of 397 cases were reviewed, 75 cases discussed at expert committee meetings and 58 feedback letters delivered to responsible doctors. The consumption of both carbapenems and glycopeptides decreased. The appropriate use of carbapenems and glycopeptides increased from 37.8% (45/119) to 53.5% (48/127, P < 0.05) and from 45.6% (36/79) to 63.9% (46/72, P < 0.05) respectively. The total cost and mortality of patients dosed with glycopeptides decreased from a median of RMB 65,700 (30,300 - 146,900) yuan to 55,700 (36,700 - 90,900) yuan, and from 39.2% to 26.4% respectively. The rate of VRE decreased from 5.63% in 2007 to 3.80% during the second half year of 2008. CONCLUSION: Antibiotic intervention program of carbapenems and glycopeptides is effective in decreasing the inappropriate antibiotic use.

[Cardiac arrest in severe acute respiratory syndrome: analysis of 15 cases].

OBJECTIVE: To investigate the causes for cardiac arrest in severe acute respiratory syndrome (SARS) patients. METHODS: Retrospective analysis of the epidemiological history, clinical presentation, the change of laboratory tests, chest radiography, and treatment of 15 SARS patients with cardiac arrest. RESULTS: The average age of the patients was 60 years. Eight had a history of exposure to SARS patients, among them 6 were household contacts. Eight patients had no underlying diseases, and another 8 complained of extreme anxiety. Abnormalities of cardiac enzymes were present in 10 patients. Myocardial ischemia and arrhythmia were present in 5 patients. Bilateral, multifocal lung infiltrates were present in 13 of the 15 patients. Four patients died after defecation and 9 died during relatively stable periods. CONCLUSIONS: It was suggested that the causes for cardiac arrest in SARS patients may include: (1) the lung injury caused by the SARS virus leads to hypoxemia and thus an unsteady state of the myocardial electricity; (2) SARS virus directly causes injury to the myocardial cells and/or the conduct system; (3) SARS infection aggravates the original myocardial pathological change, worsening the conduct block; (4) extreme anxiety leads to extra secretion of catecholamine, which causes instability of myocardial electricity; (5) defecation worsens hypoxemia, which induces arrhythmia (ventricular fibrillation) and causes cardiac arrest.

[Analysis and causation discussion of 185 severe acute respiratory syndrome dead cases].

OBJECTIVE: To proceed the retrospective analysis of the dead reasons of patients with severe acute respiratory syndrome (SARS), in order to provide experience for decreasing mortality of SARS patients in clinic. METHODS: Retrospective analyze of 185 dead cases of SARS patients, including age, basic diseases, laboratory tests, radiological test and therapy. RESULTS: There were 102 men and 83 women in 185 dead cases of SARS, in which average age was 56.4 years, 85 cases were older than 60 years. 147 cases (79.5%) had basic diseases, cardiovascular disease (57 cases) was at the first Place; diabetes mellitus (41 cases) was at the second Place; cerebrovascular disease (19 cases) was at the third place; 15 patients had alimentary disease. 52 patients (28.1%) suffered from complications, which were acute respiratory distress syndrome (ARDS), secondary infection and multiple organ dysfunctional syndrome (MODS) by order. Some of the patients having complete information showed that life symptoms were stabilization. Hemogram and blood gas analysis showed that blood sugar and white blood cell (WBC) increased (P<0.001); lymphocyte decreased significantly (P<0.005) and PaO(2), PaO(2)/FiO(2) decreased Progressively (P<0.005 P<0.001) in late stage of SARS versus just entering the hospital. Half patients showed the abnormality of biochemical indexes. CONCLUSION: Age and basic diseases are sensitive indexes for predicting dead tendency of SARS. Lung injury, obstinate hypoxemia, abnormality metabolize of hyperglycemia and misusing glucocorticoids and antibiotic leading to secondary infection are the main reasons for SARS patients dying.