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Background/Aims: Cytokines such as tumour necrosis factor (TNF-α) contribute to the pathogenesis of cirrhotic cardiomyopathy. Nuclear factor-κB (NF-κB) is crucial for cytokine regulation, and induces cardiac dysfunction in several heart disease models. We aimed to elucidate possible NF-κB involvement in cirrhotic cardiomyopathy. Methods: Rats were bile duct ligated (BDL) to produce cirrhosis; controls received sham operation. Animals were studied 4 weeks later. Two NF-κB inhibitors were used: pyrrolidine dithiocarbamate (PDTC) and Bay 11-7082. Four groups were studied in most protocols: sham control, sham+PDTC, BDL and BDL+PDTC. Additional contractility studies were performed with Bay 11-7082. Myocardial NF-κB and TNF-α expression was measured by Western blot and ELISA. The contractility of isolated cardiomyocytes was observed under direct microscopy. Results: Nuclear factor-κB and TNF-α levels were increased in cirrhotic hearts compared with controls. PDTC significantly reduced NF-κB activity and TNF-α expression in cirrhotic hearts; controls were unaffected. Cirrhotic cardiomyocytes showed decreased systolic and diatolic velocity compared with sham controls. Both PDTC and Bay 11-7082 restored contractile function in cirrhotic cardiomyocytes, but did not affect controls. Conclusions: Inhibition of the increased NF-κB activity in cirrhotic hearts was associated with improvement of attenuated cardiomyocyte contractility. NF-κB, via effects on cytokine expression, may contribute to the pathogenesis of cirrhotic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background and Aims: Alterations in the Doppler hepatic vein (HV) waveform are associated with cirrhosis and portal hypertension. We prospectively evaluated the correlation between the extent of abnormal Doppler HV waveforms expressed as damping index (DI) and the hepatic venous pressure gradient (HVPG) and response to propranolol in patients with cirrhosis. Material and Methods: In 76 patients with cirrhosis (69 men and seven women), both DI of Doppler HV waveform and HVPG were measured, and the relationship between them was analysed. DI was calculated by the minimum velocity/maximum velocity of the HV waveform. An HVPG>12 mmHg was defined as severe portal hypertension. In a subgroup of 19 patients receiving propranolol, changes in both DI and HVPG were evaluated after propranolol administration for 3 months. One author (S. K. B.) performed all DI of Doppler HV waveform studies. Results: Abnormal HV waveforms were seen in 66 of 76 patients (86.8%). DI significantly correlated with the grade of HVPG, i.e. with higher HVPG increased DI was observed ( P<0.01). By logistic regression analysis, DI>0.6 was significantly more likely to be severe portal hypertension (odds ratio: 14.19, 95% confidence interval: 4.07–49.55). Receiver-operating characteristic curve according to the value of 0.6 of DI showed a sensitivity of 75.9% and a specificity of 81.8% for the presence of severe portal hypertension. In 19 patients of the propranolol subgroup, change of DI following propranolol treatment also significantly correlated with that of HVPG ( P<0.01). Conclusions: Damping index of the HV waveform by Doppler ultrasonography might be a non-invasive supplementary tool in evaluating the severity of portal hypertension and in responding to propranolol in patients with liver cirrhosis. [ABSTRACT FROM AUTHOR]

The article reflects on the power of one or a single person, by citing various examples including Mohamed Abouazizi, a man lead to the overthrow of longstanding despotic regimes in Tunisia, Egypt and Libya. It mentions that the power of one person who make a difference is referred as whistleblowers. It highlights Enron Corp.'s example, where a single whistleblower alerted authorities to the wrongdoing. It informs that several governments have passed legislation protecting whistleblowers.